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.

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.

Diet, Blood Cholesterol, Blood Pressure and Risk of Stroke: Part II

In Part I I reviewed evidence showing that while randomized controlled trials found that lowering LDL cholesterol significantly reduces the risk of coronary heart disease, ischemic stroke and all-cause mortality, but has little appreciable effect on hemorrhagic stroke, prospective cohort studies found suggestive evidence that serum cholesterol, including LDL and possibly triglycerides and the risk of hemorrhagic stroke is modified by blood pressure. The largest meta-analysis of prospective studies found that while serum cholesterol was inversely associated with risk of hemorrhagic stroke mortality in participants with high blood pressure, in participants with near optimal or ‘physiological’ blood pressure, lower cholesterol was actually associated with a significantly reduced risk of hemorrhagic, ischemic and total stroke mortality. Furthermore another very large prospective study found suggestive evidence that the inverse association between cholesterol and risk of hemorrhagic stroke confined to participants with hypertension may not be causal but acts as a marker of binge drinking.

Taking this potential modification by blood pressure and risk of stroke into consideration, as blood pressure is universally high in developed nations among people in the age range most susceptible to stroke, this may result in biasing the results of studies towards finding a lower risk of stroke for dietary changes that raise cholesterol. Therefore this justifies considering this potential bias when evaluating the evidence regarding dietary changes and the risk of stroke.

Foods rich in fiber and flavonoids may lower blood pressure and risk of stroke*

Red Meat

Despite the possibility of the above mentioned bias, a recent meta-analysis of 6 prospective studies including >329,000 participants and >10,600 cases of stroke found that each per-day serving increase of fresh red meat and processed meat was associated with a 11% and 13% increased risk of stroke respectively, without heterogeneity among studies.1 The authors not only explained that these findings could partly be attributed to saturated fat, dietary cholesterol and sodium content in fresh red meat and processed meat, but also provided the following explanation regarding how these findings may be in part explained by intake of heme iron:

Moreover, red meat is a source of heme iron. It is well-known that iron is a redox-active metal that catalyzes the formation of hydroxyl free radicals in the Fenton reaction. High doses of iron may lead to oxidative stress, a state with increased peroxidation of lipids, protein modification, and DNA damage. If continued for a long time, oxidative stress induced by iron may lead to the development of many diseases, such as cardiovascular disease, type II diabetes, atherosclerosis, neurological disorders, and chronic inflammation.

Don Matesz previously posted an informative review addressing the evidence on the absorption animal and non-animal sources of iron and the risk of developing chronic and degenerative diseases. Similarly, Dr. Michael Greger reviewed the evidence of absorption of heme and non-heme iron and the associated risks (video below).

Risk Associated With Iron Supplements

Meat, in particular red meat intake has been consistently associated with an increased risk of weight gain in large prospective studies, suggesting that this meta-analysis may have underestimated the true association between red meat and risk of stroke, as all included studies adjusted for BMI.2 3 4 5 6 7 Furthermore, a recent meta-analysis of prospective studies found that body iron stores and intake of heme iron from meat, but not non-heme iron was associated with a significantly increased risk of developing type II diabetes, which in-turn increases the risk of stroke.8

Fish and Stress

Several recent meta-analyses of randomized controlled trials, including the highest quality double-blinded, placebo-controlled trials found no association between fish oil and risk of stroke, all other cardiovascular end points and all-cause mortality.9 10 Conversely, a recent meta-analysis of prospective studies including >402,00 participants and >10,500 cases of stroke found that fish intake was associated with a decreased risk of stroke in studies conducted in North America, but not in Europe and Asia.11 However, compared to the Asian and European cohorts, the participants in the North American cohorts may have been displacing fish with less healthful foods such as red meat which is a typical characteristic of North American cohorts, therefore possibly explaining these inconsistent findings.12 In addition, another recent study of >30,000 participants from the Stroke Belt in the U.S. not included in this meta-analysis found that fried fish was associated with a 2.8 fold increased risk of ischemic stroke.13

Another study on British adolescents whose diet was measured between 1937 and 1939 found that while childhood intake of vegetables cut the risk of developing stroke later in life in less than half, higher childhood intake of fish was associated with a two-fold increased risk of stroke.14 The researchers provided the following possible explanation for these findings:

A detrimental effect of higher fish intake on stroke risk would fit with temporal trends in fish consumption and stroke in the UK and Japan. It is also consistent with the suggestion that fish intake in early life may influence risk of stroke, particularly hemorrhagic stroke through an effect on membrane concentrations of arachidonic acid.

