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.

Debate with Dr. Colin Campbell in The Wall Street Journal

Dr. T. Colin Campbell

A recent article in The Wall Street Journal, titled Would We Be Healthier With a Vegan Diet?, featured Dr. Colin Campbell explaining the health benefits of a plant-based diet and the supporting science, with an opposing view given by Dr. Nanacy Rodriguez, a researcher who's profile shows an extensive list of grants from the livestock industry.1

Dr. Rodriguez’s opposing view raises considerable concerns as her statements are compromised by a number of serious methodological issues and relies largely on inaccurate stereotypes, stereotypes scripted and promoted by lobbying efforts of the livestock industry that promote fear of removing animal products from the diet.

Laboratory Experiments and the Promotion of Cancer

Dr. Nancy Rodriguez

Dr. Rodriguez questioned whether the cancer promoting effects of casein observed in Dr. Campbell’s laboratory can be extrapolated to other animal proteins, but provided scant evidence to the contrary. This resembles the misleading claims of the cholesterol sketpics, including Denise Minger that have been discussed in detail here.

It is well documented that dietary restriction of methionine significantly increases both the mean and maximum lifespan in the rodent model.2 3 Dietary restriction of methionine has also been shown to inhibit and even reverse human tumor growth in animal models and in culture demonstrating that tumors are methionine dependent, yet is relatively well tolerated by normal tissue.4

Compared to whole plant foods, both methionine content and bioavailability is significantly higher in most protein rich animal based foods, with little overlap.3 In addition plant foods contain thousands of phytonutrients which work together to protect against cancer. For example, studies have found that casein is still far more cancer promoting compared to soy protein even when both the diets were formulated to contain equivalent amounts methionine (Fig. 1). This was attributed largely to the difference in content of a number of protective phytonutrients.5

Figure 1. Total number (A) and total weight (B) of mammory tumors in rats, 25 weeks after N-nitrosomethylurea injection. Diet Groups: Casein, 20% casein; SPI, 19% soy protein isolate; SPI +Met., 19% soy protein isolate formulated to contain the equivalent amount of methionine as the casein group.

Due to the high content and bioavailability of methionine and lack of phytonutrients in other animal proteins, the observed cancer promoting effects of casein will therefore largely apply to other animal proteins. Furthermore, Dr. Rodriguez’s statement 'Casein is one of many proteins found in milk' made in an apparent attempt to disassociate milk protein from casein can be considered misleading when taking into account that casein makes up approximately 80% of the protein in bovine milk.6

Findings from Clinical Trials

The consensus that a number of dangerous substances including cigarette smoke promote cancer is purely based off epidemiologic, metabolic and laboratory studies. Therefore there is little justification for Dr. Rodriguez to claim as she did that a number of risk factors that have not been tested in clinical trials such as smoking play a significant role in the cause of cancer, but at the same time neglect evidence regarding replacing meat and dairy with whole plant foods and a decreased risk of cancer purely because of a lack of clinical trials.

A number of randomized controlled trials have actually demonstrated the damaging effects of animal protein in human cancers. For example, a randomized, placebo-controlled trial found that among men at high risk, those supplementing with milk protein were more than six times likely to develop prostate cancer compared to men supplementing with soy protein.7

A number of tightly controlled feeding trials with human participants have established that heme iron from the protein portion of meat increases the production of NOCs (N-nitroso compounds) in the digestive tract to concentrations similar to that found in cigarette smoke, of which most are cancerous.8 Furthermore, a controlled feeding trial found that NOCs arising from heme iron in meat forms DNA adducts in the human digestive tract, and DNA adducts are a well-established marker of cancer.9 These findings are consistent with recent meta-analyses of prospective studies that found that intake of both fresh red meat and heme from meat is associated with a significant increased risk of colorectal cancer.8 10

Based partly on these lines of evidence, in 2011 the expert panel from the World Cancer Research Fund reviewed over 1,000 publications on colorectal cancer and concluded that there is convincing evidence that both fresh and processed red meats are a cause of colorectal cancer.11 Furthermore, a more recent prospective study with over 2.24 million men and women found that compared to participants who consumed less than 1 serving per week, consuming 2 or more servings of meat significantly increased the risk of colorectal cancer.12

There is much controversy regarding the 'Dozens of randomized, controlled, clinical trials' that Dr. Roriguez’s appears to be referring to claiming that 'demonstrated that calcium and dairy products contribute to stronger bones'. For example the Harvard School of Public Health have asserted that:13

...the maximum-calcium-retention studies are short term and therefore have important limitations. To detect how the body adapts to different calcium intakes over a long period of time—and to get the big picture of overall bone strength—requires studies of longer duration.

