The Great Cholesterol Consensus, Pt. 3


“Polyunsaturated fats can help reduce the cholesterol levels in your blood and lower your risk of heart disease.” – American Heart Association


Today we will be wrapping up, at least for now, my series on cholesterol, saturated fat, and coronary heart disease (CHD). In part 2 of The Great Cholesterol Consensus we discussed some of the commonly cited observational research that is used to support the lipid hypothesis and how those studies do no such thing. We left off with me saying how we would discuss the relevant randomized controlled data looking at PUFAs and CHD, and that’s exactly what we are going to do now.

It just so has it that today’s discussion proves to be quite timely because just this morning the prestigious Annals of Internal Medicine published a new systematic review and meta-analysis of 45 observational and 27 randomized controlled trials (RCTs) looking at the association between dietary fatty acids and CHD. The article revealed that our current nutritional guidelines, which, in part, promote replacing saturated fats with PUFAs, are… well… unfounded. To those who have read my previous two articles on saturated fat, cholesterol and heart disease, these findings should come as no surprise. For the vast majority of others, I’m sure this is quite a big shock. While I do not intend on discussing the recent Annals review – as I’ve basically covered the vast majority of what it says about the observational research regarding SFAs, PUFAs and CHD – I do point it out as the findings, more or less, sum up my cholesterol, saturated fat and CHD series. Either way, I promised you all that we would dissect the relevant RCT data, and that’s what we’re going to do – not to mention that I’ve had this article typed up for some time now!

So let’s get to it!

RCTs replacing saturated fats with polyunsaturated fats

Obviously, the strongest evidence either for or against the diet-heart theory is reserved for RCTs which can better deduce cause and effect. Given that the American Heart Association recommends reducing saturated fatty acid (SFA) intake (to as little as 5% of total calories) and replacing them with more unsaturated fats, we should easily be able to see a strong effect of SFA replacement with unsaturates on CHD and overall death.

In 2010 a group of researchers wondering the exact same question conducted a systematic review and meta-analysis of all relevant RCTs that examined the effects of replacing SFAs (control) with polyunsaturated fatty acids (PUFA; diet) on CHD events and deaths [1]. There is, to my knowledge, only one RCT that evaluated the effects of monounsaturated fatty acids (MUFA) on CHD end-points – something I will come back to later on.

Of the almost 350 identified publications and abstracts, eight were ultimately selected and analyzed. Those that did not make the cut were either; review papers, observational studies, studies lasting < 1 year, studies that had multiple interventions, or studies that used only non-CHD end points (e.g. overall mortality). I have provided a tabulated representation of the eight selected trials and their results:

RCT tableBriefly looking over the table one would sensibly come to the conclusion that replacing SFAs with PUFAs does reduce ones chances of CHD events and/or death. Indeed, the meta-analysis of the authors found a reduced risk for CHD when SFAs are replaced with PUFAs. To quote from their concluding remarks;

This current meta-analysis of RCTs of clinical CHD events […] provides strong concordant evidence that consumption of PUFA, in place of SFA, lowers CHD risk… [O]ur findings demonstrate reductions in CHD events, and no evidence for increased risk, in long-term trials utilizing PUFA consumption at very high levels.”

Thus, it would seem that SFAs most likely increase one’s risk of CHD and that replacing them with PUFAs reduces one’s risk. However, when you actually analyze the papers individually, the “strong concordant evidence” quickly falls apart.

Trials on trial

Starting with the earliest, the Los Angeles Veteran’s Administration Study [2], conducted from 1959 to 1961, compared a PUFA-rich diet (38% linoleic acid) to a control diet higher in SFAs (only 10% linoleic acid) in 846 semi-institutionalized veterans. At the end of the study the researchers observed a noticeable reduction in both total serum cholesterol levels and heart disease deaths in the PUFA-rich group. Aha! Lowering cholesterol levels does prevent death from heart disease! Unfortunately, the PUFA group also saw a marked increase in cancer deaths which effectively offset any differences in overall mortality. Moreover, when one looks at the autopsy data of selected participants from both groups who succumbed to CHD during they study [10], one notices that there were virtually no differences with regards to the degree of atherosclerosis. As a matter of fact, despite having lower total serum cholesterol concentrations, those in the PUFA-rich group actually had slightly more atherosclerotic buildup, albeit to a non-significant degree.