Perhaps another explanation for these findings is that fish contains high levels of mercury and other contaminants that may increase the risk of stroke and other neurological disorders, which adolescents maybe especially susceptible to.15 16

Uffe Ravnskov, the spokesman for The International Network of Cholesterol Skeptics responded to this study explaining his alternative hypothesis:17

Dear Editor,
To estimate children’s intake of fish from total household dietary intake is a daring enterprise. Most children hate fish because of the bones. Here is a likely scenario:
Father or mother: “There is no dessert before you have eaten up that fish!”
Therefore, if the figures aren’t a result of chance, they may rather reflect the effect of childhood stress rather than the result of a high intake of fish.

This attempt to downplay the results of this study seems to be somewhat desperate coming from someone who is considered to be one of the most prominent figures in the cholesterol skeptic community. Ravnskov’s claims have long been demonstrated as being faulty by prominent researchers.18 Plant Positive has also addressed a number of his faulty claims in the Primitive Nutrition Series.

Indeed prospective studies found that depression and perceived stress is associated with a modest increased risk of stroke and coronary heart disease respectively.19 20 However, the observed plummet of cardiovascular mortality in Scandinavia and the low countries of Europe during the World Wars casts doubt as to whether stress can be considered as a primary cardiovascular risk factor as opposed to significant dietary modifications and weight loss [reviewed previously]. This plummet was also observed in what can be arguably described as the most stressful environment in modern history, as the researchers from a landmark Israelian study explain:21

…physicians who survived the Nazi concentration camps reported that during the years of their imprisonment, they never encountered patients with myocardial infarctions or patients with anginal syndrome, even in persons over 50 years of age. Moreover, persons who were previously known to them as patients with atherosclerotic heart disease became free of clinical manifestations of their disease after losing considerable weight due to the conditions prevailing in the concentration camps.

Cocoa and Beverages

A meta-analysis of 5 prospective studies with >4,200 cases of stroke found that chocolate intake was associated with a decreased risk of stroke. As the researchers suggested, these findings are likely explained by nutrients found primarily in cocoa solids such as flavonoids and antioxidants, and therefore does not support an increased intake of other ingredients typically included in chocolate.22

A large meta-analysis of observational studies provided suggestive evidence that alcohol consumption is associated with a slightly lower risk of ischemic stroke but higher risk of hemorrhagic stroke.23 A meta-analysis of 11 prospective studies with >479,000 participants and >10,000 cases of stroke found that moderate coffee intake was associated with a modest decreased risk of stroke.24 In addition, a meta-analysis of 14 prospective studies with >513,000 participants and >10,000 cases of stroke found that tea intake was associated with decreased risk of stroke in a dose response matter, therefore making it likely the favorable beverage for stroke prevention.25

Fruits and Vegetables

A meta-analysis of 9 prospective studies including >257,000 participants and >4,900 cases of stroke found that fruit and vegetable intake provided significant protection against both ischemic and hemorrhagic stroke, and that optimal intake is above five servings per day.26 These findings are consistent with more recent large prospective studies, although some found suggestive evidence that the association was stronger for white fruits and vegetables, raw fruits and vegetables, cruciferous vegetables, citrus fruits and tomatoes.27 28 29 30 31

