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Nutrition Past and Future

The Drivers of the Herd, Part 3

Catalyst Corrected 3, MRFIT and WHI

Slide 3                   Dr. Maryanne Demasi told us that major trials testing the diet-heart idea were failures. I’ve put this claim at number 5 on my list. In the next clip, watch for the names of the trials on your screen. One was called the Multiple Risk Factor Intervention Trial. Also, look for the letters “WHI,” which stands for Women’s Health Initiative.


Slide 4                   Demasi:  “Two ambitious trials, costing over $250 million – involving hundreds of thousands of patients – both failed to prove that lowering saturated fat could reduce your risk of dying from a heart attack.”

Taubes: “The way the authorities responded to this was to claim that they must have done the study wrong. Instead of saying, 'Hey, look, eating a low-fat diet doesn't apparently do anything for people, or certainly not women,' instead they respond by putting out press releases saying, 'Look, we don't know why this trial failed to confirm our hypothesis, but it doesn't mean that the advice we've been giving you is wrong, and it doesn't mean that the hypothesis that dietary fat causes heart disease is wrong.‘”

So you see we are talking about the Multiple Risk Factor Intervention Trial, or MRFIT, and the Women’s Health Initiative, or WHI.


Slide 5                   p.185. Taubes, Gary. Why We Get Fat and What to Do About It. New York: Alfred A. Knopf, 2011. Print.

Here you see that Gary Taubes, the man you just saw, uses this study in his book Why We Get Fat to make the point that the “authorities,” as he loves to call the experts, were so wedded to their idea that saturated fat causes heart disease that they were unable to acknowledge when this idea was proved false by the WHI. He gives the impression that this study was a clear demonstration that specifically targeting saturated fat doesn’t accomplish a thing. Except that is not so clear.


Slide 6                   Howard, Barbara V., et al. "Low-fat dietary pattern and risk of cardiovascular disease." JAMA: the journal of the American Medical Association 295.6 (2006): 655-666.

If you actually read the paper from the trial, you’ll see that “no formal intervention regarding saturated fat, cholesterol, trans fatty acids, or other known atherogenic factors was provided.” In addition, the researchers had no control over what the women actually ate. The women just got advice, and that advice didn’t even address saturated fat. That might make this one a bit less than ideal to address the question of what saturated fat does.


Slide 7                   Howard, Barbara V., et al. "Low-fat dietary pattern and risk of cardiovascular disease." JAMA: the journal of the American Medical Association 295.6 (2006): 655-666.

Evidence of the ineffectiveness of this intervention was the very small difference in cholesterol between the intervention and the control groups three years out. Realize it takes decades for plaques to build before an event is triggered. A fairly mild change in lifestyle probably won’t produce much of a difference in health. Notice the difference here was also small because the control group lowered their cholesterol a bit, too.


Slide 8                   How much did the intervention group really improve their diets? Notice that their protein increased but their soy consumption hardly changed. That suggests that they didn’t replace their animal proteins with plant proteins.


Slide 9                   They increased their carbs as a percentage of calories by 8% but they barely increased their fiber and whole grains.


Slide 10                 Since they didn’t eat much more quality whole plant food, the next most obvious way they could have improved their cardiovascular health through diet would have been to increase their ratio of fats in favor of more polyunsaturated fats. But you can see they hardly did that, either.


Slide 11                 Anderson, Cheryl AM, and Lawrence J. Appel. "Dietary modification and CVD prevention." JAMA: The Journal of the American Medical Association 295.6 (2006): 693-695.

As this editorial pointed out, the intervention didn’t make much difference in their diets. If their diets didn’t change much, then it makes sense that these women didn’t do much better.


Slide 12                 A table was provided by this editorial which showed very clearly how little chance this trial had of teaching us anything. Catalyst didn’t tell the viewers why this trial didn’t work. Really, there wasn’t much reason it should have worked. That’s why this wasn’t such an interesting trial, and the fact that it was big doesn’t make it any more interesting.


Slide 13                 Far more interesting was MRFIT. Dr. Demasi told us it was expensive and it failed. Part of the reason it cost so much was because testing methods and data analysis were so labor intensive back then. That’s why the cost of the trial shouldn’t mean much to us today. There’s also no principle in science that says that more expensive experiments are more important experiments. The cost is irrelevant but it’s useful for her to mention it to prejudice your judgment. Now notice the first three words here. “M.R.F.” stands for “Multiple Risk Factor.” This study wasn’t just about cholesterol.


Slide 14                 Multiple Risk Factor Intervention Trial Research Group. "Multiple Risk Factor Intervention Trial: risk factor changes and mortality results." Jama 248.12 (1982): 1465-77.

