New Evidence Strengthens the Link Between Hypothalamic Injury, Obesity, and Insulin Resistance

Obesity involves changes in the function of brain regions that regulate body fatness and blood glucose, particularly a region called the hypothalamus.  My colleagues and I previously showed that obesity is associated with inflammation and injury of the hypothalamus in rodent models, and we also presented preliminary evidence that the same might be true in humans.  In our latest paper, we confirm this association, and show that hypothalamic injury is also associated with a marker of insulin resistance, independently of BMI.

Introduction

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Insulin Resistance Predicts a Variety of Age-related Diseases

In the last post, I reviewed a study by Gerald Reaven's group showing that insulin resistance strongly predicts the risk of cardiovascular disease over a 5-year period.  In 2001, Reaven's group published an even more striking follow-up result from the same cohort (1).  This study shows that not only does insulin resistance predict cardiovascular disease risk, it also predicts a variety of age-related diseases, including hypertension, coronary heart disease, stroke, cancer, type 2 diabetes, and even overall mortality risk.

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Is Meat Unhealthy? Part V

In this post, I'll examine the possible relationship between meat intake and type 2 diabetes.  Type 2 diabetes is the most common form of diabetes, and it is strongly linked to lifestyle factors.

Non-industrial cultures

Non-industrial cultures have an extremely low prevalence of diabetes, whether they are near-vegan or near-carnivorous.  This is supported by blood glucose measurements in a variety of cultures, from the sweet potato farmers of the New Guinea highlands to the arctic Inuit hunters.  Here is what Otto Schaefer, director of the Northern Medical Research Unit at Charles Camsell hospital in Edmonton, Canada, had to say about the Inuit in the excellent book Western Diseases (Trowell and Burkitt, 1981):
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Obesity → Diabetes

A new study adds to the evidence that the prevalence of type 2 diabetes is rapidly increasing in the US, and our national weight problem is largely to blame.

The Centers for Disease Control (CDC) currently estimates that a jaw-dropping 33 percent of US men, and 39 percent of US women, will develop diabetes at some point in their lives (1).  Roughly one out of three people in this country will develop diabetes, and those who don't manage it effectively will suffer debilitating health consequences.  Has the risk of developing diabetes always been so high, and if not, why is it increasing?

In the same issue of the Annals of Internal Medicine as the low-carb vs. low-fat study, appears another study that aims to partially address this question (2).

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Metabolic Effects of a Traditional Asian High-carbohydrate Diet

A recent study supports the notion that an 'ancestral diet' focused around high-starch agricultural foods can cultivate leanness and metabolic health.

John McDougall gave Christopher Gardner a hard time at the McDougall Advanced Study Weekend.  Dr. Gardner conducts high-profile randomized controlled trials (RCTs) at Stanford to compare the effectiveness of a variety of diets for weight loss, cardiovascular and metabolic health.  The "A to Z Study", in which Atkins, Zone, Ornish, and LEARN diets were pitted against one another for one year, is one of his best-known trials (1).

Dr. McDougall asked a simple question: why haven't these trials evaluated the diet that has sustained the large majority of the world's population for the last several thousand years?  This is an agriculturalist or horticulturalist diet based around starchy foods such as grains, tubers, legumes, and plantains, and containing little fat or animal foods.  Researchers have studied a number of cultures eating this way, and have usually found them to be lean, with good cardiovascular and metabolic health.  Why not devote resources to studying this time-tested ancestral diet?  I think it's a fair question.

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Help Advance Diabetes Research

A University of Virginia researcher named Hannah Menefee contacted me recently to ask for our help.  She and her colleagues are conducting a study on how people with type 2 diabetes use Facebook to manage their health, and how that technology can be leveraged to support effective health communication.

If you have type 2 diabetes, and you'd like to participate in the study, please join their Diabetes Management Study Facebook group.  There, you'll receive more information about the study, you'll receive a short survey, and you may be invited into one of the study phases.

Does "Metabolically Healthy Obesity" Exist?

Obesity is strongly associated with metabolic alterations and negative health outcomes including diabetes, cardiovascular disease, and some types of cancer (1, 2, 3, 4).  Excess body fat is one of the primary causes of preventable health problems and mortality in the United States and many other affluent nations, ranking in importance with cigarette smoking and physical inactivity.  Obesity is thought to contribute to disease via the metabolic disturbances it causes, including excess glucose and lipids in the circulation, dysregulated hormone activity including insulin and leptin, and inflammatory effects.  This immediately raises two questions:

1. Does metabolically healthy obesity exist?
2. If so, are metabolically healthy obese people at an elevated risk of disease and death?

Does metabolically healthy obesity exist?

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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

Sisson attributes the leanness and health of the traditional living Asians to regular exercise and a diet rich in unprocessed foods including fresh meat, offal, bone broth as well as vegetables, with rice playing a neutral role. In addition, Sisson attributes much of the observed increases in rates of obesity, diabetes and coronary heart disease in Asia in more recent years to an increased intake of sugar, and the replacement of rice with wheat and saturated animal fats with omega-6 rich fats. However, Sisson provided scant evidence to support his claims regarding the composition of traditional and modern diets in Asia. Considering that obesity, diabetes and cardiovascular disease are major causes of disability and death throughout the world, this warrants an examination of these claims.2

Concerns of Low-Carb and Paleo Diets

Mark Sisson sells whey protein, among many 
other supplements. These supplements were 
certainly not available to Paleolithic humans.

Sisson advocates a diet that is rich in animal protein and fat and poor in carbohydrate. Sisson has an 80/20 rule which allows 20% of dietary intake from non-Paleolithic foods from his list of approved foods, including items such as full-fat dairy, chocolate, coffee and wine, as well as the supplements that he sells. Sisson would have his targeted audience believe that humans have conveniently adapted to many foods that were not typically available during the Paleolithic period which are popular among followers of low-carb diets, but not the foods that they typically shun. As such a dietary composition is probably not coincidentally all that different from other popular carbohydrate restricted diets, this makes the diet that Sisson promotes essentially in one variant or another a rebranded Atkins diet. Aside from the lack of originality, there is an ever-increasing amount of evidence demonstrating harm of such a diet. 

