Abstract
Vitamin D insufficiency and hyperparathyroidism have been associated with reduced muscle strength, physical performance, postural stability, well-being, and quality of life. In a double-blinded, randomized placebo-controlled trial, we aimed to investigate effects of vitamin D3 supplementation on above-mentioned outcomes in healthy community-dwelling postmenopausal women with plasma levels of 25-hydroxyvitamin D (25(OH)D) below < 50 nmol/l and high parathyroid hormone (PTH) levels. Participants (N = 81) were 1:1 treated with vitamin D3, 70 µg (2800 IU)/day or identical placebo for three months during wintertime (56°N). Vitamin D3 supplementation increased levels of 25(OH)D and 1,25(OH)2D by 230% (95% CI 189 to 272)%, p < 0.001 and 58% (190 to 271%), p < 0.001, respectively, and reduced PTH by 17% (− 23 to − 11%), p < 0.001. Compared with placebo, vitamin D3 significantly reduced maximal handgrip strength by 9% (− 15 to − 3%; p < 0.01) and knee flexion strength by 13% (− 24 to − 2%; p = 0.02) and increased the time spent on performing the Timed Up and Go test by 4.4%; (0.1–8.6%; p < 0.05). Levels of physical activity, total lean body mass, appendicular lean mass index, postural stability, well-being, and quality of life did not change in response to treatment. Compared with placebo, a daily supplement with a relatively high dose of vitamin D3 had no beneficial effects on any outcomes. In some measures of muscle strength and physical performance, we even saw a small unfavorable effect. Our data call for caution on use of relatively high daily doses of vitamin D3 in the treatment of vitamin D insufficiency.
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References
Rejnmark L, Bislev LS, Cashman KD, Eiríksdottir G, Gaksch M, Grü Bler M et al (2017) Non-skeletal health effects of vitamin D supplementation: a systematic review on findings from meta-analyses summarizing trial data. PLoS ONE 12:1–39. https://doi.org/10.1371/journal.pone.0180512
Autier P, Mullie P, Macacu A, Dragomir M, Boniol M, Coppens K et al (2017) Effect of vitamin D supplementation on non-skeletal disorders: a systematic review of meta-analyses and randomised trials. Lancet Diabetes Endocrinol 5:986–1004. https://doi.org/10.1016/S2213-8587(17)30357-1
Beaudart C, Buckinx F, Rabenda V, Gillain S, Cavalier E, Slomian J et al (2014) 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 99:4336–4345. https://doi.org/10.1210/jc.2014-1742
Annweiler C, Schott AM, Berrut G, Fantino B, Beauchet O (2009) Vitamin D-related changes in physical performance: a systematic review. J Nutr Heal Aging 13:893–898. https://doi.org/10.1007/s12603-009-0248-x
Muir SW, Montero-Odasso M (2011) Effect of vitamin D supplementation on muscle strength, gait and balance in older adults: a systematic review and meta-analysis. J Am Geriatr Soc 59:2291–2300. https://doi.org/10.1111/j.1532-5415.2011.03733.x
Raftery TC, Healy M, Cox G, McNamara D, O’Sullivan M (2013) Vitamin D supplementation improves muscle strength, fatigue and quality of life in patients with crohn’s disease in remission: Results of a randomized double-blind placebo-controlled study. Gastroenterology 144:S227. https://doi.org/10.1016/S0016-5085(13)60804-5
Stein M, Wark J, Scherer S, Waltson L, Chick P, Carlantonio M et al (1999) Falls relate to vitamin D and parathyroid hormone in an Australian nursing home hostel. J Am Geriatr Soc 47:1195–1201
de Souza Genaro P, de Medeiros Pinheiro M, Szejnfeld VL, Martini LA (2015) Secondary hyperparathyroidism and its relationship with sarcopenia in elderly women. Arch Gerontol Geriatr 60:349–353. https://doi.org/10.1016/j.archger.2015.01.005
Pfeifer M, Begerow B, Minne HW, Abrams C, Nachtigall D, Hansen C (2000) Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women. J Bone Miner Res 15:1113–1118. https://doi.org/10.1359/jbmr.2000.15.6.1113
Bird ML, El Haber N, Batchelor F, Hill K, Wark JD (2018) Vitamin D and parathyroid hormone are associated with gait instability and poor balance performance in mid-age to older aged women. Gait Posture 59:71–75. https://doi.org/10.1016/j.gaitpost.2017.09.036
