For years, measurements of blood cholesterol have been used to assess the risk of heart disease.
We have been intensively educated about the role of LDL-cholesterol (LDL-C), commonly nicknamed the bad cholesterol and HDL-cholesterol (HDL-C), often called the good cholesterol.
For many different reasons, lowering LDL-C has become a primary goal in cardiovascular prevention. There is strong evidence available suggesting a relationship between LDL-C and the risk of coronary heart disease.
Medical professionals usually recommend lifestyle measures that lower LDL-C, and statins (cholesterol-lowering drugs) are used by millions of people worldwide for the sole purpose of lowering LDL-C numbers.
However, in order to understand coronary heart disease and how plaques form in our arteries (atherosclerosis) we have to understand that focusing only on cholesterol is an oversimplification.
Because cholesterol is a fat substance, it can’t mix with water and can therefore not travel in blood on its own. The body’s solution to this problem is to bind fat molecules to lipoproteins which function as transport vehicles carrying different types of fats such as cholesterol, triglycerides (TG) and phospholipids.
It is important to understand that it is lipoprotein that interact with the arterial wall and initiate the development of atherosclerosis. Cholesterol is only one of many components of lipoproteins.
A standard lipid profile includes total cholesterol, LDL-C, HDL-C and TG. Although LDL-C usually gets the bulk of the attention, evidence suggests that other aspects of the lipid profile may not be less important. For example, non-HDL Cholesterol is a strong marker of risk, maybe more important than LDL-C.
Relying on LDL-C alone can be misleading. For example, people with obesity, metabolic syndrome or diabetic lipid disorders often have raised TG, low HDL-C and normal or close to normal LDL-C. These individuals produce very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) which may increase the risk of atherosclerosis.
Many studies have found that the triglyceride/HDL cholesterol ratio (TG/HDL-C ratio) correlates strongly with the incidence and extent of coronary artery disease. This relationship is true both for men and women.
One study found that a TG/HDL-C ratio above 4 was the most powerful independent predictor of developing coronary artery disease.
With the increasing prevalence of overweight, obesity and the metabolic syndrome this ratio may become even more important because high TG and low HDL-C is often associated with these disorders.
The Triglyceride/HDL Cholesterol Ratio. What Is Ideal?
The TG/HDL-C ratio can easily be calculated from the standard lipid profile. Just divide your TG by your HDL-C.
However, when looking at the ideal ratio you have to check if your lipid values are provided in mg/dl like in the US or in mmol/L like in Canada and most European countries.
If lipid values are expressed as mg/dl (like in the US);
TG/HDL-C ratio less than 2 is ideal
TG/HDL-C ratio above 4 is too high
TG/HDL-C ratio above 6 is much too high
If you live outside the US or are using mmol/L, you have to multiply this ratio by 0.4366 in order to attain the correct reference values. You can also multiply your ratio by 2.3 and use the reference values above.
If lipid values are expressed as mmol/L (like in Canada and Europe);
TG/HDL-C ratio less than 0.87 is ideal
TG/HDL-C ratio above 1.74 is too high
TG/HDL-C ratio above 2.62 is much too high
In this article TG/HDL-C ratio is provided as in the US (mg/dl).
Triglyceride/HDL Cholesterol Ratio and LDL Particles?
Recently, analyzing the number of LDL particles (LDL-P) and LDL particle size has become increasingly common. However, this method is not universally available, is expensive, and has not been widely applied in clinical practice.
High numbers of small, dense LDL particles are associated with increased risk for coronary heart disease in prospective epidemiologic studies. Subjects with small, dense particles (phenotype B) are at higher risk than those with larger, more buoyant LDL particles (phenotype A).
Interestingly, it has been found that the TG/HDL-C ratio can predict particle size. One study found that 79% of individuals with a ratio above 3.8 had preponderance of small dense LDL particles, whereas 81% of those with a ratio below 3.8 had a preponderance of large buoyant particles.
Obviously, people with high TG/HDL-C ratio tend to have higher than normal TG. Just like all other lipids, TG have to be transported in blood by lipoproteins, most are carried by chylomicrons and VLDL.
What happens under these circumstances is an interchange of lipids between lipoproteins. TG are moved from VLDL into LDL and HDL in exchange for cholesteryl ester. The result is that LDL and HDL particles become cholesterol poor and rich in TG. Then, when TG are removed from these particles, which generally happens, the particles shrink and become smaller as they’re only transporting small amounts of cholesterol. This explains the relationship between high TG/HDL-C ratio and the number of small LDL particles.
However, the number of LDL particles present in the blood may be more important than particle size. Furthermore, particle number appears more important than how much cholesterol is carried within these particles. Blood levels of LDL-P and apolipoprotein B are strongly correlated with the risk of coronary heart disease. Both these measurements reflect the actual number of LDL-particles.
But, can the TG/HDL-C ratio reflect particle number? In fact it can, to a certain degree. Take a look at the LDL-C, the amount of cholesterol carried in LDL-particles. A high TG/HDL-C ratio indicates that these particles are small. A small particle carries less cholesterol than a large particle. Therefore a larger number of particles is needed to carry a certain amount of cholesterol if the particles are small than if they’re large. So, a high TG/HDL-C ratio likely presents high number of LDL-particles, unless LDL-C is very low.
Triglyceride/HDL Cholesterol Ratio and Insulin Resistance
Insulin resistance is a condition in which cells fail to respond to the normal actions of insulin. Most people with this condition have high levels of insulin in their blood. Insulin resistance appears to play an important role in coronary heart disease, and can predict mortality. This condition is common among individuals with abdominal obesity and the metabolic syndrome.
A study in which most of the participants were caucasian and overweight identified TG/HDL-C ratio of 3 or greater as a reliable predictor of insulin resistance.
However, not all studies have found the TG/HDL-C ratio to be associated with insulin resistance. For example, in a relatively small study of 125 African American participants, neither fasting TG nor the TG/HDL-C ratio was shown to be a marker of insulin resistance.
Although confirmatory studies are needed, data suggests that an elevated TG/HDL-C ratio may be clinically useful for the prediction of insulin resistance.
