Estimated reading time: 12 minutes
For decades cholesterol has been a major player when it comes to preventing heart disease. Measuring blood cholesterol and knowing your numbers is of key importance. If your numbers spell danger, you need to know what to do. Otherwise, you may be in big trouble.
In their book published last year, Heart 411: The Only Guide to Heart Health You’ll Ever Need, Marc Gillinov MD and Steve Nissen MD write: “High cholesterol has no symptoms; every day, we see patients who learn about their high cholesterol only after they arrive in the coronary care unit with a heart attack. Avoid this scenario. Have your cholesterol tested. If the results suggest you are at risk, review the information in the next few pages. It might just save your life.”
Gillinov, a heart surgeon, and Nissen, a cardiologist, are both highly respected doctors and scientists at the Cleveland Clinic in Ohio. Both of them have delivered hundreds of invited lectures at hospitals, academic meetings, and seminars in the United States and many other countries. I highly recommend their book for those who want to increase their understanding of how to prevent heart disease. Of course, the book deals with many other issues than cholesterol.
In their book, Gillinov and Nissen briefly go through the role of cholesterol in our body. They point out that “every cell in your body contains cholesterol, and you can’t live without it.” They highlight the importance of cholesterol for our cell membranes and the role it plays as a building block for many important hormones. They describe the “two types of blood-borne cholesterol, which are distinguished by their attached lipoproteins: low-density lipoproteins (LDL) and high-density lipoproteins (HDL).” They point out that “high levels of LDL or “bad” cholesterol are associated with the development of plaques in the arteries. Oxidation of LDL cholesterol in the blood enables it to enter the walls of arteries, leading to a build-up of plaques. HDL or “good” cholesterol works in opposite fashion, removing cholesterol from the arteries and returning it to the liver, where it is removed from the body.
They point out that “high levels of LDL or “bad” cholesterol are associated with the development of plaques in the arteries. Oxidation of LDL cholesterol in the blood enables it to enter the walls of arteries, leading to a build-up of plaques. HDL or “good” cholesterol works in opposite fashion, removing cholesterol from the arteries and returning it to the liver, where it is removed from the body.
Gillinov and Nissen also tell us that “Eighty percent of the body’s cholesterol is made by the liver. While most people think that diet is the most important factor in determining cholesterol levels, this is a myth. Only 20 percent of your cholesterol levels comes from your diet, which explains why it is so difficult to reduce blood cholesterol levels via dietary interventions alone”. They say: “Understanding the limitations of dietary interventions often helps people accept the fact that they need to take cholesterol-lowering drugs.” However, they underscore the importance of a good diet to influence blood cholesterol. In their opinion a good diet is “low in saturated fats, high in fiber and whole grains”.
They say: “Understanding the limitations of dietary interventions often helps people accept the fact that they need to take cholesterol-lowering drugs.” However, they underscore the importance of a good diet to influence blood cholesterol. In their opinion a good diet is “low in saturated fats, high in fiber and whole grains”.
They underscore the important role of LDL cholesterol in predicting the risk of heart disease: “Study after study has confirmed the strong relationship between high levels of LDL and heart disease.” Because HDL cholesterol appears protective, they believe that total cholesterol has major limitations as a predictor of heart disease. “The LDL level is the best predictor of the risk of heart attack and stroke, and the basic concept is simple: the lower, the better.
The message from the experts is clear and simple: Know your numbers. LDL cholesterol is the most important subtype when it comes the risk of heart disease. Lowering cholesterol by diet is often not effective, but eating diets low in saturated fats and high in fiber and whole grains may be helpful. If you don’t succeed in lowering your LDL cholesterol, don’t be afraid to take drugs.
Cholesterol Clarity – Jimmy’s Army
Jimmy Moore doesn’t believe the experts. I just finished reading his recently published book Cholesterol Clarity – What the HDL is wrong with my numbers? Moore’s co-author is Eric Westman MD, an internist in Durham, North Carolina.
Jimmy Moore is well known in the United States for his iTunes podcasts and his popular blog, Livin’La Vida Low-Carb. He has effectively dealt with obesity himself, and for years his cholesterol numbers have been really bad. He is motivated by his own experience and eager to help other people who are struggling to improve their health.
In the Introduction to his book, Moore says: The title of this book is Cholesterol Clarity for a reason: The intention is to make the truth about cholesterol absolutely clear. This book is not for medical geeks. It’s not filled with complex terminology and jargon that makes the layperson’s eyes glaze over. “
Although I’m probably a medical geek according to Moore’s definition, I must say I enjoyed reading his book. More importantly, I also learned a lot from it. It is so well written, and it has this ultimate freshness about it. I never expected that I would agree with everything Moore writes in his book, and I don’t. Of course, that doesn’t mean I’m right, and he’s wrong. However, I like the way he approaches the subject, and I admire his talent when it comes to explaining complex and highly debated issues.
I never expected that I would agree with everything Moore writes in his book, and I don’t. Of course, that doesn’t mean I’m right, and he’s wrong. However, I like the way he approaches the subject, and I admire his talent when it comes to explaining complex and highly debated issues.
Moore says: “I have no doubt that this book will be controversial. It challenges conventional wisdom about how we eat and live – rules that we have grown up with and followed for most of our lives”.
I agree with Jimmy Moore. I’m afraid many of my colleagues won’t like his book. They may even believe it to be dangerous because it contradicts many of the current recommendations from medical experts and public health authorities. However, I believe that everyone who is trying to take control of his/her own health will learn a lot from reading Moore’s book.
Jimmy Moore has no formal medical or nutritional health education. He does not refer to many scientific studies in his book. Instead, he has chosen to select an army of what he calls “trusted advisers who know the answers to the most pressing questions about health”. Moore constantly quotes these individuals throughout his book.
Moore’s army consists of twenty-nine individuals. Some are nutritionists, some are physicians, and some are neither. Some are respected scientists and leaders in their field. He has chosen many trustworthy and knowledgeable individuals, although some appear more trustworthy than others.
