A randomized, double-blind, placebo-controlled trial of vitamin D supplementation with or without calcium in community-dwelling vitamin D deficient subjects

Salah Gariballa, Javed Yasin, Awad Alessa, Salah Gariballa, Javed Yasin, Awad Alessa

Abstract

Background: Although vitamin D deficiency is highly prevalent in the Middle East, very few studies have attempted to measure its health impact.

Aims: We aimed to assess whether vitamin D3 and calcium, either alone or in combination, have health benefit.

Methods: In a 2 × 2 factorial design double-blind, placebo-controlled trial, Community free living adults living in the city of Al Ain, UAE were randomly assigned to receive daily 2000 IU oral vitamin D3 alone, 600 mg calcium alone, oral vitamin D3 (2000 IU per day) combined with 600 mg calcium, or a placebo for 6 months. Primary outcomes were self-rated health and bone turnover markers.

Results: Of the 545 randomized, 277 subjects completed 6 months follow up. 25(OH)D levels marginally increased in the two groups received vitamin D3 alone or combined with calcium compared to the decline seen in those who received calcium supplement alone or a placebo. Sub-group analysis revealed that parathyroid hormone (PTH) concentration decreased and Calcium/creatinine ratio increased significantly in the combined vitamin D and Calcium group compared to the vitamin D alone or Calcium alone in contrast to the increase seen in the placebo group [p < 0.05 for between group difference at 6 months]. There were no statistically significant differences between the supplement and placebo groups at the 6 months follow-up in body weight, body mass index (BMI), blood pressure, body pains and general health.

Conclusion: PTH concentration decreased and calcium/creatinine ratio increased in subjects who received vitamin D and Calcium together compared to those who received vitamin D alone.

Trial registration: NCT02662491 , First registered on 25 January 2016 ( https://register.

Clinicaltrials: gov/prs/app/action/SelectProtocol?sid=S00060CE&selectaction=Edit&uid=U0001M6P&ts=3&cx=scu4cb , Last update: 05 August 2019.

Keywords: Body pains; Bone turnover; Calcium; Inflammation; Placebo; Sun exposure; Vitamin D.

Conflict of interest statement

The authors declare that they have no financial or non-financial competing interest or conflict of interest (see Methods section).

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Enrolment, treatment and 6-month follow up of study subjects
Fig. 2
Fig. 2
Compliance with supplement and placebo (maximum 180 tablets)
Fig. 3
Fig. 3
Effect of vitamin D3 alone, Calcium alone or in combination compared to placebo on 25(OH)D concentrations at 6 months follow up. P value = 0.12, for between group difference in cumulative changes at 6 months. Results adjusted for BMI, sun exposure, diet & physical activity

