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WHO draft guidelines on dietary saturated and trans fatty acids: time for a new approach?

BMJ 2019; 366 doi: https://doi.org/10.1136/bmj.l4137 (Published 03 July 2019) Cite this as: BMJ 2019;366:l4137

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Re: WHO draft guidelines on dietary saturated and trans fatty acids: time for a new approach?

I applaud the authors for highlighting the limitations of the WHO guidelines on saturated fat. The recommendations for adults are based on only two studies: a Cochrane review by Hooper [2] that included 15 RCTs assessing the impact of replacing SFAs with CHOs, PUFAs, MUFAs, and/or protein on mortality and cardiovascular morbidity; and a systematic review by Mensink [3] that included 84 RCTs assessing the effects of specific fats on blood lipids.

Hooper [2]
This review included studies with substantial differences in treatments/diets between control and intervention groups, preventing clear conclusions about the impact of saturated fat intake on CVD. For example, they included the 1966 Oslo Diet-Heart study, in which the treatment group, in addition to replacing saturated fat with soybean oil, received a large dose (~5 g/day) of EPA/DHS from sardines canned in cod liver oil and was advised to restrict sugar and refined carbohydrates. They also included the 2006 Women’s Health Initiative, in which the treatment group, in addition to lowering total and saturated fat, increased intake of fruits/vegetables. These are just two examples of included studies that did not isolate the effect of saturated fat on CVD and mortality. Nevertheless, while the review found a modest reduction in risk for the treatment versus control groups on combined cardiovascular events (RR 0.83 [0.72, 0.96]), it found no difference on cardiovascular mortality (0.95 [0.80, 1.12]) or all-cause mortality (RR 0.97 [0.90, 1.05]).

Mensink [3]
This review provides evidence that replacing SFAs with PUFAs or MUFAs can improve blood lipid markers, but it’s unclear whether this lowers cardiovascular morbidity or mortality. Increased intake of stearic acid had no effect on blood lipids, and increased intake of lauric acid lowered the total to HDL cholesterol and LDL to HDL cholesterol ratios compared with a mixture of carbohydrates.

The WHO guidelines also cite a meta-analysis of RCTs by Mozaffarian [4] which found replacing SFAs with PUFAs resulted in reduced CVD events (RR 0.81 [0.70, 0.05]). However, this study included trials with substantial differences in diets between treatment and control groups––the 1996 Oslo Diet-Heart study described above and other problematic studies. For example, the Finnish Mental Hospital study was not a RCT––all participants from one hospital were assigned to treatment, all from a second hospital to control. Additionally, participants in the control group were disproportionally exposed to a cardiotoxic drug thioridazine.

There are important systematic reviews and meta-analyses of RCTs and observational studies that conflict with WHO guidelines. Conclusions differ substantially depending on included/excluded studies. The two studies included for adults in the WHO guidelines have weaknesses and are not representative of the totality of evidence, which may lead to misguidance. Additional important studies highlighted below.

Ramsden [5]
Authors analyzed unpublished data from the Minnesota Coronary Experiment, which replaced SFAs with LAs in the treatment group and conducted a meta-analysis of RCTs. The analysis of the Minnesota Coronary Experiment data showed that while the treatment group had substantially lower serum cholesterol, there was no mortality benefit in the intervention group and that there was a 22% higher risk of death for each 30 mg/dL reduction in serum cholesterol (HR 1.22 [1.14, 1.32]). The meta-analysis showed no benefit of cholesterol-lowering interventions on mortality from CVDs (HR 1.13 [0.83, 1.54]) or all causes (HR 1.07 [0.90, 1.27]). Authors included different studies in the meta-analysis than Mozaffarian [4] or Hooper [2].

Hamley [6]
This analysis critically reviewed the inclusion/exclusion of controversial studies and conducted a meta-analysis of adequately controlled RCTs that replaced SFAs with omega-6 PUFAs. It found no differences between treatment and control groups for total CVD events (RR 1.02 [0.84, 1.23]), CVD mortality (RR 1.13 [0.91, 1.40]), or total mortality (RR 1.07 [0.90, 1.26]).

Chowdhury [7]
This systematic review and meta-analysis included prospective observational studies and RCTs of the impact of different fats. In observational studies there was no increased risk in coronary disease from higher saturated fat intakes (RR 1.03 [0.98, 1.07]) or other fats, between the top and bottom thirds of baseline intake. Long-chain omega-3 fats showed a benefit in reduced coronary disease (RR 0.87 [0.78, 0.97]). There were no significant results for RCTs or overall.