Obviously, Moore has handpicked a team of specialists who support his own theories. But I have to assume that all these individuals don’t agree with Jimmy Moore on everything he writes, but I could be wrong. What Moore fails to do is to also choose experts who don’t support his opinion. I assume doctors Gillinov and Nissen would not have been fit enough for his army.
What’s the Clarity All About?
After introducing his army, Moore goes on to describe the important role cholesterol plays in our body and he describes how little effect the cholesterol in our diet seems to have on blood levels of cholesterol. He discusses the evidence, or rather the lack of evidence linking saturated fat with heart disease. He touches on the evidence behind the lipid hypothesis, the fear of dietary fats, and the rising incidence of obesity and
He discusses the evidence, or rather the lack of evidence linking saturated fat with heart disease. He touches on the evidence behind the lipid hypothesis, the fear of dietary fats, and the rising incidence of obesity and type-2 diabetes, which has occurred despite Americans dutifully cutting their fat intake.
He criticizes the overwhelming emphasis on dietary fat and cholesterol consumption as the true culprits in heart disease. “Emerging evidence proves that these supposed health experts have been dead wrong and yet they continue to cling to this outdated and outright harmful information.” I assume Gillinov and Nissen belong to this group of “supposed health experts”.
Quite predictably, Moore discusses the role of inflammation in heart disease. Most specialists who doubt that cholesterol plays a direct causative role in atherosclerosis believe that inflammation is a key factor. However, although research indicates that inflammation plays a huge role, it doesn’t imply that cholesterol doesn’t matter. Indeed, atherosclerosis and heart disease may be caused by a complex interplay between different components of lipoproteins, including cholesterol, as well as oxidation, inflammation and other known or unknown mechanisms. Cholesterol and inflammation are not mutually exclusive.
Moore writes: “Without inflammation, cholesterol can’t harm you”, and he’s probably right. But he might as well have written: “Without cholesterol, arterial inflammation as we know it won’t harm you”.
Moore recapitulates what major health groups have said about cholesterol through the years. He manages very well to reflect the stringent, monotone, and scientifically unsupported view repeated for so many years, that the only thing that matters when it comes to diet and heart disease is too much cholesterol in the blood and the importance of avoiding saturated fat and cholesterol in our diet. I’m afraid this approach has produced more harm than good when it comes to public health.
Moore criticizes the widespread use of cholesterol-lowering drugs (statins). He believes there are alternatives to drug treatment when it comes to improving our health and “that lifestyle should be the first step to improving health and cholesterol numbers.
He cites Dr. Thomas Dayspring when saying: “The real problem with most people is that they just don’t do what’s required to see improvements happen. If you want to go totally drug-free, then you have to get serious about lifestyle and diet changes”. Many people could learn a lot from Jimmy Moore when it comes to improving health with serious lifestyle changes.
Moore attempts to redefine what we normally see as a heart healthy diet. This is not an easy task because the cholesterol issue has become such a big part of conventional thinking. An example of that is fearing that a highly nutritious food such as eggs is dangerous for your health because it’s rich in cholesterol.
In Jimmy Moore’s mind “heart healthy” does not imply eating less fat and more carbohydrates. He is very skeptical about sugar, grains and starchy carbohydrates as well as omega-6-rich vegetable oils.
Moore discusses the question why “so many doctors are clueless about cholesterol”. He is “troubled by how little most traditionally trained medical doctors are taught about the nutritional component of health”. Sadly, I think he has a point here. The influence of nutrition and lifestyle on health definitively played a minor role in my own medical training. This is an area where doctors have to improve.
However, Jimmy Moore could be overestimating his own and his army’s greatness when saying: “Apart from the experts quoted in this book, the mainstream medical community seems determined to stick with outdated and potentially dangerous ideas.”
Moore does a very good job in explaining the meaning of different laboratory numbers, total cholesterol, LDL cholesterol, triglycerides, as well as the role of newer tests like ApoB, LDL-P, Lipoprotein (a), particle size assessments (patterns A and B) and C-reactive Protein (CRP).
Cholesterol Clarity or More Disparity
It’s quite interesting to compare the approach by Gillinov/Nissen and Moore/Westman to the role of cholesterol in heart disease and cardiovascular prevention. Gillinov and Nissen consider a heart healthy diet to be low in saturated fats, high in fiber and whole grains. Jimmy Moore and his army, on the other hand, believe that eating less carbohydrates and more fat is beneficial.
Gillinov and Nissen consider it positive that 25-30 million Americans are taking statin drugs to lower the risk of heart disease and stroke. Jimmy Moore and a part of his army, however, see statin drugs as a marketed poison. How can we explain such a huge difference of opinion? Who’s right and who’s wrong?
I think Jimmy Moore handles the question elegantly at the beginning of his book when he writes: “For years, popular wisdom has held that having elevated levels of cholesterol in your blood is extremely dangerous, leading to heart attack, stroke, even death. Therefore, it must be lowered by any means necessary. Those means include cutting saturated fat and cholesterol from your diet and taking cholesterol-lowering prescription drugs. Sound familiar? Well, some of us took the time to stop and ask a few simple questions: Isn’t the human body a lot more complex than this simplistic solution implies? Isn’t our health dependent on more than one single marker like total cholesterol?” I suspect Gillinov and Nissen agree with these words. So maybe there is no disagreement after all.
Although I don’t believe Jimmy Moore has managed to resolve all the fog around the cholesterol issue he certainly has given it an honest and fresh try. I know I will read many chapters of his book again and again. Although I may not necessarily always find the truth, I will enjoy it, and I’m quite sure it will help me become a better doctor.
Honestly written, ignited desire to read Jimmy Moore.
Might be a good idea. One could always use a decent laugh. 🙂
Although, in terms of Moore’s health, his yo-yo -dieting and strange ideas e.g. about LDL not being important whatsoever are nothing to laugh about.
