Heart Disease and Statins – Do Women Differ From Men?

24, Jun, 2013 by

Heart Disease and Statins - Do women Differ from men?Recent studies have shown that the symptoms of heart disease may differ between men and women. For example, women are less likely than men to have chest pain while suffering an acute heart attack (acute myocardial infarction). This may delay diagnosis and may partly explain why women seem to fare worse than men under these circumstances. Furthermore, the role of risk factors for heart disease may be different between the two genders. It has also been suggested that treatment with cholesterol lowering drugs, so-called statins may be less effective for women than men, in particular in primary prevention (individuals without known cardiovascular disease).

We had the pleasure to address these important issues recently in my hometown Reykjavik, Iceland, when visited by Barbara H. Roberts MD who is a prominent expert in this field. Dr. Roberts is director of the Women’s Cardiac Center at the Miriam Hospital in Providence, R.I. and associate clinical professor of medicine at the Alpert Medical School of Brown University. She has written two hugely interesting books,  How to Keep From Breaking Your Heart: What Every Woman Needs to Know About Cardiovascular Disease and The Truth About Statins: Risks and Alternatives to Cholesterol-Lowering Drugs.

I ran across Dr. Roberts recent book on statins while visiting New York last December for a cardiovascular meeting. I became very fond of it because it is extremely well written and can easily be read both by laymen and professionals. Her discussion is objective, evidence based, and she does not jump to any conclusions. Although Dr. Roberts has a point to make, her writing is careful and unbiased. Of course, the book has a strong message which I know many of my cardiologist colleagues will not agree with.

The internet may affect our lives more than we sometimes realize. A few days after I finished reading Dr. Roberts book I mentioned it in one of my blog posts because I felt it had an important message to everyone interested in cardiovascular disease and modern-day health care. Statins are used by millions of people worldwide. Whether we like it or not, we have an obligation to look at both the positive and negative effects of this therapy.

By coincidence, Dr Roberts read my article and we became acquainted. Six months later she arrived in Reykjavik to give two talks, a public lecture on how women may reduce their risk of heart disease, and another lecture at aimed at professionals at our University Hospital on statin therapy.

 

How to Keep From Breaking Your Heart: What Every Woman Needs to Know About Cardiovascular Disease 

Barbara H Roberts

Barbara H Roberts MD is director of the Women’s Cardiac Center at the Miriam Hospital in Providence, R.I. and associate clinical professor of medicine at the Alpert Medical School of Brown University

Dr. Roberts gave her first talk on the evening June 18th 2013. It was attended by more than 300 people, mostly women.  I was really proud by the huge interest. Thank you, Icelandic women for showing so much interest in how to improve your health and reduce the risk of heart disease. Dr. Roberts gave a fascinating overview of cardiovascular disease, risk factors, lifestyle and prevention. It was a memorable evening.

She started by addressing the anatomy of the normal heart, the coronary vessels and the blood circulation.  She then discussed important symptoms and disease concepts such as angina pectoris, myocardial infarction or heart attack, congestive heart failure, and palpitations.  She touched on the underlying pathology of cardiovascular disease and introduced important disease mechanisms like atherosclerosis, plaque rupture and clot formation.

Dr. Roberts then went on to describe how the symptoms of an acute heart attack may differ between men and women. Men are more likely to experience chest pain than women. Women are more likely to have nausea, back, shoulder, abdominal or neck pain than men. Women are also more likely to have no chest pain, and just shortness of breath or sometimes fatigue.

Dr. Roberts went through most of the known modifiable risk factors for heart disease like smoking, high LDL cholesterol, low HDL cholesterol, high blood pressure, diabetes, obesity, sedentary lifestyle, the metabolic syndrome and inflammation.

Dr. Roberts dedicated a part of her talk to treatment with statin drugs. Statins are frequently used to lower cholesterol and to reduce the risk of heart disease. It is her opinion that the benefits of statins have been greatly exaggerated and that their dangers have been greatly downplayed. She mentioned the most common side effects of statin therapy like muscle pain, rhabdomyolysis, cognitive dysfunction, tendon and nerve damage, diabetes, liver and kidney damage, fatigue, cataracts and congenital defects in babies exposed before birth. She summarized the results from clinical trials addressing the effects of statins in women. She underlined that no study has ever shown that treating women who do not have established vascular disease or diabetes with a cholesterol lowering medicine lowers the risk of cardiac death or cardiac events.

Dr. Roberts concluded that high levels of LDL cholesterol appear less predictive of cardiovascular risk in women than in men. In women, HDL cholesterol appears more predictive of risk than any other lipid level. She emphasized that abnormal blood cholesterol is but one of many risk factors for cardiovascular disease and that it´s not all about the LDL-cholesterol.

After covering the health risks of diabetes, inflammation, obesity and the metabolic syndrome Dr. Roberts went on to talk about the influence of diets. She mentioned a few dietary fictions like “Eating foods high in cholesterol raises your cholesterol” and “Low fat diets are good for your heart“. She also mentioned a few dietary facts like “Low fat diets lower HDL cholesterol so they are NOT heart healthy. You need to eat heart healthy fats” and “You can eat your way through any cholesterol lowering medicine“. Finally she underlined the strong scientific evidence indicating that a Mediterranean type diet reduces cardiovascular risk.

Dr Roberts concluded her lecture with this message:

 

Prevention of heart Disease made Easy:

  • If you smoke, STOP
  • If your cholesterol is high, get it down
  • If your blood pressure is high, get it down
  • If your blood sugar is high, get it down
  • If your weight is high, get it down
  • Do moderate exercise 30 minutes/day
  • Eat a heart healthy diet
  • Pick your parents wisely

 

The Truth About Statins: Risks and Alternatives to Cholesterol-Lowering Drugs

Dr. Barbara Roberts gave her second lecture in Reykjavik on June 19th at Landspitali University Hospital. Again she did a wonderful job with a highly informative and provocative talk. Unfortunately, only about 40 people attended, among them only a handful of cardiologists. I know doctors are busy people, but I have to admit that I would have loved to see more colleagues. Statins are the most frequently prescribed drugs by cardiologists all over the world. Many of us believe they are our most important weapon when it comes to pharmacological treatment of cardiovascular disease. So, I can understand that it may be unpleasant to hear about their presumed bluntness.

m_51ftcwyw3yl._bo2-204-203-200_pisitb-sticker-arrow-click-topright-35-76_aa278_pikin4-bottomright-67-22_aa300_sh20_ou01_Dr. Roberts started by going through many of the advantages and disadvantages of statin therapy.  She quoted Doctor Rita Redberg: “There are millions of women on a drug with no known benefit and risks that are detrimental to their lifestyle — and no one is talking about it”. She also quoted Dr. Sidney Blumenthal: “The totality of the available biologic, observational and clinical-trial evidence strongly supports the selective use of statin therapy in adults demonstrated to be at high risk for heart disease”. So, “are statins angels or devils” she asked?

Next Dr. Roberts took us through the history of the lipid hypothesis, from the work of the German pathologist, Rudolph Virchow on atherosclerosis in 1856, to the modern day clinical trials. She underscored the difference between absolute and relative risk reduction. She summarized data from clinical trials on the use of statins in secondary prevention. The result was that statins significantly reduce the number of cardiac events among individuals with cardiovascular disease, although the effect appears less pronounced among women than men. Again, she underscored the fact that clinical trials have not shown that treating women who do not have established vascular disease or diabetes with a cholesterol lowering medicine lowers the risk of cardiac death or cardiac events.

Dr. Roberts then went through all the most common side effects of statin therapy. Unfortunately this list appears to be growing, not unsurprisingly though, considering the huge number of people taking these drugs. Recently the increased risk of diabetes and cognitive dysfunction associated with statin therapy has been highlighted. Finally, she talked about possible alternatives to statin therapy. Again she underscored the positive effects of the Mediterranean diet.

Dr. Roberts final conclusions were:

  • Statins confer a small reduction in the risk of heart attacks and in some studies of dying of heart disease in those with established disease. The benefit is less in women than men.
  • They confer much less benefit in men without disease and none at all in healthy women.
  • The Mediterranean Diet is more effective than statins in lowering risk, WITHOUT ANY SIDE EFFECTS.

 

The bottom line

We, cardiologists tend to focus on the positive effects of statins. This is completely reasonable because clinical trials have shown that these drugs are very effective under certain conditions, and they improve the prognosis of patients with cardiovascular disease. Statins may also be effective among individuals at high risk for developing cardiovascular disease, such as those with diabetes. Nobody doubts the important role of statins in patients with familial hypercholesterolemia (FH).

Sometimes it is much easier for doctors to prescribe a drug than not to do it. Furthermore, the positive effects of statins are highly emphasized by the medical community, and these drugs are generally considered well tolerated. I am much more likely to be criticized by my colleagues if I don´t put a patient on statin therapy who might benefit, than if I put someone on such therapy who will probably not benefit from it. Sometimes we forget the words of our ancestors: Primum non nocere; first do no harm.

Sooner or later we will have to face the fact that many people have side effects from statin therapy. Often, these effects are not obvious. As doctors, we have to be alert and monitor patients for such side effects.

It has been pointed out by some of my colleagues that highlighting the negative effects of statins may encourage some patients to stop taking their drugs. Obviously, if these are individuals who are benefitting from their therapy, this may cause harm. On the other hand, providing truthful unbiased information to our patients can never be ethically wrong. Indeed, such information is necessary for shared decision making. Otherwise, our patients will not be able to make a truly informed decision on whether they want a certain treatment or not.

Finally, I would like to sincerely thank Dr. Barbara Roberts for visiting Iceland and sharing her knowledge and experience. Again, I recommend everyone interested in cardiovascular disease and modern-day health care to read her book on statin drugs. It is a strong reminder of our limited knowledge of the long-term effects of drugs that are being prescribed to millions of people worldwide.

157 Comments

  1. Mie

    Dr Roberts’ comments and views are problematic in many ways.

    1) Mediterranean diet (from now on: Med) more effective than statins? Err nope, don’t think so. Where’s the evidence? The best piece of evidence to support this comes from the Lyon Diet Heart study, the excellent results of which haven’t been replicated since. However, the bigger problem is that at least I’m not aware of any interventional studies comparing Med with statin therapy (with a separate control group). And you certainly cannot compare & contrast between different studies!

    Not to mention the issues of adherence and compliance. Several long & large RCTs (e.g. Shai et al) have compared MD with e.g. low fat and low carb diets, and the best results come from the period of weight loss. Then, inevitably, the weight shoots back up. E.g. in the follow-up to the abovementioned Shai et al the weight loss results – weight loss being significant since it’s the single best way to improve one’s lipid levels! – were in the range of 0,6 (low fat) – 3,1 (Med.) kilos at the end of the follow-up period of six years. Now, what does the tell you about the effect of dieting to reduce CVD risks? The clinical benefit in real life is pretty limited, especially in high risk groups. Yet, it is worth the effort but quite often – when talking about high risk patients – not enough on its own.

    2) Women not benefitting in primary prevention? Not according to a recent Cochrane review

    http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004816.pub5/full

    that states that

    “The most recent systematic review, using individual participant data from the majority of statin trials, provides strong evidence that benefits from statins outweigh any possible serious adverse effects, even at very low levels of CVD event rates (CTT Collaboration 2012a). These new findings counter earlier opinion that the evidence is insufficient to support use of statins in primary prevention for women or in older men (Abramson 2007). Previous reviews, in addition, have not reported other relevant outcomes such as costs, patient quality of life nor have they focused their attention on detailed reporting of adverse side effects.

    3) Adverse effects? Of course there are adverse effects. Show me a drug that doesn’t have any. But what about the prevalence and seriousness of these effect? See another C meta-analysis

    http://www.ncbi.nlm.nih.gov/pubmed/22607822

    which states that

    “In individuals with 5-year risk of major vascular events lower than 10%, each 1 mmol/L reduction in LDL cholesterol produced an absolute reduction in major vascular events of about 11 per 1000 over 5 years. This benefit greatly exceeds any known hazards of statin therapy. Under present guidelines, such individuals would not typically be regarded as suitable for LDL-lowering statin therapy. The present report suggests, therefore, that these guidelines might need to be reconsidered.”

    And do I really need to mention that the benefits of statins both in secondary prevention and in high-risk primary prevention are larger and more robust than the benefits of healthy diets & other lifestyle interventions alone? It’s not a question of “either/or” but “both/and”. And nothing in the NORMAL use of statins according to the guidelines contradicts these.

    I cannot help but get the idea that statins get treated differently from any other group of drugs that has been shown to work in its field. How come?

  2. Axel thank you for this comprehensive and accurate summary of my remarks. I realize they will spark a lot of argument and controversy. That is not a bad thing especially if it makes us question the preconceptions we all harbor about what is best for our patients.

  3. There is an interesting analysis of the risk of diabetes in the statins trials published in a recent issue of Diabetes Care. The risk of new onset diabetes on statin therapy appears higher among women than men.
    http://care.diabetesjournals.org/content/36/7/e100.full.pdf+html?sid=b0d9a20c-86c1-470c-afc8-5c9579deea50
    The authors point out that among women at low risk for cardiovascular disease who are prescribed statins, the risk of incident diabetes may outweigh the cardiovascular benefit.

  4. Doc´s opinion

    Mie.

    Thanks for your comments which are thorough and valid as always.

    You mentioned the Cochrane analaysis when discussion the benefits of statins in women in primary prevention:
    http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004816.pub5/full
    I didn´t find any distinction between men and women in this particular analysis.

    The authors on the other hand make another interesting point in their discussion:
    “All but one of the trials had some form of pharmaceutical industry sponsorship. It is now established that published pharmaceutical industry-sponsored trials are more likely than non-industry-sponsored trials to report results and conclusions that favour drug over placebo due to biased reporting and/or interpretation of trial results (Als-Nielsen 2003). The reporting of adverse events in these trials is generally poor, with failure to provide details of severity and type of adverse events or to report on health-related quality of life. However, it seems unlikely that any major life-threatening hazards associated with statin use exist. Potential non-fatal but serious hazards of long-term statin use have not been assessed in trials (e.g. possible cognitive impairments suggested by one small trial: Muldoon 2000). We have focused on adverse events arising in randomised trial populations but these cannot adequately assess rare hazards, such as rhabdomyolysis. Large observational databases are useful for detecting rare hazards associated with use of statins but a causal attribution is more difficult to establish (Hippsley-Cox 2010; Smeeth 2008).”

    Of course clinical studies and meta analyses guide our way when selecting treatment for our patients. We know from these studies that statin drugs are important for individuals with cardiovascular disease and those at high risk.

    However, when it comes to statin treatment in individuals at low risk, such as women with high LDL cholesterol levels but no other risk factors, the efficacy of treatment is much less, and therfore side effects become more important. In this situation shared decision making is essential. The patient has to be informed about the magnitude of effect of statin therapy as well as possible side effects. Otherwise, these individuals will not be able to make an informed decision on wheheter to take a certain drug daily for many years or not.

  5. Mie

    Axel,

    I understood that the review refers to CTT 2012. In addition, this isn’t the only recent meta-analysis stating that women benefit from statins. See Kostis et al, “Meta-Analysis of Statin Effects in Women Versus Men”, 2012. The benefits in terms of primary CV endpoints were there for BOTH sexes in both primary and secondary prevention – and the results were statistically significant. Thus Roberts’ claim that healthy women (meaning women without existing CVD) don’t benefit from statins is clearly not valid.

    I agree with you on that people at low risk of CVD (such as women whose total risk is small, despite elevated LDL) shouldn’t be put on medication as a matter of routine. However, this isn’t what Roberts is stating.

    In addition, when she refers to low fat diets as not being healthy, what is her point of comparison? As far as I know, low fat diets such as DASH and Ornish have been shown to be no better nor worse than a variety of other diets – and certainly a marked improvement over the now-notorious average western diet. The best data available points to Mediterranean diet having a slight average, but the differences aren’t that huge.

  6. The question whether women benefit from statins in primary prevention depends on how the clinical trials and meta-analyzes are interpreted. In her lecture, as well as in her book Dr Barbara Roberts has criticized the use of the term “need for revascularization” as an end point. She points out that if this end-point is omitted from the major trials on statins in primary prevention which have included women, and only hard end points used, there is no significant effect of statins compared with placebo among women.

    In their meta-analysis published in JACC (Journal of The American College of Cardiology) 2012, William J Kostis and coworkers concluded that statins ar effective among men and women, in primary as well as secondary prevention. http://www.sciencedirect.com/science/article/pii/S0735109711049898

    In an accompanying editorial Lori Mosca discusses some of the problems associated with addressing the effects of statins in primary prevention by meta-analysis. Firstly, within each primary prevention population there may be substantial heterogeneity of risk. Secondly, the authors did not have enough data to critically evaluate adverse side effects. Thirdly,concerns have been raised about the long term safety of statins for primary prevention, both in men and women, due to a potential increased risk of incident diabetes. Fourthly, women without cardiovascular disease (CVD) have a lower risk for mortality and CVD than men without CVD. Therefore the absolute benefit of statins will typically be less for women than men, suggesting it might be appropriate that women receive statins less frequently than men in the setting of primary prevention. http://www.sciencedirect.com/science/article/pii/S0735109711049904

    In October 2012 William J Kostis responded with a letter in JACC providing interesting results from an additional meta-analysis examining absolute risk reduction, where they looked at the primary end-point of the respective studies. For women, the number needed to treat (NNT) over a 4-year period was 148 for primary prevention and 36 for secondary prevention. In men, the corresponding NNT over a 4-year period was 43 for primary prevention and 29 for secondary prevention. http://www.sciencedirect.com/science/article/pii/S0735109712027726

    Thus, looking at the numbers in terms of absolute reduction, the difference between men and women is quite striking. In primary prevention, the NNT for women is more than three times higher than for men. This confirms the suggestion made by Dr. Mosca that it “might be appropriate that women receive statins less frequently than men in the setting of primary prevention”.

  7. Mie

    “Secondly, the authors did not have enough data to critically evaluate adverse side effects.”

    Notice that the Cochrane review addressed this issue, too. Of course, you can always refer to the fact that the number of RCT’s in primary prevention is much smaller than in secondary prevention. However, we’ve got to operate on what we knowledge & data we have.

    “Thirdly,concerns have been raised about the long term safety of statins for primary prevention, both in men and women, due to a potential increased risk of incident diabetes.”

    Indeed. However, in high risk patients (seemingly regardless of sex), the benefits still outweigh the risks.

    “Therefore the absolute benefit of statins will typically be less for women than men, suggesting it might be appropriate that women receive statins less frequently than men in the setting of primary prevention.”

    Yes, given that this refers to people with lower risk. There is some indication of statins (as well as medication in general) being sometimes described in cases where the guidelines don’t recommend them, at least not from the start.

  8. Low-fat Richard

    Doc,

    next time have Bill Roberts speaking at your event instead (American Journal of Cardiology, editor in chief). Bill is a real expert and is not BS:ing his audience into believing there are some other options besides statins or pure (or quasi-pure) vegetarianism.

    Evaluating lipid-lowering trials in the twenty-first century.

    “…Only pure vegetarians for practical purposes do not need statins, most of the rest of us do”

    http://www.ncbi.nlm.nih.gov/pubmed/19406281

    There’s only proven approach to diet that is compatible with LDL receptor hypothesis as elucidated by Brown & Goldstein (1984) and that is the Ornish/Esselstyn/McDougall approach. This is a principle as strong as a bottle of whisky and a hangover, it will never change. There’s no improvement in diet beyond the Ornish/Esselstyn/McDougall approach. Free-ranging mammalians rarely never have their LDL cholesterol above 2mmol/l. The Ornish aapproach, whole-food plant-based diet around complex carbohydrates and low in fat is the only diet that provides biologically normal cholesterol levels for most adult humans, it’s the only approach that is able to reverse chronic disease, especially CHD without drugs. Lest not forget that in the so-called successful Lyon trial statins were in heavy usage and no reversal of the disease was demonstrated in any of the patients.

    How LDL receptors influence cholesterol and atherosclerosis.

    “If the LDL receptor hypothesis is correct, the human receptor system is designed to function in the presence of an exceedingly low LDL levels. The kind of diet necessary to maintain such levels would be markedly different from the customary diet in Western industrial countries (and much more stringent than moderate low-cholesterol diets of the kind recommended by the American Heart Association). It would call for total elimination of dairy products as well as eggs, and severely limited intake of meat and saturated fats”.

    http://www.ncbi.nlm.nih.gov/pubmed/6390676

    “Experimentella studier har visat att människor i västvärlden har 5–10 gånger högre LDL-kolesterolnivå än vad som behövs för att kroppens celler bäst skall kunna styra upptaget av LDL-kolesterol”.

    http://www.lakartidningen.se/Functions/OldArticle.aspx?articleId=5222
    http://ww2.lakartidningen.se/store/articlepdf/5/5222/LKT0643s3278_3282.pdf

    I follow the guidelines provided by T Colin Campbell (China Study). Here’s my lipid panel

    TC 3.2
    LDL 1.8
    HDL 1.07
    Trig 0.7

    My friend is on the same program; 3-warm meals per day, staple foods: oatmeal, potatoes, rågbröd med tahini, pasta (penne och spagetti), onions, broccoli, etc. Very little added fats, apart from conservative use of canola oil, his lipids are even better:

    TC 2.9
    LDL 1.3
    HDL 1.19
    Trig 0.8

    It would be impossible to get atherosclerosis if these digits are maintained. These digits probably provide immunity to wide range of chronic disease given that high cholesterol is risk factor in Alzheimer, impotence, prostate cancer, etc.

    Mie,

    the idea that Ornish would in par with med diet is ridiculous. Western people are culturally biased towards animal-based diets and Ornish diets takes more guidance. In Gardner et al, people assigned to read the Ornish book, ate 30% of their calories from fat and had very little resemblance to Ornish diet. Well, nothing of this matter in clinical praxis, since doctors such as Axel can learn to basics of the program and offer it to their patients with high motivation. Moreover, the Ornish approach has huge potential in patients from cultures with familiarity with the dietary paradigm (Asia, Central Africa, etc). It’s easy to tell a Japanese patient to start eat like his poor rural cousins or grandparents.

  9. Low-fat Richard

    Mie,

    to recommend med- or any other type of diet over the Ornish would be an act of charlatanism. It would be as if the doctor prescribed fibrates alone for his/her FH-patients. To not to encourage patients to adopt low-fat, whole-food plant-based diet (the only diet congruent with the LDL receptor theory), would not be in the best interest of the patient. As Esseltyn commented for New York Times, what PREDIMED actually proved was that the Mediterranean diet promoted heart disease in people that did not have it at the baseline. You cannot recommend a high-fat diet with a proven track record of disease promotion.

  10. Low-fat Richard

    Doctors such as Barbara Roberts pushing nonsense about dietary cholesterol not elevating blood cholesterol are the best kept secrets of the statin industry. They provide market for these drugs long into the future. Sure, let’s all pretend the Hegstedt never conducted extremely controlled feeding experiments on dietary cholesterol, let’s all forget Hopkins meta-analysis on dietary cholesterol (1992) and the fact the dietary cholesterol downregulates LDL receptors. Let’s forget that Sacks found that adding 1 egg per day to the usual diet of 17 lactovegetarians whose habitual cholesterol intake was very low (97 mg/d) significantly increased LDL cholesterol level by 12%. Instead, lets pretend that Egg center’s gimmicks, feeding egg yolks to overweight diabetic people who are not sensitive to extra dietary cholesterol, that is, is the last word on dietary cholesterol. We might just pretend the darwinian foundation of our biomedical research paradigm is flawed. Nevermind the observations that the long-term feeding of cholesterol has resulted in heart attacks, sudden death, development of gangrene, softening on the bones and numerous other serious complications in nonhuman primates. For example, it has been shown that when diets rich in cholesterol and saturated fat are fed to monkeys of the genus Macaca, including the rhesus monkey and the crab-eating macaque, they experience heart attacks at approximately the same rate as high-risk populations living in developed nations. Heck with all this.

    Axel, this is what your Canadian colleagues, Spence and David “GI”Jenkins tell us. I think the statin skeptics ought to listen. As an ardent defender of statins, I don’t like these skeptics who not only leaves their audience armless but even confuses them on important issues such as dietary cholesterol.

    “Recent media reports reflect the remarkable effectiveness of the sustained propaganda campaign of the egg producers’ lobby. Not only in Canada, but around the world, the public, nutritionists and even physicians are increasingly accepting of the notion that dietary cholesterol is not important”

    “Focusing on fasting serum cholesterol levels misses the bulk of the problem. Even though serum cholesterol rises very little after a meal, dietary cholesterol increases the susceptibility of LDL-C to oxidation, vascular inflammation, oxidative stress, and postprandial hyperlipemia and potentiates the harmful effects of saturated fat, impairs endothelial function, and increases cardiovascular events”.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989358/

  11. Mie

    Richard, once again, your resort to talking BS.

    1) There’s no comparative study suggesting that Ornish (or low fat vegan diet by any other name) is superior. There’s evidence showing the benefits of Med, more so than with any other diet (see Mente et al 2009), but all in all, the idea of one single dietary approach being superior isn’t founded in scientific evidence. However, there are a few key issues (plenty of vegetables/legumes/nuts, quality fat in moderation, avoid excess meat & especially processed meat etc. etc.) which are in common to many successful approaches – e.g. Med and Portfolio.

    2) Esselstyn’s comment shows the man has no clue. Yes, PREDIMED didn’t show that much benefit, the only statistically significant difference being in strokes. But it certainly didn’t “promote heart disease”. Esslestyn is either lying or is woefully incompetent when it comes to reading research literature.

  12. Doc´s opinion

    Richard
    The main conclusion of a recent meta-analysis published last year in the British Medical Journal was, quote:
    “Higher consumption of eggs (up to one egg per day) is not associated with increased risk of coronary heart disease or stroke.”
    http://www.bmj.com/content/346/bmj.e8539

  13. Mie

    Axel, you do realize that Richard’s just going to have a sissy fit and spam that same ol’ BS about “darwinian foundation” and animal studies, instead of looking & criticizing the meta-analysis (since he simply can’t read research literature)? Even though it directly contradicts his absurdities such as these

    “Instead, lets pretend that Egg center’s gimmicks, feeding egg yolks to overweight diabetic people who are not sensitive to extra dietary cholesterol, that is, is the last word on dietary cholesterol”

    (Richard, the meta-analysis showed that increased egg consumption INCREASES the risk of CHD in diabetic patients …)

    So yes, moderate egg consumption doesn’t seem to harm (nor yield benefits, for that matter) in healthy individuals. However, if you’re diabetic and/or suffer from CVD, be careful.

  14. Doc´s opinion

    Richard.

    I don’t disagree with you that a very low fat diet may reduce the risk for developing atherosclerosis.
    However, there is still a lot of residual risk among those with low LDL cholesterol.

    Look at the results from the TNT-trial for example (and other statin trials for that matter): http://www.ncbi.nlm.nih.gov/pubmed/15755765.

    These were patients with stable corornary heart disease. Mean LDL cholesterol was 77 mg/dl (2.0 mmol/l) with 80 mg atorvastatin, vs. 101 mg/dl (2.6 mmol/l) with 10 mg atorvastatin. After a median follow-up of 4.9 years, the primary end-point occurred in 10.9% of the 10 mg atorvastatin group, and 8.7% of the 80 mg atorvastatin group (HR 0.78, 95%CI 0.69–0.89, p < 0.001). So, a lot of end-points despite a mean LDL cholesterol of 77 mg/dl (2.0 mmol/l).

    So, if we are going to adress this residual risk, we will have to look further than the LDL cholesterol. It would be naive to believe that LDL cholesterol is the only thing that matters.

  15. Low-fat Richard

    Mie,

    I have problems with your stance. To my knowledge there’s no other diet than that of the Ornish approach that would be in congruent with LDL receptor hypothesis. Med diet cannot provide physiologic cholesterol levels for most adult humans, it’s too high in fat. And yes, I know olive lowers cholesterol next to butter or beef, but if I was to increase my consumption of oils, my cholesterol levels would go up, since I have low cholesterol already (olive oil is 14% SFA).The studies you cited come within obese, high-risk population, the usual end-point being weight-loss. We need to look people that are free from chronic disease to learn about disease prevention. I certainly would not be happy walking around LDL above 2mmol/l. This is not to say that I would be against Med diet. The Crete diet of the 1940s with only 7% of calories coming from animal sources certainly served the folk in Crete well. However, I think it’s just utter nonsense to claim that Ornish is on par (or inferior) with the Med diet. Ornish diet is on the other planet; and people adhering to it can reverse and prevent wide variety of chronic disease. There’s not a single dietary intervention on the face of this planet which would have shown regression of CHD with the high-fat approach.

    Esselstyn operates with another paradigm as opposed to you. He is soon with a study where the recurrent rate of events on people with diagnosed CHD was 1/200. The one exception did not follow his rules and went overboard with salt. Nearly all patients were able to stop progression of their disease and many of the showed reversal (200 patients). Had Ornish or Esselstyn coached the PREDIMED “low-fat” reference group, maybe some lives would have been saved. The authors of the PREDIMED study were not too interested in saving lives.

    The common feature for a healthy diet is that is almost solely based on complex carbohydrates, ~80% of calories in the form carbohydrate.