How to Improve Your Triglyceride/HDL Cholesterol Ratio
Improving your TG/HDL ratio aims at lowering TG, raising HDL-C or preferably both.
If you are overweight, losing weight will probably lower your TG levels and so will reducing your intake of added sugar. Studies have found that high intake of fructose leads to high TG. High-fructose corn syrup is a major source of fructose.
Low-fat diets are usually not effective in lowering TG. In fact, low-fat, high carbohydrate diets may raise TG. Adding omega-3 fatty acids, regular exercise and limiting alcohol may be helpful to lower TG.
Similar methods may be useful for raising HDL-C. Losing weight, exercising and not smoking may help. In controlled trials, low-fat, high-carbohydrate diets decrease HDL-C, thereby raising the TG/HDL ratio.
In 1961 a group of investigators from the Rockefeller Institute, led by Pete Ahrens published a paper entitled “Carbohydrate-induced and fat-induced lipemia”.
The authors pointed out that fat-induced increase in TG following a meal is a postprandial phenomenon (we all have high TG for a few hours following a fatty meal) caused by chylomicrons is different from the carbohydrate-induced rise in TG (later found to be caused by elevation of VLDL).
These findings have been confirmed in several more recent studies. Despite this, low fat, high carbohydrate diets are still being recommended as a primary option to reduce the risk of heart disease.
Although low-fat diets may help lowering LDL-C, low carbohydrate diets are generally more effective in improving the TG/HDL-C ratio.
This suggests that solely selecting LDL-C as a target in cardiovascular prevention is an oversimplification, and may have lead to wrong conclusions regarding the relationship between diet and heart disease.
4 years ago, I was eating HCLF and taking rosuvastatin (among other medications) with (US-type numbers):
TC 171, HDL 66, LDL 63, TG 208 (TG/HDL 3.2).
3 years ago I switched to ‘Low-ishCHF’, stopped the statin (and other medications) and after 20 months like that (May 2013) had:
TC 237, HDL 91, LDL 133, TG 64 (TG/HDL 0.7).
Along the way (first 15 months) I dropped 36kg (ca. 30% body weight).
Another year on, I have lost another 1-2kg and guess that my numbers remain about the same as last year, but see no reason to check them (my doctor says ‘get them checked in another 4 years!’)
Ir seems to me that my health has improved immeasurably and, at least for me, the TG/HDL seems to be a useful ratio.
the doctor who saw my numbers was freaking out…
TC 276
HDL 62
LDL 201
TG 68
But I’m freaking out too :'(
I think the LDL seems a bit high, although the ration of trig to hdl works out to 1.09…? Yes I know about what the article says. But can’t help noticing the higher LDL levels :'(
your numbers are very similar to mine. I have 250 cholesterol. 60 HDL and 62 triglycerides. My LDL is high. If I were going to fill my plate, I would put veggies on half the plate, a small piece of meat on the plate, a little fruit, and maybe some rice. I seriously eat like that. I don’t even like sugar and don’t even drink juice at all(no pop, no candy) whole grains. I think your case might be genetic like me. I tried statins and they made me sick! I have tried everything. There’s no way I am taking statins. I figure if I die I die. I just can’t feel like hell on statins all the time. I am trying this supplement called syntrinol now. I doubt it will work, because nothing works. Good luck to you.
Read Dr. Perlmutter “Grain Brain.” His low carb, high fat diet is the way to go.
Lucy
I may have some information for you that can help you.Email me and I will forward to you a webinar that explain it and suggests what to do.
Giora Zeevy
Health Coach
giorazeevy@gmail.com
Try telling this to NICE in the UK. Think the target for intervention is approximately 3.2 LDL-C with statins, might be wrong.
Great piece.
What do you think of the waist-to-hip ratio as another indicator of the risk for heart disease?
A question please, Dr Sigurdsson,
Regarding the units of the measurements of respective levels of the individual componenets, which can be mmol/L, or mg/dl.
I can understand that to create a ratio number, in this case between TG and HDL-C the same units of measurement need to be used for each item.
I don’t understand why a change of units, providing the same unit is used for both components, can need any further conversion when comparing ratios and assessing ‘safe’ ratio levels.
In other words, a ratio of say 4 for TG/HDL-C measured in mmol/L should be equivalent to the ratio 4 when the measurements are in mg/dl.
I hope this is a valid question.
@ Ken. When Triglycerides and HDL are converted from mg/ml to mmol/L, different constants are used causing the ratio to be different.
Let’s take an example. Person A has TG 80 mg/dl and HDL-C 40 mg/dl. His TG/HDL-C ratio is 80/40 = 2.
If we convert (you can use the convertor here) his numbers to mmol/l: TG 0.90 and HDL-C: 1.03. The TG/HDL ratio will be 0.87.
You would have had the same result if you multiplied by 0.4366.
0.4366 x 2 = 0.87
If you are using mmol/L but want to use the US reference (which is easier to remember), you can multiply your ratio by 2.3, e.g. 0.87 x 2.3 = 2.
Axel, thank you so much for such an inspiring post. I do so agree with the way your opinions and posts appear to be trending.
The father of the fat/cholesterol hypothesis thought work by Anitschkow and Chalotov (1913) proved cholesterol to be an atheorgen. But their result was really artefact and confounding error. Cholesterol impurities produced the results. Neither they nor Keys knew this and it was not until 1976 the error was properly illuminated.
Keys needed a reason to explain his perceived phenomenon of hypercholesterolemia. He sensed fat in the diet might promote hyopercholesterolemia (high levels of cholesterol in blood) and he majored his concern upon saturated fat.
Now, I can sense Keys reasoning that added dietary fats place a call for additional cholesterol to be supplied to the digestive track, and that additional cholesterol carrying lipoproteins would be passed over the gastrointestinal divide and find their way into the blood, but for the life of me I cannot see how saturated fats above all others would result in this supposed effect. Then, to complicate matters, lipoproteins fashioned in the GI track do not enter the blood directly. Instead they are called chylomicrons, despite they are still lipoproteins of a kind, and they enter the lymph system. Ergo, chylomicrons do not show up in blood test.
