A double-blind placebo controlled trial into the impacts of HMB supplementation and exercise on free-living muscle protein synthesis, muscle mass and function, in older adults

Abstract

SummaryAge-related sarcopenia and dynapenia are associated with frailty and metabolic diseases. Resistance exercise training (RET) adjuvant to evidence-based nutritional intervention(s) have been shown as mitigating strategies. Given that β-hydroxy-β-methyl-butyrate (HMB) supplementation during RET improves lean body mass in younger humans, and that we have shown that HMB acutely stimulates muscle protein synthesis (MPS) and inhibits breakdown; we hypothesized that chronic supplementation of HMB free acid (HMB-FA) would enhance MPS and muscle mass/function in response to RET in older people.We recruited 16 healthy older men (Placebo (PLA): 68.5 ± 1.0 y, HMB-FA: 67.8 ± 1.15 y) for a randomised double-blind-placebo controlled trial (HMB-FA 3 × 1 g/day vs. PLA) involving a 6-week unilateral progressive RET regime (6 × 8 repetitions, 75% 1-RM, 3 · wk−1). Deuterium oxide (D2O) dosing was performed over the first two weeks (0–2 wk) and last two weeks (4–6 wk) with bilateral vastus lateralis (VL) biopsies at 0–2 and 4–6 wk (each time 75 ± 2 min after a single bout of resistance exercise (RE)) for quantification of early and later MPS responses and post-RE myogenic gene expression. Thigh lean mass (TLM) was measured by DXA, VL thickness and architecture (fibre length and pennation angle) by ultrasound at 0/3/6 wk, and strength by knee extensor 1-RM testing and MVC by isokinetic dynamometry (approx. every 10 days).RET induced strength increases (1-RM) in the exercised leg of both groups (398 ± 22N to 499 ± 30N HMB-FA vs. 396 ± 29N to 510 ± 43N PLA (both P < 0.05)). In addition, maximal voluntary contraction (MVC) also increased (179 ± 12 Nm to 203 ± 12 Nm HMB-FA vs. 185 ± 10 Nm to 217 ± 11 Nm PLA (both P < 0.05); with no group differences. VL muscle thickness increased significantly in the exercised leg in both groups, with no group differences. TLM (by DXA) rose to significance only in the HMB-FA group (by 5.8%–5734 ± 245 g p = 0.015 vs. 3.0% to 5644 ± 323 g P = 0.06 in PLA). MPS remained unchanged in the untrained legs (UT) 0–2 weeks being 1.06 ± 0.08%.d−1 (HMB-FA) and 1.14 ± 0.09%.d−1 (PLA), the trained legs (T) exhibited increased MPS in the HMB-FA group only at 0–2-weeks (1.39 ± 0.10%.d−1, P < 0.05) compared with UT: but was not different at 4–6-weeks: 1.26 ± 0.05%.d−1. However, there were no significant differences in MPS between the HMB-FA and PLA groups at any given time point and no significant treatment interaction observed. We also observed significant inductions of c-Myc gene expression following each acute RE bout, with no group differences. Further, there were no changes in any other muscle atrophy/hypertrophy or myogenic transcription factor genes we measured.RET with adjuvant HMB-FA supplements in free-living healthy older men did not enhance muscle strength or mass greater than that of RET alone (PLA). That said, only HMB-FA increased TLM, supported by early increases in chronic MPS. As such, chronic HMB-FA supplementation may result in long term benefits in older males, however longer and larger studies m...

Health Benefits of β-Hydroxy-β-Methylbutyrate (HMB) Supplementation in Addition to Physical Exercise in Older Adults: A Systematic Review with Meta-Analysis

“…Out of the 936 publications from the database search, we included 10 RCTs [36,37,38,39,40,41,42,43,44,45] on physical activity and the additional effect of HMB on several measures in the final analysis. Figure 1 shows the PRISMA flow diagram.…”

The Effects of Calcium-β-Hydroxy-β-Methylbutyrate on Aging-Associated Apoptotic Signaling and Muscle Mass and Function in Unloaded but Nonatrophied Extensor Digitorum Longus Muscles of Aged Rats

“…HMB has also been reported to improve muscle mass and function and increase muscle mitochondria biogenesis [ 93 ] in response to muscle wasting and acute unloading and reloading in aging [ 43 , 51 , 60 ]. However, the benefits of HMB have not been universally found in humans [ 80 ] and the benefits of HMB-induced increased lipid storage in the vastus lateralis fibers of older persons after bedrest are unclear [ 97 ].…”

“…Furthermore, HMB has been shown to improve EDL and soleus muscle protein synthesis in muscle wasting that was induced by partial hepatectomy in rats [ 133 ]. In addition, adding Ca-HMB to a hypertrophic stimulus (e.g., exercise or loading) and/or other anabolic nutraceuticals has been shown to improve the hypertrophic response of plantar flexor muscles in rodents [ 80 , 134 , 135 ] or quadriceps muscles in humans [ 53 ]. However, Ca-HMB treatment to aged rats without an exercise intervention did not improve gastrocnemius mass or function [ 136 ].…”

“…This is likely because trained muscles had adapted to the increased loading and therefore did not have a large anabolic stimulus to grow further. However, Ca-HMB has been shown to improve quadriceps muscle strength when combined with the anabolic stimulus of exercise in older humans [ 59 , 80 , 141 ]. These published studies and our current data support the idea that Ca-HMB supplementation has the greatest anabolic benefits to increase mass and strength or reduce muscle wasting when the muscle has a major insult (e.g., damage or loading to induce repair and/or muscle growth after severe atrophy).…”

“…HMB is available in both calcium (Ca-HMB) salt or free acid (FA-HMB) forms, and both Ca-HMB [ 59 , 60 ] and FA-HMB [ 80 ] have been reported to improve the anabolic nature of muscle in older humans. We chose to use Ca-HMB because we and others have previously found that this form of HMB improved muscle remodeling in the plantar flexors of old rats after HS [ 43 , 51 ].…”