    The rice diet program
    http://www.ricediet.com/

    Pritikin
    http://www.pritikin.com/

    Ornish
    http://www.ornishspectrum.com/

  16. Low-fat Richard

    Axel,

    highly problematic meta-analysis. For several reasons. Ancel Keys showed already in the 1960s that if the within-person variation is larger than the between-person variation, which is common in homogenous populations where everyone consumes a similar diet, then this will especially bias the findings towards a null association. For example, in a homogenous population with a between-person variation of between 2 to 6 eggs per week on average, the variation of intake of an individual consuming on average 4 eggs per week maybe between 1 to 7 eggs per week. If this person’s diet is measured at a high or low point they will be misclassified into a high or low range of intake, typically biasing the results towards a null association (see Kromhout et al “The confusion about dietary fatty acids recommendations for CHD prevention” 2011).

    Another concern is related to the fact that observational studies addressing the association between diet and blood cholesterol and cardiovascular disease dating back to at least the early 1950s have been complicated by reverse causation. It is well documented that people will lower intake of cholesterol and saturated fat in response to elevated blood cholesterol. This is known to bias studies towards finding an association between a higher intake of cholesterol and saturated fat and lower blood cholesterol levels. This would also likely similarly bias the results for the association between intake of cholesterol and saturated fat and the risk of cardiovascular disease.

    One other major concern is that most studies do not compare saturated fat to appropriate substitutes such as complex carbohydrates, and is instead compared to all other sources of calories combined, which is predominantly junk food.

    Moreover, do not miss the last latest meta-analysis on eggs published in May 2013 in the journal of Atherosclerosis.

    Egg consumption and risk of cardiovascular diseases and diabetes: A meta-analysis

    “Our study suggests that there is a dose-response positive association between egg consumption and the risk of CVD and diabetes”

    http://www.atherosclerosis-journal.com/article/S0021-9150(13)00243-8/abstract.

    I, by no means, meant to spam your forum, Axel. If you wish that I don’t contribute to your blog in the future, just let me know, and this will be my last pots.

    Best,
    R

  17. Mie

    “Mie, the idea that Ornish would in par with med diet is ridiculous.”

    And yet, you yourself state evidence against the feasibility of Ornish:

    “In Gardner et al, people assigned to read the Ornish book, ate 30% of their calories from fat and had very little resemblance to Ornish diet.”

    And this happened in a trial where compliance rates & results in dietary intervention are BETTER than in real life. In addition, it’s pretty much a no-brainer that a diet that produces results X in clinical setting with compliance rates of Y isn’t as recommendable as a diet that produces results 0,75X with compliance rates of 2,5Y. That’s the reason why e.g. the new Scandinavian dietary recommendations are more flexible than ever before.

    “Well, nothing of this matter in clinical praxis, since doctors such as Axel can learn to basics of the program and offer it to their patients with high motivation.”

    To whom it may be suited. For those who can’t do it, something else.

    Richard, it’s the VERY basic rule of science that if the observations of the results in real life don’t back up the expected benefits (from short small-scale RCT’s), you realize the need to go back to the drawing board. The crying and moaning about people “doing it wrong” leads nowhere.

    “Moreover, the Ornish approach has huge potential in patients from cultures with familiarity with the dietary paradigm (Asia, Central Africa, etc). It’s easy to tell a Japanese patient to start eat like his poor rural cousins or grandparents.”

    Which just means that we need a multitude of approaches with flexibility.

  18. Mie

    Axel, bear in mind the difference that Richard is talking aboutf life-long risk accumulation in people with no CVD and you’re talking about people with established CVD. You can’t really expect the latter to have zero risk whatsoever.

    However, I too would like to point out that Richard’s idea of risk modification ever accounting for only LDL in real life setting is … well, daydreaming. People get treated on the basis of clinical evidence from studies, not extrapolations of what we could achieve if things were different. I suspect we’re NEVER going to see LDL levels like that (1,5 mmol/L) on a population level.

  19. Mie

    “I have problems with your stance. To my knowledge there’s no other diet than that of the Ornish approach that would be in congruent with LDL receptor hypothesis. Med diet cannot provide physiologic cholesterol levels for most adult humans, it’s too high in fat.”

    Err, you do realize that unsaturated fat ENCHANCES LDL receptor activity? This explains why unsaturated fat has been consistently shown to REDUCE LDL levels in human.

    “And yes, I know olive lowers cholesterol next to butter or beef, but if I was to increase my consumption of oils, my cholesterol levels would go up, since I have low cholesterol already (olive oil is 14% SFA)”

    Perhaps. Perhaps not.

    “The studies you cited come within obese, high-risk population, the usual end-point being weight-loss.”

    As do the studies you refer to. In addition, what evidence we have of Ornish in secondary prevention is based on multi-factorial approach, so we really can’t tell that much about its individual part (diet).

    “We need to look people that are free from chronic disease to learn about disease prevention.”

    That is a start. Then the hypothesis formed needs to be tested.

    And that is the part where you fail, simply because you choose to ignore this part.

  20. Mie

    And yet another systematic review on eggs:

    http://ajcn.nutrition.org/content/early/2013/05/15/ajcn.112.051318.abstract

    “This meta-analysis suggests that egg consumption is not associated with the risk of CVD and cardiac mortality in the general population. However, egg consumption may be associated with an increased incidence of type 2 diabetes among the general population and CVD comorbidity among diabetic patients.”

  21. Low-fat Richard

    Mie,

    I don’t fail. For the first, the Ornish trial exists already, but even if didn’t, we don’t need trials for everything. It’s good to have them but we can use our logic and fill the missing holes even without them. There’s not a single trial that has established the benefits of smoking cessation (all three trials that tested it failed), lack of exposure to asbestos, seat belts, etc. Trials belong to pharmacology, excessive obsession about them is a thingy of the low-carb/Taubes crew, people who do not believe in the darwinian legacy.

    The diet story is here, by Brown and Goldstein (1985):

    “Several lines of evidence suggest that plasma levels of LDL-cholesterol in the range of 25-60 mg/dl (total plasma cholesterol of 110 to 150 mg/dl) might indeed be physiologic for human beings. First, in other mammalian species that do not develop atherosclerosis, the plasma LDL-cholesterol level is generally less than 80 mg/dl. In these animals the affinity of the LDL receptor for their own LDL is roughly the same as the affinity of the human LDL receptor for human LDL, implying that these species are designed by evolution to have similar plasma LDL levels. Second, the LDL level in newborn humans is approximately 30 mg/dl, well within the range that seems to be appropriate for receptor binding. Third, when humans are raised on a low fat diet, the plasma LDL-cholesterol tends to stay in the range of 50 to 80 mg/dl. It only reaches levels above 100 mg/dl in individuals who consume a diet rich in saturated animal fats and cholesterol that is customarily ingested in Western societies”

    I think it’s worthwhile to point out that we do not have fundamental disagreements. It’s just that I look eagerly at the global epidemiology, atherosclerosis research and animal models, whereas you emphasize the evidence from trials and prospective cohorts mostly from USA: This is good evidence, but I don’t want rely on that piece of evidence alone. So basically, our differences comes down to the fact that I emphasize whole-starches as the fundamental part of a healthy diet, whereas you follow the lead of prominent Western epidemiologist who emphasize PUFAs and low GI as the foundation for a healthy diet. I am more for Burkitt, Ornish and Brown & Goldstein.

    The last time Michael Brown gave dietary advice that I know was in 2006 when he emphasized the importance of low-fat, low cholesterol diet. It’s sad to see that this kind of advice that has kept plenty of population at bay from chronic illness is now being ridiculed by plenty of health professionals. I am personally fascinated by the rural cultures around the world (Central-Africa, Asia, etc) where people have eaten very low-fat, starch based diets, shown very low cholesterol levels (TC 3-3.5mmol/l) and almost complete absence of chronic disease. For example, the rough estimates CHD mortality among blacks in Soweto South-Africa was once 0.2%, an extremely low proportion even allowing for uncertainties. In Europe, in the Seven Countries Study, for those in the Mediterranean countries and inland the age-standardised 25-year CHD mortality percentages were 4.7% and 7.7%, respectively. The proportions reported for countries in Northern Europe and for the USA were far higher.

    And, yes, I know oils have isolated components that lower cholesterol, it’s just that food is package deal. Ornish has written well about oils; 2-piece writing:

    The Great Olive Oil Misconception — Dr. Ornish Responds

    http://www.rd.com/health/the-great-olive-oil-misconception-dr-ornish-responds/

  22. Low-fat Richard

    ^A problematic meta-analysis for several reasons.

    Firstly, the association between egg intake and the risk of cardiovascular disease is meaningless without considering suitable substitutes for eggs. As a lower intake of eggs implies a higher intake of other foods in order to maintain caloric balance, the effect that egg intake has on coronary heart disease depends on which foods eggs are substituted for. For example, data from the Nurses’ Health Study, one of the largest studies included in these meta-analyses suggested that replacing one serving of nuts, but not red meat and dairy with one serving of eggs per day is associated with a significantly increased risk of coronary heart disease.The findings from this meta-analysis should therefore be interpreted with caution as eggs may have been primarily compared to processed foods and other animal foods which make up the majority of caloric intake in developed nations.

    Another potential important finding that has contributed to the knowledge of the dangers of eggs are the results from studies that were carried out on populations with a low habitual cholesterol intake, such as vegetarian populations. Frequent consumption of eggs was associated with a more than 2.5 increased risk of fatal coronary heart disease in the Oxford Vegetarian Study and also an increased risk in females in the Adventists Mortality Study.The characteristics of the participants in these studies differ from that of most other studies, not only because of the their lower habitual intake of dietary cholesterol, but also because of their lower rates of obesity and typically healthier overall diet. Therefore separately analyzing egg intake in this subgroup of the population may be of significant importance. The authors of a paper from the Nurses’ Health Study and the Health Professionals Follow-Up Study described the potential importance of addressing egg intake in people with very low habitual cholesterol intake and how their study may have been inadequate to test this hypothesis:

    “One potential alternative explanation for the null finding is that background dietary cholesterol may be so high in the usual Western diet that adding somewhat more has little further effect on blood cholesterol. In a randomized trial, Sacks et al found that adding 1 egg per day to the usual diet of 17 lactovegetarians whose habitual cholesterol intake was very low (97 mg/d) significantly increased LDL cholesterol level by 12%. In our analyses, differences in non-egg cholesterol intake did not appear to be an explanation for the null association between egg consumption and risk of CHD. However, we cannot exclude the possibility that egg consumption may increase the risk among participants with very low background cholesterol intake”.

    Chicago Western Electric Study which found that while dietary cholesterol was associated with a significantly increased risk of coronary heart disease in lean men over and above the adverse effects it has on serum cholesterol, increased intake had little appreciable effect on men with a greater BMI and body fatness.

    Evidence suggests a significant benefit of replacing eggs with whole plant foods, including fruits, vegetables, whole grains and nuts.As Spence and colleagues pointed out in regards to recent controversy surrounding dietary cholesterol and eggs:

    …the only ones who could eat egg yolk regularly with impunity would be those who expect to die prematurely from nonvascular causes.

    In addition, I found a rather illustrating n = 1 case study on eggs which dealt with a hyper-responding individual:

    A case report found that a 30-year-old woman with a healthy body weight who had been following a carbohydrate restricted diet for three and a half years had developed xanthomas on her hands and a chronically elevated serum cholesterol level of 940 mg/dl.44 The composition of the woman’s diet was reported as follows:

    “Each day she had consumed eight to 12 eggs, one or two lean steaks or half a small chicken and, half to one litre of milk. Sometimes some cottage cheese or tomatoes enriched the menu and, on rare occasions, fruit. She completely avoided butter, bread, potatoes, rice, noodles, alcohol, or any other food or beverage containing carbohydrate. The daily cholesterol intake, which was mainly derived from the egg yolks, was about 3500 mg. The total calorie intake was about 8-4 MJ (2000 kcal) (35 % protein, 55 % fat, and 10 % carbohydrates, polyunsaturated fat:saturated fat (P:S) ratio=0 26).

    The woman was advised to change her diet, and in particular to stop eating eggs. After 16 days her serum cholesterol dropped to 750 mg/dl, and after several years dropped to 188 mg/dl and the lipid deposits on her skin had cleared up. This woman’s diet induced xanthomas and chronically elevated cholesterol resemble the characteristics of people with homozygous familial hypercholesteromia. The authors pointed out:

    “Mann and andrus produced high cholesterol levels in adult macaccus rhesus monkey fed on a diet rich in egg yolks. After two and half years on this regimen the monkey developed xantomatosis and when killed year later exhibitet extensive atherosclerosis. Similar results were reported by Gresham et al”.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1639741/?page=1

  23. Low-fat Richard

    Yes, exactly. Thanks Mi(k)e for saving my time. The mean age at the randomization in typical statin trial is 63. There’s the residual risk. However, I’d like to point out that there will be no talk about residual risk once the PCSKY-9 inhibitors enter the market. This agents allow LDL reduction down to 20′s and 30s (mg/dl). People with existing disease need to treated more aggressively.

  24. Low-fat Richard

    What Garner et al showed was how obese people respond after reading a popular diet book. I am about being a force of change. There’s not a single people eating according to Ornish approach if they do not know what to expect. I want to change the meat-dairy laden culture to starch/plant-based culture. I am about educating people. This is the whole purpose of public measure’s for health, education, that is. What would have been the outcome if the saturated fat laden diets of the developed world of the 1960s would have continued? Luckily health educators did not just wait, sit and observe.

    “It is a reasonable inference that the sizable decline in per capita egg consumption in the United States in recent decades, and hence in per capita total cholesterol intake, has been one important component of the improved dietary patterns leading to a fall in mean serum cholesterol concentration in the adult population from ~ 6.08 mmol/L (235 mg/dL) in the 1950s to ~ 5.30 mmol/L (205 mg/dL) in the 1990s, and to the concomitant sustained marked reductions in mortality rates from CHD, all cardiovascular diseases, and all causes.”

    –Jeremiah Stamler, MD, the Chairman of the Department of Preventive Medicine of the Feinberg School of Medicine (Northwestern University), 1998

    Between 1970 and 1995 annual consumption decreased from 310 to 235 eggs per person in US.

    Why have total cholesterol levels declined in most developed countries?
    http://www.biomedcentral.com/1471-2458/11/641

  25. Doc´s opinion

    The efficacy of PCSK-9 inhibitors is currently being tested in large scale clinical trials. Until we have the results, it´s an untested hypothesis that further lowering of LDL cholesterol will improve prognosis of individuals with cardiovascular disease. Let´s hope you are right Richard that residual risk will be history when we have the trial results. Remember though that additional lowering of LDL-C by by adding ezetimibe to statins has not been proven to be beneficial in clinical terms.

    Actually I am principal investigator at one of the FOURIER – trial sites. FOURIER is a huge clinical trial testing the efficacy of PCSK-9 inhibition among patients wit a history of stroke or myocardial infarction.

  26. Richard

    Sounds awesome, Doc.

    The people at UT Southwestern medical center (Brown & Goldstein, etc) seem to be very confident with the approach of further lowering LDL.

    “If we get LDL low enough, you cannot develop atherosclerosis, no matter how much diabetes, hypertension or smoking you do” (15min.20sec).

    –Darren McGuire
    http://www.youtube.com/watch?v=DFMtoafT70c

    BTW, Doc! Have you met some of these big names in atherosclerosis research such as Brown & Goldstein, Evan Stein, Steinberg, etc.

    Best,
    R

  27. Mie

    Richard, if you’re not citing the source for the abovementioned, you’re plagiarizing. The text is copy/pasted in pieces from here

    http://healthylongevity.blogspot.fi/2013/04/cracking-down-on-eggs-and-cholesterol.html

    Unless, of course, you’re the blogger Healthy Longevity, in which case nevermind.

    I’ll address the points mentioned once you either ask Axel to remove the plagiarized part or confirm that you are the author.

    And of course: Axel, I recommend that you address the issue, too. Of course we can quote other people, but credit where credit is due.

  28. Mie

    “What Garner et al showed was how obese people respond after reading a popular diet book.”

    And these people benefitted most from reading Atkins’ book. :-)

    And if you want results showing something different, check out e.g. Dansinger et al (2005), “Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial”, where Ornish produced the greatest weight loss but in terms of CVD risk factors there were virtually no differences after 12 months of intervention.

    So there.

  29. Doc´s opinion

    Thanks Mie. Point taken. For those of you who are copy/pasting or quoting in general, please cite the source.

  30. Mie

    Richard, I’ll continue here to avoid the messages becoming too narrow to read properly (damn you, WordPress!)

    “I don’t fail. For the first, the Ornish trial exists already, but even if didn’t, we don’t need trials for everything. It’s good to have them but we can use our logic and fill the missing holes even without them. There’s not a single trial that has established the benefits of smoking cessation (all three trials that tested it failed), lack of exposure to asbestos, seat belts, etc. Trials belong to pharmacology, excessive obsession about them is a thingy of the low-carb/Taubes crew, people who do not believe in the darwinian legacy.”

    Once again, BS. Of course, you can’t always have trial evidence at hand for various reasons. However, when we have them, that’s where the focus should be primarily. Not without criticism, no, but we’re talking about the golden standards here. If a trial shows no or very little benefit in real life setting, then you can extrapolate all you want – and it’ll still be useless.

    And for Christ’s sake, stop with that “smoking-not-proven-blah-blah” nonsense. We’re talking about something else than urban legends created by cigarette companies!

  31. Mie

    Richard,

    “And, yes, I know oils have isolated components that lower cholesterol, it’s just that food is package deal. Ornish has written well about oils; 2-piece writing:
    The Great Olive Oil Misconception — Dr. Ornish Responds
    http://www.rd.com/health/the-great-olive-oil-misconception-dr-ornish-responds/

    1) You do realize that Ornish isn’t arguing that oils are unhealthy? Hell, do you even READ what you post?

    2) Ornish’s post is creating a false dilemma. Just because cold-pressed canola oil may be healthier, doesn’t mean that olive oil is unhealthy. This isn’t the case of either/or, but BOTH/AND. There’s room for all these oils (canola, olive, fish, flaxseed) in a healthy diet.

  32. Richard

    Mie & Doc,

    I should have provided a link. HealthyL is a very good friend who has given me permission to utilize and use his texts how I wish. This was the first time ever I did not cite him properly nor provided the link, I did this because I utilized mostly my own material in Axel’s blog, and used HealthyL’s egg post only for time saving purposes. However, at the risk of me having misunderstood his intentions, I forward this conversation to his email, and if he feels I did wrong, he can let you know, Doc. Right now, given my matehood with HealthyL, I suggest Doc lets the text stay intact as it is, especially since everybody knows now where the source came from.

    Mie,

    I do not argue smoking is healthy or harmless, but as HealthlyL elaborated in DietDoc’s blog, there are actually 3 such trials that tested the hypothesis that smoking cessation would lower the risk of lung cancer mortality. All 3 trials failed to produce statistically significant findings despite reporting significant reductions in smoking prevalence in the group that received counselling on smoking cessation. These trials include the Whitehall Study, the Lung Health Study, and MRFIT, which included in total over 20,000 participants and up to 20 years of follow-up. This makes these trials considerably larger in both in terms of participant size and length of follow-up than the trials that focused on replacing primarily saturated fats with polyunsaturated fats. The largest of these 3 trials found that the number of lung cancer deaths were actually 15% greater, albeit not statistically significant in the group that received counselling on smoking cessation.
    http://onlinelibrary.wiley.com/doi/10.1002/1097-0142(20001201)89:11+%3C2422::AID-CNCR16%3E3.0.CO;2-E/full

    The relative failure of these smoking cessations trials can be considered a very good example of why all forms of evidence need to be considered when evaluating a hypothesis, not just a few data points from a few randomized controlled trials. The lack of statistically significant favorable findings in the group that received counselling on smoking cessation has been explained by a lack of follow-up time sufficient to achieve the maximum benefits of smoking cessation (which is believed to be more than 2 decades), lack of participant size, a smaller than anticipated number of participants in the group that received counselling that quit smoking, and a greater than anticipated number in the group that did not receive counselling that quit smoking. These limitations are very similar to those that plague the trails that attempted to test the diet-heart hypothesis.

    Ornish thinks oils are harmful and they provide calories people do not need. One table spoon of oil has 120 easily digested, fiberless calories. You read more about how Ornish feels about oils in his landmark book “Ornish program for reversing heart disease”. Moreover, Ornish cites studies by Vogel who found that olive oil significantly reduces blood flow to different parts of your body.

  33. Mie

    “Mie,
    I do not argue smoking is healthy or harmless, but as HealthlyL elaborated in DietDoc’s blog, there are actually 3 such trials that tested the hypothesis that smoking cessation would lower the risk of lung cancer mortality.”

    Even though this is completely off-topic, I’ll address this briefly.

    1) MRFIT was a multi-factorial trial which wasn’t powered to detect such individual benefits in individual risk factors. Follow-ups have shown that the primary finding was – indeed – the difficulty of smoking cessation: relapse after relapse leads to the fact that people receiving special guidance fared no better than people receiving standard advice.

    2) The Whitehall Study: see the latest results of the follow-up which indicate clear (albeit modest, considering the expectations) benefits.

    http://www.ncbi.nlm.nih.gov/pubmed/1573365

    The trial was plaqued by the “usual” problems: intermittent “smoking-not smoking-smoking” effect, increased cessation among control group etc. etc. Not to mention the – I’d argue rather eccentric – choices for counselling, e.g. the fact that members of the intervention group who decided to switch from smoking cigarettes to smoking pipe or cigars weren’t discouraged against this …

    3) The Lung Health Study: which one? There were three LHS’s. IF you’re referring to the first one, bear in mind that primary endpoint wasn’t lung cancer mortality: the purpose was to determine whether a programme incorporating smoking intervention and use of an inhaled bronchodilator could positively affect the rate of decline in the forced expiratory volume in one second (FEV1). And the results weren’t disappointing for smoking cessation – see this

    http://bit.ly/19RzTPO

    Your blogger friend should spend his time better in the future.

  34. Low-fat Richard

    Mie,

    my blogger friend addressed the findings from tobacco trials as a response to diet-heart denialism and obsession with RCT -trials in the context of lifestyle issues. As I concluded, all 3 trials that have tested whether smoking cessation works have failed. You try to confuse the point being made as you often do. When things don’t go in your way, you resort to creating confusion, bad manners and outward nastiness. I did not not tout these findings as a strong piece of evidence.

    Shall we go into the details of your favorite Atkins paid RCT’s? I have my favorite trials too; the interpretations made in these trials receive whole new meaning when Atkins money is absent. The truth is that Atkins would loose top-down next to heroin or amphetamine therapy, the latter was actually used as weight-loss medication. Small doses of amphetamine would cause lack of appetite, weight loss, enhancement of all metabolic markers and most IMPORTANTLY it would not result in adverse outcome with LDL cholesterol unlike the Atkins diet. Why would someone create a havoc in their arteries and follow the Atkins diet to achieve short-term weight-loss when there are much safer ways of loosing weight such as amphetamine therapy.

    Hernandez et al demonstrated that Atkins diet resulted in 10% increase in LDL cholesterol despite 6kg weight-loss shown in the Atkins group. Similar weight-loss in “low-fat” group but LDL plummeted 6%. Rarely do we see any improvement in LDL cholesterol among low-carvers, despite the weight-loss. To give you some context, the Ornish program result in -40% drop in LDL cholesterol in average patient in 12-months. This has been demonstrated in multiple sites in multiple hospitals throughout the USA:
    http://www.ornishspectrum.com/wp-content/uploads/effectiveness-efficacy-of-an-intensive-cardiac1.pdf

    Now, I don’t argue against you: fat people are extremely good at keeping up with their favorite high-fat foods that made them fat in the first place, and that’s why see better compliance with Atkins in RCTs studies where patients have been provided very little counselling. However, I don’t agree with you in the sense that the public measures for healthy diet should be based on the preferences of obese people on prescription drugs. After all, a tightly controlled feeding experiment in Japan showed that low-carb diets make up an efficient tool in ruining the sugar metabolism of healthy, lean people brought up on low-fat diets. I don’t think the RCTs you have referred to are pinnacle of good science and the last word in nutrition.

    In regards to eggs, people in developed countries are at very high risk developing coronary heart disease at some point in life. One egg here and there at the top of diet already laden with dietary cholesterol does very little in modulating this risk. However, this does not imply that “eggs are ok in moderation”. My CHD risk would increase did I start consuming one egg per day. Armstrong and colleagues conducted an experiment ‘designed to demonstrate a null point of the effect of dietary cholesterol on the arterial intima’, by comparing a group of rhesus monkeys fed a cholesterol-free diet with a group fed cholesterol equivalent to that found in only half of a small egg in the average human diet of 2,000 calories per day (43µg/kcal). However, even when fed in very small amounts dietary cholesterol still had a significant adverse effect on these monkeys arteries after a period of only 18 months. Armstrong and colleagues concluded:

    No null point for the effect of dietary cholesterol on arterial intima was found even at an intake level far below that conventionally used for the induction of experimental atherosclerosis in the nonhuman primate. The intimal changes found in response to very low cholesterol intake imply that subtle qualitative alterations in lipoproteins are of critical importance to our understanding of lesion induction

    I think we ought to never forget the Darwinian foundation of our biomedical research paradigm while interpreting observational studies within high-risk populations.

    Short-term low carbohydrate/high-fat diet intake increases postprandial plasma glucose and glucagon-like peptide-1 levels during an oral glucose tolerance test in healthy men.
    http://www.ncbi.nlm.nih.gov/pubmed/22669333

    Kolhydratfattig kost ökar fria fettsyror och LDL-kolesterol
    http://ltarkiv.lakartidningen.se/2010/temp/pda37988.pdf

  35. Mie

    “my blogger friend addressed the findings from tobacco trials as a response to diet-heart denialism and obsession with RCT -trials in the context of lifestyle issues. As I concluded, all 3 trials that have tested whether smoking cessation works have failed. You try to confuse the point being made as you often do. When things don’t go in your way, you resort to creating confusion, bad manners and outward nastiness. I did not not tout these findings as a strong piece of evidence.”

    Err Richard: you do realize that I a) stated it was off-topic but decided to dissect the claim since I don’t really like BS. Thus I b) pointed to evidence showing the your pal simply wasn’t correct. Now, this changes the actual issue at hand IN NO WAY. Therefore, you really haven’t any reason to complain.

    If you want to continie discussing the original issue – or rather the issue WE started talking about – at hand (diet compliance), do so. Or if you want, I can have a look at HL’s commentary about eggs.

    P.S. Just try to focus, anyway. The ramblings above about Atkins & amphetamine & your personal favourite, the “Darwinian foundation” of which you understand nothing about simply make no sense.

  36. Low-fat Richard

    Mike,

    I don’t need to understand much about the Darwinian foundation. I just need to remind you about it. I think it’s enough, I understand the main principles as addressed by Stamler (2010): dietary cholesterol promotes atherosclerosis on numerous different omnivorous species, the most relevant being non-human primates. Dietary cholesterol has unfavorable effects on serum lipids and induces atherosclerotic lesions. Furthermore, there was no evidence of a threshold for dietary cholesterol with respect to an adverse effect on arteries. Long-term feeding of cholesterol in relatively small amounts has actually been shown to induce atherosclerosis in rabbits, chickens, pigeons and monkeys despite only small or insignificant increases in serum cholesterol. Several prospective epidemiological studies found direct relations of dietary cholesterol to CHD independent of serum total cholesterol. If you understood these principles you would probably not be trolling about eggs being ok in moderation. The current guidelines show no green light for more than 2 eggs per week and I reckon that wasn’t what you meant with “moderation”.

    Diet-heart: a problematic revisit
    http://ajcn.nutrition.org/content/91/3/497.full

    HealthyL is having a holiday, but I ask him to get back to you on the cigarette trials. Keep an eye on this blog section at least the next few weeks.

  37. Mie

    Richard, you can ask him about the cig trials if you wish, but I’m not going to address the issue again in this thread. It’s off-topic, just like I stated, and has gone on long enough. If you can’t be bothered to check the studies yourself, that’s fine by me. If your blogger friend suffers a blow to his ego as a consequence, that’s fine by me, too. :-)

  38. Low-fat Richard

    Axel,

    I apologize if this somewhat off-the-main-topic but topics may sometimes receive another tinge or an angle. I feel I still need to address this issue.

    Mie,

    I think your arguments about cigerette smoking trials and healthy diet are somewhat flawed. The failure of smoking cessation trials is a fact that ought give us some perspective. Trials are not the last word when it comes to lifestyle. Katan elucidated this very well:

    “In addition, evidence from epidemiologic, metabolic, and laboratory studies confirms that high intakes of saturated fat do cause heart disease. Ignoring this evidence leads to absurd consequences. For instance, our knowledge of the ill effects of cigarette smoking rests purely on epidemiologic, metabolic, and laboratory studies, whereas evidence from clinical trials is largely lacking,The same holds true for the ill effects of physical inactivity, the failure to use seat belts, the consumption of toxic chemicals in foods, and asbestos exposure. None of these conditions has been proven to be unhealthy in clinical trials performed according to the standards for pharmaceutical drugs. I believe that, in all of these cases, we should consider the totality of the evidence, and the totality of the evidence overwhelmingly indicts saturated fat as a cause of heart disease, just as it indicts cigarettes”

    http://ajcn.nutrition.org/content/84/6/1551.full

    You tried to confuse the reader with the main points I made. Cigarette trials have been a failure as indirectly noted by a leading diet-heart scholar. Your interpretations on these trials are most likely flawed; words are cheap and you are not an expert.

