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.

Prospective cohort study.

The UK Biobank cohort.

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.

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.

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.

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.