Walter Willett, the Chair of the Department of Nutrition, Harvard is well known for criticizing the industries unfounded claims about the health properties of dairy. In regards to the 2010 USDA Dietary Guidelines he stated that:14

The guidelines continue to recommend three daily servings of dairy products, despite a lack of evidence that dairy intake protects against bone fractures and probable or possible links to prostate and ovarian cancers.

Willett nevertheless praised parts of the guidelines, stating that:

The guidelines appropriately emphasize eating more vegetables, beans, fruits, whole grains, and nuts and highlight healthful plant-based eating patterns, including vegetarian and vegan diets.

Dr. Rodriguez suggested that 'The Dietary Guidelines are founded on evidence-based, peer-reviewed scientific literature, and take into account the entire body of research, not just a single study', and that therefore her dietary recommendations are justified. However, evidence to the contrary was made clear in the report of the Dietary Guidelines Advisory Committee on the Dietary Guidelines for Americans, 2010 that stated 'The DGAC did not evaluate the components of processed meats that are associated with increased risk of colorectal cancer and cardiovascular disease.'15 Thus the Dietary Guidelines did not sufficiently 'take into account the entire body of research', one of the reasons the guidelines have been scrutinized by the Harvard School of Public Health.13

Nutrient Density of Plant vs. Animal Foods

In regards to 'calorie efficiency', the most nutrient dense foods are dark green leafy vegetables which are leaps and bounds more nutrient dense than the phytonutrient and dietary deficient animal foods Dr. Rodriguez advocates, while also being dense in protein, calcium, iron and zinc.16 In fact, calcium from a number of dark green leafy vegetables is actually much more easily absorbed than that from bovine milk.17 In regards to protein intake, a meta-analysis of nitrogen balance studies found that the estimated requirements in healthy adults for the median and 97.5th percentile are 0.65 and 0.83 grams of protein per kg of body weight respectively,18 amounts easily obtained from plant-based dietary plans formulated by Dr. Campbell and his colleagues.19 Furthermore, there is little justification for Dr. Rodriguez as she has done to advocate dairy on the basis that it is artificially fortified with Vitamin D while at the same time downplaying the nutrient density of plant-based foods due to a lack of certain nutrients such as Vitamin B12 and Vitamin D that can be easily supplemented in plant-based diets.

In regards to lean animal protein, the 95% lean beef that Dr. Rodriguez promotes actually contains a similar amount of dietary cholesterol as that found in similar cuts of full-fat beef.16 Experiments on non-human primates have demonstrated that intake of even small amounts of dietary cholesterol as low as 43µg/kcal, the equivalent found in only half of a small egg in a human diet of 2,000 kcal induces atherosclerotic lesions. Furthermore, there was no evidence of a threshold for dietary cholesterol with respect to an adverse effect on arteries (Figs. 2, 3).20 21 Furthermore, several major prospective studies on humans found that dietary cholesterol was associated with a significant increased risk of all-cause mortality.22 23 24

Figure 2. Subclavian artery from a Rhesus monkey supplementing 43µg/kcal dietary cholesterol. Sudanophilia (black area) is intense in the area of major intimal thickening.

Figure 3. Fermoral artery from a Rhesus monkey supplementing 43µg/kcal dietary cholesterol. Intimal fibrous thickening and disruption of internal elastic membrane differentiate this artery from control vessels of monkeys supplementing 0 dietary cholesterol.   

Conflicts of Interest

Finally, Dr. Rodriguez’s financial tie to the livestock industry may explain why she appears to have misinterpreted the medical literature in regards to the disease promoting effects of animal foods and the nutrient density of plant-based foods, written in a largely textbook manner used by other livestock industry lobbyists. The tactics of the livestock industry may resemble those used by the tobacco industry that misinterpreted the medical literature in the past in order to dismiss the 'junk' science linking smoking to lung cancer and other associated diseases. Brownell et al. reminds us of how serious and real conflicts of interests can really be:25

A striking event occurred in 1994 when the CEOs of every major tobacco company in America stood before Congress and, under oath, denied believing that smoking caused lung cancer and that nicotine was addictive, despite countless studies (some by their own scientists) showing the opposite.