    Now, I did not make this up, but there’s is only approach to diet that is in congruent with the LDL receptor hypothesis and that is the Ornish/McDougall approach; we are designed by evolution to function with exceedingly low levels of LDL cholesterol. This is a principle and Atkins paid RCT’s with little counselling to patients and straw-man diets fed to control groups does not change this principle. If we fail to function with very low levels of LDL, like free-ranging mammalians, problems are expected at later stage in life. I have nothing against veggie oils and nuts, they are good plant-foods, but I just don’t believe they are going provide low LDL levels if not used in moderation. Naturally low-fat complex carbohydrates should make the absolute bulk of the diet. Atkins paid lifestyle-trials done on obese people on prescription medication is just one piece of evidence. The preferences of obese people should not dictate our reasoning around healthy, longevity promoting diet., Because Roberts did not provide this information to her audience as I did, her audience does not have much options beyond starting to take statins at very early in life. Otherwise, premature death and/or jeopardized quality of life due to chronic disease is likely to be expected. I have nothing against statins, as concluded by William Roberts, they are essential for people eating any other diet besides the plant-based, low fat one (W Roberts prefers the McDougall approach). This may sound extreme, but I did not make this up. These are principles, that will never change (pharmacological agents may be change). So, changing the dietary preferences of obese people on prescription drugs is indeed very hard, but let’s not get fooled by that.

  39. Doc´s opinion

    Apology accepted. I guess nobody’s going to read these lengthy off-topic discussions anyway.

  40. The main point I was trying to make when I mentioned the smoking cessation trials was that a few trials that fail to produce statistically significant findings does not necessarily negate a particular hypothesis in the presence of certain limitations, and that a number of problems that plagued the smoking cessation trials also plagued the trials that tested diet-heart hypothesis.

    The lack of statistically significant decreased risk of lung cancer in the smoking cessation trials is probably due to several limitations and does necessarily negate nor overrule all other forms of evidence that support this hypothesis. All forms of evidence should be considered. Poor adherence in the experimental groups and unexpected lifestyle changes in the control groups in the smoking cessation and diet-heart trials could partly explain the failure to produce statistical significant findings. Also, the length of follow-up of the smoking cessation and diet-heart trials was likely insufficient to demonstrate maximum benefit. Observational studies demonstrate that the maximum benefit of smoking cessation likely requires more than two decades while medenlian randomization studies demonstrates that the maximum benefit of LDL cholesterol lowering interventions likely requires an entire lifetime.
    http://www.ncbi.nlm.nih.gov/pubmed/9099400
    http://www.ncbi.nlm.nih.gov/pubmed/23083789

    In the Whitehall Study there was an 11% lower rate of lung cancer in the experimental group which did not even come close to statistical significance. Considering the other forms of evidence supporting the hypothesis, this non-significant finding is still typically considered causal. Therefore findings supporting the diet-heart hypothesis should at least be considered even if statistical significance is not necessarily reached.

    When Siri-Tarino et al. considered 7 of the 11 studies included in their original meta-analysis paper that addressed the association between saturated fat and fatal coronary heart disease they found an 18% excess risk that almost reached statistical significance (0.99-1.42). When Stamler considered all 11 studies he found a 32% excess risk despite over-adjustments for serum lipids and a number of other problems addressed in his editorial that would expected to have significantly weakened this finding. Perhaps if Siri-Tarino et al. had also considered all 11 studies the excess risk of fatal coronary heart disease may have been stronger and have reached statistical significance. It is interesting how you refer to the Whitehall Study as producing “clear” benefits but fail to even mention these findings of an association between saturated fat with an increased risk of fatal coronary heart disease despite emphasizing the findings of the original Siri-Tarino et al. meta-analysis.
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943062/
    http://ajcn.nutrition.org/content/91/3/497.full

    I am curious why you appear to be suggesting that the findings for lung cancer mortality rates in the Lung Health Study are irrelevant because it was not a primary end point, yet emphasize the dangers of statins likely based on findings for non-primary end points from the statin trials. Being a smoking cessation trial naturally the findings for lung cancer will be considered and if findings fail to be positive then a better explanation will need to be provided. The Lung Health Study that Richard was referring to was cited within a paper linked in his comment. The 5 year follow-up found virtually no difference in the rate of lung cancer mortality which should only have been expected due to the long follow-up likely required in order to demonstrate benefit. I have not yet found any information of the lung cancer rates in the later follow-ups.

    There is scant evidence that the other modifications made by the experimental group in the MRFIT trial resulted in the paradoxical increased the risk of lung cancer mortality. As the researchers pointed out, the non-significant increased risk of lung cancer mortality was likely due to chance and a longer follow-up may have been required to demonstrate a clear benefit of smoking cessation.
    http://www.ncbi.nlm.nih.gov/pubmed/9099400

    In regards to the MRFIT trial you stated in a previous post:
    “The Multiple Risk Factor Intervention Trial (MRFIT) studied 12,866 high-risk men. An intervention that included dietary advice to reduce cholesterol levels did not significantly reduce mortality due to cardiovascular disease nor all-cause mortality.”
    It is interesting how you conveniently state now that MRFIT was not powered to detect individual benefits in individual risk factors despite previously attributing the lack of statistical significant findings for the primary endpoints at least partly to the dietary advice given. Perhaps your sudden change of mind is due to the inconvenience of the more recent reanalysis of MRFIT which demonstrated a significant decreased risk of CHD and CVD events during the trial and that the non-fatal events during the trial were strongly associated with CVD mortality during the 20 years after the trial ended. This demonstrates that the trial was too short to demonstrate a significant benefit for the degree of change made between the intervention and control groups (it was observed that the participants of the control group also made an effort to improve risk factors).
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541632/

  41. Please ignore that first comment, I will reword it. I was confused by the e-mail that Richard sent to me which had me assuming that the Doc was the one who left the comment, not somebody else.

    The main point I was trying to make when I mentioned the smoking cessation trials was that a few trials that fail to produce statistically significant findings does not necessarily negate a particular hypothesis in the presence of certain limitations, and that a number of problems that plagued the smoking cessation trials also plagued the trials that tested diet-heart hypothesis.

    The lack of statistically significant decreased risk of lung cancer in the smoking cessation trials is probably due to several limitations and does necessarily negate nor overrule all other forms of evidence that support this hypothesis. All forms of evidence should be considered. Poor adherence in the experimental groups and unexpected lifestyle changes in the control groups in the smoking cessation and diet-heart trials could partly explain the failure to produce statistical significant findings. Also, the length of follow-up of the smoking cessation and diet-heart trials was likely insufficient to demonstrate maximum benefit. Observational studies demonstrate that the maximum benefit of smoking cessation likely requires more than two decades while medenlian randomization studies demonstrates that the maximum benefit of LDL cholesterol lowering interventions likely requires an entire lifetime.
    http://www.ncbi.nlm.nih.gov/pubmed/9099400
    http://www.ncbi.nlm.nih.gov/pubmed/23083789

    In the Whitehall Study there was an 11% lower rate of lung cancer in the experimental group which did not even come close to statistical significance. Considering the other forms of evidence supporting the hypothesis, this non-significant finding is still typically considered causal. Therefore findings supporting the diet-heart hypothesis should at least be considered even if statistical significance is not necessarily reached.

    When Siri-Tarino et al. considered 7 of the 11 studies included in their original meta-analysis paper that addressed the association between saturated fat and fatal coronary heart disease they found an 18% excess risk that almost reached statistical significance (0.99-1.42). When Stamler considered all 11 studies he found a 32% excess risk despite over-adjustments for serum lipids and a number of other problems addressed in his editorial that would expected to have significantly weakened this finding. Perhaps if Siri-Tarino et al. had also considered all 11 studies the excess risk of fatal coronary heart disease may have been stronger and have reached statistical significance.

    I find it very difficult to comprehend that someone who is apparently trying to save lives like the Doc would fail to mention that saturated fat was associated with the number one cause of death in the world despite emphasizing the findings of the original Siri-Tarino et al. meta-analysis.
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943062/
    http://ajcn.nutrition.org/content/91/3/497.full

    The Lung Health Study that Richard was referring to was cited within a paper linked in his comment. The 5 year follow-up found virtually no difference in the rate of lung cancer mortality which should only have been expected due to the long follow-up likely required in order to demonstrate benefit. I have not yet found any information of the lung cancer rates in the later follow-ups. Just because the findings for lung cancer mortality rates in the Lung Health Study were not necessarily a primary end point does not mean that they are irrelevant and should not be considered. Being a smoking cessation trial naturally the findings for lung cancer will be considered and if findings fail to be positive then a better explanation will need to be provided. Our knowledge of some of the dangers of statins which the Doc emphasizes in this post is largely derived findings for non-primary end points from the statin trials.

    There is scant evidence that the other modifications made by the experimental group in the MRFIT trial resulted in the paradoxical increased the risk of lung cancer mortality. As the researchers pointed out, the non-significant increased risk of lung cancer mortality was likely due to chance and a longer follow-up may have been required to demonstrate a clear benefit of smoking cessation.
    http://www.ncbi.nlm.nih.gov/pubmed/9099400

    If this is your opinion of the MRFIT trial perhaps you should be criticizing promoters of low-carb high-fad diets such as the Doc for partly attributing the lack of statistical significant findings for the primary endpoints to the dietary advice given. For example the Doc stated in a previous post:
    “The Multiple Risk Factor Intervention Trial (MRFIT) studied 12,866 high-risk men. An intervention that included dietary advice to reduce cholesterol levels did not significantly reduce mortality due to cardiovascular disease nor all-cause mortality.”
    Interestingly a more recent reanalysis of MRFIT which demonstrated a significant decreased risk of CHD and CVD events during the trial and that the non-fatal events during the trial were strongly associated with CVD mortality during the 20 years after the trial ended. This demonstrates that the trial was too short to demonstrate a significant benefit for the degree of change made between the intervention and control groups (it was observed that the participants of the control group also made an effort to improve risk factors).
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541632/

  42. Low-fat Richard

    Healthy Longevity,

    excellent remarks. Thanks for your contribution. Doc, what do you think about SFA and dietary cholesterol these days? Have you reconsidered your position? After all, not a single public health authority took the S-T meta-analysis seriously. And now, the results from the recent reanalysis of MRFIT has been brought to your attention. Moreover, I’d like to add that the RRs for SFA and fatal heart event that Stamler reported was 1.32 which is on line or even bigger than that of the RRs between passive smoking and lung cancer.

  43. Low-fat Richard

    Doc,

    here’s an MD colleague for you who is also interested in preventative medicine. In the course of three months his cholesterol plummeted from 240 to 150 together with other benefits. An inspiring story for you!

    Forks Over Knives Changed My Health and How I Treat My Patients

    “As the director of prevention and wellness at St. Luke’s Hospital in St. Louis, I had always considered myself knowledgeable about the importance of diet and exercise, tried to eat “healthy,” tried to stay active, and counseled my patients to do the same. My “healthy” diet centered on eating plenty of fruits and vegetables, lean meat, low-fat dairy products, and whole grains (although I wasn’t averse to an occasional bowl of ice cream!)

    http://www.forksoverknives.com/forks-over-knives-changed-my-health-and-how-i-treat-my-patients/

  44. Doc´s opinion

    Richard.

    I´m considering my position all the time. I try to keep an open mind. In terms of saturated fats and cholesterol there´s really nothing to reconsider. I have never doubted that avoiding saturated fats will lower blood cholesterol. We totally agree on that. I also believe that plant based diets are very useful when it comes to preventing heart disease. That´s another thing we agree on. I wish more people could stick to such lifestyle. I do recommend it to my patients and have done so for many years.

    However, there are other issues than blood cholesterol that we have to deal with. For example, many people with obesity and the metabolic syndrome have other problems of metabolic nature. We have to think about insulin resistance, type 2 diabetes and many other issues. Many of these individuals have a hard time sticking with the type of dietary recommendations you favor. They would probably be fine if they could. For these people other types of diets may be helpful.

    So, we have to keep an open mind. We are all different, have different body weight, different metabolism and different preferences. There is no “one size fits all” when it comes to these issues.

  45. Mie

    1) Nicely copy/pasted advertisement. Lucky for you that Axel allows this kind of spamming.

    2) Concerning the point you made to Axel about MRFIT post-trial: if you (or your blogger pal w/ a bruised ego) knew anything whatsoever about conducting an RCT or statistical analysis, you’d understand that a post-hoc analysis of a MULTIFACTORIAL NON-BLINDED trial is not without problems. Check out this article concerning the problems related to post-hoc analysis:

    http://www.medscape.com/viewarticle/409693

    What a post-hoc analysis of MRFIT tells us is another indication that life-style interventions are worth conducting when treating CVD patients and/or people belonging to risk groups. However, this recommendation is primarily based on meta-analyses and/or systematic reviews of RCT data in general – not on problematic re-visits to old data.

  46. Mie

    Heck, I’ll give this a brief look since I’ve got the time.

    1) The first point (the issue of intra/interindividual variation): irrelevant. This issue is well-known but doesn’t render the findings of ANY given meta-analysis obsolete. Or if they do, then … Well, the logical result is that epidemiological evidence per se is obsolete. Is that really the argument here?

    If it is, perhaps you should stop referencing epidemiological evidence when it suits your needs.

    Or even better: perhaps you should go read a book on epidemiology.

    2) The second point (reverse causation): cherry-picking. Yes, of course people will adjust their diets during a period of time. But it is simply illogical and without any foundation to claim that this happens ONLY in one direction. Once again, this is simply unavoidable in observational studies.

    3) The last point (SAFA not compared to appropriate substitutes): ignorance. The reason why carbs are the point of reference (e.g. Mensink et al 2003) is simply a methodological choice. This doesn’t mean that there aren’t differences between the sources of carbs – nor that SAFA shouldn’t be exchanged for complex carbs.

  47. Low-fat Richard

    Mie,

    what was your point? The tobacco trials were a success, and relying solely on evidence from RCT’s goes without problems in the context of life-style? The point that I and HealthyL tried to convey is that it is important to consider all lines of evidence in regards to the link between diet and chronic disease. You seem to have a problem with this? You don’t have to consider anything else beyond RCT evidence if one is to address the effect of a drug, obviously. Now, in regards to findings from MRFIT (including the ad hoc analysis) do you think the advice to reduce dietary cholesterol is not based on good science? What was the problem? I apologize if I get it wrong, but it appears to me that you are the one with difficulties in the ego section (see Katan’s reply to someone with an obvious problem, whatever that problem is).
    http://ajcn.nutrition.org/content/84/6/1551.full

    My advertisement for the plant-based diet to reduce chronic disease and to save lives was simply an opinion of Axel’s colleague from the preventative medicine. Doc is interested in preventative medicine and eager to hear views and opinions to learn more. In fact, I can back my advertisement with the recent position taken by the biggest cross-state hospital chain in the US, Kaiser Permanente:

    Nutritional Update for Physicians: Plant-Based Diets
    http://www.thepermanentejournal.org/files/Spring2013/Nutrition.pdf

  48. Mie,

    1) If the degree of measurement error in a study is so great that the expected result of an association would be near zero even if the hypothesis is correct, this would mean that null findings would do very little to negate a hypothesis as such results were expected. Nevertheless if a positive association is found it could be hypothesized that this finding would have potentially been attenuated due to measurement error and can still provide support for a particular hypothesis.

    Epidemiological evidence is especially useful when there is limited evidence from higher quality forms of evidence and should be considered together with all other forms of evidence. Epidemiological evidence cannot simply be ignored on the basis that it is not perfect, but can carry little weight if null findings were expected even if the hypothesis is correct.

    2) In regards to reverse causation and the diet-heart hypothesis, it is far more likely that the participants in a study with higher cholesterol levels will decrease rather than increase intake of saturated fat in comparison with the participants with lower serum cholesterol levels. As this has been observed to occur at least as far back as the late 1950s (as was the case in the Western Electric Study) after health authorities started recommending limiting saturated fat intake in order to decrease serum cholesterol intake, this may have potentially confounded most research in this area ever since. This has been documented to bias the cross-sectional association between saturated fat and serum cholesterol towards an inverse association.

    As this bias is well document I fail to see how you simply pass this comment off as cherry picking, illogical and without foundation. The chance of this biasing in the opposite direction (high cholesterol causing an increase in saturated fat intake) is very small. You have either ignored the evidence or have not comprehended Richards point.

    If a study finds an inverse cross-sectional association between saturated and fat and serum or LDL cholesterol (as was the case in the “American Paradox”), and this is due to reverse causation it would be expected that there would be an inverse association between saturated fat and heart disease even if the diet-heart hypothesis is correct.

    3) As the great majority of caloric intake in western countries is derived from junk food, it is likely that junk food would largely be the point of reference if the compared source of calories is not specific. If a null association is found between saturated fat or eggs and non-specific sources of calories this suggests that increasing saturated fat or egg intake may confer about as much benefit as increasing intake of junk food. Studies would be more informative if foods or macronutrients are compared with more appropriate sources of calories.

  49. Mie

    And why not comment on this one, too? Just got back from a 10-km-long jog & feeling nice and energetic, so … :-)

    “1) Firstly, the association between egg intake and the risk of cardiovascular disease is meaningless without considering suitable substitutes for eggs.”

    Err, the point of the individual studies included in the meta-analysis was NOT to look at the “best possible option” but to see whether egg intake was associated with increased risk in comparison with a given diet. Complaining about a different focus doesn’t mean the meta-analysis is problematic.

    “The findings from this meta-analysis should therefore be interpreted with caution as eggs may have been primarily compared to processed foods and other animal foods which make up the majority of caloric intake in developed nations.”

    And the same applies to virtually ALL base ingredients of healthy diets. E.g. whole grain products get compared to refined carbs, nuts get compared to processed meat etc. etc.

    “Another potential important finding that has contributed to the knowledge of the dangers of eggs are the results from studies that were …”

    … cherry-picked by you? How does looking at individual studies negate the findings of a meta-analysis of an entire field (or rather, the studies in the field that met the inclusion criteria)??? Certainly not when the studies themselves get a VERY different treatment than studies that report findings different than your preference. E.g. just have a look at the papers & see what kind of questionnaire was used to gather data. Now, compare this what the oh-so-beloved J. Stamler wrote about the crude/out-dated questionnaires used in cohort studies. :-)

  50. Low-fat Richard

    Mie,

    I misread your arguments somewhat. Yes, we agree that it’s worth treating risk patients and those with diagnosed CHD. These people benefit from the treatment in terms of substituting SFA and dietary cholesterol with better alternatives. I am confident everyone else will benefit from replacing SFA and cholesterol with minimally refined plant foods even though we do not have any trials directly verifying this. HealthyL’s argument for the diet-heart is not limited to MRFIT alone, he just wanted to address that the diet-heart has a solid foundation. No bruised ego’s. His arguments are in line with those of NHS:

    Eat less saturated fat

    Eating a diet that is high in saturated fat can raise the level of cholesterol in the blood. Having high cholesterol increases the risk of heart disease. These practical tips can help you cut down on saturated fat.

    http://www.nhs.uk/Livewell/Goodfood/Pages/Eat-less-saturated-fat.aspx

    Jeremiah Stamler highlights which kind of evidence is relevant for public dietary measure’s. His classic landmark article is from 1978. And fairly little has changed in terms of the relevance of the evidence (Stamler 2010). Stamler covers experimental evidence with non-human primates, low-risk populations, autopsy studies, prospective cohorts and trials. The problem with diet-heart trials is that people enrolling into them are usually way ahead in their mid-life with prediagnosed CHD. This kind of setting may not answer to all relevant questions being asked and therefore all forms of evidence is needed when addressing the linkage between diet and long-term health (Pedersen et al 2011).
    http://circ.ahajournals.org/content/58/1/3.long

  51. Mie

    1) Your comment changes nothing. Of course there are differences in study design etc. etc. but that really wasn’t the case here. Unless you can, of course, elaborate why this problem w/ epidemiological evidence seems to concern ONLY this issue? Or are you arguing that e.g. current recommendations for whole-grain which are – to a large extent – based on observational data are misguided? :-)

    2) Problems with compliance are well-known problems in any study involving diet & free-living subjects (of course elsewhere too, but let’s focus on this one). Unless you have plenty of evidence pointing out that one option (your option) is more likely to occur than another and data pointing out the clinical meaningfulness, this is mere speculation.

    So yes, let’s see the evidence.

    3) Try to focus, please. You’re not even talking about the point I made. Nothing you wrote means that the methodological choice of comparing different fats & their effects on blood lipids with “carbs en masse” as a reference point has anything wrong with it. Nope. Since the focus is on FATS and not on macronutrients in general, this really doesn’t matter. And of course Mensink et al – nor anyone with a properly functioning brain, for that matter – isn’t arguing anything concerning lipid levels and different types of carb sources. And – finally – if you didn’t consider the aforementioned meta-analysis informative enough, too bad. To me, this seems the equivalent of e.g. complaining about a meta-analysis of CVD risk marker data that it didn’t include studies of CVD end points. In other words: pointless.

    Finally, let’s digress a bit, shall we? About your statement

    “As the great majority of caloric intake in western countries is derived from junk food, it is likely that junk food would largely be the point of reference”

    Notice that in the abovementioned Mensink et al (2003) the data came from a variety of countries (34 from the USA, 26 from other countries) and from a period reaching from the 1970s to the 1990s. In addition, the ages of the participants reached from young adulthood to senior citizens.

    If you have data showing that the carb intake in these studies was indeed mostly junk, please do so.

  52. Mie

    “Now, in regards to findings from MRFIT (including the ad hoc analysis) do you think the advice to reduce dietary cholesterol is not based on good science? What was the problem? I apologize if I get it wrong, but it appears to me that you are the one with difficulties in the ego section (see Katan’s reply to someone with an obvious problem, whatever that problem is).”

    Err, what on earth are you talking about? You do realize that I commented on post-hoc analysis being problematic, not on dietary recommendations concerning dietary cholesterol? And Katan, by the way, is commenting on SAFA and plasma cholesterol – not dietary cholesterol.

    “I am confident everyone else will benefit from replacing SFA and cholesterol with minimally refined plant foods even though we do not have any trials directly verifying this.”

    I’ve got no problems with replacing excess SAFA with veggies, fruit, legumes etc. never have. That’s because that has NEVER BEEN THE ISSUE!!! The issue has been about arguing that dietary approach X (which has been shown to be better in terms of CVD, cancer etc. than what we Westeners currently eat) is clearly superior to dietary approaches Y and Z (which fill the same abovementioned criteria).

    For crying out loud, what do you do when you’re supposed to be reading what other people write???

  53. Low-fat Richard

    Mie,

    Doc wrote a blog post about fats which was somewhat problematic according to me and HealthyL.
    http://www.docsopinion.com/2013/02/17/fat-and-heart-disease-exploring-the-villain/

    He stated that the participants in MRFIT were told to reduce their intake of cholesterol with no results. HealthyL pointed out that INTERESTINGLY a more recent reanalysis of MRFIT which demonstrated a significant decreased risk of CHD and CVD events during the trial and that the non-fatal events during the trial were strongly associated with CVD mortality during the 20 years after the trial ended which demonstrated that the trial was too short to show a significant benefit for the degree of change made between the intervention and control groups. In other words, HealthyL made the point that it is important to consider all lines of evidence including post-hoc analysis.of trials. The limitations of diet-heart trials are very similar to those that are seen in trials that have attempted to test the benefits of smoking cessation. Stamler addresses the issue of diet-heart trials in his landmark article (1978, see the link above))

    You went “nuts” after the information of post-hoc analysis of MRFIT was brought to reader’s attention. That’s was why I asked did you not think that reducing dietary cholesterol was important. Post-hoc analysis are most likely problematic but in the case of MRFIT they clearly verify everything that was to be expected based on the totality of evidence. I wonder why was it important to you to angrily point out the alleged problems of post-hoc analysis given the context. That’s why I thought that it might be actually you who have an issue with a big ego.

  54. Mie

    Once again, I can read – apparently better than you. Nothing you wrote changes the fact that post-hoc analyses cannot be used convincingly to argue that a negative trial – hallelujah! – indeed produced the results YOU personally like. At best, it contributes to what you know already of the primary topic (lifestyle interventions in CHD prevention) and also adds to another matter, too (trials need to be designed carefully). Had you read the link I posted, you’d have realized why the authors are correct in pointing that post-hocs should be treated with caution.

    And what’s even worse, NONE of this matters. Axel doesn’t address MRFIT in the blog post (at least not in detail, quick glance and search with term “MRFIT” found no results) nor is he arguing against current dietary recommendations as far as I can see.

    So the only point to be made here seems to be the enormous egos that you and your pal have, egos that make you grasp at whatever straws you think you can see. And yes, I do find that stupid and somewhat repulsive. Anger? More like stupefied amusement.

  55. If you have established vascular disease — and I analyzed five of the biggest secondary prevention trials, and I looked at the outcomes in men and women. And if you look at these five trials, which included over 33,000 men, the event rate dropped from 25.5 percent in men on placebo to 19.5 percent in men on statins. So there’s a 6 percent absolute risk reduction. But when you read these trials and you read the headlines, they never give the absolute risk reduction.

  56. It is not merely how researchers of a particular field interpret the conclusions of a study, but perhaps even more importantly how the general population will. This is one of the main reasons why Katan at al. criticized the Siri-Tarino et al. meta-analysis.

    If a meta-analysis/systematic review concludes that food x is not associated with an increased risk of heart disease people may think it is safe to increase consumption of this food instead of focusing on healthier choices.
    For example, if a systematic review concludes that refined grains are not associated with an increased risk of heart disease because they are not generally associated with an increased risk when compared to non-specific sources of calories, then this may have people believe that it is safe to replace whole grains with refined grains. On the other hand, if a review concludes that whole grains reduce the risk of cardiovascular disease people may then be more likely to replace refined grains with whole grains. Although such a conclusion is not perfect it can be considered to be less problematic as it is less likely to hurt the generally public.
    http://www.ncbi.nlm.nih.gov/pubmed/17449231

    If we are interested in saving lives we would naturally want to advocate the “best possible option”. I feel that unfortunately that some researchers do not feel this way and that they are not refraining from making conclusions that is of little benefit to the general public even when it is the general public that pays for the research.

    Instead of simply angrily referring to me as cherry picking when considering certain studies separately, why not consider the rational I provide.
    It is well established that the association between dietary cholesterol and serum cholesterol is curvilinear- the effect becomes smaller when the baseline intake of cholesterol becomes larger. This justifies separately examining studies carried out on populations that habitually consume a lower intake of dietary cholesterol as an increased intake may have a greater adverse effect on such a population. This analysis is also justified as the meta-analysis paper you cited not only excluded these studies from the analysis but did not even mention these relevant studies.

  57. 1) One of the problems with testing the diet heart hypothesis as opposed to testing the health benefits of whole grain with within-population cross-sectional and cohort studies is due to the diet-hearts hypothesis reliance on the intermediate variable of serum cholesterol (which is greatly effected by interindividual variability). Studies looking at the health benefits of whole grains may not suffer as greatly if the beneficial effects are largely independent of blood lipid concentrations. I refer you to Jacobs et al. classical paper from 1979 to explain the reasoning for this as you do not appear to be familiar with these lines of research.

    “The link of diet to coronary heart disease is presumably not direct but is through its effect on serum cholesterol. Since diet and serum cholesterol have a zero correlation cross-sectionally, a study of the relationship between diet and coronary heart disease incidence will suffer from the same difficulties as the study of diet and serum cholesterol. A corollary of the mathematical model here presented is that a correlation close to zero would likely be observed between diet and coronary heart disease incidence. For another disease in which diet is a cause agent, a prospective incidence study following a cross-sectional assessment of diet would presumably be valuable.”
    http://www.ncbi.nlm.nih.gov/pubmed/313701

    2) To suggest that what I said is based on mere speculation and that it maybe almost as likely for people with high serum cholesterol to increase rather than decrease intake of saturated fat compared to people with lower serum cholesterol is to suggest that dietary recommendations made by health institutes and doctors for the last 50 years has had virtually no impact on peoples diet. It is well documented that the populations of many if not most developed countries have altered their intake of dietary lipids towards these recommendations resulting in more favourable blood lipids. I provided the example of the Western Electric study as this is perhaps one of the oldest examples and demonstrates that this problem effected even the oldest prospective cohort studies.
    http://www.biomedcentral.com/1471-2458/11/641
    http://aje.oxfordjournals.org/content/115/4/506.short

    3) I believe that one of arguments Richard was making was the point I have also previously made- that more than often prospective cohort studies are used to make simple associations in which no attempt is even made compare a particular food or macronutrients to any other sources of calories. In this case we need to assume that the particular food or macronutrient studies was compared to all other sources of calories combined in that particular populations diet which are not typically not very healthy calories. However when such studies compare carbohydrates with for example saturated fat on hard end points then it is important to consider the quality of carbohydrates especially when there is significant evidence showing that the quality of the carbohydrates strongly effects that particular hard end point (ie. CVD). The Mensink et al. meta-analysis may not be quite as problematic because there does not appear to be such a huge difference between different sources of carbohydrate and the effect that they have on the concentrations of the particular lipid fractions measured in that study as opposed to the end point CVD which is likely influenced also by a number of other factors that are determined by the quality of carbohydrates.