It is well established that weight loss has a modest favorable effect on many cardiovascular risk factors.3 4 5 Therefore the modest beneficial changes to cardiovascular risk factors observed in participants on carbohydrate restricted diets in some controlled trials can be either partly or wholly explained by weight loss. However, even in the presence of slightly greater weight loss, meta-analyses of randomized controlled trials have found that compared to diets rich in nutrient poor, low-fiber carbohydrates, carbohydrate restricted diets raise LDL cholesterol and impair flow-mediated dilatation, a measure of endothelial dysfunction which can increase the risk of cardiovascular disease.6 7 In addition, a recent intervention study on a Paleo type diet that contrary to previous intervention studies, did not focus on reducing saturated fat intake found that a Paleo diet significantly raised non-HDL cholesterol and the total cholesterol/HDL ratio despite weight loss and adherence to an exercise regime.8

The findings of a harmful effect on flow-mediated dilatation are consistent with several other controlled experiments which found that diets rich in saturated fat, including when consumed in a carbohydrate restricted diet impaired flow-mediated dilatation.9 10 11 12 13 These findings are also supported by experiments showing that diets rich in cholesterol and saturated fat cause endothelial dysfunction in numerous species of nonhuman primates.14 15 16 Taken together, these findings lend support to the findings that carbohydrate restricted diets adversely affect coronary blood flow, arterial wall function and cardiac efficiency.17 18 19

The findings of a harmful effect on LDL cholesterol are consistent with the findings from hundreds of controlled experiments establishing beyond plausible doubt that a diet lower in saturated fat, ruminant trans-fat, dietary cholesterol, and richer in soluble fiber and plant sterols significantly reduces total and LDL cholesterol.20 21 22 23 24 25 It has also been established beyond plausible doubt that lowering LDL cholesterol reduces the risk of coronary heart disease.26 However, this effect is likely to be considerably stronger the longer LDL cholesterol is maintained at a lower concentration.27 28

A meta-analysis of 108 lipid intervention trials with 300,000 participants and a mean follow-up of only three years found that for each 1 mmol/l (38.7 mg/dl) reduction in LDL cholesterol, coronary heart disease and all-cause mortality was reduced by 24% and 15% respectively, independent of HDL cholesterol, triglycerides and non-lipid effects of specific interventions.29 Comparatively, a meta-analysis of mendelian randomization studies with more than 312,000 individuals found that for each genetically predicted 1 mmol/l reduction in LDL cholesterol maintained throughout life, coronary heart disease was reduced by 55%, independent of the mechanism by which LDL was modified and other known risk factors.30 Conversely, both randomized controlled trials and mendelian randomization studies have been unable to establish a causal relationship between HDL cholesterol and triglyceride concentrations and coronary heart disease.29 31 32

Experiments on animals have found that carbohydrate restricted diets accelerate the development of atherosclerosis independently of traditional risk factors.33 Furthermore, evidence from thousands of experiments carried out over the last century have shown that the feeding of dietary cholesterol and saturated fat has accelerated the development of atherosclerosis in virtually every vertebrate species that has been sufficiently challenged. This includes mammalian, avian and fish species- herbivores, omnivores and carnivores, and over one dozen different species of nonhuman primates. 

Nations throughout Australasia, Europe and North America have experienced very dramatic declines in coronary heart disease mortality throughout the last half century, for which a substantial portion of the decline has been explained by a dietary induced reduction in serum cholesterol.34 35 After a decade of steady increases, the rates of coronary heart disease mortality in the Czech Republic and Poland fell almost immediately and halved within about 15 years following the abolishment of communist subsidies on meat and animal fats after the collapse of the Soviet Union. Nearly half of this decline has been explained by decreases in serum cholesterol.36 37 In the Nordic nations the rate of coronary heart disease mortality decreased by about 50-85% within three decades following Government initiatives which included a reduction in saturated fat intake. In Finland, Iceland, Norway and Sweden the decreases in serum cholesterol was the main contributor explaining between about one-third and more than half of this decline.38 39 40 41

Contrasting trends have however been observed in Tunisia and Beijing. Tunisia has recently experienced a significant increase in coronary heart disease mortality, of which half of this increase has been explained by an increase in serum cholesterol following a transition from the traditional wheat based diet to a diet richer in animal protein and fat.42 In Beijing where the rates of coronary heart disease mortality increased by more than 100% between 1984 and 1999, the great majority of the increase was explained by an increase in serum cholesterol following a five-fold increase in intake of meat and eggs (Fig. 1).43

Figure 1. Coronary heart disease mortality trends in Beijing 1984 to 1999

Over the last decade the population of Sweden has been shifting to a diet lower in carbohydrate and higher in fat, especially from animal sources following much positive media support for low carbohydrate-high-fat (LCHF) diets. However, despite promises of rapid weight loss, not only has there been no change to the constant increase in BMI, there has actually been an increase in serum cholesterol despite an increased use of cholesterol lowering medication.44

Following the dietary transition in Sweden there has been a sudden surge in heart attacks in women, and stoke in men and women aged 35-44 despite steady decreases in smoking prevalence in this age group, especially for women.45 This has been a great cause of concern for a number of prominent Swedish cardiologists who have attributed this to the significant increase in the popularity of LCHF diets.46 Similar concerns were raised when there was a sudden surge in sudden cardiac death among women, also aged 35-44 in the United States during the period of heightened popularity of the Atkins diet.47 48

As younger adults are considerably less likely to be treated for risk factors prior to a cardiovascular event, they may be more vulnerable to these dietary changes, possibly explaining why they have been the first group in the Swedish population to experience these adverse effects following the dietary transition. The finding that particularly young women were adversely affected may be because young women were among the first groups in the population to make this dietary transition, and also because LCHF diets are considerably more popular among Swedish women than men.44 49

Another concern with diets that are rich in meat and offal is an excess intake of heme iron, found exclusively in animal tissue. As iron is a pro-oxidant and excess iron cannot be excreted from the body, excessive absorption of iron can contribute to progressive inflammatory and degenerative diseases.50 It has been shown in controlled feeding experiments that the absorption of heme iron is considerably less regulated than that of non-heme iron, and therefore a high intake can lead to excess iron absorption.51

Recent meta-analyses of prospective cohort studies found that an increment of 1 mg/day of heme iron was associated with an 11%, 16% and 27% increased risk of colorectal cancer, type II diabetes and coronary heart disease respectively.52 53 54 When taking into consideration the fact that diets very rich in meat and offal can supply well over 10 mg of heme iron per day, these findings cast considerable doubt on the long-term safety of such diets.55 Heme iron intake has also been associated with oxidative stress and an increased risk of stroke, gestational diabetes, gallstones and cancers of the prostate, lung, stomach, esophagus, endometrium and kidneys.56 57 58 59 60 61 62 63 64 65 66 67 68 69

