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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; 351 doi: (Published 12 August 2015) Cite this as: BMJ 2015;351:h3978

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Re: 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

With great interest we read the meta-analysis by the Souza and colleagues titled "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", published in the British Medical Journal [1]. In their comprehensive article, the authors systematically reviewed observational studies investigating the associations between saturated fat (SFA) and trans unsaturated fat on health status (including: all-cause mortality, cardiovascular disease (CVD incidence and mortality), coronary heart disease (CHD incidence and mortality), ischemic stroke, and type 2 diabetes mellitus). The authors concluded that there is no association between SFA (comparing the highest category vs. lowest category) and all health outcomes, mentioning the heterogeneous evidence including methodological limitations. However, it should be noted that subgroup analysis showed a significant association between higher intakes of SFA and CHD mortality (i.e. for studies conducted in America, participants: <60 years of age, <25% smoking prevalence).

There is a plethora of systematic reviews and meta-analyses investigating the effects of SFA on CVD and CHD [2], reporting contradictory results especially when comparing data from observational studies with those from randomized controlled trials [3]. Recently, Hooper et al. 2015 [4] conducted a meta-analysis of intervention trials and observed a 17% reduced risk of combined cardiovascular events comparing low SFA vs. high SFA diets. No significant effects could be observed for all-cause mortality, CVD/CHD mortality, myocardial infarction, and stroke. The authors concluded that the "evidence supports the reduction of saturated fat to reduce cardiovascular events within the timescale of these dietary trials”[4]. Apart from the differences in the primary findings, the meta-analyses by Souza et al. [1] and by Hooper et al. [4] disagree with respect to their evaluation of the quality of evidence according to the GRADE group [5] which was rated “very low” by Souza et al. [1], but “moderate” by Hooper et al. [4]. Applying the GRADE guidelines in Nutritional Sciences has several limitations, since RCTs in nutrition research are often prone to inherent methodological constraints. E.g., they sometimes cannot be controlled with "true" placebos, but rather by a limitation of certain aspects of nutrient compositions, food groups or dietary patterns. Other limitations include lack of double blinding, poor compliance and adherence, cross-over bias and drop-out. Thus, in the field of nutritional epidemiology, well-designed prospective cohort studies will provide important evidence as well [6]. Consequently, the quality of evidence statements as recommended by the GRADE working group, where observational studies started with a initial quality of a body of evidence “low”, should be reconsidered for prospective cohort studies in Nutritional Sciences [5].

Another important point raised by de Souza et al. [1] is the substitution of SFA by unsaturated fats (PUFA and/or MUFA). Recently, we performed a systematic review on dietary fatty acids in the secondary prevention of coronary heart disease including 12 trials with 7,150 patients [7]. Following meta-analyses as well as uni- and multivariate meta-regression, it was concluded that recommendations of higher intakes of PUFA in replacement of SFA was not associated with risk reduction of all-cause mortality, CVD, and CHD in subjects with CHD. Moreover, a meta-analysis of cohort studies investigating the effects of MUFA, oleic acid, and olive oil showed that MUFA of mixed animal and vegetable sources per se did not yield any significant effects on health status (all-cause mortality, CVD, CHD, and stroke) [8], while olive oil seemed to be associated with reduced risk. Additionally, a high MUFA:SFA ratio was inversely associated with all-cause and CVD mortality [8]. The high MUFA:SFA ratio (high intake of extra virgin olive oil) is one of the main components of the Mediterranean dietary pattern [9], which was associated with reduced risk of various non-communicable diseases [10-12].

A meta-analysis of cohort studies showed that only processed meat (all-cause mortality, CVD mortality, cancer mortality), and meat (all-cause mortality) were associated with increased risk, whereas no significant association could be observed for butter, cheese and milk [13]. Therefore, future meta-analyses should not focus primarily on fatty acids (i.e. SFA, MUFA, PUFA), but on specific foods (such as butter, milk, meat, and salmon), or food patterns which are the main sources of SFA.

1. 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, 2015.
2. Astrup A, Dyerberg J, Elwood P, et al. The role of reducing intakes of saturated fat in the prevention of cardiovascular disease: where does the evidence stand in 2010? The American journal of clinical nutrition 2011;93(4):684-8 doi: 10.3945/ajcn.110.004622[published Online First: Epub Date]|.
3. Hoenselaar R. Saturated fat and cardiovascular disease: the discrepancy between the scientific literature and dietary advice. Nutrition 2012;28(2):118-23 doi: 10.1016/j.nut.2011.08.017[published Online First: Epub Date]|.
4. Hooper L, Martin N, Abdelhamid A, et al. Reduction in saturated fat intake for cardiovascular disease. The Cochrane database of systematic reviews 2015;6:CD011737 doi: 10.1002/14651858.cd011737[published Online First: Epub Date]|.
5. Balshem H, Helfand M, Schunemann HJ, et al. GRADE guidelines: 3. Rating the quality of evidence. Journal of clinical epidemiology 2011;64(4):401-6 doi: 10.1016/j.jclinepi.2010.07.015[published Online First: Epub Date]|.
6. Satija A, Yu E, Willett WC, et al. Understanding nutritional epidemiology and its role in policy. Advances in nutrition 2015;6(1):5-18 doi: 10.3945/an.114.007492[published Online First: Epub Date]|.
7. Schwingshackl L, Hoffmann G. Dietary fatty acids in the secondary prevention of coronary heart disease: a systematic review, meta-analysis and meta-regression. BMJ open 2014;4(4):e004487 doi: 10.1136/bmjopen-2013-004487[published Online First: Epub Date]|.
8. Schwingshackl L, Hoffmann G. Monounsaturated fatty acids, olive oil and health status: a systematic review and meta-analysis of cohort studies. Lipids in health and disease 2014;13:154 doi: 10.1186/1476-511X-13-154[published Online First: Epub Date]|.
9. Trichopoulou A, Costacou T, Bamia C, et al. Adherence to a Mediterranean diet and survival in a Greek population. The New England journal of medicine 2003;348(26):2599-608 doi: 10.1056/NEJMoa025039[published Online First: Epub Date]|.
10. Schwingshackl L, Hoffmann G. Mediterranean dietary pattern, inflammation and endothelial function: a systematic review and meta-analysis of intervention trials. Nutrition, Metabolism and Cardiovascular Diseases 2014(0):(accepted manuscript; doi: ) doi: Online First: Epub Date]|.
11. Schwingshackl L, Hoffmann G. Adherence to Mediterranean diet and risk of cancer: A systematic review and meta-analysis of observational studies. International journal of cancer. Journal international du cancer 2014 doi: 10.1002/ijc.28824[published Online First: Epub Date]|.
12. Schwingshackl L, Missbach B, Konig J, et al. Adherence to a Mediterranean diet and risk of diabetes: a systematic review and meta-analysis. Public health nutrition 2015;18(7):1292-9 doi: 10.1017/S1368980014001542[published Online First: Epub Date]|.
13. O'Sullivan TA, Hafekost K, Mitrou F, et al. Food sources of saturated fat and the association with mortality: a meta-analysis. American journal of public health 2013;103(9):e31-42 doi: 10.2105/ajph.2013.301492[published Online First: Epub Date]|.

Competing interests: No competing interests

17 August 2015
Lukas Schhwingshackl
Postdoctoral Research Fellow
Georg Hoffmann; Department of Nutritional Sciences; University of Vienna
Department of Epidemiology; German Institute of Human Nutrition
Arthur-Scheunert-Allee 114-116 14558 Nuthetal, Germany