Saturated Fat and Heart Disease Meta-Analyses: Were Scientists Wrong?

Was it Ancel Keys or the low carb advocates
who fabricated data on saturated fat?

In a previous review, Clearing up the Confusion Surrounding Saturated Fat, I examined several important flaws and omissions in two meta-analysis studies which are frequently cited as evidence against the hypothesis that dietary saturated fat increases the risk of heart disease. The earlier study was published in 2010 by Siri-Tarino and colleagues in the American Journal of Clinical Nutrition, and the more recent study published by Chowdhury and colleagues in the Annals of Internal Medicine. These studies were both cited in a recent Time magazine article by Bryan Walsh as evidence to "eat butter" for health. In this earlier review I focused primarily on how the studies included in these meta-analyses, as well many other studies actually provide support for the hypothesis that saturated fat increases the risk of fatal forms of heart disease.

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Vegetarian Diets and Quality of Life: Cause or Effect?

Very few would argue that simply excluding flesh from the diet will guarantee optimal health and longevity. However, the CBS Atlanta recently featured a concerning article, Study: Vegetarians Less Healthy, Lower Quality Of Life Than Meat-Eaters, suggesting that diets that exclude flesh promotes poor health. This article which has gathered much attention describes the findings of a cross-sectional survey from Austria that was published in PLoS One.1 This study has previously been addressed by Don Matesz in an very informative post. However, due to very serious omissions made by the CBS Atlanta, I felt that it was necessary to also address this study.

Vegetarian Diets and Perceived Health: Cause or Effect? 

It cannot be emphasized enough how important it is to recognize that this study, based on the Austrian Health Interview Survey (AT-HIS) examined dietary patterns after the subjects had developed health problems. Many vegetarians are not born into vegetarianism, but adopt a vegetarian diet later in life. Therefore, it is important to address why the vegetarians in this study adopted a flesh free diet. This important limitation was acknowledged by the Austrian researchers, who asserted:

Potential limitations of our results are due to the fact that the survey was based on cross-sectional data. Therefore, no statements can be made whether the poorer health in vegetarians in our study is caused by their dietary habit or if they consume this form of diet due to their poorer health status. We cannot state whether a causal relationship exists, but describe ascertained associations.

More importantly, in regards to causation the researchers asserted:

Our results have shown that vegetarians report chronic conditions and poorer subjective health more frequently. This might indicate that the vegetarians in our study consume this form of diet as a consequence of their disorders, since a vegetarian diet is often recommended as a method to manage weight and health.

The researchers suggested that if anything, it was not a flesh free diet that caused a higher rate of a number of health problems, but rather that it was poor health that caused these subjects to adopt a flesh free diet. This is similar to the phenomenon where former smokers report poorer perceived health than current smokers, because they quit smoking with the intention of alleviating poor health.2 This phenomenon is often referred to as reverse causality. 

Unfortunately, Benjamin Fearnow, the author of the article in the CBS Atlanta ignored the evidence suggesting that these results were the result of reverse causality, and instead suggested that a flesh free diet was actually the cause of a number of health problems:

...the vegetarian diet — characterized by a low consumption of saturated fats and cholesterol that includes increased intake of fruits, vegetables and whole-grain products — carries elevated risks of cancer, allergies and mental health disorders.

It is important to note that the Austrian Health Interview Survey did not measure food intake in actual detail. Subjects who reported consuming a flesh free diet were simply assumed to be consuming a diet poor in dietary cholesterol and saturated fat. However, in this study 36% of the vegetarian subjects were classified as lacto-ovo vegetarians, and 55% pescetarians (allowing fish, dairy and eggs). Only 9% were classified as vegans.1 Therefore, up to 91% of the subjects classified as vegetarians consumed dairy and eggs, being the richest sources of saturated animal fat and cholesterol, respectively. The CBS Atlanta failed to mention even the definition of a vegetarian diet used in this study, yet alone the breakdown of subjects in each category of vegetarian diet.