It’s interesting he leaves out this from Dr Dayspring
https://3.bp.blogspot.com/-66n11pqJGyA/Uh5I1Db3YTI/AAAAAAAAEBE/1joMdES7gic/s1600/Dayspring+on+TC.jpg
Actually Jimmy Moore quotes Gary Taubes saying that “LDL-P tend to increase in a small segment of those people who eat a low carb-high fat diet”. However, he doesn´t consider it a big issue. It doesn´t surprise me that Doctor Dayspring is not ready to ignore a severely elevated LDL-cholesterol. Very few doctors would.
https://eatingacademy.com/nutrition/the-straight-dope-on-cholesterol-part-v
Thomas Dayspring aka “Dr Lipid” May 26, 2012
But no way is CIMT as imformative as total LDL-P or apoB A positive IMT implies subclinical atherosclerosis – likely the apoB and LDL-P were elevated for years before the vessel wall became abnormal enough to cause a positive IMT
Thomas Dayspring aka “Dr Lipid” May 23, 2012
Peter is right on: If you have too many small LDLs or too many big LDLs you are at risk for CHD. If you have all small LDLs but total LDL-P is normal, there is no risk. If you have normal numbers of very large LDLs your LDL-C might be high but LDL-P will be fine and thus no risk exists. Peter nicely illustrates that if you have small LDLs, it will take 40-70% more LDLs to traffic a given mass of cholesterol, hence untreated folks with small LDLs always have a high LDL-P and thatis what drives risk. Likewise if one’s LDLs are pathologically carying TG instead of cholesterol (i.e. a cholesterol depleted LDL)it will take many more such cholesterol-depleted LDLs to carry a given acholesterol mass. Risk is related to particle number not to the amount of cholesterol within the LDL particles, because it is particle number that drives the LDLs into the artery
Thomas Dayspring aka “Dr Lipid” May 30, 2012
If you shift particle size upwards it will have a larger volume and thus will have to be carrying more lipid molecules. So typically the larger LDL will carry more cholesterol molecules and it takes less cholestrerol-rich LDLs to traffic a fiven LDL-C value (mass). However if the particles become larger because they are TG-rich, they will be cholesterool-depleted particles and it takes many more chol-poor than chol-rich LDLs to traffoc a given cholesterol mass
Thomas Dayspring aka “Dr Lipid” May 30, 2012
HDL-C is not apoA-I They also can be very discordant We now know thinking high HDL-C is protectove or low HDL-C is necessarily a riskfactor is BS Go with apoB The level you mention is a horrific nightmare The HDL has little meaning
So here’s the $64,000 question
As a cardiologist what is your opinion. If the markers of inflammation are low – if HDL is high and triglycerides are low – do LDL-P and LDL-C then become irrevelant?
Is a LDL-P of >2500 and and ApoB of >200 on a low carb ketogenic diet any different than the same readings of someone not on this type of diet – assuming inflammation is low
Charles. No, I don’t think LDL-C and LDL-P will become irrelevant although HDL is high and TG and CRP low. Of course they may become less relevant when other markers are good. I don’t think anybody really knows whether the relevance of high LDL – particle count (LDL-P or ApoB) is different on a ketogenic diet than on a non-ketogenic diet.
Doc,
I have to question your statement “Without Cholesterol, Inflammation can’t harm you…” Ignoring all the other problems with inflammation in general, won’t there always be enough cholesterol in the body that significant inflammation will become a problem? In other words, a low-carb/no-bad-fat diet is practical and should minimize inflammation in most people, however high inflammation such as produced by a high-carb diet would almost never be accompanied by sufficiently low Cholesterol to avoid danger..Thoughts?
And many thanks for your great blog…
Thanks for commenting Superchunk. My statement was merely hypothetical. I was trying to support my view that cholesterol and inflammation are both involved in atherosclerosis and heart disease. Without one or the other, heart disease as we know it would probably not exist.
Dr. Sigurdsson:
So, are you also advocating consuming more “heart healthy
whole grains”?
Bill. In general terms my answer to your question is no. However, we are all different when it comes body weight and metabolism in general. Healthy whole grains may be a good choice for many individuals, while in other situations I believe it is better to avoid them.
Doc,
I emphasize that the overwhelming consensus of lipid researchers is that the inflammation associated with CHD is a causal product of elevated LDL cholesterol (See Steinberg 2008). When cholesterol is reduced, the inflammation dissappears. We’ve known about 100 years that CHD is accompanied with inflammation, however, the inflammation story became the new fad of the early 2000s, kind a like the vitamin E craze in the 1970s.
Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, While Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease without Inflammation (2013).
https://www.ncbi.nlm.nih.gov/pubmed/23926208
Moreover, oxidation of LDL is just one modification process that initiates the atherosclerosis.
Passwater: Is it accurate to say that only oxidized-LDL starts the plaque process?
Steinberg: No, it seems to me very likely that other modified forms of LDL are involved in plaque formation. What we know so far is that the use of antioxidants can decrease the rate of progression of lesions by 50-80%. That would speak to a major involvement of oxidation, but other things can also lead to foam cell formation. Studies by Dr. John C. Khoo in my laboratory have shown that aggregation of LDL with itself markedly increases the rate of uptake by macrophages. [15] The uptake in that case occurs by way of the native LDL receptor, not the acetyl LDL receptor or oxidized LDL receptor.
Studies by Drs. J. S. Frank and A. M. Fogelman at UCLA have demonstrated the generation LDL aggregates in the subendothelial space. [16] Aggregation does not depend upon prior oxidative modification. So here is a quite distinct mechanism by which LDL uptake into the macrophages can be accelerated and can perhaps initiate the fatty streak lesion.
Studies by Dr. Joseph L. Witztum and others in our laboratory have shown that minor modifications in the structure of LDL can render it immunogenic. Autoantibodies against oxidized LDL have been demonstrated in rabbits and in humans as well. Therefore, a complex of a modified LDL particle and an antibody against it can be taken up into macrophages by way of a completely different receptor, the receptor for immunoglobulins (the FC receptor).
