Effect of β-hydroxy-β-methylbutyrate (HMB) on lean body mass during 10 days of bed rest in older adults

Summary

Background

Loss of muscle mass due to prolonged bed rest decreases functional capacity and increases hospital morbidity and mortality in older adults.

Objective

To determine if HMB, a leucine metabolite, is capable of attenuating muscle decline in healthy older adults during complete bed rest.

Design

A randomized, controlled, double-blinded, parallel-group design study was carried out in 24 healthy (SPPB ≥ 9) older adult subjects (20 women, 4 men), confined to complete bed rest for ten days, followed by resistance training rehabilitation for eight weeks. Subjects in the experimental group were treated with HMB (calcium salt, 1.5 g twice daily – total 3 g/day). Control subjects were treated with an inactive placebo powder. Treatments were provided starting 5 days prior to bed rest till the end rehabilitation phase. DXA was used to measure body composition.

Results

Nineteen eligible older adults (BMI: 21–33; age: 60–76 year) were evaluable at the end of the bed rest period (Control n = 8; Ca-HMB n = 11). Bed rest caused a significant decrease in total lean body mass (LBM) (2.05 ± 0.66 kg; p = 0.02, paired t-test) in the Control group. With the exclusion of one subject, treatment with HMB prevented the decline in LBM over bed rest −0.17 ± 0.19 kg; p = 0.23, paired t-test). There was a statistically significant difference between treatment groups for change in LBM over bed rest (p = 0.02, ANOVA). Sub-analysis on female subjects (Control = 7, HMB = 8) also revealed a significant difference in change in LBM over bed rest between treatment groups (p = 0.04, ANOVA). However, differences in function parameters could not be observed, probably due to the sample size of the study.

Conclusions

In healthy older adults, HMB supplementation preserves muscle mass during 10 days of bed rest. These results need to be confirmed in a larger trial.

This trial is registered at http://ClinicalTrials.gov under NCT00945581.

Introduction

Muscle inactivity due a prolonged period of immobility or bed rest induces rapid muscle atrophy and loss of force and power.1, 2, 3, 4 This is an undesirable consequence of hospitalization after illness or injury. A majority of hospitalized patients are 65 years or older, and their hospital lengths of stay tend to be longer.⁵ About 65% of older patients experience a decrease in ambulatory function with hospitalization, and between 30 and 55% report a decline in activities of daily living.6, 7

Healthy older adults have been reported to lose ∼1 kg (about 6%) of lean tissue from the lower extremities after 10 days of bed rest, with an associated ∼16% decline in isokinetic knee extensor strength.⁸ In addition, they displayed a significant decline in maximal aerobic capacity.⁹ This dramatic loss of muscle mass and strength is greater than is observed in young adults after 14 or 28 days of bed rest.4, 10 Muscle atrophy during bed rest is attributed to a marked decline in the rates of skeletal muscle protein synthesis,4, 11 although the role of accelerated muscle protein degradation in relation to the rate of synthesis cannot be ruled out. Resistance exercise has been shown to provide a potent anabolic stimulus during bed rest.12, 13 However, exercise may not always be a feasible option, especially in situations involving physical impairments, surgery or severe injury. Thus dietary interventions have been considered and are currently being explored for their efficacy in ameliorating the debilitating impact of muscle atrophy due to bed rest.

Strategies for nutritional intervention have included increasing dietary protein intake from 0.5 g protein/kg/day to more than 1 g protein/kg/day in malnourished hospitalized patients. Increasing protein intake resulted in improved nitrogen balance and greater rates of whole body protein synthesis.¹⁴ Another study showed that supplementation of the diet with essential amino acids (EAA) stimulated muscle protein synthesis and improved some functional outcomes in healthy older adults, confined to 10 days of bed rest, with no effect on muscle mass.¹⁵ In addition, daily ingestion of EAA plus carbohydrate ameliorated the loss of lean body mass and muscle strength during 28 days of bed rest in young subjects.¹⁰ Some of the beneficial effects of EAA have been attributed to the anabolic stimulus provided by branched chain amino acids (BCAA), leucine, isoleucine and valine.16, 17 However to date, no intervention has been identified that prevents the progression of muscle mass decline in older adults on bed rest.

Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite of leucine that, when ingested in combination with the amino acids glutamine and arginine, has been shown to preserve lean body mass in chronic disease conditions such as cancer and AIDS.18, 19 HMB has been shown to have an anabolic effect on muscle when ingested in conjunction with exercise (reviewed in²⁰). In healthy exercising older adult subjects, HMB (3 g/d) when consumed for 8 weeks tended to increase fat-free mass gain (p = 0.08) and significantly increased the percentage of body fat loss (p = 0.05) compared with the placebo group.²¹ In addition, a recent study has demonstrated that daily supplementation of non-exercising older women with HMB (plus arginine and lysine) for 12 weeks significantly improved their functionality and strength, with a trend toward improvement of whole body protein synthesis (p = 0.08).²²Thus it seems plausible that supplementation of the diet with HMB would ameliorate the decrease in muscle protein synthesis and attenuate loss of muscle in older adults confined to bed rest. In addition, a recent preclinical study has demonstrated the positive effects of HMB on long term immobilized muscles and recovery from immobilization.²³

In the current study we have tested the efficacy of HMB supplementation on the declines in muscle mass, strength and function that occur over 10 days of bed rest in older adults.