HMB, magnesium, omega 3s, and vitamin D are put to the test for muscle strength and function.
Supplements for Sarcopenia (Age-Related Muscle Loss)
Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
Previously, I’ve covered the evidence surrounding supplementation for older adults with protein or amino acids like leucine. What about a metabolite of leucine known as β‑hydroxy β‑methylbutyrate, known as HMB? Adding HMB to an exercise regimen fails across the board to improve muscle mass, muscle strength, or physical performance among older individuals, and since everyone should be exercising, that pretty much takes HMB off the table. But there are circumstances when you’re laid up––for example, recuperating from a broken hip.
Researchers in Spain randomized about 100 men and women over the age of 65 in rehab recovering from a hip fracture to a nutritional supplement with about 3 grams of HMB. They suffered less loss of fat-free mass loss compared to the control group who didn’t get the supplement. Unfortunately, the supplement provided other components; so, it’s impossible to tease out the HMB effects. But regardless, there was no significant change in muscle strength or muscle function. This was roughly consistent with a 10-day bedrest study of straight HMB versus placebo, in which the HMB group similarly lost less lean mass—but only when an outlier was excluded, which isn’t really kosher—and there was no apparent improvement in strength or function.
This is what meta-analyses of all such studies have found—an improvement in fat-free mass in older sedentary adults, with no change in strength or function, and no benefits for any muscle parameters when combined with physical activity. Since we all should be exercising, and there’s a questionable benefit of lean mass for lean mass’s sake, combined with the fact that HMB activates the engine-of-aging enzyme mTOR, I see little reason to recommend supplementing with HMB.
What about magnesium? Higher blood levels correlate with muscle performance. One cohort study of older adults found that those with higher magnesium intake had greater lean mass over time, though the dietary intake of magnesium appeared to be similar between those with and without sarcopenia (excessive age-related muscle loss). There was one randomized controlled trial of magnesium supplements that found that those taking about the RDA for 12 weeks had no effect on lean mass or upper or lower body strength, but it did appear to improve walking speed and chair stand times. Unfortunately, it wasn’t a randomized, placebo-controlled trial; so, that may all have just been the placebo effect.
What about omega-3 fatty acid supplements? Some population studies suggest that fish consumption is associated with greater muscle strength. In others, seafood consumption was associated with a greater loss of muscle strength over time, maybe because of its mercury content. When put to the test in placebo-controlled trials, fish oil and other omega-3 supplements showed no effect on lean mass, muscle strength, or clinically significant effects on functional performance.
What about vitamin D? Osteomalacia and rickets, softened bone diseases resulting from severe vitamin D deficiency, are often accompanied by muscle weakness. Mice genetically engineered without vitamin D receptors suffer muscle atrophy, and vitamin D-depleted rats show impaired muscle function. In a petri dish, vitamin D increased muscle fiber growth. Human observational studies show correlations between lower vitamin D blood levels and lower muscle mass, lower muscle strength, performance such as walking speed, and higher odds of prefrailty or frailty. Of course, rather than low vitamin D levels leading to frailty, frailty may be leading to low levels of the sunshine vitamin, because frail individuals may not be out walking around as much. You don’t know until you put it to the test.
Multiple meta-analyses of randomized controlled trials found that giving vitamin D supplements to people with low vitamin D levels significantly improved their muscle strength and/or performance—that is, until multiple studies were retracted for fabricated data. It turns out, if you exclude the fraudulent studies, the benefit evaporates. If anything, there may be small adverse effects to vitamin D supplementation on muscle health. The 180° turn demonstrates that the “publication of fake data can have major health implications.”
Please consider volunteering to help out on the site.
- Lin Z, Zhao Y, Chen Q. Effects of oral administration of β-hydroxy β-methylbutyrate on lean body mass in older adults: a systematic review and meta-analysis. Eur Geriatr Med. 2021;12(2):239-251.
- Gielen E, Beckwée D, Delaere A, et al. Nutritional interventions to improve muscle mass, muscle strength, and physical performance in older people: an umbrella review of systematic reviews and meta-analyses. Nutr Rev. 2021;79(2):121-147.