So, there are at least two or three alternative modifications of LDL that could account for foam cell formation. These have not yet been studied in vivo as intensively as oxidative modification, and so we are not in a position to say with any confidence how important they may be.
https://www.healthy.net/scr/interview.aspx?Id=197
I find Nissen & Gillinov book interesting but unfortunately their approach doesn’t do anything for the one who is interested in drug-free prevention of chronic disease. It’s widely known that toothless paper tiger diets such as the one promoted by the AHA do very little for the LDL cholesterol. They are too little, too late for most patients. However, Ornish’s patients reduced their LDL cholesterol on average 40% in a randomized controlled trial (Ornish et al 1991) which is the drug-free world record. This reduction happens on average within 12-weeks as multiple sites that have utilized the Ornish program have demonstrated.
https://www.ornishspectrum.com/wp-content/uploads/effectiveness-efficacy-of-an-intensive-cardiac1.pdf
Nissens and Gillinov’s colleague at Cleveland Heart Clinic, Dr. Caldwell Esselstyn has also used dietary approach to tackle CHD with great success (although his program utilizes low-dose statins). But of course not a word of his work is provided in their book, let me guess? We have tons of information, but the problem is that mainstream doesn’t want go there because of the messianic belief and cultural bias of moderation. I mean look at you, you know that plaques can be successfully regressed in patients without the drugs. How many times have you informed your patients and blog readers about the work of Ornish’s and others? People are not in this business for the sake of truth. It was very depressing for me to discover this. Unfortunately Ornish’s <10% fat diet based on complex carbohydrates is politically incorrect in contemporary medicine; the new gospel mantra is that dietary fat has no role in obesity or CHD.
https://ajcn.nutrition.org/content/70/4/572.full
Amusing. There’s nothing “politically incorrect” about a vegetarian diet, and the thought of someone actually uttering such words strikes me as … Well, nevermind. The reason why Ornish – or any other low-fat vegetarian diet, for that matter – needn’t be praised unduly is that its effectiveness isn’t that much better from the point of view of clinical studies. You know, those that COMPARE diets to other diets?
“The above stressed above is clearly nonsense. It’s clear that Nissen and Gillinov would need broader palette to operate.”
That does indeed sound odd, but instead of the usual, old epidemiological data, you could’ve stated what has actually been observed in clinical conditions: cholesterol synthesis by the human body accounts for about on half of the cholesterol in the body. Liver itself accounts for one fifth of this.
https://themedicalbiochemistrypage.org/cholesterol.php
Continues…
in regards to Nissen’s and Gillinovs statement:
“Eighty percent of the body´s cholesterol is made by the liver. While most people think that diet is the most important factor in determining cholesterol levels, this is a myth. Only 20 percent of your cholesterol levels comes from your diet, which explains why it is so difficult to reduce blood cholesterol levels via dietary interventions alone”.
The above stressed above is clearly nonsense. It’s clear that Nissen and Gillinov would need broader palette to operate. In the 7CS the lowest mean serum cholesterol of 3.7mmol/l was observed in one the Japanese cohorts with mean intake of SFA ~2,5% of calories, the highest mean serum cholesterol was observed in Eastern Finland (6.8mmol/l) with SFA intake of ~21% of calories. That’s a difference of 45% or 84% depending on which way you look at it. The variation in the intake of SFA explained 87% of the variation in the mean serum cholesterol levels across the 16 different cohorts, this finding was perfectly in line with the findings from metabolic ward. SFA intake is the most important determinant of the blood cholesterol level of an individual (Pedersen et al 2011).
However, I welcome the fact that, despite spraying nonsensical “myth busting”, the authors of the book clearly arrive at the right conclusion in regards to diet & chronic disease prevention. Fiber rich diet based on whole-grains with low intake of SFA, that is.
@Richard
Can one separate dietary saturated fat intake from dietary cholesterol intake?
https://ajcn.nutrition.org/content/19/3/175.full.pdf
DIET AND SERUM CHOLESTEEOL IN MAN: LACK OF EFFECT OF DIETARY CHOLESTEROL
ANCEL KEYS, J. T. ANDERSON, OLAF MICKELSEN, SADYE F. ADELSON AND FLAMINIO FIDANZA
Outcome:
Cross-sectional surveys in Minnesota on young men – no relationship between dietary cholesterol and the total serum cholesterol concentration
Two surveys on Island of Sardinia – failed to show any difference in the serum cholesterol concentrations of men of the same age, physical activity, relative body weight, and dietary pattern, but differing markedly in cholesterol intake
Carefulstudy during 4 years with 33 men whose diets consistently very low in cholesterol – serum cholesterol values did not differ from 35 men on very high cholesterol diet
Comparisons made of 23 men before and after they doubled their cholesterol intake and of 41 men who halved their intake – failed to show any response in serum cholesterol level in 4-12 months
Detailed study of the complete dietary intakes of 119 Minnesota businessman – failed to show any significant increase in serum cholesterol with increasing dietary cholesterol intake
4 completely controlled experiments on men – addition or removal of 500-600mg of cholesterol a day had no effect on serum cholesterol
Completely controlled experiment on 5 physically active men – changing from a diet of 500 mg cholesterol to 0 mg of cholesterol had no effect on serum cholesterol
In completely controlled experiment in 13 men – no significant effect in changing cholesterol from 374 mg/day to 1369 mg/day, or from 1369mg/day to 374 mg/day on serum cholesterol.
Comments:
The foregoing evidence is definitive, we think, in showing that variations in the intake of cholesterol over the whole range of natural diets do not influence the serum level of physically normal adult men so long as other elements in the diet are constant.
They conclude that “in adult men, the serum cholesterol is essentially independent of the cholesterol intake.”
Thanks Axel for another informative look at the cholesterol controversy. I take issue with Nissen when he and his colleague write that: . “The LDL level is the best predictor of the risk of heart attack and stroke, and the basic concept is simple: the lower the better.” Multiple studies have shown that elevations in non-HDL-cholesterol and low HDL-cholesterol are far better lipid predictors of risk. In addition, if LDL level were so predictive of risk how can they account for the fact that in the 7CS, at the very same level of LDL (no matter whether it is high or low) men in Crete had one quarter of the risk of dying of heart disease as did men in the USA. It’s clearly NOT ALL ABOUT THE LDL! Even in kindred with true Fredrickson Levy Type II hypercholesterolemia, with LDL’s in the 300 to 600 range, while there is definitely an increased risk of premature atherosclerotic CVD, not all affected people develop it. I believe that the over-emphasis on LDL as a risk factor has more to do with marketing statins than any other reason. And as you yourself have pointed out, LDL particle number is probably what we should be measuring, since LDL-cholesterol represents a broad range of densities with greater or lesser degrees of atherogenicity.