Vegetarian Diets and Cancer

At the time of the report, it was observed that 4.8% of the subjects of the Austrian Health Interview Survey classified as vegetarians had cancer, as opposed to 1.8% of the subjects following an omnivorous diet rich in meat. Unfortunately, no details were provided as to what portion of the studied population adopted a flesh free diet after diagnosis. However, data from previous studies suggest that cancer patients are highly motivated to adopt a plant based diet. As described previously: 

The results of a recent study from the Netherlands illustrates the critical importance of considering reverse causality in research on plant-based diets. The researchers found that 75% of the vegetarian participants with cancer adopted a vegetarian diet after diagnosis, consistent with previous research which found that cancer survivors are highly motivated to adopt a more plant-based diet with the intention of improving poor health.3 4

If the 75% figure from the study from the Netherlands is to be considered representative of this Austrian population, this would suggest that only 1.2% of the vegetarians adopted a flesh free diet prior to diagnosis of cancer. This is lower than the 1.8% figure for omnivores following a meat rich diet, but similar to that of the omnivores following a diet low in meat. Unfortunately, due to the lack of reliable data these estimates should be taken with a grain of salt. 

Prospective (forward-looking) studies which measure diet before diseases are diagnosed are much less likely to be complicated by reverse causality than cross-sectional studies, and therefore considered to be more appropriate for determining causality. I previously carried out a meta-analysis of 5 prospective cohort studies comparing the rates of cancer incidence in vegetarians compared to health conscious omnivores. For this review, I updated the meta-analysis to include the rates of major cancers in the Adventist Mortality and Adventist Health studies. In addition, I limited the inclusion criteria to studies that provided estimates specifically for subjects classified as either vegans, or lacto-ovo vegetarians.

In a meta-analysis including 7 prospective cohort studies, vegetarians had a statistically significant 9% lower risk of cancer incidence compared to health conscious omnivores (Fig. 1).5 6 7 8 9 It is important to note that meat intake was relatively low in the omnivorous group in these studies, especially taking into account that a significant portion of the omnivorous subjects were actually classified as semi-vegetarians. This suggests the difference in cancer incidence may be greater when compared to regular meat eaters.

FIGURE 1. Risk ratios and 95% CIs for fully adjusted random-effects models examining associations between vegetarian diets in relation to cancer incidence. ¹Mortality from cancers of the breast, colorectal, lung, prostate and stomach combined. VEG, vegetarian diet.

The finding of a decreased risk of cancer in vegetarians may be explained, in part, by a diet devoid in heme iron. Controlled feeding trials have established that NOCs (N-nitroso compounds) arising from heme iron in meat forms potentially cancerous DNA adducts in the human digestive tract, likely in part, explaining the significant association between heme iron and an increased risk of colorectal cancer in recent meta-analyses of prospective cohort studies.10 11 12 Heme iron has also been associated with numerous other cancers.

Vegetarian Diets and Heart Disease

In the Austrian Health Interview Survey, it was suggested that subjects classified as vegetarians were more likely to have had a history of heart attacks. It is important to note however, that, plant-based diets, poor in saturated fat and cholesterol have for long been adopted by individuals at risk of coronary heart disease. For example, it is known that in studies carried out as far back as the late 1950s, subjects with unfavorable blood cholesterol levels tended to limit intake of dietary cholesterol and saturated fat in order to improve cardiovascular risk factor.13

I previously carried out a meta-analysis of 7 prospective cohort studies comparing the rate of death of coronary heart disease of vegetarians compared to health conscious omnivores. For this review, I examined the incidence of coronary heart disease, and limited the inclusion criteria to studies that provided estimates specifically for subjects classified as either vegans, or lacto-ovo vegetarians. In a meta-analysis including 7 prospective cohort studies, vegetarians had a statistically highly significant 24% lower risk of coronary heart disease compared to health conscious omnivores (Fig. 2).5 6 7 14 15  

FIGURE 2. Risk ratios and 95% CIs for fully adjusted random-effects models examining associations between vegetarian diets in relation to coronary heart disease incidence. VEG, vegetarian diet.