It has been shown in a randomized controlled trial that carbohydrate-restricted diets promote metabolite profiles that may increase the risk of colorectal cancer.70 This is compatible with the strong evidence from both controlled experiments and prospective cohort studies that diets richer in heme iron and poorer in dietary fiber increase the risk of colorectal cancer. Over a century ago, high rates of cancer were observed in Argentina which was inhabited by the Gaucho, a nomadic population that for months subsisted entirely on pasture raised beef. Similarly, a study carried out in Uruguay where livestock is predominantly grass fed, and the administration of hormones is banned by law found that a high intake of fresh red meat was associated with between a 87% and 290% increased risk of 13 different major cancers, independent of other food groups.71

Another concern of diets rich in animal protein is that they can have adverse effects on phosphorus balance in the presence of declining kidney function, contributing to very serious complications associated with kidney disease including cardiovascular disease and sudden death.72 A Cochrane review of randomized controlled trials with patients with chronic kidney disease found that compared to patients with unrestricted protein intake, patients who restricted protein intake had a 32% lower risk of kidney death.73 These findings are particularly concerning when considering that the prevalence of chronic kidney disease is estimated to be between 8-16% with approximately 735,000 deaths attributed to chronic kidney disease worldwide in 2010 alone.74 75 Even in developed nations a significant portion of chronic kidney disease cases go undetected.76

The potential harm of animal protein on kidney function is evidently only in part explained by the high phosphorus content. For example, it has been shown in several randomized controlled trials in patients with declining kidney function that even when protein and phosphorous intake is held constant, plant protein from grain and soy has a favorable effect on phosphorus balance and other markers of kidney function compared to animal protein.77 78 Consistent with these findings the Adventist Health Study 2 found that those who adhered to a vegetarian type diet had less than half the rate of kidney death compared to those who consumed meat regularly.79

Low-carb and Paleo type diets are often advocated as a means of weight loss. However, consistent with the long-term trends in Sweden, randomized controlled trials have found that compared to diets rich in nutrient poor, low-fiber carbohydrates, carbohydrate restricted diets provide little benefit in terms of weight loss in the long-term.80 81 As it has been shown in randomized controlled trials that an increase in intake of dietary fiber has favorable effects on body weight and a number of other cardiovascular risk factors, this suggests that had these trials focused on high-fiber carbohydrate rich diets, carbohydrate restricted diets would have been less likely to have compared favorably.82 83 84 85 Recently Don Matesz published an informative critique of the Paleo diet as a measure for weight loss. Notably Matesz mentions: 

Consequently, any Paleolithic humans who engaged in nutritionally motivated hunting would have done so in order to increase their food energy intake in order to maintain or gain weight, not in order to achieve weight loss… In view of this, the "Paleo diet" theory that overfed sedentary modern humans who need to lose excess adipose should regularly eat the fatty flesh and eggs found in supermarkets because active, underfed, extremely lean prehistoric people who struggled to meet their basic kcaloric needs ate lean game flesh or eggs whenever possible lacks basic credibility. 

Considering the evidence it is not surprising that many of the prominent proponents of Low-Carb and Paleo diets who unlike Sisson have not partaken in caloric restriction have gained considerable amounts of weight while adhering to such diets. 

Recently a meta-analysis of prospective cohort studies with more than 272,000 participants found that carbohydrate restricted diets was associated with a 31% increased risk of death from any cause.86 Sub-analyses suggested that carbohydrate restricted diets based on animal protein and fat was associated with an even stronger risk of death from any cause as well as death from cardiovascular disease. This was despite the evidence that animal protein and fat was primarily compared to refined rather than high-fiber carbohydrates, and there is data from over one million people in cohort studies demonstrating that dietary fiber and whole grain intake is associated with a significantly reduced risk of death from any cause. Although this meta-analysis was based on observational evidence, the abovementioned evidence from randomized controlled trials provides confidence for the validity of these findings, as do other lines of evidence cited previously. 

Considering the lack of evidence when compared to healthy alternatives of a significant long-term favorable effect on body composition and strong evidence of harm, especially when animal sources of protein and fats are chosen, there is little rational to promote these fad diets.

Meat as a Staple in Asian Diets

Traditional Kirghiz nomadic pastoralists

The evidence that Sisson provides to suggest that traditional Asian diets were rich in meat and offal is based on his observations of Chinese, Japanese, Korean, Thai and Vietnamese restaurants and Asian supermarkets in modern day United States. However, the food balance sheets from the United Nations for the early 1960s for these nations that Sisson makes special reference to, suggest that total animal food intake only amounted to between 2.5% and 10% of total caloric intake, with offal intake being almost non-existent.87 As earlier dietary surveys, especially prior to World War II suggest that intake of animal foods was even lower, this casts significant doubt on Sisson's suggestion that animal foods traditionally contributed to a large portion of these populations diets.88 89

Perhaps if Sisson would only visit a Mongolian Barbeque restaurant he would observe a meaty diet that is not only largely comparable with his recommendations, but also with the traditional diet of the nomadic pastoralists of Mongolia, Central Asia and northern China. It has been observed however that many of these nomadic populations who subsist largely on pasture raised animal foods have high rates of obesity and cardiovascular disease, and this has been frequently associated with their meaty diets.90 91 92 Some of these observations were made at least as far back as ninety years ago.

In the 1920s, it was observed that the nomadic pastoralists of the Kirghiz and Dzungarian Steppes in Central Asia and northern China subsisted almost exclusively on enormous amounts of fermented mare’s milk and meat from pasture raised animals. Not only was a high rate of obesity observed, but also high rates of premature extensive atherosclerosis, contracted kidney, apoplexy, arcus senilis, and gout. These pastoralists were often observed to suffer from complications related to cardiovascular disease even in their early thirties. In contrast, their urban counterparts who based their diet on soup, bread, pickles, and potatoes with very little meat were observed to be slim, free of cardiovascular disease and had very good health, even into their seventies when they were still sexually active.

It was observed that in the 1960s the rates of coronary heart disease of the nomads from Xinjiang in northern China who largely subsisted on pasture raised animal foods was more than 7 times higher than that of other populations both within Xinjiang and throughout China which had a much lower intake of animal fat.93 These findings from non-industrialized populations in Asia are compatible with the observations of a high rate of cardiovascular disease among the Inuit populations whose staple is marine animals.94 In 1940, based on decades of clinical practice and his review of reports of medical officers dating all the way back to 1838, Bertelsen, who is considered the father of Greenland epidemiology stated in regards to the mortality patterns among the Greenland Inuit that:

...arteriosclerosis and degeneration of the myocardium are quite common conditions among the Inuit, in particular considering the low mean age of the population.

It is clear that these populations who traditionally subsisted predominantly on large amounts of naturally raised animal foods that the Low-Carb and Paleo proponents such as Sisson promote are not a good role model of health.