You said “LDL particle number is probably what we should be measuring, since LDL-cholesterol represents a broad range of densities with greater or lesser degrees of atherogenicity.”
My question remains – high LDL-P, high ApoB, low CRP, low homocysteine – is this a bad profile?
I don’t think there’s a conflict in advocating for lower LDL levels AND stating that other risk factors need to be accounted for, too. If you exercise, don’t smoke at all nor drink excessively and eat a healthy diet (plenty of veggies, fruit and berries; mostly unsaturated fat; protein from vegetable sources, fish and nuts etc.), you’ll get lower LDL, higher HDL, better blood pressure etc. etc. That is, you’ll be able to lower a whole bunch a of risk factors.
Now, unfortunately, as simple as the abovementioned seems, in real life it seems to be nearly impossible to those who’d benefit from it the most. That’s why lipid-lowering medication comes in handy with high risk individuals.
Stains can also reverse plaque
https://content.onlinejacc.org/article.aspx?articleid=1136395
Effect of lipid-lowering therapy with atorvastatin on atherosclerotic aortic plaques detected by noninvasive magnetic resonance imaging
Our study demonstrated one-year lipid-lowering therapy with 20-mg atorvastatin (the maximal approved dose in Japan) to induce a marked LDL cholesterol reduction and a significant plaque regression in the thoracic aorta. In the abdominal aorta, even the 20-mg dose resulted in only a retardation of plaque progression, and a significant progression was observed in the 5-mg dose treatment. These findings suggest that atorvastatin has a greater effect on plaques in the thoracic aorta than in the abdominal aorta. Moreover, the degree of plaque regression in the thoracic aorta correlated well with those of LDL cholesterol and hsCRP reductions. Although the change in abdominal aortic plaques weakly correlated with the degree of LDL cholesterol reduction, it also correlated with age. Thoracic and abdominal aortic plaques may have different susceptibilities to lipid lowering, whereas other factors, such as aging, may play a more important role in plaque progression in the abdominal than in the thoracic aorta.
https://www.hcplive.com/publications/cardiology-review-online/2006/february2006/February-2006-Momiyama
Lipid-lowering therapy and atherosclerotic aortic plaques
The results of our study showed that a marked reduction in thoracic aortic plaques and in LDL cholesterol level occurred after 12 months of treatment with 20 mg/day of atorva-statin. The degree of reduction in LDL cholesterol level correlated with the degree of plaque regression in the thoracic aorta. In the abdominal aorta, however, there was a weak correlation between LDL cholesterol level and plaque regression, and plaque progression increased with age. These results suggest that lipid-lowering therapy affects plaques in the thoracic aorta differently from those in the abdominal aorta and that factors such as aging may affect the progression of plaque more in the abdominal aorta. – See more at: https://www.hcplive.com/publications/cardiology-review-online/2006/february2006/February-2006-Momiyama#sthash.qvFnBqE8.dpuf
@Barbara,
did the 7CS provide data on LDL cholesterol? I am under an impression the study only looked at TC cholesterol. Once again, cholesterol damage is about cumulative exposure. We do not know what were the cholesterol levels of the Crete people during their adolescence or during the war years, do we? Certainly TC cholesterol was higher among Americans than among the Cretan people. They were not on par as you suggest. The Americans had their mean serum cholesterol around 240s during the 1960s. These were not comparable to Cretans. And we know for a fact that Americans at the time had these sky-high numbers already at an early age. And yes, it’s not all about cholesterol, but it’s just that if its very low there’s no heart disease. Don’t tell me that those African Americans with heterozygot PCSKY-9 mutation and with their life-long LDLs around 50-60s (1.3-1.8mmol/l) do not suffer from diabetes, social isolation, obesity, exposure to cigarettes, high blood pressure, etc. Not a single case of atherosclerosis has never been identified among these people. Well, actually, it’s is just as simplistic as it is. It’s all about cholesterol! Elevated blood glucose, cigarette’s, high blood pressure exacerbate the cholesterol damage, but only elevated LDL can initiate the atherosclerosis.
Moreover, I have beef with your argument about low HDL-C cholesterol. The population which have enjoyed immunity to CHD have all traditionally had very low HDLs: Okinawa, rural China, etc. Unlike LDL-C, HDL-C is not even causally related to heart disease, see the large mendelian randomization studies. HDL-C is some kind of risk-predictor, and if its low in people who consumes a diet high in saturated fat and dietary cholesterol, like all Western people do, then it’s sign of a problem.
You are correct Richard about the 7CS – those data related TC not LDL-C to CVD mortality. But at any level of TC, high or low, CVD mortality in Cretan men was a quarter of that in US men. As for HDL-C, nothing raises HDL-C more than saturated fat, with monounsaturated fat intake coming in second. The only fat that lowers HDL-C levels is trans fat.
I don’t know how you can prove that no one with heterozygous PCSKY-9 ever had atherosclerosis. I have certainly seen any number of people with low LDL-C who still develop ASCVD, and my oldest patient, who is 104, has an LDL-C of 165 mg/dl and no documented vascular disease.
In the study by Cohen and coworkers published 2006, PCSK9 mutation was associated with lower levels of LDL cholesterol and lower risk of coronary heart disease. However, coronary artery disease was found among individuals with the mutation. Despite a very low plasma level of LDL cholesterol (53 mg per deciliter [1.4 mmol per liter]), one patient died at the age of 68 years, within 24 hours after his first myocardial infarction. Thus, patients with very low LDL cholesterol can have a heart attack.
Cohen and coworkers concluded that the reduced risk of coronary artery disease among those with the PCSK9 mutation was most likely related to their low levels of LDL-C. However, they did not exclude the possibility that PCSK9 may also have direct atherogenic effects that are independent of plasma levels of LDL cholesterol.