Besides, just as you indicate, the supply of glucose to, and the presence of insulin in, the blood have more bearing upon lipid profile counts, profiles, and ratios than do fats in the diet. The effects of a high fat diet upon cholesterol levels is actually counter intuitive to the Keys view and that promoted by the fat/cholesterol hypothesis.
Neither saturated fat or cholesterol are the major issue, while certain oxides of cholesterol and homocysteine are evidentially implicated in the business of atherogenicty that is the makings of CVD and thence promotes risk of cardiovascular events such as heart attack and stroke. The principle oxides of cholesterol to be concerned for are cholestane-3B,5a,6B-triol, 25-hyrdroxycholesterol, and perhaps 7-ketocholesterol. In all probability methyl deficiency permits the rise in oxidative stress that may result in conversion of numbers of cholesterol molecules to certain cholesterol oxides.
I would like you to be made aware that this post of yours, more than any other stimulus, proved the inspiration to write a concise and summary 2000 word review that suggests what’s wrong with the fat/cholesterol hypothesis and what is most likely most correct about its much needed successor. It just needs finalising and then I would hope to be able to share it with you one way or another.
Thank you for becoming a luminary casting light upon and advancing the truth on cholesterol and CVD.
Axel,
“However, low fat diets are still being recommended as a primary option to reduce the risk of heart disease.”
Err, no, they aren’t. Unless you’re referring to Ornish et co.
@ Mie
You commented on the following conclusion in my article
“However, low fat diets are still being recommended as a primary option to reduce the risk of heart disease.”
by writing
“Err, no, they aren’t. Unless you’re referring to Ornish et co”
I have to disagree with you.
The authors of the 2013 AHA/ACC Guidelines on Lifestyle Management to Reduce Cardiovascular Risk point out that “randomized clinical trials examining the examining the effects on hard outcomes (MI, stroke, heart failure and CVD-related death) are difficult if not impossible to conduct for several reasons (e.g. long term adherence to dietary changes). The Work Group prioritized topics for evidence review and was unable to review the evidence on hard outcomes for dietary patterns and physical activity”
Later on:
“The results of the Work Group systematic review are the 10 lifestyle recommendations (8 dietary and 2 physical activity recommendations)” – these are provided in a table. The recommendations are aimed at two risk factors, LDL-C and blood pressure.
These are the main points of the recommendations (table 5 in the paper):
Consume vegetables fruits, whole grains, low fat dairy products, poultry, fish, legumes, non-tropical vegetable oils and nuts; and limit intake of sweet, sugar sweetened beverages and red meats.
Aim for a dietary pattern that achieves 5-6 % of calories from saturated fat
Reduce percent of calories from saturated fat
Reduce percent of calories from trans fat
Achieve this pattern by following a plan such as the DASH dietary pattern, USDA food pattern, or the AHA diet.
Lower sodium intake
Consume no more than 2.400 mg/sodium/d.Further restriction to 1.500 mg/ day may further improve blood pressure.
In my mind this is a low fat approach. Basically the same thing that has been advocated fro 40-50 years.
Don’t misunderstand me though. I think this approach is appropriate in many situations. However, such guidelines have limited applications for the clinician. What I am highlighting in my writing is that we have to look further. People are different. There are other targets, other approaches that may be helpful. Look at all the people with the metabolic syndrome, type 2 diabetes for example. Of course I know the US guidelines were not supposed to cover these problems. But I doubt that an approach, focusing on two targets (LDL-C and hypertension) is of much help.
Christopher,
isn’t it high tine to move on from the 50s/60s? The medical community has, but for some people it seems impossible to let go off Keys – despite the fact that his initial ideas (mind you, later on he disgarded the idea of total fat being the problem and focused on fat type AND especially of the ENTIRE dietary pattern) have nothing to do with Axel’s post.
I regret Mie I cannot discern if you are agreeing/complementing my comment or challenging/disagreeing with it.
I challenge your point that the medical community has moved on from the 50s/60s. It has but only in the sense that it is commonplace to adopt the fat/cholesterol hypothesis as virtuous and true. It isn’t.
That dietary fat (with specific emphasis on saturated fat) might raise cholesterol and that raised cholesterol causes heart disease has been the consistent mantra within general practice, primary prevention, and cardiology for six decades and shows only marginal signs of giving way.
I have been witness to Axels contributions to debate on cholesterol, upon diet, and upon CVD both here and elsewhere, especially upon the blog of Dr John Briffa. Hence I know Axel has been wrestling with the issues for a while, and I have some sense of how Axels opinions have trended. For what it’s worth, which is not much, his views are trending in the right direction.
The great problem with the fat/cholesterol hypothesis is that cholesterol is a hugely functional and ubiquitous molecule with a great dived in biology. Vertebrates have great need of cholesterol while plants have no need whatsoever. Cholesterol accounts for a great deal of difference between a vertebrate and a cabbage. Cholesterol holds the membranes of eukaryote cells together and provides for lipid rafts which can ferry important lipids across membranes.
The key thing to note is that cholesterol does not initiate the change in the behaviour of cells within the endothelial layer of the tissues of the artery that gives rise to the formation of atheromas, or ‘fatty plaques’. Also worth noting is that in the history of the formation of the hypothesis its founder, Dr Keys, never realised impurities in batch samples used in animal trials could have accounted for the results. Key impression of cholesterols capacity to cause atheromas was false. Certain oxides of cholesterol gave rise to the effect while neither the early trialists or Keys realised this was the case. More in the 70s and 80s it was establsihed that pure cholesterol is innocuous when tested in vivo and in vitro trials whereas certain oxides of cholesterol gave rise to atherogenesis. If you tried to suggest that my remarks were impertinent you could not be further from the truth.
Yes, Keys did amend his views over the years. It’s right he should.
In 1957 Yerushalmy and Hillboe exposed how Keys misused data to concoct his ‘six countries study’ alleging correlation between national consumption of saturated fat and heart related mortality. Keys 1953 study was sham science. Keys took data from the WHO, the data itself was second rate for having no standard method of collation, but the WHO had available data for 22 countries. Keys selected just six. The 22 proved no association, only the selected six did that.