Perhaps the same can be said for Dr. Rodriguez’s claim that 'It is simply untrue to suggest that animal protein causes cancer', which is clearly in discordance with the preponderance of evidence. It maybe largely explained by socioeconomic factors as to why health authorities are unable to reach similar dietary recommendations as Dr. Campbell and his colleagues. For example, Eric Rimm from the Department of Nutrition, Harvard said to Reuters in regards to a major health report produced by the National Academy of Science, which he was an author of that:

We can’t tell people to stop eating all meat and all dairy produces. Well, we could tell people to become vegetarians... If we were truly basing this on science we would, but it is a bit extreme.

As Dr. Rodiguesz’s herself stated, 'appreciating the science behind nutrition helps us make smart choices about the best way to feed ourselves and the world'. Unfortunately her scare tactics illustrated in The Wall Street Journal demonstrated very little appreciation of the preponderance of scientific evidence.

Please post any comments in the Discussion Thread. 

Forks Over Knives and Healthy Longevity: A Missed Opportunity for the Cholesterol Skeptics

This is the first part of a series of posts that addresses the science regarding plant based diets and the documentary Forks Over Knives and the very serious inaccuracies and omissions that compromise the critiques authored by the cholesterol skeptics, in particular Denise Minger. 

Food Shortages, Cardiovascular Disease and All-Cause Mortality in the World Wars

In Forks Over Knives, Dr. Caldwell Esselstyn described the classical findings from a paper authored by Strom and Jensen, who observed that in Norway between 1938 and 1948 there was a strong relationship between cardiovascular mortality and changes in intake of fat in the form of butter, milk, cheese and eggs, with the changes in mortality lagging behind dietary changes by approximately one year (Fig. 1).1 Denise Minger not only ignored these findings in her critique despite citing the mortality data from the same paper, but instead claimed in regards to a paper on rationing in Norway that animal foods did not decline until after cardiovascular disease mortality had already started declining.2 Minger misleads her readers by confusing the period when rationing was introduced with the period when the intake of animal foods declined. It can be deduced from the data from the Ministry of Supplies cited by Strom and Jensen that rationing was introduced as a result of a declining availability of such products, and therefore introduced after the intake of animal foods had already declined.1

Figure 1. Mortality from circulatory disease, correlated for age; consumption of fat in form of butter, milk, cheese and eggs, Norway 1938-48

Minger also misleads her readers into believing that there was almost an inverse relationship between the changes in animal protein intake and cardiovascular disease mortality in Norway during World War II by inaccurately reporting animal protein intake for the periods of 1936-37 and 1945. In order to verify Minger's interpretation of the statistics (Fig.3), please refer to the table below of macronutrient intake not present in Minger's post (Table 1), as well as the graph illustrating cardiovascular mortality rates (Fig. 2).1 2 In Minger’s own words, 'I pity da fool who doesn’t enlarge this image.'

Table 1. Macronutrient and micronutrient intake for Oslo men from 50 families, 1936-45 

Figure 2. Mortality from circulatory diseases, Norway 1927-48 

Figure 3. Denise Minger’s inaccurate interpretation of the Norwegian statistics 

Minger even posted a 'Fake Correlated Variable' graph, in an apparent attempt to ridicule Dr. Esselstyn, stating that 'For comparison’s sake, this is what a graph would look like if these variables were tightly linked'. Interestingly the 'Fake Correlated Variable' graph was actually remarkably consistent with the actual data (Figs. 4, 5).

Figure 4. Denise Minger’s 'Fake Correlated Variable' graph 

Figure 5. Actual animal protein intake and age-corrected circulatory disease mortality from the cited papers

In Minger’s critique she conveniently omitted the table from this study detailing animal protein intake despite posting the table of intake of individual food groups, and also failed to provide a free link to the paper claiming that she ‘couldn’t find any free copies to link’ despite one being easily locatable by googling the title of the paper, "Food Conditions in Norway during the War, 1939-45". These facts raise very serious questions as to whether Minger's inaccurate report of the data that appears to be heavily biased in favor of an agenda to promote animal foods was in fact intentional.

