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Tuesday, October 11, 2011

SATURATED FAT AND CHOLESTEROL HAVE NOTHING TO DO WITH YOUR RISK FOR DEVELOPING HEART DISEASE

Yeah it’s not a typo! You heard it right, saturated fat and cholesterol have nothing to do with your risk of developing heart disease!

In this article I’ll go on to show you examples of how people and even scientists will only believe what they want to believe, no matter how much evidence to the contrary exists. Here is a take on the popular notion that a low-fat diet low in saturated fats and cholesterol will reduce the incidence of CHD and related deaths.
Going through our education we were taught the basic science tenet that if a phenomenon occurs for a given set of conditions and if those set of conditions were to be replicated, the same phenomenon would occur. That was enough to establish causality (cause and effect). This basic tenet holds for any scientific investigation. And if what you thought was the ‘condition’ that made a certain phenomenon happen in certain cases and made the exact opposite phenomenon happen in other cases, then you would abandon the ‘condition’ as being the cause of that phenomenon…unless of course that ‘condition’ happens to be high cholesterol and the phenomenon happens to be coronary heart disease. Then, for some reason, the rules of science don’t apply!
So, any guesses as to what a CHD preventive diet should be? If you guessed a low-fat vegetarian diet, then you are in majority by a huge margin and you should be in power (after all we live in a democracy, right?). But too bad, science and democracy (or majority consensus) have nothing in common. If they did then the earth would still be flat and the sun would still be revolving around the earth.
If anyone has popularized a low-fat vegetarian diet like no one else, I would give the credit to Dr. Dean Ornish. A quick search on Google will show you that he is one of the most influential opinion leaders on dietary intervention for prevention of CHD. If you want to read more about his accolades and recognition, I suggest going to http://www.pmri.org/dean_ornish.html since his accolades are longer than what I am prepared to write in this article.

Before we jump into all the lifestyle intervention studies that have been done to prevent CHD lets have primer on the statistics behind clinical trials. Actually these principles are used in every realm of science like process control, manufacturing control and various testing methodologies and to a much more stringent level than used in clinical trials (thank the heavens!). Here are a few terms to get used to:

Sample size: This is the number of people tested. Its best to have the largest possible sample size since it randomizes for variation in lifestyle (smoking habits, alcohol consumption etc.), regional/cultural differences or other such confounding factors. Obviously it’s hard to study a large sample size due to cost/resource constraints so the experimenter has to choose from a small sub-set of the representative population. Furthermore a multi-center trail is better suited for generalization to a large population.

Factorial Design: When two or more different treatments are evaluated in single study this type of design is used to evaluate the effect of each treatment, independent of the other treatment. If two different factors are lumped into one treatment then no conclusion can be made about the effect of any one factor. It’s easy to see why this is the case because you can’t un-couple the effect that each factor has on the treatment. So it’s impossible to establish causality to any one factor. The best you can infer is that both factors have an effect on the treatment, but what percentage can be assigned to which factor will be unclear.
Blinding: The best way to remove bias from a trail is by making it blind. Blinding (masking) is a method of eliminating conscious or unconscious bias in how the experiment is conducted or how the data is analyzed or interpreted. It’s basically a way an experiment is conducted where the subject is not aware of which group is receiving the treatment (single blind) or in the best case even the test giver, investigator or the sponsor staff is unaware of which group receives which treatment. This includes anyone that is designing the test or is selecting the candidates for the test. Until such time that all opportunities for bias to affect the endpoint and data integrity is passed all involved parties are blind. This is maintained throughout the testing and analysis phase and when the data is cleaned of outliers to an acceptable level is when the appropriate authorities are un-blinded. This is the best and most objective way to conduct a clinical trail. Now realize that it’s not always possible to conduct a double blind trail especially in the case of lifestyle intervention trails, which is what we will be talking about.


Now that we got the basics down let’s look at the popular studies that have been done to assess the effect of lifestyle intervention on preventing CHD. Let’s look at the popular Ornish study also known as lifestyle heart trail [1] in which he claims that his particular diet regresses (meaning improves) the atherosclerosis in the blood vessels. Below is the abstract right from the publication:

In a prospective, randomised, controlled trial to determine whether comprehensive lifestyle changes affect coronary atherosclerosis after 1 year, 28 patients were assigned to an experimental group (low-fat vegetarian diet, stopping smoking, stress management training, and moderate exercise) and 20 to a usual-care control group. 195 coronary artery lesions were analysed by quantitative coronary angiography

And the conclusions stated (again from the publication):

The average percentage diameter stenosis regressed from 40.0 (SD 16.9)% to 37.8 (16.5)% in the experimental group yet progressed from 42.7 (15.5)% to 46.1 (18.5)% in the control group. When only lesions greater than 50% stenosed were analysed, the average percentage diameter stenosis regressed from 61.1 (8.8)% to 55.8 (11.0)% in the experimental group and progressed from 61.7 (9.5)% to 64.4 (16.3)% in the control group. Overall, 82% of experimental-group patients had an average change towards regression. Comprehensive lifestyle changes may be able to bring about regression of even severe coronary atherosclerosis after only 1 year, without use of lipid-lowering drugs.