The degree of reduction in risk of mortality from coronary heart disease observed in vegetarians in these cohort studies was generally in proportion to the expected reduced risk based on the differences in levels of total and non-HDL cholesterol, and blood pressure. This is supported by evidence from prospective cohort studies which found that diets characterized as being low in saturated fat and rich in dietary fiber decrease the risk of death from coronary heart disease. These findings are also supported by a recent meta-analysis of clinical trials and observational studies that found that vegetarian diets are associated with lower blood pressure and a lower risk of hypertension.16 Interestingly, the rates of hypertension tended to be lower in the vegetarians in the Austrian Health Interview Survey, suggesting that if the subjects adopted a vegetarian diet as a means to control hypertension, they were likely successful doing so.  

Vegetarian Diets and Mental Heath

In the Austrian Health Interview Survey, it was observed that subjects classified as vegetarians had a higher rate mental illnesses, defined as anxiety disorder or depression. Unfortunately, no data was provided as to what portion of the subjects adopted a vegetarian diet after developing these conditions. These findings have appealed to proponents of Paleoloithic diets who hypothesize that humans have a dietary requirement for meat in order to maintain large brains and mental health. However, in Powered By Plants: Natural Selection & Human Nutrition, Don Matesz examines an extensive body of research that casts considerable doubt on the hypothesis that meat is required to maintain mental health and is responsible for the evolution of the large human brain.

The findings from a number of clinical trials cast doubt on the hypothesis that an appropriately designed flesh free diet has adverse effects on, and that flesh rich diets, poor in carbohydrate have beneficial effects on overall mental health.

• Sacks and colleagues carried out a crossover trial to examine the effects of adding 250 g/day of beef isocalorically to the diet on blood cholesterol of vegetarians. As expected, during the meat phase total cholesterol and systolic blood pressure increased significantly. However, it was also observed that the participants experienced increased anger, anxiety, confusion, depression, and fatigue and less vigor compared to the vegetarian phase.17
• Beezhold and Johnston compared the mood scores of participants assigned to either a vegetarian diet, excluding all animal foods except dairy to participants assigned to either a omnivorous diet, or a diet that included fish, but excluded meat and poultry. The researchers found that the vegetarian group demonstrated significantly improved mood scores compared to both the omnivorous and fish groups.18
• Schweiger and colleagues compared the effects of a vegetarian diet and an omnivorous diet on global mood scores. They found that the vegetarian group demonstrated significantly better global mood, and that carbohydrate intake associated with better global mood.19
• Kieldsen-Kragh examined the effects of a vegetarian diet on rheumatoid arthritis. The researchers hypothesized that the participants may find the vegetarian diet too restrictive, and that therefore adherence to the diet would impose psychological distress on the them. However, contrary to their expectations, the vegetarian group demonstrated significantly improved physiological health, and were less anxious and depressed compared to the omnivorous group.20
• Brinkworth and colleagues examined the effects of a very low-carbohydrate diet and a low-fat diet on body weight and mood and cognitive function. Although there was no statistical difference in terms of weight loss between the groups, the participants assigned to the low-fat group demonstrated significantly improved mood scores compared to the participants assigned to the low-carbohydrate diet.21
• Holloway and colleagues carried out a crossover trial to examine the effects of a high-fat, low-carbohydrate diet on alterations to heart and brain function. The researchers found that the participants not only demonstrated significantly impaired cardiac health, but also impaired attention, memory recall speed, and mood while following the high-fat, low-carbohydrate diet.22
• Halyburton and colleagues examined the effects of a low and high-carbohydrate diet on mood and cognitive function. Although, unlike other studies, the researchers found that mood was similar in both groups, participants assigned to the low-fat diet demonstrated improved speed of processing compared to the participants assigned to the low-carbohydrate group.23