Minger also claimed that cardiovascular health did not actually improve in Norway during the war years, and that the decrease in cardiovascular mortality was obscured by an increase in mortality from infectious diseases. Minger appears to be either ignorant or unaware that Strom and Jensen provided additional data demonstrating that from over 15,000 operations carried out in Norway that were complicated by danger of thrombosis, the same surgeons found that the occurrence of these complications declined significantly during the period of deprivation of foods rich in animal fats, which then sharply increased after the resumption of intake.3 4 These findings provided strong evidence of actual improved cardiovascular health in Norway during the period of deprivation of animal foods. In Sweden where mortality from infectious diseases actually decreased during the war, there was a record decline in both cardiovascular disease and all-cause mortality during the war years when animal food intake decreased (Fig. 6).2 5 Other researchers also observed a striking decline in advanced atherosclerosis in Finland and Western Germany during the periods of deprivation of animal foods that returned to near pre-war levels after increasing intake.4 6

Figure 6. Percentage of energy from animal foods and mortality from arteriosclerosis and all-causes, Sweden 1940-1944

These observations from the World Wars are unlikely coincidental as they are consistent with the significant decline in serum cholesterol, and mortality from cardiovascular disease and all-causes in former communist nations of Eastern Europe, beginning in the early 1990's when the communist subsidies on meat and animal fats were abolished after the breakup of the Soviet Union (Fig. 7).7 8 Likewise, the significant decline in serum cholesterol, and mortality from cardiovascular disease and all-causes in the pre and early statin period of the second half of the century in developed nations throughout Western Europe, North America and Australasia is partly explained as a result of successful government policies that emphasized dietary changes, particularly a decreased intake of saturated animal fat. One of the best examples is Finland which experienced the most rapid decline of coronary mortality in the world, which was predominantly explained by a significant decline in serum cholesterol as the result of a large reduction in saturated animal fat and an increase in fruit and vegetable intake (Figs. 8, 9).9 10 

Figure 7. Trends in mortality from heart disease in former communist and western nations in men age ≤64

Figure 8. Observed and predicted declines in coronary mortality in males in Eastern Finland 

Figure 9. Observed and predicted decline in serum cholesterol based on dietary changes in Finish men and women without lipid-lowering medication (1, PUFA; 2, dietary cholesterol; 3, SFA; 4, PUFA + dietary cholesterol + SFA; 5, PUFA + dietary cholesterol + SFA + trans fatty acids; 6, observed serum cholesterol)

Randomized controlled trials provide further evidence of a causal association. A meta-analysis of 395 controlled feeding trials established that dietary cholesterol and isocaloric replacement of complex carbohydrates and unsaturated fat by saturated fat raises LDL and total cholesterol.11 In addition a meta-analysis of 108 randomized controlled trials of  various medical and dietary based lipid modifying interventions found that lowering LDL cholesterol significantly decreased the risk of coronary heart disease and all-cause mortality, while modifying HDL or triglycerides provided no clear benefit after controlling for LDL cholesterol.12

Not only does it appear that Denise Minger resorted to distorting the Norwegian data, she was even spineless enough to refer to the number of lives saved from cardiovascular mortality in Norway as being 'nothing to sneeze at' in an apparent attempt to downplay the importance of saving thousands of lives.

Dr. Caldwell Esselstyn and Treating the Cause of CAD

In regards to Dr. Esselstyn’s study of his initial coronary artery disease patients, Denise Minger misleads her readers into believing that 'half' the patients dropped out of the study by confusing the number of patients who had a follow-up angiogram with the number of adherent patients, simply ignoring the 7 patients who adhered to the diet but did not have a follow-up angiogram. There was actually a 75% adherence rate throughout most of this study, and in the more recent and larger decade long study of over 200 patients (known as Treating the Cause of CAD), there was an adherence rate of 91% (Vid. 1).13 14

