Saturated Fat and Heart Disease Meta-Analyses: Were Scientists Wrong?

Was it Ancel Keys or the low carb advocates
who fabricated data on saturated fat?

In a previous review, Clearing up the Confusion Surrounding Saturated Fat, I examined several important flaws and omissions in two meta-analysis studies which are frequently cited as evidence against the hypothesis that dietary saturated fat increases the risk of heart disease. The earlier study was published in 2010 by Siri-Tarino and colleagues in the American Journal of Clinical Nutrition, and the more recent study published by Chowdhury and colleagues in the Annals of Internal Medicine. These studies were both cited in a recent Time magazine article by Bryan Walsh as evidence to "eat butter" for health. In this earlier review I focused primarily on how the studies included in these meta-analyses, as well many other studies actually provide support for the hypothesis that saturated fat increases the risk of fatal forms of heart disease.

Although a number of prominent diet-heart researchers identified many serious flaws and omissions in these meta-analyses that cast doubt on the validity of the researchers conclusions, there are several other critical flaws related to how the estimates were derived for these meta-analyses that have not received adequate attention.1 2 3 4 5 This review will examine how a number of erroneous estimates may have biased the results and primary findings of these meta-analyses. Of particular concern, is in regards to how Siri-Tarino and colleagues derived negative estimates for three studies for which the original peer reviewed publications found positive associations between saturated fat and risk of heart disease. These studies and the estimates published in the meta-analysis by Siri-Tarino and colleagues are described in the table below. 

Study Name                                Risk Ratio (RR)    95% Confidence Interval (95% CI)

Framingham Heart Study6         0.92                       0.68, 1.24

Honolulu Heart Study7               0.86                       0.67, 1.12

Lipid Research Clinics Study8    0.97                       0.80, 1.18

Note: The risk ratio represents high vs low intake of saturated fat in relation to coronary heart disease. An estimate below 1 suggests a benefit of higher intake, and vice-versa. The estimates are considered statistically significant only if both the lower and upper 95% confidence intervals are on either side of 1.

The estimates published in the meta-analysis by Siri-Tarino and colleagues for all three of the abovementioned studies suggest a non-significant trend towards a benefit of saturated fat intake, greatly contrasting the findings from the original peer reviewed publications.9 This warrants an investigation into how Siri-Tarino and colleagues derived these negative estimates.

The Framingham Heart Study

Contrary to other studies included in the meta-analysis, the Framingham study reported estimated risk ratios for low vs high intake, rather than high vs low intake of saturated fat. Among the younger cohort in this study, 10% vs 15% of intake was associated with a 22% decreased risk of coronary heart disease (RR=0.78 [95% CI, 0.61-1.00]).6 Conversely this benefit of low intake was not observed among the older cohort (RR=1.06 [95% CI, 0.86-1.30]). Nevertheless, both of these estimates were controlled for serum cholesterol, which is expected to have biased these findings against showing an adverse effect of saturated fat. 

The tables in the meta-analysis clearly show that rather than converting the risk ratios for low vs high intake to appropriately reflect high vs low intake, Siri-Tarino and colleagues simply reported the estimates for 10% vs 15% of intake as representing 15% vs 10% of intake of saturated fat. The combined estimate for the younger and older groups in this cohort should therefore have been reported as RR=1.09 [95% CI, 0.81-1.47], and not as RR=0.92 [95% CI, 0.68-1.24], which was the estimate reported in the meta-analysis. The estimate provided in the meta-analysis for this study is clearly erroneous and biased the meta-analysis against showing an adverse effect of saturated fat.

The Honolulu Heart Study

In the original peer reviewed publication from the 10 year follow-up of the Honolulu Heart Study, a high intake of saturated fat was associated with a highly statistically significant increased risk of incidence of combined myocardial infarction (heart attack) and coronary heart death.7 This was despite over-adjustment for serum cholesterol. However, when combined with the incidence of the soft end points, angina and coronary insufficiency, the association was only statistically significant in the univariate analysis which did not control for serum cholesterol. The authors of this paper however, warned about misinterpreting the results for these soft end points, asserting:

When interpreting these results about whether the nutrients relate differently to the different manifestations of coronary heart disease, one should keep several problems in mind. The diagnostic certainty of the soft end points (angina pectoris or coronary insufficiency) is much less than that of the hard end points (myocardial infarction or coronary heart disease death).This could result in attenuation of a true relationship.

