Intended for healthcare professionals

Rapid response to:

Observations From the Heart

Saturated fat is not the major issue

BMJ 2013; 347 doi: (Published 22 October 2013) Cite this as: BMJ 2013;347:f6340

Rapid Response:

Re: Saturated fat is not the major issue

Dr Malhotra’s paper (1) provides some useful reminders regarding the causes of coronary heart disease (CHD) and the requirements for risk reduction but does include several instances where the existing literature has been misinterpreted.

The title is accurate. CHD has a complex aetiology and there is no single factor which can be regarded as “the major issue”. With that in mind it is not surprising that the relative importance of different risk factors can change over time. Many patients who now present with myocardial infarction are likely to be overweight and have features of the metabolic syndrome. Dyslipidaemia, dysglycaemia and raised blood pressure levels are now well-established risk factors for CHD. Given the pivotal role of central obesity in this constellation of cardiometabolic risk indicators, attempts to avoid and treat excess weight gain are central components of preventive cardiology.

In December 2012 and January 2013 the BMJ published systematic reviews and metaanalyses (commissioned by WHO) that demonstrated the potential for total fat and dietary free sugars to promote body fatness (2, 3). These findings are hardly surprising given the potential of both these macronutrients to increase the energy density of foods.

“Sugar” is increasingly regarded as the villain of the piece though many energy dense foods are rich in both sugar and fat. Sugar sweet beverages although not energy dense are also associated with excess weight gain. The BMJ sugars review provides convincing evidence that the effect of sugars in promoting body fatness is via their tendency to promote excessive calorie intakes rather than via some unique metabolic pathways, in those consuming self-selected diets (2). When calorie intakes are carefully controlled there is no effect on body weight when sugars are exchanged for other energy sources.

Whether free sugars and fructose in particular have an adverse effect on cardiometabolic risk independent of body weight is yet to be finally resolved. Individual studies suggest untoward effects on lipid and carbohydrate metabolism and distribution of body fatness but most of the studies involved higher intakes of sugars than usually consumed and were relatively short term. However a meta analysis of randomised controlled trials examining the effects of free sugars on blood pressure and lipids (presented at the 2013 Australia and New Zealand Obesity Society Conference, abstract available: suggests their potential to raise total cholesterol and triglyceride and blood pressure, especially diastolic pressure.

So, we would agree with Malhotra that replacement of fat with sugars in manufactured and other foods is totally inappropriate. However we would strongly dispute his conclusion that saturated fat is exonerated as a cause of coronary heart disease.

Contrary to Malhotra’s statement that “advice [to reduce saturated fat intake] has, paradoxically, increased our cardiovascular risks”(1) the past several decades have seen substantial declines in cardiovascular disease mortality (4), which have occurred in parallel with declines in both saturated fat intake and serum cholesterol levels in much of the western world (5). These ecological observations suggesting an association between total cholesterol and CHD, are supported by findings in cohort studies and clinical trials (6).

Metaanalysis of observational studies in nearly 900 000 adults in western countries showed a linear relationship between total cholesterol and CHD mortality, but not mortality from stroke, a more heterogeneous disease (6). A similar association has been repeatedly demonstrated between cholesterol and non-fatal CHD (7). Malhotra selectively cites two studies (both in low-risk Asian populations) which he claims show that “high cholesterol is not a risk factor” for CVD (8, 9). Both studies indeed reported associations between low cholesterol and mortality, however this association, which been repeatedly described, is likely due largely to confounding by pre-existing disease, including cancers, liver, respiratory and digestive diseases, malnutrition and smoking (10).

The direct evidence for an association between saturated fat intake and CHD is less clear, but this is hardly surprising. A recent meta-analysis of prospective cohort studies by Siri-Tarino et al (2010) suggested no association between saturated fat intake and CHD (11). However cohort studies may be confounded by not taking into account sources of replacement energy, misreporting of dietary saturated fat intakes or measurement error resulting in regression dilution effects, and by inappropriate adjustment for lifestyle factors (12). In pooled analyses of cohort studies inconsistent adjustment for potential intermediates in the diet-disease pathway, as well as for energy intake, may also result in residual confounding.

The findings are more clear when also considering what replaces saturated fat. In a data pooling study of 11 prospective cohort studies examining the effect on CHD risk of substituting carbohydrates or unsaturated fats for saturated fats, Jakobsen et al (2009) showed that replacing saturated fat with polyunsaturated fat resulted in a significant reduction in CHD risk whereas substitution with carbohydrate resulted in a modest increase in risk (13). Arguably the strongest confirmation of the diet-disease relationship comes from randomised controlled trials. In a metaanalysis of 8 relatively long-term trials Mozaffarian et al (2010) showed a significant reduction in CHD events in studies where saturated fat reduction was achieved by substitution primarily with polyunsaturated fat, thus confirming the findings of Jakobsen et al (14).

