Impact of beta‐Hydroxy‐beta‐methylbutyrate plus Vitamin D3 Supplementation on Skeletal Muscle Size, Function and Quality in Sedentary and Resistance Exercise Trained Women

Abstract

The age‐related loss of skeletal muscle mass, quality, and strength can lead to the loss of independence later in life. Beta‐hydroxy‐beta‐methylbutyrate (HMB), a leucine metabolite, can increase skeletal muscle size and function. However, emerging evidence suggests HMB may be less effective at improving muscle function in people with insufficient Vitamin D3 levels (25‐hydroxy‐Vitamin D (25‐OH‐D) <30 ng/mL,) common in middle‐aged and older adults. Therefore, our current study tested the hypothesis that combining HMB (Calcium salt) with Vitamin D3 (HMB+D) would increase skeletal muscle size, quality and function in middle aged women (53±1 yrs, 26±1 kg/m2, n=43) randomized to sedentary control (SED) or progressive resistance exercise training (RT). In a placebo‐controlled, double‐blinded fashion, women were further randomized to placebo or HMB+D (3g of HMB + 2000IU of Vitamin D3). Study enrollment and recruitment occurred before and after COVID‐19 stay at home measures. In both RT and SED, HMB+D raised circulating levels of 25‐OH‐D after 8 (33±2 ng/mL) and 12 (35±2 ng/mL) weeks to reach sufficient Vitamin D3 levels. In SED, HMB+D prevented the loss of lean arm mass observed in the placebo group (0.07±0.06 vs ‐0.19±0.06 kg; P<0.05). HMB+D also increased thigh skeletal muscle (26±13 vs ‐5±8 cm3; P<0.05) and decreased intermuscular adipose tissue (IMAT) volume (‐20±11 vs 5±6 cm3; P<0.05) compared to placebo. However, 12‐weeks of HMB+D did not change skeletal muscle function. In the RT, 12‐weeks of HMB+D decreased IMAT compared to placebo (‐22±13 vs 6±4 cm3; P<0.05) but did not influence the increase in skeletal muscle mass or function. These data show that 12‐weeks of HMB+D supplementation consistently decreased thigh IMAT volume in both SED and RT. HMB+D in sedentary middle‐aged women was beneficial for skeletal muscle size but did not lead to improved muscle function or quality. Further, HMB+D did not influence the hypertrophic or functional improvements after resistance exercise training in middle‐aged women. HMB+D may be able to help combat the age‐related loss of skeletal muscle mass in sedentary women. These results lend support to conducting a larger study for a longer duration to validate these findings as well as explore additional populations who may also benefit from HMB+D.