- Malafarina V, Uriz-Otano F, Malafarina C, Martinez JA, Zulet MA. Effectiveness of nutritional supplementation on sarcopenia and recovery in hip fracture patients. A multi-centre randomized trial. Maturitas. 2017;101:42-50.
- Deutz NEP, Pereira SL, Hays NP, et al. Effect of β-hydroxy-β-methylbutyrate (HMB) on lean body mass during 10 days of bed rest in older adults. Clin Nutr. 2013;32(5):704-712.
- Wilkinson DJ, Hossain T, Hill DS, et al. Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate on human skeletal muscle protein metabolism. J Physiol. 2013;591(11):2911-2923.
- Dominguez LJ, Barbagallo M, Lauretani F, et al. Magnesium and muscle performance in older persons: the InCHIANTI study. Am J Clin Nutr. 2006;84(2):419-426.
- Scott D, Blizzard L, Fell J, Giles G, Jones G. Associations between dietary nutrient intake and muscle mass and strength in community-dwelling older adults: the Tasmanian Older Adult Cohort Study. J Am Geriatr Soc. 2010;58(11):2129-2134.
- van Dronkelaar C, van Velzen A, Abdelrazek M, van der Steen A, Weijs PJM, Tieland M. Minerals and sarcopenia; the role of calcium, iron, magnesium, phosphorus, potassium, selenium, sodium, and zinc on muscle mass, muscle strength, and physical performance in older adults: a systematic review. J Am Med Dir Assoc. 2018;19(1):6-11.e3.
- Veronese N, Berton L, Carraro S, et al. Effect of oral magnesium supplementation on physical performance in healthy elderly women involved in a weekly exercise program: a randomized controlled trial. Am J Clin Nutr. 2014;100(3):974-981.
- Robinson SM, Jameson KA, Batelaan SF, et al. Diet and its relationship with grip strength in community-dwelling older men and women: the Hertfordshire cohort study. J Am Geriatr Soc. 2008;56(1):84-90.
- Kojima N, Kim M, Saito K, et al. Lifestyle-related factors contributing to decline in knee extension strength among elderly women: a cross-sectional and longitudinal cohort study. PLoS One. 2015;10(7):e0132523.
- Delpino FM, Figueiredo LM. Supplementation with omega-3 and lean body mass in the general population: a systematic review and meta-analysis. Clin Nutr ESPEN. 2021;44:105-113.
- Rondanelli M, Perna S, Riva A, Petrangolini G, Di Paolo E, Gasparri C. Effects of n-3 EPA and DHA supplementation on fat free mass and physical performance in elderly. A systematic review and meta-analysis of randomized clinical trial. Mech Ageing Dev. 2021;196:111476.
- Schott GD, Wills MR. Muscle weakness in osteomalacia. Lancet. 1976;1(7960):626-629.
- Endo I, Inoue D, Mitsui T, et al. Deletion of vitamin D receptor gene in mice results in abnormal skeletal muscle development with deregulated expression of myoregulatory transcription factors. Endocrinology. 2003;144(12):5138-5144.
- Rodman JS, Baker T. Changes in the kinetics of muscle contraction in vitamin D-depleted rats. Kidney Int. 1978;13(3):189-193.
- Alliband KH, Kozhevnikova SV, Parr T, Jethwa PH, Brameld JM. In vitro effects of biologically active vitamin d on myogenesis: a systematic review. Front Physiol. 2021;12:736708.
- Visser M, Deeg DJH, Lips P, Longitudinal Aging Study Amsterdam. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (Sarcopenia): the Longitudinal Aging Study Amsterdam. J Clin Endocrinol Metab. 2003;88(12):5766-5772.
- Annweiler C, Schott-Petelaz AM, Berrut G, et al. Vitamin D deficiency-related quadriceps weakness: results of the Epidemiologie De l’Osteoporose cohort. J Am Geriatr Soc. 2009;57(2):368-369.
