Skip to main content
Top
Published in: Osteoporosis International 3/2017

Open Access 01-03-2017 | Original Article

Optimum dose of vitamin D for disease prevention in older people: BEST-D trial of vitamin D in primary care

Authors: H. Hin, J. Tomson, C. Newman, R. Kurien, M. Lay, J. Cox, J. Sayer, M. Hill, J. Emberson, J. Armitage, R. Clarke

Published in: Osteoporosis International | Issue 3/2017

Login to get access

Abstract

Summary

This trial compared the effects of daily treatment with vitamin D or placebo for 1 year on blood tests of vitamin D status. The results demonstrated that daily 4000 IU vitamin D3 is required to achieve blood levels associated with lowest disease risks, and this dose should be tested in future trials for fracture prevention.

Introduction

The aim of this trial was to assess the effects of daily supplementation with vitamin D3 4000 IU (100 μg), 2000 IU (50 μg) or placebo for 1 year on biochemical markers of vitamin D status in preparation for a large trial for prevention of fractures and other outcomes.

Methods

This is a randomized placebo-controlled trial in 305 community-dwelling people aged 65 years or older in Oxfordshire, UK. Outcomes included biochemical markers of vitamin D status (plasma 25-hydroxy-vitamin D [25[OH]D], parathyroid hormone [PTH], calcium and alkaline phosphatase), cardiovascular risk factors and tests of physical function.

Results

Mean (SD) plasma 25(OH)D levels were 50 (18) nmol/L at baseline and increased to 137 (39), 102 (25) and 53 (16) nmol/L after 12 months in those allocated 4000 IU, 2000 IU or placebo, respectively (with 88%, 70% and 1% of these groups achieving the pre-specified level of >90 nmol/L). Neither dose of vitamin D3 was associated with significant deviation outside the normal range of PTH or albumin-corrected calcium. The additional effect on 25(OH)D levels of 4000 versus 2000 IU was similar in all subgroups except for body mass index, for which the further increase was smaller in overweight and obese participants compared with normal-weight participants. Supplementation with vitamin D had no significant effects on cardiovascular risk factors or on measures of physical function.

