Do Vegetarians Live Longer Than Health Conscious Omnivores?

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

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

Failing to Equal the Seventh-day Adventists

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

Minger hypothesizes that the longevity of the Adventists maybe unrelated to their low meat diet, and may rather reflect the discouraged use of tobacco and alcohol. To illustrate this, Minger points out that the Mormons who are also discouraged from the use of tobacco and alcohol, "but whose founder never endured any meat-abstinence visions"[p.194] have a greater life expectancy than the average population. Although Joseph Smith, Jr., the founder of Mormonism may not have demanded followers to completely abstain from meat, the Word of Wisdom (section 89 in The Doctrine and Covenants) which he delivered, apparently received as a revelation from god, states that:4

Yea, flesh also of beasts and of the fowls of the air, I, the Lord, have ordained for the use of man with thanksgiving; nevertheless they are to be used sparingly;

In regards to longevity, Minger then goes onto state that:

But what’s even more telling is the fact that meat-eating Mormons and vegetarian Adventists tend to live equally as long. When compared to ethnically matched folks outside their religious groups, both Adventist and Mormon men—once their birthday-cake candles start numbering in the thirties—can expect to live about seven years longer than the rest of the population.[p.194]

Unlike what Minger appears to have the reader believe, the 7 years greater life expectancy referred to in the study she cites is for the average Adventist male, and not specifically for vegetarian Adventist men. Less than one third of the men in the cited study were considered vegetarians, with more than half considered regular meat eaters.5 What these studies specifically found was that the life expectancy for active Mormon men who reached the age of 35 was about 7.5 years greater than the average U.S. white male, whereas the life expectancy of the average Californian Seventh-day Adventist male who reached the age of 30 was about 7.3 years greater than the average Californian white male.5 6 When specifically looking at the average vegetarian Californian Adventist male, their life expectancy was found to be about 9.5 years greater than the average Californian white male. It is important to note that the Californian whites that the Adventists were compared to have one of the highest life expectancies of any American state, and are expected to live up to a year longer than the average U.S. white that the Mormons were compared to.7

The more recent 25 year follow-up of the Mormons may allow for a more informative comparison, as like the Adventist study, it included both men and women from California, and examined the effects of other lifestyle factors on mortality. Mormon men and women over the age of 25 with four favorable lifestyle factors associated with significantly reduced mortality were expected to live about 9.8 and 5.6 years longer, respectively, compared to U.S. whites.8 In comparison, vegetarian Adventist men and women over the age of 30 with three favorable lifestyle factors were expected to live about 13.2 and 8.9 years longer, respectively, compared to non-Adventist Californians whites.5 9 Compared to the average U.S. white however, this difference in life expectancy would be expected to be closer to about 14 and 10 years.7 However, and more importantly, a later paper on the Californian Adventists found that those who adhered to a vegetarian diet for at least 17 years were expected to live 3.6 years longer than those who adhered for fewer years.10 This suggests that when restricting the analysis to long-term vegetarian Adventists, the difference in life expectancy compared to the Mormons would be even greater.

There are also other lines of evidence lending support to the observed greater life expectancy of the vegetarian Seventh-day Adventists compared to health conscious Mormons. For example, one study in which vegetarian Adventists and Mormons were matched for strength of religious affiliation, and consumption of tobacco, alcohol, tea and coffee, the vegetarian Adventists were found to have significantly lower levels of serum cholesterol, blood pressure and rates of obesity (Fig. 1).11 12 The difference in blood pressure remained significant even after controlling for BMI, and could not be explained by differences in sodium intake. Another study also found that vegetarian Adventists had lower blood pressure than Mormons, and that the difference increased with age, suggesting a greater favorable effect of long-term adherence to a flesh-free diet.12 

Figure 1. All percentiles of distribution of blood pressure were found to be lower in the vegetarian Adventists compared to health conscious omnivorous Mormons.

Although some of the many factual errors in Minger’s book may be passed off as sloppy research rather than as being intentional (one example perhaps being when she confuses Crete for Ikaria), given the number of occasions she has discussed the Adventist studies previously, it is difficult to believe that she was truly being honest and simply was not even aware of the data in the very studies she cites. Furthermore, Minger acknowledges in this book that she had others with knowledge in this field review her manuscript and assist her with the completion of this book (almost exclusively individuals who have demonstrated an anti-vegetarian stance), allowing for little excuse for these misleading statements.