Keys also coined the term Mediterranean diet and did much to promote the notion. Actually there are all manner of reasons why the Mediterranean lifestyle and environmental experience differs from that of the urbanised countries of more temperature latitudes. Keys did much to have the establishment convince almost everybody that diet is paramount. Diet is important up to a point, but there are other factors that are causally implicated in the etiology of CVD. Low fat high carbohydrate diets have been championed as representing diminished risks for CVD, yet this is actually the reverse of the truth.
The key to understanding the real cause of heart disease is to appreciate that oxidative stress is the big driver of risk of atherogenicity. Oxidative stress is not an easy concept to grasp but levels of oxidative stress are always present within the body. Levels of oxidative stress can rise above that which is merely basal, and stress is a big driver of this, so too is methyl deficiency.
Methyl deficiency arises when not enough antioxidants of the right kind are available to donate methyl groups (CH3) to reactive oxygen species to ‘zap’ them and detoxify them. being stressed raises competition for methyl groups and so can determine there are not enough donors to match demand. When this happens level;s of a substance called homocysteine rise and homocyteine may convey oxidative stress the way of cholesterol resulting that some cholesterol molecules are converted to certain oxides of cholesterol. This then has bearing for the behaviour of cells and degeneration of tissues of the artery sets in.
Mie, you may think you are contributing to the discussion but your remarks read like you are scoffing at comments passed by people who have given matters more contemplation than you have. If you are malcontent it is better and healthier for you to address the cause. And do not get me wrong, there is much about our world to be malcontent about.
Christopher,
“I regret Mie I cannot discern if you are agreeing/complementing my comment or challenging/disagreeing with it.”
I thought it was obvious? I couldn’t understand the reason to bring Keys into the discussion here. Notice the past tense “couldn’t” – your latest message clarified the reason why you did this. I’ll address it later.
“I challenge your point that the medical community has moved on from the 50s/60s. It has but only in the sense that it is commonplace to adopt the fat/cholesterol hypothesis as virtuous and true. It isn’t.”
First of all, lipid hypothesis and diet/heart hypothesis aren’t the same things. This
“That dietary fat (with specific emphasis on saturated fat) might raise cholesterol and that raised cholesterol causes heart disease has been the consistent mantra within general practice, primary prevention, and cardiology for six decades and shows only marginal signs of giving way.”
implies that you’re mixing them up on purpose. Of course diet has a role in CVD prevention- this has been established – and the development of atherosclerosis but it cannot be reduced the SAFA as such. Nope, it’s a lot more complicated. However, lipid levels in BLOOD are what counts and improving them isn’t just about the diet alone, let alone the fat content in one’s diet. And yes, lipid levels (such as increased levels of e.g. LDL) have been proven to be a risk factor (you do know what a “risk factor” is, don’t you?). To suggest anything else is to utter a religious statement.
Now, this doesn’t mean that they’re the ONLY thing that matters in the development of atherosclerosis and/or that we know every little detail there is to know. Nonetheless, the amount of the irrelevant Internet mumbo-jumbo, including the fraudulent “Keys-faked-data” claim, you chose to spam at the end of your message doesn’t contribute to this nor does it change anything. It’s just crap that people who sell popular books and rule the low carb/paleo forums spew out. I’ve seen it thousands of times. No new information, no facts, no nothing except a virulent meme.
Regarding this:
“Mie, you may think you are contributing to the discussion but your remarks read like you are scoffing at comments passed by people who have given matters more contemplation than you have.”
You’re probably the last person who should complain that I’m not “contributing”. Stating that nonsense is nonsense is contribution too. Science advances by sorting out disinfo from info. Axel brought out information concerning TG/HDL ratio and its role in predicting CVD risk. You chose to spam his blog with religious dogma. Unfortunately so.
Axel,
“In my mind this is a low fat approach. Basically the same thing that has been advocated fro 40-50 years.”
You’re somewhat cutting corners here. There’s NO mention of how many percent of total E should come from fat (or the other macronutrients for that matter). And DASH, which is low on total fat, isn’t the only dietary pattern mentioned.
The same goes for ESC guidelines
http://www.escardio.org/guidelines-surveys/esc-guidelines/GuidelinesDocuments/guidelines-CVD-prevention.pdf
Nothing about total fat. Nada.
“But I doubt that an approach, focusing on two targets (LDL-C and hypertension) is of much help.”
Well not to those who have no problems with these. But bear in mind that particularly hypertension management (by diet) is a major issue nowadays. And guidelines are by no means there to limit the clinician’s practical work in cases where the problem is e.g. low HDL and high TG etc.
@ Mie
In fact there is mention of percent fat in the AHA/ACC Guidelines. The two diet patterns recommended are a Mediterranean (MED) type diet and DASH.
According to the paper, “The MED patterns examined tended to be moderate in total fat (32% to 35% of total calories), relatively low in saturated fat (9% to 10% of total calories), high in fiber (27 to 37 g/day), and high in polyunsaturated fatty acids (particularly omega–3s)”.
The guideline’s authors own words on DASH: “The DASH dietary pattern is high in vegetables, fruits, low-fat dairy products, whole grains, poultry, fish, and nuts; and low in sweets, sugar-sweetened beverages, and red meats. The DASH dietary pattern is low in saturated fat, total fat, and cholesterol“.
So, I guess it’s a matter of definition (or opinion for that matter), whether the AHA/ACC approach is low-fat or not.
By the way, because you mention hypertension it is worth pointing out that a systematic review and meta-analysis has shown a very positive effect of low carbohydrate diets on both systolic and diastolic blood pressure.
Mie,
If I asked you to give a brief account of your take on the business of atherogenicity how might you describe the process?
If I asked you to name the most potent f the established atherogens which biochemicals would you name?
If I invited you to discuss the issue of ‘convergence’ that must apply to risk factors and the pathophysiology of the proliferation of atheromas how might you go about this?
If I invited you to discuss the difference between stable plaques and unstable ones that rupture what ’cause’ might you identify to account for the ‘effect’?
Does the lipid profile test account for qualitative variation amongst lipoproteins?
