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Intake of individual saturated fatty acids and risk of coronary heart disease in US men and women: two prospective longitudinal cohort studies

BMJ 2016; 355 doi: (Published 23 November 2016) Cite this as: BMJ 2016;355:i5796

Unresolved issues with the previous dietary fat study from the NHS and HPFS cohorts still need addressing, but concerns about palm oil may be valid.

The authors of this analysis mention that it is discordant with other recent cohort studies such as EPIC-Netherlands, which came to essentially the opposite conclusion,
"Total SFA intake was associated with a lower IHD risk (HR per 5% of energy: 0.83; 95% CI: 0.74, 0.93). Substituting SFAs with animal protein, cis monounsaturated fatty acids, polyunsaturated fatty acids (PUFAs), or carbohydrates was significantly associated with higher IHD risks (HR per 5% of energy: 1.27–1.37)."[1]

The answer to why two similar studies have produced different conclusions may lie in unresolved questions about the NHS/HPFS study that were raised on PubPeer after the previous study from these cohorts by Wang et al. "Association of Specific Dietary Fats With Total and Cause-Specific Mortality".[2, 3] Some of these were:

1) in eTable 3 (Associations between total mortality and type/amount of fat) in the supplementary data for this paper, the number of deaths in NHS for women in the top quintile for SFA was half of that in the lowest, yet after age-adjustment the HR is not in favour of SFA. The age difference between quintiles was only ~2 years.
2) the exclusion criteria for energy reporting in NHS and HPFS were very loose and allowed for reporting of biologically invalid extremes of intake. The mean intake in NHS over the 18 years of its duration was around ~1,500 kcal/day which is implausible, and this may have affected the present analysis because macronutrient intakes are measured as % of energy.
3) the data from these cohorts may not have been properly adjusted for smoking, as the Wang et al paper found that higher SFA intake was associated with a substantial increase of mortality due to respiratory disease (HR comparing extreme quintiles, 1.56; 95% CI, 1.30-1.87; P < .001 for trend). This biologically implausible finding is described by Wang et al as novel and lacking support. Respiratory mortality is usually associated with smoking and air quality. A very obvious explanation is that US health professionals have under-reported smoking. If the weight given to the smoking adjustment in NHS/HPFS was increased till the association between SFA and respiratory mortality sat at a more appropriate 1.0, would this attenuate the association between all or some SFAs and CVD mortality, given that SFA and smoking are already correlated in NHS/HPFS?

Dairy fat, which does not correlate with CVD in meta-analyses,[4] is 31% C:16, less than the 43.5% found in palm oil. C:16 is also the SFA in serum which correlates with the carbohydrate content of the diet.[5, 6]
Therefore the conclusion of this paper, that palm oil in processed food may be of concern, seems valid, as palm oil is used in the manufacture of goods where most energy comes from sugar and high-GI refined starch, whereas butter can be used in baking but is also used to prepare low carbohydrate foods such as eggs, sauces, and vegetables.
If "several lines of evidence have suggested increased use of palm oil in food production, especially in developing countries and higher 16:0 contents in snacks and bakery products over the past years" it might be useful to have an analysis that compares fats from snacks and bakery products with fats from other sources. We have had this kind of analysis for sugar for some time.

Because epidemiological research from high-profile institutions will tend to be reported in an "over-exaggerated" fashion and thus can have unintended consequences, methods need to be rigourous enough to minimise both type 1 and type 2 errors, and be interpreted strictly in the light of higher quality experimental evidence into the same questions. The questions raised on PubPeer about the earlier NHS/HPFS paper are also relevant to this one. In particular, the estimation of health effects by substitution analysis, in populations where no real substitutions were measured, should not be overstated as a "finding". The projections of such statistical modelling are best guesses and untested predictions, and may not be "most important".

Directions to reduce saturated fat by using reduced fat dairy and lean meat may have been misguided if the impact of saturated fat on health was more likely to come from vegetable oils high in C:16 used to prepare sweet and high-GI snacks and desserts, the consumption of which appears to have increased while the world has dutifully been cutting down on "saturated" animal fats, which are in fact good sources of C:18, MUFA, in the case of dairy the shorter-chain SFAs, in the case of pork and chicken of PUFAs, and which produce lower C:16 levels in serum if they are eaten in the context of lower carbohydrate diets.

[1] Praagman J, Beulens JW, Alssema M, et al. The association between dietary saturated fatty acids and ischemic heart disease depends on the type and source of fatty acid in the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort. Am J Clin Nutr2016;103:356-65.

[2] Wang DD, Li Y, Chiuve SE, Stampfer MJ, Manson JE, Rimm EB, Willett WC, Hu FB, Association of Specific Dietary Fats With Total and Cause-Specific Mortality. JAMA Intern Med. 2016 Aug 1;176(8):1134-45.


[4] Drouin-Chartier J-P, Brassard D, Tessier-Grenier M et al. Systematic Review of the Association between Dairy Product Consumption and Risk of Cardiovascular-Related Clinical Outcomes. Adv Nutr. 2016;7:1026–40.

[5] Volk BM, Kunces LJ, Freidenreich DJ, et al. Effects of Step-Wise Increases in Dietary Carbohydrate on Circulating Saturated Fatty Acids and Palmitoleic Acid in Adults with Metabolic Syndrome. PLoS ONE. 2014;9(11):e113605. doi:10.1371/journal.pone.0113605.

[6] Lossow WJ, Chaikoff IL. Carbohydrate sparing of fatty acid oxidation. I. The relation of fatty acid chain length to the degree of sparing. II. The mechanism by which carbohydrate spares the oxidation of palmitic acid. Arch Biochem Biophys. 1955; 57(1):23-40.

Competing interests: Grant Schofield is co-author of What The Fat?, a guide to the science and practice of low-carbohydrate eating. George Henderson is a part-time waged employee of the company that distributes What The Fat?

24 November 2016
George Henderson
research associate
Grant Schofield, Professor of Public Health
Human Potential Centre, Auckland University of Technology
17 Antares Place