Mortality in Vegetarians and Health Conscious Omnivores

As there are no published meta-analyses examining all of the current available prospective cohort studies comparing mortality in vegetarians and health conscious non-vegetarians, I performed a simple meta-analysis using the results for the fully adjusted model from the most recent follow-up of each cohort. For mortality from all-causes, based on 7 cohorts, the vegetarian group had a statistically significant 7%, and a borderline significant 6% reduced risk, using the fixed effects and random effects models, respectively (Fig. 2).10 13 14 15 16 The 6 cohorts that stratified data by sex suggested an even stronger protective effect of a vegetarian diet for men.16 17

Figure 2. All-cause mortality for vegetarians compared to health conscious non-vegetarians in a meta-analysis using the fixed effects model. 

*Indicates that participants classified as semi-vegetarians were included in the vegetarian group

It should be stressed that the meat intake in the non-vegetarian group in most of these studies was significantly lower than that of the general population. As described in a different review, the selection criteria for the non-vegetarians in these studies generally included being affiliated with vegetarians in some way or another, likely explaining their relatively low meat intakes. Furthermore, evidence suggests that many of the self-proclaimed vegetarians in these studies actually consumed meat on a regular basis, resulting in minimal differences in meat intake between the groups.10

Considering the lack of difference in meat intake between the vegetarian and non-vegetarian groups, it would only be expected that these studies would not have the statistical power to demonstrate a significant benefit of a vegetarian diet. Two studies which may be considered as especially having limited statistical power due to such limitations were the Heidelberg Study and Health Food Shoppers Study. In the Heidelberg Study, the non-vegetarian group were predominantly semi-vegetarians, while in the Health Food Shoppers Study, a validity assessment of the survey used to classify the participants vegetarian status suggested that 34% of the participants classified as vegetarians actually consumed meat. In fact, a slightly greater percentage of participants classified as vegetarians in the Health Food Shoppers Study were found to consume meat 3 or more times a week than the non-vegetarians in the Heidelberg Study (7.6% and 6.9%, respectively).14 18 Taking this into consideration, I performed a sensitivity analysis excluding either the Heidelberg Study or Health Food Shoppers Study from the meta-analysis. Excluding the Health Food Shopper Study alone reduced heterogeneity and strengthened the association between vegetarian status and a reduced risk of mortality from all-causes (RR 0.91 [95% CI, 0.87-0.94], and 0.92 [95% CI, 0.86-0.98] using the fixed effects and random effects model, respectively).

Most of these studies did not provide separate data for length of adherence to a vegetarian diet. As already described earlier in this review, evidence from several of these studies suggest a stronger effect on mortality would have been observed if the analysis was restricted to long-term vegetarians.10 Another important limitation was that most studies also did not verify changes to vegetarian status of the participants throughout the follow-up, which may in part explain why the association between a vegetarian diet and a reduced risk of mortality weakened over time in several of the studies.9 10

Another important potential limitation of these studies described in detail in the next section, is that some of the participants likely adopted a vegetarian diet in order to improve poor health, such as symptoms of an undiagnosed or developing illness that would ultimately became fatal. Each of these limitations described are expected to have either biased these findings towards null, or even in favor of the non-vegetarian group, suggesting that the findings of this meta-analysis may have significantly underestimated the benefits of an appropriately planned vegetarian diet.

In order to determine which factors may have contributed to the observed reduced risk of death in vegetarians, I also performed separate meta-analyses for the major causes of death. This included mortality from coronary heart disease and cardiovascular disease, and the incidence of all cancers combined. For mortality from coronary heart disease, based on 7 cohorts, the vegetarian group had a statistically significant 25% and 24% reduced risk, using the fixed effects and random effects models, respectively (Fig. 3).13 14 15 16 17 For mortality from cardiovascular disease, based on 7 cohorts, the vegetarian group had a statistically significant 17% and 14% reduced risk, using the fixed effects and random effects models, respectively (Fig. 4).13 14 15 16 17 For the Adventist Mortality Study and Adventist Health Study, mortality from cardiovascular disease was derived from pooling the relative risk for mortality from coronary heart disease and stroke.17 Excluding the Adventist Mortality Study and the Adventist Health Study, the vegetarian group had a statistically significant 8% reduced risk of mortality from cardiovascular disease, using both the fixed effects or random effects model (0.92 [95% CI, 0.85-0.99]).