How did we get so hung up on those ‘cholesterol numbers’ in the first instance?
How about this: instead of trying to hide the fact that you offered a dose of nonsense (incoherent blabbering about Keys, fat etc. etc. you posted earlier) by asking a bunch of questions NOT related to the topic of Axel’s post, comment on the issue at hand.
If not, answer your own questions instead.
Axel,
“In fact there is mention of percent fat in the AHA/ACC Guidelines. The two diet patterns recommended are a Mediterranean (MED) type diet and DASH.”
Yes, there’s a mention of fat (as in “the amount of fat of total E”) in the case of these two dietary patterns. However, nowhere is it stated that these two are the ONLY alternatives. And there’s no convincing indication that total fat, unless you go super-low or super-high, has a role in decreasing/increasing CVD risk.
“By the way, because you mention hypertension it is worth pointing out that a systematic review and meta-analysis has shown a very positiev effect of low carbohydrate diets on both systolic and diastolic blood pressure”
Care to provide a reference? A variety of higher quality diets (that is, diets that aren’t the standard Western diet) improve blood pressure. E.g. vegetarian:
http://www.ncbi.nlm.nih.gov/pubmed/24566947
And Med (not a review but from a recent RCT):
http://www.ncbi.nlm.nih.gov/pubmed/24050803
I have no doubt that low carb diets can show similar benefits. But are they better than the abovementioned alternatives?
Well, let’s see the paper you mentioned.
Ah, for some reason the link to the review didn’t appear in your post when I read it first? Ok, thanks for the reference. Yes, it seems that I was right on the money: in short-term trials, low carb works in lowering blood pressure – as do a number of other dietary patterns, too.
@ Axel, re unit conversions.
ok, thanks for your reply.
A millimole (mmol) is apparently not a measure of mass, but of “an amount of substance”, obviously not simply mass.
So we are not, as I was thinking, converting from one mass/volume figure to another mass/volume figure.
Appreciate your forbearance.
It is my understanding/novel research that CHD/CVD is precipitated by inflammation.
(1) Hyperglycaemia oxidises LDL
(2) This oxidised LDL works it’s way under the endothelium and forms plaque.
(3) The plaque will gradually build up and eventually rupture causing an infarct.
So! a Heart attack will primarily occur with
(a) Electrical current causing V Fib. Causing the heart to go spasmodically s**thouse and end in cardiac arrest (low survival rate)
(b) Heart attack (infarct) where heart muscle dies, leaving a % of the heart depleted. This % of damage is expressed as a ‘Ejection Fraction’ which determines the blood flow that the heart can pump in and out through the ventricles.
I experienced an MI in 1988 at age 38.
Since then, I have changed diet radically, got educated with this c**t of a disease, and survive on medication and supplements.
Michael, Hi.
I think what you say is broadly correct.
1) It is oxidative stress that delivers atherogenic agents to the site where the atheroma will form.
2) The atherogenic agents interfere with the behaviour of cells destabilising them, making them less viable and killing some. Results have been obtained in vivo and vitro.
3) When cells are destabilised and, say, smooth muscle cells in the area begin dying other cells are triggered into response. The response in part is to invoke healing mode.
4) That de-differentiation of cells may take place is a possibility, and that alteration to electrical balances in the zone may take place highly likely. Cells can have an embryonic phase. In this phase they lack differentiation of function seen in mature tissues. They are cells that haven’t adopted specialised function.
5) All cells maintain electrical potential. The potential inside a cell differs with space around it. This is called resting potential. There is a pd even across the bilayer of the cells membrane. This means there are gradients of electrical potential across interfaces that delineate the cell, its structure, and the medium beyond. These potentials govern what and how stuff may pass in and out. Some metabolites and signalling molecules are ions, and some are zwitterions. Zwitterions are shifty, They have polar charge, but the charge they display is responsive to aspects of the medium around. That an alteration to resting potential displayed by a cell can influence the the greeting it signals to ions and zwitterions especially is implied.
6) De-differentiation and re-differentiation has been achieved under study and while details may be sketchy the mechanism may be that alterations to potential and the flow of weak currents has bearing for DNA. The current reorganises the methyl switches that flag a gene as being turned on or off. The first phase of healing then is to recode epigenetic tags (switches) so that cells can revert to basic type, then as healing advances the epigenome (switching layer attached to genes) is recoded so cells begin to form alternate ‘species’ and take on specialised function.
7) Heat is generated when energy meets with resistance. When medics mention ‘inflammation’ the term doesn’t mean much beyond saying heat is present. The heat arises because current is flowing, as ions perhaps, and is meeting with resistance. Inflammation is evidence of an immune or healing response in which the flow of ions or electricity signals something to cells.
8) Oxides of cholesterol get interesting. They seem to signal something to cells, adjusting or interfering with the way cells behave. Some cholesterol oxides seem to have legitimate physiological function, some can interfere with enzymic expression, some interfere with HMG-Co reductase and inhibit it, and some seem just plain toxic to cells.
9) LDL, nor any other lipoprotein, can become oxidised. However reactive oxygen species, antioxidants, and oxidised lipids may be present in lipoproteins. In other words liporteins can harbour oxidised agents.
10) LDL may convey oxidised lipids to the LDL receptors in the region but it is not the LDL that does the harm, it is aspects of its constituents that are present. That lipoproteins, including LDL, can convey oxidised cholesterol molecules alongside ‘healthy’ cholesterol ought not be in doubt.
11) The study of cholesterol oxides has resulted some have been identified as being cytotoxic and/or atherogenic. Prominent atherogens in the family of cholesterol oxides are cholestane-3beta,5alpha,6beta-triol and 25-hydroxycholesterol. Another potent atherogen is homocysteine which is a potent oxidising agent and notable zwitterion.
12) If it were established beyond doubt that homcysteine may oxidise cholesterol to form atherogenic oxides of cholesterol then that would be the breakthrough needed. The question then would follow on, where does this contact arise? Is it in liporproteins, in the liver where cholesterol is reprocessed and manufactured, or does it arise in the cell where cholesterol is a vital feature of the cell and a structural component of its membrane?
