Skip to main content

Advertisement

Log in

A parallel group double-blind RCT of vitamin D3 assessing physical function: is the biochemical response to treatment affected by overweight and obesity?

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

Vitamin D may affect skeletal muscle function. In a double-blind, randomised, placebo-controlled trial, we found that vitamin D3 supplementation (400 or 1,000 I.U. vs. placebo daily for 1 year with bimonthly study visits) does not improve grip strength or reduce falls.

Introduction

This study aimed to test the supplementation effects of vitamin D3 on physical function and examine associations between overweight/obesity and the biochemical response to treatment.

Methods

In a parallel group double-blind RCT, healthy postmenopausal women from North East Scotland (latitude—57° N) aged 60–70 years (body mass index (BMI), 18–45 kg/m2) were assigned (computer randomisation) to daily vitamin D3 (400 I.U. (n = 102)/1,000 I.U. (n = 101)) or matching placebo (n = 102) (97, 96 and 100 participants analysed for outcomes, respectively) from identical coded containers for 1 year. Grip strength (primary outcome), falls, diet, physical activity and ultraviolet B radiation exposure were measured bimonthly, as were serum 25(OH)D, adjusted calcium (ACa) and phosphate. Fat/lean mass (dual energy X-ray absorptiometry), anthropometry, 1,25-dihydroxyvitamin D and parathyroid hormone were measured at baseline and 12 months. Participants and researchers were blinded throughout intervention and analysis.

Results

Treatment had no effect on grip strength (mean change (SD)/year = −0.5 (2.5), −0.9 (2.7) and −0.4 (3.3) kg force for 400/1,000 I.U. vitamin D3 and placebo groups, respectively (P = .10, ANOVA)) or falls (P = .65, chi-squared test). Biochemical responses were similar across BMI categories (<25.25–29.99, ≥30 kg/m2) with the exception of a small change at 12-months in serum ACa in overweight compared to non-overweight participants (P = .01, ANOVA; 1,000 I.U. group). In the placebo group, 25(OH)D peak concentration change (winter to summer) was negatively associated with weight (r = −.268), BMI (r = −.198), total (r = −.278) and trunk fat mass (r = −.251), with total and trunk fat mass predictive of winter to summer 25(OH)D change (P = .01/.004 respectively, linear regression).

Conclusion

We found no evidence of an improvement in physical function following vitamin D3 supplementation for 1 year.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Ceglia L, Harris SS (2013) Vitamin D and its role in skeletal muscle. Calcif Tissue Int 92:151–162

    Article  CAS  PubMed  Google Scholar 

  2. Simpson RU, Thomas GA, Arnold AJ (1985) Identification of 1,25-dihydroxyvitamin D3 receptors and activities in muscle. J Biol Chem 260:8882–8891

    CAS  PubMed  Google Scholar 

  3. Bischoff-Ferrari HA, Dietrich T, Orav EJ, Hu FB, Zhang Y, Karlson EW, Dawson-Hughes B (2004) Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged > or =60 y. Am J Clin Nutr 80:752–758

    CAS  PubMed  Google Scholar 

  4. Visser M, Deeg DJ, Lips P (2003) 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 88:5766–5772

    Article  CAS  PubMed  Google Scholar 

  5. Houston DK, Tooze JA, Davis CC, Chaves PH, Hirsch CH, Robbins JA, Arnold AM, Newman AB, Kritchevsky SB (2011) Serum 25-hydroxyvitamin D and physical function in older adults: the Cardiovascular Health Study All Stars. J Am Geriatr Soc 59:1793–1801

    Article  PubMed Central  PubMed  Google Scholar 

  6. Murad MH, Elamin KB, Abu Elnour NO, Elamin MB, Alkatib AA, Fatourechi MM, Almandoz JP, Mullan RJ, Lane MA, Liu H, Erwin PJ, Hensrud DD, Montori VM (2011) Clinical review: the effect of vitamin D on falls: a systematic review and meta-analysis. J Clin Endocrinol Metab 96:2997–3006

    Article  CAS  PubMed  Google Scholar 

  7. Michael YL, Whitlock EP, Lin JS, Fu R, O'Connor EA, Gold R (2010) Primary care-relevant interventions to prevent falling in older adults: a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 153:815–825