Furthermore, with regards to randomization, one notices that the control group – simply due to chance – had significantly more heavy smokers (>1 pack/day) than the PUFA-rich group (70 vs. 45, respectively) [11] [12]. Smoking is a complete and utter juggernaut when it comes to ruining cardiovascular health. Compared to non-smokers, smokers have been shown to have endothelial dysfunction leading to thrombosis as well as a heightened susceptibility to undergo vascular spasm which can cause a heart attack [13]. It’s no wonder the control group had a higher incidence of CHD events!

Moving down the list, in our second study the Medical Research Council of London, England [3] randomized 393 male patients, between 50-60 years old and who had survived their first heart attack, to either a PUFA-rich diet supplemented with soybean oil, or to their normal diet, high in SFAs. Despite greater reductions in serum cholesterol levels (12% in the diet group compared to less than 6% in the control), the PUFAs offered little benefit towards preventing future heart disease events or death. To quote the author’s concluding remarks;

Indeed, the results of this trial alone lend little support […] to the suggestion that a diet of the kind used should be recommended in the treatment of patients who have suffered a [heart attack].”

The Oslo Diet-Heart Study [4] – the next investigation supportive of replacing PUFAs for SFAs in prevention of CHD – randomized 412 men between 30-64 years old with previous heart attack to one of two groups. The diet group, as in the last study, was PUFA-rich and low in SFA. The control group was told to consume their normal diet, high in animal products and SFAs. By the end of study the diet group had significantly lowered their blood cholesterol levels and suffered from significantly less CHD, CVD, and all-cause mortality. On the surface this seems like an obvious win for PUFAs and heart disease treatment. Unfortunately, some major methodological limitations make this claim very weak.

Firstly, dietary intake between the two groups was horribly reported (only 4% in diet group and none in control group). Secondly, the diet group was receiving multiple dietary interventions at once! A fact that could only be found out by digging through the 92-page original publication in Acta Medica Scandinavica [14]. The other often cited publication, that doesn’t include dietary information, is available in the Bulletin of NY Academic Medicine [15] and Circulation [4]. Indeed, in addition to replacing their SFAs with PUFAs, subjects were also told to increase their fruit, nut, and vegetable consumption and to completely eliminate margarines rich in trans fats. Soybean oil and omega-3-rich sardine/cod liver oils were also supplied, free of charge. In aggregate, those in the diet group were already at an advantage of increasing their antioxidant, as well as, omega-3 status – all of which could potentially have beneficial impacts on cardiovascular health. Lastly, the diet group was shown to lose weight over the course of the study, another very important confounding factor when considering cardiovascular health and disease risk. All in all, this study is hardly evidence that replacing PUFAs for SFAs is beneficial for one’s heart – saying so would be cherry-picking from a host of multiple dietary interventions and confounding factors.

Moving on to the Finnish Mental Hospital study [5, 6] we see yet another reason to conclude that PUFAs, when substituted for SFAs, reduce one’s risk of CHD. In this study, the primary dietary alteration was replacing SFAs with PUFA-rich soybean oil. The results were published in two separate papers: one for the men and one for the women. Unfortunately, the Finnish Mental Hospital study was a NON-randomized affair. It should not have even been in the meta-analysis in the first place. Rather, the study was a cluster-randomized trial, meaning that, of the two hospital locations (abbreviated N and K), one was randomly assigned to the diet group while the other was assigned to the control – i.e. there was absolutely no randomization of the actual patients whatsoever. Furthermore, they used a crossover study design (usually a methodological strength) wherein, after 6 years, the hospitals simply reversed the diets. However, in this case, there was no washout period between diets. Lastly, some patients were discharged intermittently throughout the study wherein they could eat whatever they wanted to at home and thus affecting the dietary treatment. All in all, this study is nothing more than a bad joke.

