A novel oral nutritional supplement improves gait speed and mitochondrial functioning compared to standard care in older adults with (or at risk of) undernutrition: results from a randomized controlled trial

Pol Grootswagers, Ellen Smeets, Antwi-Boasiako Oteng, Lisette de Groot, Pol Grootswagers, Ellen Smeets, Antwi-Boasiako Oteng, Lisette de Groot

Abstract

Undernutrition in older adults is mainly addressed by oral nutritional supplements, which do not affect physical functioning. In this study, we tested a novel oral nutritional supplement that included whey and casein protein, ursolic acid, free branch-chained amino acids and vitamin D against a standard supplement. We included older adults (>65y) with (or at risk of) undernutrition (n=82) and randomized them to 12 weeks of novel or standard supplement. Both groups showed significant increases in body mass. No within or between-group differences in lean body mass were observed. Fat mass increased significantly more in the standard than the novel supplement group (time*treatment effect P=0.045). The novel supplement group showed a larger improvement in walking performance on distances of 4m (treatment x time interaction P=0.048) and 400m (treatment x time interaction P=0.038) than the standard treatment group. Gene sets related to mitochondrial functioning and oxidative phosphorylation were upregulated in the novel supplement group and downregulated in the standard supplement group. We conclude that a 12-week intervention with the novel supplement improved walking performance both during short and long distance as compared to a standard supplement, which can largely be explained by increased mitochondrial functioning in the group receiving the novel supplement.

Trial registration: ClinicalTrials.gov NCT02683720.

Keywords: malnutrition; mitochondria; muscle; ursolic acid; walking performance.

Conflict of interest statement

CONFLICTS OF INTEREST: Lisette de Groot has received research grants from VitalNext B.V. Pol Grootswagers, Ellen Smeets and Antwi-Boasiako Oteng declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of participants.
Figure 2
Figure 2
(A) Change in lean mass and fat mass over the course of the intervention period in the two treatment groups. ***, significant increase in fat mass within both groups between week 0 and 6; **, significant increase in fat mass within the standard supplement group between week 6 and 12; *, significant increase in lean mass between week 0 and 6 in the standard supplement group. (B) proportion of fat mass (79.5% in novel supplement, 87.7% in standard supplement) and (appendicular) lean mass (20.5% in novel supplement, 12.2% in standard supplement) as part of the total weight gain in the two groups.
Figure 3
Figure 3
Change in time to complete 4 m (left, time*treatment effect P=0.047) and 400 m (right, time*treatment effect P=0.038, n=81).
Figure 4
Figure 4
Enrichment of the top enriched gene sets (FDR<1.5 E-8, overlap < 75%) from differential analysis in ClusterProfiler using MsigDB C2 Curated gene sets. From left to right, differential enrichment of gene sets, enrichment of these gene sets in standard supplement group (n=13, blue bars), and enrichment of these gene sets in novel supplement group (n=7, pink bars). FDR, false detection rate; NS, not significant.
Figure 5
Figure 5
Fold change in PGC1-α expression between baseline and week 12 in the two treatment arms.

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