Association between plasma docosahexaenoic acid levels and the incidence of frailty: A prospective analysis of the UK Biobank

OBJECTIVES: The blood level of n-3 polyunsaturated fatty acids (PUFAs) has been associated cross-sectionally with frailty, but its relationship with incident frailty remains unclear. The present study investigates the hypothesis that plasma levels of n-3 PUFAs, particularly docosahexaenoic acid (DHA), are inversely associated with the incidence of frailty and individual frailty criteria. DESIGN: Prospective cohort study. SETTING: The UK Biobank cohort. PARTICIPANTS: A total of 38,577 non-frail adults aged 40-69 years who enrolled between 2006 and 2010 were followed for a maximum of 13 years. MEASUREMENTS: Frailty was defined as meeting at least 3 of 5 separate criteria (low physical activity, exhaustion, slow walking speed, weight loss, and low grip strength), and plasma levels of total n-3 PUFAs, DHA, and non-DHA n-3 PUFAs were measured by nuclear magnetic resonance. Cox-proportional hazards models were used to predict incident frailty after adjusting for demographic, medical history and other potential confounding factors. RESULTS: After a median follow-up of 9.37 years, 1,024 individuals became frail. The incidence of frailty was inversely associated with plasma level of DHA (hazard ratio [HR] per inter-quintile range: 0.82, 95% confidence interval [CI] 0.69-0.97; p=0.019) after adjusting for confounding factors. Plasma level of DHA was inversely associated with the incidence of two frailty criteria-low physical activity and exhaustion. On the other hand, neither plasma levels of non-DHA n-3 PUFAs (HR 0.98, 95% CI 0.83-1.16) nor those of total n-3 PUFAs (HR 0.91, 95% CI 0.77-1.07) was significantly associated with the incidence of frailty after adjusting for confounding factors. CONCLUSIONS: The incidence of frailty was inversely associated with the plasma level of DHA but not with the levels of other n-3 PUFAs, suggesting that a low plasma DHA level could help identify individuals at high risk for developing frailty, enabling preventive measures to be initiated.