Recent developments in vitamin D deficiency and muscle weakness among
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Correspondence to: G Venning venning@hdd.co.uk
Higher plasma concentrations of calcidiol are associated with muscle strength, physical activity, and ability to climb stairs and lower concentrations with falls among elderly people.6 7 Indeed, in a randomised controlled trial elderly women given 800 IU vitamin D daily with calcium had a 47% reduction in falls and fractures compared with controls receiving calcium alone over 12 months.8 In another trial with three month follow up, the incidence of falls was almost halved and musculoskeletal function improved among elderly people who had 800 IU vitamin D with calcium compared with calcium alone.9
Being housebound as a risk factor
Scanning electron micrograph of skeletal muscle fibres
Credit: STEVE G SCHEISSNER/SPL
If vitamin D deficiency is associated with musculoskeletal weakness and falls among elderly people, why does supplementation with the vitamin sometimes fail to help? The explanation seems to be inadequate dose. Two randomised controlled trials have found 400 IU/day of vitamin D to be ineffective in reducing the frequency of fractures,15 19 and two descriptive studies have noted deficiency despite supplementation at a dose of 400 IU daily.13 14 Furthermore, one trial of high dose treatment showed no evidence of reduction in falls among frail outpatients.20 But vitamin D deficiency is only one risk factor for falls and fractures among elderly people, and in this study the patients who received placebo had near normal mean calcidiol concentrations and still had a high frequency of falls, probably because they had other disabilities that were not amenable to vitamin D treatment.
In contrast, five randomised controlled trials have shown that 800 IU/day of vitamin D significantly reduces the incidence of falls8 9 and fractures.21 22 The fifth trial showed a reduction in fractures using 100 000 IU of vitamin D every four months (a dose equivalent to 800 IU/day).23 These high dose studies strengthen the evidence for and the public health importance of preventive treatment with adequate doses of vitamin D among housebound elderly people and suggest priorities for future research. But are there enough data on the safety of high dose vitamin D?
Safety of high dose supplementation
Blake AJ, Morgan K, Bendall MJ, Dallosso H, Ebrahim SB, Arie TH, et al. Falls by elderly people at home: prevalence and associated factors. Age Ageing 1988;17: 365-72.
Semba RD, Garrett E, Johnson BA, Guralnik JM, Fried LP. Vitamin D deficiency among older women with and without disability. Am J Clin Nutr 2000;72: 1529-34.
Jacques PF, Felson DT, Tucker KL, Mahnken B, Wilson PW, Rosenberg IH, et al. Plasma 25 hydroxy vitamin D and its determinants in an elderly population sample. Am J Clin Nutr 1997;66: 929-36.
Institute of Medicine. Dietary reference intakes. Washington, DC: National Academic Press, 1997.
Holick MF. Vitamin D: a millennium perspective. J Cell Biochem 2003;88: 296-307.
Mowé M, Haug E, Bohmer T. Low serum calcidiol concentration in older adults with reduced muscular function. J Am Geriatr Soc 1999;47: 220-6.
Dhesi JK, Bearne LM, Moniz C, Hurley MV, Jackson SH, Swift CG, et al. Neuromuscular and psychomotor function in elderly subjects who fall and the relationship with vitamin D status. J Bone Miner Res 2002;17: 891-7.
Pfeiffer M, Begerow B, Minne HW, Abrams C, Nachtigall D, Hansen C. Effects of a short term Vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women. J Bone Miner Res 2000;15: 1113-8.
Bischoff HA, St?helin HB, Dick W, Akos R, Knecht M, Salis C, et al. Effects of vitamin D and calcium supplements on falls: a randomised controlled trial. J Bone Miner Res 2003;18: 343-51.
Evans JG. Falls and fractures. Age Ageing 1988;17: 361-4.
Chang JT, Morton SC, Rubenstein LZ, Mojica WA, Maglione M, Suttorp MJ, et al. Interventions for the prevention of falls in older adults: systematic review and meta-analysis of randomised clinical trials. BMJ 2004;328: 680.
Heikinheimo RJ, Inkovaara JA, Harju EJ, Haavisto MV, Kaarela RH, Kataja JM, et al. Annual injection of vitamin D and fractures of aged bones. Calcif Tissue Int 1992;51: 105-10.