Fiber and Micronutrients

A very recent meta-analysis of 6 prospective studies including >314,000 participants and >8,900 cases of stroke found that a 10 g/day increment of dietary fiber was associated with a 12% reduction in stroke.32 In addition, a meta-analysis of 10 prospective studies including >268,000 participants and >8,600 cases of stroke found that an increment of 1000 mg/day of dietary potassium was associated with a 11% reduction of stroke.33 Furthermore, a meta-analysis of 8 prospective studies including >304,000 participants and >8,300 cases of stroke found that dietary potassium was associated with a decreased risk of stroke.34 There is also growing evidence that dietary flavonoids decrease the risk of stroke.35

These findings should be interpreted with caution as these nutrients maybe markers of other protective constituents in whole-plant foods. Increasing intake of these nutrients with supplements or fortified foods may provide little benefit, and therefore would be advisable to increase intake of whole-plant foods naturally rich in these nutrients.36

Regarding supplements, a meta-analysis of placebo controlled trials including >28,000 participants found that calcium supplements with or without vitamin D increased the risk of cardiovascular events, including stroke.37 Consistent with these findings a meta-analysis of prospective studies found that circulating calcium in >22,000 participants was associated with a significantly increased risk of total stroke.38 Conversely, this meta-analysis found that circulating vitamin D in >47,000 participants was associated with a significantly lower risk of stroke, consistent with suggestive evidence from a meta-analysis of randomized controlled trials that evaluated the efficacy of sunlight exposure.39

A meta-analysis of 12 studies with >225,000 participants and 3,100 cases of stroke found that high salt intake was associated with an increased risk of stroke.40 In addition, a recent large prospective study also found that dietary cholesterol was associated with an increased risk of stroke.41

Macronutrients

Although prospective studies have found that saturated fat, trans fat and animal protein are associated with an increased risk of coronary heart disease mortality, studies of these cholesterol raising macronutrients and the risk of stroke have been less consistent.42 43 44 This could be because as previously explained the association between serum cholesterol, which is typically raised by these nutrients and risk of stroke maybe modified by blood pressure. A limited number of studies have tested whether the association between macronutrient intake and the risk of stroke is modified by hypertension status, but not whether it is further modified by optimal compared to high normal blood pressure.

In the Nurses’ Health Study intake of trans-fat, saturated fat and animal protein was inversely associated with risk of hemorrhagic stroke. The researchers found that the inverse association for saturated fat was confined to women with a history of hypertension, but did not observe this interaction for trans-fat or animal protein.45 However, a recent study on Swedish women with a significantly larger number of stroke cases found that the inverse association between animal protein and risk of stroke was confined to participants with hypertension.46 A Japanese study found that the findings of an inverse association between saturated fat and hemorrhagic stroke was not confined to participants who were hypertensive at study baseline, but noted that many cases of stroke were recorded in participants who had high-normal blood pressure at study baseline and that blood pressure likely increased as the participants aged during the follow-up period.47

This Japanese study raises two important limiting factors typically not accounted for that should be considered in future studies. Firstly as previously explained, the majority of the participants who are in the age range most susceptible to stroke typically have either high normal blood pressure or hypertension, and secondly that many participants will likely develop high blood pressure as they age during the follow-up period. As studies at most usually only examine whether hypertension status at study baseline modifies the risk of stroke and not whether this association is further modified by maintaining an optimal blood pressure throughout the follow-up, this may explain the inconsistency of the results for different cholesterol raising macronutrients and the risk of stroke.

Another recent study on Swedish women found that carbohydrate restricted diets rich in animal protein was associated with an increased risk of subarachnoid hemorrhage and overall cardiovascular disease.48 In the Health Professionals Follow-up Study, there was a non-significant positive and inverse association for animal protein and vegetable protein and risk of stroke respectively.49 Another study in a U.S. population found that higher intake of total fat, especially >65 g/day was associated with an increased risk of ischemic stroke. The excess risk was primarily explained by intake of saturated fat, which showed a trend towards an increased risk of ischemic stroke.50