Doc,
some people of European origin may have partially degraded PCSKY-9 function and thus lower levels of blood cholesterol because of this. However, I referring to people with heterozygot mutation. The ones who have been identified are all black. In addition, there are few individuals with full-blown homozygot form of the mutation, these people have their lifelong LDLs around 7-14 mg/dl. All so far identified have been the epitomes of good health.
I suspect the one who died with CHD was one pf with partial degration of PCSKY9 function and with life long LDL only slightly lower than average LDL which is 3mmol/l in adult Western population. We do not what was the life-long LDL of this individual unless he carried the heterozygot version. Remember, the LDL cholesterol reduces after the ages of 65-70 years because of metabolic changes in the intestine resulting in lower absorption of synthesis of cholesterol.
@Barbara,
I found out about the fact that there’s 0 cases of atherosclerosis identified among those with heterozygot form of the PSCK9 knockout mutation from Darren McGuire’s interview at the AHA session in 2012. He works in UT Southwestern medical center in Dallas with Brown & Goldstein, Hobbes & Cohen. Starts after 7min.
https://www.youtube.com/watch?v=DFMtoafT70c&feature=player_embedded
See also:
https://www.nytimes.com/2013/07/10/health/rare-mutation-prompts-race-for-cholesterol-drug.html?pagewanted=1&smid=tw-share&_r=0
Brown & Goldstein, Evan Stein, McGuire, William Roberts, etc basically all the biggest shots in cardiology and atherosclerosis research believe that atherosclerosis is only about LDL cholesterol. Castelli from Framingham has concluded that when LDL is <1.8mmol/l HDL does not matter. I am sure he meant the midlife and pre-midlife years. Cholesterol, BMI and blood pressure all become less optimal risk predictors after that.
Other risk factors besides LDL can only make thing worse but LDL is the only factor that can initiate atherosclerosis and it can do it even at the absence of other risk factors which I believe you have no hard time to believe based on observation with homozygot FH kids. McGuire concludes that with new PCSKY9 antibodies LDLs will come down to 30s and patients become immune to CHD even though cigarette smoking, elevated blood glucose and hypertension is present. Notice, that in Japan in the 1950s even diabetics have significantly lower risk of developing CHD compared to Western diabetics.
https://circ.ahajournals.org/content/118/6/672.full
See Williams Roberts landmark article, the cause of atherosclerosis. W Roberts is from Dallas as well.
https://ncp.sagepub.com/content/23/5/464.extract
I want to be immune against CHD, prostate cancer, impotence… heck elevated cholesterol is a risk factor even in developing Alzheimer and lower back pains that's why I follow low-fat, vegan diet promoted by Ornish, McDougall MD certified internist, etc. My LDL is 1.8mmol/l. I hope it is couple decimal lower the next time. I am going easier on nuts and other high SFA containing plant-foods, and instead eat more unrefined starch, fruits and dried fruits at expense of nuts. I am planning to check my digits next month. I am bit envy to my friend who follows similar diet and has his LDL at 1.3mmol/l (50mg/dl) and HDL at 1.19mmol/l. The lower, the better. I take this business seriously!
Yes, butter and cream will elavate HDL cholesterol, and I am not sure if that is a good thing 🙂
Anyways Doc,
I admit that the person you referred to should not have died in CHD. Very unlucky individual. But then again, unless we have information of his/her cholesterol at midlife, it’s hard to consider this case as a true exception. If there was atherosclerosis in people with heterozygot PCSK9 mutation, then obviously I’d have to rethink my ideas and it would mean that you had been right about cholesterol all the way. Time will tell 🙂
Also, I do not know the details of the study you referred to, but thanks to these Swedish experts I do know that the cholesterol levels comes temporarily down after MI. It’s unclear to me whether the LDL numbers were attained earlier or at the hospital immediately after the MI.
https://www.lakartidningen.se/07engine.php?articleId=14031
“But then again, unless we have information of his/her cholesterol at midlife, it’s hard to consider this case as a true exception.”
Since this patient still had an LDL-level of 1.4 mmol/L at the age of 68, I’d argue that its likely that he had significantly lower LDL levels during most of his life. And in any case, his LDL-level was well below the upper end of the sc. physiological level (1.5 mmol/L).
Now, the guy was severely obese, suffered from hypertension and smoked. All “classical” risk factors. What this case hints is that you simply CANNOT and SHOULDN’T rely on looking at LDL levels alone when considering who is at increased risk of CHD.
“I am going easier on nuts and other high SFA containing plant-foods”
What, are you nuts? 🙂 E.g. walnuts, cashew nuts, hazelnuts etc. etc. are LOW on safa. About 83% of the fat in cashew nuts is unsaturated; 92% in hazelnuts; 90% in walnuts. Not to mention that the data (both clinical risk marker data & epidemiological risk marker & end point data) is consistent in showing the benefits of nuts in obesity and CHD prevention.
https://atvb.ahajournals.org/content/15/8/1043.long
Predominance of Large LDL and Reduced HDL2 Cholesterol in Normolipidemic Men With Coronary Artery Disease
The association between large LDL size and CAD was significant (P26.8 nm) was more prevalent among subjects with CAD (43%) than among control subjects (25%) (P<.002). Among subjects with this LDL size profile, subjects with CAD had significantly higher (P<.05) VLDL triglyceride, VLDL cholesterol, and VLDL apo B levels and significantly lower (P<.0001) HDL2 cholesterol levels than controls. Thus, in this normolipidemic population with CAD, a predominance of very large rather than small LDL particles was associated with increased VLDL and reduced HDL2 cholesterol levels and with increased CAD risk, independent of other plasma lipid and lipoprotein levels.
In the present study, the association between large LDL particles and CAD risk was independent of HDL2 cholesterol levels and other CAD risk factors. Although there may be other metabolic factors, not measured here, that could be responsible for this finding, the present results raise the possibility that some large LDL particles are atherogenic in humans.
Charles. I agree with you. Large particles can be atherogenic. Patients with familial hypercholesterolemia often have large LDL particles. Nonetheless, their risk of atherosclerosis and heart disease is high. Their LDL cholesterol is high and so is their LDL particle number (LDL-P). Large particles don´t prevent them from developing atherosclerosis. This may support the theory that the number of LDL particles is more important than particle size when it comes to estimate risk.