Egsmose C, Lund B, McNair P, Lund B, Storm T, Sorensen OH, et al. Low serum levels of 25-hydroxy vitamin D and 1,25 dihydroxy vitamin D in institutionalized old people: influence of solar exposure and vitamin D supplementation. Age Ageing 1987;16: 35-40.
Gloth FM, Gundberg CM, Hollis BW, Haddad JG Jr, Tobin JD. Vitamin D deficiency in homebound elderly persons. JAMA 1995;274: 1683-6.
Lips P, Graafmans WC, Ooms ME, Bezemer PD, Bouter LM. Vitamin D supplementation and fracture incidence in elderly persons: a randomized placebo-controlled trial. Ann Intern Med 1996;124: 400-6.
Nesby-O'Dell S, Scanlon KS, Cogswell ME, Gillespie C, Hollis BW, Looker AC, et al. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994. AmJClin Nutr 2002;76: 187-92.
Gallagher JC, Kinyamu HK, Fowler SE, Dawson-Hughes B, Dalsky GP, Sherman SS, al. Calciotropic hormones and bone markers in the elderly. J Bone Miner Res 1998;13: 475-82.
McKenna MJ. Differences in vitamin D status between countries in young adults and the elderly. Am J Med 1992;93: 69-77.
Meyer HE, Smedshaug GB, Kvaavik E, Falch JA, Tverdal A, Pedersen JI. Can vitamin D supplementation reduce the risk of fracture in the elderly? A randomized controlled trial. J Bone Miner Res 2002;17: 709-15.
Latham NK, Anderson CS, Lee A, Bennett DA, Moseley A, Cameron ID, et al. A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people: the frailty interventions trial in elderly subjects (FITNESS). J Am Geriatr Soc 2003;51: 291-9.
Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, et al. Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 1992; 327-42.
Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 1997;337: 670-6.
Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ 2003;326: 469-72.
Vieth R. Vitamin D supplementation, 25-hydroxy vitamin D concentrations and safety. Am J Clin Nutr 1999;69: 842-56.
Mingrone G, Greco AV, Castagneto M, Gasbarrini G. A woman who left her wheelchair. Lancet 1999;353: 806.(Geoff Venning, consultant in pharmaceuti)
Correspondence to: G Venning venning@hdd.co.uk
Higher plasma concentrations of calcidiol are associated with muscle strength, physical activity, and ability to climb stairs and lower concentrations with falls among elderly people.6 7 Indeed, in a randomised controlled trial elderly women given 800 IU vitamin D daily with calcium had a 47% reduction in falls and fractures compared with controls receiving calcium alone over 12 months.8 In another trial with three month follow up, the incidence of falls was almost halved and musculoskeletal function improved among elderly people who had 800 IU vitamin D with calcium compared with calcium alone.9
Being housebound as a risk factor
Scanning electron micrograph of skeletal muscle fibres
Credit: STEVE G SCHEISSNER/SPL
If vitamin D deficiency is associated with musculoskeletal weakness and falls among elderly people, why does supplementation with the vitamin sometimes fail to help? The explanation seems to be inadequate dose. Two randomised controlled trials have found 400 IU/day of vitamin D to be ineffective in reducing the frequency of fractures,15 19 and two descriptive studies have noted deficiency despite supplementation at a dose of 400 IU daily.13 14 Furthermore, one trial of high dose treatment showed no evidence of reduction in falls among frail outpatients.20 But vitamin D deficiency is only one risk factor for falls and fractures among elderly people, and in this study the patients who received placebo had near normal mean calcidiol concentrations and still had a high frequency of falls, probably because they had other disabilities that were not amenable to vitamin D treatment.
In contrast, five randomised controlled trials have shown that 800 IU/day of vitamin D significantly reduces the incidence of falls8 9 and fractures.21 22 The fifth trial showed a reduction in fractures using 100 000 IU of vitamin D every four months (a dose equivalent to 800 IU/day).23 These high dose studies strengthen the evidence for and the public health importance of preventive treatment with adequate doses of vitamin D among housebound elderly people and suggest priorities for future research. But are there enough data on the safety of high dose vitamin D?
Safety of high dose supplementation
Blake AJ, Morgan K, Bendall MJ, Dallosso H, Ebrahim SB, Arie TH, et al. Falls by elderly people at home: prevalence and associated factors. Age Ageing 1988;17: 365-72.