Figure 3. Coronary heart disease mortality for vegetarians compared to health conscious non-vegetarians in a meta-analysis using the fixed effects model. 

*Indicates that participants classified as semi-vegetarians were included in the vegetarian group

Figure 4. Cardiovascular disease mortality for vegetarians compared to health conscious non-vegetarians in a meta-analysis using the fixed effects model. 

*Indicates that participants classified as semi-vegetarians were included in the vegetation group

As described in a previous review, the degree of reduction in risk of mortality from coronary heart disease observed in vegetarians in these cohort studies was generally in proportion to the expected reduced risk based on the differences in levels of total and non-HDL cholesterol, and blood pressure. There is a plethora of evidence, not only from epidemiological studies, but also clinical trials that plant-based diets and nutrients have favorable effects on total and LDL cholesterol, blood pressure, among several other factors which are established risk factors for cardiovascular and all-cause mortality.19 20 21 22

In the Oxford Vegetarian Study, high compared to low intake of saturated animal fat was associated with a nearly 3-fold increased risk of coronary heart disease mortality.23 Similarly, in a meta-analysis of 11 cohort studies, high compared to low intake of saturated fat was associated with a 32% increased risk of coronary heart disease mortality, despite the inclusion of over-adjustments for dietary and serum lipids.24 It was also found in the Oxford Vegetarian Study that high compared to low intake of total animal fat and dietary cholesterol was associated with a greater than 3-fold increased risk of coronary heart disease mortality.23 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 animal species in which researchers were able to find a method to sufficiently elevate cholesterol concentrations. This includes herbivores, omnivores and carnivores from mammalian, avian and fish species, and over one dozen different species of nonhuman primates.

In both the Oxford Vegetarian Study and the Adventist Mortality Study, high compared to low intake of eggs was associated with an increased risk of coronary heart disease mortality.23 25 However, for ill-defined reasons, these studies were excluded from several recent meta-analyses. In the Adventist Mortality Study and Heidelberg Study, high compared to no intake of meat was associated with a 50% and almost 5-fold increased risk of coronary heart disease mortality, respectively.14 25 Similarly, in the Adventist Health Study, high compared to no intake of beef was associated with a greater than 2-fold increased risk for men.26 In addition, recent meta-analyses of prospective cohorts found that an increment of 1 mg/day of heme iron, found only in animal tissue, is associated with a 16% and 27% increased risk increased risk of type II diabetes and coronary heart disease, respectively.27 28 Therefore, the totality of evidence strongly suggests that the observed greater longevity of vegetarians can be explained, at least in part, by the reduced risk of cardiovascular disease as the result of the replacement of animal foods with minimally processed plant foods.

For incidence of all cancers combined, based on 5 cohorts, the vegetarian group had a statistically significant 8%, and borderline significant 6% reduced risk, using the fixed effects and random effects model, respectively (Fig. 5).13 14 29 30 Excluding the Health Food Shoppers Study removed evidence of heterogeneity and strengthened these findings (RR 0.90 [95% CI, 0.85-0.99] using both the fixed effects and random effects models).

Figure 5. Cancer incidence for vegetarians compared to health conscious non-vegetarians in a meta-analysis using the fixed effects model. 

*Indicates that participants classified as semi-vegetarians were included in the vegetation group

The finding of a decreased risk of cancer in vegetarians may also be explained, in part, by a diet devoid in heme iron. Controlled feeding trials have established that NOCs (N-nitroso compounds) arising from heme iron in meat forms potentially cancerous DNA adducts in the human digestive tract, likely in part, explaining the significant association between heme iron and an increased risk of colorectal cancer in recent meta-analyses of prospective cohort studies.31 32 33 Heme iron has also been associated with numerous other cancers. These lines of evidence also provide confidence in the validity of the findings of greater longevity in vegetarians.

Why Some People Choose to Become Health Conscious

Which came first,
vegetarianism or ill health?