In the meta-analysis by Siri-Tarino and colleagues, the estimates for the 10 year follow-up of the Honolulu Heart Study were derived not from a peer reviewed publication, but rather from a separate data set obtained from the NHLBI. The primary reason that these estimates provided in the meta-analysis greatly contrasted with that of the peer reviewed publication can likely be explained by difference in the inclusion criteria of the participants. The tables in the meta-analysis show that the data used was based on 1177 cases of coronary heart disease from 8006 participants. However, in the peer reviewed publication there was a total of only 456 cases of coronary heart disease from 7088 participants.  Due to several important factors, the researchers of the original peer reviewed publication excluded 918 of the total 8006 participants from their analysis, asserting:

Men who reported that their intake was atypical for the day covered by the 24 hour recall, or who could not recall their intake, were excluded from the present analyses (n=502). Additionally, all men assessed as being prevalent cases of coronary heart disease (n=301), stroke (n=111), or cancer (n=49) were excluded from the analyses.

It is therefore evident that more than 60% of coronary events included in the meta-analysis for this particular study occurred in participants who had pre-existing disease at study baseline and/or reported unreliable dietary intake. As these additional participants made up less than 12% of the population, yet experienced more than 60% of the total events, this suggests the likelihood that these events occurred primarily among the participants with pre-existing cardiovascular disease, rather than the healthy participants reporting unreliable dietary intake. It should be noted that Siri-Tarino and colleagues clearly stated that one of the inclusion criteria for the meta-analysis was that “study participants were generally healthy adults at study baseline”, suggesting that the data they selected did not meet their own criteria.

When considering the fact that the estimate for this study used in the meta-analysis was negatively associated with coronary heart disease, rather than positively associated as was the case in the peer reviewed publication, this suggests that the participants excluded in the peer reviewed publication who experienced coronary events, largely being those with pre-existing disease, were reporting a lower intake of saturated fat. This is concerning considering the evidence that people who are diagnosed of being at risk of cardiovascular disease tend to limit saturated fat intake post-diagnosis. For example, in the earliest study included in the meta-analysis, participants diagnosed with high cholesterol had a tendency to reduce intake of saturated fat in order to improve risk factors.10 It should therefore not be surprising that participants with established cardiovascular disease likely reported a lower intake of saturated fat in this study, suggesting that a lower reported intake was only a marker of more disease, rather than a cause of it. This phenomenon is known as reverse causality, and is one of the important reasons why participants with pre-existing disease are either excluded, or examined separately from healthy participants in such studies. The inclusion of such data in a meta-analysis could significantly distort the findings. 

It is not entirely clear why a null estimate was reported for this study in the more recent meta-analysis published by Chowdhury and colleagues. However, the sample size described in supplement section of the meta-analysis paper suggests that the estimates were based on the same misleading data used by Siri-Tarino and colleagues, and not the original peer reviewed publication.11

The Lipid Research Clinics Study

In the Lipid Research Clinics study, it was observed that among the younger cohort that a 1% increased intake of energy from saturated fat was associated was a statistically significant 11% increased risk of death from coronary heart disease (RR=1.11 [95% CI, 1.04-1.18]).8 However, similar to the Framingham study, this study also included over-adjustments for serum cholesterol and the adverse effect of a high intake of saturated fat was not apparent among the older cohort (RR=0.96 [95% CI, 0.88-1.05]).

In the meta-analysis by Siri-Tarino and colleagues, the estimate for both the younger and older cohorts combined using the random-effects model was reported as RR=0.97 [95% CI, 0.80-1.18]. It is clear that this estimate is erroneous. When using the random-effects model for two estimates, the estimate with the narrowest confidence intervals should carry more weight, and therefore the combined estimate should have been much closer to the estimate for that of the younger cohort. The estimate for a 1% increase of energy from saturated fat should have been reported as RR=1.04 [95% CI, 0.90-1.19]. Similar to the abovementioned studies, this erroneous estimate biased the meta-analysis against showing an adverse effect of saturated fat.