  58. Low-fat Richard

    Mie,

    I referred to a wrong link. Doc wrote about the MRFIT here:

    http://www.docsopinion.com/2012/06/19/should-i-take-cholesterol-lowering-drug-2/

    HealthyLongevity quoted Doc directly in his response and thus this should not have been a problem. Not sure, how well good you read after all. I was very busy and screwed it up with the links. What’s your excuse?

    We, obviously, disagree strongly, but I think it’s a idea to leave it at that. To bring this back to the issue, I think B Roberts ignores the evidence on dietary cholesterol which a) elevates cholesterol and b) is associated with CHD in several prospective cohorts under and above its effect on serum cholesterol levels.

    Moreover, B Roberts fails to provide her readers powerful means to lower their cholesterol drug-free which should be her priority since she is not a fan of statins and even refers to Rita Redberg who allowed de Lorgiril to publish his horrible attack against the chief inspectors of the Jupiter trial in her journal. These people are intellectually deeply invested in the anti-statin agenda.

  59. Low-fat Richard

    I regards to my previous post I just made, I feel slightly bad for being too rough on B Roberts. Apologies! Mie, great to debate with you. Axel, thanks for the patience and tolerance for differing views. Summer calling and I need to leave the scene.

    Best,
    R

  60. Mie

    “It is not merely how researchers of a particular field interpret the conclusions of a study, but perhaps even more importantly how the general population will. This is one of the main reasons why Katan at al. criticized the Siri-Tarino et al. meta-analysis. If a meta-analysis/systematic review concludes that food x is not associated with an increased risk of heart disease people may think it is safe to increase consumption of this food instead of focusing on healthier choices.”

    I find this VERY problematic. Virtually ALL meta-analyses clearly mention the limitations. You cannot expect different meta-analyses be stopped/go without publishing just because the general population doesn’t understand them. And in no way are the scientists to be held responsible for e.g. low-carb blog posts, press articles etc. which ignore these limitations.

    So please tell me that you’re NOT arguing in favor of shutting your eyes on the very nature of science (trying to gain new information via critical endeavour). ‘Cause this post of yours sure smells of it.

    “If we are interested in saving lives we would naturally want to advocate the “best possible option”. I feel that unfortunately that some researchers do not feel this way and that they are not refraining from making conclusions that is of little benefit to the general public even when it is the general public that pays for the research.”

    Smells even stronger now. Are you truly advocating censorship?

    “It is well established that the association between dietary cholesterol and serum cholesterol is curvilinear- the effect becomes smaller when the baseline intake of cholesterol becomes larger. This justifies separately examining studies carried out on populations that habitually consume a lower intake of dietary cholesterol as an increased intake may have a greater adverse effect on such a population.”

    If you want to look at specific sub-populations, fine. This, however, wasn’t my point. Read my post again. I must warn you though: after suffering Low-fat Richard’s off-topic mumble & continuous spamming of irrelevant issues instead of directly addressing my points, I won’t tolerate similar behavior much longer.

    “This analysis is also justified as the meta-analysis paper you cited not only excluded these studies from the analysis but did not even mention these relevant studies.”

    You don’t think the inclusion criteria might have had something to do with the exclusion? Oh please. If you, on the other hand, want to criticize the inclusion criteria, do so. But you’ll have to focus on THEM in order to do that.

  61. Mie

    HL, I’ll continue down here due to WordPress’ tendency to shrink Reply-boxes:

    “1) One of the problems with testing the diet heart hypothesis …”

    Not convincing. The direct benefits of whole-grain products are based – in my opinion quite extensively – on blood lipids, too (soluble fibre lowers LDL). And the fact that there are more than just this factor in the picture doesn’t really differentiate them from fats which too have effects on CVD beyond their effect on LDL receptor activity.

    “2) To suggest that what I said is based on mere speculation and that it maybe almost as likely for people with high serum cholesterol to increase rather than decrease intake of saturated fat compared to people with lower serum cholesterol is to suggest that dietary recommendations made by health institutes and doctors for the last 50 years has had virtually no impact on peoples diet.”

    Careful now, don’t twist my words. Of course dietary recommendation have had impact on people’s diet. However, this is not what I talked about. Read below:

    “It is well documented that the populations of many if not most developed countries have altered their intake of dietary lipids towards these recommendations resulting in more favourable blood lipids.”

    This isn’t the issue. To quote myself:

    “Unless you have plenty of evidence pointing out that one option (your option) is more likely to occur than another and data pointing out the clinical meaningfulness, this is mere speculation.”

    Neither of these two papers addresses this issue – in the context of a given COHORT, that is. You need to back your claim up with data showing the quantity & the magnitude of the effect in people taking part in a prospective study who change their diet towards better (recommendations) AND compare it to data on people who – at the beginning of the cohort – are consuming a healthier diet & slip towards the worse as the cohort progresses. If you want to do more than just speculate, that is.

    No such calculations exist, to my knowledge, so good luck. :-)

    “3) I believe that one of arguments Richard was making was the …”

    You do like to ramble, don’t you? The first part here was totally irrelevant, the latter … Well:

    “The Mensink et al. meta-analysis may not be quite as problematic because there does not appear to be such a huge difference between different sources of carbohydrate and the effect that they have on the concentrations of the particular lipid fractions measured in that study as opposed to the end point CVD which is likely influenced also by a number of other factors that are determined by the quality of carbohydrates.”

    So there. You know, you could’ve just stated that you were barking up the wrong tree here. :-)

  62. Mie

    “I was very busy and screwed it up with the links. What’s your excuse?”

    Trusting that you could provide a correct link.

    Dietary cholesterol has less influence on plasma cholesterol than e.g. SAFA when we’re talking about people eating a mixed diet. See this

    http://www.ncbi.nlm.nih.gov/pubmed/1534437

    and figure 2.

    It has also been well established that some people react much more severely to dietary chol. than others and thus should watch out for it. For others, this isn’t as important as e.g. quality of fat, intake of fibre etc. etc. issues that influence plasma cholesterol levels.

  63. 1) As the observed benefit of soluble fiber seen in prospective cohorts is much greater than the predicted effect it has on serum lipids, and as benefit has also been observed for insoluble fiber which his little effect on serum lipids, this suggests that the benefits of fiber (or perhaps foods rich in fiber which fiber intake may merely be a marker of) are largely independent of serum lipids.
    http://archinte.jamanetwork.com/article.aspx?articleid=216689
    I agree that dietary fats probably influence CVD via mechanisms that are also independent of serum lipids, but cohort studies may have limited ability to test the additive effects of serum cholesterol and therefore are likely insufficient to test the diet-heart hypothesis.

    2) The data from the Chicago Electric Study suggested that the participants made dietary changes in response to unfavourable serum lipids, and that the degree of these changes was large enough to influence the cross-sectional association between dietary fats and serum cholesterol towards the opposite of the expected direction.
    It is possible for participants with a higher intake of saturated fat to have a lower serum cholesterol than the participants with a lower intake of saturated fat as serum cholesterol is not merely determined by the intake of saturated fat alone, but by other factors such as interindividual variability response to saturated fat and other genetic factors. Therefore it is possible for reverse causation (participants with lower saturated fat intake having higher serum cholesterol) to occur when participants within a particular range of saturated fat intake decrease intake of saturated fat in response to high serum cholesterol without the need for participants within the same range of intake but with lower serum cholesterol to make any dietary changes. The participants remaining in the higher saturated fat groups after the dietary change may merely have favourable genes resulting in low serum cholesterol levels and may have continued consuming a high saturated fat diet as their risk factors were less unfavourable than the participants who decreased intake.
    In this respect reverse causation does not necessarily depend on participants with a “healthy diet” slipping towards a “worse diet” (whatever definition you are probably giving these words). You are demanding for additional data that is not required in order to demonstrate this point. Perhaps it is your intention to just demand for unavailable data rather than taking into consideration the all of the current available data.

    3) These comments were relevant for the original point that Richard was originally trying to point out.

  64. It is obvious that I am not suggesting censorship, but a call for more informative conclusions. The researchers should make it clear that the analysis suggests that increasing food or macronutrient x is unlikely to confer any benefit compared to other foods typically not considered health. It is especially problematic when the conclusions appear to be written in a way that is purposely intended to mislead the public.

    As Hu FB and Sun Q, two authors of the Siri-Tarino et al. meta-analysis pointed out in a different paper they co-authored, “in this meta-analysis saturated fat was compared with other calorie sources, primarily refined carbohydrates, and high intake of refined carbohydrates has been associated with a high risk of CHD.“ Not only was this not made clear in the conclusions of the original meta-analysis paper, this limitation was not made clear in the paper at all. It only seems natural that researchers would cast doubt on the intentions of researchers who criticize the diet-heart hypothesis based on findings that have been adjusted for serum cholesterol (as well as the other limitations described by Stamler) without even mentioning this as a potential limitation. These researchers are intelligent and should have been able to predict the effect their wording would make. Perhaps these authors known conflicts of interest got in the way here.

    In the discussion section under “Results in relation to other studies” of the egg meta-analysis you cited, the researchers should have mentioned these studies. Also, as the researchers used the word cardiovascular throughout the paper in a way that would suggest their findings apply to cardiovascular disease, the other studies that found a significant association with total cardiovascular disease and heart failure should have also been mentioned. This is not good enough for a review as someone reading this paper maybe mislead into believing that it was only the study from Western Australia that found a significant association. Again these researchers are intelligent and should have been able to predict this.

  65. Low-fat Richard

    Mie,

    the points you’ve made, inter alia, are the following:

    a) Dietary cholesterol is not a top priority for people on mixed diets.
    b) Trials which have tested the effect of smoking cessation have been successful.
    c) The magnitude of reverse causation (sick quitter effect) has gone unnoticed in prospective cohorts

    All of the arguments are flawed. In fact, you act like low-carb apostles with a messianic belief in your own faulty reasoning. So far, you’ve provided very little beyond rudeness, confusion and outward lies.

    Dietary cholesterol downregulates LDL receptors. If dietary cholesterol is an issue for vegetarians and people with low baseline intake of cholesterol, it’s certainly a problem for people on mixed diets as well.

    Both can be true at the same time:

    a) Eggs (up to 1 per day) is not associated with increased risk of CHD.
    b) Eggs promote CHD and hence their consumption should be kept at minimum.

    You attempt to confuse the reader into thinking that trials which have tested the effect of smoking cessation have been a success, no they haven’t (Katan 2011) which highlight the importance of weighting the totality of evidence, not just evidence from one particular line of research (see Pedersen et al 2011).

    In regards to part c:

    Dietary lipids and serum cholesterol level: change in diet confounds the cross-sectional association.
    Shekelle RB, Stamler J, Paul O, Shryock AM, Liu S, Lepper M.

    “In the Chicago Western Electric Company study, diet was assessed at the initial examination, in 1957-1958, of 1900 middle-aged men and again at their second examination about one year later. At the first examination, lipid composition of the diet, as summarized by a score based on the formula of Keys, Anderson and Grande, was positively associated with level of serum cholesterol. Between the first and second examinations, however, hypercholesterolemic men were more likely than others to have reduced intake of dietary saturated fatty acids and cholesterol. As a result, at the second examination the cross-sectional linear association between the diet score and serum cholesterol concentration was significantly positive for men with initial levels of serum cholesterol less than 250 mg/dl, significantly negative for men with initial levels of 250 mg/dl or higher and not significantly different from zero for all men together. The bias introduced by change in diet among hypercholesterolemic men differs importantly from bias due to unreliability of measurement and to interindividual differences in intrinsic level of serum cholesterol, because it can produce statistically significant but spurious correlations”.

    Moreover, the questionable interpretations of scholars affiliated with the dairy industry were questioned by top-tier diet-heart researchers (Katan et al):

    We believe that the conclusions of Siri-Tarino et al are invalid and are likely to mislead the general population

    I am personally forever thankful for HealthyLongevity for providing elaborate insights to the diet-heart. I think it’s astonishing to see you act the way you do! You should thank HealthyLongevity for raising awareness against diets high in dietary cholesterol and saturated fats and for his interest to promote plant-based diets to save lives and the nature. .

  66. Low-fat Richard

    Moreover,

    as one of the co-authors of the Pedersen et al editorial (Uusitupa & Schwabb 2011) pointed out in a separate publication, the meta-analysis of prospective cohorts do not gauge the structural changes in the diet that already occurred in all developing nations earlier (before the survey): the intake of SFA plummeted. This is a separate issue from the observation that people change their diet DURING the survey as a response to unfavorable blood lipids (sick-quitter effect).

    Between 1970 and 1995 annual consumption decreased from 310 to 235 eggs per person in US, a one important component of the improved dietary patterns leading to a fall in mean serum cholesterol concentration in the adult population. Did the authors of these new egg reviews discussed these structural changes in the diet that occurred earlier? If they didn’t, I wonder why? Campaigns against dietary cholesterol and eggs in particular have saved lives and proven to be successful (see Stamler 1998).

    All this highlights the importance to weight the totality of evidence while discussing diet-heart! B Roberts did not take totality of evidence into consideration while discussing dietary cholesterol!

  67. Mie

    “As Hu FB and Sun Q, two authors of the Siri-Tarino et al. meta-analysis pointed out in a different paper they co-authored, “in this meta-analysis saturated fat was compared with other calorie sources, primarily refined carbohydrates, and high intake of refined carbohydrates has been associated with a high risk of CHD.“ Not only was this not made clear in the conclusions of the original meta-analysis paper, this limitation was not made clear in the paper at all.”

    Now, it’s kinda hard to assess the claims unless you provide a REFERENCE. I suggest you do so first, then we may continue clearing out your fears – and I what I fear – BS claims.

    “In the discussion section under “Results in relation to other studies” of the egg meta-analysis you cited, the researchers should have mentioned these studies.”

    A couple of sub-group studies one of which had not-so-strong methodology and weak results – and both of which didn’t ? Now, notice that they didn’t mention SEVERAL other individual studies either, on the account that the focus wasn’t on MULTIFACTORIAL cohorts. The reasons for this is kinda obvious, don’t you think.

    “Also, as the researchers used the word cardiovascular throughout the paper in a way that would suggest their findings apply to cardiovascular disease, the other studies that found a significant association with total cardiovascular disease and heart failure should have also been mentioned.”

    Mentioned because …? The bottom line: the meta-analysis showed no increased risk of moderate egg consumption among HEALTHY individuals in general population. If you consider this flawed, explain why INDIVIDUAL studies negate the findings of a meta-analysis. This require either a) a new meta-analysis or b) explanation why studies that didn’t meet the inclusion criteria should’ve been allowed in (that is, studies you mentioned). Go ahead.

    And yes, your next post had better make sense. If you continue talking off-topic/addressing issues not relevant to the matter at hand (e.g. mumbling about multifactorial studies in relation to a meta-analysis with MUCH stricter inclusion criteria), our discussion will end.

  68. Mie

    Richard, it seems that – once again – we’re done. You’re exhibiting the “usual” signs of an Internet crank:

    “a) Dietary cholesterol is not a top priority for people on mixed diets.”

    Refusal to study the evidence. I pointed out Hopkins (1997), a meta-analysis of metabolic ward studies, which clearly shows that the effect of dietary cholesterol is negligible compared to e.g. the effects of dietary fat modification – which, in turn is, is again minor compared to a more thorough dietary change. In addition, by replacing the sources of saturated fat in one’s diet with fat sources richer in unsaturated fat and/or with complex carbs, the intake of dietary cholesterol decreases at the same time.

    So yes, it’s clearly not a top priority among healthy individuals. Not even among people suffering of dyslipidemias: see e.g. the Finnish “Käypä hoito” recommendations or the 2011 ESC guidelines, both of which place e.g. dietary fat modification well before decreasing cholesterol intake. And, on the whole, both argue for a MULTIFACTORIAL lifestyle intervention.

    “b”: pure off-topic, pursued apparently only because of flaws in character.

    “c) The magnitude of reverse causation (sick quitter effect) has gone unnoticed in prospective cohorts”

    A strawman. I never claimed this, but I stated that it’s not reasonable to presume that it’s a “one-way street”, considering what I’ve stated earlier. Changing diet in BOTH ways has been documented to happen: improvement and slipping are inherent parts of human behavior.

    Not to mention that pointing out reverse causation (which is of course only one of the problematic issues in prospective cohorts) brings nothing new to our understanding, is clearly cherry-picked (see above) and simply as banal as uttering the “correlation-doesn’t-equal-causation” while discussing epidemiological evidence in general.

  69. Mie

    “Did the authors of these new egg reviews discussed these structural changes in the diet that occurred earlier? If they didn’t, I wonder why?”

    Oh jeez. Answer: a meta-analysis/review of prospective cohorts need not discuss epidemiological correlations.

    This thread of discussion is indeed SO over. Even though it’s been kinda amusing watching both you and HL struggle in a sea of strawmen, off-topic and red herrings, it’s also fundamentally a waste of time.

  70. In regards to the statement from the paper co-authored by Hu FB and Sun Q here is the link to the paper below:
    http://circ.ahajournals.org/content/122/9/876.full
    You did not seem to have any difficulties searching for where Richard copied some of his previous quotes from so obviously you should have been able to find this paper.

    There is also the other meta-analysis eggs and cardiovascular disease that Richard cited that found that eggs were associated with an increased risk of cardiovascular disease even when they did not restrict the analysis to diabetics. Although I agree more with the conclusions of this meta-analysis I do not believe it was carried out as well as it could have been. As eggs were associated with an increased risk of diabetes in healthy people in this meta-analysis, and eggs were associated with an increased risk of either cardiovascular disease or heart disease among diabetics in the two meta-analyses this also suggests potential harm of modest intake of eggs even in “healthy people”.

    However this was not the main point I was making about the egg studies. I was stressing the point that eggs need to be compared to more healthy foods in order to make an informed decision. This was elaborated on in a large research panel organised by Walter Willett:
    “For example, it may not be useful, as is usually done, to compare a specific food to all other sources of energy, which are usually mainly refined starches, sugars, red meat, and fat-rich dairy products in typical Western diets.”
    http://www.ajcn.org/content/93/4/684.full#xref-fn-1-1

    For example, using the data from the Nurses Health Study presented in the paper in the first link it can be concluded that there is suggested evidence that replacing eggs with nuts would decrease the risk of coronary heart disease. Although the authors of this paper did not specifically mention this in the paper as they were focusing more on the replacing different protein sources other than eggs, the data from the multivariate analysis for the RR for 1 serving per day of eggs and nuts shows virtually non-overlapping confidence intervals, suggesting benefit of replacing eggs with nuts.

  71. “Hopkins (1997)”? Are you confusing Hopkins 1992 and the Clarke et al. meta-analyses of metabolic ward studies? I cannot find such a paper published by Hopkins PN from 1997. The Hopkins 1992 meta-analysis suggests that for a person consuming a near cholesterol free diets, adding cholesterol from a couple large eggs per day would increase serum cholesterol by about 0.5 mmol/l (Fig. 2). This is actually quite considerable and is about the same as change in serum cholesterol that Clarke et al. 1997 found for replacing 10% of calories complex carbohydrates with saturated fat. Even if dietary cholesterol is to be considered of secondary importance it is still very important considering that heart disease is the leading cause of death in the world.

    You said “changing diet in BOTH ways has been documented to happen”. You clearly know that we were referring to reverse causation in regards to the diet-heart hypothesis. If reverse causation happens in the opposite direction – ie. dietary change biasing the association towards overestimating the association between saturated fat and serum cholesterol or coronary heart disease, then this would suggest that the participants within a particular range of saturated fat intake, the participants with a higher serum cholesterol increase the intake of saturated fat in comparison with the participants with a lower serum cholesterol. As this is comparatively it is different than both the participants with high and low serum cholesterol simply increasing saturated fat intake. If you are saying that such a change has been documented then provide a reference for this. I certainly doubt that such a finding has been documented as frequently the opposite.

    Pointing out reverse causation is a possible explanation for a particular finding, while pointing out “correlation-doesn’t-equal-causation” provides little explanation.

  72. Mie

    “You did not seem to have any difficulties searching for where Richard copied some of his previous quotes from so obviously you should have been able to find this paper.”

    Ahem, whose job is it to provide references to his own claims?

    As for the point in the paper mentioning S-T et al (2010): yes, the authors were pointing out the correct context for S-T. But as for S-T not mentioning the refined carb -thing: try reading the paper a bit more carefully the next time. Here’s a quote from “Discussion” in S-T:

    “With respect to dietary carbohydrate, the type of carbohydrate (ie, a high or low glycemic index) that replaces saturated fat is likely important in influencing dietary effects on CVD risk (47). However, there was insufficient information in the component studies of this meta-analysis to permit examination of this issue.”

    So there.

    “There is also the other meta-analysis eggs and cardiovascular disease that Richard cited that found that eggs were associated with an increased risk of cardiovascular disease even when they did not restrict the analysis to diabetics.”

    You mean this?

    http://www.atherosclerosis-journal.com/article/S0021-9150(13)00243-8/abstract

    I don’t have access to full-length article, so unfortunately I can’t comment on it. However, considering that the two other meta-analyses didn’t indicate problems with moderate egg intake in general population, I fail to see why this on in particular would be “The One and Only Piece of Legitimate Egg Science”.

    “I was stressing the point that eggs need to be compared to more healthy foods in order to make an informed decision.”

    Been there, done that. Do you not understand that I’ve already stated – in effect – the same thing several times?

  73. The S-T could not have carried out a full examination into the effect of replacing saturated fat with other macronutrients with the data they used. However, the fact that the greatest source of calories in the studied population was derived from foods rich in carbohydrates and many of the larger studies adjusted for either unsaturated fats, dietary fiber and fruits and vegetables (leaving almost all but refined carbohydrates) strongly suggests that this is what saturated fat was “primarily compared” with. As was my point, it should have been made very clear that saturated fat was likely compared with other sources of calories that are not generally considered health. Furthermore, S-T were only emphasizing the importance of reducing refined carbohydrates instead of both refined carbohydrates and saturated fat. This is one of the many reasons why it was obvious to many prominent researchers that this paper was potentially designed to mislead the public.

    I have the full paper for this other egg meta-analysis. Although I do not believe that the inclusion criteria was perfect, these researchers included 6 additional epidemiological studies that found significant associations between egg intake a cardiovascular disease end points for which most findings were significant or near significant findings even when the analyses were not limited to diabetics:
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2706003/
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2650810/
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892297/
    http://www.sciencedirect.com/science/article/pii/S0091743506003781
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911502/
    http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2006.01638.x/pdf

    I believe that the other egg meta-analyses that you referred to did not perform a meta-analysis of egg intake and the risk of diabetes which can be considered especially important as egg intake among diabetics has been consistently associated with an increased risk of coronary heart disease or cardiovascular disease in these meta-analyses. This is one of the reasons why modest egg intake in apparently healthy people may confer harm.

    In regards to my main point about the egg studies you said: “Been there, done that. Do you not understand that I’ve already stated – in effect – the same thing several times?”
    Throughout your comments you keep inferring that modest egg intake likely causes little harm to the general public instead of pointing out the likely benefits of replacing eggs with other healthier foods. It is important to try and decrease the leading cause of death in the world, not leave it where it is.

    Perhaps you are less interested in saving lives and more interested in misleading the general public towards nutritional stupidity.

  74. There’s been a lengthy discussion here on saturated fats and low fat diets. However, nobody’s mentioned the recent Cochrane meta-anlysis here, or maybe I just missed it.

    http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002137.pub3/abstract

    It showed that reducing the total amount of fat in our diet, by replacing them with starchy foods does not reduce the risk of cardiovascular disease. However, modifying the fat we eat, by replacing saturated fat with mono- and polyunsaturated alternitives may provide som protection.

  75. Mie

    “As was my point, it should have been made very clear that saturated fat was likely compared with other sources of calories that are not generally considered health.”

    Made clear despite adequate means to investigate the issue (cherry-picking among studies)? No, most certainly not. It’s clear that you enjoy speculation ONLY when it suits your needs. The rest of us have higher standards.

    “Furthermore, S-T were only emphasizing the importance of reducing refined carbohydrates instead of both refined carbohydrates and saturated fat. This is one of the many reasons why it was obvious to many prominent researchers that this paper was potentially designed to mislead the public.”

    S-T discussed – in addition to the benefits of complex carbs – also the benefits of fat modification. Combine these two, and I’m forced to conclude that your stance on the topic is BS, stemming from your inability to accept “a wrong finding”.

    “Throughout your comments you keep inferring that modest egg intake likely causes little harm to the general public instead of pointing out the likely benefits of replacing eggs with other healthier foods.”

    The first point is indeed one backed up by several meta-analyses of cohort data. And according to metabolic ward data (Hopkins 1997) and several RCTs, this indeed seems to be the case: modest intake of eggs has a negligible effect on known risk factors.

    The latter MAY be the case. However, you should know that a mere replacement of a few eggs per week might as well provide no benefits at all, depending on what you use to replace them. I prefer to look at diets as a whole, and so far there’s nothing to suggest that in the context of a healthy diet, occasional use of eggs has any kind of profound effect.

    “Perhaps you are less interested in saving lives and more interested in misleading the general public towards nutritional stupidity.”

    I’m interested in the issue at hand, not extrapolating on the basis of cherry-picking and ideological dogma.

  76. The reduction in LDL and total cholesterol in these reduced fat randomized controlled trials included in the Cochrane meta-analysis was very minimal. As it has been demonstrated in dozens of rigorously controlled metabolic ward trials that replacing saturated fat with carbohydrates significantly lowers total and LDL cholesterol, the lack of decrease of LDL and total cholesterol likely reflects lack of appropriate dietary changes required to test the diet-heart hypothesis. The RR of 0.96 for cardiovascular mortality in the Cochrane meta-analysis is consistent with the expected results when considering the small decrease in LDL cholesterol.

    The Womens Health Initiative which was given the majority of the weight in the Cochrane meta-analysis was not even designed to lower LDL cholesterol, and as a result reductions in saturated fat intake and LDL cholesterol were fairly negligible. As the researchers of the WHI stated:
    “Because there are no apparent changes that would have mitigated a potentially favorable effect on CVD, the lack of an appreciable CVD effect maybe attributable to the limited decrease(only 2.7 mg/dL [0.07 mmol/L]) in LDL-C level, as well as the modest differences in other potentially favorable dietary components. Based on a large body of evidence from LDL-C–lowering trials, this magnitude of change in LDL-C level would be predicted to produce only a small (2%-4%) decrease in CVD risk, a value far below the power for detection in the current study. As delivered, the dietary intervention was not expected to have substantial effects on lipoprotein levels, but it is possible that a diet specifically lower in saturated and trans fat combined with increased intakes of vegetables ,fruits, and grains might have led to a decrease in CVD risk.”

    The researchers of the WHI also stated:
    “Compared with those in the entire comparison group, a trend was observed toward reduction of CHD risk among those in the intervention group who reached the lowest levels of saturated fat (HR, 0.81; 95% CI, 0.69-0.96 in the group that consumed <6.1% energy; P<.001 [adjusted HR, 0.82; 95%CI, 0.67-0.99; P=.05])… While these additional analyses are subject to residual confounding because of reporting bias or the lack of a comparable comparison group, some confidence in their validity is supported by parallel patterns of LDL-C reductions in participants stratified by changes in saturated fat at year 1 (−10.1; 95% CI, −13.5 to −6.6 mg/dL[0.26; 95% CI, −0.36 to −0.17 mmol/L]in the quartile with the greatest reduction;P=.005 for trend)”
    http://jama.jamanetwork.com/article.aspx?articleid=202339

  77. Mie

    “Hopkins (1997)”? Are you confusing Hopkins 1992 and the Clarke et al. meta-analyses of metabolic ward studies?”

    Indeed, I mentioned the wrong year. Apologies.

    “The Hopkins 1992 meta-analysis suggests that for a person consuming a near cholesterol free diets, adding cholesterol from a couple large eggs per day would increase serum cholesterol by about 0.5 mmol/l (Fig. 2). This is actually quite considerable and is about the same as change in serum cholesterol that Clarke et al. 1997 found for replacing 10% of calories complex carbohydrates with saturated fat.”

    Notice that this applies only to people consuming very little dietary cholesterol. In addition, bear in mind the limitations of metabolic ward studies: small n, short time, not real life setting. Therefore, their strength lies in discovering whether a mechanism suggested by e.g. animal data can indeed occur in humans. In RCTs studying egg consumption and changes in risk markers, it’s been discovered that some people (10-30%) respond to eggs markedly, others showing virtually no effect at all.

    In addition, notice that the studies in Hopkins present the findings in changes in TC. Eggs, however, raise both LDL (dietary cholesterol, SAFA) and HDL (most of the fat in eggs is unsaturated), which further complicates the findings.

    “Even if dietary cholesterol is to be considered of secondary importance it is still very important considering that heart disease is the leading cause of death in the world.”

    I already made my claim here. If you know anything about e.g. ESC guidelines, you know the big picture.

    “If reverse causation happens in the opposite direction – ie. dietary change biasing the association towards overestimating the association between saturated fat and serum cholesterol or coronary heart disease, then this would suggest that the participants within a particular range of saturated fat intake, the participants with a higher serum cholesterol increase the intake of saturated fat in comparison with the participants with a lower serum cholesterol.”