Minger also suggested that Dr. Esselstyn’s results may have been due to luck as his study was an uncontrolled intervention study. Dr. Esselstyn however did compare the adherent and non-adherent patients. Despite having similar measurable amounts of disease at baseline as the other 18 patients, the 6 non-adherent patients had 13 new cardiac events within the first 12 years of the study despite the fact that they were still receiving standard care. On the other hand, the 18 compliant participants had no further cardiac events while being fully compliant, despite having 49 events during the 8 years prior to the study, of for which most of this time were receiving standard care.13 14 In the newer decade long study of over 200 patients, recurrent cardiac events only occurred in 0.5% of adherent participants, which is approximately 40 fold lower than other dietary or statin based trials (Vid. 1). Minger suggests that these results were due to luck but provided no evidence demonstrating that coronary artery disease can be spontaneously halted or reversed this frequently even when years of medical intervention have failed.

Video 1. TEDxCambridge - Caldwell Esselstyn on making heart attacks history

Dietary Cholesterol, Cardiovascular Disease and All-Cause Mortality

In regards to the information in Forks Over Knives about the disease promoting effects of dietary cholesterol, Denise Minger claimed that one of the reasons the consensus of the medical community that dietary cholesterol raises serum cholesterol and is unhealthy is due to experiments performed on ‘obligate herbivores’, primarily being ‘rabbits’. Minger is ignorant of the fact that literally hundreds of experiments on numerous different omnivorous species, the most relevant being non-human primates have demonstrated that dietary cholesterol has unfavorable effects on serum lipids and induces atherosclerotic lesions.15 Experiments on non-human primates have demonstrated that intake of even small amounts of dietary cholesterol as low as 43µg/kcal, the equivalent found in only half of a small egg in a human diet of 2,000 kcal induces atherosclerotic lesions. Furthermore, there was no evidence of a threshold for dietary cholesterol with respect to an adverse effect on arteries (Figs. 10, 11).16 [Click here for more information regarding study 16]

Figure 10. Subclavian artery from a Rhesus monkey supplementing 43µg/kcal dietary cholesterol. Sudanophilia (black area) is intense in the area of major intimal thickening.

Figure 11. Fermoral artery from a Rhesus monkey supplementing 43µg/kcal dietary cholesterol. Intimal fibrous thickening and disruption of internal elastic membrane differentiate this artery from control vessels of monkeys supplementing 0 dietary cholesterol.   

Minger also failed to mention that several large forward-looking prospective studies on humans found that dietary cholesterol was associated with a significantly increased risk of all-cause mortality, and that it has been consistently shown in studies on diabetic participants that intake of dietary cholesterol and eggs significantly increased the risk of cardiovascular disease and all-cause mortality.17 18 19 20 21 22

Protein Restriction and Healthy Longevity

Denise Minger suggested in regards to the original Indian study cited by Dr. Colin Campbell that in the presence of aflatoxins rats on low protein compared to high protein diets experience an increased risk of premature death. Minger appears to be ignorant in light of the fact that in the majority of studies on rats, especially those that have not been complicated by the administration of large doses carcinogens, protein restriction actually significantly increased maximum lifespan. For example, a review found that in 16 out of 18 studies protein restriction increased average maximum lifespan by approximately 20%, independent of caloric restriction.23 As for carbohydrate intake, increased intake has either been associated with no change or increased longevity.23 The association between protein restriction and longevity has been primarily attributed to methionine restriction, which has shown to increase both mean and maximum lifespan in rodents by on average up to 40%.23 24

Dietary restriction of methionine has also been shown to inhibit and even reverse human tumor growth in animal models and in culture demonstrating that tumors are methionine dependent, yet is relatively well tolerated by normal tissue.25 A review found that the benefit of replacing casein with soy protein on tumor suppression in the animal model was explained in part by the lower quantity of methionine and in part by numerous beneficial plant based compounds.26 For the sake of comparing 'apples and apples' as Minger put it, studies have found that casein is still far more cancer promoting compared to soy protein even when the casein and soy protein diets were formulated to contain equivalent amounts of the 'limiting amino acid' methionine (Fig. 12).26

Figure 12. Total number (A) and total weight (B) of mammory tumors in rats, 25 weeks after N-nitrosomethylurea injection. Diet Groups: Casein, 20% casein; SPI, 19% soy protein isolate; SPI +Met., 19% soy protein isolate formulated to contain the equivalent amount of methionine as the casein group

