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Wednesday, 27 May 2020

My Letter to Cochrane on the Hooper 2020 saturated fat meta

I submitted this on the Cochrane form at

Others will have points to add about study quality and other factors, I have stuck to what I know (not wanting to waste my life battling an opponent who can obviously be reanimated an unlimited number of times).

The introduction to this meta-analysis includes an error uncorrected from the 2015 version.

Oliver 1953 measured total cholesterol, not LDL cholesterol. Further, it is relevant that every subject in Oliver 1953 had been eating the same hospital diet for at least 5 weeks before the cholesterol samples were taken, which does not support a diet-heart interpretation of the results.[1] (The presence of FH in the sample, and/or survivorship bias, are probably more reasonable interpretations)

[1] The Plasma Lipids in Coronary Artery Disease. Oliver MF, Boyd GS. Br Heart J. 1953 Oct;15(4):387-92. 

The section headed "Agreements and disagreements with other studies or reviews" has not addressed any written after 2014, meaning that this section has not been updated. There are several analyses of the diet heart trials since 2015 that should have been addressed (indeed, that should have been read before the current Cochrane review was designed). Some are listed below.[2,3.4]

[2] 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 16, 30 (2017).

[3] Thornley S, Schofield G, Zinn C, Henderson G. How reliable is the statistical evidence for limiting saturated fat intake? A fresh look at the influential Hooper meta-analysis. Intern Med J. 2019;49(11):1418‐1424. doi:10.1111/imj.14325

[4] Jeffery L Heileson, Dietary saturated fat and heart disease: a narrative review, Nutrition Reviews, Volume 78, Issue 6, June 2020, Pages 474–485,

The discussion of Siri-Tarino 2010 in "Agreements and disagreements with other studies or reviews" claims that adjustment for lipids has confounded its null result, however Siri-Tarino at al had already addressed this by isolating studies not adjusted for lipids with no difference in their null result. This is quite understandable as adjusting for lipids also means adjusting for TG and HDL, cardiometabolic risk markers which can be beneficially infuenced by saturated fat and worsened by carbohydrate.
Studies which do not adjust for lipids can be favourable to saturated fat, for example the Malmo DCS, a high-quality observational study using a 7-day food diary and more rigorous exclusion criteria than is usual, or the 2019 dose-response meta-analysis of observational studies by Zhe et al.[5,6]

[5] Leosdottir M, Nilsson PM, Nilsson JA, MÃ¥nsson H, Berglund G. Dietary fat intake and early mortality patterns--data from The Malmö Diet and Cancer Study. J Intern Med. 2005;258(2):153‐165. doi:10.1111/j.1365-2796.2005.01520.x

[6] Zhu, Y., Bo, Y. & Liu, Y. Dietary total fat, fatty acids intake, and risk of cardiovascular disease: a dose-response meta-analysis of cohort studies. Lipids Health Dis 18, 91 (2019).

The claim that greater lowering of LDL in trials being associated with greater reduction of events supports the diet-heart hypothesis may be unsound. Persons in good metabolic health are at significantly lower risk of CVD events despite other risk factors.[7] Persons who are obese, have diabetes, or the metabolic syndrome do not usually experience drops in LDL cholesterol when fat in the diet is changed; the subjects in the feeding studies cited, who did experience such drops, were healthy volunteers.[8,9,10]

[7] Jeppesen J, Hein HO, Suadicani P, Gyntelberg F. Low triglycerides-high high-density lipoprotein cholesterol and risk of ischemic heart disease. Arch Intern Med. 2001;161(3):361‐366. doi:10.1001/archinte.161.3.361

[8] Flock MR, Green MH, Kris-Etherton PM; Effects of Adiposity on Plasma Lipid Response to Reductions in Dietary Saturated Fatty Acids and Cholesterol, Advances in Nutrition. 2011;2,(3):261–274,

[9] Benatar JR, Sidhu K, Stewart RAH. Effects of High and Low Fat Dairy Food on Cardio-Metabolic Risk Factors: A Meta-Analysis of Randomized Studies. Tu Y-K, ed. PLoS ONE. 2013;8(10):e76480. doi:10.1371/journal.pone.0076480.

[10] Lefevre M, Champagne CM, Tulley RT,et al. Individual variability in cardiovascular disease risk factor responses to low-fat and low-saturated-fat diets in men: body mass index, adiposity, and insulin resistance predict changes in LDL cholesterol. Am J Clin Nutr. 2001;82(5):957–963,

It is also relevant that from 2004 the Swedish population began to reject diet-heart advice, to such an extent that butter sales rose and margarine sales dropped; cholesterol levels also rose.[11] Yet as recently as 2018 mortality from, and incidence of, AMI was continuing to decline in Sweden. In fact incidence of AMI had stayed stable from 1987 to 2005, after which it began to drop from 42,263 PA to 25,789 PA in 2018.[12]

[11] Johansson I, Nilsson LM, Stegmayr B, Boman K, Hallmans G, Winkvist A. Associations among 25-year trends in diet, cholesterol and BMI from 140,000 observations in men and women in Northern Sweden. Nutr J. 2012;11:40.

[12] Data accessed from Swedish Social Registry website 28/05/20

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