De Souza [8]
This systematic review and meta-analysis included observational studies that reported associations between saturated fat and all-cause mortality, CHD/CVD mortality, total CHD, ischemic stroke, or type 2 diabetes. Saturated fats were not associated with all-cause mortality, CVD, CHD, stroke, or type 2 diabetes.

Siri-Tarino [9]
This meta-analysis included prospective observational studies analyzing the association between saturated fat intake with CHD/CVD or stroke. Intake of saturated fat was not associated with an increased risk of CHD, stroke, or CVD.

There are also important findings from the 18-country observational PURE study. Dehghan [10]: Total and specific fats were not associated with CVD, myocardial infarction, or CVD mortality, whereas saturated fat had an inverse association with stroke. Mente [11]: Reducing saturated fat intake and replacing it with carbohydrate had an adverse effect on blood lipids. Substituting saturated with unsaturated fats might improve some risk markers but worsen others. Simulations suggest the ApoB-to-ApoA1 ratio provides a good indication of the effect of saturated fats on CVD risk. Focusing on a single lipid marker such as LDL cholesterol does not capture the net clinical effects of nutrients on cardiovascular risk.

Individual dietary components are not eaten separately, they are bundled together as diets. The impact of any one nutrient, such as saturated fat, varies depending on the food matrix and total diet. For example, a RCT by Shih [12] found that in the context of a weight-loss diet, people on a high-quality low-fat diet developed increased risk of CVD, compared to those on a high-quality low-carbohydrate diet higher in saturated fat. Refined carbohydrates were an important risk factor for CVD, not the proportion of total or saturated fat. Overall diet quality influences the impact of saturated fat on CVD risk––consuming > 10% of energy from saturated fat may be healthy if the diet is energy-balanced, composed of high-quality whole foods, and low in refined carbohydrates.

References
1 Astrup A, Bertram HC, Bonjour J-P, et al. WHO draft guidelines on dietary saturated and trans fatty acids: time for a new approach? BMJ 2019;366:l4137. doi:10.1136/bmj.l4137
2 Hooper L, Martin N, Abdelhamid A, et al. Reduction in saturated fat intake for cardiovascular disease. Cochrane Database of Systematic Reviews Published Online First: 10 June 2015. doi:10.1002/14651858.CD011737
3 Mensink RP. Effects of saturated fatty acids on serum lipids and lipoproteins: a systematic review and regression analysis. 2016.
4 Mozaffarian D, Micha R, Wallace S. Effects on Coronary Heart Disease of Increasing Polyunsaturated Fat in Place of Saturated Fat: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. PLoS Med 2010;7:e1000252. doi:10.1371/journal.pmed.1000252
5 Ramsden CE, Zamora D, Majchrzak-Hong S, et al. Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73). BMJ 2016;:i1246. doi:10.1136/bmj.i1246
6 Hamley S. The effect of replacing saturated fat with mostly n-6 polyunsaturated fat on coronary heart disease: a meta-analysis of randomised controlled trials. Nutr J 2017;16:30. doi:10.1186/s12937-017-0254-5
7 Chowdhury R, Warnakula S, Kunutsor S, et al. Association of Dietary, Circulating, and Supplement Fatty Acids With Coronary Risk: A Systematic Review and Meta-analysis. Ann Intern Med 2014;160:398. doi:10.7326/M13-1788
8 de Souza RJ, Mente A, Maroleanu A, et al. Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies. BMJ 2015;:h3978. doi:10.1136/bmj.h3978
9 Siri-Tarino PW, Sun Q, Hu FB, et al. Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. The American Journal of Clinical Nutrition 2010;91:535–46. doi:10.3945/ajcn.2009.27725
10 Dehghan M, Mente A, Zhang X, et al. Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study. The Lancet 2017;390:2050–62. doi:10.1016/S0140-6736(17)32252-3
11 Mente A, Dehghan M, Rangarajan S, et al. Association of dietary nutrients with blood lipids and blood pressure in 18 countries: a cross-sectional analysis from the PURE study. The Lancet Diabetes & Endocrinology 2017;5:774–87. doi:10.1016/S2213-8587(17)30283-8
12 Shih CW, Hauser ME, Aronica L, et al. Changes in blood lipid concentrations associated with changes in intake of dietary saturated fat in the context of a healthy low-carbohydrate weight-loss diet: a secondary analysis of the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) trial. Am J Clin Nutr 2019;109:433–41. doi:10.1093/ajcn/nqy305

Competing interests: No competing interests

10 July 2019
Ty Beal
Technical Specialist, Knowledge Leadership
Global Alliance for Improved Nutrition (GAIN)
1509 16th Street NW, 7th Floor Washington, DC 20036, USA