Compared to whole plant foods, both methionine content and bioavailability is significantly higher in most protein rich animal based foods, with little overlap.24 Therefore protein combining of unrefined plant foods will result in a quality sufficient to support normal tissue, but not the quality found in animal foods that promote cancer and premature death. These rodent studies are consistent with a number of prospective studies on humans that found that diets higher in protein and often fat, primarily of animal origin at the expense of vegetable protein or carbohydrates are associated with an increased risk of all-cause mortality.27 28 29 30

Minger suggested in regards to a study on non-human primates that in the presence of lower amounts of aflatoxins, higher compared to lower intakes of casein do not promote tumor growth. These findings are in disagreement with other studies that administered low amounts of aflatoxin cited by Dr. Campbell that Minger apparently ignored.31 However, the study on non-human primates did not test intermediate levels of protein intake or specific amino acids such as methionine, and Minger failed to cite any studies comparing casein with plant protein, therefore not allowing for a clear interpretation of these results. In studies on non-human primates, compared to casein, soy protein not only leads to genetic changes that are associated with a decreased risk of cancer, but also improvements in body weight, insulin sensitivity, lipid profile, and even decreases atherosclerosis plaques by on average up to 90% (Fig. 13).32 33 34 35

Figure 13. a, Proportion of each group of Cynomolgus monkeys with CAA plaques, defined as intimal thickness greater than half the medial thickness. b, Average lesion size for those monkeys with atherosclerotic plaques. Soy(-), Soy protein with phytoestrogens mostly extracted. Soy(+), Soy protein with phytoestrogens.

A number of randomized controlled trials have demonstrated the damaging effects of animal protein in human cancers. For example, a randomized, placebo-controlled trial found that among men at high risk, those supplementing with milk protein were more than six times likely to develop prostate cancer compared to men supplementing with soy protein.36 Also, a number of tightly controlled feeding trials with human participants have established that heme iron from the protein portion of meat increases the production of NOCs (N-nitroso compounds) in the digestive tract to concentrations similar to that found in cigarette smoke, of which most are cancerous.37 38 Furthermore, a controlled feeding trial found that NOCs arising from heme iron in meat forms DNA adducts in the human digestive tract, and DNA adducts are a well-established marker of cancer.39 These findings are consistent with recent meta-analyses of prospective studies that found that intake of both fresh red meat and heme from meat is associated with a significant increased risk of colorectal cancer.37 40 Based partly on these lines of evidence, in 2011 the expert panel from the World Cancer Research Fund reviewed over 1,000 publications on colorectal cancer and concluded that there is convincing evidence that both fresh and processed red meats are a cause of colorectal cancer.41 Furthermore, a more recent prospective study with over 2.24 million men and women found that compared to participants who consumed less than 1 serving per week, consuming 2 or more servings of meat significantly increased the risk of colorectal cancer.42

The China Study

Denise Minger suggested in regards to the raw data from the China Study that the counties who had the lowest serum cholesterol levels and had the lowest intakes of animal foods had an increased risk of mortality. However, in the China Study animal protein intake was very strongly associated with numerous favorable socioeconomic factors, with household income explaining between 60% and 80% of the variance of intake between counties, likely biasing towards such findings.  Animal food intake was also associated with other favourable socioeconomic factors including access to doctors and hospitals for antenatal consultation and child births, immunisation, avoidance of famine, owning a fridge, a toilet and the ability to read, of which many were associated to some degree with a lower risk of mortality.43 Among the younger population studied in the China Study II, animal food intake was actually a significant predictor of an increased risk, and plant foods of a decreased risk of all-cause mortality despite the fact that the significant inverse relationship between mortality and household income would have biased these results towards the opposite direction (Tables. 2, 3).43 This resembles Dr. Campbell’s observations in the Philippines where the children from the wealthier families that consumed diets rich in animal foods were more likely to develop liver cancer.31

Table 2. Significant predictors of all-cause mortality in the raw data from the China Study II, ages 0-4

Table 3. Significant predictors of all-cause mortality in the raw data from the China Study II, ages 5-14