Reanalysis of the Data

The use of erroneous estimates for several studies included in the meta-analysis by Siri-Tarino and colleagues warrants a reanalysis of the original data. I therefore performed a revised meta-analysis of the same 16 prospective cohort studies included in this meta-analysis. The methods used to derive the estimates have been described previously, and were mostly consistent with those used by Siri-Tarino and colleagues. For the Honolulu Heart Study, I derived the estimates based on only the hard coronary end points due to the concern of the accuracy of the estimates for the soft end points being less certain. As the exact P-value was not available for this publication, and indicated only as being between 0.01 and 0.001, I chose to derive the corresponding standard error using a P-value of 0.01, as this was the most conservative estimate.7

In a meta-analysis based on the 16 studies included in the meta-analysis published by Siri-Tarino and colleagues, dietary saturated fat intake was associated with a statistically significant 16% increased risk of coronary heart disease (Fig. 1).

FIGURE 1. Risk ratios and 95% CIs for fully adjusted random-effects models examining associations between saturated fat intake in relation to incidence of coronary heart disease. ¹Studies that included adjustments for serum or LDL cholesterol. SAT, saturated fat intake.

I also carried out an updated meta-analysis, including prospective cohort studies published up until November 2014 that provided the necessary data to derive risk ratios and the corresponding 95% confidence intervals. If a study was published multiple times, the estimate for the longest period of follow-up was used. A total of 21 studies were included, including recent publications not included in either the meta-analyses by Siri-Tarino and colleagues, and Chowdhury and colleagues.7 8 9 12 13 14 15 16 17 18 19 20 21 22 23 24 25 In a meta-analysis of 21 studies, dietary saturated fat was associated with a statistically significant 15% increased risk of coronary heart disease (Fig. 2).

FIGURE 2. Risk ratios and 95% CIs for fully adjusted random-effects models examining associations between saturated fat intake in relation to incidence of coronary heart disease. ¹Studies that included adjustments for serum or LDL cholesterol. SAT, saturated fat intake.

The findings from these meta-analyses presented here are compatible with the findings from a broad range of evidence described previously. This includes findings from randomized controlled trials showing an adverse effect of saturated fat on blood cholesterol and arterial function, as well as the demonstrated unequivocal causal relationship between diets rich in cholesterol and saturated fat, and the development of atherosclerosis in nonhuman primates, among dozens of other animal species. Furthermore, these findings are supported by numerous ecological studies, including the Seven Countries Study. 

The estimates of this meta-analysis are clearly stronger than that of the Siri-Tarino and Chowdhury meta-analyses, neither of which produced statistically significant estimates. One of the primary reasons for these contrasting estimates was due to the correction of the estimates for several studies described above. These contrasting estimates can also in part be explained by the correction of erroneous estimates for the confidence intervals reported in the Siri-Tarino meta-analysis for the Ireland-Boston Diet Heart Study, and in the Chowdhury meta-analysis for the EPIC-Greece study. It is clear that in the original peer reviewed publications that the estimates in these studies were statistically significant to the 95% confidence level, yet non-statistically significant estimates were reported in the meta-analyses for these studies, biasing against showing an adverse effect of saturated fat.13 20

Another important difference in the meta-analyses presented here, is that the estimates for studies reporting estimates as a 1% increase of energy were transformed to represent a 5% increase of energy from saturated fat. In the Siri-Tarino meta-analysis the researchers either simply reported the estimates for a 1% increase, or transformed the estimates to represent a similarly small increase of energy. Similarly, Chowdhury and colleagues multiplied the estimates from these studies by the power of 2.18, effectively representing the effect of an increase of only a 2.18% increase of energy. The researchers rational for this was that this equation would be expected to show the effect of mean top vs bottom third of intake. While this equation may be suitable for some studies using different scales of measurement, it requires a leap of faith to assume a difference of only 2.18% of energy represents high vs low intake in these studies. Reporting estimates as a 5% increase of energy, as was done here would make differences for high vs low intake much more comparable to that of the other included studies, while still being moderately conservative. As the studies that reported estimates as a 1% increase of energy were more likely to show a positive relationship between saturated fat and coronary heart disease, failing to transform the estimates to represent a sufficient change in intake may result in minimizing the statistical power of these studies, and in-turn biasing a meta-analysis against showing an adverse effect of saturated fat.