So the authors concluded that the artery diameter stenosis (ADS) improved by 5.5% ([40-37.8]/40) in the experimental group (intervention group) while it deteriorated by 8% in the control group (no intervention). So apparently the intervention improved things by 13.5%. A pretty big number if you ask me.  So now you tell me, OK its settled, so will you please give in, bow down, bow out, take a hike, buzz off and shut up and agree that a vegetarian diet low in cholesterol and saturated fat is the answer to preventing CHD. I’ll say wait a minute, but let’s look a little closer at the results.

A few points to note about this trial: The sample size is pretty small (48) so making a generalization based on this study would be premature because it couldn’t have possibly accounted for regional, cultural, dietary and other socio economic factors in the sample size. How could you possibly make dietary recommendations for people world over based on the 48 people you tested? You wouldn’t.

The second point I would like to bring forth is the measurement error in coronary angiography. The numbers reported are absolute, without any error bars. Any real instrument has repeatability and reproducibility errors. Also take a closer look at the standard deviation in the measurements (the % numbers in parenthesis). It’s in the range of 16%. A quick search on google for measurement errors in coronary angiography shows the error to be about 10% standard error (http://spo.escardio.org/eslides/view.aspx?eevtid=33&fp=3022). In light of this fact do you think the numbers reported in the research have any statistical significance? Absolutely not! The measurement variation reported is in the signal noise.

The third point I would like to bring out is that the study made an attempt to correlate the effect of 4 parameters (low-fat vegetarian diet, stopping smoking, stress management training, and moderate exercise) on ADS. So this study cannot isolate the individual contributions from any one parameter and its effect on ADS. So based on this study can we recommend that a vegetarian diet will lower your chances of developing arterial lesions? I bet you, even the most diehard vegan wouldn’t agree if someone made a claim like that based on this data. And yet this study is cited for recommending a vegetarian diet low in saturated fat as a preventive step to lower your risk of CHD. Hilarious isn’t it?

Now let’s look at the other side of the coin and see how many studies have failed to show a correlation between dietary lifestyle modification and the development of CHD. The most popular one that is cited over and over again is called MRFIT (Multiple Risk Factor Intervention Trial) [2]. This one was special intervention (SI) program consisting of stepped-care treatment for hypertension, counseling for cigarette smoking, and dietary advice for lowering blood cholesterol levels for the treatment group and no intervention for the control group. Below figure 1 shows the results of this study in a snap shot.


Figure 1. MRFIT study parameters and results snapshot.

Quoting straight from the research paper:

            The Multiple Risk Factor Intervention Trial was a randomized primary prevention trial to test the effect of a multifactor intervention program on mortality from coronary heart disease (CHD) in 12,866 high-risk men aged 35 to 57 years. Men were randomly assigned either to a special intervention (SI) program consisting of stepped-care treatment for hypertension, counseling for cigarette smoking, and dietary advice for lowering blood cholesterol levels, or to their usual sources of health care in the community (UC).

Here you can at least see that the study had a large enough sample size and went on for long enough to make some conclusions. Here again it was a multifactor intervention program where they modulated three parameters (smoking, cholesterol lowering diet and anti-hypertensive drugs) simultaneously and studied its effect on CHD. The primary end point was any MI event. The first thing that should stand out is that the control group had 132% more smokers than the treatment group.  Now looking at the improvement area we can see that it reduced the coronary death events in the treatment group by 9 people. Now let’s look at people that died of other causes. Wait, the difference is not 5 from what it seems like from the first results line (265-260). All the first line states that 5 more people died in the treatment group than in the control group. So overall more people died in the treatment group then in the control group. Doing the math it seems like 150 people in the treatment group died from other causes and 136 people in the control group died of other causes. So, overall 14 more people died in the treatment group from other causes. Now would you call the intervention program successful? I wouldn’t call it successful. So would I call it unsuccessful? I wouldn’t conclude that either. Basically I couldn’t conclude anything from these results. I think the results were statistically insignificant and study was inconclusive. But wait here is what the authors concluded (drum roll please):