A recent study of >71,000 Norwegians found that intake of trans-fat from hydrogenated vegetable oils decreased and risk of stroke mortality and cancer incidence, but increased the risk of coronary heart disease mortality. Conversely, intake of trans-fat from hydrogenated fish oil increased the risk of stroke mortality and cancer incidence. Intake of ruminant trans-fat from meat and dairy was not associated with stroke mortality but increased the risk of coronary heart disease mortality, sudden death and cardiovascular mortality in women, and increased the risk of cancer incidence and all-cause mortality in both sexes.43 51 As any increase in intake of trans-fat has significantly unfavorable effects on serum lipids, which in-turn increases the risk of chronic diseases, it is advisable to eliminate all forms of trans-fat from the diet.52 53

Plant Based Diets

A meta-analysis of 5 prospective studies that compared vegetarians to health conscious non-vegetarians found that male vegetarians had a near statistical significant 23% lower risk of stroke and 14% lower risk of all-cause mortality, independent of age and smoking status. For female vegetarians, only ischemic heart mortality was noted to be significantly lower.54 However, this meta-analysis included studies where a large percentage of the participants in the non-vegetarian group were actually infrequent meat eaters and at least one study where one third of the participants in the vegetarian group were found to include meat in their diets, thus minimizing the differences in dietary intake between groups and essentially biasing the true association towards null.55

In Dr. Caldwell Esselstyn’s follow-up of 18 compliant participants with severe coronary artery disease, there were no cases of cardiac events during the 20 year follow-up among compliant participants. This is despite the fact that these 18 participants experienced 49 cardiac events, including 3 cases of stroke during the eight years prior to the study, of which during this time all had been receiving state-of-the-art cardiac care at the Cleveland Clinic.56 In the newer decade long study of over 200 patients, recurrent cardiac events only occurred in 0.5% of compliant participants, which is approximately 40 fold lower than other dietary or statin based trials [reviewed previously].

The Better Way to Prevent Stroke

The preponderance of evidence demonstrates that for stroke prevention, diets should be predominantly composed of minimally refined plant based foods rich in fiber and low in added salt, with an emphasis on reducing LDL cholesterol, blood pressure and body fat to optimal levels. In addition healthy lifestyles should include regular exercise and sunlight exposure for maximum protection. In the presence of these factors, increasing the intake of cholesterol lowering plant foods will not only likely result in a decreased risk of stroke, but also a decreased risk of many other chronic and degenerative diseases.


Please post any comments in the Discussion Thread. 

Diet, Blood Cholesterol, Blood Pressure and Risk of Stroke

The controversy surrounding the lipid hypothesis, in particular the relationship between elevated total and LDL cholesterol and coronary heart disease was considered largely resolved and regarded as scientific fact within the scientific community by 1984 when the expert panel from the National Institutes of Health (NIH) reviewed the relevant literature and agreed that the relationship was causal.1 2 The panel concluded:

Elevated blood cholesterol level is a major cause of coronary artery disease. It has been established beyond a reasonable doubt that lowering definitely elevated blood cholesterol levels (specifically blood levels of low-density lipoprotein cholesterol) will reduce the risk of heart attacks due to coronary heart disease… Further, we are persuaded that the blood cholesterol level of most Americans is undesirably high, in large part because of our high dietary intake of calories, saturated fat, and cholesterol… There is no doubt that appropriate changes in our diet will reduce blood cholesterol levels.

Since 1984 evidence accumulated from over 100 randomized controlled trials of various medical and dietary based lipid modifying interventions has further established that lowering LDL cholesterol significantly decreases the risk of coronary heart disease and all-cause mortality, independent of changes to HDL cholesterol and triglycerides, and non-lipid effects of specific drugs.3 4

Controversy however has lingered over whether medical and dietary based interventions to lower total and LDL cholesterol, and perhaps triglycerides may increase the risk of certain stroke subtypes, in particular hemorrhagic stroke. Controversy has arisen in part due to the interpretation of certain statin trials, prospective cohort studies, and observational studies in certain populations with unique cardiovascular profiles, in particular the Japanese.5 6 7 This has led some to suggest that physiological levels of LDL cholesterol (less than 70 mg/dl; 1.8 mmol/l), the levels observed in newborn humans, free-ranging mammals, and human populations on low cholesterol diets that do not develop atherosclerosis [reviewed previously] may somehow increase the risk of hemorrhagic stroke.