Conflicts of Interest

The meta-analyses published by Siri-Tarino and colleagues and Chowdhury and colleagues contained erroneous estimates for several positive studies which in-turn biased against showing an adverse effect of saturated fat. Given the fact that these researchers were well informed in this area of research, it is difficult to accept that they were simply unaware of any of the issues described here. In the meta-analysis by Siri-Tarino and colleagues there was clear evidence of potential conflicts of interest. The meta-analysis was funded in part by the National Dairy Council, and the senior researcher, Ronald Krauss had reported receiving grants from the National Dairy Council, the National Cattleman’s Beef Association and the Robert C. and Veronica Atkins Foundation. Similarly, several of the researchers of the meta-analysis by Chowdhury and colleagues have reported receiving grants from the food industry. Suggestive evidence of these researchers intention to downplay the role of saturated fat on fatal heart disease have also been described previously.

Although receiving grants from a particular industry does not necessarily negate the findings of a study, when errors are made that bias the study results in favor of the concerned industry, the intentions of the researchers should be questioned. The lines of evidence described here lends support to the likelihood that these researchers put their own interests before that of the general public, driving the public to follow dangerous dietary patterns at the hands of fad diet advocates who promote these studies.

Putting Data into Context

It is important to note that the influence that saturated fat has on the risk of disease is not primarily determined by intake per se, but by which foods saturated fat is substituted for. As the intake of dietary fiber was universally low among participants in these studies, this suggests that participants consuming diets lower in saturated fat were substituting saturated fat primarily with lean animal foods and heavily processed foods.26 In addition, as dietary fiber was associated with a decreased risk of coronary heart disease in a number of these studies, the estimates described here therefore could be a significant underestimation of the effect of replacing saturated fat with more healthful, fiber rich foods.26 Furthermore, in the studies included in this meta-analysis, the difference for high vs low intake of saturated fat was relatively low, often only ranging between about 5% and 10% of energy. This suggests that individuals following popular diets which emphasize far greater intakes of saturated fat than recommended levels may be at a much greater risk.

It is also important to note that the effect that a particular food has on the risk of coronary heart disease cannot be fully explained by the amount of one particular nutrient, but rather by multiple nutrients that likely operate together in a complex manner to modify the risk of disease. Therefore, it would be more appropriate to compare the substitution of different foods, rather than focusing entirely on substituting single nutrients. Focusing attention on recommending healthy dietary patterns that are naturally low in saturated fat, while rich in dietary fiber and other beneficial nutrients; primarily, minimally processed, plant-based diets would likely be a more effective measure to improve overall dietary quality, resulting in greater improvements to heart health compared to the more contemporary reductionist approach of focusing on modifying single nutrients. The effectiveness of such a diet was recently demonstrated again by Caldwell Esselstyn in a follow-up of 200 high-risk patients. In this study, coronary artery disease was either arrested or reversed in the great majority of adherent patients, clearly contrasting that of any other peer-reviewed study of similar size.27

This review demonstrates that the conclusions of several meta-analysis studies which suggest that dietary saturated fat unlikely increases the risk of heart disease are misleading, and that the current evidence supports the recommendations to replace foods rich in saturated fat with minimally refined plant based foods. Recommendations based on the findings of these meta-analyses made by the media and low carb advocates to consume more saturated fat rich foods are therefore unsubstantiated and likely dangerous. While it may make an interesting read being told that scientists, such as Ancel Keys have intentionally deceived us into believing that saturated fat-rich foods are unhealthy, it is appears that it may actually be the authors of such articles who lack in the way of honesty. 