    Article  PubMed  Google Scholar 

  8. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA (2011) The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 96:53–58

    Article  CAS  PubMed  Google Scholar 

  9. Gillespie LD, Robertson MC, Gillespie WJ, Lamb SE, Gates S, Cumming RG, Rowe BH (2009) Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev: CD007146

  10. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, Orav JE, Stuck AE, Theiler R, Wong JB, Egli A, Kiel DP, Henschkowski J (2009) Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ 339:b3692

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Stockton KA, Mengersen K, Paratz JD, Kandiah D, Bennel KL (2011) Effect of vitamin D supplementation on muscle strength: a systematic review and meta-analysis. Osteoporosis Int 22:859–871

    CAS  Google Scholar 

  12. Rejnmark L (2011) Effects of vitamin D on muscle strength, gait and balance in older adults: a systematic review and meta-analysis. J Am Geriatr Soc 59:2291–2300

    Article  Google Scholar 

  13. Girgis CM, Clifton-Bligh RJ, Hamrick MW, Holick MF, Gunton JE (2013) The roles of vitamin D in skeletal muscle: form function and metabolism. Endocr Rev 34:33–83

    Article  CAS  PubMed  Google Scholar 

  14. Cheng S, Massaro JM, Fox CS, Larson MG, Keyes MJ, McCabe EL, Robins SJ, O'Donnell CJ, Hoffmann U, Jacques PF, Booth SL, Vasan RS, Wolf M, Wang TJ (2009) Adiposity, cardiometabolic risk, and vitamin D status: The Framingham Heart Study. Diabetes 59:242–248

    Article  PubMed  Google Scholar 

  15. Lagunova Z, Porojnicu AC, Lindberg F, Hexeberg S, Moan J (2009) The dependency of vitamin D status on body mass index, gender, age and season. Anticanc Res 29:3713–3720

    CAS  Google Scholar 

  16. Macdonald H, Mavroeidi A, Barr R, Black A, Fraser W, Reid D (2008) Vitamin D status in postmenopausal women living at higher latitudes in the UK in relation to bone health, overweight, sunlight exposure and dietary vitamin D. Bone 42:996–1003

    Article  CAS  PubMed  Google Scholar 

  17. Hypponen E, Power C (2006) Vitamin D status and glucose homeostasis in the 1958 British birth cohort: the role of obesity. Diabetes Care 29:2244–2246

    Article  CAS  PubMed  Google Scholar 

  18. Jacques PF, Felson DT, Tucker KL, Mahnken B, Wilson PW, Rosenberg IH, Rush D (1997) Plasma 25-hydroxyvitamin D and its determinants in an elderly population sample. Am J Clin Nutr 66:929–936

    CAS  PubMed  Google Scholar 

  19. Jorde R, Sneve M, Emaus N, Figenschau Y, Grimnes G (2010) Cross-sectional and longitudinal relation between serum 25-hydroxyvitamin D and body mass index: the Tromso study. Eur J Nutr 49:401–407

    Article  CAS  PubMed  Google Scholar 

  20. Young KA, Engelman CD, Langefeld CD, Hairston KG, Haffner SM, Bryer-Ash M, Norris JM (2009) Association of plasma vitamin D levels with adiposity in Hispanic and African Americans. J Clin Endocrinol Metab 94:3306–3313

    Article  CAS  PubMed  Google Scholar 

  21. Bolland MJ, Grey AB, Ames RW, Mason BH, Horne AM, Gamble GD, Reid IR (2007) The effects of seasonal variation of 25-hydroxyvitamin D and fat mass on a diagnosis of vitamin D sufficiency. Am J Clin Nutr 86:959–964

    CAS  PubMed  Google Scholar 

  22. Arunabh S, Pollack S, Yeh J, Aloia JF (2003) Body fat content and 25-hydroxyvitamin D levels in healthy women. J Clin Endocrinol Metab 88:157–161

    Article  CAS  PubMed  Google Scholar 

  23. Kremer R, Campbell PP, Reinhardt T, Gilsanz V (2009) Vitamin D status and its relationship to body fat, final height, and peak bone mass in young women. J Clin Endocrinol Metab 94:67–73