Conclusions

After accounting for average 70% compliance in long-term trials, doses of 4000 IU vitamin D3 daily may be required to achieve plasma 25(OH)D levels associated with lowest disease risk in observational studies.
Appendix
Available only for authorised users
Literature
1.
go back to reference van Staa TP, Dennison EM, Leufkens HG, Cooper C (2001) Epidemiology of fractures in England and Wales. Bone 29:517–522CrossRefPubMed van Staa TP, Dennison EM, Leufkens HG, Cooper C (2001) Epidemiology of fractures in England and Wales. Bone 29:517–522CrossRefPubMed
3.
go back to reference Bischoff-Ferrari HA, Kiel DP, Dawson-Hughes B, Orav JE, Li R, Spiegelman D, Dietrich T, Willett WC (2009) Dietary calcium and serum 25-hydroxyvitamin D status in relation to BMD among U.S. adults. J Bone Miner Res 24:935–942CrossRefPubMed Bischoff-Ferrari HA, Kiel DP, Dawson-Hughes B, Orav JE, Li R, Spiegelman D, Dietrich T, Willett WC (2009) Dietary calcium and serum 25-hydroxyvitamin D status in relation to BMD among U.S. adults. J Bone Miner Res 24:935–942CrossRefPubMed
4.
go back to reference Kuchuk NO, van Schoor NM, Pluijm SM, Chines A, Lips P (2009) Vitamin D status, parathyroid function, bone turnover, and BMD in postmenopausal women with osteoporosis: global perspective. J Bone Miner Res 24:693–701CrossRefPubMed Kuchuk NO, van Schoor NM, Pluijm SM, Chines A, Lips P (2009) Vitamin D status, parathyroid function, bone turnover, and BMD in postmenopausal women with osteoporosis: global perspective. J Bone Miner Res 24:693–701CrossRefPubMed
5.
go back to reference Gerdhem P, Ringsberg KA, Obrant KJ, Akesson K (2005) Association between 25-hydroxy vitamin D levels, physical activity, muscle strength and fractures in the prospective population-based OPRA Study of Elderly Women. Osteoporosis Int 16:1425–1431CrossRef Gerdhem P, Ringsberg KA, Obrant KJ, Akesson K (2005) Association between 25-hydroxy vitamin D levels, physical activity, muscle strength and fractures in the prospective population-based OPRA Study of Elderly Women. Osteoporosis Int 16:1425–1431CrossRef
6.
go back to reference Khaw KT, Luben R, Wareham N (2014) Serum 25-hydroxyvitamin D, mortality, and incident cardiovascular disease, respiratory disease, cancers, and fractures: a 13-y prospective population study. Am J Clin Nutr 100:1361–1370CrossRefPubMedPubMedCentral Khaw KT, Luben R, Wareham N (2014) Serum 25-hydroxyvitamin D, mortality, and incident cardiovascular disease, respiratory disease, cancers, and fractures: a 13-y prospective population study. Am J Clin Nutr 100:1361–1370CrossRefPubMedPubMedCentral
7.
go back to reference Tomson J, Emberson J, Hill M, Gordon A, Armitage J, Shipley M, Collins R, Clarke R (2013) Vitamin D and risk of death from vascular and non-vascular causes in the Whitehall study and meta-analyses of 12,000 deaths. Eur Heart J 34:1365–1374CrossRefPubMed Tomson J, Emberson J, Hill M, Gordon A, Armitage J, Shipley M, Collins R, Clarke R (2013) Vitamin D and risk of death from vascular and non-vascular causes in the Whitehall study and meta-analyses of 12,000 deaths. Eur Heart J 34:1365–1374CrossRefPubMed
10.
go back to reference Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, Delmas PD, Meunier PJ (1992) Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med 327:1637–1642CrossRefPubMed Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, Delmas PD, Meunier PJ (1992) Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med 327:1637–1642CrossRefPubMed
11.
go back to reference Chapuy MC, Arlot ME, Delmas PD, Meunier PJ (1994) Effect of calcium and cholecalciferol treatment for three years on hip fractures in elderly women. BMJ 308:1081–1082CrossRefPubMedPubMedCentral Chapuy MC, Arlot ME, Delmas PD, Meunier PJ (1994) Effect of calcium and cholecalciferol treatment for three years on hip fractures in elderly women. BMJ 308:1081–1082CrossRefPubMedPubMedCentral
12.
go back to reference Lips P, Graafmans WC, Ooms ME, Bezemer PD, Bouter LM (1996) Vitamin D supplementation and fracture incidence in elderly persons. A randomized, placebo-controlled clinical trial. Ann Intern Med 124:400–406CrossRefPubMed Lips P, Graafmans WC, Ooms ME, Bezemer PD, Bouter LM (1996) Vitamin D supplementation and fracture incidence in elderly persons. A randomized, placebo-controlled clinical trial. Ann Intern Med 124:400–406CrossRefPubMed
13.
go back to reference Porthouse J, Cockayne S, King C, Saxon L, Steele E, Aspray T, Baverstock M, Birks Y, Dumville J, Francis R, Iglesias C, Puffer S, Sutcliffe A, Watt I, Torgerson DJ (2005) Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care. BMJ 330:1003CrossRefPubMedPubMedCentral Porthouse J, Cockayne S, King C, Saxon L, Steele E, Aspray T, Baverstock M, Birks Y, Dumville J, Francis R, Iglesias C, Puffer S, Sutcliffe A, Watt I, Torgerson DJ (2005) Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care. BMJ 330:1003CrossRefPubMedPubMedCentral
