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

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

The term diseases of civilization, which Stefansson has contributed to the popularization of is frequently referred to by proponents of Low-Carb, Paleo, Primal and Weston A. Price Foundation type diets. Many of these proponents have extrapolated limited suggestive evidence that obesity, type 2 diabetes, coronary heart disease, certain cancers, and a number of other chronic and degenerative diseases were uncommon during the Paleolithic period to suggesting that foods derived from naturally raised, grass-fed animals, as was consumed by Paleolithic humans must therefore somehow provide protection against these so-called diseases of civilization. Many of these proponents have also claimed that a vast number of scientific studies that have been used as evidence to conclude that animal foods increase the risk of such diseases have been complicated by confounding of other unhealthy foods and lifestyle factors, or by the use of unnaturally raised animal foods. This series of posts will examine the evidence to help determine whether these claimed confounding variables can actually explain the evidence linking animal foods with certain chronic and degenerative diseases, often referred to as diseases of civilization, but also as western diseases, lifestyle diseases and diseases of affluence.

In 1928, Stefansson and his colleague Karsten Anderson participated in a monitored experiment partly funded by the meat industry in which they consumed a flesh exclusive diet for the period of one year. Although the researchers concluded that these two men were in good health throughout the experiment, Anderson experienced a severe elevation in blood cholesterol, with measurements as high as 800 mg/dl on one occasion, which returned to pre-experiment levels after resuming a higher carbohydrate diet.2 A glucose tolerance test carried out immediately after the termination of the meat based experiment showed a marked rise in blood sugar in both men compared to a subsequent test carried out after resuming a higher carbohydrate diet. Glucose was detected in the urine of Anderson in the test following the meat based experiment, a marker of untreated diabetes. This abnormality was not detected in the subsequent test after resuming a higher carbohydrate diet.3

Short-term experiments such as this cannot provide adequate insight into the long-term consequences of following such a diet, as it can take many decades for diseases caused by exposure to harmful substances to become clinically significant. For example, the greatest risk of excess death from radiation-related solid cancers among the atomic bomb survivors of Hiroshima and Nagasaki was more than half a century after exposure.4 Furthermore, other flesh based experiments have resulted in considerably more unfavorable outcomes. For example, in 1906, Russell noted an even earlier experiment: 

A recent instance occurred in South Africa, where about twenty natives out of some hundreds who were supplied with a large amount of flesh, as an experiment, by mine-owners, died, and many others were ill.5

Cardiovascular Disease in Ancient Civilizations

The traditional living Inuit's were certainly
not immune from atherosclerosis

If a diet rich in naturally raised animal foods provides protection against cardiovascular disease as many proponents of Low-Carb type diets claim, it would be expected that traditional living populations consuming such a diet, particularly those living prior to the rapid westernization of the globe would demonstrate evidence of superior cardiovascular health compared to those populations who subsisted primarily on starchy staples, including grains, legumes and tubers. Populations who have inhabited the arctic, where scant plant matter is available throughout most parts of the year, such as the Inuit and Aleut were forced to subsist almost exclusively on hunted marine animals for extensive periods of time.1 6 This should make these populations suitable to study the hypothesis that naturally raised animal foods protect against cardiovascular disease.

Contrary to claims of the traditional living Inuit being immune from cardiovascular disease, evidence of severe atherosclerosis has been identified in several frozen mummies of Alaskan Inuit dating back to 400 CE and 1520 CE, both instances predating European contact.7 8 Atherosclerosis has also previously been identified in several artificially prepared mummies of Aleut-Unangan hunter gatherers who lived in the 18th century in the Aleutian Islands in Alaska.9 10 Recently the HORUS study, which examined an additional five recovered mummies of Unangan hunter gatherers who lived in the mid and late 19th century found definite evidence of atherosclerosis in several major arteries in all three who were over the age of 25.11

When considering the findings from all of these Alaskan Inuit and Aleut mummies it becomes evident that these Alaskan natives likely experienced a greater incidence of atherosclerosis, especially given the young mean age compared to the three other ancient populations studied in the HORUS study. Unlike the Alaskan natives, these other three populations, which were the ancient Egyptians, ancient Peruvians and Ancestral Puebloans practiced agriculture and consumed grains. 