Wheat as a Staple in Asian Diets

Unleavened bread, the traditional Bedouins
predominant source of food

There had been a considerable amount of research carried out in regards to diet and the health of populations within the greater Asia region that consumed a semi-vegetarian diet based largely on wheat. Examples include the Arab Bedouins and Yemenite Jews, both of which traditionally consumed on average more than 500 grams of bread per day.95 These populations are known for their exceptionally low rates of coronary heart disease and obesity when following their traditional wheat based diet. Perhaps the largest consumers of wheat that there is considerable data available for are the Bedouins from southern Israel. The great majority of the dietary intake of the traditional Bedouins comes from wheat, typically in the form of full-grain bread, which is especially the case for the poor who eat very little else. It was estimated that the Bedouins traditionally consumed on average 750 gm, or the equivalent of 25 slices of full-grain bread per day.95

The traditional Bedouins had many dietary traits besides an extremely high intake of whole-grain wheat that are considered by advocates of Low-Carb and Paleo diets as being primary causes of obesity and the so-called ‘diseases of civilization’, including diabetes and coronary heart disease. For example sugar intake was observed to be modestly high, a trait comparable to that of the populations in Colombia, Cuba and Venezuela who have traditionally had among the highest rates of per capita sugar consumption in the world and low rates of coronary heart disease mortality.96 97 It was estimated that dietary cholesterol intake was only 53 mg/day and saturated fat was less than 3% of caloric intake, suggesting that animal foods as a whole contributed very little to the Bedouins diet. Meat was consumed only about once per month, and virtually never eaten by the poor. Similarly egg and especially fish intake was very infrequent, although animal milk is frequently consumed. Fat intake only contributed to about 11% of total caloric intake, with a relatively low intake of omega-3 fat and a high ratio of omega-6/omega-3 fat. Vitamin A intake was very low, and for the many women who virtually never exposed their skin outside, blood concentrations of vitamin D would have likely been on the low side.96

It has been documented that diabetes and heart attacks were all but entirely absent in the traditional living Bedouins which had an average serum cholesterol of 4 mmol/l (155 mg/dl), and that the great majority of the population were exceptionally lean by western standards, both in terms of weight and skin thickness.96 98 The rates of inflammatory bowel disease were also considered to be very low.99 The few Bedouins that were observed to be obese were exclusively the wealthier elderly who rarely even walked. Being a semi-nomadic population that largely relied on walking as a means of transport, exercise has been suggested as one explanation for their exceptional low rates of obesity. However, many of the women were forced to stay inside their tents all day allowing for little exercise, yet these women with almost no exceptions were slim and free of vascular disease.96 

Researchers believe that it is the Bedouins small appetite that partly contributed to their exceptional leanness.96 Considering that about 90% of caloric intake was derived from full-grain wheat suggests that the wheat consumed was not a low satiety food, nor was it fattening. This hypothesis is consistent with the findings from a recent review of 38 epidemiological studies that found suggestive evidence that whole-grain bread intake favorably influences body weight.100 Similarly, a number of controlled experiments found suggestive evidence that wheat bread assists with satiety and weight loss in low-calorie diets.101 102 103 In addition, a recent large systematic review found that whole-grain cereals and bread are associated with a significantly decreased risk of colorectal cancer, type 2 diabetes and cardiovascular disease.104

One clear downside of the Bedouins traditional diet was a very low intake of fruits and vegetables. Although an increased intake of fruits and vegetables would likely have helped to prevent a number of potential vitamin deficiencies and improved overall health, it is clear that the traditional Bedouins were very slim and had very low rates of diabetes and heart disease despite consuming a diet that Sisson considers as a primary cause of diseases of civilization. 

Sisson referred to an article from a blogger, Ned Kock who analyzed the data from the China Study II with minimal control for confounding factors and found a positive association between wheat flour intake and cardiovascular disease mortality. However, Michel Blomgren, a statistics enthusiast who conducted a much more comprehensive analysis found that intake of wheat and a number of other staple grains were associated with a decreased risk of ischemic heart disease mortality.105 The opposite was found for animal protein and both animal and vegetable fat (Fig. 2).

Figure 2. Various foods and nutrients and risk of ischemic heart disease in a multivariate regression analysis in the China Study II, ages 35-69

Although these findings may contrast the more simple analyses produced by people like Ned Kock and Denise Minger, the greater consistency with other ecological studies, as well as other lines of evidence described previously does provide some confidence for the validity of these findings.106 107 This is not to say that this analysis is without its limitations, nor to say that an analysis with a similar degree of control examining all causes of cardiovascular disease mortality would not be more informative. However, when considered together with all other lines of evidence, this suggests that a modest intake of whole-grain wheat can be part of a health promoting diet for most people. These contrasting findings may not be considered to be all that surprising when considering that animal food intake was very strongly associated with favorable socioeconomic factors, with household income explaining up to 80% of the variance of intake between counties. Such favorable socioeconomic factors were not typically enjoyed in those counties with higher intakes of wheat, which would inevitably have had an unfavorable influence on cardiovascular disease mortality.108

In the China Study, a higher wheat intake can probably be considered as a marker of a higher concentration of certain ethnic groups, such as those from Central Asia living in northern China. Without specific data on the ethnic breakdown of each county, this makes it difficult to determine how ethnicity may have impacted these findings. However, a number of studies examining people within some of the major ethnic groups living in northern China have investigated the association between dietary factors and obesity and other cardiovascular risk factors. For example, a study found that within several ethnic groups living in Xinjiang, the region with the highest average BMI in the China Study and home to a number of nomadic populations, meat intake was associated with an increased risk of obesity, consistent with studies carried out in other regions of northern China.90 109

Although it is clear that a small portion of the population, such as those with celiac disease will benefit from eliminating wheat from their diet, there is no need to resort to making up nonsense as Low-Carb and Paleo diet advocates such as Sisson and Wheat Belly author William Davis have done about whole-grain wheat being a primary cause of obesity and diseases of civilization.110 111 The idea that whole-grain wheat should be replaced with fatty meats and eggs is clearly a step in the wrong direction, and there are certainly better alternatives for people who cannot tolerate wheat.

What is the evidence?

The assertion that the populations of Eastern and Southeast Asia were traditionally slim and healthy while consuming a high carbohydrate diet is somehow a paradox suggests that populations in other parts world have not thrived on a high carbohydrate diet. Such a suggestion ignores the evidence from healthy populations all throughout the world.

