Applied nutritional investigationEffect of β-hydroxy-β-methylbutyrate, arginine, and lysine supplementation on strength, functionality, body composition, and protein metabolism in elderly women☆
Introduction
Beginning at approximately age 40 y, muscle mass in humans atrophies at a rate of approximately 8% per decade1, 2, 3, 4 until age 70 y, when this loss increases to 15% per decade.3 The underlying cause of this loss is multifactorial and appears to involve motor unit remodeling,5 possibly age-related disease effects,6 and a decrease in hormonal activity,7 all of which can contribute to the decrease in the rate of protein synthesis observed with age.8, 9, 10 It is estimated that the rate of protein synthesis in humans decreases by as much as 38% by middle age (50 y) and by 55% with advanced age (70+ y) when compared with younger individuals (∼20 y).10
Several strategies have been proposed to stem age-associated muscle loss, such as exercise, complete nutrition intervention, and hormone therapy. However, only resistance training has been proven effective.11, 12, 13 Unfortunately, exercise training is adopted only by a very small percentage of elderly individuals. Although relatively easy to implement, complete nutritional intervention has not always been effective,13, 14, 15, 16 and hormonal therapy poses significant potential side effects without consistent effects on muscle.17
One strategy with potential is to use targeted nutritional supplementation that stimulates the process of protein synthesis over that of protein breakdown. For example, a recent study has shown that supplementation of essential amino acids increases muscle protein anabolism in the elderly.18 Other studies have successfully implemented such a strategy to minimize muscle loss related to acquired immunodeficiency syndrome19 and cancer-related cachexia20 by supplementing an amino acid mixture of arginine (ARG) and glutamine to support protein synthesis in addition to the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) to blunt the rate of protein breakdown. In both diseases, muscle wasting was reversed over an 8-wk period by daily supplementation of this mixture.
The objective of the current studies was to determine whether a once-daily dosage of HMB, ARG, and lysine (LYS) could improve the age-associated changes in muscle mass, functionality, and protein metabolism in elderly women. LYS was used in this nutrient mixture because it is one of the only true essential amino acids,21 and data have shown that supplementation of essential amino acids in the elderly may stimulate muscle protein anabolism.18 In addition, recent studies have demonstrated that the requirement for LYS is much higher than generally accepted22, 23; thus, supplemental LYS may help meet this requirement in the diet of the elderly person. ARG was used because it has been shown to stimulate whole-body protein synthesis.24, 25 HMB was included in the mixture because it has been shown to prevent excessive muscle proteolysis during metabolic stress26, 27, 28 and has recently been shown to enhance muscle mass gains in exercising older men and women.29
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Subjects
Twenty-nine women in study 1 (65 to 90 y) and 28 women in study 2 (62 to 85 y) were recruited from senior citizen centers and adult assisted-living and care facilities. One week before the initiation of the study, each subject filled out a questionnaire detailing her medical history. Subjects were excluded if they were receiving active treatment for liver or kidney disease. They also were excluded for uncontrolled hypertension or uncontrolled diabetes. All subjects gave written informed consent
Subjects
Table I summarizes the data for body weight, composition, and strength measures. In study 1, 10 subjects (81.1 ± 1.8 y) assigned to the placebo supplement and 13 subjects (84.2 ± 1.6 y) assigned to the HMB/ARG/LYS supplement completed the 12-wk study. Four of the 14 placebo-supplemented subjects (29%) withdrew from the study. Two withdrew because of flu symptoms, one dropped out because of a pre-existing medical condition, and the fourth subject died of an unrelated cardiovascular accident. Two
Discussion
The current study demonstrated that using a nutritional supplement containing HMB, ARG, and LYS results in increased fat-free mass, increased limb circumferences, enhanced strength, and improved functionality in elderly women. Previous attempts to increase muscle mass in the elderly without exercise use various hormonal treatments. Administrations of growth hormone, insulin-like growth factor, and testosterone have significant potential side effects that are of concern, and each has been tested
Summary
Daily supplementation of HMB, ARG, and LYS for 12 wk positively altered measurements of functionality, strength, fat-free mass, and protein synthesis, suggesting that the strategy of targeted nutrition has the ability to affect muscle health in elderly women.
Acknowledgements
The authors thank Dr. John Rathmacher for his contribution in acquisition of data, Dr. Naji Abumrad for his critical review of the manuscript, Metabolic Technologies, Inc. for supplying the supplements, and the volunteers for their faithful participation in this study. They also thank the nursing staffs of the General Clinical Research Center (GCRC, RR-00095) at Vanderbilt University and Meg Speer and the staff of Eastern Star Masonic Home, Boone, Iowa. They appreciate the excellent technical
References (42)
The pathophysiology of wasting in the elderly
J Nutr
(1999)- et al.
Randomized clinical trial of nutritional supplementation shows little effect of functional status among free-living frail elderly
J Nutr
(1995) - et al.
Endocrinological aspect of aging in menIs hormone replacement of benefit?
Eur J Obstet Gynecol Reprod Biol
(2000) - et al.
Essential amino acids are primarily responsible for the amino acid stimulation of muscle protein anabolism in healthy elderly adults
Am J Clin Nutr
(2003) Dispensable and indispensable amino acids for humans
J Nutr
(2000)- et al.
Twenty-four-hour oral tracer studies with L- [l-13C] lysine at a low (15 mg.kg (−1).d(−1)) and intermediate (29 mg.kg (−1).d(−1)) lysine intake in healthy adults
Am J Clin Nutr
(2000) - et al.
Statistical analysis of nitrogen balance data with reference to the lysine requirement in adults
J Nutr
(1999) - et al.
Nutritional role of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB)
J Nutr Biochem
(1997) - et al.
Nutritional supplementation of the leucine metabolite β-hydroxy β-methylbutyrate (HMB) during resistance training
Nutrition
(2000) - et al.
Body composition in 70-year old adults responds to dietary β-hydroxy-β-methylbutyrate (HMB) similar to that of young adults
J Nutr
(2001)
Protein pulse feeding improves protein retention in elderly women
Am J Clin Nutr
Amino acid analysis by reverse-phase high-performance liquid chromatographyPrecolumn derivatization with phenylisothiocyanate
Anal Biochem
Analysis of β-hydroxy-β-methyl butyrate in plasma by gas chromatography and mass spectrometry
Anal Biochem
The ageing muscle
Clin Physiol
Skeletal muscle mass and distribution in 468 men and women aged 18–88 yr
J Appl Physiol
Morphology and enzymatic capacity in arm and leg muscles in 78–82 yr old men and women
Acta Physiol Scand
Muscle strength and speed of movement in relation to age and muscle morphology
J Appl Physiol
Skeletal muscle weakness in old ageUnderlying mechanisms
Med Sci Sports Exerc
Intrinsic and extrinsic factors in muscle aging
Ann NY Acad Sci
Postprandial myofibrillar and whole body protein synthesis in young and old human subjects
Am J Physiol
Myofibrillar protein synthesis in young and old men
Am J Physiol Endocrinol Metab
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The study was supported in part by a gift from Metabolic Technologies, Inc., Ames, Iowa and the Clinical Nutrition Research Unit (DK-26657) and the General Clinical Research Center (RR-00095) at Vanderbilt University.