Nutrient Supplementation

NSUP: Vitamin D (2008)

• Assessment
  What is the evidence regarding the effect of supplemental vitamin D on bone density in post-menopausal women and older adult men?

  • Conclusion

    One meta-analysis (a systematic review of 19 studies), five RCTs and two cross-sectional studies found an association between supplemental vitamin D and bone mineral density (BMD) in post-menopausal women and older adult men. Vitamin D dosage ranged from 400 IU to 1,400 IU (10mcg to 35 mcg) per day, however it is difficult to determine the optimal dosage and the effect of vitamin D alone, since varying combinations of nutrients were used including calcium and vitamin K. One additional RCT with a supplement containing 200 IU (five mcg) of Vitamin D and other nutrients found an improvement in bone turnover markers, but no effect in bone mineral density. Further research is needed to determine the independent association between supplemental vitamin D and bone mineral density in post-menopausal women and older adult men.

  • Grade: II
    • Grade I means there is Good/Strong evidence supporting the statement;
    • Grade II is Fair;
    • Grade III is Limited/Weak;
    • Grade IV is Expert Opinion Only;
    • Grade V is Not Assignable.
    • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
    • Moderate (B) means we are moderately confident in the effect estimate;
    • Low (C) means our confidence in the effect estimate is limited;
    • Very Low (D) means we have very little confidence in the effect estimate.
    • Ungraded means a grade is not assignable.
  • Evidence Summary: What is the evidence regarding the effect of supplemental vitamin D on bone density in post-menopausal women and older adult men?
    • Detail
    • Quality Rating Summary
      For a summary of the Quality Rating results, click here.
    • Worksheets
      • Bolton-Smith C, McMurdo ME, Paterson CR, Mole PA, Harvey JM, Fenton ST, Prynne CJ, Mishra GD and Shearer MJ. Two-Year Randomized Controlled Trial of Vitamin K1 (Phylloquinone) and Vitamin D3 Plus Calcium on the Bone Health of Older Women. J Bone Miner Res. 2007 Apr; 22 (4 : 509-519.
      • Bunout D, Barrera G, Leiva L, Gattas V, de la Maza MP, Haschke F, Steenhout P, Klassen P, Hager C, Offoard E, Hirsch S. Effect of a Nutritional Supplementation on Bone Health in Chilean Elderly Subjects with Femoral Osteoporosis. J Am Coll Nutr. 2006 Jun; 25 (3): 170-177.
      • Cranney, Horsley, O’Donnell, Weiler, Puil, Ooi, Atkinson, Ward, Moher, Hanley, Fang, Yazdi, Garritty, Sampson, Barrowman, Tsertsvadze, Mamaladze. Effectiveness and Safety of Vitamin D in Relation to Bone Health. EvidenceReport/Technology Assessment No. 158 (Prepared by the University of Ottawa Evidence-based Practice Center (UO-EPC) under Contract No. 290-02-0021. AHRQ Publication No. 07-E013. Rockville, MD: Agency for Healthcare Research and Quality. August 2007. [Abstracted: 3.a. Vit D on Bone Density].
      • Daly RM, Bass S, Nowson C. Long-term effects of calcium-vitamin-D3-fortified milk on bone geometry and strength in older men. Bone. 2006 Oct; 39 (4): 946-953.
      • Daly RM, Brown M, Bass, S, Kukuljan S, Nowson C. Calcium and vitamin D3-fortified milk reduces bone loss at clinically relevant skeletal sites in older men: A two-year randomized controlled study. J Bone Miner Res. 2006 Mar; 21 (3): 397-405. Epub 2005 Dec 19.
      • Hitz MF, Jensen JE, Eskildsen PC. Bone mineral density and bone markers in patients with a recent low-energy fracture:effect of 1 y of treatment with calcium and vitamin D. Am J Clin Nutr. 2007 Jul; 86(1): 251-259.
      • Lips P, Hosking D, Lippuner K, Norquist JM, Wehren L, Maalouf G, Ragi-eis S, Chandler J. The prevalence of vitamin D inadequacy amongst women with osteoporosis: an international epidemiological investigation. J Intern Med. 2006 Sep; 260 (3): 245-254. Erratum in: J Intern Med. 2007 Apr; 261 (4): 408.
      • Nuti R, Bianchi G, Brandi ML, Caudarella R, D'Erasmo E, Fiore C, Isaia GC, Luisetto G, Muratore M, Oriente P, Ortolani S. Superiority of alfacalcidol compared to vitamin D plus calcium in lumbar bone mineral density in postmenopausal osteoporosis. Rheumatol Int. 2006 Mar; 26(5): 445-453. Epub, 2005 Nov 10.
      • Rizzoli R, Eisman JA, Norquist J, Ljunggren O, Krishnarajah G, Lim S-K, Chandler J. Risk factors for vitamin D inadequacy among women with osteoporosis: an international epidemiological study. Int J Clin Pract. 2006 Aug; 60 (8): 1,013-1,019. Erratum in; Int J Cl Pract. 2007 Mar; 61 (3): 534.
  • Search Plan and Results: NSUP: Vitamin D and Bone Health 2008
     
