Intended for healthcare professionals

Observations From the Heart

Saturated fat is not the major issue

BMJ 2013; 347 doi: https://doi.org/10.1136/bmj.f6340 (Published 22 October 2013) Cite this as: BMJ 2013;347:f6340

Re: Saturated fat is not the major issue

The Zhang paper reported that almost 1 in 5 (17.4%) or 18,778 out of 107,835 patients treated with a statin in a routine care setting had a “statin-related adverse event documented.” The most commonly documented side effect was myalgia or myopathy with others including musculoskeletal and connective tissue disorders , general disorders, hepatobiliary disorders, gastrointestinal disorders, memory problems and drug intolerance.1,2

In fact the overall initial rate of discontinuation for all causes that occurred at least once for the 107,835 patients analysed in the study was far higher at 53.1% (57,292 patients) for reasons that also included the drug being “no longer necessary” or the patients not wanting to take it.

Although it is true that 92.2% that were re-challenged representing 6579 out of 11,124 patients who at least temporarily discontinued their medication because of side effects were on “a statin” 12 months later, only 15.1% (996) patients were on the same statin or a higher dose which suggests the remaining majority were either on a different statin or a lower dose.

There is a clearly a discrepancy between side effects reported in clinical trials and real world experience. Professor Rory Collins, co-director of the University of Oxford’s Clinical Trialists Service Unit, citing a meta-analysis which he co-authored of 27 (predominantly industry funded) RCTs of statin therapy3, recently told the Guardian that “We have really good data from over 100,000 people that show that the statins are very well tolerated. There are only one or two well-documented (problematic) side effects. Myopathy, or muscle weakness, occurred in one in 10,000 people, he said, and there was a small increase in diabetes.”4

A double blinded randomised controlled trial published in the Archives of Internal Medicine involving 1016 low risk patients receiving simvastatin 20mg, pravastatin 40mg or placebo revealed that both drugs had a significant adverse effect on energy/fatigue exercise score with 40% of women reporting reduced energy or fatigue with exertion.5,6

In reference to diabetes risk a large observational study involving 153,840 postmenopausal women between 50 and 80 years of age who were enrolled in the Womens Health Initiative study revealed statins had a 48% increased risk of developing diabetes in this group.7

Although there has been evidence of benefit in reducing cardiovascular events and mortality for a heterogeneous group of patients with cardiovascular disease that includes patients with stable angina using standard dose Pravastatin 40mg or Simvastatin 20-40mg from earlier clinical trials, more recent studies have mandated maximum dose therapy for all patients post acute-coronary syndromes. The PROVE-IT study randomised 4162 patients hospitalised with acute myocardial infarction or unstable angina to receive either atorvastatin 80mg or pravastatin 40mg revealing a significant 16% reduction in death and cardiovascular events in the those on maximum dose atorvastatin within 24 months.8 In a systematic review of randomised trials, high dose statin therapy in the setting of acute coronary syndromes demonstrated a 22% reduction in all cause mortality as well as a 25% reduction in cardiovascular mortality.9 Subsequently the European Society of Cardiology recommends that all patients presenting with acute myocardial infarction with high intensity statins early after admission unless contraindicated.10

The primary prevention of cardiovascular disease with a Mediterranean Diet (PREDIMED) study randomly assigned participants who were at high cardiovascular risk to one of three diets: a Mediterranean diet supplemented with extra virgin olive oil (1 litre/week), a Mediterranean diet supplemented with 30g of mixed nuts per day ( 15g of Walnuts, 7.5g of hazelnuts and 7.5g of almonds) or a control diet ( advice to reduce dietary fat). The intervention group had a significant 30% reduction in the primary endpoint of major cardiovascular events ( myocardial infarction, stroke or death from cardiovascular causes).11 Despite the participants in the control group receiving advice to reduce fat intake the difference in total fat were small however there were large differences in the fat subtypes reflected by the supplemental items, specifically olive oil and nuts, which were most likely responsible for most of the observed benefits of the Mediterranean diet. The fact that the control group were still advised to follow a healthy diet suggests a potentially greater benefit of a Mediterranean diet as compared to western diets. The authors conclude that the results of PREDIMED compare favourably with those of the Women’s Health Initiative Dietary Modification Trial revealed no cardiovascular benefit for the “low fat” dietary approach.12

Our focus on one specific nutrient or grouping all fats together has unfortunately led to an over obsession on “low fat” diets as being healthy. It is in fact the synergy of nutrient rich whole foods such as vegetables, fruits, nuts, legumes, fish and olive oil that may account for the health benefits of the Mediterranean diet by inducing positive changes in intermediate pathways of cardiometabolic risk through their impact on blood lipids, insulin sensitivity, resistance to oxidation, inflammation and vasoreactivity.13