Study acronyms: ATBC, Alpha-Tocopherol Beta Carotene Study; BLSA, Baltimore Longitudinal Study of Aging; EPIC-Greece, European Prospective Investigation into Cancer Greece; EUROASPIRE, European Action on Secondary and Primary Prevention through intervention to reduce events; FHS, Framingham Heart Study; GPS, Glostrup Population Study; HHS, Honolulu Heart Study; HLS, Health and Lifestyle Survey; HPFS, Health Professionals' Follow-Up Study; IBDH, Ireland-Boston Diet Heart Study; IIHD, Israeli Ischemic Heart Disease Study; JACC, Japan Collaborative Cohort Study; JPHC, Japan Public Health Center Based Study; KIHD, Kuopio Ischaemic Heart Disease Risk Factor Study; LRC, Lipid Research Clinics; MALMO, Malmo Diet and Cancer Study; NHS, Nurses' Health Study; SHS, Strong Heart Study; WES, Western Electric Study.

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.

Traditional Diets in Asia Pacific and Implications for Health, and the History of Disease Prevention

I previously reviewed the health of a number of primitive populations, including evidence from numerous preserved Inuit mummies that predate western contact, demonstrating that without consuming a morsel of modern processed food throughout their entire lifetimes, the traditional Inuit developed atherosclerosis, osteoporosis, breast cancer and numerous other chronic and degenerative diseases that are evidently partly explained by their carnivorous diet. The diets and incidence rates of disease in traditionally living populations can provide implications for disease prevention, which can be used to supplement the current knowledge of the impact of dietary and lifestyle factors on diseases from other forms of evidence, including observational, laboratory and clinical studies in order to achieve maximum protection.

The Nomadic Kirghiz and Dzungarian Plainsmen

In the 1920’s, Kuczynski reported on the nomadic plainsmen of the Kirghiz and Dzungarian Steppes in Central Asia and estimated that they consumed an astonishing 20 liters of fermented mare’s milk, and between 10 to 20 pounds (4.5 to 9kg) of meat per day.1 2 Lack of systematically documented dietary data however suggests that these findings could have been slightly overestimated, as evidently has been the case for early researcher's estimates of the Masai's intake of milk, meat, cholesterol and total energy.3 Nevertheless, these nomadic plainsmen consumed enormous quantities of organic pasture raised animals foods, perhaps among the largest ever documented. 

Kuczynski noted that these nomads, evidently largely as a result of their diet experienced a high incidence of obesity, premature extensive atherosclerosis, contracted kidney, apoplexy, arcus senilis, and gout.4 5 In specific, Kuczynski asserted that:2

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.

The Nomadic Kirghiz Plainsmen

Kuczynski compared the diet and health of these nomadic plainsmen with Russian peasants, who had an apparent low incidence of these conditions while consuming a vastly different diet. Their diet was based on soup, bread, pickles, potatoes, with very little meat, but consumed large amounts of alcohol.5 In comparison to the nomadic plainsmen, Kuczynski asserted in regards to these Russian peasants that:2

Repeatedly I found at the age of about seventy years no signs of arteriosclerosis, no arcus senilis, etc.; they were men of youthful appearance, with no grey in their still abundant growth of hair, and with their sexual functions still intact.

For more information regarding the health of nomadic populations, Don Matesz has previously posted an informative review addressing the high rates of obesity, cardiovascular disease and cancer among the modern, still largely nomadic Mongols consuming diets rich in organic pasture raised animal foods.

The Native Indonesians 

In 1916, Cornelis D. de Langen observed that the native Javanese, the indigenous people of the Indonesian island of Java who consumed a diet which was 'mainly vegetarian with rice as the staple, that is very poor in cholesterol and other lipids', had very low levels of serum cholesterol and incidence of coronary heart disease.6 Conversely, de Langen observed that their Javanese counterparts who worked as stewards on Dutch passenger ships and consumed traditional cholesterol laden Dutch food had much higher levels of serum cholesterol and incidence of coronary heart disease.7 Blackburn noted in regards to de Langen's classical findings from Indonesian hospitals that:6 

Pursuing this clinical impression, he reviewed 10 years of admissions charts and found only 5 cases of acute gallbladder disease among many thousands of patients passing through the medical wards and only 1 case on the surgery service among 70,000 admissions surveyed. 