I realize that this blog is nearly six months old, however, I could not keep my comments to myself. The problem with FH does not revolve around cholesterol or its carriers. No, the body raises those levels as a solution to the real problem, which is disheartening to me that it is not part of the knowledge base of a doctor writing on the subject. Moreover, although some people hetero- or homo-zygous for FH perish as a result of atherosclerosis, most do not. Rather, they die of valve issues and other non-atherosclerotic CVD.
Thanks for the comment Laurence. I’m quite impressed that you believe you know what is and what is not a part of my knowledge base. That shows a wonderful insight on your behalf.
Then you probably know, as well as I do, that prior to the widespread use of statin therapy for patients with heterozygous FH, the risk of premature coronary heart disease (CHD) was very high https://aje.oxfordjournals.org/content/160/5/421.long
In a 1974 study of over 1.000 first and second degree relatives of 116 index patients, the risk of fatal or nonfatal CHD by age 62 was 52 percent for male and 32 percent for female relatives https://circ.ahajournals.org/content/49/3/476.long. In relatives without FH, the comparable rates were 13 and 9 percent respectively.
Is your belief that individuals with FH are not at increased risk of atherosclerotic heart disease supported by scientific evidence?
Please note that I didn’t say they didn’t get atherosclerosis, I said it wasn’t the cause of death of most people with FH. Even so, the main question is what is the real problem with FH? You must know that it isn’t the cholesterol. It’s the…
Following up, as I see no one has responded, the problem with FH–a misnomer–isn’t the cholesterol, it’s deficient cholesterol receptors. Much like in insulin resistance the body compensates by producing too much insulin, when cholesterol receptors are insufficient, the body produces too much cholesterol and its carriers, because cholesterol is such a vital molecule.
See for example:
https://drmalcolmkendrick.org/2013/07/16/you-are-a-very-black-swan-indeed/
The role of LDL receptors and their availability is certainly an important issue. The PCSK-9 inhibitors that are now being tested in clinical trials increase the availability of LDL-receptors which probably is the main reason why they lower blood cholesterol. Of course we still don’t know about the clinical efficacy of these drugs.
You’re absolutely right that the underlying problem with FH is lack of or dysfunctional LDL-receptors. This commonly leads to high levels of circulating LDL-cholesterol in blood. The numbers of LDL-particles (LDL-P) is also high due to the lack of clearance of these particles from the blood stream. However, whether it is due to high blood levels of LDL-cholesterol, high LDL particle number, or something else, individuals with FH are at increased risk of coronary heart disease. Secondly, statin therapy appears to lower the risk of coronary events in these individuals, whether it’s due to the cholesterol lowering effects of these drugs or something else.
Lower the risk of coronary events on patients that have already had a coronary event? By how much and at what cost?All statin trials utilize relative risk instead of absolute risk obfuscating the real benefit, which is negligible in absolute terms, at the cost of diabetes, pain, memory loss, et al.
Many researchers today think that inflammation is the cause of atherosclerosis. The problem is that all anti-inflammatory trials have resulted in a significant increase of CHD mortality.
A better interpretation of these findings taken together is that inflammation is beneficial; it is not the cause. I think that atherosclerosis is a process of damage to the arteries, and that inflammation represents the body’s attempts to repair that damage.
Just as I do not believe that inflammation causes torn ligaments, or broken legs, I do not believe that inflammation causes atherosclerosis.
The process is simple: damage -> repair -> inflammation. If you interfere with repair/inflammation, things get worse. Which is why all anti-inflammatory agents make CVD worse….unless they have other effects, e.g., aspirin, statins.
The effect of statins on NO synthesis nearly fully explains their benefits, though, on the subject of “pleiotropic” benefits of statins, they inhibit platelet production of thromboxane which is proaggregatory and prothrombotic; see Schrör K. Eicosanoids 1990; 3:67-73.
If and when inflammation is present in the atheromatous process one is still stuck with the question as to what initiates or triggers the inflammation. The same is true of any so-called auto-immune disease. In rheumatoid arthritis for instance, joints can become inflamed but one would say that inflammation was part of the disease processs, not that it caused the disease. Is not atherosclerosis similar?
Best wishes… – lc
https://www.lecturepad.org/pdf/tomdayspring/human_lipid_transportation_system.pdf
Lipid and Lipoprotein Basics
Thomas Dayspring MD, FACP, FNLA, NCMP
It is crucial to have a clear understanding of how particle size contributes to atherogenesis (it does not). All LDL particles, large or small are atherogenic (will enter the arterial wall) if present in increased numbers (elevated LDL-P). If LDL-P is low (physiologic), there is little risk whether one has large or small LDL particles. Indeed, once LD-P is known, LDL size is no longer an independent risk factor for CHD.
If LDL-P is high, CHD risk is high no matter whether the high LDL-P is driven by toomany large LDLs, too many small LDLs or both. Keep in mind that the most lethal lipid/lipoprotein disorder is familial hypercholesterolemia. Such patients typically have very increased numbers of the larger (PatternA) particles. All of the older studies that suggested risk is related to small LDLs per se, were never adjusted for LDL-P.
Once that adjustment is made, the risk related to LDL size is no longer statistically significant.
Because the volume of a sphere or circular particle is a third power of the radius (V = 4/3π r3), there are considerable volume differences between particles that vary only slightly in diameter. Thus if a patient has an LDL-C of 100 mg/dL it will take 40 to 70% (depending on the exact diameter) more small LDL than large LDL to carry the 100 mg of cholesterol. Therefore, even though an LDL-C may be 100 mg/dL, the LDL-P will be
40-70% higher in patients with smaller rather than large LDL. Also if one has TG-rich and thus cholesterol-poor LDL particles, it will take increased numbers of particles to traffic a given level of cholesterol. And it is LDL-P that primarily determines risk. Since any apoB particle 80-100 mg/dl. Ideal is less than 80mg/dL or perhaps even 60mg/dL in very high risk patients. It is more accurate to measure LDL particle concentration (LD-P) using the NMR(nuclear magnetic resonance spectroscopy) technique (n<1000 nmol/L).