14.
go back to reference Grant AM, Avenell A, Campbell MK, McDonald AM, MacLennan GS, McPherson GC, Anderson FH, Cooper C, Francis RM, Donaldson C, Gillespie WJ, Robinson CM, Torgerson DJ, Wallace WA, RECORD Trial Group (2005) Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial. Lancet 365:1621–1628CrossRefPubMed Grant AM, Avenell A, Campbell MK, McDonald AM, MacLennan GS, McPherson GC, Anderson FH, Cooper C, Francis RM, Donaldson C, Gillespie WJ, Robinson CM, Torgerson DJ, Wallace WA, RECORD Trial Group (2005) Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial. Lancet 365:1621–1628CrossRefPubMed
15.
go back to reference Jackson RD, LaCroix AZ, Gass M et al (2006) Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 354:669–683CrossRefPubMed Jackson RD, LaCroix AZ, Gass M et al (2006) Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 354:669–683CrossRefPubMed
16.
go back to reference Cranney A, Horsley T, O’Donnell S, Weiler H, Puil L, Ooi D, Atkinson S, Ward L, Moher D, Hanley D, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, Mamaladze V (2007) Effectiveness and safety of vitamin D in relation to bone health. Evid Rep Technol Assess (Full Rep) 158:1–235 Cranney A, Horsley T, O’Donnell S, Weiler H, Puil L, Ooi D, Atkinson S, Ward L, Moher D, Hanley D, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, Mamaladze V (2007) Effectiveness and safety of vitamin D in relation to bone health. Evid Rep Technol Assess (Full Rep) 158:1–235
17.
go back to reference Lyons RA, Johansen A, Brophy S, Newcombe RG, Phillips CJ, Lervy B, Evans R, Wareham K, Stone MD (2007) Preventing fractures among older people living in institutional care: a pragmatic randomised double blind placebo controlled trial of vitamin D supplementation. Osteoporosis Int 18:811–818CrossRef Lyons RA, Johansen A, Brophy S, Newcombe RG, Phillips CJ, Lervy B, Evans R, Wareham K, Stone MD (2007) Preventing fractures among older people living in institutional care: a pragmatic randomised double blind placebo controlled trial of vitamin D supplementation. Osteoporosis Int 18:811–818CrossRef
18.
go back to reference Boonen S, Lips P, Bouillon R, Bischoff-Ferrari HA, Vanderschueren D, Haentjens P (2007) Need for additional calcium to reduce the risk of hip fracture with vitamin D supplementation: evidence from a comparative metaanalysis of randomized controlled trials. J Clin Endocrinol Metab 92:1415–1423CrossRefPubMed Boonen S, Lips P, Bouillon R, Bischoff-Ferrari HA, Vanderschueren D, Haentjens P (2007) Need for additional calcium to reduce the risk of hip fracture with vitamin D supplementation: evidence from a comparative metaanalysis of randomized controlled trials. J Clin Endocrinol Metab 92:1415–1423CrossRefPubMed
20.
go back to reference Bischoff-Ferrari HA, Willett WC, Wong JB, Stuck AE, Staehelin HB, Orav EJ, Thoma A, Kiel DP, Henschkowski J (2009) Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med 169:551–561CrossRefPubMed Bischoff-Ferrari HA, Willett WC, Wong JB, Stuck AE, Staehelin HB, Orav EJ, Thoma A, Kiel DP, Henschkowski J (2009) Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med 169:551–561CrossRefPubMed
21.
go back to reference Bischoff-Ferrari HA, Willett WC, Orav EJ, Lips P, Meunier PJ, Lyons RA, Flicker L, Wark J, Jackson RD, Cauley JA, Meyer HE, Pfeifer M, Sanders KM, Stähelin HB, Theiler R, Dawson-Hughes B (2012) A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med 367:40–49CrossRefPubMed Bischoff-Ferrari HA, Willett WC, Orav EJ, Lips P, Meunier PJ, Lyons RA, Flicker L, Wark J, Jackson RD, Cauley JA, Meyer HE, Pfeifer M, Sanders KM, Stähelin HB, Theiler R, Dawson-Hughes B (2012) A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med 367:40–49CrossRefPubMed
22.
go back to reference Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JP (2014) Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ 348:g2035CrossRefPubMedPubMedCentral Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JP (2014) Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ 348:g2035CrossRefPubMedPubMedCentral
23.
go back to reference Garland CF, Kim JJ, Mohr SB, Gorham ED, Grant WB, Giovannucci EL, Baggerly L, Hofflich H, Ramsdell JW, Zeng K, Heaney RP (2014) Meta-analysis of all-cause mortality according to serum 25-hydroxyvitamin D. Am J Pub Health 104:e43–e50CrossRef Garland CF, Kim JJ, Mohr SB, Gorham ED, Grant WB, Giovannucci EL, Baggerly L, Hofflich H, Ramsdell JW, Zeng K, Heaney RP (2014) Meta-analysis of all-cause mortality according to serum 25-hydroxyvitamin D. Am J Pub Health 104:e43–e50CrossRef
24.