  What is the evidence regarding the effect of supplemental Vitamin D on fractures in post-menopausal women and older adult men?

  • Conclusion

    One meta-analysis/systematic review, combining the results of 13 RCTs suggest that supplementation with vitamin D₃ (400 IU to 800 IU) plus calcium (500mg to 1,200mg) may be beneficial in reducing the incidence of fractures in institutionalized older adults. The reduction of fractures might be accounted for by higher mean serum levels of 25(OH)D (at least 74nmol per L), due to good volunteer compliance. One RCT concluded that supplementation with 100,000 IU vitamin D₂ every four months, does not significantly reduce fractures in institutionalized older adults. Further research is needed to determine the role of vitamin D₃ and vitamin D₂ supplementation alone in reducing the incidence of fractures.

  • Grade: II
    • Grade I means there is Good/Strong evidence supporting the statement;
    • Grade II is Fair;
    • Grade III is Limited/Weak;
    • Grade IV is Expert Opinion Only;
    • Grade V is Not Assignable.
    • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
    • Moderate (B) means we are moderately confident in the effect estimate;
    • Low (C) means our confidence in the effect estimate is limited;
    • Very Low (D) means we have very little confidence in the effect estimate.
    • Ungraded means a grade is not assignable.
  • Evidence Summary: What is the evidence regarding the effect of supplemental Vitamin D on fractures in post-menopausal women and older adult men?
    • Detail
    • Quality Rating Summary
      For a summary of the Quality Rating results, click here.
    • Worksheets
      • Cranney, Horsley, O’Donnell, Weiler, Puil, Ooi, Atkinson, Ward, Moher, Hanley, Fang, Yazdi, Garritty, Sampson, Barrowman, Tsertsvadze, Mamaladze. Effectiveness and Safety of Vitamin D in Relation to Bone Health. EvidenceReport/Technology Assessment No. 158 (Prepared by the University of Ottawa Evidence-based Practice Center (UO-EPC) under Contract No. 290-02-0021. AHRQ Publication No. 07-E013. Rockville, MD: Agency for Healthcare Research and Quality. August 2007. [Abstracted: 3.b. Vit D on Fractures].
      • Lyons RA, Johansen A, Brophy S, Newcombe RG, Phillips CJ, Lervy B, Evans R, Wareham K, Stone MD. Preventing fractures among older people living in institutional care:a pragmatic randomised double blind placebo controlled trial of vitamin D supplementation. Osteoporos Int. 2007 June; 18(6): 811-818.
  • Search Plan and Results: NSUP: Vitamin D and Bone Health 2008
     
  What is the evidence regarding the effect of supplemental vitamin D on falls in post-menopausal women and older adult men?

  • Conclusion

    One meta-analysis/systematic review, one RCT and one prospective cohort study found that evidence is inconsistent regarding the effect of supplemental vitamin D₂ or vitamin D₃ on the reduction of falls in older adult men and women. Further research is needed to determine the role of vitamin D₂ or vitamin D₃ alone in preventing falls in older adults.