The influence of saturated fat intake on CHD is supported by many shorter term experimental studies examining the effects of saturated fats on metabolic biomarkers for CHD. Mensink et al. (2003) have aggregated data relating to the effects on blood lipids of substituting carbohydrates, mono or polyunsaturated fats for saturated fats in controlled experimental trials (15). In all comparisons replacement of saturated fat was associated with an improved total:HDL cholesterol ratio, with the greatest effect seen with polyunsaturated fat replacement.. Clinical trials involving cholesterol lowering by diet or drugs confirm CHD risk reduction in proportion to the extent of cholesterol lowering (16, 17).

Dietary advice is given in terms of foods or dietary patterns rather than nutrients. There is no evidence that any particular dietary pattern is superior when adhering to the core components of cardioprotection, including reduction of saturated fat and free sugars and an increase in the ratio of unsaturated to saturated fatty acids.

1. Malhotra A. Saturated fat is not the major issue. BMJ 2013;347. doi: 10.1136/bmj.f6340.
2. Te Morenga L, Mallard S, Mann J. Dietary sugars and body weight: systematic review and meta-analyses of randomised controlled trials and cohort studies. BMJ 2013;346:e7492. doi: 10.1136/bmj.e7492.
3. Hooper L, Abdelhamid A, Moore HJ, Douthwaite W, Skeaff CM, Summerbell CD. Effect of reducing total fat intake on body weight: systematic review and meta-analysis of randomised controlled trials and cohort studies. BMJ 2012;345:e7666. doi: 10.1136/bmj.e7666.
4. Tunstall-Pedoe H. The decline in coronary heart disease; did it fall or was it pushed? BMJ 2012;344. doi: 10.1136/bmj.d7809.
5. Farzadfar F, Finucane MM, Danaei G, Pelizzari PM, Cowan MJ, Paciorek CJ, Singh GM, Lin JK, Stevens GA, Riley LM. National, regional, and global trends in serum total cholesterol since 1980: systematic analysis of health examination surveys and epidemiological studies with 321 country-years and 3• 0 million participants. The Lancet 2011;377(9765):578-86.
6. Prospective Studies Collaboration. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths. The Lancet 2007;370(9602):1829-39. doi:
7. Asia Pacific Cohort Studies Collaboration. Cholesterol, coronary heart disease, and stroke in the Asia Pacific region. International Journal of Epidemiology 2003;32(4):563-72. doi: 10.1093/ije/dyg106.
8. Nago N, Ishikawa S, Goto T, Kayaba K. Low cholesterol is associated with mortality from stroke, heart disease, and cancer: the Jichi Medical School Cohort Study. Journal of epidemiology / Japan Epidemiological Association 2011;21(1):67-74.
9. Bae J-M, Yang Y-J, Li Z-M, Ahn Y-O. Low Cholesterol is Associated with Mortality from Cardiovascular Diseases: A Dynamic Cohort Study in Korean Adults. J Korean Med Sci 2012;27(1):58-63.
10. Jacobs D, Blackburn H, Higgins M, Reed D, Iso H, McMillan G, Neaton J, Nelson J, Potter J, Rifkind B. Report of the Conference on Low Blood Cholesterol: mortality associations. Circulation 1992;86(3):1046-60.
11. Siri-Tarino PW, Sun Q, Hu FB, Krauss RM. Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. The American journal of clinical nutrition 2010;91(3):535-46. doi: 10.3945/ajcn.2009.27725.
12. Mamdani M, Sykora K, Li P, Normand SL, Streiner DL, Austin PC, Rochon PA, Anderson GM. Reader's guide to critical appraisal of cohort studies: 2. Assessing potential for confounding. BMJ 2005;330(7497):960-2. doi: 10.1136/bmj.330.7497.960.
13. Jakobsen MU, O'Reilly EJ, Heitmann BL, Pereira MA, Balter K, Fraser GE, Goldbourt U, Hallmans G, Knekt P, Liu S, et al. Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies. The American journal of clinical nutrition 2009;89(5):1425-32. doi: 10.3945/ajcn.2008.27124.
14. 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 medicine 2010;7(3):e1000252. doi: 10.1371/journal.pmed.1000252.
15. Mensink RP, Zock PL, Kester AD, Katan MB. Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. The American journal of clinical nutrition 2003;77(5):1146-55.
16. Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010;376(9753):1670-81. doi: 10.1016/S0140-6736(10)61350-5.
17. Dayton S, Pearce ML, Goldman H, Harnish A, Plotkin D, Shickman M, Winfield M, Zager A, Dixon W. Controlled trial of a diet high in unsaturated fat for prevention of atherosclerotic complications. Lancet 1968;2(7577):1060-2.

Competing interests: No competing interests

31 October 2013
Jim Mann
Professor of Medicine and Human Nutrition
Rachael McLean, Lisa Te Morenga
University of Otago
P O Box 56, Dunedin 9054, New Zealand