As Sisson correctly pointed out, there has been a surge in the rates of obesity, diabetes and other chronic diseases in Asia in recent decades (Fig. 1). Sisson suggests that this surge could partly be explained by changes to dietary habits, but provides scant evidence to support his claims. This merits further exploration into how the trends in dietary habits may have had an impact. As the intake of not only several of the items mentioned by Sisson, but also animal foods, especially meat has increased dramatically in Eastern and Southeast Asia over the last half century, naturally emphasis on how this has impacted the health of these populations has been the focus of much research. Part II of this review will focus on the composition of traditional diets in Asia and how certain dietary and lifestyle changes may help explain this epidemic of obesity and chronic diseases sweeping across Asia.


Please post any comments in the Discussion Thread.

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.

In contrast to this conclusion, the authors of the earlier meta-analysis paper limited their review to studies that specifically addressed coronary heart disease and stroke and concluded:

Higher consumption of eggs (up to one egg per day) is not associated with increased risk of coronary heart disease or stroke. The increased risk of coronary heart disease among diabetic patients and reduced risk of hemorrhagic stroke associated with higher egg consumption in subgroup analyses warrant further studies.

The second meta-analysis paper is problematic in part because the authors failed to consider the relevant findings from dozens of rigorously controlled feeding experiments on humans and thousands of experiments on animals, including nonhuman primates that strongly support the recommendations to limit the intake of eggs and cholesterol [reviewed previously]. This paper is also problematic in part because the authors failed to consider many other relevant findings from prospective cohort studies which suggest that egg and cholesterol intake increases the risk of coronary heart disease, diabetes, heart failure, cardiovascular disease and all-cause mortality.

Firstly, the association between egg intake and the risk of cardiovascular disease is meaningless without considering suitable substitutes for eggs. As a lower intake of eggs implies a higher intake of other foods in order to maintain caloric balance, the effect that egg intake has on coronary heart disease depends on which foods eggs are substituted for. For example, data from the Nurses’ Health Study, one of the largest studies included in these meta-analyses suggested that replacing one serving of nuts, but not red meat and dairy with one serving of eggs per day is associated with a significantly increased risk of coronary heart disease.3 The authors of both meta-analyses failed to address this factor despite the fact that the importance of evaluating suitable food alternatives has been strongly emphasized by many prominent diet-heart researchers.4 The findings from these meta-analyses should therefore be interpreted with caution as eggs may have been primarily compared to processed foods and other animal foods which make up the majority of caloric intake in developed nations.4 5

Eggs, Cholesterol and Diabetics

The authors of the most recent meta-analysis paper found that among diabetics, frequent egg intake was associated with a 83% increased risk of cardiovascular disease, whereas the authors of the earlier meta-analysis paper found that frequent intake was associated with a 54% increased risk of coronary heart disease. The authors of the most recent meta-analysis paper excluded one, while the authors of the earlier meta-analysis paper excluded two additional cohort studies that found that among diabetics, high compared to low intake of eggs was associated with an approximately five-fold increased risk of cardiovascular disease.6 7 These additional studies had they been addressed by these authors would have potentially strengthened the association between egg intake and an increased risk of cardiovascular disease in diabetics.

The authors of the most recent meta-analysis found that frequent egg intake was associated with a 68% increased risk of type II diabetes, a major risk factor for cardiovascular disease. However, the authors of the earlier meta-analysis largely failed to address this evidence. A literature search I performed produced papers from 5 separate prospective cohort studies addressing egg intake and the risk of developing type II diabetes, including two additional studies that were not addressed in both meta-analyses papers.8 9 10 11 In addition, I also found one additional cohort study addressing egg intake and the risk of developing gestational diabetes.12 All except one smaller cohort found a statistically significant association after adjusting for potential confounders. These cohorts also found suggestive evidence that the increased risk persisted regardless of whether eggs were consumed in the presence of a higher or lower carbohydrate diet, and that the association was even stronger when repeated measurements of egg intake were considered.9 In addition, these cohorts also found suggestive evidence that the increased risk could partly be explained by the dietary cholesterol and protein content of eggs, and that substituting eggs with carbohydrate-rich foods, especially fiber-rich bread and cereals significantly decreases the risk of developing type II diabetes.8 9 11 12

In the one cohort that did not find a statistically significant association, average egg intake was relatively low and there was suggestive evidence of an increased risk when a follow-up measurement of egg intake was used to update exposure overtime.10 In addition to these findings, a paper from the Health Professionals Follow-Up Study also found suggestive evidence that egg intake is associated with an increased risk of type II diabetes.13 Furthermore, papers from an additional 5 cohort studies found that dietary cholesterol was associated with a significantly increased risk of developing either type II diabetes or gestational diabetes.14 15 16

Overall findings from 12 prospective cohort studies with 265,675 participants and 14,497 cases of type II diabetes and gestational diabetes strongly implies that egg and cholesterol intake are significant risk factors in the development of diabetes. In addition to the findings from cohort studies, 4 cross-sectional studies found that egg or cholesterol intake was associated with between a nearly two-fold and greater than four-fold increased risk of developing type II diabetes and gestational diabetes.12 17 18 19 Also consistent with these findings, in the Adventist Health Study 2 it was observed that vegans had a lower risk of developing type II diabetes compared to lacto-ovo vegetarians, and especially non-vegetarians.20

One cohort included in these meta-analyses that used repeated egg intake measurements to update exposure over time found that in diabetics, intake of at least 7 eggs compared to less than 1 egg per week was associated with a two-fold increased risk of all-cause mortality, whereas another cohort that did not use repeated measurements found suggestive evidence of a 30% increased risk of all-cause mortality.21 22 The authors of the first study stated:

…among male physicians with diabetes, any egg consumption is associated with a greater risk of all-cause mortality, and there was suggestive evidence for a greater risk of MI [heart attack] and stroke.

An additional study found that in diabetics, an increment of one egg per day was associated with a greater than three-fold increased risk of all-cause mortality.6

According to the International Diabetes Federation, globally approximately 183 million people, or half of those who have diabetes have not been diagnosed. Even in high-income countries about one-third of people with diabetes have not been diagnosed.23 Given this data and the data that egg and cholesterol intake is associated with a significantly increased risk of developing diabetes, and that in diabetics egg intake is associated with a significantly increased risk of coronary heart disease, cardiovascular disease and all-cause mortality, there is likely a significantly greater number of people at risk than suggested by the authors of these recent meta-analyses.