There are two major categories of stroke, ischemic and hemorrhagic. Ischemic stroke occurs as a result of an obstruction with the blood supply to the brain, while hemorrhagic stroke occurs as a result of a rapture of a weakened blood vessel. In contrast to the observed decline of stroke incident in Japan where there was a significant improvement in a number of major risk factors but an increase in mean serum cholesterol, Finland experienced one of the highest rates of stroke mortality in the world as well as one of the largest declines, which was in part explained by a decrease in serum cholesterol.8 Unlike Japan, Finland also experienced the highest rate of coronary heart disease mortality in the world as well as the largest decline, which was predominantly explained by cholesterol lowering dietary changes [reviewed previously]. Furthermore, evidence suggests that Japanese Zen monks who consume significantly less meat and fish than the general Japanese population experience lower rates of stroke and all-cause mortality, independent of BMI, alcohol intake and other lifestyle factors.9

At the opposite end of the dietary spectrum higher rates of stroke mortality have been observed among the three main Inuit populations, including those in Greenland, Canada and Alaska compared to their non-Inuit Western counterparts, yet experience similar rates of non-stroke cardiovascular mortality.10 Evidence of atherosclerosis and other chronic and degenerative diseases have been observed in numerous preserved Inuit mummies that date back to pre-western contact, suggesting that their high rate of cardiovascular mortality cannot be entirely explained by influences of modern dietary and lifestyle factors [reviewed previously]. Furthermore, the declining rates of cardiovascular mortality, including stroke among the Inuit undergoing a rapid transition towards a western diet and lifestyle has raised questions regarding the health properties of the traditional Inuit diet based on marine animals.10

Coronary atherosclerosis in a pre-contact Inuit mummy dating back 1,600 years*

The Interaction between Blood Cholesterol, Blood Pressure and Risk of Stroke

Recently the largest meta-analysis of statin based randomized controlled trials on the effect of lowering LDL cholesterol and risk of stroke was published, including 31 trials with >182,000 participants and >6,200 cases of stroke. Statins significantly decreased the risk of total and ischemic stroke and all-cause mortality, without evidence of publication bias, consistent with findings from animal studies.5 11 There was however a small statistically insignificant increase in incidence of hemorrhagic stroke in the statin group which was not related to either the degree of reduction of LDL or the achieved LDL. The researchers provided the following possible explanation for these findings:

In addition to their lipid-lowering properties, statins may have antithrombotic properties by inhibiting platelet aggregation and enhancing fibrinolysis. The antithrombotic affects of statins could account for a theoretically increased risk of bleeding complications.

All of the very large prospective cohort studies that included >300,000 participants have either found no association between total and LDL cholesterol and risk of hemorrhagic stroke, or an inverse association confined to participants with hypertension, or a positive association confined to participants with low blood pressure.6 12 13 14 15 A prospective study with >787,000 Korean participants and >9,900 cases of stroke found that while serum cholesterol was associated with a higher risk of ischemic stroke, the researchers found suggestive evidence that the inverse association between serum cholesterol and hemorrhagic stroke confined to hypertensive participants was not causal, but acted as a marker of binge drinking.14 The researchers explained:

In our study, increased risk of hemorrhagic stroke in people with low concentrations of blood cholesterol (less than 4.14 mmol/l) was restricted to those with high GGT values [a measure of alcohol intake]; this relation was less evident when alcohol consumption was measured by self report. The measures of blood pressure might not have been a true reflection of risk, as transient high blood pressure associated with binge drinking may have an important role in hemorrhagic stroke. At low concentrations of GGT, low serum cholesterol was not associated with a higher risk of hemorrhagic stroke. In effect, low blood cholesterol may act as a marker of the health damaging effects of alcohol, rather than be a cause of hemorrhagic stroke.