    Article  CAS  PubMed  Google Scholar 

  24. Beydoun MA, Boueiz A, Shroff MR, Beydoun HA, Wang Y, Zonderman AB (2010) Associations among 25-hydroxyvitamin D, diet quality, and metabolic disturbance differ by adiposity in adults in the United States. J Clin Endocrinol Metab 95:3814–3827

    Article  CAS  PubMed  Google Scholar 

  25. Freedman BI, Wagenknecht LE, Hairston KG, Bowden DW, Carr JJ, Hightower RC, Gordon EJ, Xu J, Langefeld CD, Divers J (2010) Vitamin D, adiposity, and calcified atherosclerotic plaque in African-Americans. J Clin Endocrinol Metab 95:1076–1083

    Article  CAS  PubMed  Google Scholar 

  26. Lee P, Greenfield JR, Seibel MJ, Eisman JA, Center JR (2009) Adequacy of vitamin D replacement in severe deficiency is dependent on body mass index. Am J Med 122:1056–1060

    Article  CAS  PubMed  Google Scholar 

  27. Blum M, Dallal GE, Dawson-Hughes B (2008) Body size and serum 25 hydroxy vitamin D response to oral supplements in healthy older adults. J Am Coll Nutr 27:274–279

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF (2000) Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 72:690–693

    CAS  PubMed  Google Scholar 

  29. Barger-Lux MJ, Heaney RP, Dowell S, Chen TC, Holick MF (1998) Vitamin D and its major metabolites: serum levels after graded oral dosing in healthy men. Osteoporos Int 8:222–230

    Article  CAS  PubMed  Google Scholar 

  30. Forsythe LK, Livingstone MB, Barnes MS, Horigan G, McSorley EM, Bonham MP, Magee PJ, Hill TR, Lucey AJ, Cashman KD, Kiely M, Strain JJ, Wallace JM (2012) Effect of adiposity on vitamin D status and the 25-hydroxycholecalciferol response to supplementation in healthy young and older Irish adults. Br J Nutr 107:126–134

    Article  PubMed  Google Scholar 

  31. Gallagher JC, Sai A, Templin T 2nd, Smith L (2012) Dose response to vitamin D supplementation in postmenopausal women: a randomized trial. Ann Intern Med 156:425–437

    Article  PubMed  Google Scholar 

  32. Canto-Costa MH, Kunii I, Hauache OM (2006) Body fat and cholecalciferol supplementation in elderly homebound individuals. Braz J Med Biol Res 39:91–98

    Article  CAS  PubMed  Google Scholar 

  33. Nelson ML, Blum JM, Hollis BW, Rosen C, Sullivan SS (2009) Supplements of 20 microg/d cholecalciferol optimized serum 25-hydroxyvitamin D concentrations in 80% of premenopausal women in winter. J Nutr 139:540–546

    Article  CAS  PubMed  Google Scholar 

  34. Wood AD, Secombes KR, Thies F, Aucott L, Black AJ, Mavroeidi A, Simpson WG, Fraser WD, Reid DM, Macdonald HM (2012) Vitamin D3 supplementation has no effect on conventional cardiovascular risk factors: a parallel-group, double-blind, placebo-controlled RCT. J Clin Endocrinol Metab 97:3557–3568

    Article  CAS  PubMed  Google Scholar 

  35. Fraser WD, Durham BH, Berry JL, Mawer EB (1997) Measurement of plasma 1,25 dihydroxyvitamin D using a novel immunoextraction technique and immunoassay with iodine labelled vitamin D tracer. Ann Clin Biochem 34(Pt 6):632–637

    CAS  PubMed  Google Scholar 

  36. Harrison GI, Young AR (2002) Ultraviolet radiation-induced erythema in human skin. Methods 28:14–19

    Article  CAS  PubMed  Google Scholar 

  37. Mavroeidi A, Macdonald H, Stewart A, Reid D (2004) Validity and repeatability of the Aberdeen bone specific physical activity questionnaire. Osteoporos Int 15

  38. Masson LF, McNeill G, Tomany JO, Simpson JA, Peace HS, Wei L, Grubb DA, Bolton-Smith C (2003) Statistical approaches for assessing the relative validity of a food-frequency questionnaire: use of correlation coefficients and the kappa statistic. Pub Health Nutr 6

