Research Paper Volume 13, Issue 7 pp 9398—9418

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 Grootswagers1, , Ellen Smeets1, , Antwi-Boasiako Oteng1, , Lisette de Groot1, ,

  • 1 Division of Human Nutrition and Health, Wageningen University, Wageningen, The Netherlands

Received: December 10, 2020       Accepted: March 23, 2021       Published: April 2, 2021
How to Cite

Copyright: © 2021 Grootswagers et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


AMPK: AMP-activated protein kinase; BCAA: branched-chain amino acids; CPM: counts per minute; DXA: dual-energy x-ray absorptiometry; EDTA: Ethylenediaminetetraacetic acid; eGFR: estimated glomerular filtration rate; EWGSOP2: European Working Group on Sarcopenia in Older People 2; FDR: false discovery rate q-value; IBMT: intensity-based moderated T-statistic; IFNγ: interferon-gamma; IGF-1: Insulin-like growth factor 1; IL-13: interleukin-13; MNA-sf: mini nutritional assessment tool short form; mTOR: mammalian target of rapamycin; MuRF-1: Muscle RING finger 1; NES: normalized enrichment score; NK: Natural Killer cells; ONS: oral nutritional supplements; PBMC: peripheral blood mononuclear cells; PGC1α: Peroxisome proliferator-activated receptor gamma coactivator 1 alpha; ProMO: PROtein supplementation in Malnourished Older adults; PVDF: Polyvinylidene difluoride; RMA: robust multichip average; SD: standard deviation; SPPB: short physical performance battery; TBS: Tris Buffered Saline; TCA: tricarboxylic acid; TFAM: mitochondrial transcription factor a; UA: ursolic acid.