It was also a trial intended to lower high blood pressure and to decrease cigarette smoking behavior. No other tobacco use was addressed. So when Dr. Maryanne Demasi tells you that this trial was a failure, she is telling you that cigarette smoking and high blood pressure, like high cholesterol, were not shown to be harmful. Is she actually a doctor who is comfortable communicating the message that hypertension and smoking won’t hurt you?


Slide 15                 The men in the Special Intervention group, here called “SI,” really did reduce their smoking. There was a big difference between them and the men in the “UC” group, which stands for “Usual Care.” The researchers verified this by measuring a metabolic byproduct of smoking in their saliva. Does Dr. Demasi really mean to say that quitting smoking did these men no good?


Slide 16       

If that’s her opinion, then she sees things the way the Tobacco Institute saw them. This internal memo reveals that the muddled results of MRFIT made it a great subject for their future advertising and publicity. The perceived failure of MRFIT placed it on their agenda. MRFIT was also useful for Dr. Demasi’s agenda.


Slide 17       

You see that the friends of tobacco liked to mention the cost of the trial, too. It’s so much easier to harp about this than it is to actually try to understand what happened.


Slide 18       

Here you see the tobacco industry had experts they trotted out to make the same lame criticisms of the science on smoking’s harms that we hear from the cholesterol deniers today. The experts just knew there must be a problem with smoking. They just assumed it, and took it as fact. But they couldn’t prove it even though they spent so much money trying to prove it. Do you see that sentence at the bottom? “(The warning label on cigarette packs) doesn’t say the Surgeon General has any proof – in spite of more than a century and hundreds of millions spent in trying to find it.” Now think about that. Hundreds of millions of dollars of taxpayer money, taxes paid by nonsmokers as well as smokers, were wasted on their industry’s denials of the harm they knew their products caused. They demanded proof of something we all know today to be true. Their demands for “proof” wasted money and, more importantly, lives.


Slide 19                 Holford, Theodore et al. “Tobacco Control and the Reduction in Smoking-Related Premature Deaths in the United States, 1964-2012” JAMA. 2014;311(2):164-171.

It’s a good thing we didn’t waste decades trying to satisfy the doubts of a few entrenched skeptics. Anti-smoking policies in the United States were recently estimated to have prevented 8 million premature deaths. I’m sure some people with advanced degrees were left in high dudgeon as their personal ideas of “proof” were never forthcoming, but in retrospect, who cares?


Slide 20       

The tobacco industry really loved the word “proof” because they found it so useful. Search their documents for “proof” and you’ll get over 258,000 hits.

Dr. Demasi prefers to sow doubt with the word “prove” rather than “proof.”


Slide 21                 Demasi: “… it doesn’t prove anything … but in science, you have to prove it … both failed to prove … so if they can’t prove it …”

I suppose Dr. Demasi feels she is doing some critical thinking for us.


Slide 22       

When someone like Dr. Demasi or a tobacco shill demands proof of a hypothesis, what he or she is really trying to do is exploit a common misconception about science. “Proof” isn’t really a part of the culture of science. All knowledge in science is provisional. Nothing is ever considered proven. Proofs are for mathematicians. Scientists only have validated theories and plausible hypotheses.


Slide 23                 p.24. Rothman, Kenneth J, Sander Greenland, and Timothy L. Lash. Modern Epidemiology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2008. Google Books.

To expect that “proofs” will emerge from experiments dependent upon human behavior is especially unreasonable. Public health policy can only proceed on the basis of good evidence, not proof. You’ll see in the next video how the evidence she has chosen isn’t even good enough to provide support for the claims she makes, much less prove anything.


Slide 24                 The internal tobacco industry documents I just showed you were made available to us all as a result of the settlement achieved by the National Association of Attorneys General. The Master Settlement Agreement of 1998 established the Legacy Tobacco Documents Library, which is hosted online by the University of California at San Francisco. I encourage you to go to this site and read more about MRFIT and the ways of that industry.


Slide 25       

I also urge you to read the book Merchants of Doubt by Naomi Oreskes and Erik Conway. If you do you’ll learn how a few scientists used their expertise to cause confusion in the public about important issues and thereby delay appropriate evidence-based policies. The cholesterol deniers of today use the very same methods.


Slide 26                 Multiple Risk Factor Intervention Trial Research Group. "Multiple Risk Factor Intervention Trial: risk factor changes and mortality results." Jama 248.12 (1982): 1465-77.

So what actually went wrong with MRFIT? Why didn’t it succeed? You’ll notice that more of the men in the Special Intervention group received medications to treat hypertension than did the men in the Usual Care group. Remember, high blood pressure was one of the risk factors targeted in the design of MRFIT. They targeted it through drugs.


Slide 27                 Multiple Risk Factor Intervention Trial Research Group. "Multiple Risk Factor Intervention Trial: risk factor changes and mortality results." Jama 248.12 (1982): 1465-77.