In health research, the reasons why some people chose to become health conscious is critically important when interpreting data from observational studies. This is because it is possible that it may not have been the health conscious lifestyle that caused the examined outcome, but rather the outcome that caused the health conscious lifestyle, ie. reverse causality. As previously described in a different review, reverse causality occurs when the studied effect precedes the cause. An example in health research is the frequent paradoxical observation that former smokers have worse health outcomes than current smokers. These unfavorable outcomes are not explained as being caused by smoking cessation, but rather that those who quit smoking tend to have done so because they were showing symptoms of illness, illnesses that ultimately resulted in the observed unfavorable health outcomes. A similar phenomenon has been observed in nutritional research where sick people tend to adopt a more plant-based diet, suggesting that this would bias observational studies towards showing an unfavorable effect of plant-based diets and nutrients, and therefore a favorable effect of animal based diets and nutrients.34

Although Denise Minger suggests that the favorable health outcomes for vegetarians observed in many studies maybe unrelated to dietary factors, but rather explained by other healthy habits associated with vegetarianism, she fails to consider the possibility that these vegetarians may have become health conscious, including adopting a vegetarian diet, in order to improve poor health. The results of a recent study from the Netherlands illustrates the critical importance of considering reverse causality in research on plant-based diets. The researchers found that 75% of the vegetarian participants with cancer adopted a vegetarian diet after diagnosis, consistent with previous research which found that cancer survivors are highly motivated to adopt a more plant-based diet with the intention of improving poor health.35 36

Although health researchers often attempt to partially control for reverse causality by excluding participants who were diagnosed with cancer, cardiovascular disease and other life threatening conditions prior to baseline of a study, it is nearly impossible to fully control for reverse causality, as participants may make dietary changes due to symptoms or unfavorable risk factors that act as markers of an undiagnosed or developing disease. For example, it is known that in studies carried out as far back as the late 1950s, participants with unfavorable blood cholesterol levels tended to reduce the intake of dietary cholesterol and saturated fat (ie. in part, by abstaining from animal foods). This resulted in paradoxical findings where participants who consumed more dietary cholesterol and saturated fat actually had lower serum cholesterol levels. These paradoxical findings were produced, in part, because those participants who continued to consume a diet rich in these lipids were choosing to do so because they were able to maintain lower cholesterol levels despite consuming such a diet (ie. due to favorable genetics).37 Many individuals who attempt to downplay the harmful effects of these lipids, such as Minger has done in her book have chosen to ignore this critical factor when reviewing research on the diet-heart hypothesis.24

In the chapter Herbivore’s Dilemma, Minger reviews several prospective cohort studies that compared the mortality rates of vegetarians to health conscious non-vegetarians, carefully selecting only those studies in which vegetarians were not found to live longer. These studies were the Oxford Vegetarian Study, the Health Food Shoppers Study and the Heidelberg Study, all included in my meta-analysis. Minger emphasizes the lack of reduced risk of mortality in the vegetarian groups, while neglecting to mention that the difference in intake of meat between the groups was relatively small. Minger especially focuses on the Heidelberg Study, happening to be the smallest study, which found a non-significant increased risk of all-cause mortality in the vegetarian group. Minger points out that in this particular cohort, the vegetarians had greater levels of physical activity, consumed less alcohol and smoked less. Minger then states “Mortality and disease rates, in this case, might be expected to turn up in favor of the vegetarian crowd, even though the opposite ended up happening”[p.270]. This statement is outright misleading as all these factors were controlled for in the analysis. One could also correctly point out that the vegetarians tended to be older than the meat eaters, but suggesting that this would be expected to turn up in favor of the meat eaters would also be misleading, as age was also controlled for. Either way, the differences in mortality between the groups did not even come close to being statistically significant.

There are several important findings that Minger neglected to mention that cast doubt on the suggestion that a vegetarian diet had a harmful effect on the participants in the Heidelberg Study. For example, it was shown in an earlier follow-up of this study that, similar to the Adventist studies, the participants who adhered to a very low meat diet for at least 20 years had a 29% lower risk of all-cause mortality compared to those who adhered to such a diet for fewer years.10 Excluding the first 5 years of follow-up significantly strengthened this association, resulting in a 45% lower risk of all-cause mortality, suggesting that reverse causation may have attenuated the results for the entire follow-up.38 This difference in mortality was considerably stronger than the mortality difference between vegetarians and non-vegetarians. Unfortunately the researchers appear to not have provided any data comparing mortality in long-term vegetarians and non-vegetarians. Indeed, in other cohorts it has been observed that compared to non-vegetarians, short-term vegetarians had a higher rate, whereas long-term vegetarians had a lower rate of all-cause mortality.34 These findings suggest that those who adopted a vegetarian diet more recently had done so due to deteriorating health, biasing the results in favor of the non-vegetarians. 