References

    1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–281. doi: 10.1056/NEJMra070553.
    1. Chu MP, Alagiakrishnan K, Sadowski C. The cure of ageing: vitamin D--magic or myth? Postgrad Med J. 2010;86(1020):608–616. doi: 10.1136/pgmj.2010.101121.
    1. Al Zarooni A, Al Marzouqi F, Al Darmaki S, Prinsloo E, Nagelkerke N. Prevalence of vitamin D deficiency and associated comorbidities among Abu Dhabi emirates population. BMC Res Notes. 2019;12(1):503. doi: 10.1186/s13104-019-4536-1.
    1. Ritu G, Gupta A. Vitamin D deficiency in India: prevalence, causalities and interventions. Nutrients. 2014;6(2):729–775. doi: 10.3390/nu6020729.
    1. Lerchbaum E, Trummer C, Theiler-Schwetz V, Kollmann M, Wölfler M, Pilz S, Obermayer-Pietsch B. Effects of vitamin D supplementation on bone turnover and bone mineral density in healthy men: a Post-Hoc analysis of a randomized controlled trial. Nutrients. 2019;11(4):731. doi: 10.3390/nu11040731.
    1. Holvik K, Meyer HE, Sogaard AJ, et al. Biochemical markers of bone turnover and their relation to forearm bone mineral density in persons of Pakistani and Norwegian background living in Oslo Norway. Eur J Endocrinol. 2006;155:693–699. doi: 10.1530/eje.1.02282.
    1. Lowe NM, Mitra SR, Foster PC, et al. Vitamin D status and markers of bone turnover in Caucasian and Southy Asian postmenopausal women living in the UK. Br J Nutr. 2010;103:1706–1710. doi: 10.1017/S0007114509993850.
    1. Farrar MD, Kift R, Felton SJ, et al. Recommended summer sunlight exposure amounts fail to produce sufficient vitamin D status in UK adults of south Asian origin. Am J Clin Nutr. 2011;94:1219–1224. doi: 10.3945/ajcn.111.019976.
    1. Cranney A, Weiler HA, O’Donnell, Puil L. Summary of evidence-based review on vitamin D efficacy and safety in relation to bone health. Am J Clin Nutr. 2008;88(suppl):513S–519S. doi: 10.1093/ajcn/88.2.513S.
    1. Autier P, Gandini S, Mullie P. A systematic review: influence of vitamin D supplementation on serum 25-hyroxyvitamin D concentration. J Clin Endocrinol Metab. 2012;97:2606–2613. doi: 10.1210/jc.2012-1238.
    1. Jesudason J, Need AG, Horowitz M, et al. Relationship between serum 25-hyroxyvitamin D and bone resportption markers in vitamin D insufficiency. Bone. 2002;31(3):626–630. doi: 10.1016/S8756-3282(02)00866-9.
    1. Gariballa S, Shah I, Yasin Y, Alessa A. Vitamin D [25 (OH) D] metabolites and epimers in obese subject: interaction and correlations with adverse metabolic health risk factors. J Steroid Biochem Mol Biol. 2022;215:106023. doi: 10.1016/j.jsbmb.2021.106023.
    1. European Food Safety European Food Safety Authority (EFSA) General principles for the collection of national food consumption data in the view of a pan-European dietary survey. EFSA J. 2009;7(12):143. doi: 10.2903/j.efsa.2004.143.
    1. Gariballa, Afandi B, Abu Haltem A, Yassin J, Alessa A. Effect of antioxidants and B-group vitamins on risk of infections in patients with type 2 diabetes mellitus. Nutrients. 2013;5(3):711–724. doi: 10.3390/nu5030711.
    1. Saadi HF, Dawodu A, Afandi BO, Zayed R, Benedict S, Nagelkerke N. Eifficancy of daily and monthly high dose califerol in vitamin D-deficient nulliparous and lactating woemen. Am J Clin Nutr. 2007;85:1565–1571. doi: 10.1093/ajcn/85.6.1565.
    1. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr. 2000;72(690–693):38.
    1. Maki KC, Rubin MR, Wong LG, McManus JF, Jensen CD, Lawless A. Effects of vitamin D supplementation on 25-hydroxyvitamin D, high-density lipoprotein cholesterol, and other cardiovascular disease risk markers in subjects with elevated waist circumference. Int J Food Sci Nutr. 2011;62:318–332. doi: 10.3109/09637486.2010.536146.
    1. Ekwaru JP, Zwicker JD, Holick MF, Giovannucci E, Veugelers PJ. The importance of body weight for the dose response relationship of oral vitamin D supplementation and serum 25-hydroxyvitamin D in healthy volunteers. PLoS One. 2014;9:e111265. doi: 10.1371/journal.pone.0111265.
    1. Drincic AT, Armas LA, Van Diest EE, Heaney RP. Volumetric dilution, rather than sequestration best explains the low vitamin D status of obesity. Obesity. 2012;20(7):1444–1448. doi: 10.1038/oby.2011.404.
    1. Veugelers PJ, Pham TM, Ekwaru JP. Optimal vitamin D supplementation doses that minimize the risk for both low and high serum 25-Hydroxyvitamin D concentrations in the general population. Nutrients. 2015;7(12):10189–10208. doi: 10.3390/nu7125527.
    1. Crowe FL, Steur M, Allen NE, Appleby PN, Travis RC, Key TJ. Plasma concentrations of 25-hydroxyvitamin D in meat eaters, fish eaters, vegetarians and vegans: results from the EPIC-Oxford study. Public Health Nutr. 2011;2:340–346. doi: 10.1017/S1368980010002454.
    1. Dawson-Hughes B, Staten MA, Knowler WC, Nelson J, Vickery EM, LeBlanc ES, et al. Intratrial exposure to vitamin D and new-onset diabetes among adults with Prediabetes: a secondary analysis from the vitamin D and type 2 diabetes (D2d) study. Diabetes Care. 2020;43(12):2916–2922. doi: 10.2337/dc20-1765.
    1. Jesudason D, Need AG, Horowitz M, O'Loughlin PD, Morris HA, Nordin BEC. Relationship between vitamin D and bone resorption. Bone. 2002;31(2):626–630. doi: 10.1016/S8756-3282(02)00866-9.
    1. Gariballa S, Alkaabi J, Yasin J, Al EA. Oxidative damage and associated inflammatory risk factors in obese Emirati women. Body mass index versus waist circumference. Saudi Med J. 2017;38(9):960–964. doi: 10.15537/smj.2017.9.19629.
    1. Malik A, Babir A, Abi Saab B, Roglic G, King H. Glucose intolerance and associated factors in the UAE. Diabetes Res Clin Pract. 2005;69:188–195. doi: 10.1016/j.diabres.2004.12.005.
    1. Gariballa S, Kosanovic M, Yasin J, Essa AE. Oxidative damage and inflammation in obese diabetic emirati subjects. Nutrients. 2014;6(11):4872–4880. doi: 10.3390/nu6114872.
    1. Afzal S, Brøndum-Jacobsen P, Bojesen SE, Nordestgaard BG. Vitamin D concentration, obesity, and risk of diabetes: a mendelian randomisation study. 2014.
    1. Norman AW, Frankel JB, Heldt AM, Grodsky GM. Vitamin D deficiency inhibits pancreatic secretion of insulin. Science. 1980;209:823–825. doi: 10.1126/science.6250216.
    1. Cade C, Norman AW. Vitamin D3 improves impaired glucose tolerance and insulin secretion in the vitamin D-defi cient rat in vivo. Endocrinology. 1986;119:84–90. doi: 10.1210/endo-119-1-84.
    1. Jorde R, Sneve M, Torjesen PA, Figenschau Y, Gøransson LG, Omdal R. No effect of supplementation with cholecalciferol on cytokines and markers of inflammation in overweight and obese subjects. Cytokine. 2010;50:175–180. doi: 10.1016/j.cyto.2009.12.006.
    1. Beilfuss J, Berg V, Sneve M, Jorde R, Kamycheva E. Effectsofa1-year supplementation with cholecalciferol on interleukin-6, tumor necrosis factor-alpha and insulin resistance in overweight and obese subjects. Cytokine. 2012;60:870–874. doi: 10.1016/j.cyto.2012.07.032.
    1. Wamberg L, Kampmann U, Stødkilde-Jørgensen H, Rejnmark L, Pedersen SB, Richelsen B. Effects of vitamin D supplementation on body fat accumulation, inflammation, and metabolic risk factors in obese adults with low vitamin D levels – results from a randomized trial. Eur J Intern Med. 2013;24:644–649. doi: 10.1016/j.ejim.2013.03.005.

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