  • Grade: III
    • Grade I means there is Good/Strong evidence supporting the statement;
    • Grade II is Fair;
    • Grade III is Limited/Weak;
    • Grade IV is Expert Opinion Only;
    • Grade V is Not Assignable.
    • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
    • Moderate (B) means we are moderately confident in the effect estimate;
    • Low (C) means our confidence in the effect estimate is limited;
    • Very Low (D) means we have very little confidence in the effect estimate.
    • Ungraded means a grade is not assignable.
  • Evidence Summary: Effect of Supplemental Vitamin D on Falls in Post-Menopausal Women and Older Adult Men
    • Detail
    • Quality Rating Summary
      For a summary of the Quality Rating results, click here.
    • Worksheets
      • Cranney, Horsley, O’Donnell, Weiler, Puil, Ooi, Atkinson, Ward, Moher, Hanley, Fang, Yazdi, Garritty, Sampson, Barrowman, Tsertsvadze, Mamaladze. Effectiveness and Safety of Vitamin D in Relation to Bone Health. EvidenceReport/Technology Assessment No. 158 (Prepared by the University of Ottawa Evidence-based Practice Center (UO-EPC) under Contract No. 290-02-0021. AHRQ Publication No. 07-E013. Rockville, MD: Agency for Healthcare Research and Quality. August 2007. [Abstracted: 3.c. Vitamin D on Falls].
      • Gallagher JC, Rapuri P, Smith L. Falls are associated with decreased renal function and insufficient calcitriol production by the kidney. J Steroid Biochem Mol Biol. 2007 Mar; 103 (3-5): 610-613. Epub 2006 Dec 22. PMID: 17236758.
      • Prince RL, Austin N, Devine A, Dick IM, Bruce D, Zhu K. Effects of ergocalciferol added to calcium on the risk of falls in elderly high-risk women. Arch Intern Med. 2008 Jan 14; 168 (1): 103-108. PMID: 18195202.
  • Search Plan and Results: NSUP: Vitamin D and Bone Health 2008
     
  Are specific circulating concentrations of 25 hydroxyvitamin D [25(OH)D] associated with bone health outcomes in post-menopausal women and older adult men?

  • Conclusion

    Two RCTs and one meta-analysis (a systematic review of 42 papers) found that evidence is inconclusive regarding the association of specific circulating concentrations of 25-hydroxyvitamin D [25(OH)D] and bone health outcomes in post-menopausal women and older adult men. In those studies reporting a positive association in the meta-analysis, specific 25(OH)D concentrations ranging from 40nmol to 80nmol per L were shown to have declines in bone health outcomes (fractures, falls and bone loss). Further research is needed to determine the association of specific circulating concentrations of 25(OH)D with bone health outcomes.

  • Grade: III
    • Grade I means there is Good/Strong evidence supporting the statement;
    • Grade II is Fair;
    • Grade III is Limited/Weak;
    • Grade IV is Expert Opinion Only;
    • Grade V is Not Assignable.
    • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
    • Moderate (B) means we are moderately confident in the effect estimate;
    • Low (C) means our confidence in the effect estimate is limited;
    • Very Low (D) means we have very little confidence in the effect estimate.
    • Ungraded means a grade is not assignable.
  • Evidence Summary: Association of Circulating Concentrations of 25 Hydroxy vitamin D [25(OH)D] and Bone Health Outcomes in Post-Menopausal Women and Older Adult Men
    • Detail
    • Quality Rating Summary
      For a summary of the Quality Rating results, click here.
    • Worksheets
      • Aloia JF, Talwar SA, Pollack S, Feuerman M, Yeh JK. Optimal vitamin D status and serum parathyroid hormone concentrations in African-American women. Am J Clin Nutr. 2006 Sep; 84 (3): 602-609. PMID: 16960175.
      • Cranney, Horsley, O’Donnell, Weiler, Puil, Ooi, Atkinson, Ward, Moher, Hanley, Fang, Yazdi, Garritty, Sampson, Barrowman, Tsertsvadze, Mamaladze. Effectiveness and Safety of Vitamin D in Relation to Bone Health. EvidenceReport / Technology Assessment No. 158. Prepared by the University of Ottawa Evidence-based Practice Center (UO-EPC) under Contract No. 290-02-0021. AHRQ Publication No. 07-E013. Rockville, MD: Agency for Healthcare Research and Quality. August 2007. [Abstracted: 1.c. Circulating Conc. of 25(OH)D and Bone Health]. 
      • Rejnmark L, Lauridsen AL, Brot C, Vestergaard P, Heickendorff L, Nexo E, Mosekilde L. Vitamin D and its binding protein Gc: Long-term variability in peri-and postmenopausal women with and without hormone replacement therapy. Scand J Clin Lab Invest. 2006; 66 (3): 227-238
  • Search Plan and Results: NSUP: Vitamin D and Bone Health 2008
     