Semba RD, Garrett E, Johnson BA, Guralnik JM, Fried LP. Vitamin D deficiency among older women with and without disability. Am J Clin Nutr 2000;72: 1529-34.
Jacques PF, Felson DT, Tucker KL, Mahnken B, Wilson PW, Rosenberg IH, et al. Plasma 25 hydroxy vitamin D and its determinants in an elderly population sample. Am J Clin Nutr 1997;66: 929-36.
Institute of Medicine. Dietary reference intakes. Washington, DC: National Academic Press, 1997.
Holick MF. Vitamin D: a millennium perspective. J Cell Biochem 2003;88: 296-307.
Mowé M, Haug E, Bohmer T. Low serum calcidiol concentration in older adults with reduced muscular function. J Am Geriatr Soc 1999;47: 220-6.
Dhesi JK, Bearne LM, Moniz C, Hurley MV, Jackson SH, Swift CG, et al. Neuromuscular and psychomotor function in elderly subjects who fall and the relationship with vitamin D status. J Bone Miner Res 2002;17: 891-7.
Pfeiffer M, Begerow B, Minne HW, Abrams C, Nachtigall D, Hansen C. Effects of a short term Vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women. J Bone Miner Res 2000;15: 1113-8.
Bischoff HA, St?helin HB, Dick W, Akos R, Knecht M, Salis C, et al. Effects of vitamin D and calcium supplements on falls: a randomised controlled trial. J Bone Miner Res 2003;18: 343-51.
Evans JG. Falls and fractures. Age Ageing 1988;17: 361-4.
Chang JT, Morton SC, Rubenstein LZ, Mojica WA, Maglione M, Suttorp MJ, et al. Interventions for the prevention of falls in older adults: systematic review and meta-analysis of randomised clinical trials. BMJ 2004;328: 680.
Heikinheimo RJ, Inkovaara JA, Harju EJ, Haavisto MV, Kaarela RH, Kataja JM, et al. Annual injection of vitamin D and fractures of aged bones. Calcif Tissue Int 1992;51: 105-10.
Egsmose C, Lund B, McNair P, Lund B, Storm T, Sorensen OH, et al. Low serum levels of 25-hydroxy vitamin D and 1,25 dihydroxy vitamin D in institutionalized old people: influence of solar exposure and vitamin D supplementation. Age Ageing 1987;16: 35-40.
Gloth FM, Gundberg CM, Hollis BW, Haddad JG Jr, Tobin JD. Vitamin D deficiency in homebound elderly persons. JAMA 1995;274: 1683-6.
Lips P, Graafmans WC, Ooms ME, Bezemer PD, Bouter LM. Vitamin D supplementation and fracture incidence in elderly persons: a randomized placebo-controlled trial. Ann Intern Med 1996;124: 400-6.
Nesby-O'Dell S, Scanlon KS, Cogswell ME, Gillespie C, Hollis BW, Looker AC, et al. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994. AmJClin Nutr 2002;76: 187-92.
Gallagher JC, Kinyamu HK, Fowler SE, Dawson-Hughes B, Dalsky GP, Sherman SS, al. Calciotropic hormones and bone markers in the elderly. J Bone Miner Res 1998;13: 475-82.
McKenna MJ. Differences in vitamin D status between countries in young adults and the elderly. Am J Med 1992;93: 69-77.
Meyer HE, Smedshaug GB, Kvaavik E, Falch JA, Tverdal A, Pedersen JI. Can vitamin D supplementation reduce the risk of fracture in the elderly? A randomized controlled trial. J Bone Miner Res 2002;17: 709-15.
Latham NK, Anderson CS, Lee A, Bennett DA, Moseley A, Cameron ID, et al. A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people: the frailty interventions trial in elderly subjects (FITNESS). J Am Geriatr Soc 2003;51: 291-9.
Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, et al. Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 1992; 327-42.
Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 1997;337: 670-6.
Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ 2003;326: 469-72.
Vieth R. Vitamin D supplementation, 25-hydroxy vitamin D concentrations and safety. Am J Clin Nutr 1999;69: 842-56.
Mingrone G, Greco AV, Castagneto M, Gasbarrini G. A woman who left her wheelchair. Lancet 1999;353: 806.(Geoff Venning, consultant in pharmaceuti)