go back to reference Roddam AW, Neale R, Appleby P, Allen NE, Tipper S, Key TJ (2007) Association between plasma 25-hydroxyvitamin D levels and fracture risk: the EPIC-Oxford study. Am J Epidemiol 166:1327–1336CrossRefPubMed Roddam AW, Neale R, Appleby P, Allen NE, Tipper S, Key TJ (2007) Association between plasma 25-hydroxyvitamin D levels and fracture risk: the EPIC-Oxford study. Am J Epidemiol 166:1327–1336CrossRefPubMed
25.
go back to reference Saquib N, von Muhlen D, Garland CF, Barrett-Connor E (2006) Serum 25-hydroxyvitamin D, parathyroid hormone, and bone mineral density in men: the Rancho Bernardo study. Osteoporosis Int 17:1734–1741CrossRef Saquib N, von Muhlen D, Garland CF, Barrett-Connor E (2006) Serum 25-hydroxyvitamin D, parathyroid hormone, and bone mineral density in men: the Rancho Bernardo study. Osteoporosis Int 17:1734–1741CrossRef
26.
go back to reference Luxwolda MF, Kuipers RS, Kema IP, Dijck-Brouwer DA, Muskiet FA (2012) Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/l. Br J Nutr 108:1557–1561CrossRefPubMed Luxwolda MF, Kuipers RS, Kema IP, Dijck-Brouwer DA, Muskiet FA (2012) Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/l. Br J Nutr 108:1557–1561CrossRefPubMed
27.
go back to reference Valcour A, Blocki F, Hawkins DM, Rao SD (2012) Effects of age and serum 25-OH-vitamin D on serum parathyroid hormone levels. J Clin Endocrinol Metab 97:3989–3995CrossRefPubMed Valcour A, Blocki F, Hawkins DM, Rao SD (2012) Effects of age and serum 25-OH-vitamin D on serum parathyroid hormone levels. J Clin Endocrinol Metab 97:3989–3995CrossRefPubMed
28.
go back to reference Heaney RP (2004) Functional indices of vitamin D status and ramifications of vitamin D deficiency. Am J Clin Nutr 80(6 Suppl):1706S–11709CrossRefPubMed Heaney RP (2004) Functional indices of vitamin D status and ramifications of vitamin D deficiency. Am J Clin Nutr 80(6 Suppl):1706S–11709CrossRefPubMed
29.
go back to reference Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B (2006) Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 84:18–28CrossRefPubMed Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B (2006) Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 84:18–28CrossRefPubMed
30.
go back to reference Clarke R, Newman C, Tomson J, Hin H, Kurien R, Cox J, Lay M, Sayer J, Hill M, Emberson J, Armitage J (2015) Estimation of the optimum dose of vitamin D for disease prevention in older people: rationale, design and baseline characteristics of the BEST-D trial. Maturitas 80:426–431CrossRefPubMedPubMedCentral Clarke R, Newman C, Tomson J, Hin H, Kurien R, Cox J, Lay M, Sayer J, Hill M, Emberson J, Armitage J (2015) Estimation of the optimum dose of vitamin D for disease prevention in older people: rationale, design and baseline characteristics of the BEST-D trial. Maturitas 80:426–431CrossRefPubMedPubMedCentral
31.
go back to reference Roberts HC, Denison HJ, Martin HJ, Patel HP, Syddall H, Cooper C, Sayer AA (2011) A review of the measurement of grip strength in clinical and epidemiological studies: towards a standardised approach. Age Ageing 40:423–429CrossRefPubMed Roberts HC, Denison HJ, Martin HJ, Patel HP, Syddall H, Cooper C, Sayer AA (2011) A review of the measurement of grip strength in clinical and epidemiological studies: towards a standardised approach. Age Ageing 40:423–429CrossRefPubMed
32.
go back to reference Vlachopoulos C, Aznaouridis K, Stefanadis C (2010) Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol 55:1318–1327CrossRefPubMed Vlachopoulos C, Aznaouridis K, Stefanadis C (2010) Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol 55:1318–1327CrossRefPubMed
33.
go back to reference Ring M, Eriksson MJ, Zierath JR, Caidahl K (2014) Arterial stiffness estimation in healthy subjects: a validation of oscillometric (Arteriograph) and tonometric (SphygmoCor) techniques. Hypertens Res 37:999–1007CrossRefPubMed Ring M, Eriksson MJ, Zierath JR, Caidahl K (2014) Arterial stiffness estimation in healthy subjects: a validation of oscillometric (Arteriograph) and tonometric (SphygmoCor) techniques. Hypertens Res 37:999–1007CrossRefPubMed
34.
go back to reference Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, Scherr PA, Wallace RB (1994) A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol 49:M85–M94CrossRefPubMed Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, Scherr PA, Wallace RB (1994) A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol 49:M85–M94CrossRefPubMed
35.
go back to reference Martin HJ, Syddall HE, Dennison EM, Cooper C, Sayer AA (2008) Relationship between customary physical activity, muscle strength and physical performance in older men and women: findings from the Hertfordshire Cohort Study. Age Ageing 37:589–593CrossRefPubMed Martin HJ, Syddall HE, Dennison EM, Cooper C, Sayer AA (2008) Relationship between customary physical activity, muscle strength and physical performance in older men and women: findings from the Hertfordshire Cohort Study. Age Ageing 37:589–593CrossRefPubMed
