Oxidative stress and frailty: A systematic review and synthesis of the best evidence.

OBJECTIVE: Oxidative stress (OS) is associated with accelerated aging. Previous studies have suggested a possible relationship between OS and frailty but this association remains unclear. We conducted a systematic review to investigate potential interactions between OS and frailty.

METHODS: A systematic literature search of original reports providing data on 'OS and antioxidant' parameters and frailty was carried out across major electronic databases from inception until May 2016. Cross-sectional/case control and longitudinal studies reporting data on the association between frailty and anti-oxidants-OS biomarkers were considered for inclusion. Results were summarized with a synthesis based on the best evidence.

RESULTS: From 1856 hits, 8 studies (cross-sectional/case control) were included (N=6349; mean age of 75±12years; 56.4% females). Overall, there were 588 (=9.3%) frail, 3036 pre-frail (=47.8%), 40 (=0.6%) pre-frail/robust, and 2685 (=42.3%) robust subjects. Six cross-sectional/case control studies demonstrated that frailty was associated with an increase in peripheral OS biomarkers, including lipoprotein phospholipase A2 (1 study), isoprostanes (2 studies), malonaldehyde (2 studies), 8-hydroxy-20-deoxyguanosine (2 studies), derivate of reactive oxygen metabolites (2 studies), oxidized glutathione/glutathione (1 study), 4-hydroxy-2,3-nonenal (1 study), and protein carbonylation levels (1 study). In addition, preliminary evidence points to lower anti-oxidant parameters (vitamin C, E, α-tocopherol, biological anti-oxidant potential, total thiol levels) in frailty.

CONCLUSION: Frailty and pre-frailty appear to be associated with higher OS and possibly lower anti-oxidant parameters. However, due to the cross-sectional design, it is not possible to disentangle the directionality of the relationships observed. Thus, future high-quality and in particular longitudinal research is required to confirm or refute these relationships and to further elucidate pathophysiological mechanisms.