Effectiveness of nutrition interventions and combined nutrition and physical activity interventions in older adults with frailty or prefrailty: a systematic review and meta-analysis

Background: Although nutrition interventions may reverse frailty, it is unclear which interventions are optimal. We conducted a systematic review and meta-analysis to identify effective nutrition interventions that improve outcomes related to frailty. Methods: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and CINAHL (inception to July 2019) for English-language trials of nutrition and combined-approach (nutrition and exercise) interventions (with a control group) involving prefrail or frail adults aged 65 years or more. Outcomes of interest were frailty, mobility, health (body weight, body mass index), physical function (e.g., activities of daily living, muscle strength, appendicular lean mass), use of health care services (e.g., hospital admissions), quality of life, diet quality, mortality, and caregiver and social support. After data extraction, we assessed the risk of bias using the Cochrane Collaboration risk of bias tool for randomized controlled trials, rated the certainty of evidence with the Grading of Recommendation, Assessment, Development and Evaluations (GRADE) approach, and assessed statistical and methodologic heterogeneity. In addition, we conducted subgroup analyses of studies based on the primary intervention of protein supplementation. Results: We identified 15 studies involving 1825 prefrail or frail older participants: 7 were nutrition trials, 7 were combined-approach trials, and 1 trial had both a nutrition arm and a combined-approach arm. Seven studies had low risk of bias, 2 studies had high risk of bias, and for 6 studies the risk of bias was unclear. Nutrition interventions had small but significant effects on measures of physical function (standardized mean difference [SMD] 0.16, 95% confidence interval [CI] 0.02 to 0.29), mobility (SMD 0.15, 95% CI 0.00 to 0.30) and frailty (SMD −0.22, 95% CI −0.44 to −0.01) outcomes. Nutrition interventions combined with physical activity also had small but significant effects on physical function (SMD 0.19, 95% CI 0.06 to 0.32), mobility (SMD 0.25, 95% CI 0.02 to 0.48) and frailty (SMD −0.41, 95% CI −0.68 to −0.14; risk ratio 0.72, 95% CI 0.52 to 1.00) measures. Protein supplementation (5 studies) had small but significant effects on physical function measures (SMD 0.16, 95% CI 0.01 to 0.31) and mobility measures (SMD 0.20, 95% CI 0.02 to 0.39), with moderate certainty of evidence. Interpretation: There is moderate evidence that nutrition (including protein supplementation) and combined interventions are beneficial for prefrail or frail older adults. Trials with clear definitions of frailty and outcomes that reflect frailty identification and diagnosis are needed. PROSPERO registration: CRD42020144819