- Annweiler C, Schott AM, Berrut G, Fantino B, Beauchet O. Vitamin D-related changes in physical performance: a systematic review. J Nutr Health Aging. 2009;13(10):893-898.
- Annweiler C, Henni S, Walrand S, Montero-Odasso M, Duque G, Duval GT. Vitamin D and walking speed in older adults: Systematic review and meta-analysis. Maturitas. 2017;106:8-25.
- Vogt S, Decke S, de Las Heras Gala T, et al. Prospective association of vitamin D with frailty status and all-cause mortality in older adults: Results from the KORA-Age Study. Prev Med. 2015;73:40-46.
- Beaudart C, Buckinx F, Rabenda V, et al. The effects of vitamin D on skeletal muscle strength, muscle mass, and muscle power: a systematic review and meta-analysis of randomized controlled trials. J Clin Endocrinol Metab. 2014;99(11):4336-4345.
- Muir SW, Montero-Odasso M. Effect of vitamin D supplementation on muscle strength, gait and balance in older adults: a systematic review and meta-analysis. J Am Geriatr Soc. 2011;59(12):2291-2300.
- Stockton KA, Mengersen K, Paratz JD, Kandiah D, Bennell KL. Effect of vitamin D supplementation on muscle strength: a systematic review and meta-analysis. Osteoporos Int. 2011;22(3):859-871.
- Rejnmark L. Effects of vitamin d on muscle function and performance: a review of evidence from randomized controlled trials. Ther Adv Chronic Dis. 2011;2(1):25-37.
- Bislev LS, Grove-Laugesen D, Rejnmark L. Vitamin D and muscle health: a systematic review and meta-analysis of randomized placebo-controlled trials. J Bone Miner Res. 2021;36(9):1651-1660.
- Bouillon R. Vitamin D: good or bad for muscle strength? J Bone Miner Res. 2021;36(9):1649-1650.
Motion graphics by Avo Media
Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
Previously, I’ve covered the evidence surrounding supplementation for older adults with protein or amino acids like leucine. What about a metabolite of leucine known as β‑hydroxy β‑methylbutyrate, known as HMB? Adding HMB to an exercise regimen fails across the board to improve muscle mass, muscle strength, or physical performance among older individuals, and since everyone should be exercising, that pretty much takes HMB off the table. But there are circumstances when you’re laid up––for example, recuperating from a broken hip.
Researchers in Spain randomized about 100 men and women over the age of 65 in rehab recovering from a hip fracture to a nutritional supplement with about 3 grams of HMB. They suffered less loss of fat-free mass loss compared to the control group who didn’t get the supplement. Unfortunately, the supplement provided other components; so, it’s impossible to tease out the HMB effects. But regardless, there was no significant change in muscle strength or muscle function. This was roughly consistent with a 10-day bedrest study of straight HMB versus placebo, in which the HMB group similarly lost less lean mass—but only when an outlier was excluded, which isn’t really kosher—and there was no apparent improvement in strength or function.
This is what meta-analyses of all such studies have found—an improvement in fat-free mass in older sedentary adults, with no change in strength or function, and no benefits for any muscle parameters when combined with physical activity. Since we all should be exercising, and there’s a questionable benefit of lean mass for lean mass’s sake, combined with the fact that HMB activates the engine-of-aging enzyme mTOR, I see little reason to recommend supplementing with HMB.
What about magnesium? Higher blood levels correlate with muscle performance. One cohort study of older adults found that those with higher magnesium intake had greater lean mass over time, though the dietary intake of magnesium appeared to be similar between those with and without sarcopenia (excessive age-related muscle loss). There was one randomized controlled trial of magnesium supplements that found that those taking about the RDA for 12 weeks had no effect on lean mass or upper or lower body strength, but it did appear to improve walking speed and chair stand times. Unfortunately, it wasn’t a randomized, placebo-controlled trial; so, that may all have just been the placebo effect.