In addition to evidence of atherosclerosis from native Alaskan mummies, reports from medical officers provide further evidence of unfavorable rates of cardiovascular disease among the Inuit before the rapid transition to the western diet. In 1940, based on decades of clinical practice and reviewing reports of medical officers dating all the way back 175 years ago, 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.12

Bjerregaard and colleagues performed a literature review for studies addressing the incidence of atherosclerosis and cardiovascular disease among the Inuit of Alaska, Canada and Greenland spanning from the 1930s to more recent decades. The researchers found that the incidence of atherosclerosis was generally similar to that of other western populations that suffered from high rates of cardiovascular disease. Mortality from stroke was found to be even higher, and mortality from all cardiovascular diseases combined was found to be similar or even higher among the Inuit. The researchers also found that mortality from coronary heart disease among the Inuit was not significantly different after adjusting for ill-defined causes of cardiovascular death, suggesting that the substantial proportion of cardiovascular deaths being classified as ‘garbage codes’, particularly in Greenland may have hidden a significant portion of deaths from coronary heart disease. The researchers concluded: 

The mortality from all cardiovascular diseases combined is not lower among the Inuit than in white comparison populations. If the mortality from IHD [ischemic heart disease] is low, it seems not to be associated with a low prevalence of general atherosclerosis. A decreasing trend in mortality from IHD in Inuit populations undergoing rapid westernization supports the need for a critical rethinking of cardiovascular epidemiology among the Inuit and the role of a marine diet in this population.12

A similar phenomenon to the misclassification of deaths from coronary heart disease among the Inuit populations has also been observed in France, which may largely explain the so-called French Paradox. Data from the World Health Organization MONICA Project suggests that the official mortality statistics for France significantly underreport deaths from cardiovascular disease compared to other countries, with deaths from coronary heart disease being underestimated by 75%. Other reports suggest that this is likely explained by a much higher rate of French doctors classifying deaths as due to ‘other causes’ than in other countries.13 14

It has been observed that among the Alaskan Inuit a higher intake of saturated fat is associated with elevated blood pressure, insulin resistance, glucose intolerance and carotid atherosclerosis, suggesting that the traditional Inuit foods relatively rich in saturated fat were likely to have been detrimental to the cardiovascular health of the Inuit.15 16 17 It has also been observed that among Alaskan Inuit elevated LDL cholesterol is associated with a greater than fourfold increased risk of cardiovascular disease.18 Furthermore, rheumatic disorders that have been linked to cardiovascular disease, such as gout and rheumatoid arthritis have been found to be just as, or even more common among the Eskimo populations compared to that of the general North American population.19 20 Established risk factors, a number of which are likely adversely affected by the traditional Inuit diet can probably in part explain the evidence of severe atherosclerosis and unfavorable rates of cardiovascular disease observed among the traditional living Inuit and Aleut populations. 

In the HORUS study it was found that two of the four Ancestral Puebloan who lived in southwestern United States dating between 1500 BCE and 500 CE exhibited probable evidence of atherosclerosis, the two other both being under the age of 30. These Ancestral Puebloans were identified as being from a time when they were transitioning from hunter-gatherers to farmer-foragers, and were likely to have relied on hunted animal foods to supply at least a modest portion of their diet. An additional Ancestral Puebloan mummy aged 18-22 found from a later period after a greater transition towards agriculture did not exhibit any evidence of atherosclerosis.11