Sambrook PN, Chen JS, March LM, Cameron ID, Cumming RG, Lord SR et al (2004) Serum parathyroid hormone predicts time to fall independent of vitamin D status in a frail elderly population. J Clin Endocrinol Metab 89:1572–1576. https://doi.org/10.1210/jc.2003-031782
Rolighed L, Rejnmark L, Sikjaer T, Heickendorff L, Vestergaard P, Mosekilde L et al (2015) No beneficial effects of vitamin D supplementation on muscle function or quality of life in primary hyperparathyroidism: results from a randomized controlled trial. Eur J Endocrinol 172:609–617. https://doi.org/10.1530/EJE-14-0940
Rejnmark L (2011) Effects of vitamin D on muscle function and performance: a review of evidence from randomized controlled trials. Ther Adv Chronic Dis 2:25–37. https://doi.org/10.1177/2040622310381934
Latham NK, Anderson CS, Reid IR (2003) Effects of vitamin D supplementation on strength, physical performance, and falls in older persons: a systematic review. J Am Geriatr Soc 51:1219–1226. https://doi.org/10.1046/j.1532-5415.2003.51405.x
Stockton KA, Mengersen K, Paratz JD, Kandiah D, Bennell KL (2011) Effect of vitamin D supplementation on muscle strength: a systematic review and meta-analysis. Osteoporos Int 22:859–871. https://doi.org/10.1007/s00198-010-1407-y
Rosendahl-Riise H, Spielau U, Ranhoff AH, Gudbrandsen OA, Dierkes J (2017) Vitamin D supplementation and its influence on muscle strength and mobility in community-dwelling older persons: a systematic review and meta-analysis. J Hum Nutr Diet 30:3–15. https://doi.org/10.1111/jhn.12394
Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, Orav JE, Stuck AE, Theiler R et al (2009) Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ 339:843. https://doi.org/10.1136/bmj.b3692
Murad MH, Elamin KB, Abu Elnour NO, Elamin MB, Alkatib AA, Fatourechi MM et al (2011) The effect of vitamin D on falls: a systematic review and meta-analysis. J Clin Endocrinol Metab 96:2997–3006. https://doi.org/10.1210/jc.2011-1193
Bouillon R (2017) Comparative analysis of nutritional guidelines for vitamin D. Nat Rev Endocrinol 13:466–479. https://doi.org/10.1038/nrendo.2017.31
Bislev LS, Langagergaard Rødbro L, Nørgaard Bech J, Bjerregaard Pedersen E, Rolighed L, Sikjaer T et al (2018) Effects of treatment with an angiotensin 2 receptor blocker and/or vitamin D3 on parathyroid hormone and aldosterone: a randomized, placebo-controlled trial. Clin Endocrinol (Oxf). https://doi.org/10.1111/cen.13734
Hermann AP, Thomsen J, Vestergaard P, Mosekilde LCP (1999) Assessment of calcium intake. A quick method comparerd to a 7 days food diary. Calcif Tissue Int 64:82
Curb JD, Ceria-Ulep CD, Rodriguez BL, Grove J, Guralnik J, Willcox BJ et al (2006) Performance-based measures of physical function for high-function populations. J Am Geriatr Soc 54:737–742. https://doi.org/10.1111/j.1532-5415.2006.00700.x
Podsiadlo D, Richardson S (1991) The timed “Up & Go”: a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc 39:142–148
Annuzzi-Sucich M, Prestwood KM, Kenny AM (2002) Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women. J Gerontol 57:M772–M777
Aadahl M, Jørgensen T (2003) Validation of a new self-report instrument for measuring physical activity. Med Sci Sports Exerc 35:1196–1202. https://doi.org/10.1249/01.MSS.0000074446.02192.14
Bjorner JB, Thunedborg K, Kristensen TS, Modvig J, Bech P (1998) The Danish SF-36 health survey: translation and preliminary validity studies. J Clin Epidemiol 51:991–999
Topp CW, Østergaard SD, Søndergaard S, Bech P (2015) The WHO-5 well-being index: a systematic review of the literature. Psychother Psychosom 84:167–176. https://doi.org/10.1159/000376585
Glerup H, Mikkelsen K, Poulsen L, Hass E, Overbeck S, Andersen H et al (2000) Hypovitaminosis D myopathy without biochemical signs of osteomalacic bone involvement. Calcif Tissue Int 66:419–424
Pfeifer M, Begerow B, Minne HW, Suppan K, Fahrleitner-Pammer A, Dobnig H (2009) Effects of a long-term vitamin D and calcium supplementation on falls and parameters of muscle function in community-dwelling older individuals. Osteoporos Int 20:315–322. https://doi.org/10.1007/s00198-008-0662-7