What about omega-3 fatty acid supplements? Some population studies suggest that fish consumption is associated with greater muscle strength. In others, seafood consumption was associated with a greater loss of muscle strength over time, maybe because of its mercury content. When put to the test in placebo-controlled trials, fish oil and other omega-3 supplements showed no effect on lean mass, muscle strength, or clinically significant effects on functional performance.
What about vitamin D? Osteomalacia and rickets, softened bone diseases resulting from severe vitamin D deficiency, are often accompanied by muscle weakness. Mice genetically engineered without vitamin D receptors suffer muscle atrophy, and vitamin D-depleted rats show impaired muscle function. In a petri dish, vitamin D increased muscle fiber growth. Human observational studies show correlations between lower vitamin D blood levels and lower muscle mass, lower muscle strength, performance such as walking speed, and higher odds of prefrailty or frailty. Of course, rather than low vitamin D levels leading to frailty, frailty may be leading to low levels of the sunshine vitamin, because frail individuals may not be out walking around as much. You don’t know until you put it to the test.
Multiple meta-analyses of randomized controlled trials found that giving vitamin D supplements to people with low vitamin D levels significantly improved their muscle strength and/or performance—that is, until multiple studies were retracted for fabricated data. It turns out, if you exclude the fraudulent studies, the benefit evaporates. If anything, there may be small adverse effects to vitamin D supplementation on muscle health. The 180° turn demonstrates that the “publication of fake data can have major health implications.”
Please consider volunteering to help out on the site.
- Lin Z, Zhao Y, Chen Q. Effects of oral administration of β-hydroxy β-methylbutyrate on lean body mass in older adults: a systematic review and meta-analysis. Eur Geriatr Med. 2021;12(2):239-251.
- Gielen E, Beckwée D, Delaere A, et al. Nutritional interventions to improve muscle mass, muscle strength, and physical performance in older people: an umbrella review of systematic reviews and meta-analyses. Nutr Rev. 2021;79(2):121-147.
- Malafarina V, Uriz-Otano F, Malafarina C, Martinez JA, Zulet MA. Effectiveness of nutritional supplementation on sarcopenia and recovery in hip fracture patients. A multi-centre randomized trial. Maturitas. 2017;101:42-50.
- Deutz NEP, Pereira SL, Hays NP, et al. Effect of β-hydroxy-β-methylbutyrate (HMB) on lean body mass during 10 days of bed rest in older adults. Clin Nutr. 2013;32(5):704-712.
- Wilkinson DJ, Hossain T, Hill DS, et al. Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate on human skeletal muscle protein metabolism. J Physiol. 2013;591(11):2911-2923.
- Dominguez LJ, Barbagallo M, Lauretani F, et al. Magnesium and muscle performance in older persons: the InCHIANTI study. Am J Clin Nutr. 2006;84(2):419-426.
- Scott D, Blizzard L, Fell J, Giles G, Jones G. Associations between dietary nutrient intake and muscle mass and strength in community-dwelling older adults: the Tasmanian Older Adult Cohort Study. J Am Geriatr Soc. 2010;58(11):2129-2134.
- van Dronkelaar C, van Velzen A, Abdelrazek M, van der Steen A, Weijs PJM, Tieland M. Minerals and sarcopenia; the role of calcium, iron, magnesium, phosphorus, potassium, selenium, sodium, and zinc on muscle mass, muscle strength, and physical performance in older adults: a systematic review. J Am Med Dir Assoc. 2018;19(1):6-11.e3.
- Veronese N, Berton L, Carraro S, et al. Effect of oral magnesium supplementation on physical performance in healthy elderly women involved in a weekly exercise program: a randomized controlled trial. Am J Clin Nutr. 2014;100(3):974-981.
- Robinson SM, Jameson KA, Batelaan SF, et al. Diet and its relationship with grip strength in community-dwelling older men and women: the Hertfordshire cohort study. J Am Geriatr Soc. 2008;56(1):84-90.
- Kojima N, Kim M, Saito K, et al. Lifestyle-related factors contributing to decline in knee extension strength among elderly women: a cross-sectional and longitudinal cohort study. PLoS One. 2015;10(7):e0132523.