Following these observations, de Langen stated in regards to the rarity of vascular disease among the Javanese that:6 

thrombosis and emboli, so serious in Europe, are most exceptional here. This is not only true of internal medicine, but also on surgery, where the surgeon needs take no thought of these dreaded possibilities among his native patients. Out of 160 major laparotomies and 5,578 deliveries in the wards, not a single case of thrombosis or embolism was seen.

These findings closely resemble observations from over 15,000 operations carried out in Norway during the period around World War II, where the changes in incidence of post-operative thrombosis was consistent with changes in the availability of cholesterol laden foods [reviewed previously]. Blackburn also noted in regards to de Langen’s 1922 experiment, which is regarded as apparently the first ever systematic feeding experiment of diet in relation to serum cholesterol levels, that:6

…he found an average 40 mg/dl increase in cholesterol in 5 Javanese natives who were shifted from a rice-based vegetarian cuisine to a 6-week regimen high in meat, butter, and egg fats.

These findings were reproduced decades later in hundreds of tightly controlled feeding experiments, firmly establishing that dietary cholesterol and isocaloric replacement of complex carbohydrates and unsaturated fat by saturated fat raises LDL and total cholesterol in humans.8

In 1908, Williams noted in regards to the findings of early doctors who practiced in Indonesia and the rarity of cancer among the Javanese that:9

...a single example of a malignant tumour in a native being esteemed a great rarity.

The Okinawans

In 1949, a government survey found that in Okinawa, known to have the highest concentration of centenarians in the world, the population consumed about 85% of their total energy intake from carbohydrates, with the staple at the time being the sweet potato. The dietary survey also showed that the Okinawans derived about 9% of their energy intake from protein and less than 4% of energy from all sources of animal foods combined (Table 1).10 These findings were largely consistent with previous dietary surveys dating back to 1879 and 1919.11

In 1946, Steiner examined autopsies of 150 Okinawans, of which 40 were between the age of 50 and 95. Steiner noted only seven cases of slight aortic atherosclerosis, all of which were found in those over the age of 66, and only one case of calcification in the coronary arteries. In 1946 Benjamin reported similar findings from a study of 200 autopsies on Okinawans.12

Even in 1995 the observed rates of coronary heart disease and dietary related cancers, including that of the colon, prostate, breast and ovarian in Okinawa were not only many fold lower than that of the United States, but even significantly lower than that of mainland Japan.10 This may be explained by the likelihood that these diseases are slowly progressive diseases and therefore the more traditional Okinawan diet consumed several decades prior would still have played a major role in the development and manifestation of these diseases.13 14 15

The Papua New Guineans

The Papua New Guineans traditionally subsisted on a plant based diet, of which a number of varieties of sweet potatoes typically supplied over 90% of dietary intake. They also grew a number of other crops including corn, as well as sugar cane which was consumed as a delicacy. Pig feasts are organised a few times a year, but at which pork is not consumed in excess of 50 grams. A dietary survey on the Papua New Guineans highlanders estimated that carbohydrate accounted for 94.6% of total energy intake, among the highest recorded in the world. Total energy intake was adequate, however only 3% of energy intake was derived from protein (25g for men and 20g for women), yet there was no evidence of dietary induced protein deficiency or anemia. Furthermore, this surveyed population was described as being muscular and mostly very lean, physically fit and in good nutritional state.16 17 They also drank 'soft' water which is considered a risk factor for cardiovascular disease. It was estimated that tobacco was smoked by 73% of males and 20% females. Also, the highlanders spend up to twelve hours a day inside a smoke-filled house due to centrally placed open wood fires with little ventilation and no chimneys in their homes, resulting in a very high exposure to hazardous smoke in this population.16 