Bischoff H, Stahelin HB, Dick W, Akos R, Knecht M, Salis C et al (2003) Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res 18:343–351
Bunout D, Barrera G, Leiva L, Gattas V, de la Maza MP, Avendaño M et al (2006) Effects of vitamin D supplementation and exercise training on physical performance in Chilean vitamin D deficient elderly subjects. Exp Gerontol 41:746–752. https://doi.org/10.1016/j.exger.2006.05.001
Gupta R, Sharma U, Gupta N, Kalaivani M, Singh U, Guleria R et al (2010) Effect of cholecalciferol and calcium supplementation on muscle strength and energy metabolism in vitamin D-deficient Asian Indians: a randomized, controlled trial. Clin Endocrinol (Oxf) 73:445–451. https://doi.org/10.1111/j.1365-2265.2010.03816.x
Moreira-Pfrimer LDF, Pedrosa MAC, Teixeira L, Lazaretti-Castro M (2009) Treatment of vitamin D deficiency increases lower limb muscle strength in institutionalized older people independently of regular physical activity: a randomized double-blind controlled trial. Ann Nutr Metab 54:291–300. https://doi.org/10.1159/000235874
Patil R, Karinkanta S, Tokola K, Kannus P, Sievänen H, Uusi-Rasi K (2016) Effects of vitamin D and exercise on the wellbeing of older community-dwelling women: a randomized controlled trial. Gerontology 62:401–408. https://doi.org/10.1159/000442441
Mason C, Tapsoba JD, Duggan C, Imayama I (2016) Effects of vitamin D3 supplementation on lean mass, muscle strength, and bone mineral density during weight loss: a double-blind randomized controlled trial. J Am Geriatr Soc. https://doi.org/10.1111/jgs.14049
Diamond T, Wong YK, Golombick T (2013) Effect of oral cholecalciferol 2,000 versus 5,000 IU on serum vitamin D, PTH, bone and muscle strength in patients with vitamin D deficiency. Osteoporos Int 24:1101–1105. https://doi.org/10.1007/s00198-012-1944-7
Janssen HCJP, Samson MM, Verhaar HJJ (2010) Muscle strength and mobility in vitamin D-insufficient female geriatric patients: a randomized controlled trial on vitamin D and calcium supplementation. Aging Clin Exp Res 22:78–84. https://doi.org/10.1007/BF03324819
Lips P, Binkley N, Pfeifer M, Recker R, Samanta S, Cohn DA et al (2010) Once-weekly dose of 8400 IU vitamin D 3 compared with placebo: effects on neuromuscular function and tolerability in older adults with. Am J Clin Nutr 91:985–991. https://doi.org/10.3945/ajcn.2009.28113.Vitamin
Rafiq R, Prins HJ, Boersma WG, Daniels JM, den Heijer M, Lips P et al (2017) Effects of daily vitamin D supplementation on respiratory muscle strength and physical performance in vitamin D-deficient COPD patients: a pilot trial. Int J Chron Obstruct Pulmon Dis 12:2583–2592. https://doi.org/10.2147/COPD.S132117
Saha S, Goswami R, Ramakrishnan L, Vishnubhatla S, Mahtab S, Kar P et al. Vitamin D and calcium supplementation, skeletal muscle strength and serum testosterone in young healthy adult males: randomized control trial. Clin Endocrinol (Oxf) 2017:217–226. https://doi.org/10.1111/cen.13507
Witte KK, Byrom R, Gierula J, Paton MF, Jamil HA, Lowry JE et al (2016) Effects of vitamin D on cardiac function in patients with chronic HF: the VINDICATE study. J Am Coll Cardiol 67:2593–2603. https://doi.org/10.1016/j.jacc.2016.03.508
Uusi-Rasi K, Patil R, Karinkanta S, Kannus P, Tokola K, Lamberg-Allardt C et al (2015) Exercise and vitamin din fall prevention among older women a randomized clinical trial. JAMA Intern Med 175:703–711. https://doi.org/10.1001/jamainternmed.2015.0225
Bischoff-Ferrari HA, Dawson-Hughes B, John Orav E, Staehelin HB, Meyer OW, Theiler R et al (2016) Monthly high-dose vitamin D treatment for the prevention of functional decline a randomized clinical trial. JAMA Intern Med 176:175–183. https://doi.org/10.1001/jamainternmed.2015.7148
Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D et al (2010) Annual high-dose oral vitamin D and falls and fractures in older women. JAMA 303:1815. https://doi.org/10.1001/jama.2010.594