    In cohort studies the confounding factors cannot be accounted for so well as to be able to pinpoint to SAFA alone, like you’re trying to. Remember that the instructions back in the 1950s-1980s were to lower TOTAL FAT intake. Thus when people with higher LDL/TC complied, they lowered the intake of unsaturated fats as well but in all likelihood did not replace them with complex carbs (at least not totally). Therefore, the total value of this … Well, in the light of the very small differences and/or the conflicting findings, it seems that BOTH ways are plausible, just like I suggested.

    So, in the end we’re – once again – back to speculating. Which is unavoidable, given the very nature of epidemiological studies. Now, I’m perfectly OK with this. You, on the other hand, seem unable to accept the fact that the findings can often be only suggestive.

  78. Mie

    Axel, the discussion has focused on cohort data & eggs. But yes, good point. Let’s see what HL can make out of this.

  79. Mie

    Clarification to my messages above, this part:

    “Thus when people with higher LDL/TC complied, they lowered the intake of unsaturated fats as …”

    What I meant that this presumed compliance to dietary advice may not have changed the dietary fat relations (SAFA/PUFA/MUFA) in connection with TC/LDL that much, if at all, and thus it would bias the results in a way, too.

    Not to mention that there is no quantified data on the size and scope of this effect. Therefore, pointing out reverse causation nonetheless remains observative speculation.

  80. As I provided references to 2 papers in which 3 out of the 4 authors of the S-T co-authored emphasized the issue of saturated fat in the S-T meta-analysis as likely being compared primarily to unhealthy sources of calories, this cannot be simply be passed off as being cherry picked. This is an obvious issue (as well as many others) that merited a greater emphasis in the original meta-analysis (and by others those who cite it).
    http://ajcn.nutrition.org/content/93/4/684.full#xref-fn-1-1
    http://www.ajcn.org/content/93/4/684.full#xref-fn-1-1

    In regards to reverse causation and fat between the 1950s and 1980s, for example in the US intake of saturated fat and monounsaturated fats were declining during this period whereas intake of polyunsaturated fats were increasing. The advice to decrease saturated fat and increase polyunsaturated fat dates back almost as far as the advice to reduce total fat, such as was the case for the American Heart Association. Considering these factors and the fact of the very low polyunsaturated to saturated fat ratio because fat was largely derived from saturated animal fat, a decrease in total fat intake replaced largely with carbohydrates would have most likely resulted in lower total and LDL cholesterol levels.
    http://ajcn.nutrition.org/content/52/3/457.short
    http://circ.ahajournals.org/content/23/1/133.full.pdf

    Whenever a valid point is made that you do not like you often pass it off as cherry picking or BS or some sort of name calling.

    In regards to the Hopkins 1992 meta-analysis you said that “this applies only to people consuming very little cholesterol”. No this also applies to people lowering their cholesterol intakes to very low levels. Even a reducing cholesterol down to 100-150 mg/day would significantly decrease serum cholesterol and this can be achieved while still eating small to modest amounts of low cholesterol meat and dairy. Although I do not necessarily agree that such a dietary pattern would be optimal this would hardly seem like an impossible target for at least a modest portion of the population to reach. As in regards to the limitations of metabolic ward studies, meta-analyses reduce the limitation of small n; the great majority of changes in serum lipids has been shown to occur within 3 weeks; studies in free living people have produced similar but slightly weaker results which is to be expected considering the likely poorer adherence. This was an unnecessary swipe at such a high quality form of evidence. Perhaps you would could provide data showing that the great majority of the population do not respond to eggs when baseline intake of cholesterol is negligible.

    As I pointed out in my post you linked to earlier:
    “It has been demonstrated in multiple meta-analyses of rigorously controlled feeding experiments that dietary cholesterol, including that from eggs yolks does have a modest adverse effect on the LDL:HDL cholesterol ratio.57 58 Furthermore, unlike for LDL cholesterol, there is limited causal evidence that simply raising HDL will lower the risk of coronary heart disease. For example, a meta-analysis of 108 randomized controlled trials found that while lowering LDL cholesterol significantly decreased the risk of coronary heart disease and all-cause mortality, modifying HDL had little appreciable effect after controlling for LDL cholesterol.47 In addition, a recent meta-analysis of mendelian randomization studies found that while genetically modified LDL significantly influenced the risk of coronary heart disease, genetically modified HDL had little appreciable influence.59 This evidence together with the evidence that dietary cholesterol adversely influences both concentrations of LDL as well as the LDL:HDL ratio, especially in healthy people reinforces the recommendations to limit egg and cholesterol intake.”
    “More recently a meta-analysis of mendelian randomization studies with over 312,000 individuals found that inheriting any of nine studied genetic variants that modify lifelong LDL cholesterol concentrations, but not any other known risk factors predicted a 55% lower risk of coronary heart disease for each mmol/l (38.7 mg/dl) lower LDL cholesterol.48″

    As coronary heart disease is the leading cause of death in the world and even modest decreases of LDL cholesterol translate into a modest decreased risk of coronary heart disease over an entire lifetime, decreasing intake of cholesterol will likely confer significant benefit at the population levels even if an increase in HDL actually does partly attenuate the risk.

    An optimal diet is a whole foods plant based diet with little or negligible other foods. If you were suggesting the consumption of a couple eggs per week in the context of such a diet for someone at low risk of vascular disease then I would have little concern with your comments, but this is not what you appear to be implying. As I would like this to be one of my last comments I would again like to emphasize that the focus should be on a whole foods plant based diet to reduce the risk of human suffering and death.

  81. Low-fat Richard

    Axel,

    the intervention arm in WHI did not increase their consumption of whole-grains, fruits, legumes or vegetables. The intervention group tinkered on fat in the form of choosing animal products lower in fat. The fiber intake was pathetic, 15g/day. This is indeed the “golden standard” of nutrition research as some would say. “Low-fat doesn’t work” is just one one interpretation of the trial, however I think that is a misleading and flawed interpretation. T Colin Campbell pointed out in his book “China Study” that better interpretation of the trial is that diets high in animal products do not work. The intervention diet consumed 3/4 of their protein from animal sources. This is pretty much the reality in all of the studies used in the Cochrane review.

    The intake of carbohydrates was once very high in rural China and the intake of animal protein very low (1/10 of the protein intake). The caloric intake was 30% higher than in US. This was a low-fat diet that had no resemblance to the diet consumed by the intervention group in WHI. Incase you are interested in preventative medicine, I highly recommend this article by Campbell et al.

    Diet and chronic degenerative diseases: perspectives from China.
    http://ajcn.nutrition.org/content/59/5/1153S.abstract

    Mie,

    I don’t what you mean with “extrapolation” given the context. However, we will never have any good trials around diet-heart, such trials would be either a) impossible to conduct because of logistics or b) unethical, but that’s ok. We have work what we have. If evolution has any predictive power, I think the darwinian foundation of our biomedical research is something we should not forget while discussing themes such as the effect of dietary cholesterol on humans. Even when fed in very small amounts, dietary cholesterol still had a significant adverse effect on monkeys arteries.

  82. Richard.

    Back to the Cochrane data I mentioned. This is a meta-analysis, based on a systematic review of randomized intervention trials addressing the issue. This is the clinical data that is available for us to draw our conclusions from. I understand that you hold another opinion, but I don’t believe it is supported by available clinical trial data. Citing epidemiological data won’t change this fact.

  83. As I pointed out metabolic ward experiments have demonstrated that replacing saturated fat with complex carbohydrates can significantly lower LDL and serum cholesterol. Therefore the fact that the decrease in LDL and serum cholesterol in these trials were very small reflects the lack of appropriate dietary changes required in order to test the diet-heart hypothesis.

    The Womens Health Initiative which was given the majority of the weight in the Cochrane meta-analysis was not even designed to lower LDL cholesterol, and as a result reductions in saturated fat intake and LDL cholesterol were fairly negligible. The researchers of the WHI pointed out “Based on a large body of evidence from LDL-C–lowering trials, this magnitude of change in LDL-C level would be predicted to produce only a small (2%-4%) decrease in CVD risk, a value far below the power for detection in the current study”

    This suggests that the Cochrane meta analysis finding of the small non significant decreased risk of cardiovascular mortality is actually consistent with that predicted by the very small decrease in LDL cholesterol and therefore does little to negate the diet heart hypothesis.

    The smoking cessation trials do not provide strong support for the hypothesis that smoking causes lung cancer, but that does not give us an excuse to turn off our brains and not consider all the other forms of evidence that support the hypothesis. This is what is done by people who try to deny the link between smoking and lung cancer.

  84. Low-fat Richard

    Doc,

    John McDougall MD certified internist interviewed the chief inspectors of WHI-trial in his radio show. The inspectors believed in moderation. Well, the “low-fat” -group had actually 9% reduction in breast cancer occurrence which was the primary end-point of this failed trial. The whole story can be read here:
    http://www.drmcdougall.com/res_whi_report.html

    McDougall came out recently with a new book. The book, Starch solution, was reviewed by the current editor-in-chief of Medcape, the former editor of JAMA, George Lundberg who also sits in at the board of IOM. I recommend McDougall’s new book to everyone interested in preventative med.

    The diet book to end all diet books
    http://www.medpagetoday.com/Columns/At-Large/32834

  85. Mie

    “As I provided references to 2 papers in which 3 out of the 4 authors of the S-T co-authored emphasized the issue of saturated fat in the S-T meta-analysis as likely being compared primarily to unhealthy sources of calories, this cannot be simply be passed off as being cherry picked. This is an obvious issue (as well as many others) that merited a greater emphasis in the original meta-analysis (and by others those who cite it).”

    And as your “merited a greater …” is still based on … Yes, what (Lack of enough words? Lines?) is it based on?

    I’ll answer that for you: nonsense & ego.

    “In regards to the Hopkins 1992 meta-analysis you said that “this applies only to people consuming very little cholesterol”. No this also applies to people lowering their cholesterol intakes to very low levels.”

    And how is consuming very little cholesterol and lowering cholesterol intake different in practice, when the results are seen in the curve? Pray, do tell me.

    “Even a reducing cholesterol down to 100-150 mg/day would significantly decrease serum cholesterol and this can be achieved while still eating small to modest amounts of low cholesterol meat and dairy. Although I do not necessarily agree that such a dietary pattern would be optimal this would hardly seem like an impossible target for at least a modest portion of the population to reach.”

    Err, you’re going off on a tangent. My point was that in the context of moderate baseline dietary cholesterol, added dietary cholesterol means very little. Furthermore, dietary cholesterol as such doesn’t mean that much compared to other issues, which is reflected in the ESC guidelines. Now, it’s obvious that this doesn’t go for ALL the possible sub populations which is why guidelines recommend caution.

    “As in regards to the limitations of metabolic ward studies, meta-analyses reduce the limitation of small n; the great majority of changes in serum lipids has been shown to occur within 3 weeks; studies in free living people have produced similar but slightly weaker results which is to be expected considering the likely poorer adherence. This was an unnecessary swipe at such a high quality form of evidence.”

    Here is the fundamental problem: you’re unable to understand that RCTs at least try and mimic the free-living conditions. If dietary advice doesn’t work in practice, you don’t go on blaming the real world & fall back on metabolic ward conditions which are artificial & limited for methodological purposes. Now, you try to create more effective solutions and/or ways to improve the advice.

    As for meta-analyses: the addition of studies with small n & short durations doesn’t fundamentally change the limitations of such studies to begin with. Or where you really under the impression that meta-analyses “fix” the inherent issues with the methodology in the original studies?

    “Perhaps you would could provide data showing that the great majority of the population do not respond to eggs when baseline intake of cholesterol is negligible.”

    Err, was this news to you? This is discussed in the abovementioned Rong et al meta-analysis.

    “It has been demonstrated in multiple meta-analyses of rigorously controlled feeding experiments that dietary cholesterol, including that from eggs yolks does have a modest adverse effect on the LDL:HDL cholesterol ratio.57 58 Furthermore, unlike for LDL cholesterol, there is limited causal evidence that simply raising HDL will lower the risk of coronary heart disease. For example, a meta-analysis of 108 randomized controlled trials found that while lowering LDL cholesterol significantly decreased the risk of coronary heart disease and all-cause mortality, modifying HDL had little appreciable effect after controlling for LDL cholesterol…”

    Ah, this HDL nonsense again. Had you bothered to read this meta-analysis, you’d have realized that a) the HDL -levels achieved remained FAR below optimal and b) changes brought about dietary interventions etc. were small – apart from certain HDL-raising medications which, however, had deleterious effects on lipid metabolism on the whole. This, together with the fact that the studies on HDL-improving medication were carried out on populations who were getting effectively treated w/ statins (further reducing the chance of statistically significant findings), explains the findings of ths meta-analysis very nicely. Therefore, the results aren’t surprising. The take-home message isn’t that HDL doesn’t matter but that interventions aimed at specifically raising HDL have disappointing results.

    And BTW, this is PRECISELY the same point which you make about Hooper et al and fat interventions (minor LDL changes –> no reason the expect major changes CVD end points). With which I tend to agree.

    And, in addition, when we count in the evidence AS A WHOLE, we’ve got a) robust findings in prospective studies pointing out that having high HDL is predictive of a smaller risk, even after adjusting for confounders and b) studies showing the predicted benefits of HDL infusion therapy.

    So I’m kinda looking forward to seeing you backtrack/cherry-pick yourself out of this “HDL-means-nothing” nonsense. If you even care to try :-)

    “As coronary heart disease is the leading cause of death in the world and even modest decreases of LDL cholesterol translate into a modest decreased risk of coronary heart disease over an entire lifetime, decreasing intake of cholesterol will likely confer significant benefit at the population levels even if an increase in HDL actually does partly attenuate the risk.”

    Or then not – referring to the findings of Hooper et al. However, I do agree that in general, lowering LDL is a good thing. But not in any way possible & in the light of the entirety of lipid changes.

    “An optimal diet is a whole foods plant based diet with little or negligible other foods.”

    Most of the calories (at least over 50%) should be plant-based, yes. Totally agree with that. Little or negligible amount of other foods? Hard to say exactly WHERE to draw to line. Vegan? Not sufficient evidence for that. The most robust evidence of CVD end points is for Mediterranean diet which has fish and small amounts of other animal products in it. If I had to pick one, I’d pick that.

    “If you were suggesting the consumption of a couple eggs per week in the context of such a diet for someone at low risk of vascular disease then I would have little concern with your comments, but this is not what you appear to be implying.”

    I suggest that you refrain from making interpretations which are false.

  86. Mie

    Just like I mentioned, this was quite good stuff. Nice to see you can produce, after all. :-)

    I’d like to add a couple of points:

    a) Quality of the individual studies (most are quite old, thus problems with methodology) –> the “carbage in, carbage out” is difficult to avoid

    b) Quality of the fat used in fat modification: many times the amount of PUFA & n-6 increases considerably, which (in the context of otherwise sub-optimal diet, smoking etc. etc.) isn’t prone to improve things

    However, the lack of statistically significant findings does indeed suggest the need to focus on a) more thorough and b) better controlled dietary interventions with c) medication to those who are at high risk. The limits of lifestyle interventions are painfully obvious even in trials, so in real life setting …

    Any ideas how to improve compliance and adherence to healthy diets?

  87. Mie

    Now Richard, this all would mean something if

    a) you’d stop the advertising of popular, commercial books

    and if

    b) McDougall’s diet plan had any scientific evidence to back up his claims

  88. Mie

    Richard, you’re wrong – yet again – in a couple of issues:

    a) Just because a trial doesn’t produce the results some people wanted doesn’t mean it was badly conducted or “wrong”. WHI showed precisely the same problem as virtually all trials: the difficulties people have in adjusting and modifying their diet & behaviour. There really are no major differences between … well, virtually all known diets. E.g. Ornish and vegetarian diets: adherence and compliance is no better than w/ others.

    b) This “Darwinian foundation” you speak of is a strawman. Yes, we all have the same origin. But no, this doesn’t mean that all the species have the same metabolism – or, in the context of the conversation, that extrapolation from animal studies is meaningful. E.g. rats: often used in animals studies, indeed. But bear in mind that e.g. in de novo lipogenesis differs considerably between rats & humans – which is why I often face-palm myself when seeing Taubesians churn out their “insulin-kills-because-carbs” nonsense based on extrapolation of these rat studies.

    This is why we have human studies and not just animal studies. No clinical guidelines on diet & nutrition get drafted and written on the basis of animal studies, they don’t factor in. Their usefulness is PRECISELY in testing out possible mechanisms and creating workable hypotheses. That’s all.

    Resorting to referencing animal studies in issues that are FAR BEYOND this level is de facto religious nonsense. No matter whether is vegan or low carber doing it.

  89. Mie

    One correction: the RR for CV mortality was 0.94, not 0.96.

  90. Low-fat Richard

    Mie,

    your ideological belief in the supremacy of the “golden standards of evidence” disappear immediately when HDL-C is being discussed. Where are the trials supporting the HDL-C theory? Your “robust association” disappears immediately when global perspective is taken into consideration. HDL-C levels were once very low in rural China and Okinawa with near-absence of clinical CHD. Moreover, people carrying APo1 Milano mutation in their HDL-C live long with very low rates of heart disease despite having elevated triglycerides and low HDL-C.

    The best evidence of McDougall approach is that it’s the only dietary paradigm that guarantees biologically normal “physiologic” cholesterol levels for most adult humans. For me, this is the strongest piece of evidence one can ever provide. Physiologic LDL cholesterol ranges from 40 to 80 (1.-1.9mmol), lower is better. I rather eat according to the McDougall plan than take statins, no offense to statins.

  91. Low-fat Richard

    Doc,

    what do you think of HDL-C modulation? Have you seen lean & fit people with very low levels of HDL-C? I think there’s only one biomarker in the lipid fraction that is sensitive to diet independent of weight and that is LDL-C. Elevated triglycerides and low HDL-C probably function as a marker of abdominal obesity and HDL-C goes up after weight-loss independent of the mechanism used. In other words, everything goes: amphetamine, chemo therapy, diet; everything that result in weight-loss probably elevates HDL-C on obese people. What do you think, Doc? There are papers that highlight the importance of HDL-C as a biomarker but reduces the importance to Western epidemiology and people following high-fat, animal food laden diets. People in third-world countries sustaining on low-fat diets have traditionally often had low HDL and minimal risk of heart disease.

  92. Doc´s opinion

    At least it appears that HDL-C modulation by drugs hasn´t been successful thus far. HDL-C is a complicated molecule and there are many subtypes which may play a slightly different role. I agree that weight loss usually helps in elevating HDL-C, at least for those who are overweight and/or obese.

  93. Low-fat Richard

    One more thing about HDL-C,

    the association in Western epidemiology applies only to baseline. No one has quantified the effect of HDL modulation, e.g. change of diet.

    Moreover, in my view, one of strongest pieces of evidence for low fat diet comes from Cuba, after the collapse of S. Union. Sudden change to almost vegan diet, sudden drop in mortality. Ecologic data showed that the intake of carbs increased to 70% calories with rice, beans and sugar cane being dietary staples. Although, the effect of increased physical activity cannot be ruled out. See Fanatic Coock’s blogpost about Cuba for references.

    Mie,

    the intervention arm in WHI managed to make changes, substantial drop in fat intake, more skim milk, more chicken: no effect. Failed trial. Moderation did not work.

  94. Low-fat Richard

    One more thing with the Darwinian foundation,

    evolution has predictive power: the effect of a stimuli should be rather similar, albeit not necessarily identical, in closely related species. Rats, unlike humans, carry most of their cholesterol in HDL fraction. Apes have a similar lipid metabolism with humans and thus they make bettet diet-heart models for humans than rats do.

  95. Mie

    Richard, please stop creating strawmen. I’ve clearly stated that yes, I’m in favour of looking at the evidence as a whole but that I also do regard RCTs (or rather, systematic reviews/meta-analyses of them) as the top of the evidence hierarchy. Which is, BTW, the standard. Now, obviously that doesn’t mean that trial evidence cannot or shouldn’t be scrutinized.

    If you’d bothered to read (which I’m beginning to doubt) my messages, you’d noticed that I agreed w/ HL’s take on the Hooper et al meta-analysis on fat modification RCTs. Now why would it be any different to take a critical look at trials aimed at raising HDL & meta-analysis done on them – especially since the main problems seem to be common for both of these.

    And no, no one’s arguing that LDL doesn’t matter – or that especially low LDL might be superior in preventing CHD than a combination of a bit higher LDL & HDL. However, this question isn’t resolved by ecological fallacies, certainly not when there’s ample amount of a) observational prospective evidence, b) mechanisms and c) trial data.

    And yes, HDL isn’t as “simple” as LDL where “the lower the better” seems to be the norm. Function and amount mostly coincide, but not always (ApoA-I Milano). However, this in no way changes the abovementioned points a), b) and c).

    If you can follow McDougall, fine. Not everyone can. Nor is there clinical evidence to suggest that it’s superior to statins in e.g. secondary prevention. If you know anything about statin trials & lifestyle interventions, I’m sure you’ll agree.

  96. Mie

    Now Richard, have a look at the ESC guidelines for the management of dyslipidemia

    http://www.escardio.org/guidelines-surveys/esc-guidelines/GuidelinesDocuments/guidelines-dyslipidemias-FT.pdf

    and notice (p. 1786) that weight loss doesn’t have the same magnitude of effect on HDL-levels as reducing transfat and exercise: If you lose 10 kg of body weight, your HDL can go up ca. 0,1 mmol/L whereas exercising worth 1500-2200 kcal creates the SAME or even LARGER increase.Of course, these need not be mutually exclusive options, not by any means. However, this does put that “amphetamine and chemo” nonsense of yours into context. It would be analogous – and equally stupid – to claim that cancer is a good thing since it effectively brings down your cholesterol levels.

    Now, I reckon I’ve got the answer why you choose to cherry-pick in the case of HDL:

    It’s all about fat.

    Since you follow a low-fat, starch-based diet – the likes of which don’t raise HDL levels nor reduce TG levels, independent of weight loss, in the light of the ESC guidelines – you’ve created this little bubble for yourself in which you like to float and pretend that HDL doesn’t matter.
    Perhaps it doesn’t in your case. However, in the light of the evidence around, I consider this stance of yours (and HL’s) to be virtually the same as cholesterol denialism in general and don’t really see there much difference between your cherry-picking and that of e.g. THINCS.

  97. Mie

    Richard at it again:

    “One more thing about HDL-C, the association in Western epidemiology applies only to baseline. No one has quantified the effect of HDL modulation, e.g. change of diet.”

    Now, what does “HDL modulation” mean if not change when compared to baseline?

    BTW; in a post-hoc analysis (which I consider somewhat problematic as such, but you & HL seemed to appreciate them…) of TNT having high HDL was an independent predictor of lower risk of CVD events, even with people with LDL levels below 1,8 mmol/L.

    http://www.ncbi.nlm.nih.gov/pubmed/17898099

    “Moreover, in my view, one of strongest pieces of evidence for low fat diet comes from Cuba …”

    Yes yes, ecological correlations. Everyone has their own favourite. Stop trolling.

    “Mie,the intervention arm in WHI managed to make changes, substantial drop in fat intake, more skim milk, more chicken: no effect. Failed trial. Moderation did not work.”

    So … Reducing dietary fat substantially didn’t work, eh? Now, how does this fit in the picture with your idea that reducing dietary fat is of uttermost importance? Pray, do tell me. :-)

  98. Low-fat Richard

    Mie,

    stop wasting your time in trying to make the other side look like idiots. Show some respect. Low-carb diet are often rationalized with the HDL-C sales-speech. This is nonsense, since HDL-C is not causally related to CHD. Ornish was able to regress the artery disease in his patients despite their HDL-C went down (together with moderate increase in triglycerides). New research shows that many of those with elevated HDL have other protective features in their HDL. However, this does not imply that eating eggs or other animal foods will enhance the quality of HDL despite they’d cause elevation of HDL-C. There’s not a single piece of evidence that would indicate that modulation of HDL-C will enhance the prognosis. People with genetically elevated HDL-C are not protected from CHD.

    We must understand the difference between risk predictor and causal factor. Poverty is a risk factor in Western epidemiology, but the prognosis won’t change even though the poor makes a bank. Moreover, pay attention to the context. HDL-C is important only within a population where basically everyone has elevated cholesterol. Most hunter-gatherets and other low-risk population have traditionally had low HDL-C’s.

    An elevation of triglycerides reflecting decreased triglyceride clearance may not be pathogenic — relevance to high-carbohydrate diets.

    Triglyceride levels are relatively high in certain Third World societies which are virtually immune to coronary disease so long as they persist in their traditional very-low-fat diets; in Ornish’s celebrated study, a moderate rise in triglycerides coincided with a marked reduction in coronary events. Although the particle size of both LDL and HDL tends to decrease when triglyceride levels are high, it is questionable whether this effect has a major pathogenic impact. The one clear drawback of high-carbohydrate diets is a decrease in HDL particle number, resulting from decreased hepatic production of apoA-I; this effect is seen whether or not triglycerides increase. The very favorable effects of very-low-fat, whole food, quasi-vegan diets on LDL cholesterol, insulin sensitivity, and body weight appear to more than compensate for this decrease in HDL; it is notable that HDL levels tend to be quite low in Third World cultures at minimal risk for coronary disease. On the other hand, this decrease in HDL may be of more significance in the context of omnivore diets only moderately low in fat, as suggested by the fact that diets higher in unsaturated fats emerge as more protective in Western prospective epidemiology.The tendency of high-carbohydrate diets to boost triglycerides can be minimized by exercise training, supplemental fish oil, an emphasis on fiber-rich, low-glycemic-index whole foods, and the “spontaneous” weight loss often seen with ad libitum consumption of such diets — measures which are highly recommendable whether or not triglycerides are a concern.

    http://www.ncbi.nlm.nih.gov/pubmed/15504577

    Great paper on HDL;

    The HDL hypothesis: does high-density lipoprotein protect from atherosclerosis?

    1) Men have on average lower HDL-C levels than women

    2) Smokers have 14% lower HDL-C levels than nonsmokers, and this relationship appears to be dose-dependent, whereas individuals who quit smoking show a subsequent increase in HDL-C levels

    3) A recent meta-analysis of 25 studies shows that programs of regular aerobic exercise increased HDL-C levels by 2.5 mg/dl on average

    4) Obesity, especially abdominal obesity, is also associated with lower HDL-C levels, whereas weight loss results in an elevation of HDL-C levels

    5) Patients with type 2 diabetes mellitus display several lipid abnormalities of which a low HDL-C level is a prominent feature

    6) Metabolic syndrome, a cluster of pathologies comprising abdominal obesity, hypertension, impaired glucose tolerance, high triglycerides, and low HDL-C levels, is regarded by investigators as a single disease entity resulting from insulin resistance

    7) In parallel, (postprandial) hypertriglyceridemia results in low HDL-C levels, associated with an increased cholesteryl ester transfer protein (CETP) driven exchange of cholesteryl esters and triglycerides between pro-atherogenic apolipoprotein (apo)B-containing lipoproteins (VLDL and LDL) and HDL. In fact, over 50% of the patients with low HDL-C levels also present with increased fasting triglycerides. With this in mind, HDL-C levels may be seen as a stable reflection of disturbances in triglyceride metabolism, whereas plasma triglyceride levels themselves are subject to large inter-individual and intra-individual variability.

    8) Systemic inflammation (as observed in rheumatoid arthritis and systemic lupus erythematosus), a recognized risk factor for CVD, is associated with a secondary dyslipidemia characterized by low HDL-C levels

    9) Finally, a low socioeconomic status is an independent predictor of low HDL-C

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903818/

  99. Mie

    “Show some respect. Low-carb diet are often rationalized with the HDL-C sales-speech. This is nonsense, since HDL-C is not causally related to CHD.”

    Respect to a person who’s trolling? I haven’t said a word about low carb -diets here, nor do I support such rationalization which focuses on one marker alone. Especially in the light on conflicting evidence, e.g. this

    http://www.ncbi.nlm.nih.gov/pubmed/16904539/

    As for the latter claim, let’s inspect that:

    “Ornish was able to regress the artery disease in his patients despite their HDL-C went down (together with moderate increase in triglycerides).”

    … which means nothing. We’ve got studies where LDL-C -levels didn’t change in the intervention group, yet CVD mortality went down. E.g. Lyon Diet Heart. Does that prove that LDL doesn’t matter? No. So does Ornish prove that HDL doesn’t matter? Nope.

    In addition, the Ornish approach is MULTIFACTORIAL which means that we simply cannot say anything meaningful on the issue of the diet alone – let alone the meaningfulness of individual biomarkers.

    “New research shows that many of those with elevated HDL have other protective features in their HDL. However, this does not imply that eating eggs or other animal foods will enhance the quality of HDL despite they’d cause elevation of HDL-C.”

    Yes, HDL isn’t just about the levels but there are other factors involved. But since it has been shown that low HDL levels are associated w/ poorer function and that in specific patient groups (e.g. MI patients) the function further degrades, how does that mean that HDL doesn’t matter? It would be analogous to argue that since e.g. statins don’t provide the same kind of benefits in specific target groups, they don’t matter in general CVD management.

    And I haven’t mentioned eggs, either. The ESC guidelines mention reducing trans fat and increasing physical activity as having the best effect on HDL levels.