Eggs, Cholesterol and Non-Diabetics

The Nurses’ Health Study found that an increment of cholesterol equivalent to one medium size egg per day was associated with a 17% increased risk of all-cause mortality, consistent with the findings from several other studies.24 25 26 Another study included in these meta-analyses found that in non-diabetics, intake of at least 7 eggs compared to less than 1 egg per week was associated with a 22% increased risk of all-cause mortality.21 Also, another cohort from Japan found that frequent egg intake was associated with an increased risk of all-cause mortality in women, consistent with the findings from the Adventists Mortality Study.27 28 In addition, a cohort of elderly found suggestive evidence that egg intake was associated with a significantly increased risk of all-cause mortality, and that substituting eggs with fruits, vegetables and grains significantly decreases risk.29

The authors of the most recent meta-analysis paper found that in largely non-diabetic populations that frequent egg intake was associated with 19% increased risk of cardiovascular disease compared to all other sources of calories combined, which is predominantly processed foods and other animal foods. The authors of the earlier meta-analysis that did not reach this conclusion suggested that their findings are relevant for total cardiovascular disease but failed to address the findings from prospective cohort studies regarding the risk for heart failure. For example, two cohort studies which were included in the most recent meta-analyses found that intake of at least 7 eggs compared to less than 1 egg per week was associated with an approximately 30% increased risk of heart failure.30 31

Another potential important finding that has contributed to the knowledge of the dangers of eggs are the results from studies that were carried out on populations with a low habitual cholesterol intake, such as vegetarian populations. The authors of the most recent meta-analysis paper excluded one, while the authors of the earlier meta-analysis paper excluded two cohort studies that were carried out on largely vegetarian populations. Frequent consumption of eggs was associated with a more than 2.5 increased risk of fatal coronary heart disease in the Oxford Vegetarian Study and also an increased risk in females in the Adventists Mortality Study.28 32 The characteristics of the participants in these studies differ from that of most other studies, not only because of the their lower habitual intake of dietary cholesterol, but also because of their lower rates of obesity and typically healthier overall diet. Therefore separately analyzing egg intake in this subgroup of the population may be of significant importance. The authors of a paper from the Nurses’ Health Study and the Health Professionals Follow-Up Study cited in these meta-analyses described the potential importance of addressing egg intake in people with very low habitual cholesterol intake and how their study may have been inadequate to test this hypothesis: 33

One potential alternative explanation for the null finding is that background dietary cholesterol may be so high in the usual Western diet that adding somewhat more has little further effect on blood cholesterol. In a randomized trial, Sacks et al found that adding 1 egg per day to the usual diet of 17 lactovegetarians whose habitual cholesterol intake was very low (97 mg/d) significantly increased LDL cholesterol level by 12%. In our analyses, differences in non-egg cholesterol intake did not appear to be an explanation for the null association between egg consumption and risk of CHD. However, we cannot exclude the possibility that egg consumption may increase the risk among participants with very low background cholesterol intake.

As it is well documented that cholesterol intake has a much greater effect of raising serum cholesterol when baseline intake is very low, this may in part explain why egg and cholesterol intake was more strongly associated with coronary heart disease in studies on largely vegetarian populations.34 35 Another explanation for a possibly stronger association in vegetarian populations is that egg intake may have a greater effect in leaner people, and it has been well documented that vegetarians are generally leaner than their omnivorous counterparts [reviewed previously]. This hypothesis is supported by several dietary experiments which found that dietary cholesterol had a greater effect of raising serum cholesterol among leaner compared to overweight participants.36 37 This hypothesis is also supported by the findings from the Chicago Western Electric Study which found that while dietary cholesterol was associated with a significantly increased risk of coronary heart disease in lean men over and above the adverse effects it has on serum cholesterol, increased intake had little appreciable effect on men with a greater BMI and body fatness.38 Another explanation for these findings is that vegetarians may choose healthier substitutes for eggs, such as nuts which was associated with a significantly lower risk of coronary heart disease compared to eggs in the Nurses’ Health Study.3

It was found in a sub-analysis based on 4 cohorts included in the earlier meta-analyses that egg intake was associated with an 18% non-significant increased risk of fatal coronary heart disease. The addition of the mortality findings from the two largely vegetarian cohorts that were excluded from this meta-analysis would have likely strengthened this association.28 32 This suggests that similar to saturated fat intake, egg intake may increase the risk of fatal coronary heart disease more than non-fatal coronary heart disease [reviewed previously]. The lack of a significant association likely reflects the fact that eggs were not compared to healthy foods, and also likely due to misclassification of participants into ranges of usual dietary intake as the result of measurement error [reviewed previously].

In the video below Dr. Michael Gregor addresses recent research on choline when consumed from eggs and other animal foods and the risk of cardiovascular disease and cancer.

Carnitine, Choline, Cancer and Cholesterol: The TMAO Connection

Egg Intake and Stroke

In regards to a sub-group analysis of 5 cohort studies, the authors of the earlier meta-analysis suggested that egg intake was associated with a lower risk of hemorrhagic stroke. The authors suggested that the inverse association between egg intake and hemorrhagic stroke is supported by findings of an inverse association between serum cholesterol and hemorrhagic stroke in several cohort studies. However, in the largest cohort study the authors cited, the inverse association was confined to participants with elevated blood pressure.39 A similar interaction between blood pressure and serum cholesterol and hemorrhagic stroke was observed in much larger cohort studies in both Asian and Western populations that the authors of this meta-analysis conveniently failed to cite.40 41 In a meta-analysis of 61 cohort studies it was found that among participants with near optimal systolic blood pressure (<125 mmHg), lower serum cholesterol was actually associated with a significantly lower risk of hemorrhagic, ischemic and total stroke mortality [reviewed previously]. Furthermore, most mammalian species have very low LDL levels (mean value of 42 mg/dl in 18 species), and there is very scant evidence that these animals are at high risk of having a stroke.42

This data demonstrates that continued emphasis should be placed on lowering both LDL cholesterol and blood pressure which have been proven in hundreds of randomized controlled trials to lower not only the risk of cardiovascular disease, but also all-cause mortality.43 44 Increasing the intake of eggs after achieving a near optimal blood pressure is unlikely to reduce the risk of hemorrhagic stroke and will likely increase the risk of dying of any cause.

Unwarranted Mediocre Health Recommendations

The conclusions of the earlier meta-analysis are misleading and inconsistent with the body of literature. What is more concerning is that these findings will likely be used in marketing campaigns to confuse the general population, of which the great majority are already at risk of cardiovascular disease. The most recent meta-analysis paper while being overall informative and more clearly demonstrating the dangers of eggs for both diabetics and non-diabetics, the authors still failed to address many important findings that have been addressed in this series of posts. A greater emphasis on the effects of replacing eggs with other suitable foods is required, and the available evidence suggests a significant benefit of replacing eggs with whole plant foods, including fruits, vegetables, whole grains and nuts.3 11 29 As Spence and colleagues pointed out in regards to recent controversy surrounding dietary cholesterol and eggs:45

…the only ones who could eat egg yolk regularly with impunity would be those who expect to die prematurely from nonvascular causes.