  39. Macdonald HM, Mavroeidi A, Fraser WD, Darling AL, Black AJ, Aucott L, O'Neill F, Hart K, Berry JL, Lanham-New SA, Reid DM (2011) Sunlight and dietary contributions to the seasonal vitamin D status of cohorts of healthy postmenopausal women living at northerly latitudes: a major cause for concern? Osteoporos Int 22:2461–2472

    Article  CAS  PubMed  Google Scholar 

  40. Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, Nicholson GC (2010) Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA 303:1815–1822

    Article  CAS  PubMed  Google Scholar 

  41. Smith H, Anderson F, Raphael H, Maslin P, Crozier S, Cooper C (2007) Effect of annual intramuscular vitamin D on fracture risk in elderly men and women—a population-based, randomized, double-blind, placebo-controlled trial. Rheumatology (Oxford) 46:1852–1857

    Article  CAS  Google Scholar 

  42. Dawson-Hughes B, Harris SS (2010) High-dose vitamin D supplementation: too much of a good thing? JAMA 303:1861–1862

    Article  CAS  PubMed  Google Scholar 

  43. Kuchuk NO, Pluijm SM, van Schoor NM, Looman CW, Smit JH, Lips P (2009) Relationships of serum 25-hydroxyvitamin D to bone mineral density and serum parathyroid hormone and markers of bone turnover in older persons. J Clin Endocrinol Metab 94:1244–1250

    Article  PubMed  Google Scholar 

  44. Earthman CP, Beckman LM, Masodkar K, Sibley SD (2011) The link between obesity and low circulating 25-hydroxyvitamin D concentrations: considerations and implications. Int J Obes 36(3):387–396

    Google Scholar 

  45. McCarty MF, Thomas CA (2003) PTH excess may promote weight gain by impeding catecholamine-induced lipolysis-implications for the impact of calcium, vitamin D, and alcohol on body weight. Med Hypotheses 61:535–542

    Article  CAS  PubMed  Google Scholar 

  46. Zemel MB (2002) Regulation of adiposity and obesity risk by dietary calcium: mechanisms and implications. J Am Coll Nutr 21:146S–151S

    Article  CAS  PubMed  Google Scholar 

  47. Drincic AT, Armas LA, Van Diest EE, Heaney RP (2012) Volumetric dilution, rather than sequestration best explains the low vitamin d status of obesity. Obesity, Silver Spring

    Google Scholar 

  48. Rubenstein LZ (2006) Falls in older people: epidemiology, risk factors and strategies for prevention. Age Ageing 35(Suppl 2):ii37–ii41

    PubMed  Google Scholar 

Download references

Acknowledgements

This work was funded partly by the UK Food Standards Agency, the Department of Health and the National Osteoporosis Society. Any views expressed are the authors own. We thank Mrs. Lismy Cheripelli (Registered General Nurse, University of Aberdeen, UK) who made significant contributions to the acquisition of data and the continued welfare of our study participants; Prof. Roger Francis (University of Newcastle, UK) for his role as Trial Steering Committee Chair; Prof. Juliet Compston (University of Cambridge, UK) and Prof. Bernard Keavney and Dr. Mark Pearce (both of University of Newcastle, UK) as members of the Data Monitoring Committee; Mrs. Gladys McPherson (University of Aberdeen, UK), for providing randomization service, generating study codes to ensure blinding throughout data analysis, and performing code breaks after analysis; Ms. Katie Wilde (University of Aberdeen, UK) for developing and maintaining our electronic study database; Mrs. Lana Gibson (University of Aberdeen, UK) and Mrs. Jennifer Scott (University of Aberdeen, UK) for performing DXA scans; Mr. William Mutch (University of Aberdeen, UK) for contribution to biochemical analyses, and Ms Katrina Galbreith for help with data entry. Finally, we would like to thank all of the women who took part in our study.

Conflicts of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to H. M. Macdonald.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOCX 14 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wood, A.D., Secombes, K.R., Thies, F. et al. A parallel group double-blind RCT of vitamin D3 assessing physical function: is the biochemical response to treatment affected by overweight and obesity?. Osteoporos Int 25, 305–315 (2014). https://doi.org/10.1007/s00198-013-2473-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-013-2473-8

Keywords

Navigation