International Journal of Clinical Pharmacy

, Volume 36, Issue 4, pp 771–778 | Cite as

Comparative efficacy and safety of different doses of ergocalciferol supplementation in patients with metabolic syndrome

  • Nakarin Sansanayudh
  • Supakit WongwiwatthananukitEmail author
  • Nongluk Phetkrajaysang
  • Sarinee Krittiyanunt
Research Article


Background Vitamin D deficiency is a common problem worldwide. Several studies have shown an association between vitamin D deficiency and the increased risk of metabolic syndrome. No previous study has compared the efficacy and safety of ergocalciferol at 40,000 versus 20,000 IU/week in patients with metabolic syndrome. Objective To evaluate the efficacy of ergocalciferol supplementation on serum 25-hydroxyvitamin D [25(OH)D] concentrations and to examine safety parameters in metabolic syndrome patients. Setting Outpatient department of Phramongkutklao Hospital, Bangkok, Thailand. Method A randomized, double-blinded, parallel study was conducted in metabolic syndrome patients with vitamin D deficiency [25(OH)D <20 ng/mL]. Ninety patients were randomly assigned into three groups of 30 patients each. Group 1 was given two capsules of placebo/week, group 2 was given ergocalciferol 20,000 IU/week, and group 3 was given ergocalciferol 40,000 IU/week for 8 weeks. Main outcome measure serum 25(OH)D concentrations, serum calcium, safety, and corrected QT (QTc) interval. Results Of the 90 patients enrolled, 84 patients completed the study. At the end of the study, the mean serum 25(OH)D in groups 2 and 3 significantly increased from the baseline (15.1 and 14.3 to 26.8 and 30.0 ng/mL, respectively). The increase in serum 25(OH)D in groups 2 and 3 were comparable and significantly greater than that of the placebo group. The percentage number of patients achieving normal vitamin D levels in groups 1, 2 and 3 were 3.3, 33.3, and 60.0 %, respectively, which were significantly different between groups (p < 0.001). Adverse reactions in both ergocalciferol treatment groups were not different from the placebo group (p > 0.05). Serum calcium levels did not change within and between groups of treatment. No significant change in QTc was observed in any patient. Conclusions Both 20,000 and 40,000 IU/week of ergocalciferol supplementation for 8 weeks were able to increase serum 25(OH)D concentrations significantly. However, more patients in the ergocalciferol 40,000 IU/week treatment group achieved a normal serum 25(OH)D level than in the group which received 20,000 IU/week. Clinicians would have informed of choosing the dosing regimen of ergocalciferol in metabolic syndrome patients.


Efficacy Ergocalciferol 25-hydroxyvitamin D Metabolic syndrome Safety Vitamin D 



We would like to thank Ms. Dollapas Punpanich and Mrs. Siriwan Tribanyatkul for their dedication and technical assistance. Additional support was provided by The British Dispensary (LP) Co., Ltd, Thailand, who supplied the ergocalciferol supplement and the placebo.



Conflicts of interest

All authors in this article have no conflicts of interest regarding the publication of this article.


