Saturated Fat, Heart Disease and Death. Results of observational research

All About Saturated Fat Part 1: What do we know about saturated fat, mortality, and heart disease from meta-analyses of the observational evidence?

All About Saturated Fat Part 1: Meta-Analyses of Observational Studies

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The debate between proponents of reducing saturated fat in the diet and those who suggest that saturated fat is either innocuous or even beneficial continues to rage. Arguments for reducing saturated fat typically rest upon associations between increased saturated fat intake and increases in LDL-cholesterol which in turn is associated with increased cardiovascular disease risk, while proponents of saturated fat point to the lack of clear evidence for the effect of saturated fat intake on both cardiovascular and all-cause mortality.

What are ‘saturated’ fats?

Dietary ‘fats’ are triglycerides. This means that each fat molecule (or lipid) consists of a glycerol ‘backbone’ onto which three fatty acid chains are attached.

Example of an unsaturated fat triglyceride (C55H98O6). Left part: glycerol; right part, from top to bottom: palmitic acidoleic acidalpha-linolenic acid. From https://en.wikipedia.org/wiki/Triglyceride

The fatty acids are carbon chains joined by single (C-C) or double bonds (C=C). Saturated fatty acids are free from double bonds and are ‘saturated’ with hydrogen (double bonds react with hydrogen to form single bonds). This makes fatty acid chains typically more stable than unsaturated fatty acids and renders them more heat (and environment) resistant).

Saturated fats are typically found in abundance in dairy and meat, whereas unsaturated fats make up a greater proportion of the fats in vegetable oils with the notable exceptions of coconut oil (~87% saturated fats) and palm kernel oil (86%). It is important to note that the foods we eat contain varying amounts of saturated, monounsaturated, and polyunsaturated fats. For example, butter contains nearly two-thirds saturated fat with most of the remainder being monounsaturated fats, while beef and chicken breast each contain under one-third saturated fats (by weight of total fat).

Meta-analyses of observational studies

Siri-Tarino et al., 20101

https://academic.oup.com/ajcn/article/91/3/535/4597110

No significant effects found for extreme intakes of saturated fat on coronary heart disease, stroke, or cardiovascular disease[1].

O’Sullivan et al., 20132

https://ajph.aphapublications.org/doi/full/10.2105/AJPH.2013.301492

No significant relationship was found between the intake of milk, cheese, butter, or all dairy and all-cause mortality. High intakes of meat and processed meat were significantly associated with an increased risk of all-cause mortality[2]. However, there were no significant associations of high intake of meat, milk, cheese, or all dairy products with cardiovascular disease mortality, yet high intake of processed meat was significantly associated with increased risk of CVD mortality.[3] Interestingly, while high intakes of both meat and processed meat were significantly associated with an increased risk of mortality they were associated with a decreased risk in a sub-analysis of Asian studies.

The discrepancies between meat and all-cause mortality and the lack of an association between meat and cardiovascular disease mortality, along with a decrease in risk of mortality seen in Asians, cast doubt upon the veracity of the finding that foods higher in saturated fats are independently associated with worsened health outcomes. The foods that are highest in saturated fat (dairy products) were not associated with increased mortality risk.

Cheng et al., 20163

https://link.springer.com/article/10.1007/s10072-016-2548-3

In this analysis, higher saturated fat intake was associated with reduced stroke risk[4]. Subgroup analysis indicated that higher saturated fat intake was associated with reduced stroke risk for East-Asians, males, and individuals with body mass index (BMI) <24 but not for non-East-Asians, females, and individuals with BMI ≥24. Additionally, doses over 25 g/day were not protective.

Mutu & Ezaki, 20184

https://www.jstage.jst.go.jp/article/jat/25/5/25_41632/_article/-char/ja/

Saturated fat was associated with reduced risk of intracerebral haemorrhage and ischaemic stroke in Japanese people but not in non-Japanese people[5]. The authors noted that the differences between Japanese and non-Japanese people might be “due to differences in the range of intake of saturated fat, genetic susceptibility, incidence of lacunar infarction, and/or confounding factors such as dietary proteins.”