Over an average follow-up period of seven years, risk factor levels declined in both groups, but to a greater degree for the SI men. Mortality from CHD was 17.9 deaths per 1,000 in the SI group and 19.3 per 1,000 in the UC group, a statistically non-significant difference of 7.1% (90% confidence interval, -15% to 25). Total mortality rates were 41.2 per 1,000 (SI) and 40.4 per 1,000 (UC). Three possible explanations for these findings are considered: (1) the overall intervention program, under these circumstances, does not affect CHD mortality; (2) the intervention used does affect CHD mortality, but the benefit was not observed in this trial of seven years' average duration, with lower-than-expected mortality and with considerable risk factor change in the UC group; and (3) measures to reduce cigarette smoking and to lower blood cholesterol levels may have reduced CHD mortality within subgroups of the SI cohort, with a possibly unfavorable response to antihypertensive drug therapy in certain but not all hypertensive subjects. This last possibility was considered most likely, needs further investigation, and lends support to some preventive measures while requiring reassessment of others.

Let me put it in simple terms for you. The data screams that the intervention didn’t work! At least not to a statistical significance. But wait there is a possible explanation of why it didn’t work. The authors hypothesize  (because data is telling otherwise) that the intervention may have worked within sub-groups of the intervention group but a possibly unfavorable response to antihypertensive drug therapy confounded the results and that the last possibility is considered most likely. And why is that? Let me tell you why? Because the authors don’t want to give up the original hypothesis (that the intervention works). So they already were expecting (AKA bias) which way the results should have gone even before testing the hypothesis. Wow, this is new age statistics for all of us! Old school taught us to start an experiment with the null hypothesis and if data disproves the null hypothesis then you take the alternate hypothesis. This new way of still holding on to the null hypothesis when experiment shows otherwise is called ad-hoc hypothesis and you will see many instances of this with respect to the cholesterol hypothesis. It’s a nifty way to explain away unfavorable results.

Ok so moving on now lets look at another one. This is the famous Helsinki Study [3] that was conducted in Poland. The primary intervention in this one was not only diet, smoking and exercise but also anti-hypertensive drugs and for all the cholesterol haters they also gave the preventive treatment group cholesterol lowering drugs. So it must have been a win-win for the treatment group and I feel sorry for the control group that didn’t receive any of the life saving miracle drugs or dietary advice or counseling. The primary end-point was mortality. Figure 2 is the snap shot of the test methodology and results.


Figure 2. The Helsinki heart study methodology and results


Looking at the snapshot of the results it seems like there were 8.5% more smokers in the control group. And lo and behold only one person from the control group died of a coronary even while 4 people in the treatment group died from coronary event. If it were the other way around you would be hearing things like “miracle drugs save your chance of heart attack by 75%” ([4-1]/4). But no such miracles happened and no wonder you don’t hear much about this study.  Also note that 6 people in the treatment group died from other causes while only 4 in the control group died from other causes. Suddenly I don’t feel so bad for the people in the control group. The treatment group however…that’s another story.

During the next 18 years (Between 1974 and 1989) post trail mortality in the Helsinki Study was followed up and the results straight from the publication are:

the total number of deaths was 67 in the intervention group and 46 in the control group (relative risk [RR], 1.45; 95% confidence interval [CI], 1.01 to 2.08; P = .048); there were 34 and 14 cardiac deaths (RR, 2.42; 95% CI, 1.31 to 4.46; P = .001), two and four deaths due to other CVD (not significant), 13 and 21 deaths due to cancer (RR, 0.62; 95% CI, 0.31 to 1.22; P = .15), and 13 and one deaths due to violence (RR, 13.0; 95% CI, 1.70 to 98.7; P = .002), respectively. Multiple logistic regression analysis of treatments in the intervention group did not explain the 15-year excess cardiac mortality.

Well here again you see the researchers in denial as to why they got unexpected results. Even though they aren’t able to explain the high cardiac mortality in the treatment group they aren’t able to fathom the possibility that cholesterol has nothing to do with heart disease.

Let move on to the next study. This one was called the Finnish mental hospital study [4] which had 600 women aged 49 yrs av. The treatment intervention was cholesterol lowering diet low in saturated fats and increased polyunsaturated vegetable oils. The control group had no intervention. This was the only study that looked at dietary intervention alone. So anyone that understands anything about statistics should put the most faith in this study. And for all the saturated fat and cholesterol haters this is the basket you should be putting all your eggs (no pun intended) into.


Figure 3. The Finnish Mental Hospital study methodology and results

Here is a description of the study conditions and methodology straight from the research article:

A controlled intervention trial, with the purpose of testing the hypothesis that the incidence of coronary heart disease (CHD) could be decreased by the use of a serum-cholesterol-lowering (SCL) diet, was carried out in two mental hospitals near Helsinki in 1959-71. The subjects were hospitalized middle-aged women. One of the hospitals received the SCL diet, ie a diet low in saturated fats and cholesterol and relatively high in poly-unsaturated fats, while the other served as the control with a normal hospital diet. Six years later the diets were reversed, and the trial was continued another six years. The use of the SCL diet was associated with markedly lowered serum cholesterol values. The incidence of CHD, as measured by the appearance of certain electrocardiographic patterns and by the occurrence of coronary deaths, was in both hospitals during the SCL-diet periods lower than during the normal-diet periods.