13) Homocysteine levels can rise for alternate reasons. In otherwise healthy people elevated levels of homocysteine arise due to stress or to a deficiency of methyl donating antioxidants. Stress raises the demand for methyl donations. If supply cannot match overall demand methyl deficiency occurs with a corresponding rise in homocysteine. Methyl deficiency permits levels of oxidation and oxidative stress to rise above that which could be considered merely basal and normal.
14) Much the same body of work that identified cholesterol oxides, and that then identified which may act as potent atherogens, has also established cholesterol is not the atherogen the fat/cholesterol hypothesis makes it out to be.
15) A lot of confusion has arisen amongst medical professionals. Few leave med school with a real understanding of the difference between lipoproteins and cholesterol.Unless studied at length, and from first base, the terminology, discussion, and nomenclature is designed to confuse. The notion of good cholesterol / bad cholesterol is completely misleading as is the branding of HDL-c and LDL-c. LDL-cholesterol has no real meaning. And another gripe and insult to a science is that the term ‘triglyceride’ has been granted alternate meaning. Its original and pure meaning, which refers to three fatty acids linked with a molecule of glycerol, has been de-emphasised, while its new meaning is applied to a summing of certain lipoprotein factions.
16) The issue of plaque formation (atherogenicity) is one matter, while the contrast between stable and unstable plaques that rupture is another, and as you direct the rupture of the plaque has consequence.
Mie, has accused me of spamming and posting off-topic. I cannot think why. The concept of dyslipidemia is firmly rooted in the will to apply the fat.cholesterol hypothesis – to test for dyslipdemia. The notion began with a weird notion of surplus cholesterol doing harm. Cholesterol only does good. It does no harm. Any harm associating with cholesterol arises only under the conditions under cholesterol molecules may be oxidised to form certian of a large family of cholesterol oxides. Testing for ‘cholesterol’ is dishonest. Testing for cholesterol is impractical so they test for lipoproteins instead. This ‘lipid profile test’ is next to meaningless. Lipoproteins resemble snowflakes for being infinitely variable one to next, not just in terns of size or density but in detailed variation in composition. The branding of terms like HDL, LDL IDL, VlDL is a disserviuce to their sophistication and diversity. As Axel suggests above lipoproteins overcome a significant natural challenge in the biology of vertebrates.
In my first post I wanted to be circumspect and avoid offending Axels feelings. If oxidative stress is the cause of CVD then the lipid profile test informs very little indeed. No amount of ad-hoc interprtation and reinterpretation of results will really inform much, not in the sense of conventional wisdom upon these matters.
The alteration to lipid counts and profiles seems to vary for reasons that are several. Its counter intuitive. Keys assumed additional fat in the diet would raise the count of lipoproteins and cholesterol, and he that saturated fat would have the strongest effect. It was outright speculation on Keys part. As you suggest, Michael, and as is intimated in Axels post, hyperglyceamia may bear upon lipoprotein counts and profiles. So lipid profile counts may rise or alter under conditions of a high carbohydrate diet and not a high fat diet as has always been promoted and remains the case. Conventional wisdom then has this wrong and backwards roads about. When they insist you cut back on dietary fat to reduce your cholesterol they’re actually recommending the opposite of what is needed.
To be plain then discussion of HDL/triglyceride ratios doesn’t impress me much. They do not inform much about how epiphysiological risk factors result in atherogenicity. On the other hand come at this from an endocrinological perspective and there is a strong indication that hormonal alterations that accompany stress increased demand for methyl groups and could result in methyl deficiency and a rise in oxidative stress. And while this last statement may still rest upon conjectural basis there is a lot about the statement that is in accord accord with evidence that has been established but ignored by the mainstream who remain insistent that cholesterol and dyslipidemia cause heart disease, which is contrary to the evidence on cholesterol and cholesterol oxides entirely.
Peng and Morin, ‘Biological effects of cholesterol oxides’ (book) is a good source doubters could visit.
@ Christopher
Thanks for your comments. I appreciate your input. However, please avoid such lengthy posts with so much off topic discussion. I usually reject such comments because I don’t think people read them and they take up a lot of space. The purpose of the discussion is to debate around the subject presented in the blog article.
“Mie, has accused me of spamming and posting off-topic. I cannot think why.”
Perhaps the fact that you try to “educate” people here by uttering oh-so-goddamn-obvious claims as “good and bad cholesterol are misleading terms” etc. etc. and the fact that you – evidently without ANY regard for integrity and honesty – spread out the same lies as n other internet spam bots might have something to do with it? And e.g. here
“The notion began with a weird notion of surplus cholesterol doing harm. Cholesterol only does good. It does no harm.”
you provide further evidence for the matter. No one’s claiming that cholesterol per se is the problem, understand? And as for oxidative stress and lipoprotein oxidation in atherosclerosis … Well, it’s been TEXTBOOK material for decades. As well as the roles of different types of fat and lipid levels (FYI, saturated fat does indeed increase both LDL and HDL levels in blood). Etc. etc.
Therefore, nothing you’ve brought into the discussion is new nor does it benefit the discussion of the topic itself (predictive and/or therapeutic value of TG/HDL ratio). Judging by your messages, you’re a case in point of an Internet-era “expert”: a person who doesn’t have a clue of basic calculus but who nonetheless goes on repeating a few catch phrases from the field of theoretical physics he’s picked up on a random website.
Thanks Axel, you make a good point. People appreciate explanations that are simple and concise, and that is understandable.
Even the people advising NICE are much the same. They think the case for lipid modification through prescription of pharmacological agents makes for good policy, and they asses the patients risk factors through the QRISK2 calculation tool, whose computation relies heavily upon the results of the lipid profile test. the case for lipid modification is based more upon absence of evidence than upon evidence, and a lot of the distraction stems from this obsession with those ‘cholesterol’ numbers.
Unfortunately simple and concise does not do great service to the processes at work, so peoples preference for simple and concise is the reason they fall victim to poor information or outright cons.