Forward-looking prospective studies that controlled for socioeconomic factors found that plant based dietary patterns are associated with a decreased risk of all-cause mortality.27 44 45 46 Furthermore, it has been well established from evidence from over 100 randomized controlled trials that lowering LDL cholesterol significantly reduces the risk of all-cause mortality, even in individuals who already have very low baseline LDL cholesterol concentrations similar to that observed in the rural Chinese.12 47 The great majority of the surge in coronary heart disease mortality in Beijing between 1984 and 1999 has been attributed to a significant increase in serum cholesterol explained largely by a 5-fold increase in red meat and egg intake as well as a decline in fruit and vegetable intake. Without improvements in medical interventions the increase in deaths would have been substantially higher.48

Minger also previously claimed that Dr. Campbell’s findings of an relationship between fat, a marker of animal food intake, and an increased risk of breast cancer mortality in the China Study was attributed to the intake of ‘hormone-injected livestock’. She however provided no evidence that consumption of such livestock was widespread in rural China long enough before the mortality data was collected almost four decades ago for this questionable claim to be plausible. However, she did agree that Dr. Campbell’s findings of early menarche as a risk factor for breast cancer as perhaps reflecting a causal relationship ‘given what we know about hormone exposure and breast cancer’. Not surprisingly she failed to mention that animal protein was associated with elevated circulating estrogen in the China Study, and has been associated with a higher risk of early menarche in numerous studies including a cohort of girls born during the 1930s and 1940s, before the widespread consumption of ‘hormone-injected livestock’.31 49 50 51

In addition, Minger previously criticized a number of Dr. Campbell's statements that he made apparently in regards to both the China Study I & II, yet she cited data only from the China Study I.52 With the addition of the data from the China Study II, the relationship between animal foods and an increased risk of breast cancer mortality became significantly stronger, as did plant foods with a decreased risk (Table 4).43

Table 4. Significant predictors of female breast cancer mortality in the raw data from the China Study II, ages 35-69

Furthermore, consistent with the findings from the China Study, the expert panel from the World Cancer Research Fund concluded in 2011 that there is convincing evidence that dietary fiber protects against colorectal cancer, clearly refuting Minger's claims that research on dietary fiber 'outside' of the China Study does not support Dr. Campbell's findings.41 52

Many of Dr. Campbell’s findings in regards to plant based diets and the risk of chronic diseases in China are consistent with much earlier studies from China and around the world. For example, Williams reviewed the medical literature and documentations on cancer from around the world in 1908 long before the widespread use of intensive farming practices, finding strong evidence of an association between plant based dietary patterns and exceptional longevity and very low rates of cancer. Williams also documented that compared to the less affluent parts of Asia that subsisted on plant based diets, cancer was relatively common in the affluent parts of China that could afford animal foods on a frequent basis. He asserted that:53

…cancer is comparatively uncommon in those parts of China where the bulk of the people live on an almost exclusively vegetarian diet, being too poor to purchase any of the various flesh foods which are there used for culinary purposes.

Consistent with Williams's findings on cancer, Snapper found a similar phenomenon for vascular disease. He asserted that:54

In 1940, I confirmed De Langen’s results... by the observation that in North China, coronary disease, cholesterol [gall]stones and thrombosis were practically nonexistent among the poorer classes. They lived on a cereal-vegetable diet consisting of bread baked from yellow corn, millet, soybean flour and vegetables sautéed in peanut and sesame oil. Since cholesterol is present only in animal food, their serum cholesterol content was often in the range of 100 mg. per cent. These findings paralleled the observation of De Langen that coronary artery disease was frequent among Chinese who had emigrated to the Dutch East Indies and followed the high fat diet of the European colonists.

Overall Impressions of Forks Over Knives

Overall, Forks Over Knives provides a lot of very useful information to help viewers make life saving and longevity promoting dietary changes, and best of all comes directly from the doctors who have actually reversed many of the chronic diseases which are leading causes of disability and death. Ignoring the preponderance of evidence favoring a predominately plant based diet, low in saturated fat that is recommended by virtually every respected healthy authority around the world, and instead blindly following the unfounded dietary advice of the cholesterol skeptics can result in absurd consequences and a missed opportunity for healthy longevity.55


Part II: Forks Over Knives and Health Longevity: Perhaps the Science is Legit After All

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