Please note that the SCL diet resulted in markedly lowered serum cholesterol values during both phases of the study, so there is no ambiguity about the cholesterol lowering capability of the intervention diet. So now you can’t wait to see the conclusions of this study. Well I won’t keep you holding your breath too much longer, so here are the conclusions, again, straight from the paper:

The differences, however, failed to reach statistical significance. An examination of a number of potential confounding variables indicated that the changes in them were small and failed to account for the reduction in the incidence of CHD. Although the results of this trial do not permit firm conclusions, they support the idea that also among female populations the SCL diet exerts a preventive effect on CHD.

Now wait a minute. I am jumping up and down! How did we come to this conclusion? Where did I see that this diet exerts a preventive effect on CHD when 50% ([10-5]/10) more people died in the intervention group of all causes, and 75% ([4-1]/4) more died of cardiac deaths compared to the untreated control group? Am I missing something here? Can someone please explain?  I am dumbfounded, or maybe I am just plain dumb!
The next one was a better controlled study because the total fat intake was kept constant between the two groups but the composition of fat in terms of saturated, poly-unsaturated, mono-unsaturated and total cholesterol intake percentages were varied. This was the Minnesota Coronary study [5]. The test design and administration, straight from the paper states:

The Minnesota Coronary Survey was a 4.5-year, open enrollment, single end-time double-blind, randomized clinical trial that was conducted in six Minnesota state mental hospitals and one nursing home. It involved 4393 institutionalized men and 4664 institutionalized women. The trial compared the effects of a 39% fat control diet (18% saturated fat, 5% polyunsaturated fat, 16% monounsaturated fat, 446 mg dietary cholesterol per day) with a 38% fat treatment diet (9% saturated fat, 15% polyunsaturated fat, 14% monounsaturated fat, 166 mg dietary cholesterol per day) on serum cholesterol levels and the incidence of myocardial infarctions, sudden deaths, and all-cause mortality. The mean duration of time on the diets was 384 days, with 1568 subjects consuming the diet for over 2 years. The mean serum cholesterol level in the pre-admission period was 207 mg/dl, falling to 175 mg/dl in the treatment group and 203 mg/dl in the control group.

So this intervention dropped the total cholesterol level for the intervention group to 175 mg/dl and didn’t change it for the control group (203 mg/dl). All good right? But when you look at the summary of results in figure 4 (below) it seems like coronary deaths were about 13% higher and deaths from cancer were 25% higher in the intervention group. All cause deaths and coronary events were insignificantly different. But the results quoted from the paper state:

For the entire study population, no differences between the treatment and control groups were observed for cardiovascular events, cardiovascular deaths, or total mortality. A favorable trend for all these end-points occurred in some younger age groups.

Now what does the term “A favorable trend occurred in some younger age groups” mean? Does it mean that younger people will benefit from the cholesterol lowering diet? And does it mean that by the time they get old this diet wouldn’t save them the first heart attack because they are not young anymore? I don’t know what it means but the results speak for themselves and no one in their right minds could argue with such glaring data.


Figure 4. The Minnesota Coronary study methodology and results

Now the next one is a study with a dietary intervention of changing total fat intake to below 20% of total calorie intake (from 32% or more before the intervention) and to include at least 5 servings of vegetables and fruits and 6 servings of grains. This would be an ideal textbook diet for the healthiest of them all. I am mean, vegetables and fruits and grains and fat less than 20% of total calories! Who can argue with the CHD preventive benefits of such a diet? No changes were made in the control group diet. This was the Women’s Health Initiative (WHI) low-fat study [6]. Figure 5 shows the test summary snapshot below.

Here again the test description states that the objective of this study was:

To test the hypothesis that a dietary intervention, intended to be low in fat and high in vegetables, fruits, and grains to reduce cancer, would reduce CVD risk.

And the test itself was:

Randomized controlled trial of 48,835 postmenopausal women aged 50 to 79 years, of diverse backgrounds and ethnicities, who participated in the Women's Health Initiative Dietary Modification Trial. Women were randomly assigned to an intervention (19,541 [40%]) or comparison group (29,294 [60%]) in a free-living setting. Study enrollment occurred between 1993 and 1998 in 40 US clinical centers; mean follow-up in this analysis was 8.1 years.