In the HORUS study the ancient Egyptian mummies exhibited the next greatest frequency of atherosclerosis, with 29 (38%) of the 76 of the mummies exhibiting at least probable evidence of atherosclerosis.11 In their book Protein Power, Michael and Mary Eades assert that the ‘diet of the average [ancient] Egyptian consisted primarily of carbohydrates’, which they suggest was ‘a veritable nutritionist’s nirvana… rich in all the foods believed to promote health and almost devoid of saturated fat and cholesterol'. These authors go on to suggesting that the carbohydrate rich diet of the ‘average Egyptian’ which they describe as being based on whole-grain wheat and barley supplemented by a variety of fruits, vegetables, legumes, nuts and some goats milk is responsible for the atherosclerosis and obesity exhibited by the ancient Egyptian mummies.21

The authors of Protein Power suggest that complex carbohydrates, such as wheat made the ancient Egyptians obese

There is much evidence that casts doubt on these authors description of the diets of the ancient Egyptian mummies. For example, Macko and colleagues have shown that isotope analyses of the amino-acid composition of hair from the ancient Egyptian mummies far more closely resemble that of modern westerners following an omnivorous diet than a vegetarian, and especially vegan diet.22 In addition, David and colleagues showed that evidence from hieroglyphic inscriptions on ancient Egyptian temples suggest that the elites of ancient Egyptian society, being those who were primarily mummified consumed a diet rich in flesh and saturated animal fat. These researchers addressed the confusion surrounding the diet and atherosclerosis of the ancient Egyptian mummies, asserting: 

It is important to point out that there was a marked difference between the mainly vegetarian diet most Egyptians ate and that of royalty and priests and their family members whose daily intake would have included these high levels of saturated fat. Mummification was practised by the elite groups in society, ensuring that their remains have survived to provide clear indications of atherosclerosis; by contrast, there is a lack of evidence that the condition existed among the less well-preserved remains of the [mainly vegetarian] lower classes.23

The findings of a lower incidence of atherosclerosis among the lower classes of ancient Egypt who subsisted primarily on a carbohydrate-rich vegetarian diet are consistent with observations in Egypt in the early 20th century. In 1934, Rosenthal asserted:

Of interest is the report of Ismail in Egypt, who has communicated that among his private patients, whose diet is similar to that of the Europeans, the incidence of atherosclerosis is high, while in his hospital practice, composed mainly of natives, who subsist largely on a carbohydrate diet, the incidence of atherosclerosis is low.24

It is clear that the authors of Protein Power have confused the diet of the elites of the ancient Egyptian society, who certainly cannot be considered as the 'average Egyptian' with the largely vegetarian diet of the of the lower classes who exhibit a lack of atherosclerosis, and which scant evidence suggests were obese. The findings from ancient Egyptian mummies do not support the claimed benefits of a low carbohydrate, high saturated fat diet promoted by these authors.

In the HORUS study, despite having the highest mean age, nearly 10 years older than that of the Unangan and Ancestral Puebloans mummies, the ancient Peruvians exhibited the lowest incidence of atherosclerosis, being evident in 13 (25%) of 51 of the mummies. Compared to these other studied ancient populations, the Peruvians likely relied more on staple plant foods, such as corn, beans and tubers, although did consume some domesticated and hunted animals.11

The researchers of the HORUS study suggested that exposure to smoke from fire used for cooking and25

heating may help explain some of the degree of atherosclerosis identified in these ancient populations. However, the description of the use of fire for cooking in ancient Egypt provided by these researchers would apply primarily to the lower classes of ancient Egypt which exhibit a lack of atherosclerosis, rather than the mummified elites that these researchers examined who would typically have had servants to cook for them.