Mass Media as a Source of Health Information

The article featured in the CBS Atlanta is just one example of many studies that are misinterpreted, likely intentionally by the mass media. Unfortunately, the mass media is certainly not a reliable source for health information, as their primarily concern is to publish news that appeal to their targeted audience. In this case it was meat eaters who desired to hear negative things about vegetarian diets. This is likely why many important studies do not receive appropriate media attention,  and why consumers are either left in the dark or simply confused about health information.

Although there is convincing evidence of the health benefits of an appropriately planned diet that either excludes or significantly limits the intake of flesh, such findings cannot be extrapolated to all diets that exclude flesh. The definition of a vegetarian diet only provides information as to what foods an individual restricts, and not which foods are included. This is why the emphasis of a healthy diet also needs be on which foods are included, not only on those that are excluded. Future research in this area should address what foods vegetarians are substituting meat with,  the length of adherence to a vegetarian diet, and whether subjects adopted a vegetarian diet in order to alleviate poor health. This would allow for a considerably more meaningful interpretation of the effects of vegetarian diets.

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Clearing Up The Confusion Surrounding Saturated Fat

In 2010, Siri-Tarino and colleagues published a meta-analysis of prospective cohort studies evaluating the association between dietary saturated fat and cardiovascular disease in the American Journal of Clinical Nutrition.1 Based on the results of this meta-analysis, these researchers concluded that there was insufficient evidence from prospective cohort studies to conclude that dietary saturated fat increases the risk of coronary heart disease. However, a number of prominent diet-heart researchers identified many serious flaws and omissions in this meta-analysis that cast doubt on the validity of these researchers conclusions.2 3 4 5 6

More recently, Chowdhury and colleagues published a separate meta-analysis in the Annals of Internal Medicine, and reached similar conclusions to that of Siri-Tarino and colleagues regarding the association between saturated fat and coronary heart disease.7 Unfortunately, this meta-analysis also failed to sufficiently address a number of important limitations that it shares with the meta-analysis by Siri-Tarino and colleagues. Furthermore, in this meta-analysis, although positively, but not significantly associated in the random-effects model, both dietary and total circulating concentrations of saturated fat were associated with a small, but statistically significant increased risk of coronary heart disease in the fixed effects model (RR=1.04 [95% CI, 1.01, 1.07] and RR=1.13 [95% CI, 1.03-1.25], respectively). These significant findings were however ignored in the conclusions of this study. Nevertheless, the media and proponents of popular Low-Carb and Paleo diets have repeatedly cited these meta-analyses as evidence to support a diet rich in saturated fat. 

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Do Vegetarians Live Longer Than Health Conscious Omnivores?

Proponents of Paleo and Low-Carb diets suggest that plant-based diets, particularly those rich in grains and legumes, promote disease, ultimately resulting in premature death. However, there is a substantial amount of evidence casting doubt on such suggestions, with many studies providing evidence that plant-based diets increase longevity. This review will focus on studies examining the longevity of plant-based populations, and some of the criticisms of these studies, particularly in reference to Denise Minger's recently published book, Death By Food Pyramid.

It is not news that Denise Minger has a tendency to downplay the health benefits of plant foods and plant-based diets. In her critique of the China Study, Minger claimed that “as a plant-nosher”, she was hoping to find evidence to support Dr. T. Colin Campbell's findings from the China Study linking dietary fiber to lower rates of colorectal cancer.1 Somehow, however, despite her vegan bias apparently creeping into her critique, Minger suggested that she was unable to find sufficient evidence outside of the China Study supporting the hypothesis that dietary fiber protects against colorectal cancer. And yet, several months later the omnivorous panel of experts of the World Cancer Research Fund concluded based on a review of over 1,000 publications that there was convincing evidence that dietary fiber protects against colorectal cancer.2 In Death By Food Pyramid, Minger continues this trend of downplaying the health benefits of plant-based diets. 