Guirguis-Blake JM, Michael YL, Perdue LA, Coppola EL, Beil TL (2018) Interventions to prevent falls in older adults: updated evidence report and systematic review for the US preventive services task force. JAMA 98405:1705–1716. https://doi.org/10.1001/jama.2017.21962
Carrillo AE, Flynn MG, Pinkston C, Markofski MM, Jiang Y, Donkin SS et al (2013) Impact of vitamin D supplementation during a resistance training intervention on body composition, muscle function, and glucose tolerance in overweight and obese adults. Clin Nutr 32:375–381. https://doi.org/10.1016/j.clnu.2012.08.014
Close G, Russell J, Cobley J, Owens D, Wilson G, Gregson W et al (2013) Assessment of vitamin D concentration in non- supplemented professional athletes and healthy adults during the winter months in the UK: implications for skeletal muscle function. J Sports Sci 31:344–353. https://doi.org/10.1080/02640414.2012.733822
Hornikx M, Van Remoortel H, Lehouck A, Mathieu C, Maes K, Gayan-Ramirez G et al (2012) Vitamin D supplementation during rehabilitation in COPD: a secondary analysis of a randomized trial. Respir Res 13:84. https://doi.org/10.1186/1465-9921-13-84
Wyon MA, Wolman R, Nevill AM, Cloak R, Metsios GS, Gould D et al (2016) Acute effects of vitamin D 3 supplementation on muscle strength in Judoka athletes: a randomized placebo-controlled double. -blind Trial 26:279–284
Brett NR, Parks CA, Lavery P, Agellon S, Vanstone CA, Kaufmann M et al (2018) Vitamin D status and functional health outcomes in children aged 2–8 y: A 6-mo vitamin D randomized controlled trial. Am J Clin Nutr 107:355–364. https://doi.org/10.1093/ajcn/nqx062
El-Hajj Fuleihan G, Nabulsi M, Tamim H, Maalouf J, Salamoun M, Khalife H et al (2006) Effect of vitamin D replacement on musculoskeletal parameters in school children: a randomized controlled trial. J Clin Endocrinol Metab 91:405–412. https://doi.org/10.1210/jc.2005-1436
Manios Y, Moschonis G, Koutsikas K, Papoutsou S, Petraki I, Bellou E et al (2009) Changes in body composition following a dietary and lifestyle intervention trial: the postmenopausal health study. Maturitas 62:58–65. https://doi.org/10.1016/j.maturitas.2008.11.005
Acknowledgements
Most importantly, we thank all participants for their extraordinary commitment and goodwill. We acknowledge the laboratory technicians and the hospital pharmacy at Aarhus University Hospital.
Funding
The study was funded by Aarhus University, T, The Augustinus Foundation, The Foundation of Endocrinology Aarhus University Hospital, Toyota Foundation, A.P. Møller & wife Chastine MC-Kinney Møllers Foundation, and P. A. Messerschmidt & wife foundation. Orkla Health A/S donated vitamin D and vitamin D placebo tablets free of charge, but had no influence on analyses or interpretation of data.
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Lise Sofie Bislev, Lene Langagergaard Rødbro, Lars Rolighed, Tanja Sikjaer, and Lars Rejnmark declare that they have no conflict of interest.
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The study was carried out in accordance with the Helsinki Declaration. The study was approved by The Danish Data Protection Agency (1-16-02-492-14), the Regional Committee on Biomedical Research Ethics (1-10-72-326-14), The Danish Health Authority (2014-003645-10), and Danish Health Data Authority (FSEID-00001274). The local unit for Good Clinical Practice at Aarhus University Hospital monitored the study. Clinicaltrials.gov identifier: #NCT02572960.
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This article does not contain any studies with human or animal subjects performed by any of the authors.
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Bislev, L.S., Langagergaard Rødbro, L., Rolighed, L. et al. Effects of Vitamin D3 Supplementation on Muscle Strength, Mass, and Physical Performance in Women with Vitamin D Insufficiency: A Randomized Placebo-Controlled Trial. Calcif Tissue Int 103, 483–493 (2018). https://doi.org/10.1007/s00223-018-0443-z
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DOI: https://doi.org/10.1007/s00223-018-0443-z