Diet-Heart Posts

Part I - Diet-Heart: A Problematic Revisit
Part II - Diet-Heart: Saturated Fat and Blood Cholesterol
Part III - Diet-Heart: The Role of Vegetarian Diets in the Hypothesis
Part IV - Cracking Down on Eggs and Cholesterol

Please post any comments in the Discussion Thread.

Neuronal Control of Appetite, Metabolism and Weight

Last week, I attended a Keystone conference, "Neuronal Control of Appetite, Metabolism and Weight", in Banff.  Keystone conferences are small, focused meetings that tend to attract high quality science.  This particular conference centered around my own professional research interests, and it was incredibly informative.  This post is a summary of some of the most salient points.

Rapid Pace of Scientific Progress

Read more »

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.

This review will focus on the evidence from randomized controlled trials and long-term prospective cohort studies addressing the influence of vegetarian dietary patterns on the risk of coronary heart disease, and how these findings have contributed to the current understanding of the diet-heart hypothesis. This review will also consider the question as to whether the simple definition of a vegetarian diet is meaningful in the context of a healthy diet to reduce the risk of coronary heart disease. Regarding cohort studies, this review will primarily consider the influence of lacto-ovo vegetarian diets on the risk of coronary heart disease due to limited evidence from these studies addressing the long-term adherence to other types of vegetarian diets. A more informative analysis maybe possible after a longer follow-up of the on-going and largest cohort of vegetarians, the Adventist Health Study 2, which has observed more favorable cardiovascular risk factors within different vegetarian subgroups, particularly vegans.3

Skeptics of the diet-heart hypothesis often suggest that there are no plausible mechanisms in which a vegetarian dietary pattern can lower the risk of coronary heart disease, and often ascribe the observed benefits of vegetarianism to factors other than the avoidance of animal foods. Typically either ignored or downplayed by these skeptics is the convincing evidence that vegetarian dietary patterns can lower LDL cholesterol, which is an established risk factor for coronary heart disease.4 5 6

Establishing Causation

In the 6 cohorts described, a sizable portion of the non-vegetarians consumed significantly less meat than the general population. For example, in the EPIC-Oxford cohort, most participants were either occasional meat eaters, or affiliated with vegetarians or with vegetarian societies. Also, a potential problem in these cohorts is that measurement error of usual dietary intake of meat may have resulted in misclassifying a sizable portion of non-vegetarians as vegetarians. For example, in the Health Food Shoppers Study included among these cohorts, a validity assessment of the survey used to classify the participants vegetarian status suggested that 34% of the participants classified as vegetarians actually consumed meat. This data strongly suggests a much smaller than otherwise expected difference in dietary intake between the groups classified as vegetarians and non-vegetarians, potentially masking a stronger protective effect of a vegetarian dietary pattern.7

Another potential problem in these cohorts is the possibility that a sizable portion of participants classified as vegetarians stopped consuming meat or other animal foods in response to deteriorating health or unfavorable risk factors that would ultimately become life-threatening. This has been referred to as the ‘sick quitter effect’, which is known to mask the protective effect of smoking cessation in studies due to participants quitting in response to deteriorating health.8 In regards to diet, it has been documented that people tend to lower intake of saturated fat and cholesterol in response to unfavorable serum cholesterol levels, which has actually been shown to bias the association between diet and serum cholesterol in the opposite direction than expected [reviewed previously]. This bias is known as reverse causation, and may explain why in the Adventist studies that participants with short-term adherence (less than 5 years) to a vegetarian diet experienced an increased risk of mortality, while participants with long-term adherence (more than 17 years) to a vegetarian diet experienced a significantly lower risk of mortality compared to non-vegetarians (Fig. 1).8

Figure 1. Life expediencies for long-term vegetarians and short-term vegetarians in the Adventist Health Study and Adventist Mortality Study*

These factors should be taken into account when testing for causality as failing to do so may mask a protective effect of a vegetarian dietary pattern. One of the most important factors in order to establish causality is to address whether the association is biologically plausible, which in this case requires examining how vegetarian dietary patterns can influence cardiovascular risk factors.

Serum Lipids

In 1922, de Langen published what was perhaps the first study that provided strong evidence that a vegetarian dietary pattern favorably effects serum cholesterol when he placed five native Indonesians consuming a rice-based vegetarian diet into a metabolic ward and shifted the diet to one rich in meat, butter and egg fats, resulting in significant elevations in serum cholesterol [reviewed previously]. In 1954, Hardinge and Stare published what was perhaps the first observational study comparing the serum lipids of vegetarians to non-vegetarians in an affluent population. Lacto-ovo vegetarians and especially vegans had significantly lower serum cholesterol concentrations despite relatively high intakes of saturated fat.9 10 In 2009, Ferdowsian and Barnard published a systematic review of 27 randomized controlled trials and observational studies on either vegetarian or predominantly plant-based diets, and found that certain plant-based dietary patterns can lower LDL cholesterol by up to 35%, independent of changes to body weight (Figs 2, 3).4

Figure 2. Effects of plant-based diets in normolipidemic individuals: Randomized controlled trials*

Figure 3. Effects of plant-based diets in hyperlipidemic individuals: randomized controlled trials*

In the Lifestyle Heart Trial lead by Dr. Dean Ornish, intensive lifestyle changes including a vegetarian diet that allowed a small amount of non-fat dairy foods successfully reduced LDL by 37.2%, angina episodes by 91% and regressed coronary atherosclerosis in the experimental group after 1 year. In both the experimental and control group LDL and total cholesterol was correlated with changes in coronary atherosclerosis.11 

A recent meta-analysis of statin based randomized controlled trials found that lowering LDL cholesterol to less than 100 mg/dl was associated with regression of coronary atherosclerosis in participants with coronary heart disease.12 Similarly, a recent mendelian randomization study of over 100,000 individuals found that genetically-predicted higher LDL cholesterol was associated with greater carotid atherosclerosis, but there was no causal association for HDL cholesterol and triglycerides.13 Consistent with these lines of evidence, it has been consistently demonstrated in experiments on non-human primates that coronary atherosclerosis induced by feeding of dietary cholesterol and saturated fat can be reversed by a cholesterol lowering diet [reviewed previously]. Therefore the preponderance of evidence strongly suggests that the findings from the Lifestyle Heart Trial of a correlation between lower LDL cholesterol and regression of coronary atherosclerosis was causal, and can at least partly be explained by the intervention of a cholesterol lowering vegetarian diet. 