The professionals sitting on panels that guide NICE ought to be able to grasp explanations that are a step above the merely simple, concise and dogmatic. They should approach curiosity from more cause centric approaches simply because all chronic disease has a cause. Unfortunately they do not and this inadequate level of curiosity that prevails within medicine is blighting standards of delivery and hindering real progress in the development of much improved hypotheses. Even professionals seem to like to go about their business wearing blinkers simply because it eases the work and cognitive loads.
If cardiologists are afflicted that is lamentable.
After so many millions of years of evolution the inner workings of the human species defy simple and concise explanation. Simple and concise can only lead to misunderstandings.
Christopher wrote:
“Even the people advising NICE are much the same. They think the case for lipid modification through prescription of pharmacological agents makes for good policy, and they asses the patients risk factors through the QRISK2 calculation tool, whose computation relies heavily upon the results of the lipid profile test.”
Gee, wonder why? Perhaps due to the fact that both are soundly founded on existing evidence on CVD risk factors and disease management/prevention?
Cholesterol denialism is a zombie that just won’t die, now matter what.
Recently, I had to fire both my primary physician and cardiologist. Despite my moving the Trig/HDL ratio into very favorable territory (1.1 – mg/dl), they both kept insisting that I needed statins due to higher than normal LDL-C (my particle size is phenotype A). Both doctors demanded I switch my diet back to the high carb, low fat diet that I had abandoned two years ago.
Prior to my changing to a moderately low carb/high fat diet, my Trig/HDL ratio was consistently in the danger zone – as high as 9.3! My trigs are well below 100 now and HDLs have climbed from the high 20’s to a current mid-70s level.
Besides changing my diet dramatically, I added a very moderate exercise (cardio and weights) plan to my lifestyle. At least 5 days per week, I do my exercise plan.
As a result of these major changes, both my weight and blood pressure have dropped to attractive levels. And all my inflammation markers are now in the healthy zones too.
The only negatives, per my past doctors, are higher total cholesterol and LDL-C levels. And my LDL-P still is at an abnormally high level, but it has been cut in half with the new diet/exercise lifestyle.
I have yet to locate doctors in my area of the U.S. who have moved away from the antiquated, conventional low fat, low cholesterol paradigm. It’s unfortunate, but my impression from personal experience is that the old model of heart disease still rules at the ground level of medical practice.
Axel,
a critic to your text would say that risk-predictor is not a synonym with a causal factor. Low carb results in better trig/hdl ratio, so? Does this translate to a) regression of CHD within the artery wall and/or b) less risk of developing clinical cardiadic event?
The early experimental scholars induced severe atherosclerosis in rabbits and mices by feeding them cholesterol and saturated fats….standard textbook material. The early critics pointed out that rabbits were vegeterians and thus the result might not have relevance to humans. The experimental scholars responded by designing an experiment in which the serum of a rabbit (fed high cholesterol/SFA fare) was switched into another rabbit on a typical rabbit diet. It was shown that CHD was caused by elevated blood cholesterol not by by diet per se. SFA/cholesterol was only a vehicle to elevate blood cholesterol.
I wonder if you can show me an experimental model in which atherosclerosis was reversed by modulating HDL-C and/or triglycerides with high SFA diet, at the presence of elevated LDL. I emphasize the wording “at the presence of elevated LDL” since this is what low carbers are left with.
Richard. This figure from The Framingham study clearly show that cholesterol levels are associated with risk of CAD (coronary artert disease). However, there is a lot of overlap. High cholesterol is present among many individuals with no CAD and low cholesterol is present among many with CAD.
It all comes down to the fact that people are different. For some people cholesterol levels certainly appear important when it comes to assessing risk and target treatment. For other people cholesterol appaears less important and other aspects of the lipid profile or inflammatory markers (hs-CRP) may become more important.
Regarding the experimental model you mentioned I can only say that I’m not going to “chase rabbits” at your demand. It’s out of my scope.
“I have yet to locate doctors in my area of the U.S. who have moved away from the antiquated, conventional low fat, low cholesterol paradigm. It’s unfortunate, but my impression from personal experience is that the old model of heart disease still rules at the ground level of medical practice.”
JamesK is living prof that medicine is now so sophisticated there are barely any healthy people left. Even people who take initiatives to improve markers and profiles for health and achieve results still feel pressured to succumb to the diagnosis and prescription that stems from ‘counting cholesterol’. Something is amiss somewhere.
Richard, everything doesn’t evolve around mere LDL count as there are people in whom it isn’t enough as a risk predictor nor can CAD prevention on population level be reduced to examining mechanisms in the formation of atheroma – problems understanding that?
And Axel, surely we all do realize that on a population level risk factors don’t mean that everyone with one is going to get CAD? Why point out the obvious?
Mie. It, I don’t think its obvious at all, although it may to you. If cholesterol is an important causative factor, why doesn’t everyone with high levels get atherosclerosis?. Well I would guess it’s because other factors come into play, and because cholesterol’s role as a causative factor is minimal. Isn’t cholesterol merely a passenger that happens to be there?.
This also highlights another question. How can we tell when high cholesterol is important and when it’s not? Many people reach high age with extremely high cholesterol levels, without ever taking statins. How can we differentiate those who may benefit from cholesterol lowering from those who don’t?
Doc,
cigarette’s CAUSE lung cancer, yet most smokers don’t get lugn cancer. Many of them do, though. Moreover, we need to seperate atherosclerosis as a a) process within the artery wall and b) atherosclerosis as a clinical manifestation, cardiadic events. This is the root of confusion. All Western people have atherosclerotic arteries at old age due to cumulative exposure to high LDL but not all of us have cardiadic event during our lifetime. Cardiadic events can reduced even though atherosclerotic process within the artery is progressing. Evidence based meditation protocol, lowering blood pressure, loosing weight, smoking cessation etc all helps but only LDL lowering can result in regression of atherosclerotic process within the wall. This is basic stuff.
Christopher Palmer wrote, ” If oxidative stress is the cause of CVD then the lipid profile test informs very little indeed.”