  What is the effect of vitamin D supplementation on circulating 25(OH)D in post-menopausal women and older adult men?

  • Conclusion

    Two RCTs and one meta-analysis (systematic review of 44 RCTs) found a direct effect of oral vitamin D₃ supplementation on circulating levels of 25(OH)D in post-menopausal women and older adult men. In studies reporting a treatment effect, specific doses ranging from five mcg to 50mcg (200 IU to 2,000 IU) of vitamin D₃ were utilized. Meta-regression results suggested that 100 IU (2.5mcg) of vitamin D₃ will increase the serum 25(OH)D concentrations by one nmol to two nmol per L suggesting doses of 400 IU to 800 IU (10mcg to 20mcg) daily may be inadequate to prevent vitamin D deficiency in at-risk individuals. It is difficult to determine adequate intake since there is a lack of agreement regarding optimal levels of serum 25(OH)D. Additional research is needed to determine the vitamin D dosage necessary to reach optimal serum 25(OH)D levels in post-menopausal women and older adult men.

  • Grade: II
    • Grade I means there is Good/Strong evidence supporting the statement;
    • Grade II is Fair;
    • Grade III is Limited/Weak;
    • Grade IV is Expert Opinion Only;
    • Grade V is Not Assignable.
    • High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
    • Moderate (B) means we are moderately confident in the effect estimate;
    • Low (C) means our confidence in the effect estimate is limited;
    • Very Low (D) means we have very little confidence in the effect estimate.
    • Ungraded means a grade is not assignable.
  • Evidence Summary: Vitamin D Supplementation on Circulating 25(OH)D in Post-Menopausal Women and Older Adult Men
    • Detail
    • Quality Rating Summary
      For a summary of the Quality Rating results, click here.
    • Worksheets
      • Cranney, Horsley, O’Donnell, Weiler, Puil, Ooi, Atkinson, Ward, Moher, Hanley, Fang, Yazdi, Garritty, Sampson, Barrowman, Tsertsvadze, Mamaladze. Effectiveness and Safety of Vitamin D in Relation to Bone Health. EvidenceReport / Technology Assessment No. 158 (Prepared by the University of Ottawa Evidence-based Practice Center (UO-EPC) under Contract No. 290-02-0021. AHRQ Publication No. 07-E013. Rockville, MD: Agency for Healthcare Research and Quality. August 2007. [Abstracted: 2.c. Vit D Supplementation on Circulating 25(OH)D].
      • Talwar SA, Aloia JF, Pollack S, Yeh JK. Dose response to vitamin D supplementation among postmenopausal African American women. Am J Clin Nutr. 2007 Dec; 86 (6): 1,657-1,662. PMID: 18065583.
      • Viljakainen H, Palssa A, Karkkainen M, Jakobsen J and Lamberg-Allardt C. How much Vitamin D3 do the elderly need? J Am Coll Nutr. 2006 Oct; 25 (5): 429-435.
  • Search Plan and Results: NSUP: Vitamin D and Bone Health 2008