Circulating Very-Long-Chain Saturated Fatty Acids and Incident Coronary Heart Disease in US Men and Women

Abstract

Background Circulating very-long chain saturated fatty acids (VLCSFAs) may play an active role in the etiology of cardiometabolic diseases. Methods and Results We measured three VLCSFAs (C20:0, C22:0, and C24:0) in plasma and erythrocytes using gas-liquid chromatography among 794 incident coronary heart disease (CHD) cases who were prospectively identified and confirmed among women in Nurses' Health Study (NHS; 1990–2006) and among men in Health Professionals Follow-up Study (HPFS; 1994–2008). A total of 1233 CHD-free controls were randomly selected and matched to cases in these two cohorts. Conditional logistic regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI). Plasma VLCSFAs were correlated with favorable profiles of blood lipids, C-reactive protein, and adiponectin in the NHS and HPFS, as well as with fasting insulin and C-peptide levels in a nationally-representative U.S. comparison population. After multivariate adjustment for lifestyle factors, body mass index (BMI), diet, and long-chain n-3 and trans fatty acids, total VLCSFAs in plasma was associated with a 52% decreased risk of CHD [pooled HR (95% CI); 0.48 (0.32, 0.72), comparing extreme quintiles; Ptrend<0.0001]. For VLCSFAs in erythrocytes, a non-significant inverse trend with CHD risk was observed [pooled HR (95% CI); 0.66 (0.41, 1.06), comparing extreme quintiles; Ptrend=0.16]. Conclusions In U.S. men and women, plasma VLCSFAs were independently associated with favorable profiles of blood lipids and other CVD risk markers and a lower risk of CHD. Erythrocyte VLCSFAs were associated with non-significant trends of lower CHD risk. Future studies are warranted to elucidate underlying biological mechanisms.

A prospective analysis of circulating saturated and monounsaturated fatty acids and risk of non‐Hodgkin lymphoma

“…Emerging evidence suggests a beneficial association of VLCSFAs (but not shorter chain SFAs) with several health outcomes including atrial fibrillation, diabetes mellitus, and sudden cardiac arrest. [32][33][34][35] The present findings appear to extend this evidence to B-NHLs other than CLL/ SLL, suggesting an inverse association via mechanisms that are as yet unknown. One plausible mechanism by which VLCSFA could protect against B cell lymphomagenesis is the activation of proliferator-activated receptor gamma (PPARg).…”

“…To our knowledge, this is the first study exploring the association between circulating VLCSFA and risk of hematological malignancies. Emerging evidence suggests a beneficial association of VLCSFAs (but not shorter chain SFAs) with several health outcomes including atrial fibrillation, diabetes mellitus, and sudden cardiac arrest . The present findings appear to extend this evidence to B‐NHLs other than CLL/SLL, suggesting an inverse association via mechanisms that are as yet unknown.…”

Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity

“…For instance, palmitic acid (16:0) exhibits in vitro adverse effects; whereas medium-chain (6:0-12:0), odd-chain (15:0, 17:0), and very long-chain (20:0-24:0) saturated fats may have metabolic benefits. 61, 338, 339 This biologic and metabolic diversity does not support the grouping together of all saturated fatty acids based on a single chemistry characteristic: the absence of double bonds. 340 …”

Red blood cell oleic acid levels reflect olive oil intake while omega-3 levels reflect fish intake and the use of omega-3 acid ethyl esters: The Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico–Heart Failure trial

“…There are multiple controversies surrounding the effects of saturated, mono-unsaturated and omega-6 polyunsaturated fatty acids (FAs) on coronary heart disease (CHD) risk [1][2][3][4], and even around the omega-3 FA, which for many years have enjoyed virtually universal support as being cardioprotective [5,6]. In the Chowdhury et al meta-analysis [1], both intakes and blood levels of the long-chain, marine-derived omega-3 FAs (eicosapentaenoic, docosahexaenoic, and docosapentaenoic acids; EPA, DHA, and DPAn-3) were inversely related to risk, but randomized trials have, at least in recent years, not supported this relationship.…”