36.
go back to reference Zigmond AS, Snaith RP (1983) The hospital anxiety and depression scale. Acta Psychiatra Scand 67:361–370CrossRef Zigmond AS, Snaith RP (1983) The hospital anxiety and depression scale. Acta Psychiatra Scand 67:361–370CrossRef
37.
go back to reference Bjelland I, Dahl AA, Haug TT, Neckelmann D (2002) The validity of the Hospital Anxiety and Depression Scale. An Updated Literature Review J Psychosom Res 52:69–77CrossRefPubMed Bjelland I, Dahl AA, Haug TT, Neckelmann D (2002) The validity of the Hospital Anxiety and Depression Scale. An Updated Literature Review J Psychosom Res 52:69–77CrossRefPubMed
38.
go back to reference Borm GF, Fransen J, Lemmens WA (2007) A simple sample size formula for analysis of covariance in randomized clinical trials. J Clin Epidemiol 60(12):1234–1238CrossRefPubMed Borm GF, Fransen J, Lemmens WA (2007) A simple sample size formula for analysis of covariance in randomized clinical trials. J Clin Epidemiol 60(12):1234–1238CrossRefPubMed
39.
go back to reference Pocock SJ, McMurray JJ, Collier TJ (2015) Making sense of statistics in clinical trial reports: part 1 of a 4-part series on statistics for clinical trials. J Am Coll Cardiol 66(22):2536–2549CrossRefPubMed Pocock SJ, McMurray JJ, Collier TJ (2015) Making sense of statistics in clinical trial reports: part 1 of a 4-part series on statistics for clinical trials. J Am Coll Cardiol 66(22):2536–2549CrossRefPubMed
40.
go back to reference Vieth R, Chan PC, MacFarlane GD (2001) Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level. Am J Clin Nutr 73:288–294CrossRefPubMed Vieth R, Chan PC, MacFarlane GD (2001) Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level. Am J Clin Nutr 73:288–294CrossRefPubMed
41.
go back to reference Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ (2003) Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 77:204–210CrossRefPubMed Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ (2003) Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 77:204–210CrossRefPubMed
42.
go back to reference Institute of Medicine (2011) Dietary reference intakes for calcium and vitamin D. The National Academies Press, Washington, DC Institute of Medicine (2011) Dietary reference intakes for calcium and vitamin D. The National Academies Press, Washington, DC
43.
go back to reference Gallagher JC, Sai A, Templin T, Smith L (2012) Dose response to vitamin D supplementation in post-menopausal women: a randomized trial. Annals of Int Med 156:425–437CrossRef Gallagher JC, Sai A, Templin T, Smith L (2012) Dose response to vitamin D supplementation in post-menopausal women: a randomized trial. Annals of Int Med 156:425–437CrossRef
45.
go back to reference Meyer HE, Holvik K, Lips P (2015) Should vitamin D supplements be recommended to prevent chronic diseases? BMJ 350:h321CrossRefPubMed Meyer HE, Holvik K, Lips P (2015) Should vitamin D supplements be recommended to prevent chronic diseases? BMJ 350:h321CrossRefPubMed
46.
47.
go back to reference Durup D, Jørgensen HL, Christensen J, Tjønneland A, Olsen A, Halkjær J, Lind B, Heegaard AM, Schwarz P (2015) A reverse J-shaped association between serum 25-hydroxyvitamin D and cardiovascular disease mortality: the CopD study. J Clin Endocrinol Metab 100:2339–2346CrossRefPubMed Durup D, Jørgensen HL, Christensen J, Tjønneland A, Olsen A, Halkjær J, Lind B, Heegaard AM, Schwarz P (2015) A reverse J-shaped association between serum 25-hydroxyvitamin D and cardiovascular disease mortality: the CopD study. J Clin Endocrinol Metab 100:2339–2346CrossRefPubMed
49.
go back to reference Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group, Armitage JM, Bowman L, Clarke RJ, Wallendszus K, Bulbulia R, Rahimi K, Haynes R, Parish S, Sleight P, Peto R, Collins R (2010) Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial. JAMA 303:2486–2494CrossRef Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group, Armitage JM, Bowman L, Clarke RJ, Wallendszus K, Bulbulia R, Rahimi K, Haynes R, Parish S, Sleight P, Peto R, Collins R (2010) Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial. JAMA 303:2486–2494CrossRef
Metadata
Title
Optimum dose of vitamin D for disease prevention in older people: BEST-D trial of vitamin D in primary care
Authors
H. Hin
J. Tomson
C. Newman
R. Kurien
M. Lay
J. Cox
J. Sayer
M. Hill
J. Emberson
J. Armitage
R. Clarke
Publication date
01-03-2017
Publisher
Springer London
Published in
Osteoporosis International / Issue 3/2017
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-016-3833-y

Other articles of this Issue 3/2017

Osteoporosis International 3/2017 Go to the issue