Nutritional supplementation with ginseng extract and CaHMB in older adults with cognitive impairment and sarcopenia: A randomized controlled trial

Cognitive impairment and sarcopenia frequently coexist in older adults and are associated with loss of independence; evidence for nutritional interventions targeting both conditions remains limited. To evaluate the efficacy and safety of a nutritional formula enriched with ginseng extract and calcium β-hydroxy-β-methylbutyrate (CaHMB) in older adults with cognitive impairment and sarcopenia. In this single-center, randomized, participant- and outcome assessor-blinded trial, 136 adults aged ≥ 65 years were assigned to receive either the enriched formula or a nutritionally matched control formula (100 g/day) for 6 months. Outcomes were assessed at baseline and at months 3 and 6. The four primary outcomes were MMSE, MoCA, handgrip strength, and ASMI, with month 6 as the primary analysis time point. The prespecified principal efficacy analysis used the per-protocol set (PPS; n = 121), while a supportive full-analysis-set/intention-to-treat (FAS/ITT) analysis included all 136 randomized participants with multiple imputation for missing follow-up outcomes. Primary outcomes were analyzed using baseline-adjusted mixed models for repeated measures (MMRM), with Holm adjustment applied to the month-6 primary-outcome family. Additional supportive and missing-data sensitivity analyses included HC3 ANCOVA, jump-to-reference, delta-adjusted, and tipping-point analyses. At month 6, adjusted between-group differences favored the intervention for MMSE (1.40 points; 95% CI, 1.14 to 1.67), MoCA (1.71 points; 95% CI, 1.49 to 1.93), and handgrip strength (1.44 kg; 95% CI, 1.20 to 1.69; all Holm-adjusted P < 0.001). These three findings remained statistically significant across the missing-data sensitivity analyses. The ASMI difference favored the intervention in the principal analysis (0.227 kg/m²; 95% CI, 0.005 to 0.448; Holm-adjusted P = 0.045) and under multiple imputation, but was not statistically significant under jump-to-reference or delta-adjusted assumptions. Month-6 secondary outcomes also showed Holm-adjusted between-group differences favoring the intervention. Events judged at least possibly related to the study product were more frequent in the intervention group, largely because of bitterness-related sensory/tolerability complaints; no serious adverse events occurred. The between-group findings for MMSE, MoCA, and handgrip strength were consistent across the principal and missing-data sensitivity analyses, whereas the ASMI finding was sensitive to assumptions regarding missing outcomes. Over 6 months, the combined ginseng- and CaHMB-enriched nutritional intervention was associated with modest between-group differences favoring the intervention in cognitive scores and handgrip strength. The ASMI estimate was less robust and remains uncertain. Larger, prospectively registered multicenter trials are needed to confirm these findings and determine their clinical relevance. Chinese Clinical Trial Registry, ChiCTR2400087204, July 22, 2024; retrospectively registered.