Good point. There’s frequent mention of oxidative stress in relation to arterial damage but the role of omega-6s is rarely mentioned. It’s interesting that calves cannot tolerate soybean oils unless their ration of skim milk and soybean oil also contains sufficient vitamin E to prevent oxidative stress. For decades, researchers testing alternatives to butter fat on veal calves, found that polyunsaturated seed oils made calves sick ultimately killing many of them. Beef tallow and lard caused no problems. In 1973 someone finally realized that seed oils need to be protected from oxidation, so they utilized vitamin E. Excerpt: “Weekly veterinary evaluation of the appearance and health of the calves revealed no abnormalities associated with the dietary treatments. The calves were examined for condition of coat, abnormalities of stance or gait, stiffness and evidence of muscular dystrophy, excitability or nervousness, and respiratory infections or abnormality. This result contrasts with the reports of others (Adams et al., 1959a,b; Gullickson, Fountaine and Fitch, 1942) who experienced poor weight gains, bad health, and considerable mortality of calves on rations high in unsaturated vegetable fat. All the calves in our study, whether fed milk containing high or normal amounts of polyunsaturated fatty acids, received supplemental vitamin E. The presence of this vitamin E during these early growth stages may be the explanation for the very satisfactory growth and weight gains during the milk feeding period, which contrasts with the growth deficiencies and health problems encountered by Adams et al.” http://www.journalofanimalscience.org/content/37/6/1419.full.pdf
In that same article the researchers said, “The possibility exists that food products containing high levels of polyunsaturated fatty acids may be useful in dietary prevention and alleviation of atherosclerosis. If clinicians prove an associative effect of dietary fatty acid saturation with incidence of cardiovascular disease, it will become desirable for dairy and beef producers to develop methods of increasing the degree of polyunsaturation in milk and meat fat.”
One wonders how levels of polyunsaturated fat intake that destroy the health of veal calves could possibly prevent heart disease in humans, especially without vitamin E supplementation.
Axel,
“Mie. It, I don’t think its obvious at all, although it may to you. If cholesterol is an important causative factor, why doesn’t everyone with high levels get atherosclerosis?. Well I would guess it’s because other factors come into play, and because cholesterol’s role as a causative factor is minimal. Isn’t cholesterol merely a passenger that happens to be there?”
Oh please. Do you really need to be explained the etiology of CAD vs the pathophysiology of atheroma? Risk factors vs mechanism? (Richard already mentioned this, although simplified it somewhat).
You know this all. Then why ask such a question?
“This also highlights another question. How can we tell when high cholesterol is important and when it’s not? Many people reach high age with extremely high cholesterol levels, without ever taking statins. How can we differentiate those who may benefit from cholesterol lowering from those who don’t?”
Same here. Don’t know about Icelandic treatment guidelines, but e.g. in Finland the risk is assessed as a WHOLE, not just based on LDL. Just because the current evidence in risk management and/or disease prevention shows this to be the best approach.
In addition, the fundamental nature of PREVENTATIVE medicine is such that we’re not dealing with absolute certainties, especially not in the case of an individual. Should that prevent us from treating the patient?
Mie.
It’s not a simple as that. Sometimes treatment decisions are based solely on LDL-C. The AHA/ACC guidelines recommend statins to all individuals with LDL-C above 190 mg/dl (4.9 mmol/L).
In fact it seems that you’re totally missing my point here and deliberately trying to twist my words. I’ll let our discussion rest here. Furthermore, remember that I usually reject comments that are impolite and disrespectful.
Doc,
you can perceive cholsterol as ionizing radition (stochastic risk).More ionizing radiation, more cancer in a given population, but not all individuals exposed to radiation get cancer. Some individuals are protected from cancer. When cholesterol levels are a high in a given population very many suffer cardiadic event, even when food additives, excess weight gain, McDonald’s, Coca-Cola etc are entirely absent in this population (f.ex see Finnish baseline cohort data at the 7CS). However, when cholesterol levels in a given population are <3,7mmol/l atherosclerotic CHD is basically non-existent. There's a hefty ecologic data to back this assertion.
Mie,
btw, did you see Blackburn's response to Big Fat Lie Book. Good stuff.
http://www.startribune.com/opinion/267581481.html
Axel,
“Sometimes treatment decisions are based solely on LDL-C. The AHA/ACC guidelines recommend statins to all individuals with LDL-C above 190 mg/dl (4.9 mmol/L).”
Sometimes, yes. You’re right. I mentioned Finnish guidelines which don’t recommend treating mere elevated LDL unless it’s very high, 6 mmol/l.
“In fact it seems that you’re totally missing my point here and deliberately trying to twist my words. I’ll let our discussion rest here. Furthermore, remember that I usually reject comments that are impolite and disrespectful.”
If you feel I missed something, please don’t let it rest. If I was mistaken, I’d prefer an explanation to see the error of my ways rather than a “not-talking-to-you”. Nor was I deliberately twisting your words – I’m sorry if that’s how it seemed. I respect your opinions and enjoyed this blog post (and agree with the basic idea that there are patients in whom the risk can be substantial although common markers don’t show this) but couldn’t really understand how else I should’ve interpreted e.g. the abovementioned ” How can we tell when high cholesterol is important and when it’s not?” part.
So please, do explain a bit further.
Richard,
I’ve read Blackburn’s response. Good show, although bloggers like Seth at “Science of Nutrition” and our Finnish colleague, Jussi Riekki, have essentially covered the same topic earlier. And I – once again – wish you’d give ecological data a rest.
Doc,
the upcoming president of your professional body, American Collage of Cardiology, shares his ideas about a healthy diet. This is the stuff I’ve been trying to tell your for what…years, now. But you choose to bang your head in the wall. You exemplify the fact that in the future we need to force doctors to adopt new treatment protocols. We cannot rely on their own judgement since stubborn cranks like you, who get it 180-degree wrong are always present among us.
http://www.medpagetoday.com/Cardiology/Prevention/46860
@ Richard.
I’ve never said anything negative on my blog about vegan diets. I may have said that they’re hard to stick with. Otherwise I think people do very well on vegan diets in terms of cardiovascular risk.
So I’m not sure there is so much disagreement between us, apart from the fact that I don’t prefer using words like “stubborn cranks” when communicating with other people. I’m letting this one pass, but generally I reject comments that are impolite and disrespectful. You should know that by now.