Nutritional factors and physical frailty: Highlighting the role of functional nutrients in the prevention and treatment

Physical frailty, an age-related decline in the physiological capacity and function of various organs, is associated with higher vulnerability to unfavorable health outcomes. The mechanisms proposed for physical frailty including increased inflammation and oxidative stress are closely related to nutritional status. In addition to traditional nutritional factors such as protein malnutrition and nutrient deficiencies, emerging evidence has focused on the role of functional nutrients including polyphenols, carotenoids, probiotics, prebiotics, omega-3 long-chain polyunsaturated fatty acids (n-3 PUFAs), β-hydroxy-β-methylbutyrate (HMB), coenzyme Q10 (CoQ10), and L-carnitine in modifying the risk of physical frailty syndrome. Although several clinical trials have suggested the beneficial effects of supplementation with polyphenols, HMB, and prebiotics on frailty indices, the current evidence is still not robust to support recommendations on the routine clinical use of such functional nutrients for the management of frailty. Similarly, the association between CoQ10 and frailty was mainly assessed in observational studies, and more randomized controlled trials are needed in this regard. A limited number of studies have reported the beneficial effect of L-carnitine supplementation on frailty indices. Since carnitine is mainly found in skeletal muscle and its measurement is thus challenging due to ethical constraints, it is necessary to examine the effect of different doses of L-carnitine on frailty and its indices in future studies. A large number of interventional studies evaluated the impact of n-3 PUFA supplementation on physical frailty in the elderly and many of them reported improved physical performance following supplementation, especially when combined with resistance training programs. Although promising findings from experimental and observational studies have been reported on functional nutrients, high-quality evidence from randomized controlled trials as well as detailed mechanistic studies are still required to affirm their role in the prevention and/or treatment of physical frailty. This review aims to describe the current state of research on functional nutrients that may modify the development or prognosis of frailty syndrome.