Despite cardiac risk factors including high exposure to smoke and soft drinking water, a number of authors observed a great rarity of incidence of atherosclerosis, coronary heart disease and stroke among the traditional Papua New Guineans, but also noted an increase in incidence paralleling the Westernization of the nation. In 1958, Blackhouse reported on autopsies of 724 individuals between 1923 and 1934 and found no evidence of heart attack incidence and only one case of slight narrowing of the coronary arteries. However, it has been suggested that this study was selective as only a small portion of the autopsies were performed on females or the elderly. In 1969, Magarey et al. published a report on the autopsy results of 217 aortas and found a great rarity of atherosclerosis. The authors noted that the prevalence and severity of atherosclerosis was less than had been reported in any previously investigated population.18 In 1973, Sinnett and Whyte published findings from a survey of 779 highlanders using electrocardiograms among other methods, and found little probable evidence of coronary heart disease, and no clinical evidence of diabetes, gout, Parkinson’s disease, or any previous incidence of stroke.16

For a population that consumed virtually the highest intake of carbohydrates out of any population to also have virtually the lowest incidence of atherosclerosis and diabetes ever recorded highlights the vital importance of the health properties of specific carbohydrate rich foods. These findings further question certain 'carbohydrate-induced dyslipidemia' hypotheses, emphasized by certain researchers, who perhaps intentionally do not always take the quality of carbohydrate rich foods into careful consideration.19

In 1900, Sir William MacGregor reported in the Lancet in regards to the observed rarity of cancer among the native Papua New Guineans, asserting that:20

For nine and a half years I never saw a case in British New Guinea ; but at the end of that time there occurred an example of sarcoma of the tibia in a Papuan, who had for seven or eight years lived practically a European life, eating tinned Australian meat daily.

In 1974, Clezy brought to attention the rarity of mortality from colorectal cancer among the Papua New Guineans, for which the observed annual rate per 100,000 was 0.6 for men and 0.2 for women. These rates were 100 fold lower than that of many developed nations during the same time period, although this could have been in part explained by underdiagnosis.17

Even in more recent statistics after modest changes towards a western diet, the Papua New Guineans still had among the lowest rates of hip fractures in the world, which Frassetto et al. observed was more than 50 fold lower than that of the Scandinavian nations.21 Although these researchers ascribed the worldwide differences in rates of hip fractures to the ratio of vegetable to animal protein, evidence from prospective cohort studies and randomized controlled trials, as well as experimental animal models suggests that saturated fat may be at least as great, if not an even greater contributor to poor bone health.22 23 24 25 26

The Tokelauans and Pukupukans

In the video below, Plant Positive reviews the diet and health of the Tokelauans and Pupukans whose diet is rich in coconuts, as well as the diet and health of other South Pacific island populations.

The Tokelauns, and more on the Masai

A 1908 Review on the Causation of Cancer

In 1908, William Roger Williams published an extensive review of the medical literature and documentations from a large number of populations around the world before the widespread use of intensive farming practices. Williams observed that compared to the nations with carnivorous dietary patterns there was a significantly lower incidence of cancer among the nations subsisting predominantly on a plant-based diet. He also noted that groups within nations with carnivorous dietary patterns that largely abstained from animal foods, such as nuns, monks, slaves and prison inmates had a similar low incidence of cancer.9

Williams reported on the cancer rates of the area inhabited by the Gaucho of the Argentina Pampas, another nomadic population that subsisted predominantly on organic pasture raised animal foods, noting that:9

Cancer is commoner in Argentina which comprises the pampas region inhabited by the Gauchos, who for months subsist entirely on beef, and never touch salt than in other parts of South America. On the other hand, among the natives of Egypt, who are of vegetarian habits, and consume immense quantities of salt, cancer is almost unknown.

The Nomadic Argentinean Gaucho

These findings are largely consistent with modern reviews from prominent health authorities, including the report from the expert panel of the World Cancer Research Fund that produced convincing evidence that red meat is a major risk factor for cancer and that dietary fiber provides significant protection [reviewed previously]. However, these findings raise questions as to whether the Egyptians plant-based diet that is centered on wheat provides significant protection against salt sensitive cancers. In regards to the cancer incidence among the different ethnic groups of Egypt, Williams quoted from a 1902 publication in the British Medical Journal authored by Dr. F. C. Madden of Cairo that:9

The consensus of opinion among medical men in Egypt is, that cancer is never found either in male or female, among the black races of that country. These include the Berberines and the Sudanese, who are all Mussulmans, and live almost entirely upon vegetarian diet. Cancer is fairly common, however, among the Arabs and Copts, who live and eat somewhat after the manner of Europeans.