Also as already briefly mentioned, in this study it was also found that intake of meat 3 or more time per week was associated with an almost 5-fold increased risk of mortality from ischemic heart disease, whereas there was a greater than 2-fold risk increase for those who consumed fish more than once per month. One of the reasons that this did not translate into an increased risk of all-cause mortality in the non-vegetarian group may have been due to the very low intake of meat, with less than 7% of the non-vegetarians consuming meat 3 or more times a week.14 Another important finding was that there was a trend towards a favorable effect of a vegetarian diet on mortality in the early years of follow-up, which declined over time (Fig. 6).14 This suggests the likelihood of undocumented changes in vegetarian status in a portion of the participants throughout the follow-up, which would be expected to have attenuated a possible favorable effect of a vegetarian diet. A similar phenomenon was also observed in several other studies included in my meta-analysis.9

Figure 6. Standard Mortality Rates (SMRs) and their 95% CIs for all-cause mortality, dietary group, and 5-year follow-up period, separately for males and females. (○, female vegetarians; •, female nonvegetarians; □, male vegetarians; ▪, male nonvegetarians).

Minger also points out that there was a trend towards a higher rate of mortality among the vegans in the Heidelberg Study, which included only 60 vegans, while neglecting to mention that in the Adventist Health Study 2, which included almost 100 times many vegans found that compared to the non-vegetarians, the vegans, especially male vegans experienced a lower rate of mortality.16 In the Heidelberg Study, while current smokers had the same mortality rate from cancer as never smokers, past smokers suffered from a 70% greater risk of cancer mortality than current smokers. This strongly suggests that many of the past smokers in this cohort quit smoking because they had deteriorating health.14 This raises the question as to whether the participants in this cohort also had a tendency to adopt a vegetarian diet after becoming ill, possibly explaining the unfavorable mortality rates in the vegetarian group. Perhaps the reason why the vegetarians in this group tended to be older, was not because they were becoming more ethical with old age, but because they were becoming more health conscious, which included adopting a vegetarian diet due to deteriorating health with old age. As these lines of evidence described suggest, the trends towards elevated mortality in the vegetarian groups in the Heidelberg Study may be explained by reverse causation. It is more than possible that it was not the vegetarian diet that caused these unfavorable outcomes, but deteriorating health, which would ultimately resulted in these unfavorable outcomes that caused a portion of the participants to adopt a vegetarian diet.

Ignoring the difficult

There is strong evidence that plant-based diets, including those rich in whole-grains and legumes reduces the risk of premature death from chronic and degenerative diseases, which in-turn helps explain the longevity of a number of plant-based populations. Contrary to the findings for plant-based diets, there is a plethora of evidence demonstrating the harms of popular carbohydrate restricted diets. For example, meta-analyses of clinical trials have found that low-carbohydrate diets elevate LDL cholesterol and impair endothelial function.39 Furthermore, a recent meta-analysis of prospective cohort studies with more than 272,000 participants found that low-carbohydrate diets, particularly those rich in animal foods are associated with an increased risk of all-cause mortality.40 Evidence also shows that the hazardous effects of diets rich in animal foods are also applicable to that of organic, grass-fed animal foods. These, and other lines of evidence described throughout this review appear to have been almost entirely ignored by proponents of these diets, perhaps because they find it too difficult to explain. 

Although there is strong evidence that plant-based diets promote longevity, it is important to replace animal foods with minimally refined plant foods in order to achieve the maximum benefits. This may in part explain why the benefits of a vegetarian diet were more evident in the Adventists than other populations.9 In conclusion, the totality of evidence supports the hypothesis that appropriately planned whole foods, plant-based diets promote longevity. 


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-Heart: The Role of Vegetarian Diets in the Hypothesis

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

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

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

Establishing Causation

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

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

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

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

Serum Lipids

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

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

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

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

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

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

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

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

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

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

Beyond Cholesterol

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

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

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

Caldwell Esselstyn on making heart attacks history

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

Diet-Heart Posts

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

Please post any comments in the Discussion Thread.