Gout was known to be common among 

the Mongols of the Golden Horde

In regards to the traditional living Inuit and Aleut, it has been suggested that the extensive exposure to seal oil lamps may help explain the relatively severe degree of atherosclerosis in these populations.  These findings should however be considered in light of evidence of atherosclerosis in other populations which have high exposure to hazardous smoke but consume contrasting diets. For example, it has been observed that the Papua New Guinean highlanders have a smoking prevalence of greater than 70% for males and 20% for females while also being exposed to smoke for up to twelve hours a day due to the use of centrally placed open wood fires in their houses which lack both ventilation and chimneys. Despite such a high exposure to hazardous smoke it has been observed that the Papua New Guinean highlanders have among the lowest age-adjusted incidence of atherosclerosis of any studied population. However, unlike the Inuit, the Papua New Guinean highlanders traditionally consumed a plant based diet with carbohydrate supplying more than 90% of total energy intake, predominantly derived from sweet potatoes.26 27

Another population that have historically been documented to subsist almost exclusively on a diet derived from grass-fed, free-ranging animals are the largely nomadic Mongolians. John of Plano Carpini who visited the Mongols in the mid-13th century noted:

[The Mongols] have neither bread nor herbs nor vegetables nor anything else, nothing but meat… They drink mare’s milk in very great quantities if they have it; they also drink the milk of ewes, cows, goats and even camels.28

Smith reviewed the literature regarding the health of the Mongols from the 13th century and noted that a number of unfavorable cardiovascular risk factors, including obesity and gout were both common disorders. Smith went on to state:

Cardio-vascular problems, although not then subject to diagnosis, may be suspected as well.29

In 1925, Kuczynski reported on the nomadic pastoralists of the Kirghiz and Dzungarian Steppes in Central Asia and northern China that were of Mongolian descent. Similar to the observations of the diet of the nomadic Mongols of the 13th century, Kuczynski observed that these nomadic pastoralists subsisted almost exclusively on enormous quantities of meat and milk from grass-fed, free-ranging animals. Other authors have also come to the same conclusions regarding the composition of the diet of the nomadic pastoralists of the Central Asian Steppes. For example, Tayzhanov asserted:

…the people [of the steppe] lived exclusively on meat, fat and sour milk. Bread was added only later and even then some households did not adopt or consume this food.30

Similarly, Barfield asserted:

In good legendary style, the pure Central Asian nomads eat only meat, marrow, and milk products {preferably ferments}. They despise farmers, farming, and grain…31

These findings suggest that the diet of these nomadic pastoralists of the Central Asian Steppes was almost exclusively animal based, virtually devoid of grains, legumes and refined carbohydrates. This should make these populations also suitable to study the hypothesis that naturally raised animal foods protect against cardiovascular disease. However, not only did Kuczynski observe that these nomadic pastoralists suffered from high rates of obesity and gout similar to the Mongols of the 13th century, Kuczynski's observations further extended to the diagnosis of cardiovascular disease and other dietary related disorders. Kuczynski asserted:

They get arteriosclerosis in an intense degree and often at an early age as shown by cardiac symptoms, nervous disordes, typical changes of the peripheral vessels, nephrosclerosis and, finally, apoplectic attacks. Even in men thirty-two years old I frequently observed arcus senilis.32

It was also observed that in the 1960s the prevalence of coronary heart disease among the nomadic pastoralists in Xinjiang in northern China who consumed large quantities of animal fat from grass-fed, free-ranging animals was more than seven times higher than that of other populations both within Xinjiang and throughout China which consumed significantly less animal fat.33 These observations support the suggestion that cardiovascular disease was common among the Mongols of the 13th century who subsisted almost exclusively on a diet based on grass-fed, free-ranging animals.

Dispelling Grass-Fed Fairy Tales

These findings from populations living before the 20th century suggest that similar to the findings from people studied in more modern times, a greater intake of minimally refined plant foods strongly predicts a lower prevalence of atherosclerosis and cardiovascular disease. These findings cast doubt on the hypothesis that foods from organic, naturally raised animals protect against cardiovascular disease compared to staple plant foods. Furthermore, these findings suggest that the traditional living populations that relied predominantly on naturally raised animal based foods suffered from complications related to cardiovascular disease at a relatively young age and are poor role models for health.

Future posts in this series will further address how naturally raised animal foods influence cardiovascular disease, as well as other so-called diseases of civilization.


Please post any comments in the Discussion Thread.

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.