Next, the Minnesota Coronary Study (MCS) [7] was a double-blind RCT and self-described “outgrowth” of the National Diet-Heart Feasibility Study – the predecessor of a highly anticipated NHBLI-sponsored national trial using over 100,000 men. The feasibility project, however, was a rather huge disappointment when the results showed absolutely no benefit of replacing PUFAs for SFAs on heart disease in over 2,000 subjects. The subsequent NHBLI study was then abandoned due to “reasons of cost” [16]. Nevertheless, MCS randomized over 9,000 men and women free of CHD to either a diet high in PUFAs, low in SFAs or one high in SFAs and low in PUFAs. Despite greater reductions in cholesterol levels in the high PUFA group, there were no statistical differences in CHD events, death or total mortality between the groups. In actuality the treatment group had slightly more cases of CHD and overall deaths in both men and women, albeit to a non-statistically significant degree.

In the Diet and Myocardial Reinfarction Trial (DART) [8] over 2,000 men who had a recent heart attack were randomized to one of three advice-groups or a non-advice control (Group 4): Group 1 was advised to reduce fat intake and achieve a high PUFA to SFA ratio; Group 2 was a high fatty fish advice group; and Group 3 was a high cereal fiber advice group. In the end there were no significant differences in mortality between the fat intake and cereal fiber advice groups. Total mortality in the fatty fish advice group, however, was significantly reduced, attributed entirely to a decrease in ischemic heart disease deaths. With regards to the failure of the high PUFA group, the authors state that, “If serum cholesterol had decreased more in our trial, mortality might have been reduced.” Perhaps they forgot that those in fish advice group managed to reduce their mortality despite increasing their cholesterol levels by over 2% during the first two years of follow-up before falling back to initial levels. Either way, there was no overall decrease in cholesterol levels in the fish advice group yet a significant reduction in heart disease deaths.

Rounding out our RCTs, just like the Oslo Diet-Heart Study, the St. Thomas Atherosclerotic Regression Study (STARS) [9] is rife with multiple interventions in the diet group – e.g. reducing their intake of junk food, avoiding trans-fat-rich margarines, and increasing their intake of fruits and vegetables. All in all, this is just another weak example in support of replacing PUFAs for SFAs.

But what about Sydney?

Remember when the authors of the meta-analysis stated that their, “findings demonstrate reductions in CHD events, and [that there was] no evidence for increased risk, in long-term trials utilizing PUFA consumption at very high levels.Well that’s because they left out (albeit, not purposefully) one of the most telling RCTs, to-date, on the effects of PUFA consumption and CHD.

The study not mentioned in the meta-analysis is that of the Sydney Diet-Heart Study (SDHS), conducted between 1966 and 1973 [17]. This study was excluded based solely on its non-CHD end-point (i.e. overall mortality). However, had this meta-analysis been published in 2013 or later, the re-evaluation of the SDHS – which does include CHD and CVD end-points – would most certainly have made the cut [18].

The SDHS randomized 458 men aged 30-59 years with a recent coronary event to either replace their saturated fat intake with safflower oil – a PUFA devoid of any omega-3 – or to continue their normal diet rich in SFAs. This study is unique in that it provides a dietary source of PUFAs that is not confounded by the potential cardiovascular benefits of omega-3s. Only two other studies exist that utilized a similar protocol – the first of which was the Minnesota Coronary Study which resulted in slightly more deaths in the PUFA group (despite not being significant), followed by an RCT in England that used corn oil in patients with previous heart attack [19]. The latter was not analyzed in the 2010 meta-analysis based on the fact that all of the patients were also receiving “conventional treatments” for heart disease. Nonetheless, what did the researchers find in their re-evaluation of SDHS?

Despite reducing their cholesterol levels by 13% – compared to only 5% in the control group – and comparatively doubling their PUFA:SFA ratio, those receiving the cholesterol-lowering safflower oil enjoyed statistically significant increased rates of death from CVD (17% vs. 11%) and CHD (16.3% vs. 10.1%) compared to control (all-cause mortality was only borderline significant with death rates of 17% vs. 11.8% in treatment and control groups, respectively). So much for no evidence demonstrating an increased risk with regards to long-term PUFA intake and CHD.