    “There’s not a single piece of evidence that would indicate that modulation of HDL-C will enhance the prognosis.”

    Err, yes there is. See what I posted earlier.

    “People with genetically elevated HDL-C are not protected from CHD.”

    You’re referring to this Mendelian randomization study?

    http://www.ncbi.nlm.nih.gov/pubmed/22607825

    You do realize that such a study design cannot penetrate the issue beyond correlations? These people might have other aspect in their HDL that explain the lack of protection. Or in some other factor. We simply don’t know that, due to the lack of explanatory power in the study design.

    Not to mention that you’re cherry-picking here: there are plenty of studies where a life-long exposure to significant reductions in HDL-C levels as a consequence of mutations has been shown to predict increased CVD risk. See e.g.

    http://www.ncbi.nlm.nih.gov/pubmed/11809185

    “We must understand the difference between risk predictor and causal factor.”

    Indeed. Now, there is ample proof – both in humans and in animals – of the mechanisms (e.g. that HDL a) acts as a transport for cholesterol back to liver, b) helps to inhibit oxidation, inflammation, c) improves the activation of the endothelium, coagulation, and platelet aggregation) and evidence from prospective cohorts.

    Take that apart, piece by piece. If you can.

    “HDL-C is important only within a population where basically everyone has elevated cholesterol.”

    And therefore … It doesn’t matter in the context of western population??

    Jeez, what have you been smoking?

  100. Mie

    To correct myself:

    ” We’ve got studies where LDL-C -levels didn’t change in the intervention group …”

    I forgot to add “in relation to the control group”.

  101. I believe the point Richard is making about the Darwinian foundation of biomedical research is that because it has been demonstrated that elevated serum cholesterol and the feeding of dietary cholesterol and saturated fat accelerates the development of atherosclerosis in virtually all vertebrates (including nonhuman primates) that have been sufficiently challenged (so long as a way is found to raise serum cholesterol high enough for a sufficient period of time), very compelling evidence is required in order to safely say that this does not apply to humans. This is very different than the Taubesians whose claims are based off a much more limited set of animal data.

    It is not uncommon for food additives to be banned in certain nations when it is found in a very limited number of animal species that the additives can cause cancer. Furthermore, animal studies have actually been considered when creating guidelines. One example of this is the 1984 NIH consensus on lowering blood cholesterol to prevent heart disease. When presented with this much data from animal studies it is as you put it “religious nonsense” to suggest that it has no relevance to humans.

  102. Low-fat Richard

    Mie,

    HDL-C is a very important risk-predictor just like poverty is in a given context. Second, Esseltyn has been producing even more dramatical results than Ornish did (albeit with the help of low-dose statins). Watch out his upcoming study. Both Pritikin & Esselstyn produced similar results than did Ornish without the help of yoga or streching, so yes we can say very meaningful things about the role of diet in the Ornish trial…if you just take take your head out from the sand and look the totality of evidence. Third, no one in the Lyon study showed regression of their disease, the disease just progressed quicker and more aggressively among the controls. Reduction of LDL is needed to demonstrate regression of CHD. In other words, poor reasoning from your behalf.

    I look more carefully your HDL paper when I get home. Maybe I learn something new, maybe HL was wrong all the way when he wrote his blog post; maybe butter and eggs are heart healthy foods, after all they cause elevation of HDL. Heck, maybe the authors of mendelian trial were dumb enough to not to look pleitrophy, maybe they did not look several polymorphisms with each having unique pathway in influencing HDL-C levels to minimize co-founding. Maybe they just forgot all that.

  103. You again repeat: “I’ll answer that for you: nonsense & ego.”

    My point is even that the authors of the S-T meta-analysis pointed out the weakness that saturated fat was likely compared to unhealthy sources of calories and called for more of a focus on studying the effects of replacing foods with other suitable alternatives. These researchers had a good idea of the composition of the diet was of the populations in these studies which is why they are able to make such a statement. It is not very meaningful to compare the worst foods with the worst foods which has been taken advantage of by the food industry and promoters of fad diets in order to promote an unhealthy diet. I strongly agree that food should be compared with other healthy alternatives. This is not nonsense and ego but is about saving lives.

    You stated in regards to the Hopkins 1992 meta-analysis “And how is consuming very little cholesterol and lowering cholesterol intake different in practice…”
    What I was trying to point out is that this meta-analysis effectively shows that increasing intake of cholesterol when baseline intake is very low significantly raises serum cholesterol concentrations, and that decreasing intake of cholesterol from a modestly high intake to very low intakes significantly decreases serum cholesterol concentrations. I agree that increasing cholesterol intake when baseline intake is modestly high will do very little to serum cholesterol concentrations for a large portion of the populations, but that decreasing intake from a modestly high to very low levels will significantly lower serum cholesterol in a significant portion of the population. The Hopkins 1992 meta-analysis wouldn’t have shown such a significant change in serum cholesterol concentrations between very low levels and modestly high intakes if this was not the case.

    In regards to the ESC guidelines which do not appear to be as strict as the AHA guidelines, I noticed that the guidelines still mention that:
    “The cholesterol intake in the diet should ideally be <300 mg/day”
    Also in the guidelines it is pointed out that:
    “A positive relationship exists between dietary cholesterol and CAD mortality, which is partly independent of TC levels.”

    You stated "Here is the fundamental problem: you’re unable to understand that RCTs at least try and mimic the free-living conditions."
    Studies on free-living people have confirmed the findings from metabolic ward studies on the effects of dietary lipids on serum cholesterol concentrations as was the case with the Howell et al. 1997 and Weggemans et al. 2001 meta-analyses which also included experiments carried out on free-living people. In the WHI the observed changes of dietary fat and serum lipids was consistent with the Katan score. The WHI researchers pointed out that the intervention should have been more focused on decreasing intakes of saturated fat and trans fat and increasing intakes of fruit and vegetable intake in order to decrease the risk of CHD and CVD. The participants who were observed to make such changes, especially decreasing saturated fat intake experienced significantly lowers rates of CHD.

    As I already pointed out in regards to studies carried out on free-living people, "unexpected lifestyle changes in the control groups in the smoking cessation and diet-heart trials could partly explain the failure to produce statistical significant findings.” As was observed in WHI and MRFIT, participants in the control group also made dietary changes which minimized the differences in diets between the groups. A similar phenomenon with smoking cessation was also observed in the smoking cessation trials which may partly explain the lack of statistical significant findings for rates of lung cancer.

    In regards to HDL, in the meta-analysis of 108 randomized controlled trials the changes in HDL ranged from between +28 to -12mg/dl. The authors pointed out in regards to this:
    "Nevertheless, variability was sufficient that if a strong effect of high density lipoprotein cholesterol existed we would probably have detected it."

    It was not only the findings form this meta-analysis that suggests that merely raising HDL concentrations via a number of mechanisms will not necessarily translate into a decreased risk of CHD. As I pointed out there are also the mendelian randomization studies which demonstrate that genetically influenced high or low lifetime concentrations of HDL do not influence the risk of CHD. Furthermore, prospective cohort studies have not consistently shown that modifying HDL influences the risk of CHD.
    http://www.ncbi.nlm.nih.gov/pubmed/22447463

    This evidence suggests that at best HDL should be a secondary target for lipid intervention, unlike LDL which is a primary target. It is almost exclusively the promoters of diets rich in cholesterol and saturated fat that are skeptic of the influence of LDL on the risk of CHD, whereas it is not only promoters of low fat diet who cast doubt on the hypothesis that merely raising HDL concentrations will lower the risk of CHD. Perhaps it is you who is trying to defending HDL concentrations in order to promote a higher fat diet.

    Studies show that people who follow a Mediterranean type diet still have a substantial residual risk of CVD. The recent findings from Dr. Esselstyn’s study of around 200 people demonstrate that the participants who adhered to his recommendations had virtually no residual risk of CVD, even if they were previously at very high risk.

    There is little point in debating any further with you as you will just keep ridiculing people who say things you do not like and take their comments out of context. Any lines of evidence you do not like you simply refer to as a being a strawman or cherry-picked and will continue to proclaim yourself as the winner.

  104. In regards to mendelian randomization studies the researchers of the meta-analysis pointed out “Naturally occurring genetic variation could be a useful instrument to assess causality provided that several requirements have been satisfied” and showed how their inclusion criteria is likely sufficient to satisfy these requireiments.

    You said:
    “Not to mention that you’re cherry-picking here: there are plenty of studies where a life-long exposure to significant reductions in HDL-C levels as a consequence of mutations has been shown to predict increased CVD risk. See e.g.”

    How does this study you cite of 30 people from families with ABCA1 mutations demonstrate that Richard was cherry-picking when this large meta-analysis which also considered people with the ABCA1 mutation found no such association between genetically modified HDL cholesterol and CHD? The researchers were not able to find any pleiotropic effects that would explain this null association. Perhaps it is you who claim that everyone else that you disagree with is cherry-picking who the real cherry-picker is.

  105. Low-fat Richard

    HealthyLongevity,

    excellent remarks. Unfortunately Mie is a pathological confusionist who tries to sabotize my efforts. Thanks for providing a helping hand for my attempts to save lives and to make Doc understand the nonsense of the low carb/Taubes position. Potatoes & oatmeal are friends not foes.

    BTW, the only model, that I am aware of, in which CHD has been partly regressed without change in LDL involved Probucol and reduction in HDL-C itself (in a mouse). Scientist at UCLA demonstrated that low-fat diet reduced HDL-C but enhanced the quality of HDL. This is important since confusionist often rationalize their aversion to ecologically feasible low-fat, vegeterian, starch-based diets with the HDL sales pitch.

  106. Mie

    Good point there, I’ll withdraw the cherry-picking accusation in this case and apologize. Now, my general impression of the case (Mendelian randomization) doesn’t change, however: observed genetic variation & benefit in the case of LDL doesn’t mean that the lack of benefit in the case of genetic HDL variants translates to the lack of predictive power in the case of HDL altogether.

  107. Low-fat Richard

    Mie,

    do not miss HLs second post he posted today. A response to you. Unbelievably Good material. Just scroll upwards a bit.believably Good

  108. Mie

    “It is not very meaningful to compare the worst foods with the worst foods which has been taken advantage of by the food industry and promoters of fad diets in order to promote an unhealthy diet. I strongly agree that food should be compared with other healthy alternatives. This is not nonsense and ego but is about saving lives.”

    Yes, it is nonsense. You’re essentially claiming that because established methodological solutions can be exploited & twisted by some people, these solutions are to be discarded. That is – simply put – idiotic. An analogous argument would be to stop having prospective cohorts because the inherent methodological issues inevitably limit the nature of information we can gain from them.

    And yes, since you refuse to understand the apparent double standards of your stance, there’s no point in exploring this issue any further.

    “… but that decreasing intake from a modestly high to very low levels will significantly lower serum cholesterol in a significant portion of the population.”

    Hopkins et al 1992 doesn’t prove this, simply because it doesn’t address the issue of efficacy of interventions to reduce dietary cholesterol. The authors themselves do a bit of pondering on the issue, though, and state

    “People desiring maximal reduction of serum cholesterol by dietary means may have to reduce their dietary cholesterol to minimal levels (< 100-150 mg/d) to observe MODEST serum cholesterol reductions" (emphasis mine)

    In addition, remember what I mentioned about the limitations of metabolic ward studies as such? Now, care to point out large-scale interventions that would prove this claim? Or meta-analyses of prospective cohorts?

    "In regards to the ESC guidelines which do not appear to be as strict as the AHA guidelines, I noticed …"

    Indeed. However, no reference is given here. In addition, later on the guidelines state that in managing elevated TC/LDL-C the magnitude of the effect of reducing dietary cholesterol is less than that of fat modification and that the evidence pointing this out is class B.

    And this is for the management of dyslipidemias. The relevance in healthy population?

    “A positive relationship exists between dietary cholesterol and CAD mortality, which is partly independent of TC levels.”

    Err, TC levels, anyone? This remark, unfortunately too, remains a mystery as neither of the references in this section discuss the issue.

    "…. the case with the Howell et al. 1997 and Weggemans et al. 2001 meta-analyses which also included experiments carried out on free-living people."

    1) Howell et al 1997 found out that the totality of various lipid changes had an effect of ca. 5% reduction in LDL-C. Yes, 5%!!!

    "compliance with current dietary recommendations (30% of energy from fat, < 10% from saturated fat, and w/ HDL, no such thing)

  109. Mie

    It seems that the rest of my reply vanished? I’ll try again from the Howell part:

    1) Howell et al 1997 found out that the totality of various lipid changes had an effect of ca. 5% reduction in LDL-C. Yes, 5%!!!

    “compliance with current dietary recommendations (30% of energy from fat, < 10% from saturated fat, and w/ HDL, no such thing)

  110. Mie

    “HDL-C is a very important risk-predictor just like poverty is in a given context.”

    But is there in vivo & in vitro evidence of poverty e.g. enhancing the transport of cholesterol back into the liver?

    Didn’t think so …

    “Second, Esseltyn has been producing even more dramatical results than Ornish did (albeit with the help of low-dose statins). Watch out his upcoming study.”

    I googled around. You mean the study that was supposed to come out a year ago?

    http://sonic.net/~mcdsite/drmcdougall.com/forums/viewtopic.php?f=1&t=37244&view=next

    I’ll have a look as soon as it gets out.

    “Both Pritikin & Esselstyn produced similar results than did Ornish without the help of yoga or streching, so yes we can say very meaningful things about the role of diet in the Ornish trial…”

    Now, before this soon-to-be-out-within-a-year-well-next-year-then…-Chinese-Democracy -study, Esselstyn has published (to my knowledge) one study

    http://www.ncbi.nlm.nih.gov/pubmed/7500065

    which didn’t have a control group and in which only 50% of the patients succeeded in completing 5,5 years of follow-up. So excuse me if I don’t hold my breath.

    About Pritikin: I’m unaware of him having published any data concerning CVD end points.

    “Third, no one in the Lyon study showed regression of their disease, the disease just progressed quicker and more aggressively among the controls. Reduction of LDL is needed to demonstrate regression of CHD. In other words, poor reasoning from your behalf.”

    Err, if you insist on focusing on regression, which means nothing without the context of compliance & adherence. Those plaques’ll grow right back if you slip. Now, in LHS, the clinical endpoints showed benefits around 70%, with a dropout rate of less than 10%. But of course this was … a case of putting out the wrong fire?

    “Maybe I learn something new, maybe HL was wrong all the way when he wrote his blog post;”

    You COULD learn something new, that is if you wanted to. And HL wasn’t wrong all the way, he has simply going after some fresh cherries.

    “maybe butter and eggs are heart healthy foods, after all they cause elevation of HDL.”

    Err, did you catch the analogue of LDL lowering w/ cancer?

    “Heck, maybe the authors of mendelian trial were dumb enough to not to look pleitrophy,”

    Do you know that population-based studies have inherent problems in this case (adjusting for confounders very unlikely even in the optimal case)?

  111. Mie

    “I believe the point Richard is making about the Darwinian foundation of biomedical research is that because it has been demonstrated that elevated serum cholesterol and the feeding of dietary cholesterol … ”

    … it’s ok for him to refer to animal studies when he sees fit. The ego question again. And false solidarity, in your case.

    “Furthermore, animal studies have actually been considered when creating guidelines. One example of this is the 1984 NIH consensus …”

    So nearly 30 years ago animal studies were referenced? Yes, on the issue of experimental pathology/pathophysiology, which is precisely the purpose why animal studies are used. That doesn’t mean they have jack shit to do with the issue at hand (the need for human studies).

    Educate yourself on a little thing called “evidence hierarchy”. Animal studies don’t factor in at the relevant level when clinical guidelines are made.

  112. Low-fat Richard

    Mie wrote:

    “Yes, it is nonsense. You’re essentially claiming that because established methodological solutions can be exploited & twisted by some people, these solutions are to be discarded. That is – simply put – idiotic. An analogous argument would be to stop having prospective cohorts because the inherent methodological issues inevitably limit the nature of information we can gain from them.”

    HL made a valuable point why discussing with you is worthless. You are too opinionated about issues you have no clue. Let go, it’s over. It’s time for you to retire.

    “For example, it may not be useful, as is usually done, to compare a specific food to all other sources of energy, which are usually mainly refined starches, sugars, red meat, and fat-rich dairy products in typical Western diets.”

    –Walter Willet, Harvard School of Public Health

    http://healthylongevity.blogspot.fi/2012/08/forks-over-knives-and-healthy-longevity_17.html

    Thanks HealthyL for sorting out the issue of dietary cholesterol and the European guidelines. I did not have the time myself to fact-check Mie. I just reviewed the Finnish recommendations (gängse vård) for treating dyslipidemia that Mike was referring to in another post. They explicitly highlighted that the consumption of eggs should be limited to two per week.

  113. Low-fat Richard

    Mike,

    you also dismiss the evidence suggesting that dietary cholesterol influences the risk of CHD independently from serum cholesterol. In other words, dietary cholesterol promotes atherosclerosis under and above its effect on blood cholesterol levels.

  114. Low-fat Richard

    Mie,

    I don’t have much time replying to your arguments which are getting more & more bizarre. However, you wrote:

    which didn’t have a control group and in which only 50% of the patients succeeded in completing 5,5 years of follow-up. So excuse me if I don’t hold my breath.

    Healthy Longevity has already sorted things out with the nonsense around Esselstyn’s study that the low-carb echo-chamber keeps repeating. See HealthyL’s complete rebuttal of Denise Minger. It’s unfortunate that you keep resorting to spray this level of nonsense. But hey, at least we all know where you stand-up and which are your favorite blogs. It is getting clearer why you are vehemently against my arguments for a vegetarian, starch-based solutions to save lives (“Chinese democracy study”).

    Forks Over Knives and Healthy Longevity: A Missed Opportunity for the Cholesterol Skeptics

    In regards to Dr. Esselstyn’s study of his initial coronary artery disease patients, Denise Minger misleads her readers into believing that ‘half’ the patients dropped out of the study by confusing the number of patients who had a follow-up angiogram with the number of adherent patients, simply ignoring the 7 patients who adhered to the diet but did not have a follow-up angiogram. There was actually a 75% adherence rate throughout most of this study, and in the more recent and larger decade long study of over 200 patients (known as Treating the Cause of CAD), there was an adherence rate of 91% (Vid. 1).13 14

    Minger also suggested that Dr. Esselstyn’s results may have been due to luck as his study was an uncontrolled intervention study. Dr. Esselstyn however did compare the adherent and non-adherent patients. Despite having similar measurable amounts of disease at baseline as the other 18 patients, the 6 non-adherent patients had 13 new cardiac events within the first 12 years of the study despite the fact that they were still receiving standard care. On the other hand, the 18 compliant participants had no further cardiac events while being fully compliant, despite having 49 events during the 8 years prior to the study, of for which most of this time were receiving standard care.13 14 In the newer decade long study of over 200 patients, recurrent cardiac events only occurred in 0.5% of adherent participants, which is approximately 40 fold lower than other dietary or statin based trials (Vid. 1). Minger suggests that these results were due to luck but provided no evidence demonstrating that coronary artery disease can be spontaneously halted or reversed this frequently even when years of medical intervention have failed.

    http://healthylongevity.blogspot.fi/2012/08/forks-over-knives-and-healthy-longevity.html

    Do miss the second post HL made:

    Forks Over Knives and Healthy Longevity: A Missed Opportunity for the Cholesterol Skeptics
    http://healthylongevity.blogspot.fi/2012/08/forks-over-knives-and-healthy-longevity.html

  115. When the evidence from animal studies is so compelling it would be preferable to have strong evidence from human studies in order to guarantee the safety of a particular substance. We wouldn’t want those who we care about to consume a substance known to hurt virtually all species of animals without strong evidence demonstrating its safety in humans. Of course, this may not apply to someone like you who appears to prioritize their ego over saving lives.

  116. You said: “You’re essentially claiming that because established methodological solutions can be exploited & twisted by some people, these solutions are to be discarded.”

    I am currently debating with a person who refuses to accept this and exploits this data to suggest that diet rich in saturated fat and cholesterol can be healthy. I am not saying that these findings should be discarded but that the findings from these studies should be considered with great caution as the foods/macronutrients at question are most likely being compared to foods that are not likely healthy alternatives.
    As the researchers of the Astrup et al. paper I cited stated:
    “When specific foods are examined, are they being compared with appropriate alternatives? For example, it may not be useful, as is usually done, to compare a specific food to all other sources of energy, which are usually mainly refined starches, sugars, red meat, and fat-rich dairy products in typical Western diets. Other comparisons may be more informative, eg, cheese compared with butter compared with peanut butter compared with sausage compared with liver paste. Such analyses can be conducted on the basis of existing observational prospective studies, but can also be addressed in short-term human experimental intervention studies with surrogate endpoints. “

    There is no need to stop carrying out prospective studies, but rather focus on these points by Astrup et al. in order to provide a more informative analysis. Of course when testing the diet-heart hypothesis with prospective cohort studies there still exists the previously described issue related to the fact that the effect that diet has on CHD is partly mediated by serum lipids and therefore findings will likely be obscured as the result of interindividual variability.

    You said: “Hopkins et al 1992 doesn’t prove this, simply because it doesn’t address the issue of efficacy of interventions to reduce dietary cholesterol.”

    If you look at the papers cited in this meta-analysis you will find that they show that reducing cholesterol intake form moderately high levels down to very low levels has essentially the same magnitude of change on serum cholesterol levels as increasing cholesterol intake from near zero to modestly high levels. Two good example of this are references number 5 and 14. It would hardly seem biologically plausible to suggest that significantly increasing cholesterol intake from zero to modestly high levels would have such a great effect on serum cholesterol, while decreasing cholesterol intake from modestly high levels to zero have little effect. Of course you appear to be more interested in arguing than actually considering whether something is biologically plausible or not.

    You said: “In addition, remember what I mentioned about the limitations of metabolic ward studies as such?”
    A good example of an experiment carried out in a free-living population is Sacks et al. 1984. This experiment found that providing lactovegetarians with a relatively low baseline cholesterol intake with one extra-large egg per day raised LDL cholesterol by 12%.
    http://www.ncbi.nlm.nih.gov/pubmed/6142348

    You said: “Indeed. However, no reference is given here.”
    You mean these?
    http://circ.ahajournals.org/content/106/25/3143.long
    http://jn.nutrition.org/content/131/1/132.long
    For people with high LDL, the AHA and NCEP guidelines recommend restricting cholesterol intake to <200mg/day (and <300mg/day for people without elevated cholesterol)

    You said: “In addition, later on the guidelines state that in managing elevated TC/LDL-C the magnitude of the effect of reducing dietary cholesterol is less than that of fat modification and that the evidence pointing this out is class B.”

    Even if the importance of reducing dietary cholesterol is to be considered of secondary importance compared to reducing saturated fat intake, it should still be considered as CHD is the leading cause of death in the world.

    “This remark, unfortunately too, remains a mystery as neither of the references in this section discuss the issue.”

    My guess is that they were referring to animal experiments and human epidemiological studies which found suggestive evidence that dietary cholesterol has an adverse effect on CHD that is partly independent of serum cholesterol levels. Stamler has previously reviewed some of these papers:
    http://www.ncbi.nlm.nih.gov/pubmed/3052353

    You said: “Howell et al 1997 found out that the totality of various lipid changes had an effect of ca. 5% reduction in LDL-C. Yes, 5%”

    It appears that you are unable to comprehend these findings. This 5% figure is the predicted effect of what would happen by modifying the dietary fat intake of the average Americans diet (based on data from NHANES II) to levels comparable the recommendations of the NCEP Step I diet. Since the average intake of saturated fat and dietary cholesterol in NHANES II was not that much greater than the NCEP Step I diet recommendations, a large change in LDL-C would not have been expected.

    As expected the findings from free-living people tends to be a little weaker than that of metabolic ward experiments (although this was not the case for Sacks et al. 1984) as free-living people are not obliged to adhere to the diet. They are however comparable with metabolic ward studies and therefore provide confidence for the validity of the findings from metabolic ward studies.

    Another form of evidence is the natural experiments and policy interventions in entire populations. Good examples of large decreases of saturated fat resulting in significant decreases in serum cholesterol observed at a population levels is that of Mauritius, Finland and the former communist nations of Eastern Europe. A good example of the exact opposite situation is that of Beijing. These observations provide further confidence for the validity of the findings from metabolic ward studies.
    http://eurheartj.oxfordjournals.org/content/32/10/1187.full
    http://www.biomedcentral.com/1471-2458/11/641
    http://circ.ahajournals.org/content/110/10/1236.long

  117. Low-fat Richard

    Mike,

    in regards to Esselstyn, do NOT miss HLs second blog post, that is. Esselstyn followed his patients for 12 years. One of his patients was a cardiologist in his 40s who managed to drop his LDL down 38mg/dl and demonstrated virtually 100% regression of his CHD. Essy’s results are easy for us to accept: low fat diets have been shown to result in regression of CAD in non-human primates (as well). You certainly pay lip service to the importance of weighting the totality of evidence, however, seldom do I see you considering evidence as a whole in your own reasoning.

  118. Z.M.

    Esselstyn’s study didn’t have a control group (6 non-adherent subjects cannot be regarded as a proper control group) and his study employed multiple interventions making it impossible to know what factors were responsible for the result. Why is this so hard for Richard and HL to understand? The constant appeal to animal studies show just how poor the human evidence is in supporting their position. They also claim the “evidence as a whole” support their position. Well, that’s only true if you interpret the “evidence as a whole” in such a biased manner as they do.

  119. Dr. Esselstyn’s intervention only focused on dietary change and for many but not all patients cholesterol lowering medication was prescribed until patients reached desirable cholesterol levels. In the newer decade long study of around 200 patients, recurrent cardiac events only occurred in 0.5% of adherent participants, which is approximately 40 times lower than statin based trials. This strongly suggests that cholesterol lowering medication played only a minor role in the studies success, especially considering that many of the patients were likely prescribed statins prior to the study yet were unable arrest their condition until partaking in the dietary intervention. Although it was not a controlled trial it is very difficult to conclude that the results, especially that of the newer study was the result of luck considering the number of patients and the fact that years of medical intervention failed to prevent reoccurring coronary events.

    It has been demonstrated throughout the animal kingdom, including multiple species of nonhuman primates that a cholesterol-free diet results in regression of atheroma that was induced experimentally induced by a diet rich in cholesterol and saturated fat. However, this is not the only piece of evidence that supports the benefit of Esselstyn’s diet on atheroma. Both randomized controlled trials and mendelian randomization studies support the hypothesis that lowering LDL cholesterol has favorable effects on atheroma.
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468364/
    http://www.ncbi.nlm.nih.gov/pubmed/23275344

    Prospective cohort studies have fairly consistently shown that frequent intake of fruits, vegetables, whole grains, legumes and dietary fiber significantly lower the risk of cardiovascular disease, which could not be entirely explained by traditional risk factors. In populations that consume a diet somewhat comparable to the recommendations of Dr. Esselstyn, atherosclerosis has be shown to be all but entirely absent. Examples includes the traditional Okinawans, the Papua New Guinean highlanders, and the native Indonesians.
    http://www.ncbi.nlm.nih.gov/pubmed/5406469
    http://www.ncbi.nlm.nih.gov/pubmed/21002846
    http://www.ajconline.org/article/S0002-9149(11)03212-7/fulltext

  120. Low-fat Richard

    ZM,

    the patient I was referring to refused to eat statins throughout the whole study.statins throughout the whole study.

  121. Mie

    “But hey, at least we all know where you stand-up and which are your favorite blogs.”

    Err. you don’t remember me criticizing Minger in Jussi’s blog? :-)

    But yes, let’s have a look at HL’s points:

    “In regards to Dr. Esselstyn’s study of his initial coronary artery disease patients, Denise Minger misleads her readers into believing that ‘half’ the patients dropped out of the study by confusing the number of patients who had a follow-up angiogram with the number of adherent patients, simply ignoring the 7 patients who adhered to the diet but did not have a follow-up angiogram. ”

    Now, if these seven people didn’t go through the angiogram, we don’t know about the their condition, do we? Or do you think it’s just a conincidence that the results were reported FOR THOSE 11 who had the angiogram taken? Jeez, the both of you: put down that pipe!

    “Dr. Esselstyn however did compare the adherent and non-adherent patients.”

    Which is NOT the same as having a CONTROL group!!! Good lord, I didn’t expect HL to sink to THIS level. Seriously Richard and HL, go read a book on methodology of clinical trials. Please.

    Now, the value of a longitudinal study like this is to observe whether treatment such as this might be viable to be tested in larger studies. That is. This is a good & promising starting point, but nothing more.

  122. Mie

    “I am currently debating with a person who refuses to accept this and exploits this data to suggest that diet rich in saturated fat and cholesterol can be healthy.”

    Yet again, I resort to mischaracterizations.

    “I am not saying that these findings should be discarded but that the findings from these studies should be considered with great caution as the foods/macronutrients at question are most likely being compared to foods that are not likely healthy alternatives.”

    And I’ve clearly stated that yes, the results of the two aforementioned meta-analyses don’t mean that e.g. carbohydrates should/could be treated as one single entity. However, the point was and has been that your take on the fact that S-T et al (or Mensink et al) could be used by e.g. cholesterol denialists and therefore these two are problematic is clearly BS. You call for de facto silencing of studies & authors on the basis of questionable assumptions.