I love this study for three reasons. One that the sample size was huge and the participants were from a diverse background so the results would be applicable to the general population. Second, the diet was an ideal text-book diet that we have grown-up believing was beneficial to heart health and third that the mean follow-up period was pretty long (8.1 years). Looking at the summary of results in figure 5 we can see that the risk reduction for heart disease was insignificant even with this textbook perfect diet. Quoting the authors straight from the paper:

Over a mean of 8.1 years, a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVD risk.


Figure 5. WHI low-fat study test methodology and results.

So it seems like the textbook perfect low-fat diet with fruits and vegetables and grains didn’t do squat in reducing the risk for heart disease. The authors still had a back-alleyway for explaining away the unfavorable results by saying that the lifestyle intervention wasn’t focused enough and there was more room for improvement. Seems like ad-hoc-hypothesis land to me!

There are many more studies that failed to show a direct correlation between fat or cholesterol intake and the risk of developing CHD no matter how hard the cholesterol haters have tried. I have yet to find a single one that succeeded to show a correlation. And if someone can find that one elusive study that we all have chased for the last half a century then please let me know. I am sure the researchers would also love to hear about it. By now it should be fairly clear that diet has nothing to do with your risk for developing CHD. So eat what you want and you will not develop heart disease just because of a certain type of food in your diet, be it saturated fat or cholesterol. And in fact I have reasons to believe that a low-fat high carb diet will pre-dispose you to developing CHD not directly but by impairing your body’s insulin response and making you type II diabetic, because the correlation between a high carb diet and developing type II diabetes has been shown in studies after studies. And studies have also shown that having type II diabetes predisposes you to developing CHD. Now that data is un-ambiguous and incontrovertible. Smoking and stress are the two other significant risk factors for developing CHD.

So eat all the saturated fat and cholesterol you like and you won’t develop heart disease just because of that. There are of course merits to eating a diet rich in vegetables and fruits (for preventing cancer, type II diabetes etc) but not for reasons of preventing heart disease. Heart disease is a completely different animal that is caused due to reasons other than diet. In fact in the coming series of articles I will even show that a lower lipid cholesterol increases your risk of dying of other causes after a certain age (47 yrs to be precise) than having a higher level of cholesterol in your blood.
Why, then you ask, is cholesterol and fat made out to be such a toxin if there are no studies that show a correlation between lipid cholesterol levels and CHD? For that you have to understand the relation between the expert opinion leaders in the medical community and the pharmaceutical industry that sell the cholesterol lowering drugs and the American Heart Association (AHA) that makes hundreds of millions of dollars endorsing low-fat products with the famous AHA logo shown below.


But this is a topic for another article. For now I will just say that cholesterol hypothesis is based on pseudoscience or consensus science or what I like to call as ‘puppet science’. Just as puppets can seem to defy the laws of physics because of the attached strings, cholesterol science can be made to defy the laws of real science because of the attached ‘strings’ that make us ‘see’ something that doesn’t exist. Noble laureate Richard Feynmann had an interesting take on pseudoscience that he called Cargo Cult science (http://www.physics.brocku.ca/etc/cargo_cult_science.php).

More to come, but in the mean time enjoy that piece of steak that you have been avoiding because your doctor told you so. And if your doctor has a problem with it please direct him to this blogJ

References:

1)    Ornish D, Brown SE, Scherwitz LW, Billings JH, Armstrong WT, Ports TA, McLanahan SM, Kirkeeide RL, Brand RJ, Gould KL. Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial. Lancet 1990;336:129-33

2)    Multiple risk factor intervention trial. Risk factor changes and mortality results. Multiple Risk Factor Intervention Trial Research Group. JAMA 1982;248:1465-77

3)    Strandberg TE, Salomaa VV, Naukkarinen VA, Vanhanen HT, Sarna SJ, Miettinen TA. Long-term mortality after 5-year multifactorial primary prevention of cardiovascular diseases in middle-aged men. JAMA 1991;266:1225-9

4)    Miettinen M, Turpeinen O, Karvonen MJ, Pekkarinen M, Paavilainen E, Elosuo R. Dietary prevention of coronary heart disease in women: the Finnish mental hospital study. Int J Epidemiol 1983;12:17-25

5)    Frantz ID Jr, Dawson EA, Ashman PL, Gatewood LC, Bartsch GE, Kuba K, Brewer ER. Test of effect of lipid lowering by diet on cardiovascular risk. The Minnesota Coronary Survey. Arteriosclerosis 1989;9:129-35

6)    Howard BV, Van Horn L, Hsia J, Manson JE, Stefanick ML, Wassertheil-Smoller S, Kuller LH, LaCroix AZ, Langer RD, Lasser NL, Lewis CE, Limacher MC, Margolis KL, Mysiw WJ, Ockene JK, Parker LM, Perri MG, Phillips L, Prentice RL, Robbins J, Rossouw JE, Sarto. Low-fat dietary pattern and risk of cardiovascular disease: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006 Feb 8;295:655-66

Thursday, September 15, 2011

FAT CONTROVERSY: HOW BIASED SCIENCE LED TO THE DEMONIZATION OF FAT AND FATTENING OF AMERICA

In this article I am going to present the history and (pseudo)science behind the demonization of fat. What I am going to show is how a researcher’s bias can play into the results of a study (or experiment). What followed from the conclusions of that study is the fattening of America (and the rest of the world) and the current state of obesity and heart disease around the world.