Lastly, remember the other two studies that used omega-3-devoid oils? Well, along with the SDHS re-evaluation, the authors also conducted a meta-analysis on the three studies that used PUFAs lacking omega-3s and saw a marked increase in both CHD and CVD deaths compared to controls. The increases in deaths, however, were only approaching significance (p=0.06 and p=0.07 for CHD and CVD, respectively). Either way, replacing SFA with PUFAs lacking omega-3s seem to be nothing but detrimental to heart health.

MUFAs: under-researched and over-hyped 

Lastly, let us touch upon monounsaturated fatty acids (MUFAs) and their effects on heart health. Unfortunately, the research here is considerably lacking. In the aforementioned English study that used corn oil as their PUFA source, the researchers also had an olive oil (MUFA) arm. Olive oil is commonly touted as a “heart healthy,” cardio-protective oil based on its high MUFA content. This, however, is largely based on studies replacing SFAs with MUFAs and measuring blood cholesterol levels – or worse yet, studies involving the “Mediterranean diet” which institutes a whole host of dietary changes in addition to olive oil – rather than actual incidents of CHD events/deaths. Nevertheless, the English corn oil/olive oil study is the only RCT conducted on olive oil/MUFAs and their effects on CHD mortality. What’s more is that the results do not support all of the hype surrounding the poster-child of MUFAs.

Indeed, by the end of the study the researchers tallied 12 major cardiac events in the corn oil group, nine in the olive oil group, and only six in the SFA-rich control group. In terms of cardiac deaths, the corn oil group had five, the olive oil group had three, and the control group had but one. Therefore, despite all the wonderful claims about olive oil being “heart healthy,” the only relevant findings bear out a strikingly different conclusion. This, however, isn’t to condemn olive oil, per se, as drawing conclusions from one study would be wrong. Rather, the moral of the story is that olive oil’s “heart-healthy” claims are largely based on extrapolation from blood cholesterol measurements rather than actual data on incidents of heart disease events/deaths.

Comments and conclusions

Well, there you have it, almost five decades’ worth of diet-heart RCTs and not one single study provides a shred of convincing evidence that you or anyone else (either with or free of heart disease) should replace their SFA intake with unsaturated fats (e.g. MUFAs and omega-6-rich PUFAs). Instead, one could argue that replacing their SFA intake with unsaturates might actually increase their risk of heart disease and death. If the lipid hypothesis were as strong a hypothesis as we are made to believe, such that people should drastically alter their diets and take potentially life-threatening drugs (e.g. statins), then the evidence should be overwhelming. Sadly (for lack of a better word), it is not – a finding that is echoed in today’s Annals publication. Rather, cherry-picked and misquoted studies make up the backbone of our current nutrition and medical recommendations for the prevention of heart disease. What is even worse is that copious amounts of tax-payer money have been wasted in the process. If you truly want to do your heart a favor, a) don’t smoke; b) eat a well-balanced diet that includes plenty of fruits and vegetables and high-quality proteins like fish, chicken and yes, steak; and c) exercise regularly and maintain a healthy body weight/composition (something to talk about in subsequent articles!). Trying to replace your SFAs with PUFAs in order to prevent and/or treat heart disease has been shown to be nothing more than a complete and utter farce, not to mention a potentially life-threatening undertaking.


1.         Mozaffarian D, Micha R, Wallace S: Effects on coronary heart disease of increasing polyunsaturated fat in place of saturated fat: a systematic review and meta-analysis of randomized controlled trials. PLoS Med 2010, 7:e1000252.

2.         Dayton S, Pearce ML, Goldman H, Harnish A, Plotkin D, Shickman M, Winfield M, Zager A, Dixon W: Controlled trial of a diet high in unsaturated fat for prevention of atherosclerotic complications. Lancet 1968, 2:1060-1062.

3.         Controlled trial of soya-bean oil in myocardial infarction. Lancet 1968, 2:693-699.

4.         Leren P: The Oslo diet-heart study. Eleven-year report. Circulation 1970, 42:935-942.

5.         Turpeinen O, Karvonen MJ, Pekkarinen M, Miettinen M, Elosuo R, Paavilainen E: Dietary prevention of coronary heart disease: the Finnish Mental Hospital Study. Int J Epidemiol 1979, 8:99-118.