    “If you look at the papers cited in this meta-analysis you will find that they …”

    … don’t discuss the issue of interventions to limit tot.cholesterol intake & plasma lipid levels. Now, you can go back and forth that graph all you wish to, but that is simply the result of either a) your inability to understand the difference I’m talking about here and/or b) the wish to downplay the main findings of the paper – you know, the one that the authors themselves summarized:

    “People desiring maximal reduction ofserum cholesterol by dietary means may have
    to reduce their dietary cholesterol to minimal levels (< 100-150 mg/d) to observe modest serum cholesterol reductions"

    In addition, you resort to quote/study mining:

    "A good example of an experiment carried out in a free-living population is Sacks et al. 1984. This experiment found that providing lactovegetarians with a relatively low baseline cholesterol intake with one extra-large egg per day raised LDL cholesterol by 12%."

    So you've got a) one small trial (n=17) with b) quite specific subgroup in which b) the amount of cholesterol quadrupled? Now, do tell me what kind of extrapolations can we make on the basis of this? And do you consider this a) a large scale trial and/or b) one rivalling the two abovementioned meta-analyses of prospective cohorts? (And yes, I'm aware of the third one, which can possibly show the issue in new light – however, it's kinda hard to account for it since I haven't been able to access the full text).

    "You mean these?"

    No, I meant what I said. There was no reference number after that particular sentence.

    "Even if the importance of reducing dietary cholesterol is to be considered of secondary importance compared to reducing saturated fat intake, it should still be considered as CHD is the leading cause of death in the world."

    Considered? If there's reason to consider it.

    "My guess is that they were referring to animal experiments and human epidemiological studies which found suggestive evidence that dietary cholesterol has an adverse effect on CHD that is partly independent of serum cholesterol levels. Stamler has previously reviewed some of these papers:
    http://www.ncbi.nlm.nih.gov/pubmed/3052353&quot;

    1) In the light of the meta-analyses above ("slightly" more that four cohorts), this 20+ year-old paper has … What kind of meaning? Is it referenced in e.g. the ESC guidelines?

    2) I'd be interested in knowing what is this adverse effect (partly) independent of plasma cholesterol levels?

    "It appears that you are unable to comprehend these findings. This 5% figure is the predicted effect of what would happen by modifying the dietary fat intake of the average Americans diet (based on data from NHANES II) to levels comparable the recommendations of the NCEP Step I diet. Since the average intake of saturated fat and dietary cholesterol in NHANES II was not that much greater than the NCEP Step I diet recommendations, a large change in LDL-C would not have been expected."

    Please, don't try that easy-to-expose BS with me. Now, the changes were clearly described as the precise recommendations of e.g. older ATP (III), that is the recommendations YOU earlier referenced as justification for e.g. limiting dietary cholesterol. And – presto! – the recommendations get invalidated when the minor effect they have is brought out!

    Now, what OTHER kind of justification did you find from Howell et al, if the ENTIRE range of fat modification accounts for very little?

    "As expected the findings from free-living people tends to be a little weaker than that of metabolic ward experiments (although this was not the case for Sacks et al. 1984) as free-living people are not obliged to adhere to the diet. They are however comparable with metabolic ward studies and therefore provide confidence for the validity of the findings from metabolic ward studies."

    The same as above w/ the "drop-the-weasel-act". They aren't "a little weaker", they lack clinical meaning in the light of up-to-date clinical guidelines, apart from the management of dyslipidemias (in the case of ATP-IV, we shall see what comes out … eventually). And they show PRECISELY that extrapolation on the basis of metabolic ward studies should be treated with caution.

  123. Mie

    “Dr. Esselstyn’s intervention only focused on dietary change and for many but not all patients cholesterol lowering medication was prescribed until patients reached desirable cholesterol levels.”

    It’s kinda hard to take your word for the latter, since according to Esselstyn himself:

    “During the 7 years since the conclusion of the 5-year study, all but 1 patient have continued to adhere to the prescribed diet and MEDICATION.” (capitals mine, since you tend to have a poor eyesight)

    http://www.icardio.me/wp-content/uploads/2012/04/updatingA12Year.pdf

    BTW, if you go through Esselstyn’s follow-up paper, you’ll notice that 1 of the 18 patients died right after the 5-year mark, which means 5,5% CAD mortality in the treatment group. Now, he was one of the 11 patients to have their angiography taken so if we calculate the total mortality on the basis of these patients (since we do have data on the condition of their arteries & regression of CAD), that makes 1/11 = 9,1% CAD mortality in the group of people in whom CAD regressed.

    “In the newer decade long study of around 200 patients, recurrent cardiac events only occurred in 0.5% of adherent participants, which is approximately 40 times lower than statin based trials. This strongly suggests that cholesterol lowering medication played only a minor role in the studies success, especially considering that many of the patients were likely prescribed statins prior to the study yet were unable arrest their condition until partaking in the dietary intervention.”

    Now folks, remember to take that “suggests” in the LOOSEST possible sense of the term. You simply CANNOT compare the results of different trials to each other like that and expect to come up w/ definitive answers. You’d need a single randomized trial COMPARING these things.

    “Prospective cohort studies have fairly consistently shown that frequent intake of fruits, vegetables, whole grains, legumes and dietary fiber significantly lower the risk of cardiovascular disease, which could not be entirely explained by traditional risk factors.”

    Now, the traditional risk factors are e.g. dyslipidemias, blood pressure, overweight, metabolic syndrome etc. etc. Epidemiological studies – or rather the meta-analyses done on them (since epidemiological data is prone to counfounders, looking at individual studies is questionable – especially given HL’s penchant for cherry-picking those favourable to his position) – haven’t, to my knowledge, given any meaningful indication that these risk factors lack explanatory power.

    Perhaps you’d care to reference one such meta-analysis.

  124. Mie

    Richard:

    “HL made a valuable point why discussing with you is worthless. You are too opinionated about issues you have no clue. Let go, it’s over. It’s time for you to retire.”

    Now DO tell me where in the bit above is there an argument directed at the point I made?

    As regards to this

    “For example, it may not be useful, as is usually done, to compare a specific food to all other sources of energy, which are usually mainly refined starches, sugars, red meat, and fat-rich dairy products in typical Western diets.”

    quote from Willett: of course the comparison isn’t “useful” in the sense of clinical recommendations concerning the diet as a whole.That, however, wasn’t the point of e.g. Mensk et al (2003): the point there was to compare FATTY ACIDS to EACH OTHER in the sense of the different effects they – and different foods, extrapolated on the basis of their fatty acid content – have on plasma cholesterol (excuse the capitals, but since you too have demonstrated an appalling lack of reading comprehension, I feel compelled to use them – for your benefit, of course).

    “I just reviewed the Finnish recommendations (gängse vård) for treating dyslipidemia that Mike was referring to in another post. They explicitly highlighted that the consumption of eggs should be limited to two per week.”

    Now in this case Richard, you inadvertently stumbled upon the problematic point in the guidelines. (Which, of course, are NOT for treating healthy individuals but people with a major risk factor for CVD). The references in this part

    “Runsaasti kolesterolia sisältävistä elintarvikkeista kananmunia on suositeltavaa nauttia enintään kaksi viikossa (ottamalla myös huomioon ruoissa ja leivonnaisissa mukana oleva kananmuna) 112, 113, 114. Yhdessä kananmunan keltuaisessa on päivittäisen enimmäismäärän verran kolesterolia (300 mg)”

    http://www.kaypahoito.fi/web/kh/suositukset/naytaartikkeli/tunnus/hoi50025

    point to

    1) 112: A popular, non peer-reviewed article – the likes of which shouldn’t be used in clinical guidelines since they ought to be based on peer reviewed literature
    2) 113: A meta-analysis that HL references above, problematic since a) it contained both free-living and controlled subjects, b) in which two of the 17 studies didn’t report changes in LDL and c) in which the changes in LDL with the cholesterol equivalent of one XL-egg per day were the greatest in the abovementioned Sacks et al (1984), thus further attenuating the findings.

    http://ajcn.nutrition.org/content/73/5/885/T1.expansion.html

    3) 114: a single prospective cohort study, in which the key finding was that

    ” we showed that infrequent egg consumption (ie, ≤6 eggs/wk) was not associated with MI, stroke, or total mortality in healthy US male physicians. In addition, consumption of ≥7 eggs/wk was associated with a modestly but significantly greater risk of total mortality in this population.”

    http://www.ncbi.nlm.nih.gov/pubmed/18400720

    The references, in other words, are quite poor.

    Now, bear in mind that the guidelines do point out that one egg yolk contains they amount of cholesterol (300 mg) recommended for people who have dyslipidemia. However, this doesn’t translate directly into such a recommendation as is made here: they ask to account for the cholesterol found in foods and especially pastries etc., which is nonsensical since a) you can always drop e.g. red meat etc. in favour of eggs and b) pastries and other products of that sort shouldn’t be consumed by people with dyslipidemia any way.

    Richard, thank you indeed! This could be a matter worth bringing to the attention of the people responsible for these guidelines. Their stance on this issue simply lacks scientific “muscle”.

  125. Mie

    Concerning the first comment

    “Yet again, I resort to mischaracterizations.”

    Scratch that. I failed to check my text properly before I sent it and that remark isn’t related to the issue at hand. However, the following will be:

    EVERYTHING can be utilized by people with a dogma. Studies or the lack of studies, it matters not. Therefore, to “criticize” (again, I’m using this in the loosest possible sense, thanks to you guys) a paper on the basis of a subjective conception of “lacks” in the “Discussion” part – or because of a misconception concerning a methodological choice – is nonsensical and cannot be justified with the behavior of other dogmatists with similar intent but different goals.

  126. Z.M.

    It seems you do not understand how vital a control group is and how important it is to control variables. If there are other plausible explanations for the result then you cannot know that your explanation is the correct one.

    HL:”In the newer decade long study of around 200 patients, recurrent cardiac events only occurred in 0.5% of adherent participants,”

    It would be nice to see a reference. However if it involves no control group and multiple interventions don’t waste my time.

    HL:”Prospective cohort studies have fairly consistently shown that frequent intake of fruits, vegetables, whole grains, legumes and dietary fiber significantly lower the risk of cardiovascular disease”

    Prospective cohort studies are also severely limited by bias and confounding. It seems that observational studies are a problem (e.g. measurement error) when it contradicts your views but are not a problem when it suits yourself. It may well be the case that if saturated fat is suddenly recommended as a health food we may start seeing consistent associations of protective effects of saturated fat in observational studies.

    HL:”It has been demonstrated throughout the animal kingdom, including multiple species of nonhuman primates that a cholesterol-free diet results in regression of atheroma that was induced experimentally induced by a diet rich in cholesterol and saturated fat.”

    It also has been demonstrated throughout the animal kingdom that oxidative stress is a major part of the disease process and significant reductions in atherosclerosis can take place in the face of severe hypercholesterolemia (which is not a desirable state to be in). Saturated fat has never been found to induce atheroma in humans (which is why you complain about every saturated fat study in humans which contradicts your views) and regression in monkeys can take place in the presence of saturated fat without cholesterol – http://www.ncbi.nlm.nih.gov/pubmed/3579722

  127. Mie

    “Unfortunately Mie is a pathological confusionist who tries to sabotize my efforts.”

    Now, since it’s you saying this, I’ll take that as a compliment. Just like I take the cries of die-hard low-carbers on other blogs, accusing me of being on the payrolls of “statin industry” as compliments, too. :-)

    “Scientist at UCLA demonstrated that low-fat diet reduced HDL-C but enhanced the quality of HDL. This is important since confusionist often rationalize their aversion to ecologically feasible low-fat, vegeterian, starch-based diets with the HDL sales pitch.”

    Now, I thought that HDL didn’t matter? And suddenly the quality does, in the context of low-fat diets, of course… .-)

    I think someone already mentioned that high intakes of safa (among other things such as DM2) can mess up the anti-inflammatory properties of HDL. In that context the abovementioned finding doesn’t seem that odd. Of course, this tells nothing about the relevance of HDL in the context of diets low in safa but higher in unsaturated fatty acids – which improve these properties.

    http://www.ncbi.nlm.nih.gov/pubmed/16904539

  128. Low-fat Richard

    Mike,

    In the light of the meta-analyses above (“slightly” more that four cohorts), this 20+ year-old paper has … What kind of meaning? Is it referenced in e.g. the ESC guidelines?

    mechanical evidence for these findings (dietary cholesterol influencing CHD independently of serum cholesterol) exist, these findings provide biological plausibility for the association.

    Eggs, Too, May Provoke Bacteria to Raise Heart Risk
    http://www.nytimes.com/2013/04/25/health/eggs-too-may-provoke-bacteria-to-raise-heart-risk.html?_r=0

    You seem enunciate that public dietary recommendations are shaped & developed in order to provide best solutions for long-term health. This is not the case. Eric Rimm from Harvard School of Public Health disclosed to Reuters in regards to a major health report produced by the National Academy of Science, which he was an author of that:

    “We can’t tell people to stop eating all meat and all dairy produces. Well, we could tell people to become vegetarians… If we were truly basing this on science we would, but it is a bit extreme”

    In regards to Esselstyn: you wrote :

    “BTW, if you go through Esselstyn’s follow-up paper, you’ll notice that 1 of the 18 patients died right after the 5-year mark, which means 5,5% CAD mortality in the treatment group”

    Yes, you are right. However, curious readers would be interested in the details and Esselstyn has provided them:

    When I was accepting patients for my original study, I received a call from a cardiologist who was eager for me to accept one of his patients. The patient was a 67 year old male pediatrician who had recently sustained a massive heart attack during an angioplasty for diffuse coronary artery disease.

    He had lost so much heart muscle he was in congestive heart failure, his left ventricular ejection fraction was less than 20% and his life expectancy was less than 6 – 12 months.

    I momentarily hesitated. I was reluctant to accept anyone with such an extremely poor prognosis into what I hoped would be a long term study of coronary disease patents. As he could be offered nothing else, I gladly accepted him. He turned out to be a wonderful man and a magnificent patient.

    He did not die at 6 or 12 months. He far outlived his original prognosis and after 5 years on our program had a repeat angiogram which confirmed disease reversal. Nevertheless, 6 months following his follow up angiogram he succumbed to a cardiac arrhythmia which had been predicted as his ultimate fate at the time he joined the program. At his autopsy there was no evidence of a new heart attack.
    http://www.heartattackproof.com/clarification.htm

    In regards to eggs, serum cholesterol has a strong, independent, log-linear association association with strokes and CHD starting from very low levels. The National Research Council, in its 1989 report “Diet and Health” felt that setting the cut-off too low would merely frustrate the public. The council also surmised, INCORRECTLY, that if the upper level were set at 200 mg/dL, most Americans would achieve a total cholesterol level of 150 mg/dL or less. My best argument against eggs is that, most adult humans cannot achieve biologically normal and safe cholesterol levels if eggs are present in the diet.

    A study looking at large population took regression dilution bias into consideration and concluded that optimal cholesterol levels is <3.8mmol/l which for most adult humans can only be achieved if eggs (and other animal foods) play non-existent or minor role in the diet.
    http://www.ncbi.nlm.nih.gov/pubmed/18677162

  129. Low-fat Richard

    Moreover, Brown & Goldstein on eggs:

    How LDL receptors influence cholesterol and atherosclerosis.

    “If the LDL receptor hypothesis is correct, the human receptor system is designed to function in the presence of an exceedingly low LDL levels. The kind of diet necessary to maintain such levels would be markedly different from the customary diet in Western industrial countries (and much more stringent than moderate low-cholesterol diets of the kind recommended by the American Heart Association). It would call for total elimination of dairy products as well as eggs, and severely limited intake of meat and saturated fats”.

    http://www.ncbi.nlm.nih.gov/pubmed/6390676

    In regards to co-founding in mendelian trials looking at biomarkers in the lipid fraction, Ference et al concluded:

    “We found no evidence of any heterogeneity of effect on the risk of CHD per unit lower LDL-C among any of the polymorphisms included in our study. This lack of heterogeneity of effect strongly suggests that the results of our study are unlikely to be significantly confounded by pleiotropy or linkage disequilibrium because it is unlikely that each of the included polymorphisms are acting through similar pleiotropic effects or have similar linkage disequilibrium patterns…This finding suggests that the effect of long-term exposure to lower LDL-C on the risk of CHD appears to be independent of the mechanism by which LDL-C is lowered. Therefore, the method of lowering LDL-C is likely to be less important than the magnitude and timing of LDL-C reduction. As a result, diet and exercise are probably as effective at reducing the risk of CHD as are statins or other treatments that lower LDL-C when started early in life (and when measured per unit lower LDL-C).”

    As we know, similar trial was done in regards to HDL-C and the scientist, who know the science behind HDL best, concluded to NYT:

    “I’d say the HDL hypothesis is on the ropes right now,” said Dr. James A. de Lemos, a professor at the University of Texas Southwestern Medical Center, who was not involved in the study.

    Dr. Michael Lauer, director of the division of cardiovascular sciences at the National Heart, Lung and Blood Institute, agreed.

    http://www.nytimes.com/2012/05/17/health/research/hdl-good-cholesterol-found-not-to-cut-heart-risk.html

  130. Mie

    “You seem enunciate that public dietary recommendations are shaped & developed in order to provide best solutions for long-term health.”

    Yes, I do. Notice that “best” and “long-term” coincide: that is, a solution producing e.g. 20% decrease in risk marker X & with adherence levels of 60% is NOT as recommendable on a general level as a solution producing 15% decrease in risk markers X and Y & with adherence levels of 75%.

    And I’m supposed to change my belief on a basis of an anecdote?

    “Yes, you are right. However, curious readers would be interested in the details and Esselstyn has provided them:”

    And this changes the situation … How? How are we supposed to evaluate the cases of the others? Were they that much worse off? Better? How do we know?

    Would you care to tell us, if you do?

    “In regards to eggs, serum cholesterol has a strong, independent, log-linear association association with strokes and CHD starting from very low levels.”

    Which is irrelevant in relation to eggs since you’re talking about SERUM cholesterol, not DIETARY cholesterol. These two have a weakish link, apart from sick people (e.g. diabetes, CVD etc.) and/or hyperresponders.

    “The National Research Council, in its 1989 report … ”

    And yes, once again 20+-year-old reference, despite the fact that current recommendations are a) either not very well-crafted in this sense (Finnish Käypä Hoito: poor references and reasoning) and b) consider the issue relevant to people with a MAJOR RISK FACTOR.

  131. Mie

    This

    “http://www.ncbi.nlm.nih.gov/pubmed/6390676″

    is extrapolation in the level of speculation. Your quotemining of “eggs” out of the main point (low LDL levels desirable) is simply unfounded, as is the speculation B & G practice in relation to e.g. dairy products. If you have any data on low-fat dairy products increasing the risk of CVD, please share it.

    Of course, the issue of comparing different studies w/ different diets, populations, durations etc. etc. is pointless. If you have COMPARATIVE studies – or better yet, a meta-analysis – showing the superiority of a low-fat vegan/semivegan diet as compared to other contenders (e.g. MD, DASH, Atkins or other forms of low carb etc. etc.), please do so.

    As for the HDL issue, you might want to reply to my earlier points before flooding more quotes concerning the same study.

  132. Low-fat Richard

    Mike,

    “Now, since it’s you saying this, I’ll take that as a compliment. Just like I take the cries of die-hard low-carbers on other blogs, accusing me of being on the payrolls of “statin industry” as compliments, too”

    You don’t play this game fair. You resort to creating confusion and pushing half-truths. So far you’ve claimed:

    1) The cigarette trials that tested the effects of smoking cessation were successful.

    -You couldn’t accept the fact that we need to consider the totality of evidence rather than just one piece of it.

    2) Dietary cholesterol is not important in preventing chronic disease.

    -You push your denialism without any regard to Darwinian foundation of our biomedical research paradigm: even small amounts of dietary cholesterol have adverse effect on the arteries of non-human primates. Neither do you accept the evidence suggesting that dietary cholesterol influences CHD independently of serum cholesterol levels; recent research to eggs and gut bacteria provide confidence to these findings.

    3) We cannot say anything meaningful about the effect of diet in the outcomes of Ornish’s trial.

    -Again, you refuse look at the totality of evidence. Regression of CAD has been shown to mediate via low-fat feeding pattern in non-human primates.

    Furthermore, you insist that HDL-C is causally related to CHD. You keep parroting that I do not think HDL cholesterol is important. This is nonsense.

    You wrote:

    Good lord, I didn’t expect HL to sink to THIS level. Seriously Richard and HL, go read a book on methodology of clinical trials. Please.

    The findings from Esselstyn’s study were brought up by me since they add confidence that much of the benefits seen in Ornish’s patients indeed mediated via a) the diet induced ~40% drop in LDL cholesterol and b) the diet which excluded almost all the foods that have harmful on the endothelium function. I did not refer to Esselstyn for him providing the perfect, randomized controlled trial (Ornish did that). Esselstyn’s study proved that coronary artery disease can be reversed with low-fat diet in humans.

    This is what nearly 100% drug-free reversal of atherosclerosis looks like. This patient, cardiologist, refused to take any statins and relied purely on diet. This man was lean and athletic already prior his myocardial infarction. After 5-years adherence to low-fat diet:
    http://www.heartattackproof.com/cardio1.jpg

    Which is irrelevant in relation to eggs since you’re talking about SERUM cholesterol, not DIETARY cholesterol

    You are confused. The relevance is that most adult egg eaters do not have low-cholesterol. The fact that dietary cholesterol does not have much effect on people with “normal” cholesterol, which is BTW 200% above what is biologically normal, does not indicate that people desiring to have biologically normal and healthy cholesterol levels can eat eggs. I am sure this is what B & G was out after. Just because paper is 20 years old, does not mean that outdated. This is based on solid science, not on some fad that changes every second year.

    Yes, I do. Notice that “best” and “long-term” coincide: that is, a solution producing e.g. 20% decrease in risk marker X & with adherence levels of 60% is NOT as recommendable on a general level as a solution producing 15% decrease in risk markers X and Y & with adherence levels of 75%.

    Ok, good that you clarified this. I don’t care about the dietary habits and adherence of sick Western people on prescription drugs. I care about saving lives, saving the planet and healthy longevity. I am interested in science, I am in control of my own adherence. You can have your mainstream lip service to healthy diet, I am about making the environment more open to starch rich, plant-based diets..

    Btw, I think statins are jewel and best thing in medicine next to vaccinations and aspirin. For optimal effect, everybody, besides pure vegeterians, should start considering taking statins already in their 20s-30s.

  133. In addition to what Richard pointed out about Esselstyn’s patient who died of a ventricular arrhythmia.

    From Esselstyn’s book:

    “The emphasis was on absolute adherence to my nutritional program, which I reinforced through… All of the participants in my research were severely ill, with disease in all three-coronary arteries. Most had undergone a previous heart bypass operation or an angioplasty that eventually had failed. Several had failed these procedures twice. And several had been told by their cardiologists that there was nothing further to be done — that they must prepare for the inevitable progression of their disease.”

    From Esselstyn’s website:

    “Clearly some of our most profound successes in arresting and reversing disease were with patients who either refused or were incapable of taking statins. Nothing is as powerful for the prevention of cardiovascular disease as plant based nutrition.”

    “Adherent patients have experienced no extension of clinical disease, no coronary events, and no interventions. This finding is all the more compelling when we consider that the original compliant 18 participants experienced 49 coronary events in the 8 years before the study.”

    We know clearly that all these patients were very sick and that they had virtually no coronary events through the 20 year follow-up. We also know that the main emphasis was on the prescribed diet and that a number of the patients did not take statins.

    In the newer decade long study of around 200 patients, recurrent cardiac events only occurred in 0.5% of adherent participants. In one of Esselstyn’s videos he pointed out that this one event was a non-fatal stroke in a hypertensive prone patient who gauged on salt, and therefore wasn’t exactly adhering to Esselstyn’s recommendations.

    ZM, you said “It seems you do not understand how vital a control group is and how important it is to control variables. If there are other plausible explanations for the result then you cannot know that your explanation is the correct one.”
    Where is the evidence that suggests this is can be explained by other factors? Statins have not been shown to be that successful and a number of the patients did not even take them. Although there is was not control group it would be very difficult to explain this finding as the result of sheer luck, unless you can find some evidence demonstrating that coronary artery disease can be spontaneously halted or reversed this frequently even when years of medical intervention have failed.

    A control group is not everything, many impart health and safety recommendations have not been based on randomized controlled trials. You seem to dislike epidemiology just about as much as those who deny that smoking is a cause of lung cancer. Of course you two will refuse to look at the strengths of this study and will stop at nothing to downplay these very impressive findings.

    Low-carbohydrate diets have been promoted as being healthy in Sweden for some time now but the prospective cohort studies coming out of Sweden haven’t exactly shown the low-carb diets to be associated with a decreased risk of mortality. When I pointed out the issue of measurement error I cited high quality evidence showing that based on mathematical formulas that close to null results are to be expected even if a causal relationship does exist.

    Dietary cholesterol has been recognized as the sine qua nons for the dietary modification of experimental atherosclerosis in many species of animals. In many species saturated fat will not induce atherosclerosis nor elevate serum cholesterol in the presence of a cholesterol free diet. There are exceptions when saturated fat will accelerate atherosclerosis in a number of species when cholesterol is not presence, such as in the presence of semi purified diets. However when dietary cholesterol is available in sufficient amounts saturated fat will typically accelerate atherosclerosis in many species, including nonhuman primates. Few researchers however have succeeded in inducing atherosclerosis in animals by dietary means in the presence of a cholesterol-free diet very low in saturated fat. I am guessing that you are not suggesting people should consume a very low cholesterol diet.

    Mie, you said “Perhaps you’d care to reference one such meta-analysis.” Perhaps you would like to read the meta-analysis on fiber I previously cited. For a meta-analysis on fruits and vegetables: “Firstly, the relation is biologically plausible with abundant clinical and laboratory data demonstrating that the micro- and macro-constituents of fruit and vegetables improve important risk factors of CHD, such as hypertension, dyslipidemia, and diabetes (1–3). Secondly, the association persists after adjustment on these risk factor, suggesting a specific effect of fruit and vegetables.”
    http://jn.nutrition.org/content/136/10/2588.full

  134. Low-fat Richard

    Now Mie,

    you have problems with sound reasoning around dietary cholesterol, so please, allow me to break it down for with simple example:

    My LDL was 1.8 mmol/l at the least measurement. These digits are equivalent to the upper-limit of free-ranging monkeys who have LDLs generally around 1.00-1.8mmol/l, rarely exceeding over 2mmol/l. I am on a egg-free diet. If I eat eggs, my LDL increase, and I will not have biologically normal, physiologic serum cholesterol anymore. Do you understand? Now, I am quite happy with my LDL levels, but I’d like them to be couple decimal lower. My buddy had his LDL at 1.3mmol/l (50mg/dl), but he is somewhat more stringent with his diet, and eat less SFA containing nuts and seeds than I do.

    Although, I am probably immune to CHD already now. Most of Esselstyn’s patients who showed reversal of CAD had their LDLs around 2mmol/l (80mg/dl) and even above. And, I started already in my 20s. Cholesterol is important, but even more important is eating a plant-based diet and not to eat foods that bring havoc to endothelium function.

    Anyways, don’t worry. When we promote starch-based diets for long-term health, we make people more open to them and once they understand the potential health benefits related to these diets, such as immunity to many chronic disease, their adherence for plant-based diets gets better. Not really rocket-science.

  135. In regards to the Weggeans et al. meta-analysis (Reference 113?) your criticisms is not justified as they were already addressed by these authors:
    “Stratification of the studies for study design (crossover or Latin-square compared with parallel), setting (metabolic ward compared with free-living), or adjustment of the change in dietary cholesterol for energy intake did not materially alter the results… We found no publication bias in our meta-analysis by use of funnel plots. In the studies that failed to fulfill our selection criteria”

    You downplay high quality studies because you refuse to consider the evidence.

    One of the major advantages of the Physicians Health Study over many other cohort studies that addressed the association between egg intake and all-cause mortality is that dietary intake was updated over time, and therefore it is less likely to suffer so badly from regression dilution bias. In regards to the Physicians Health Study it is important to consider that the linear trend for the association between egg intake and mortality was significant.

    It is also important to consider high vs low intake separately as participants with a high and low intake are much more likely to be misclassified into the medium ranges of intake than participants with an extreme range of intake being misclassified into the opposite extreme range of intake. Here is a well-cited reference explaining this issue:
    http://www.sciencedirect.com/science/article/pii/0021968178900048

    The findings form the Physicians Health Study also suggest that any intake of egg increases the risk of type II diabetes, and any intake of egg among diabetics increases the risk of all-cause mortality.
    “Updating egg consumption using time-dependent Cox regression (PHS I) yielded a stronger relation between egg consumption and incident type 2 diabetes in men with HRs of 1.0 (reference), 1.10 (95% CI 0.99–1.23), 1.31 (1.16–1.47), 1.40 (1.10–1.77), 1.77 (1.39–2.26), and 1.99 (1.23–3.23), from the lowest to the highest category of egg consumption, respectively, using a multivariable model as above”
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2628696/

  136. Low-fat Richard

    BTW,

    speaking of adherence of sick, obese people on prescription drugs. Neal Barnard tested the effect of oil-free, low-fat vegan diet to diabetic people. The diet was adlibitum, participants were encouraged to eat all they want. Neal Barnard got really impressive adherence in his RCT and many of participants were able to reduce or drop entirely their medication during the trial. 75% carbs. Obviously, not perfect adherence, since many patients showed intake of dietary cholesterol even though they were told to eat vegan. Anyways, Neal Barnard demonstrated we should be going, and luckily Kaiser Permanente is listening. There’s a future for starch-based, vegan approach. Me & HealthyLongevity are on the right path. To be healthy and to have biologically normal serum cholesterol we need to eat like the native Indonesians once did, as documented by de Langen.