There maybe limitations with the studies which only address whether blood pressure considered by hypertension status modifies the association between serum cholesterol and risk of stroke. As with hypercholesterolemia, the definition of hypertension, blood pressure of >140/90 mmHg, far exceeds levels that have been clearly scientifically documented as being optimal. For example, a meta-analysis of 61 prospective studies including >958,000 participants and >11,900 cases of stroke deaths found that lower usual blood pressure was associated with a reduced risk of mortality from stroke and coronary heart disease, without any evidence of a threshold down to at least 115/75 mmHg.16 These findings are consistent with a meta-analysis of 147 randomized controlled trials that administered blood pressure lowering medication.17 This justifies investigating whether optimal blood pressure compared to high-normal blood pressure further modifies the association between serum lipids and the risk of stroke subtypes.

A meta-analysis of 61 prospective studies with >892,000 participants and >11,600 cases of stroke deaths found not only that serum cholesterol was inversely associated with total and hemorrhagic stroke mortality in participants with very high baseline systolic blood pressure (>145 mmHg), but that lower serum cholesterol was actually associated with a significantly lower risk of hemorrhagic, ischemic and total stroke mortality in participants with near optimal or ‘physiological’ baseline systolic blood pressure (less than 125 mmHg)(Fig. 1).6 As most participants in the age range most susceptible to stroke had either high-normal blood pressure or hypertension, the combined results were biased towards finding an inverse association between serum cholesterol and hemorrhagic stroke mortality.

Figure 1. Systolic blood pressure specific hazard ratios for 1 mmol/L lower usual total cholesterol and risk of stroke mortality

If this association is causal and not obscured by other factors such as binge drinking, this may explain why populations with low cholesterol and high blood pressure such as the Japanese have high rates of stroke, in particular hemorrhagic stroke, and populations that maintain physiological levels of both cholesterol and blood pressure throughout life have an observed absence of stroke.18

There is limited suggestive evidence that the atherosclerosis build-up process in the carotid and major cerebral arteries caused by excess LDL cholesterol in-turn reduces arterial blood supply to the brain that would otherwise cause the blood vessels in the brain to rupture in the presence of high blood pressure, thus explaining why elevated cholesterol may lower the risk of cerebral hemorrhage in people with high blood pressure.19 Indeed, a Japanese study found there was an inverse association between cholesterol and hemorrhagic stroke in an earlier cohort when the mean blood pressure was high and atherosclerosis was relatively low, but no association in the later cohort of the same population when mean blood pressure was reduced from hypertensive to high-normal blood pressure.20

Evidence from several but not all observational studies also found that low triglycerides were associated with a statistically significant or non-significant increased risk of hemorrhagic stroke.12 21 22 23 24 25 26 There is limited data regarding whether the association between low triglycerides and hemorrhagic stroke is modified by blood pressure or alcohol intake, but at least one large study found that the association was stronger among participants with high blood pressure.22

As there is convincing evidence that blood pressure increases the risk of stroke at any given cholesterol concentration, it would be advisable that everyone should aim to achieve an optimal blood pressure of less than 115/75 mmHg. Although a number of lifestyle changes including exercise and weight loss can lower blood pressure, a number of dietary changes can also effectively lower blood pressure.27 28 This includes reducing intake of salt and increasing intake of dietary fiber rich foods including whole grains, flavonoid rich foods including berries, soy, cocoa solids, and vitamin C and magnesium.29 30 31 32 33 34 35 36 37 38 These nutrients derived primarily from whole-plant foods may in-turn explain why intervention and observational studies have found that vegetarian diets, in particular vegan diets have favorable effects on blood pressure.39 40 41 42 43 44 45 46

The Better Way to Lower Cholesterol

As statins provide little appreciable protection against cancer, and like all drugs have adverse effects including but not limited to an increased risk of developing type II diabetes and memory loss or impairment, a significantly greater benefit would be achieved by lowering LDL cholesterol with a whole-foods plant based diet combined with regular exercise in order to not only lower the risk of cardiovascular disease but many other chronic and degenerative diseases.47 48 49 50 In Part II I review the evidence of dietary factors and the risk of stroke.


Please post any comments in the Discussion Thread.