6.         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.

7.         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, 9:129-135.

8.         Burr ML, Fehily AM, Gilbert JF, Rogers S, Holliday RM, Sweetnam PM, Elwood PC, Deadman NM: Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet 1989, 2:757-761.

9.         Watts GF, Lewis B, Brunt JN, Lewis ES, Coltart DJ, Smith LD, Mann JI, Swan AV: Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas’ Atherosclerosis Regression Study (STARS). Lancet 1992, 339:563-569.

10.       Dayton S, Hashimoto S, Pearce ML: Influence of a diet high in unsaturated fat upon composition of arterial tissue and atheromata in man. Circulation 1965, 32:911-924.

11.       Dayton S, Pearce ML, Hashimoto S, Dixon WJ, Tomiyasu U: A controlled clinical trial of a diet high in unsaturated fat in preventing complications of atherosclerosis. Circulation 1969, 40 (Suppl 2):1-63.

12.       Los Angeles Veterans Administration diet study. Nutr Rev 1969, 27:311-316.

13.       Nitenberg A, Antony I, Foult JM: Acetylcholine-induced coronary vasoconstriction in young, heavy smokers with normal coronary arteriographic findings. Am J Med 1993, 95:71-77.

14.       Leren P: The effect of plasma cholesterol lowering diet in male survivors of myocardial infarction. A controlled clinical trial. Acta Med Scand Suppl 1966, 466:1-92.

15.       Leren P: The effect of plasma-cholesterol-lowering diet in male survivors of myocardial infarction. A controlled clinical trial. Bull N Y Acad Med 1968, 44:1012-1020.

16.       The National Diet-Heart Study Final Report. Circulation 1968, 37:I1-428.

17.       Woodhill JM, Palmer AJ, Leelarthaepin B, McGilchrist C, Blacket RB: Low fat, low cholesterol diet in secondary prevention of coronary heart disease. Adv Exp Med Biol 1978, 109:317-330.

18.       Ramsden CE, Zamora D, Leelarthaepin B, Majchrzak-Hong SF, Faurot KR, Suchindran CM, Ringel A, Davis JM, Hibbeln JR: Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis. BMJ 2013, 346:e8707.

19.       Rose GA, Thomson WB, Williams RT: Corn Oil in Treatment of Ischaemic Heart Disease. Br Med J 1965, 1:1531-1533.

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2 Responses to The Great Cholesterol Consensus, Pt. 3

  1. Pingback: 40 “LOCO” Good Articles and Videos | Dynamic Duo Training

  2. Jane Sanchez says:

    You are a clueless individual. As Alexi Filippenko notes, in science, we need MANY MULTIPLE DIFFERENT TECHNIQUES and METHODS to test an idea. The randomized clinical trial is ONE method ONLY. It is farrr from perfect or the gold standard. No such thing exists. Even when we can ” tweak the knobs” a bit more, there are still MILLIONS of variables present in real live human beings. The randomized clinical trial is NOT the be all, end all. In fact, a poor randomized clinical trial is not worth nearly what a GREAT observational study is… In fact, these randomized clinical trials are from SEVERELY LIMITED TO OUTRIGHT USELESS for medical doctors in many cases. They do NOT tell them , quote often, WHICH specific patients will benefit , NOR do they present the sick population doctors treat. In many situations they are USELESS. These BEST they can do is tell us if we are not dealing with snake oil. As Dr. Planck said ” The causality principle itself is not right OR wrong, it is a heuristic act of faith on the part of the scientist….

    EVEN WITH MANY , MANY METHODS to test an idea those various methods could STILL lead us to a wrong result as Filippenko stresses. It is less likely though BUT STILL VERY POSSIBLE.

    Scientists are still unraveling how cells work and how nutrient affect them. We are nowhere even close to knowing the ideal diet IF such a thing exists.

    It is a TOTAL MYTH that the randomized clinical trial is the ONLY reliable method . In fact, this was discussed in Edge where they note it is an idea for RETIREMENT.

    GET OFF your high horse and LEARN a thing or four…… Until we understand HOW CELLS WORK, even the almighty randomized clinical trial is STILL rather WEAKER evidence.

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