  1. 1.
    Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008;87:1080–6.Google Scholar
  2. 2.
    Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–81.PubMedCrossRefGoogle Scholar
  3. 3.
    Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911–30.PubMedCrossRefGoogle Scholar
  4. 4.
    Trang HM, Cole DE, Rubin LA, Pierratos A, Siu S, Vieth R. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr. 1998;68:854–8.PubMedGoogle Scholar
  5. 5.
    Romagnoli E, Mascia ML, Cipriani C, Fassino V, Mazzei F, D’Erasmo E, et al. Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly. J Clin Endocrinol Metab. 2008;93:3015–20.PubMedCrossRefGoogle Scholar
  6. 6.
    Tjellesen L, Hummer L, Christiansen C, Rodbro P. Serum concentration of vitamin D metabolites during treatment with vitamin D2 and vitamin D3 in normal premenopausal women. Bone Miner. 1986;1:407–13.PubMedGoogle Scholar
  7. 7.
    Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004;89:5387–91.PubMedCrossRefGoogle Scholar
  8. 8.
    Leventis P, Kiely PD. The tolerability and biochemical effects of high-dose bolus vitamin D2 and D3 supplementation in patients with vitamin D insufficiency. Scand J Rheumatol. 2009;38:149–53.PubMedCrossRefGoogle Scholar
  9. 9.
    Binkley N, Gemar D, Engelke J, Gangnon R, Ramamurthy R, Krueger D, et al. Evaluation of ergocalciferol or cholecalciferol dosing 1,600 IU daily or 50,000 IU monthly in older adults. J Clin Endocrinol Metab. 2011;96:981–8.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Glendenning P, Chew GT, Seymour HM, Gillett MJ, Goldswain PR, Inderjeeth CA, et al. Serum 25-hydroxyvitamin D levels in vitamin D-insufficient hip fracture patients after supplementation with ergocalciferol and cholecalciferol. Bone. 2009;45:870–5.PubMedCrossRefGoogle Scholar
  11. 11.
    Heaney RP, Recker RR, Grote J, Horst RL, Armas LA. Vitamin D3 is more potent than vitamin D2 in humans. J Clin Endocrinol Metab. 2011;96:E447–52.PubMedCrossRefGoogle Scholar
  12. 12.
    Holick MF, Biancuzzo RM, Chen TC, Klein EK, Young A, Bibuld D, et al. Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab. 2008;93:677–81.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Biancuzzo RM, Young A, Bibuld D, Cai MH, Winter MR, Klein EK, et al. Fortification of orange juice with vitamin D2 or vitamin D3 is as effective as an oral supplement in maintaining vitamin D status in adults. Am J Clin Nutr. 2010;91:1621–6.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Soontrapa S, Soontrapa S, Chailurkit L. The prevalence and the calcidiol levels of vitamin D deficiency in the elderly Thai women in municipality of KhonKaen province, Thailand. Srinagarind Med J. 2002;17:231–8.Google Scholar
  15. 15.
    Pinelli NR, Jaber LA, Brown MB, Herman WH. Serum 25-hydoxyvitamin D and insulin resistance, metabolic syndrome, and glucose intolerance among Arab Americans. Diabetes Care. 2010;33:1373–5.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Hossein-Nezhad A, Khoshniat NM, Maghbooli Z, Karimi F, Mirzaei K, Hosseini A, et al. Relationship between serum vitamin D concentration and metabolic syndrome among Iranian adults population. DARU. 2009;17:1–5.Google Scholar
  17. 17.
    Park HY, Lim YH, Kim JH, Bae S, Oh SY, Hong YC. Association of serum 25-hydroxyvitamin D levels with markers for metabolic syndrome in the elderly: a repeated measure analysis. J Korean Med Sci. 2012;27:653–60.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Athisakul S, Songmuang SB, Buddhari W. Prevalence of hypovitaminosis D in heart failure patients at King Chulalongkorn memorial hospital. Thail Heart J. 2010;23:154–63.Google Scholar
  19. 19.
    Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007;167:1730–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Vilarrasa N, Vendrell J, Maravall J, Elio I, Solano E, San JP, et al. Is plasma 25(OH)D related to adipokinesis, inflammatory cytokines and insulin resistance in both a healthy and morbidly obese population? Endocrine. 2010;38:235–42.PubMedCrossRefGoogle Scholar
  21. 21.
    Rotondi M, Chiovato L. Vitamin D deficiency in patients with Graves’ disease: probably something more than a casual association. Endocrine. 2012; doi:  10.1007/s12020-012-9776-y.
  22. 22.
    Ford ES, Zhao G, Li C, Pearson WS. Serum concentrations of vitamin D and parathyroid hormone and prevalent metabolic syndrome among adults in the United States. J Diabete. 2009;1(4):296–303.CrossRefGoogle Scholar
  23. 23.
    Chiu KC, Chu A, Go VL, Saad MF. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr. 2004;79(5):820–5.PubMedGoogle Scholar
  24. 24.
    Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insufficiency. Lancet. 1998;351:805–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement executive summary. Circulation. 2005;112:2735–52.PubMedCrossRefGoogle Scholar
  26. 26.
    Montgomery DC. Design and analysis of experiments. 6thed. Hoboken, NJ: John Wiley & Sons, Inc., (2005).Google Scholar
  27. 27.
    Jorde R, Sneve M, Torjesen P, Figenschau Y. No improvement in cardiovascular risk factors in overweight and obese subject after supplementation with vitamin D3 for 1 year. J Intern Med. 2010;267:462–72.PubMedCrossRefGoogle Scholar
  28. 28.
    Looker AC, Pfeiffer CM, Lacher DA, Scleicher RL, Picciano MF, Yetley EA. Serum 25-hydroxyvitamin D status of the US population: 1988–1994 compared with 2000–2004. Am J Clin Nutr. 2008;88:1519–27.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr. 2000;72:690–3.PubMedGoogle Scholar
  30. 30.
    Sugden JA, Davies JI, Witham MD, Morris AD, Strothers AD. Vitamin D improves endothelial function in patients with type 2 diabetes mellitus and low vitamin D levels. Diabet Med. 2008;25:320–5.PubMedCrossRefGoogle Scholar
  31. 31.
    Von Hurst PR, Stonehouse W, Coad J. Vitamin D supplementation reduces insulin resistance in south Asian women living in New Zealand who are insulin resistant and vitamin D deficient-a randomized, placebo-controlled trial. Br J Nutr. 2010;103:549–55.CrossRefGoogle Scholar
  32. 32.
    Sneve M, Figenschau Y, Jorde R. Supplementation with cholecalciferol does not result in weight reduction in overweight and obese subjects. Eur J Endocrinol. 2008;159:675–84.PubMedCrossRefGoogle Scholar
  33. 33.
    Jorde R, Figenschau Y. Supplementation with cholecalciferol does not improve glycaemic control in diabetic subjects with normal serum 25-hydroxyvitamin D levels. Eur J Nutr. 2009;48:349–54.PubMedCrossRefGoogle Scholar
  34. 34.
    Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003;77:204–10.PubMedGoogle Scholar
  35. 35.
    Pietras SM, Obayan BK, Cai MH, Holick MF. Vitamin D2 treatment for vitamin D deficiency and insufficiency for up to 6 years. Arch Intern Med. 2009;169:1806–8.PubMedCrossRefGoogle Scholar

Copyright information

© Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2014

Authors and Affiliations

  • Nakarin Sansanayudh
    • 1
  • Supakit Wongwiwatthananukit
    • 2
    Email author
  • Nongluk Phetkrajaysang
    • 3
  • Sarinee Krittiyanunt
    • 3
  1. 1.Department of Internal MedicinePhramongkutklao HospitalBangkokThailand
  2. 2.Department of Pharmacy Practice, The Daniel K. Inouye College of PharmacyUniversity of Hawaii at HiloHiloUSA
  3. 3.Department of Pharmacy Practice, Faculty of Pharmaceutical SciencesChulalongkorn UniversityBangkokThailand

Personalised recommendations