Early Work
It all began in 1912 by a Russian military doctor by the name of Nikolai N. Anichkov, who was the pioneer in establishing the role of cholesterol in the formation of plaque in the arteries. His theory stated that cholesterol alone was responsible for the physical changes in the arterial walls that led to the subsequent development of plaque.

His early work on Arteriosclerosis involved putting rabbits on a diet of bacon and eggs and studying the changes in their arterial walls from a period of 2 hrs to 1 yr.  This work titled “Inflammatory changes in myocardium: apropos of myocarditis,” formed the crux of his doctoral thesis which he successfully defended on 21st April, 1912. This preliminary work in the experimental model of atherosclerosis was considered a pioneering “classic” and was used by a great number of subsequent researchers in the field.

The early work of Anichkov was published in the Russian literature but his first English medical literature publication was a chapter in Cowdry’s Arteriosclerosis in 1933[1]. Worldwide recognition of Anichkov’s work came only after a science [2] publication by Dr. John Gofman and his associates in 1950. Using Anichkov’s experimental techniques they confirmed the fact that introducing cholesterol in a rabbits diet rapidly led to atherosclerosis. They went a step further and were able to use an ultracentrifuge (which was unavailable to Anichkov during his time), and separate out the hypercholesteremic serum samples of their cholesterol-fed rabbits into 2 distinct groups. The fraction that floated to the surface of the serum sample was designated as low-density lipoprotein (LDL) cholesterol, and the fraction settled at the bottom was designated high-density lipoprotein (HDL) cholesterol. They further went on to show that low-density lipoprotein cholesterol is responsible for the rapid progression of atherosclerosis. This created a great interest in the worldwide medical community and a spate of research in cholesterol-induced atherosclerosis followed.

Follow up work of Ancel Keys and the Lipid Hypothesis:
Following Anichkov’s work, in 1952 a biochemist by the name of Ancel Keys came up with the lipid hypothesis, which, simply stated that the amount of fat in ones diet was directly correlated to the the incidence of coronary heart disease (CHD). Seems pretty common sense, right? So in order to back-up his “hypothesis”, he looked at epidemiological data from several populations across the globe to correlate dietary fat intake to the incidence of CHD. This led to what was called the ‘7 countries study’ which was a landmark study that changed the course of health for million to follow. The study involved looking at dietary habits of populations from 7 countries (Japan, Italy, Canada, Australia, USA, England and Wales) and the incidence of heart disease over period of a decade. The study didn’t account for any other lifestyle variables like, smoking, exercise habits, pollution levels, stress levels etc. Figure 1 shows the results of this study:



Figure 1. Correlation between CHD Vs. total fat intake (%) in Ancel Keys 7 countries study. Red line is a linear (least-squares) fit to the data.

From these results it’s pretty obvious that the more fat one consumed the more the likelihood for developing CHD. There is no disputing this data. But it didn’t end there. Ancel keys further went on to ‘show’ with his data that the amount of cholesterol in ones diet was directly correlated to the amount of dietary fat and again to the incidence of CHD. This earned him the title of ‘monsieur cholesterol’ and put him on the cover of Time magazine in 1961. He showed us the light and from there on began a crusade to put an end to all fats especially animal (saturated) fats as they were a rich source of cholesterol.

This landmark finding was hailed as the most important discoveries in the quest to end CHD. In fact it was so important that 211 prominent experts in the medical community’s were gathered in a conference in 1978[3] and asked if they thought cholesterol was the biomarker of CHD and 90% of them answered with a resounding ‘YES’! The National Institute of Health (NIH) held a conference in 1984 where they asked a panel of 14 experts if they thought blood cholesterol was the cause of CHD and weather reducing it would prevent heart disease, during which they voted with a unanimous “yes”. The panel further concluded [4]:

It has been established beyond a reasonable doubt that lowering definitely elevated blood cholesterol levels (specifically, blood levels of low-density lipoprotein (LDL) cholesterol) will reduce the risk of heart attacks caused by coronary heart disease...

 But little did they know that this was just the beginning of CHD! This was just the tip of the iceberg!

The Trans-Fat Revolution
So from the time Ancel Keys started his land mark study till now, deaths from CHD grew 600-fold, from 1 in a million to 600 in million! In the mean time the banishment of all fat and cholesterol from diet led to the trans-fat revolution and the low-fat fad. The gold rush had just begun!