Failing to Equal the Seventh-day Adventists

In the chapter of her book, Herbivore’s Dilemma, Denise Minger provides a brief overview of the history and the growth of the popularity of vegetarian diets, bringing into picture the earliest of the studies on the Californian Seventh-day Adventists. Loma Linda, California which is highly concentrated by Adventists is considered to be a Blue Zone because of the greater life expectancy compared to other parts of North America. Loma Linda shares the title of Blue Zone with four other populations which are all characterized by traditionally consuming plant-based diets, typically rich in legumes and grains.3 These other Blue Zones include, Ikaria, Greece; Nicoya, Costa Rica; Okinawa, Japan; and Sardinia, Italy. It seems that Minger was not even able to get these simple details right in her book, claiming that the Greek island of Crete is considered a Blue Zone, while citing an article that clearly refers to Ikaria.

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Denise Minger: Death By Food Pyramid or Saved By Food Pyramid?

A few years back, Denise Minger instantly rose to fame in the Low-Carb and Paleo diet circles shortly after publishing a blog post criticizing the chapter describing the findings from the China-Cornell-Oxford Project in the book, The China Study, written by Dr. T. Colin Campbell.1 This blog post was very welcomed by proponents of these diets as it provided them with a reference which they used to attempt to use refute much criticism they had been receiving for promoting a diet rich in animal foods.

One reason Minger’s critique likely received much attention, was that unlike other individuals who have attempted to criticize the China Study, rather than making her intention of defending a diet rich in animal foods obvious, Minger attempted to give readers a false impression that if anything she was bias towards a plant-based diet. Minger’s intentions became somewhat apparent when Paleo diet proponent Richard Nikoley posted an e-mail that he received from Minger on his blog.2 The contents of this e-mail made it obvious that Minger had been sending e-mails to proponents of Low-Carb and Paleo diets, suggesting that they cite her blog post as "ammo" to shoot down "vegans" who cite The China Study. The language used by Minger in the e-mail, such as the statement “Of course, they aren't”, in reference to whether animal foods are linked to chronic diseases, suggested the likelihood of confirmation bias in favor of downplaying the harms of animal foods. This raises the question as to whether it was her intention to simply downplay Dr. Campbell’s work, rather than producing an honest review.

As described previously by Plant Positive, and myself, there were a number of serious concerns with Minger’s interpretations of the data from the China Study which further casted doubt on her true intentions. One particular example was Minger's attempt to attribute the association between fat intake, a marker of animal food intake, and an increased risk of breast cancer mortality in the China Study to the consumption of "hormone-injected livestock".3 The fact that the mortality data that Minger examined was from the early to mid-1970s, a time when the use of hormone injections was not exactly widely practiced throughout rural China casts serious doubt on this claim. Furthermore, it is important to consider that the time lag between exposure to a causal agent and when breast cancer becomes life threatening is more than often several decades. For example, the greatest risk of excess death from radiation-related solid cancers, such as breast cancer among the atomic bomb survivors of Hiroshima and Nagasaki was more than half a century after exposure.4 It is therefore likely that most of the dietary related deaths from breast cancer that occurred in the early 1970s would more likely to have been caused by the diets consumed several decades earlier, likely even before hormone injections was used to any meaningful extent in China. This provides further suggestive evidence that Minger was merely trying to downplay the evidence of the harms of animal foods, rather than producing an honest review.

Given Denise Minger’s misleading blog posts, naturally I was more concerned than interested to see what sort of take home message Minger would be attempting to provide readers of her recently published book, Death By Food Pyramid. I have therefore decided to review a number of the key sections of the book to help readers to decide whether to purchase and incorporate the dietary advice in this book.