In the meta-analysis of 5 cohorts it was found that in a sample of participants from 3 of the cohorts that serum cholesterol ranged from between 13 mg/dl to 23 mg/dl lower in the vegetarians compared to non-vegetarians. The researchers suggested that the difference in serum cholesterol could have largely explained the difference in fatal coronary heart disease between these groups.2 In the EPIC-Oxford cohort, serum lipids and blood cholesterol were measured in a sample of the participants. Non-HDL cholesterol was 17 mg/dl lower and systolic blood pressure was 3.3 mmHg lower in the vegetarians compared to the non-vegetarians. The researchers calculated that the differences between these two risk factors alone would expect to lower the risk of coronary heart disease by 24%, which is less than the observed 32% lower risk.1 

The researchers from the EPIC-Oxford cohort suggested that the high ratio of polyunsaturated fat to saturated fat largely explained the difference in non-HDL cholesterol between groups, but failed to mention that a number of other plant based nutrients may have also contributed to this difference.1 It has been repeatedly demonstrated in randomized controlled trials that intake of plant protein, particularly from soy, plant sterols, and dietary fiber can also lower LDL cholesterol.14 15 16 In fact in many of the interventions with the greatest diet induced decrease in LDL cholesterol, the decrease could not be explained by changes in dietary fat and cholesterol intake alone, but also likely due to the additive effects of a number of plant based nutrients.17 18 19

It is clear that the LDL cholesterol levels of the vegetarians in these cohort studies far exceeded optimal levels, likely due to a diet deficient in whole plant foods and still relatively rich in animal foods. If these vegetarians had adhered to a much more phytonutrient rich cholesterol lowering diet such as that used in the aggressive dietary experiments, an even significantly lower risk of coronary heart disease may have been observed. Plant Positive recently referred to this informative statement made by Michael Brown and Joseph Goldstein the year before they were awarded the Nobel Prize for their research on the LDL-receptor:20

If the LDL-receptor hypothesis is correct, the human receptor system is designed to function in the presence of an exceedingly low LDL level. The kind of diet necessary to maintain such a level would be markedly different from the customary diet in Western industrial countries (and much more stringent than moderate low-cholesterol diets of the kind recommended by the American Heart Association). It would call for the total elimination of dairy products as well as eggs, and for a severely limited intake of meat and other sources of saturated fat.

Evidence from over one hundred randomized controlled trials has proven beyond plausible doubt that changing from a diet rich in animal foods to a dieter richer in certain whole plant foods significantly lowers LDL cholesterol.4 14 15 16 21 22 Similarly, evidence from over one hundred randomized controlled trials has proven beyond plausible doubt that lowering LDL cholesterol decreases the risk of coronary heart disease and all-cause mortality.5 6 Therefore consistent with the diet-heart hypothesis, there is convincing evidence that an appropriately designed vegetarian diet would reduce the risk of coronary heart disease, and that this reduction can at least be partly explained by lower LDL cholesterol.

Beyond Cholesterol

There are likely a number of dietary related factors that contribute to the lower risk of coronary heart disease observed in people with vegetarian dietary patterns that cannot entirely be explained by lower LDL cholesterol. For example, it has been shown in randomized controlled trials that a number of plant based nutrients can lower blood pressure, which may explain the lower blood pressure observed in vegetarians in a number of observation and intervention studies [reviewed previously]. Furthermore, appropriately designed vegetarian diets likely reduce the risk of being overweight and developing type II diabetes.23 24 25 26 27 Other factors such as reduced oxidation of LDL and changes in blood clotting have also been suggested as explanations for the lower risk of coronary heart disease observed in vegetarians.28 29

Perhaps the main concern with an inappropriately designed vegetarian diet is that it may result in elevated homocysteine due to an inadequate intake of vitamin B12, suggested to be a risk factor for coronary heart disease. Although deficiency of vitamin B12 is rarely observed in some populations in the developed world consuming a predominantly plant based diet, perhaps due to regular contact with vitamin B12 producing bacteria, health authorities strongly recommended that vegetarians diets be supplemented regularly with a bioavailable source of vitamin B12.30 31 Jack Norris, RD regularly posts informative reviews on the latest research on vitamin B12 intake and homocysteine, and updates his recommendations for vitamin B12 supplementation in response to new findings.

In all of the cohort studies, and perhaps most intervention studies carried out on vegetarians, there is little doubt that only very few vegetarians were actually consuming a diet predominantly based on whole plant foods, and as expected although these vegetarians experienced a significantly lower risk of coronary heart disease than their omnivorous counterparts, they still experienced a substantial residual risk of coronary heart disease.32 In Dr. Caldwell Esselstyn’s more recent decade long study (pending publication) of around 200 patients that were advised to consume a whole foods, plant-based diet, it was found that recurrent cardiac events only occurred in 0.5% of adherent participants. This is an approximately 40 fold lower risk than achieved in other dietary or statin based trials, strongly suggesting that these results can only partially be explained by the use of LDL cholesterol lowering medication [reviewed previously]. This is an excellent example of how a whole foods, plant-based diet can confer significant benefit over-and-above favorable changes to traditional risk factors.

Caldwell Esselstyn on making heart attacks history

The definition of a vegetarian diet typically only defines which type of animal foods are restricted and not the quantity and quality of plant foods consumed. As all vegetarian diets are not created equal, studies on vegetarians may only provide limited information of the influence a more nutrient dense vegetarian dietary pattern on the risk of coronary heart disease.33 The restriction of certain animal foods however may encourage at least a modest increase of intake of high quality plant matter, including fruits, vegetables, whole grains, legumes and nuts in order to make up for calories and certain nutrients otherwise consumed from animal foods. Nevertheless, even the studies examining less than optimal vegetarian diets may contribute more to the knowledge of optimal dietary patterns than many studies on homogenous populations due to greater differences in intake of specific foods and nutrients. Vegetarian diets should be designed according to not only which animal foods are restrict, but also the quality of plant foods consumed in order to minimize and preferably eliminate the risk of developing coronary heart disease. There is very strong evidence that such a diet would also lower the risk of numerous other chronic and degenerative diseases.

Diet-Heart Posts

Part I - Diet-Heart: A Problematic Revisit
Part II - Diet-Heart: Saturated Fat and Blood Cholesterol
Part IV - Cracking Down on Eggs and Cholesterol
Part V - Cracking Down on Eggs and Cholesterol: Part II

Please post any comments in the Discussion Thread.