The vegetable oil companies that were looking to expand in the human consumption market (before this most of the applications for vegetable oils was in the paints industry) found a gold mine in this study. They then started promoting hydrogenated fats which were vegetable oils with an extra hydrogen atom to make the oil solid at room temperature. This gave the consumer the ‘taste’ of butter (which was the fat of choice prior to this study) without having any of the ‘bad’ cholesterol. The other beneficiary of the results of this study was the pharmaceutical industry that found another gold nugget, selling drugs to lower lipid cholesterol levels. A $27 billion gold nugget to be exact (and it continues to grow!). This started a whole new low-fat food revolution that created factory foods where the calories from fat were replaced by calories from simple carbs and sugars. This brings forth the third beneficiary of the gold rush which was the American Heart Association (AHA) which started selling the AHA label endorsements to the low-fat industry, certifying low-fat products.

So while the pharmaceutical and vegetable oil industry and the AHA were reaping the benefits of this gold rush, the consumer was losing all along. The consumer didn’t reap any of the purported health benefits of the low-fat, cholesterol free products and drugs these entities were peddling. Furthermore, the US Department of Agriculture (USDA) was mandated with coming up with the recommended dietary guidelines for the general population and they came up with the food pyramid in the 1980’s which relied heavily on simple carbs from grains (at the bottom of the pyramid) and put fat in the prohibited category (on top of the pyramid). This was the turning point in the obesity epidemic, in that from there on the general population started getting fatter and sicker. Americans today are 30 lbs heavier than they were before the USDA guidelines.  The graph in figure 2 shows the trends in obesity and the adoption of carbs (over fat) over the years following the 7 countries study.






Figure 2: Trends in obesity and carb consumption from 1960 (courtesy Donald W. Miller, Jr., MD)

Analysis and Discussion
So what went wrong? Shouldn’t Ancel Keys’ study have unraveled the mystery of CHD? Or did he completely misinterpret the data and some other variable confounded the results of his study? Actually it was none of these. The whole thing started with a wrong experiment and later on was reinforced by incomplete data and poor science and then consensus was built around the faulty notion by the so called medical “experts” and from there on this so called “fact” propagated time and again until it reached epic proportions as we now see it. A quote from Joseph Goebbels aptly sums it up:

If you tell a lie big enough and keep repeating it, people will eventually come to believe it...”

There were three main reasons why this whole thing was wrong to begin with. And it wouldn’t take a rocket scientist to figure out these inconsistencies in experimentation that led to this sorry state of affairs (at at least for the consumer’s health). Let’s delve into the simplistic early models and the methodology of the 7 countries study. But before we go any further let me bring forth a few common sense principles that all of us engineers and scientists have been taught to follow during the course of any experimentation. It will all fall in place once you hear me out.

1)    The results of an experiment are only as good as the model it is based upon.

For this let’s step back to the original Nikolai Anichkov’s experiment of putting rabbits on a diet of bacon and eggs. His model assumed that a rabbit’s body could be used to simulate the effect of cholesterol on a human body. So while his interpretation of the results of his tests was absolutely right, his model wasn’t a good predictor of the effect of cholesterol on human body. He plugged the right variables in the wrong equation! You see, rabbits are genetically adapted to a zero cholesterol diet. Their diet is devoid of any cholesterol so their body doesn’t adapt well to cholesterol in diet and will naturally lead to inflammation and plaque formation in the arteries. Humans on the other hand are omnivores that are genetically adapted (for over 140,000 years) to dietary cholesterol, via meat and dairy, and so the effect of cholesterol on a human body would be different from that of a Rabbit’s. Let me give you an example. I propose a test where I put a lion on a diet of carrots and broccoli and see the effect on its health. I am pretty certain that the lion will soon fall sick and perhaps not last 1 year on that diet. So, am I to conclude that carrots and broccoli are fatal to health? I am sure you get the point!



2)    Experimenter bias always has the potential to skew the results

Ancel keys proposed the lipid hypothesis, but a hypothesis needs to be proved through careful experimentation. But when an experimenter is so attached to his hypothesis that he/she starts ‘expecting’ the results in alignment with his hypothesis he only sees data that fits his hypothesis. This is exactly what happened with Ancel Keys. He was so attached to his hypothesis that he only cherry picked data from the 7 countries that fit his model. In fact during his time there was epidemiological data available from 25 countries but he only chose the data points that fit his hypothesis. Again to illustrate my point, let me propose my own lipid hypothesis (call it the Yogi Lipid HypothesisJ) which states that the more dietary fat one consumes the lower ones risk for CHD. I’ll go even better than Ancel Keys and pick data from 8 countries (bigger sample size) and show you the correlation. Figure 3 shows the results of my study:






Figure 3. Correlation between CHD Vs. total fat intake (%) in Yogesh Verma’ 8 countries study. Green line is a linear (least-squares) fit to the data.