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Grass-Fed Animal Foods and Diseases of Civilization: Cardiovascular Disease in Ancient Civilizations

Vilhjalmur Stefansson was an Artic explorer known for his observations on the traditional living Inuit-Eskimo, which he lived together with in the winter of 1906-1907 in the Mackenzie Delta of Canada. Stefansson asserted that during this time he subsisted on traditional Inuit fare, based almost exclusively on flesh. In part based on less than extensive observations of the health of the Inuit, Stefansson hypothesized that a number of chronic and degenerative diseases, including cancer are diseases of civilization which can be prevented by adherence to a pre-modern diet and lifestyle. However, Stefansson did not suggest that only flesh based dietary patterns, such as that consumed by the traditional living Inuit, but also primarily vegetarian diets, such as that consumed by the Hunza may protect against such diseases.1 

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The Asian Paradox: End of the Line for Low Carb Diets?

The fact that the populations of many parts of Eastern and Southeast Asia have traditionally been slim while consuming a high carbohydrate diet, typically rich in white rice is often considered as a ‘Asian Paradox’ by advocates and followers of carbohydrate restricted Low-Carb, Paleo and Primal type diets who hypothesize that such a dietary pattern promotes weight gain. Mark Sisson, a prominent Paleo diet advocate recently explained that the so-called ‘Asian Paradox’ is not a paradox because he believes that Asians have traditionally conformed to a lifestyle and diet that is comparable with his recommendations.1

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Cracking Down on Eggs and Cholesterol: Part II

Recently two meta-analysis papers were published addressing the findings from population studies of the association between egg intake and the risk of cardiovascular disease.1 2 Unfortunately the authors of these two review papers reached contradictory conclusions regarding the dangers of egg intake which is likely to lead to unnecessary public confusion. The authors of the most recent meta-analysis paper reviewed studies on coronary heart disease, heart failure, diabetes and all cardiovascular diseases (CVD) combined and concluded:

Our study suggests that there is a dose-response positive association between egg consumption and the risk of CVD and diabetes.

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Cracking Down on Eggs and Cholesterol

Since the breakthrough led by Nikolai Anichkov a century ago, the feeding of cholesterol, and to an extent, dietary fat have been recognized as the sine qua nons for the dietary modification of experimental atherosclerosis, and have been used in thousands of experiments to successfully accelerate the development of atherosclerosis in mammalian, avian and fish species, not only of herbivorous, but also omnivorous and carnivorous nature.1 2 3 4 5 6 7 8 9 10 11 This includes the promotion of experimental atherosclerosis in over one dozen different species of nonhuman primates- New World monkeys, Old World monkeys, and great apes including the closest living relative to humans, the chimpanzee (Fig. 1).2 3 12 13 14 15 16 17 18 19 20 21 The atherosclerotic lesions induced by cholesterol feeding, including in the form of fresh eggs yolks in many opportunistic omnivores, such as various species of nonhuman primates, birds and pigs have been shown to closely resemble the disease in humans.1 2 3 4 22 23 24

Figure 1. Aortic atherosclerosis of a chimpanzee which died of a heart attack after long-term feeding of a diet rich in cholesterol and artery-clogging saturated fat

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Diet-Heart: The Role of Vegetarian Diets in the Hypothesis

A recent publication from the EPIC-Oxford cohort with 15,000 vegetarians and 30,000 non-vegetarians found that the vegetarians had a 32% lower risk of hospitalization or death from coronary heart disease.1 These findings are consistent with a previous meta-analysis of 5 cohort studies with 48,000 non-vegetarians and 28,000 vegetarians which found that lacto-ovo vegetarians had a 34% lower risk of fatal coronary heart disease compared to regular meat eaters.2 These findings remained significant even after adjusting for non-dietary factors and alcohol intake. In addition, in each of these 6 cohort studies, vegetarians and non-vegetarians shared a similar interest in healthy lifestyles or were of a similar religious background, therefore limiting the number of potential confounders that could have obscured these findings.

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