If Demasi or Taubes would have bothered to read the study, they would have noticed, as I did, this passage explaining that MRFIT actually was successful in a subgroup of the study population – those not receiving medications for high blood pressure.


Slide 28                 The authors raised the possibility that one of their drugs for hypertension might have been increasing death rates.


Slide 29                 The two drugs they used were hydrochlorothiazide and chlorthalidone. Hydrochlorothiazide turned out to be the problem drug.


Slide 30                 Multiple Risk Factor Intervention Trial Research Group. "Mortality rates after 10.5 years for participants in the Multiple Risk Factor Intervention Trial: findings related to a priori hypotheses of the trial." JAMA 263.13 (1990): 1795-801.

Hydrochlorothiazide was preferentially prescribed at the start of the study to the Special Intervention men, and usually at very high doses. 50mg is a lot for this drug.


Slide 31                 It was later shown that there is no benefit to increasing its dosage beyond 12.5mg so those high doses were totally unnecessary.


Slide 32                 Van Brummelen, P., J. A. Gevers Leuven, and C. M. Van Gent. "Influence of hydrochlorothiazide on the plasma levels of triglycerides, total cholesterol and HDL-cholesterol in patients with essential hypertension." Current medical research and opinion 6.1 (1979): 24-29.

This is especially important to understand, because a study published while MRFIT was underway showed that at a 50mg dose, hydrochlorothiazide tends to raise cholesterol. This would have confounded any benefits the men should have enjoyed as a result of their improved diets. MRFIT failed, in part, because of the use of a cholesterol-raising drug.


Slide 33                 Multiple Risk Factor Intervention Trial Research Group. "Multiple Risk Factor Intervention Trial: risk factor changes and mortality results." Jama 248.12 (1982): 1465-77.

Here’s another reference to that excessive dosage. Read on and you’ll see the researchers running MRFIT acted on their suspicions and eventually changed the drug protocol from hydrochlorothiazide to chlorthalidone.


Slide 34                 Dorsch, Michael P., et al. "Chlorthalidone Reduces Cardiovascular Events Compared With Hydrochlorothiazide A Retrospective Cohort Analysis."Hypertension 57.4 (2011): 689-694.

These researchers recently remarked on the success of that switch. Mortality in the Special Intervention group improved. These authors pointed out that hydrochlorothiazide seemed to have been specifically raising LDL cholesterol. It also seemed to have been worsening their glycemic control.


Slide 35                 Ernst, Michael E., et al. "Long-term effects of chlorthalidone versus hydrochlorothiazide on electrocardiographic left ventricular hypertrophy in the multiple risk factor intervention trial." Hypertension 58.6 (2011): 1001-1007.

These weren’t the only apparent harms of hydrochlorothiazide. A recent study reexamined the MRFIT data. It was found that the group using this drug experienced more cardiac abnormalities.  LVH here means “left ventricular hypertrophy.”


Slide 36                 Rosendorff, Clive. "Why Are We Still Using Hydrochlorothiazide?." The Journal of Clinical Hypertension 13.12 (2011): 867-869.

Evidence like this has caused some doctors to ask why hydrochlorothiazide is still prescribed.


Slide 37                 Leren, P., and A. Helgeland. "Oslo hypertension study." Drugs 31.1 (1986): 41-45.

MRFIT wasn’t the only trial in which hydrochlorothiazide-treated patients experienced serious problems. The Oslo Hypertension Study also used hydrochlorothiazide. Those receiving hydrochlorothiazide were more likely to experience coronary events.


Slide 38                 Multiple Risk Factor Intervention Trial Research Group. "Multiple Risk Factor Intervention Trial: risk factor changes and mortality results." Jama 248.12 (1982): 1465-77.

One other change was made in protocol. Patients in the Special Intervention group were asked to restrict their saturated fat and cholesterol consumption even more.


Slide 39                 Multiple Risk Factor Intervention Trial Research Group. "Mortality rates after 10.5 years for participants in the Multiple Risk Factor Intervention Trial: findings related to a priori hypotheses of the trial." JAMA 263.13 (1990): 1795-801.

These two changes are probably why when researchers followed up on their patients years later, the Special Intervention patients had experienced a very clear 24% reduction in their death rate from heart attacks. MRFIT actually did demonstrate the success of saturated fat reduction and cholesterol lowering. Don’t let the cranks [convince] you otherwise.


Slide 40                 Multiple Risk Factor Intervention Trial Research Group. "Multiple Risk Factor Intervention Trial: risk factor changes and mortality results." Jama 248.12 (1982): 1465-77.