From this data it’s quite obvious that the more fat one consumed the less the likelihood of developing CHD! Makes sense, right? My point being, that any scrupulous researcher should consider all data before making any conclusions. Figure 4 shows the data from all 25 countries that were available to Ancel Keys.




Figure 4. Correlation between CHD Vs. total fat intake (%) for all 25 countries. Blue line is a linear (least-squares) fit to the data (left). Table showing the 25 country data (right)

Here, if you look at the (blue) least squares fit it shows a flat line, i.e., no correlation! The variation in the data is of a random variable! That’s exactly right there is absolutely no correlation between the amount of dietary fat consumed and the incidence of CHD! Hard to believe, eh? That’s because we have been fed this utter non-sense about dietary fat and how it increases our chances of developing CHD for so long that we have forgotten that the lipid hypothesis was a hypothesis to begin with and it still is to this day. This brings us to the third important failing point.

3)    Epidemiological studies cannot be used to determine causal relationships.

Epidemiological studies (ES) are the observations of certain behaviors of populations in terms of diet and other health habits. It is the cornerstone of public health research and is used to determine the possible causes to a certain disease or physical condition. ES alone cannot be used to determine a cause and effect relationship between a variable and a particular disease (in our case fat/cholesterol and CHD). At best the role of an ES is to link possible variables to a disease and to form a hypothesis about the cause and effect, which then needs to be verified through carefully designed controlled studies. For example in the 7 countries study (if that was the only data available) the data should have only been used to formulate the lipid hypothesis. Ancel Keys should then have conducted carefully controlled studies to determine the cause and effect relationship between fat intake and CHD, not the other way around, i.e., assume a causal relationship and then look for ES data that fits the hypothesis. The data gathered in any ES can have a lot of confounding variables, like smoking habits, drinking habits, socio-economic stresses, etc. that need to be carefully eliminated in a well designed controlled study.

So the whole fat and cholesterol hypothesis was wrong on three counts. It was driven by a few powerful and influential people and organizations that had to prowess to influence public policy decisions. It was built on consensus by the medical community (AHA) “experts” and other NIH personnel because there was no science to back it up. No one could have said it better than Michael Crichton (the author of Jurassic Park):

I regard consensus science as an extremely pernicious development that ought to be stopped cold in its tracks. Historically, the claim of consensus has been the first refuge of scoundrels; it is a way to avoid debate by claiming that the matter is already settled. Whenever you hear the consensus of scientists agrees on something or other, reach for your wallet, because you're being had.

"Let's be clear: The work of science has nothing whatever to do with consensus. Consensus is the business of politics. Science, on the contrary, requires only one investigator who happens to be right, which means that he or she has results that are verifiable by reference to the real world. In science consensus is irrelevant. What is relevant is reproducible results. The greatest scientists in history are great precisely because they broke with the consensus.

"There is no such thing as consensus science. If it's consensus, it isn't science. If it's science, it isn't consensus. Period. . . .

"I would remind you to notice where the claim of consensus is invoked. Consensus is invoked only in situations where the science is not solid enough. Nobody says the consensus of scientists agrees that E=mc2. Nobody says the consensus is that the sun is 93 million miles away. It would never occur to anyone to speak that way. ."

I am not saying that the research community isn’t realizing the flaw with the lipid hypothesis. A recent (Jan, 2010) meta-analysis of 21 cohort studies showed no correlation between saturated fat intake and the incidence of CHD[5]. The recent revision of the food pyramid to a “my plate” is evidence of this change. The emphasis on whole grains and vegetables instead of just any carb is evidence of this change. But fat still remains the pariah of the macro-nutrient group and that needs to change. We have been lied to for the last half century and that needs to stop! The medical and research community needs to come clean because thats the least they owe us.


References:
1)    Anichkov NN. Experimental arteriosclerosis in animals. In: Cowdry EV, editor, Arteriosclerosis: A survey of the problem. New York: MacMillan Publishing; 1933. p. 271-322.
2)    Gofman JW, Lindgren F. The role of lipids and lipoproteins in atherosclerosis. Science 1950;111:166-71.
3)    Norum KR (1978). "Some present concepts concerning diet and prevention of coronary heart disease.". Nutr Metab 22 (1): 1–7. PMID 619310
4)    from NIH Consensus Development Conference, JAMA 1985, 253:2080
5)    Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease, Patty W Siri-Tarino, Qi Sun, Frank B Hu, and Ronald M Krauss, Am J Clin Nutr doi: 10.3945/ajcn.2009.27725.