Association of branched chain fatty acids with cardiometabolic disorders in humans: a systematic review

Context Despite advances in treatments for cardiometabolic disorders such as type 2 diabetes mellitus and obesity, the increasing frequency of these conditions is of major clinical and public health concern. Therefore, primary prevention including diet and lifestyle approaches continues to play a key role in risk reduction. Meta-analyses of prospective cohort studies have documented inverse associations of dairy consumption with the incidence of different cardiometabolic disorders. Dairy is the largest dietary contributor of branched chain fatty acids (BCFAs), which have been suggested to not only serve as biomarkers of dairy consumption but may also have bioactive properties contributing to reducing the risk of cardiometabolic outcomes. To date, however, the literature on this topic has not been systematically reviewed. Objective The aim here was to report the results of a systematic review of the association of BCFAs with cardiometabolic disorders in humans. Data Sources Search terms were developed and run through the Ovid MEDLINE, Ovid Embase, and the Cochrane Library databases. Data Extraction Articles were selected on the basis of prespecified inclusion criteria and assessed for risk of bias by independent reviewers. Results Four studies (n = 2 cross sectional; n = 1 randomized feeding trial and n = 1 pre-post study) were identified. Two studies reported significant inverse associations between serum BCFAs and insulin resistance, triglycerides and/or body mass index. One study identified an inverse association between adipose tissue monomethyl BCFAs and skeletal muscle insulin resistance. In contrast, the randomized feeding trial reported no significant differences to stool BCFA concentrations or body mass index in obese participants following assignment to fruit-vegetable or whole-grain diet groups compared with a refined-grain control group. Conclusions Current evidence suggests beneficial associations of circulating BCFAs with cardiometabolic risk phenotypes, although data in human participants are limited, indicating that additional research is required. PROSPERO registration no CRD42021224975.