The authors of the original MRFIT paper didn’t know all this at the start of their trial. They couldn’t have explained their underwhelming results the way we can today. But they did key into another very important factor. These are the average cholesterol values for the two groups in MRFIT. Look to the right at the difference at the 6-year mark. That’s only a 4.2 mg/dL difference between the two groups. These numbers make MRFIT just like the WHI trial in one respect: the two groups in each trial didn’t differ all that much. This is what happens sometimes when the outcome of your trial depends upon human behavior.


Slide 41                 The MRFIT paper commented on this. Simply placing half the men in a control group in a heart disease trial would have had a treatment effect. Remember, the control group was not a no-treatment group. It was a “Usual Care” group. These men continued going to doctors and those doctors continued treating their patients.


Slide 42                 Lundberg, George D. "MRFIT and the goals of the Journal." JAMA: The Journal of the American Medical Association 248.12 (1982): 1501-1501.

Imagine you’ve just received word that you have been selected to participate in a trial examining mortality outcomes in men at high risk of dying from heart disease. In effect, you’ve just been told you are someone a team of researchers thinks has a good chance of dying soon because your risk factors are so bad. Also, imagine that as a participant in MRFIT you’ll receive annual tests of your cholesterol and blood pressure, and these tests will be seen by your doctor. Then remember that over the length of this trial the whole medical establishment was starting to wake up to the problem of high cholesterol. This editorial by George Lundberg accompanying MRFIT in JAMA put it the right way. MRFIT’s control group started getting better medical care from their doctors because they were put in the trial.


Slide 43                 If you want a clean scientific experiment examining what an intervention will do, you need a control group in which no treatment is given. But a study like this is conducted by doctors. No treatment just isn’t an option if they feel their patients should receive treatment. The ideal experiment is not ethically permissible.


Slide 44                 If you were placed in the Usual Care group, you might have been motivated to try to live a little longer, too. Smoking rates among these men declined. Cholesterol dropped. More of them were trying to control their blood pressure.


Slide 45                 Here is the range of differences in cholesterol between the two groups. Notice one number is negative. That means that for at least one of the clinics involved in the trial, the Usual Care men were actually doing a better job bringing down their cholesterol than the Special Intervention men.


Slide 46                 Multiple Risk Factor Intervention Trial Research Group. "Multiple Risk Factor Intervention Trial: risk factor changes and mortality results." Jama 248.12 (1982): 1465-77.

In the end the difference in cholesterol between the groups was only 2%.


Slide 47                 A 2% difference over 6 years just isn’t going to create a large contrast in results if you are looking at a disease that develops over decades.


Slide 48                 p.39. Bowden, Jonny, and Stephen T. Sinatra. The Great Cholesterol Myth: Why Lowering Your Cholesterol Won't Prevent Heart Disease and the Statin-Free Plan That Will. Beverly, MA: Fair Winds Press, 2012. Google Books.

Two of the fringe characters seen on Catalyst’s terrible program actually acknowledged the lack of difference between the two arms of the study, but they want you to think this means there should have been an obvious difference in outcomes. Read that sentence. Blood pressure and cholesterol were “slightly” different. It’s as if they don’t even understand the meanings of the words they’ve chosen. Notice they had to mention the cost of the trial, which was irrelevant, but they left out the problem with the drug treatment. They are using MRFIT to misinform you and not to help you. I think the Tobacco Institute would have liked these guys.


Slide 49                 p.60 Bickman, Leonard, and Debra J. Rog. The Sage Handbook of Applied Social Research Methods. Los Angeles: SAGE, 2009. Google Books.

Understand this very important point. It applies to MRFIT and WHI and many more studies I’ll be telling you about in these videos. Quoting this textbook by Leonard Bickman and Debra Rog, “The researcher’s choice of a control group, therefore, will influence the size of the potential contrast and hence of the potential effect size that appears in a study.” They are talking about research in the social sciences but the principle is universal. Both WHI and MRFIT suffered because they didn’t create adequate contrasts between their experimental and control groups. Whether you blame that on the organizers or blame it on the subjects, the effect is the same. This is a very obvious point. It should be intuitive and clear to anyone.

The cholesterol deniers use the rhetoric of critical thinking but they don’t practice it. Instead they do shabby research and hide key facts from you. This is what Maryanne Demasi has done.


Slide 50                 Hjermann, I., et al. "Effect of diet and smoking intervention on the incidence of coronary heart disease: report from the Oslo Study Group of a randomised trial in healthy men." The Lancet 318.8259 (1981): 1303-1310.

Why didn’t she tell you about a similar study in Oslo? Again, multiple risk factors were addressed, including cholesterol lowering.


Slide 51                 And here there were very clear differences in survival for those who quit smoking and improved their diets. Demasi didn’t tell you about this one because it didn’t serve her agenda.


Slide 52                 Don’t forget this point about the need for meaningful contrasts in studies that look at diet. We’ll need to understand this as we look at false claim number 2 in the next two videos.