Kang et al., 2020 (stroke)5

https://doi.org/10.1016/j.numecd.2019.09.028

This analysis of 14 studies (n = 598,435) for high vs. low meta-analysis and 12 studies (n = 462,268) for dose-response relation assessment found that higher dietary saturated fat intake was associated with a decreased overall risk for stroke[6]. The authors concluded that “higher consumption of dietary SFA is associated with a lower risk of stroke, and every 10 g/day increase in SFA intake is associated with a 6% relative risk reduction in the rate of stroke”.

Does adjustment matter?

A challenge to the meta-analyses of observational studies is that many of the studies (for example, 7 of 16 studies for CVD outcomes in Siri-Tarino et al.) have adjusted for cholesterol (or LDL cholesterol). Given that it is well established that saturated fat can raise cholesterol and LDL-cholesterol, and that these have an association with CVD events, this adjustment is inappropriate and skews the results of the meta-analyses.6 This does cast doubt on the results of the analyses of the observational data. However, this is merely one of the challenges with the observational evidence. Broader challenges are ones inherent to observational studies, namely that they do not provide direct interventions and are inherently confounded by the psychosocial food and lifestyle milieu. So, observational studies can help to indicate broad population trends which should then be considered in concert with randomised controlled trials and analyses thereof to get a clearer picture of the true effects of dietary modification.

Summary

Overall, these results from observational studies suggest that there is no effect of saturated fat intake on mortality or the incidence of cardiovascular disease.

Read All About Saturated Fat Part 2: What do we know from randomised controlled trials?

References

1.         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.

2.         O’Sullivan TA, Hafekost K, Mitrou F, Lawrence D. Food Sources of Saturated Fat and the Association With Mortality: A Meta-Analysis. American Journal of Public Health. 2013;103(9):e31-e42.

3.         Cheng P, Wang J, Shao W, Liu M, Zhang H. Can dietary saturated fat be beneficial in prevention of stroke risk? A meta-analysis. Neurological Sciences. 2016;37(7):1089-98.

4.         Muto M, Ezaki O. High Dietary Saturated Fat is Associated with a Low Risk of Intracerebral Hemorrhage and Ischemic Stroke in Japanese but not in Non-Japanese: A Review and Meta-Analysis of Prospective Cohort Studies. Journal of atherosclerosis and thrombosis. 2018;25(5):375-92.

5.         Kang Z-Q, Yang Y, Xiao B. Dietary saturated fat intake and risk of stroke: Systematic review and dose–response meta-analysis of prospective cohort studies. Nutrition, Metabolism and Cardiovascular Diseases. 2020;30(2):179-89.

6.         Scarborough P, Rayner M, van Dis I, Norum K. Meta-analysis of effect of saturated fat intake on cardiovascular disease: overadjustment obscures true associations. The American Journal of Clinical Nutrition. 2010;92(2):458-9.


[1] CHD RR = 1.07; 95% confidence interval (CI)I: 0.96, 1.19; p = 0.22. Stroke RR = 0.81; 95% CI: 0.62, 1.05; p = 0.11

[2] Meat RR = 1.17; 95% CI = 1.08, 1.27. Processed meat RR = 1.21; 95% CI = 1.16, 1.28

[3] RR = 1.17; 95% CI = 1.02, 1.33

[4] Overall stroke risk RR = 0.89; 95 % CI 0.82–0.96. Fatal stroke risk RR = 0.75; 95 % CI 0.59–0.94

[5] Intracerebral haemorrhage excluding subarachnoid haemorrhage HR = 0.55; 95% CI 0.32–0.94 (but not in non-Japanese) HR=0.98; 95% CI 0.62–1.53. Meta-analysis of ischaemic stroke showed a mild inverse association in Japanese (n=4, HR=0.82; 95% CI 0.71–0.93) but not in non-Japanese (n=7, HR= 0.93; 95% CI 0.84–1.03).

[6] RR = 0.87; 95% CI, 0.78–0.96; I2 = 37.8%

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