|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.12345This 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.
The Framingham Heart Study
The Honolulu Heart Study
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.
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.
The Lipid Research Clinics Study
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 estimateshave 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-valuewas 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).
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.78912 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).
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 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
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.