Williams also observed that the increases in incidence of cancer within populations coincided with increases in animal food intake. For example, in regards to the observed marked increase cancer incidence among the Native American’s after gaining easier means to hunt buffaloes, Williams asserted:9 

In this connexion it should be borne in mind, that in their primitive condition these savages had no horses and no firearms ; consequently it was no easy matter for them to kill the fleet buffaloes, on which they mainly depended for subsistence ; hence, in their primitive condition, they were generally less well nourished than when, after contact with whites, they had, by the acquirement of horses and firearms, become assured of a constant supply of their favourite food [coinciding with an increase in cancer incidence].

Historical Overview of the Reversal of Chronic Diseases 

In 1903, John Harvey Kellogg, the founder of the Kellogg Company asserted:

Dr John Bell, who was, about a hundred years ago [now two hundred years ago], professor in a leading college in London, wrote that a careful adherence to a vegetarian dietary tended to prevent cancer. He also stated that in some cases persons who had already acquired cancer had been cured by adherence to a non-flesh dietary. When I first read this book, I did not agree with the author; I thought he was mistaken; but I have gradually come to believe that what he says on this subject is true. 

These findings are consistent with Dr. Dean Ornish’s on-going Prostate Cancer Lifestyle Trial which has already produced strong suggestive evidence of reversal of prostate cancer growth.27 These findings are also consistent with experiments showing that dietary restriction of methionine, typically found in higher quantity and bioavailability in protein rich animal foods compared to unprocessed plant foods can inhibit and even reverse human tumor growth in animal models and in culture [reviewed previously]. 

Publications producing evidence of regression of atherosclerosis in humans dates back to the periods following both the World Wars in Scandinavia and the low countries of Europe, where a number of researchers found a trend between changes in intake of cholesterol laden foods throughout periods of food scarcity in the war and changes in the severity of atherosclerosis at autopsy [reviewed previously]. Several decades later during the 1960's and 70's experiments involving modest dietary and lifestyle changes or drugs produced the first angiographic evidence of modest regression of atherosclerosis.28

In experimental animal models, the first suggestive evidence of regression of atherosclerosis came from rabbit models produced by Anichkov and colleagues during the 1920’s. Beginning from 1957 much more substantial evidence of regression was produced in rabbits and then later replicated in a number of other species, including non-human primates.29 30

In 1970, Armstrong et al. published the first study producing substantial evidence of regression of atherosclerosis in non-human primates. Armstrong et al. induced severe autopsy proven atherosclerosis in Rhesus monkeys resembling that of human atherosclerosis by feeding a diet with 40% of energy from egg yolks for 17 months. The egg yolks were then removed from the diet of the remaining monkey’s and replaced by either linoleic acid rich chow or sugar rich low fat chow for three years reducing serum cholesterol to 140 mg/dl and resulting in a marked regression of atherosclerosis.28 31 These results were later reproduced in well over a dozen experiments in various primate species in which severe atherosclerosis was induced typically by feeding diets rich in dietary cholesterol and saturated fat and then reversed the process either by removing these atherogenic components, or by other means which significantly reduce serum cholesterol.30

During the late 1980’s, Dr. Dean Ornish and Dr. Caldwell Esselstyn began reversing atherosclerosis, and more importantly greatly decreased the number of reoccurring cardiac events in participants who adhered to a plant-based diet and often other lifestyle modifications.32 33 34 35 More recently Dr. Esselstyn has replicated his initial findings in around 200 participants over the period of a decade, with publication pending results showing a phenomenal success rate of a 99.5% reduction in reoccurring cardiovascular events [reviewed previously].

Caldwell Esselstyn on making heart attacks history

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