- Delpino FM, Figueiredo LM. Supplementation with omega-3 and lean body mass in the general population: a systematic review and meta-analysis. Clin Nutr ESPEN. 2021;44:105-113.
- Rondanelli M, Perna S, Riva A, Petrangolini G, Di Paolo E, Gasparri C. Effects of n-3 EPA and DHA supplementation on fat free mass and physical performance in elderly. A systematic review and meta-analysis of randomized clinical trial. Mech Ageing Dev. 2021;196:111476.
- Schott GD, Wills MR. Muscle weakness in osteomalacia. Lancet. 1976;1(7960):626-629.
- Endo I, Inoue D, Mitsui T, et al. Deletion of vitamin D receptor gene in mice results in abnormal skeletal muscle development with deregulated expression of myoregulatory transcription factors. Endocrinology. 2003;144(12):5138-5144.
- Rodman JS, Baker T. Changes in the kinetics of muscle contraction in vitamin D-depleted rats. Kidney Int. 1978;13(3):189-193.
- Alliband KH, Kozhevnikova SV, Parr T, Jethwa PH, Brameld JM. In vitro effects of biologically active vitamin d on myogenesis: a systematic review. Front Physiol. 2021;12:736708.
- Visser M, Deeg DJH, Lips P, Longitudinal Aging Study Amsterdam. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (Sarcopenia): the Longitudinal Aging Study Amsterdam. J Clin Endocrinol Metab. 2003;88(12):5766-5772.
- Annweiler C, Schott-Petelaz AM, Berrut G, et al. Vitamin D deficiency-related quadriceps weakness: results of the Epidemiologie De l’Osteoporose cohort. J Am Geriatr Soc. 2009;57(2):368-369.
- Annweiler C, Schott AM, Berrut G, Fantino B, Beauchet O. Vitamin D-related changes in physical performance: a systematic review. J Nutr Health Aging. 2009;13(10):893-898.
- Annweiler C, Henni S, Walrand S, Montero-Odasso M, Duque G, Duval GT. Vitamin D and walking speed in older adults: Systematic review and meta-analysis. Maturitas. 2017;106:8-25.
- Vogt S, Decke S, de Las Heras Gala T, et al. Prospective association of vitamin D with frailty status and all-cause mortality in older adults: Results from the KORA-Age Study. Prev Med. 2015;73:40-46.
- Beaudart C, Buckinx F, Rabenda V, et al. The effects of vitamin D on skeletal muscle strength, muscle mass, and muscle power: a systematic review and meta-analysis of randomized controlled trials. J Clin Endocrinol Metab. 2014;99(11):4336-4345.
- Muir SW, Montero-Odasso M. Effect of vitamin D supplementation on muscle strength, gait and balance in older adults: a systematic review and meta-analysis. J Am Geriatr Soc. 2011;59(12):2291-2300.
- Stockton KA, Mengersen K, Paratz JD, Kandiah D, Bennell KL. Effect of vitamin D supplementation on muscle strength: a systematic review and meta-analysis. Osteoporos Int. 2011;22(3):859-871.
- Rejnmark L. Effects of vitamin d on muscle function and performance: a review of evidence from randomized controlled trials. Ther Adv Chronic Dis. 2011;2(1):25-37.
- Bislev LS, Grove-Laugesen D, Rejnmark L. Vitamin D and muscle health: a systematic review and meta-analysis of randomized placebo-controlled trials. J Bone Miner Res. 2021;36(9):1651-1660.
- Bouillon R. Vitamin D: good or bad for muscle strength? J Bone Miner Res. 2021;36(9):1649-1650.
Motion graphics by Avo Media
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Supplements for Sarcopenia (Age-Related Muscle Loss)
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For more on muscle loss, check out What Is Creatine? Can It Treat Sarcopenia (Muscle Loss with Age)? and Does Increasing Protein Intake Slow Age-Related Muscle Mass Loss?.
I have a lot of videos on aging. See the topic page.
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