Most recently a meta-analysis of 72 unique studies with over 600,000 participants from 18 countries led by the Cambridge Medical Research Council concluded that current evidence does not support guidelines that restrict the consumption of saturated fats and encourage consumption of polyunsaturated fats in order to prevent heart disease. The study raised questions regarding current nutritional guidelines that focused principally on the total amount of fat from saturated or unsaturated rather than the food sources of the fatty acid subtypes. One interesting finding was that the consumption of one particular fatty acid (margaric acid) which is a dairy fat, significantly reduced the risk of cardiovascular disease. 14 These findings support those from the dietary intake of saturated fat by food source and incident cardiovascular disease analysis which concluded that a higher intake of dairy saturated fat was inversely associated with lower CVD risk. Otto, Mozaffarian et al explain this finding by stating that “dairy foods, which are a major source of saturated fat in most populations, are also sources of beneficial nutrients including Vitamin D, potassium, phosphorus, and calcium…”.15 However Professor Simon Pearce is right to point out that unlike the United States where dairy products are fortified with Vitamin D, this is not the case in the UK where the best sources come from foods such as oily fish and egg yolk. The suggestion of the UK adopting a similar Vitamin D fortification policy may hold some validity but the evidence is mounting that the health effects of the entire food and absorbing nutrients through natural means, not through supplementation, may be key to understanding associations between dietary consumption and health outcomes.

1. Zhang H, Plutzky J, Skentzos S, Morrison F, Mar P, Shubina M, et al. Discontinuation of statins in routine care settings. Ann Intern Med2013;158:526-
2. http://www.medscape.com/viewarticle/781767
3. Cholesterol Treatment Trialists’ (CTT) Collaborators, Mihaylova B, Emberson J, Blackwell
L, Keech A, Simes J, et al. The effects of lowering LDL cholesterol with statin therapy in
people at low risk of vascular disease: meta-analysis of individual data from 27 randomised
trials. Lancet 2012;380:581-90.
4. http://www.theguardian.com/society/2014/mar/21/-sp-doctors-fears-over-st...
5. http://www.medscape.com/viewarticle/765472
6. Golomb BA, Evans MA, Dimsdale JE, White HL. Effects of Statins on Energy and Fatigue With Exertion: Results From a Randomized Controlled Trial. Arch Intern Med. 2012;172(15):1180-1182. doi:10.1001/archinternmed.2012.2171.
7. Culver AL, Ockene IS, Balasubramanian R, Olenzki BC, Sepavich DM, Wactawski-Wende
J, et al. Statin use and risk of diabetes mellitus in postmenopausal women in the Women’s
Health Initiative. Arch Intern Med 2012;172:144-52.
8. http://www.nejm.org/doi/full/10.1056/NEJMoa040583#t=citedby
9. http://www.ncbi.nlm.nih.gov/pubmed/17503884
10. http://www.escardio.org/guidelines-surveys/esc-guidelines/GuidelinesDocu...
11. Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med2013;368:1279-90
12. Howard BV, Van Horn L, Hsia J, et al. Low-fat dietary pattern and risk of cardiovascular disease: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006;295:655-66.

13. Jacobs DR Jr, Gross MD, Tapsell LC. Food synergy: an operational concept for
understanding nutrition. Am J Clin Nutr 2009;89:1543S-1548S

14. Rajiv Chowdhury, Samantha Warnakula, Setor Kunutsor, Francesca Crowe, Heather A. Ward, Laura Johnson, Oscar H. Franco, Adam S. Butterworth, Nita G. Forouhi, Simon G. Thompson, Kay-Tee Khaw, Dariush Mozaffarian, John Danesh, Emanuele Di Angelantonio; Association of Dietary, Circulating, and Supplement Fatty Acids With Coronary RiskA Systematic Review and Meta-analysis. Annals of Internal Medicine. 2014 Mar;160(6):398-406.

15. De Oliveira Otto MC, Mozaffarian D, Kromhout D, Bertoni AG, Sibley CT, Jacobs DR Jr, et al. Dietary intake of saturated fat by food source and incident cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis. Am J Clin Nutr2012;96:397-404

Competing interests: No competing interests

29 March 2014
Aseem Malhotra
Interventional Cardiology Specialist Registrar
Croydon University Hospital
Croydon University Hospital, 530 London Rd, CR7 7YE