    George Lundberg, the ex-editor of JAMA and boarmember of IOM reviews Barnards study.

    Low-Fat, High-Carb Diets Reverse Insulin Resistance

    The subjects assigned to the high-carbohydrate diet lost more weight, had better laboratory values (including lower HbA1c and LDL cholesterol), and were more likely to be able to discontinue taking at least one of their prescription medications.

    They were also more likely to stick to their diet. Although their food choices were restricted (they could eat nothing but vegetables, fruits, whole grains, and legumes), they could eat as much as they wanted. They didn’t have to count or weigh anything, and they never had to go hungry.

    A shift to a low-fat diet based on unrefined starches and vegetables is a promising approach for reversing type 2 diabetes and has also been beneficial in cases of type 1 diabetes.

    Not only does this kind of diet promote weight loss, it helps to reverse insulin resistance even before the individual has lost much weight. It also has beneficial effects on blood pressure, cholesterol levels, and other problems that can contribute to the complications of diabetes.

    http://www.medpagetoday.com/Columns/At-Large/31400?utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=WC&eun=g423506d0r&userid=423506&email=donnapfeldman@mac.com&mu_id=

  137. Many high quality smaller experiments focusing on the effect on diet on surrogate end points are typically considered sufficient to show a causal relationship between diet and surrogate end points. Large intervention studies and prospective cohort studies that meet certain criteria may help to demonstrate the relationship between lifestyle and hard endpoints (which requires a large number of people and long follow-up in order to demonstrate statistical significance), but are not necessarily required to prove a causal association between diet and surrogate end points.

    You have not produced any strong data to refute the findings from metabolic ward studies. For cholesterol intake the Weggemans et al. (I realize I made a typo in this name before) the results were virtually the same even when separating the metabolic ward and free-living studies. These meta-analyses demonstrate that lowering cholesterol favorably influences serum lipids, in particular LDL and TC concentrations to extents that could be considered to be clinically significant when maintain long-term. Of course many people would need to greatly limit intake of some of their favorite foods in order to achieve such benefits.

    There is no point in debating with you anymore because you refuse to accept any quality of evidence if the findings are not to your liking. You will always claim that the findings from studies are largely irrelevant either because the study had insufficient control or excessive control – there is no middle point. You will only look at the limitations rather than strengths of studies and suggest that therefore the studies are largely irrelevant even when these limitation you mention were addressed within the studies. You will also always demand for more evidence regardless of the quality of evidence presented.

    You have intentionally created an impossible to fulfill criteria for studies that you do not like. You can do this because you know that the studies you demand will not be completed anytime soon. Because such forms of evidence have not been produced you just simply pass of any study you disagree with as “BS” or “cherry-picked”. No study is absolutely perfect and therefore it is the job of health authorities to make a call based on the preponderance of evidence. This is why prominent health authorities have concluded that diets should ideally be predominately made up of minimally refined plant foods and relatively low in saturated fat and cholesterol. Perhaps the guidelines would be even stricter if there was not the problem of socioeconomic pressures.

  138. Of course you are allowed to demand for studies, but do not need to cite any studies yourself showing that low-fat dairy lower the rate of CVD compared to whole plant foods, or meta-analyses that allow for proper comparisons showing other diets are superior to whole food plant based diets. Just keep on doing what you are doing now – thinking of what type of other studies you can demand for that you know will not be completed anytime soon, this way you can win no matter what.

    I on the other hand prefer to look at all the current data I can find and make decisions based on that. This means doing a systematic review rather than carrying out meta-analysis, as many valuable available studies are not suitable for direct comparisons in meta-analysis.

  139. Mie

    “-You push your denialism without any regard to Darwinian foundation of our biomedical research paradigm: even small amounts of dietary cholesterol have adverse effect on the arteries of non-human primates.”

    Richard, repeating something doesn’t make it any more true than it is. Small amounts of dietary cholesterol have very little effect on the arteries of PEOPLE, which is what matters. Animal studies are secondary in this question.

    “Neither do you accept the evidence suggesting that dietary cholesterol influences CHD independently of serum cholesterol levels; recent research to eggs and gut bacteria provide confidence to these findings.”

    You mean the study mentioned e.g. here?

    http://www.medicalnewstoday.com/articles/259607.php

    The “bad boy” here is lecithin, stuff that gut bacteria love & digest which in turn leads to increase in plasma TMAO levels. And having higher TMAO levels increased the risk of CVD events. Now, this is problematic due to several accounts:

    1) After being administered antibiotics, gut bacteria died & further addition of eggs didn’t have any effect on TMAO. Thus, the problem is gut bacteria, which in that case can & should be managed.

    2) Lecithin inhibits the absorption of cholesterol – which seems to be the reason why egg intake has minor effects on plasma cholesterol. See e.g. this

    http://nutrition.highwire.org/content/131/9/2358.full

    on animals and this

    http://www.hindawi.com/journals/chol/2010/824813/

    on humans.

    3) Why the lack of effect between moderate egg consumption & CVD events in prospective cohorts? There’s no such problem w/ e.g. red meat or trans fat.

    “-Again, you refuse look at the totality of evidence. Regression of CAD has been shown to mediate via low-fat feeding pattern in non-human primates.”

    … which is irrelevant considering the fact that a) we’re talking about people and that b) the benefit seen in multifactorial interventions (medication, diet) cannot be reliably reduced to any single factor.

    “I did not refer to Esselstyn for him providing the perfect, randomized controlled trial (Ornish did that).”

    You have no idea what you’re talking about, do you? The Ornish program is multifactorial, too: it involves exercise and stress management.

    “Esselstyn’s study proved that coronary artery disease can be reversed with low-fat diet in humans.”

    Now, the quality of this finding is – at best – under the category “interesting, need further research”, due to methodological issue mentioned.

    “This is what nearly 100% drug-free reversal of atherosclerosis looks like.”

    ???? The patients in Esselstyn’s study received lipid-lowering medication!

    “This patient, cardiologist, refused to take any statins and relied purely on diet. This man was lean and athletic already prior his myocardial infarction. After 5-years adherence to low-fat diet:
    http://www.heartattackproof.com/cardio1.jpg

    Now, if the one patient who refused statins & relied only on diet DIED, what does that tell you about diet?? :-)

    “You are confused. The relevance is that most adult egg eaters do not have low-cholesterol. The fact that dietary cholesterol does not have much effect on people with “normal” cholesterol, which is BTW 200% above what is biologically normal, does not indicate that people desiring to have biologically normal and healthy cholesterol levels can eat eggs.”

    Go back to Hopkins et al. They showed that the effect of added dietary cholesterol is mediated by BASELINE dietary cholesterol. And when you get e.g. the amount mentioned in the old ATP-III guidelines (300 mg or less), the effect of adding another 200 mg in the form of one large egg produces a “staggering” change of less that 0.2 mmol/L in total serum cholesterol (which means that some of it is HDL-C).

    “Ok, good that you clarified this. I don’t care about the dietary habits and adherence of sick Western people on prescription drugs. I care about saving lives, saving the planet and healthy longevity. I am interested in science, I am in control of my own adherence. You can have your mainstream lip service to healthy diet, I am about making the environment more open to starch rich, plant-based diets.”

    “For optimal effect, everybody, besides pure vegeterians, should start considering taking statins already in their 20s-30s.”

    There’s no evidence to support this. You need to have elevated risk to benefit from statins and not everybody has that.

  140. Mie

    Richard, your personal lipid levels mean … well, nothing in this case (population level risk assessment and dietary guidelines). Good for you, having a low LDL.

    (And for the record: I haven’t got anything against vegan diets as such. In the context of climate change & ecology they are superior. My “beef” is with people like you who promote them with unfounded claims & as the “one truth” in nutrition).

  141. Low-fat Richard

    Again,

    while eating eggs, most adults cannot have low cholesterol. Eggs need to wiped out incase cholesterol levels are to be lowered to physiologic levels. Cholesterol levels do not just magically come down if cholesterol elevating foods are consumed, even if saturation point for intake was small. An alcoholic person does not get intoxicated after 5 beer like most people would, but it’s still better he/she reduces the consumption close to zero for the sake of his/her general health. Eggs certainly do not decrease cholesterol levels, eggs keep the cholesterol levels up, not necessarily increasing them.

    Richard, repeating something doesn’t make it any more true than it is. Small amounts of dietary cholesterol have very little effect on the arteries of PEOPLE, which is what matters. Animal studies are secondary in this question.

    LOL! As if any ethical research board would allow a study to be conducted in which, let say, egg yolk feeding in humans is continued up for several months, if even weeks. Don’t be an idiot. Dietary cholesterol and CHD has huge ecologic correlation as demonstrated by Connors (1961). Populations consuming less dietary cholesterol have less CHD. Don’t tell me we humans are an offshoot of intelligent design and above any dietary cholesterol feeding model conducted in non-human primates.

    Why the lack of effect between moderate egg consumption & CVD events in prospective cohorts? There’s no such problem w/ e.g. red meat or trans fat.

    This is utter nonsense, and the source of this is most likely Mozzafarian, let me guess. The 7CS is prospective cohort for god’s sake. Stamler considered 11 prospective studies and found a 32% excess risk for fatal heart end point despite over-adjustments for serum lipids and a number of other problems addressed in his editorial such as regression dilution bias that would expected to have significantly weakened this finding. Stamler is the most leading authority in diet-heart. Here are some SFA-CHD RRs in famous cohort studies:

    -Strong Heart Study 5.17 (ages 47-59, high vs low intake)
    -Mann et al. 2.77 (high vs low intake)
    -Health Professionals Follow-Up Study 1.72 (high vs low intake)
    -Health and Lifestyle Survey 1.40 (women, per 100 g higher intake)

    Now, I wonder what is the low-carb, anti-vegetarian, anti-climate change blog you’ve read this time to educate yourself on the issue of eggs and gut bacteria.

  142. Mie

    “Stratification of the studies for study design (crossover or Latin-square compared with parallel), setting (metabolic ward compared with free-living), or adjustment of the change in dietary cholesterol for energy intake did not materially alter the results…”

    … which cannot be taken as a very reliable statement, given e.g. the lack of reporting in LDL changes.

    In addition, if you check the table, you’ll see that the results in individual studies varied quite a bit in terms of the amount of added dietary cholesterol & the effect it produced. This calls the samples used in the original studies in question: how reliably do they represent the general population?

    Obviously you have decided to ignore the inherent issues w/ meta-analyses of heterogenous studies. Which is … interesting since you (quite rightly so) seem to agree with such observations concerning the Hooper et al fat modification meta-analysis.

    “We found no publication bias in our meta-analysis by use of funnel plots.”

    Err, did I address publication bias or not? Care to check my message?

    “One of the major advantages of the Physicians Health Study over many other cohort studies that addressed the association between egg intake and all-cause mortality is that dietary intake was updated over time, and therefore it is less likely to suffer so badly from regression dilution bias.”

    In case you missed the key findings on the issue of eggs & CVD, check out tables 2 and 3. What do they tell you? :-) Or the key findings, summarized by the authors themselves:

    “In this prospective cohort, we showed that infrequent egg consumption (ie, 6 eggs/wk) was not associated with MI, stroke, or total mortality in healthy US male physicians. In addition, consumption of 7 eggs/wk was associated with a modestly but significantly greater risk of total mortality in this population. In contrast, egg consumption was associated with a greater risk of all-cause mortality in a dose-response fashion among physicians with diabetes (2 times the risk of death in
    people consuming 7 eggs/wk than in those consuming 1 egg/wk). Furthermore, our data provided suggestive evidence for a greater risk of MI and stroke with egg consumption among male physicians with diabetes.”

    To sum it up: from the point of view of CVD: egg consumption had no statistically significant effects (after adjusting for confounders) on MI or stroke prevalence in the healthy study population. Those w/ diabetes, on the other hand, had better be careful. Now, this is in perfect agreement w/ the findings of the two meta-analyses on egg consumption & CVD referenced above.

    About this

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2628696/

    “The findings form the Physicians Health Study also suggest that any intake of egg increases the risk of type II diabetes, and any intake of egg among diabetics increases the risk of all-cause mortality.”

    Yep, that’s what it seems to suggest.

  143. Mie

    “Many high quality smaller experiments focusing on the effect on diet on surrogate end points are typically considered sufficient to show a causal relationship between diet and surrogate end points.”

    You know, you sound JUST like Richard Feinman when I pointed out the limitations of low carb studies investigating surrogate end points in terms of CVD outcomes. Now, what does that tell you? :-)

    “Large intervention studies and prospective cohort studies that meet certain criteria may help to demonstrate the relationship between lifestyle and hard endpoints (which requires a large number of people and long follow-up in order to demonstrate statistical significance), but are not necessarily required to prove a causal association between diet and surrogate end points.”

    … and since the highest place in evidence hierarchy is received for studies demonstrating the effect of different interventions (lifestyle, medication) on hard end points… Well, see e.g. this simple but well-crafted illustration (which excludes systematic reviews/meta-analyses):

    https://twitter.com/JussiRiekki/status/359342026170454016/photo/1

    Now, clinical guidelines get crafted on the basis of this. If you disagree with the current procedure, I’d like to hear WHY. E.g. why larger intervention studies and epidemiological evidence isn’t necessary when compared to e.g. metabolic ward studies. And remember, it’s NUTRITION that we’re discussing here.

    “There is no point in debating with you anymore because you refuse to accept any quality of evidence if the findings are not to your liking.”

    Coming from the person who e.g. sets double standards to HDL as opposed to saturated fat, this is quite a claim.

    “This is why prominent health authorities have concluded that diets should ideally be predominately made up of minimally refined plant foods and relatively low in saturated fat and cholesterol.”

    Now, the benefits of plant-based diets (which is a broad term, encompassing virtually everything from MD to vegan) cannot be reduced to safa and total cholesterol. Yes, low on safa seems to be the norm, but the VERY SAME authorities who point this (e.g. HSPH) also make it very clear that relying on safa alone is simply unfounded & that the diet as a whole is what matters.

    “Perhaps the guidelines would be even stricter if there was not the problem of socioeconomic pressures.”

    Perhaps. But in this case – just like in any other case – scientific evidence is what matters, not speculation.

  144. Low-fat Richard

    Moreover, Mike. Pay attention that most prospective cohorts come from an era that came after the large structural changes in the diet of Western countries had taken place as pointed out by several diet-heart scholars. In other words, the consumption of butter, eggs and whole-milk had already plummeted prior the new prospective studies were launched, whereas meat intake per se had not plummeted, it may have got leaner, though. Furthermore, the margins of consumption in regards to meat may be bigger in Western countries as opposed sat fat per se, but this my own speculation. There may be more variation between individuals in regards to meat intake as opposed to SFA intake. Even the vegetarians in Western countries consume lot of animal fat. SFA intake may be more uniform in high-risk populations. Let’s not either forget that the old studies that used 24-dietary recall method were really poor in terms of methodology. The new meat studies have used state-of-the art methodology with repeated dietary recalls.

    The authors of Siri-Tarino meta-analysis know that saturated fat causes heart disease.

    “Why is red meat harmful? “Saturated fat, which can lead to cardiovascular disease, is really just the beginning of the story,” explains Hu”

    http://harvardmagazine.com/2012/01/a-diabetes-link-to-meat

    “It is well known that the SFA intake is far lower in Japan than in Western countries; for example, the median intake of SFAs for the highest quartile of a Japanese rural population (1970–1980s) was 17 g/d (16) lower than that for the lowest quartile of intake in the Nurses’ Health Study in 1980 (20 g/d) (11). These findings indicated almost no overlap of SFA intakes between the 2 populations”.

    http://www.ncbi.nlm.nih.gov/pubmed/20685950?dopt=AbstractPlus

  145. Mie

    “Clearly some of our most profound successes in arresting and reversing disease were with patients who either refused or were incapable of taking statins. Nothing is as powerful for the prevention of cardiovascular disease as plant based nutrition.”

    And we’re just supposed to believe this? As opposed to the man himself stating that these 18 all adhered to MEDICATION too?

    “We know clearly that all these patients were very sick and that they had virtually no coronary events through the 20 year follow-up. We also know that the main emphasis was on the prescribed diet and that a number of the patients did not take statins.”

    … which in no way removes the fact the without a control group, the value of a study like this is very limited. Stop weaseling around a fact that is obvious to anyone who knows anything about methodology in trials!

    “In the newer decade long study of around 200 patients …”

    … which still hasn’t been published. Now, I myself want to have a look at the paper with my own two eyes before saying anything about it.

    “Where is the evidence that suggests this is can be explained by other factors? Statins have not been shown to be that successful and a number of the patients did not even take them.”

    That’s just THE POINT, god dammit! Without a control group, this can be due to ANY factor.

    And the statin point: are we to believe you or Esselstyn himself? His words were:

    “During the 7 years since the conclusion of the 5-year study, all but 1 patient have continued to adhere to the prescribed diet and MEDICATION.”

    And this

    “A control group is not everything, many impart health and safety recommendations have not been based on randomized controlled trials.”

    is just stupid, stupid, stupid. You cannot compare two different types of studies (trial, cohort studies) and suggest that since the latter don’t have X, it’s ok for the former not to have one, either. NO: the requirements in terms of methodology are dictated separately on the basis of the type of a study. If we we’re to follow your line of reasoning, it’d be ok to e.g. have prospective cohorts with 20+ people & observation time of a month – hey, this is the norm in metabolic ward studies so …

    “Low-carbohydrate diets have been promoted as being healthy in Sweden for some time now but the prospective cohort studies coming out of Sweden haven’t exactly shown the low-carb diets to be associated with a decreased risk of mortality.”

    … which is exactly why we need epidemiologal evidence to support studies which focus on SURROGATE end points.

    Care to explain yourself out of the hole you’ve dug yourself in? :-)

    “Secondly, the association persists after adjustment on these risk factor, suggesting a specific effect of fruit and vegetables.”

    Ok. Thanks.

    Now we need to know the mechanism. Epidemiological studies cannot unfortunately help us with that.

  146. Mie

    “Of course you are allowed to demand for studies, but do not need to cite any studies yourself showing that low-fat dairy lower the rate of CVD compared to whole plant foods, or meta-analyses that allow for proper comparisons showing other diets are superior to whole food plant based diets.”

    Err, you do realize that this thing just here is the point: R claiming something which isn’t really based on criteria set by e.g. guidelines? You don’t extrapolate on the basis of different studies, you need direct comparison.

  147. Mie

    “while eating eggs, most adults cannot have low cholesterol.”

    This comment which pays no attention to the relevant issues (serum cholesterol. diet as a whole etc.). Simply put: cherry-picking.

    “Cholesterol levels do not just magically come down if cholesterol elevating foods are consumed, even if saturation point for intake was small.”

    A diet and its effects on CVD risk cannot be narrowed down to e.g. intake of one egg a day & cholesterol levels. If we we’re to follow this reductionist thinking, we’d argue for a diet based mostly on pufa (on the basis of e.g. Clarke et al 1997). Or, in a plant-based diet, eat nothing but vegetables & nuts. Etc. etc.

    “LOL! As if any ethical research board would allow a study to be conducted in which, let say, egg yolk feeding in humans is continued up for several months, if even weeks. Don’t be an idiot.”

    WTF? Feeding studies on humans usually DO last for weeks.

    “Dietary cholesterol and CHD has huge ecologic correlation as demonstrated by Connors (1961).”

    … and once again with the ecological fallacies, this time even older than before.

    “Populations consuming less dietary cholesterol have less CHD. ”

    … and once again here. They also have less stress, better family ties, more exercise etc. etc.

    “This is utter nonsense, and the source of this is most likely Mozzafarian, let me guess.”

    With egg consumption? No, see the two meta-analyses above. With red meat, Mozaffarian et al is one of several meta-analyses conducted on red meat. Do you disagree with their finding on the problems related with meat consumption? :-)

    “Moreover, Mike. Pay attention that most prospective cohorts come from an era that came after the large structural changes in the diet of Western countries had taken place as pointed out by several diet-heart scholars.”

    … which is meaningless since we can still see the differences in people’s diets and observe the connection between them & CVD events. The reduction in risk factors worldwide by no means negates the fact that there still are high risk populations & we can conduct cohorts on them. Do you have an even REMOTE idea what you’re talking about?

    Then, after skipping a lot of meaningless mumbo-jumbo:

    “The new meat studies have used state-of-the art methodology with repeated dietary recalls.”

    So are you indeed arguing that Mozaffarian et al are WRONG in their conclusions that red meat intake is associate with e.g. increased risk of cancer?

  148. Z.M.

    HL:”Where is the evidence that suggests this is can be explained by other factors?”

    So reductions in processed foods, increases in fruits and vegetables, weight loss and cholesterol-lowering drugs (which according to Esselstyn almost every patient was using) could not have contributed to the results seen? Luck doesn’t need to explain it as there are many plausible explanations here.

    HL:”A control group is not everything, many impart health and safety recommendations have not been based on randomized controlled trials.”

    Nice way to avoid the science. Control groups are essential. How do you that a diet similar to Esselstyn’s intervention but includes fat couldn’t produce the same results or even better? You know, if I were a vegan I would want the diet to be compared to other diets in a randomized controlled trial on hard endpoints. If you really cared about saving lives you would promote a Mediterranean type diet because at least this diet has actually been shown in a randomized controlled single blinded trial to save lives. According to the vegan ideology such a diet couldn’t be healthy because it includes animal foods and monounsaturated fat which has been found in animal studies to increase atherosclerosis. Well, human research suggests otherwise.

    HL:”You seem to dislike epidemiology just about as much as those who deny that smoking is a cause of lung cancer. Of course you two will refuse to look at the strengths of this study and will stop at nothing to downplay these very impressive findings.”

    No, I don’t dislike epidemiology. I just keep in mind the limitations when interpreting such studies (as with any type of study) and keep an open mind to all possibilities. I’m not sure what’s so impressive about a study which contains no comparison group.

    HL:”Dietary cholesterol has been recognized as the sine qua nons for the dietary modification of experimental atherosclerosis in many species of animals.”

    A major factor you ignore in these studies is oxidative stress which can be lowered without any changes in cholesterol at all. As I said before there are numerous studies which show significant reductions in atherosclerosis in animal models independent of cholesterol.
    It’s not just about cholesterol as you try to imply.

  149. Low-fat Richard

    You failed to understand the take-home-message of my post. Sorry, but I cannot help you anymore.

  150. Low-fat Richard

    You keep repeating the words “meaningless” or “ecologic fallacy” whenever you encounter something you don’t have any clue about.

    1) Connors did not show an “ecologic fallacy” but association that is biologically highly plausible! If stress played any major role in CHD, then CHD rates would not have plummeted in countries were German forces confiscated the dairy and meat industries. War is probably quite stressful after all.

    2) If the intake of meat has more variation between individuals than the intake of SFA has, then meat has more explanatory power to explain differences in end outcomes in a given model. If there’s no variation in variable x, it cannot show an association with disease y, even though it’s causally related to that disease.

    3) After the structural changes that took place in Western diets, even the control group in, let say, WHI-trial showed lower intake of SFA than they would had done had the trial launched few decades earlier. The margins of intake between the groups were small.

    4) Its easy to show difference between the intake of SFA and CHD mortality when comparing populations, both intraindividual and interindividual variation is cancelled out. When the unit of measurement is individual, special attention need to paid to regression diluation bias/intraindividual variation and other issues. The methodology of the older prospective cohorts that looked SFA consuption were not up to the notch, which has most likely biased associations more towards the null.

    Now, what is meaningless in these points which are essentially the same that have been raised by leading diet-heart scholars.

    See HealthyL’s blog post about the issues related to part 4.
    http://healthylongevity.blogspot.fi/2013/01/diet-heart-problematic-revisit.html

    No, I am not against Mozzafarian’s findings, Mozzafarian just has an track record of saying/writing very stupid things and thus confusing lot of people.

  151. Low-fat Richard

    DOC;

    great article in NYT. We need to eat in a way that leads to lowest LDLs possible. We starch-based, plant-foodist are the avant-gardists when it comes to this.

    Rare Mutation Ignites Race for Cholesterol Drug

    “Those who had even a single mutated gene seemed almost immune to heart disease, even though many had risk factors, including high blood pressure, diabetes and smoking”

    http://www.nytimes.com/2013/07/10/health/rare-mutation-prompts-race-for-cholesterol-drug.html?pagewanted=2&smid=tw-share.

  152. Low-fat Richard

    Sorry, wrong link. Healthy L discusses intraindividual variation and interindividual variation here:
    http://healthylongevity.blogspot.fi/2013/01/diet-heart-problematic-revisit-part-ii.html

  153. Low-fat Richard

    LOL,

    Yeah, Mike. You sure know the evidence on dietary cholesterol better than the people who set out the national guidelines.

  154. Low-fat Richard

    Mie wrote:

    “Yes, low on safa seems to be the norm, but the VERY SAME authorities who point this (e.g. HSPH) also make it very clear that relying on safa alone is simply unfounded & that the diet as a whole is what matters”.

    Mike, i get where you are coming from, but you do not really consider the evidence here. CHD rates dropped in Western countries for a large part because of public health measures heavily encourages people drop down SFA and egg consumption. They did not encourage to adopt mediterranian diet. Public health measures which focused on SFA reduction have been immensely successful in tackling the number one killer (Pedersen et al 2011).

  155. Low-fat Richard

    Mickey,

    there is actually a nice term describing the silly set of beliefs you are pushing, “methodolatry”: the profane worship of the randomized clinical trial as the only valid method of investigation.

    I like RCTs, but I like to use my brain and sound rules of logic too.

  156. I am aware that anyone who is opposed to the idea that a plant based diet is most optimal for cardiovascular health will resort to every last excuse in the book to try and downplay Esselstyn’s new study. These jaw-dropping results will be seen as a major threat for promoters of fad diets.

    In regards to Esselstyn’s study pending publications, he has already disclosed that there were almost 200 adherent CAD patients and that they remained virtually free of any serious cardiac events during the decade of follow-up. It is phenomenal that this number of sick patients can remain free from reoccurring events for such a long period of time. Open minded people would naturally be impressed by such findings, even without a control group as it is painfully obvious that these results were not the result of luck. Of course people who try to downplay this study will focus largely on the lack of control group so that they do not have to think very hard.

    Unlike his original study, a good portion of the CVD patients in this newer study would have been on statins before entering the study, but nerveless many still suffered from cardiac events. This provides further evidence that diet largely contributed to the success of this study, and was the decisive factor for many of the patients. Although people who are slim are not immune to CVD, dietary induced weight was likely beneficial but unlikely the decisive factor.

    People on the Mediterranean diet still have a substantial residual risk of CVD, and therefore hardly seems like an optimal diet to promote. Although we cannot say for sure whether the people in Esselstyn’s study had the exact same risk factors as the participants in the Mediterranean diets trials, we know for example the Lyon study lasted 46 months and was limited to individuals that only had previously had one heart attack. As Esselstyn’s intervention lasted much longer and the participants were not limited to those who had experienced only one cardiac event prior to the intervention, it hardly seems likely that these participants would have had a lower 10 year risk of vascular disease than the Lyon participants 4 year risk prior to entering the study.

    I am guessing ZM is trying to extrapolate some experiments using peanut oils to suggest that monounsaturated fat is atherogenic in animals. The atherogenic properties of peanut oil has typically been attributed to factors other than monounsaturated fat, and experiments which used low amounts of dietary cholesterol found that peanut oil is typically less atherogenic than fats rich in saturated fat. This is especially the case when randomized peanut oil was used.
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2032521/

    Perhaps a similar diet to that Esselstyn recommends with some added nuts may have similar benefits. However until this is demonstrated Esselstyn’s diet remains the best bet.

    In humans LDL cholesterol has been far more proven as a causal factor for CVD then oxidative stress. However as a whole foods plant based diet can have significant favorable effects on both risk facts, you can get the best of both worlds.
    In regards to what Mie said “which is exactly why we need epidemiologal evidence to support studies which focus on SURROGATE end points.” The changes to surrogate end points are not as favorable as low carb promoters make them out to be. For example, low carb diets, especially those that focus on animal fat and protein have shown to increase LDL cholesterol, cause endothelial dysfunction and promotes metabolite profiles that may increase the risk of colorectal cancer.

  157. Z.M.

    Hmm… Esselstyn’s study had no control group. Period. There is no getting around this. It does not even deserve to be compared to the Lyon diet study so stop trying.

    “HL”: However until this is demonstrated Esselstyn’s diet remains the best bet.

    No, until Esselstyn’s diet demonstrates superiority in hard outcomes in controlled trials compared to other healthy diets there is no reason to adopt such a diet.
    You have it backwards. Esselstyn’s diet is not by default the best diet, it has to prove itself as better than other alternatives.

Let me know what you think!