Key points
"If LDL-P is low (physiologic), there is little risk whether one has large or small LDL particles. Indeed, once LD-P is known, LDL size is no longer an independent risk factor for CHD."
"Since any apoB particle < 70 nm in diameter can penetrate the vascular endothelium, LDL size does not influence LDL particle entry into the subintimal space(the largest LDL is 23nm. Likewise the number of cholesterol molecules per particle has no influence on LDL particle entry. The only variables that affect vascular entry are LDL-P and endothelial integrity."
https://www.dislipemias.com.ar/pdf/apoBandrisk.pdf
Apo B versus cholesterol in estimating cardiovascular risk and in guiding therapy: report of the thirty-person/ten country panel
In brief, this paradigm posits that the total number of atherogenic particles is a more important determinant of the risk of vascular disease than any of the conventional lipid measures. This is the case because the number of particles within any lipoprotein fraction determines the likelihood of any member of that class entering and lodging within an arterial wall. The conventional lipid indices equate the risk due to a specific lipoprotein fraction to the plasma lipid concentration of that fraction. Thus, triglycerides are the estimate of the risk due to VLDL, LDL cholesterol the estimate of the risk due to LDL, and non-HDL cholesterol the estimate of the combined risk of VLDL, IDL, LDL and Lp(a). But there is an error in this equation. The lipid composition of the principal atherogenic lipoproteins differs substantially amongst individuals. Therefore, lipid levels do not automatically equal lipoprotein particle levels.
Most studies divide LDL into only two subclasses: large and buoyant LDL particles that are relatively enriched in cholesterol (LB-LDL) and small and dense LDL that contain less cholesterol (SD-LDL). Whilst useful, this is an oversimplification and it is biologically and clinically more accurate to recognize at least three subclasses: very large LDL (LDL I), large LDL (LDL II) and small LDL (LDL III) (Fig. 1). Indeed, none of us have just one subclass, although one does tend to predominate at any time. A correspondence between the predominant LDL subclass and disease was noted first by Teng et al. Low-risk individuals were characterized by a lower than average number of LDL particles and the dominant LDL subclass was LDL II. Patients with familial hypercholesterolaemia (FH) were characterized by markedly increased numbers of LDL I and LDL II, whereas patients with hyperTg hyperapo B were characterized by markedly increased numbers of LDL II, particularly LDL III particles . Because the amount of LDL cholesterol per LDL particle varies substantially both between and within individuals, LDL cholesterol does not necessarily equal the most critical variable, the total number of LDL particles. This is the key point.
So – it would appear that high LDL-c usually equals high LDL-P (ApoB) and that the particle size is of very little importance. Would that not mean that a diet that produces high levels of these markers – regardless of low inflammation – is dangerous?
Hello,
I haven’t read through all of the comments so please forgive me if I’m repeating anything. You wrote:
Jimmy Moore has no formal medical or nutritional health education. He does not refer to many scientific studies in his book. Instead, he has chosen to select an army of what he calls “trusted advisers who know the answers to the most pressing questions about health”. Moore constantly quotes these individuals throughout his book.
Moore´s army consists of twenty-nine individuals. Some are nutritionists, some are physicians, and some are neither. Some are respected scientists and leaders in their field. He has chosen many trustworthy and knowledgeable individuals, although obviously some may appear more trustworthy than others. Obviously Moore has handpicked a team of specialists who support his own theories. But I have to assume that all these individuals don´t agree with Jimmy Moore on everything he writes, but I could be wrong. What Moore fails to do is to also choose experts who don´support his opinion.
The problem is that a few of his experts do differ with Jimmy’s opinions and the opinions of many of the other “experts”. Without ANY scientific references the readers are left to rely on Jimmy’s designation of “world renowned”, “cream of the crop”, etc. Most have no special training either. Furthermore, the most prominent expert in the field of LDL particles, Dr. Dayspring, is given short shrift in the chapter about LDL particles — and there is little to no evidence that large particle sizes are benign or even “protective”.
Did you take a look at the cholesterol profiles in the last chapter? The test of sorts to determine if profiles are healthy, needs some work or poor? Utterly irresponsible. I encourage you to look at them. I took the liberty of compiling them according to Jimmy’s designations (that presumably Westman signed off on … sigh). The top row (including his on the far right) are deemed healthy, middle left as work needed, and middle right as poor. Would YOU as a physician class these lipid profiles in this manner?? His own “expert” and Amazon cheerleader Dr. “Wheat Belly” Davis wouldn’t: https://www.trackyourplaque.com/forum/topics.aspx?ID=14844
https://3.bp.blogspot.com/-nRgf0ZwSjrA/UjuHoDJ8a8I/AAAAAAAAERM/Fch9nUnhk00/s640/Screenshot+-+9_19_2013+,+10_44_57+AM.png
I do believe this sort of unsubstantiated reliance on super low triglycerides as being better than “normal” and/or higher and higher HDL being somehow protective is indeed dangerous to readers. Jimmy Moore is hopelessly biased trying to convince himself that his ever-more-extreme diets are healthy as his health declines (not just lipids). Here is what he said when he got a somewhat similar report in 2009 (lower LDL-P) https://www.examiner.com/article/the-nmr-lipoprofile-cholesterol-particle-size-test-more-accurate-measure-of-heart-health-risk
More here (much more): https://carbsanity.blogspot.com/2013/08/jimmy-moores-cholesterol-clarity.html
Thanks Evelyn for your important comments.
As I wrote in my article I don´t agree with Jimmy Moore on everything he writes in his book and the interpretation of some of the lipid profiles is an example of that. I also agree that handpicking “specialists” and quoting them as Jimmy does is a problem because he has obviously selected individuals and quotes that support his own opinion. Of course this may be interpreted as one type of “cherry picking”.
Again, thanks for sharing your thoughts.
Jimmy said to email him and he’ll get on it 🙂 livinlowcarbman@charter.net. Email jimmy and he will have you on his show to chat more.