Impact of beta-Hydroxy-beta-methylbutyrate plus Vitamin D 3 Supplementation on Skeletal Muscle Size, Function and Quality in Sedentary and Resistance Exercise Trained Women.

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.