October 2017 – Dr Chee L Khoo
We have all been brought up to advise reducing total fat and saturated fatty acid intake, based on the presumption that replacing saturated fatty acids with carbohydrate and unsaturated fats will lower LDL cholesterol and should therefore reduce cardiovascular disease (CVD) events. Several meta-analyses of randomised trials and prospective cohort studies8–10 and ecological studies,2 largely done in European and North American countries showed either no association or a lower risk between saturated fatty acid consumption with total mortality and CVD events. This “well accepted” dietary recommendation is now being questioned.
The uncertainty regarding the effect of saturated fatty acids on clinical outcomes in part might be due to the fact that most observational cohort studies have been done in high-income countries 3, 4 where saturated fatty acid intake is within a limited range (about 7–15% of energy). It is uncertain whether these findings can be extrapolated to other regions of the world where nutritional inadequacy might be more common.
The Prospective Urban Rural Epidemiology (PURE) study was designed to explore the impact of diet macronutrients on total mortality and CVD. The study recruited 135 332 individuals between 35-70 years from 18 countries in 5 continents covering low income, middle income and high income communities. The countries in Asia included Bangladesh, China, India, Malaysia, and Pakistan. Countries from North America (Canada, Poland, Sweden), South America (Argentina, Brazil, Chile, Columbia), Africa (South Africa, Zimbabwe) and Middle East (Iran, Palestine, Turkey, UAE) were represented. Average follow up was 7.4 years.
Standardised questionnaires were used to collect information about demographic factors, socioeconomic status, lifestyle (smoking, physical activity, and alcohol intake), health history and medication use. Physical activity was assessed. History of diabetes was self-reported. Physical assessment included weight, height, waist and hip circumferences, and blood pressure. Detailed follow-up occurred at 3, 6, and 9 years and repeated measures of selected risk factors, causes of death, other health outcomes, and community data were collected.
Of note, participants’ habitual food intake was recorded using country-specific (or region-specific in India) validated food frequency questionnaires (FFQs) at baseline but not during follow up.
The primary outcomes were total mortality and major cardiovascular events (fatal cardiovascular disease, nonfatal myocardial infarction, stroke, and heart failure). Secondary outcomes were all myocardial infarctions, stroke, CVD mortality, and non-CVD mortality. What did they find?
High carbohydrate intake was associated with higher risk of total mortality.
The rise appeared to occur among those who consumed more than 60% when energy intake from carbohydrate > 70% energy. When socioeconomic status was adjusted, the results were unchanged. The results were similar in both Asian and non-Asian countries.
These findings would appear to be contrary to our current dietary guidelines. In the distance past, it was thought that fats were so evil that replacing fats with carbs was a good thing. But pooled analysis of two large studies (Health Professional Follow up and Nurses’ Health Study) 5, showed an inverse association between total fat and total mortality when fat was replaced by carbs.
Higher carbohydrate intakes is known to increase some forms of dyslipidaemia (ie, higher triglycerides and lower HDL cholesterol), apolipoprotein B (ApoB)-to apolipoprotein A1 (ApoA1) ratios and increased small dense LDL (the most atherogenic particles) 6,7 as well as increase blood pressure. Not surprisingly then, replacing total fat with more carbs was not a good idea after all.
In the PURE study, the opposite was done. Isocaloric (5% of energy) replacement of carbohydrate with polyunsaturated acids was associated with an 11% lower risk of mortality and 16% lower risk of non-CVD mortality whereas replacing carbs with saturated fats, MUFA or protein did not reduce mortality. Further, replacing carbs with saturated fats reduced stroke risk by 20%!
Total fat and individual types of fat were related to lower total mortality
Saturated fats was associated with a lower total mortality, non-CVD mortality, and stroke risk but not associated with of an increase in major CVD, myocardial infarction, and CVD mortality.
This is not that unexpected though. The Health Professionals Follow up and the Nurses’ Health Study did not find significant associations between saturated fatty acid intake and risk of cardiovascular disease when replacement nutrients were not taken into account 8-11. Randomised controlled trials of saturated fatty acid reduction (replaced by polyunsaturated fatty acids) have also not shown a statistically significant impact on total mortality.9,35–37. It is important to note that the subjects in the two North American studies had much higher total fat intake than those in the PURE studies. Yet, there was lower stroke risk in patients with higher saturated fats intake. Adjustment for socioeconomic status in the PURE study did not alter the results.
The authors of PURE acknowledged the following potential shortcomings:
- Using food frequency questionnaires is not an absolute nor accurate measure of intake
- Dietary intake was only assessed at baseline and not on subsequent reviews. It is possible that changes were made during the follow up period
- Socioeconomic confounders cannot be fully adjusted. Individuals who are more health conscious may adopt other healthy lifestyles. It may also account for differences in ability to afford fats and animal proteins. High carbs may be a proxy for poverty and access to health care
- The types of carbs were not fully quantify. Carb consumption from lower and middle income countries tend to be from refined sources.
It is also worth noting that >60% of the participants came from Asia where carb intake is high. Is 7.4 years long enough follow up for CVD mortality. The PURE study has open up a conversation on global dietary guidelines. Saturated fats may not be that evil after all. Saturated fat in moderation appears to be good for you.
- Mahshid Dehghan, Andrew Mente, Xiaohe Zhang 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. August 29, 2017.
- Grasgruber P, Sebera M, Hrazdira E, Hrebickova S, Cacek J. Food consumption and the actual statistics of cardiovascular diseases: an epidemiological comparison of 42 European countries. Food Nutr Res 2016; 60: 31694.
- 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; 351: h3978.
- Hooper L, Martin N, Abdelhamid A, Davey SG. Reduction in saturated fat intake for cardiovascular disease. Cochrane Database Syst Rev 2015; 6: CD011737.
- Wang DD, Li Y, Chiuve SE, et al. Association of specific dietary fats with total and cause-specific mortality. JAMA Intern Med 2016; 176: 1134–45.
- Hoogeveen RC, Gaubatz JW, Sun W, et al. Small dense low-density lipoprotein-cholesterol concentrations predict risk for coronary heart disease: the Atherosclerosis Risk In Communities (ARIC) study. Arterioscler Thromb Vasc Biol 2014; 34: 1069–77.
- Parish S, Offer A, Clarke R, et al. Lipids and lipoproteins and risk of different vascular events in the MRC/BHF Heart Protection Study. Circulation 2012; 125: 2469–78.
- Hu FB, Stampfer MJ, Manson JE, et al. Dietary saturated fats and their food sources in relation to the risk of coronary heart disease in women. Am J Clin Nutr 1999; 70: 1001–08.
- Ascherio A, Rimm EB, Giovannucci EL, Spiegelman D, Stampfer M, Willett WC. Dietary fat and risk of coronary heart disease in men: cohort follow up study in the United States. BMJ 1996; 313: 84–90.
- Hu FB, Stampfer MJ, Manson JE, et al. Dietary fat intake and the risk of coronary heart disease in women. N Engl J Med 1997; 337: 1491–99.
- Li Y, Hruby A, Bernstein AM, et al. Saturated fats compared with unsaturated fats and sources of carbohydrate in relation to risk of coronary heart disease: a prospective cohort study. J Am Coll Cardiol 2015; 66: 1538–48.