Review Article

Effect of vitamin D supplementation on serum C-reactive protein level: a meta-analysis of randomized controlled trials


Objective: Vitamin D may have anti-inflammatory actions however; there is no consensus on the effects of vitamin D supplementation on C-reactive protein (CRP) level in randomized clinical trials. In a systematic review and meta-analysis, we hypothesized that vitamin D supplementation would reduce serum CRP levels.
Materials and Methods: A systematic research of randomized controlled trials has been conducted on MEDLINE and EMBASE through PubMed, Scopus, and completed by a manual review of the literature up from January 2000 to May 2015. Pooled effect estimated by using random-effect model and heterogeneity was assessed by Cochran’s Q and I2 tests.
Results: Of 157 potentially relevant studies we found in a systematic search, 20 clinical trials met the inclusion criteria. Mean baseline CRP levels in the intervention group and in the control group were 3.5±2.6 and 3.3±2.3 mg/L, respectively. Mean duration of the studies were 29.0±30.2.0 (SD) weeks (8 to 144 weeks). Doses of vitamin D3 supplementation varied between 200 to 57142 IU/day. Pooled analysis showed a non-significant increase of 0.04 mg/L (95% CI, −0.12 to 0.21; p < 0.61), with no evidence of heterogeneity (I2 = 17.8%, p < 0.17).
Conclusion: The results of this meta-analysis showed that vitamin D supplementation may not be effective for the reduction of CRP. However, a more accurate estimate of the effect requires further large and well-designed clinical trials.

Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008;87(4):1080S-6S.

Holick MF. Vitamin D deficiency. New England Journal of Medicine. 2007;357(3):266-81.

Adams JS, Hewison M. Update in vitamin D. The Journal of Clinical Endocrinology & Metabolism. 2010;95(2):471-8.

Guillot X, Semerano L, Saidenberg-Kermanac’h N, Falgarone G, Boissier M-C. Vitamin D and inflammation. Joint Bone Spine. 2010;77(6):552-7.

May E, Asadullah K, Zugel U. Immunoregulation through 1, 25-dihydroxyvitamin D 3 and its analogs. Current Drug Targets-Inflammation & Allergy. 2004;3(4):377-93.

Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO, Criqui M, et al. Markers of inflammation and cardiovascular disease application to clinical and public health practice: a statement for healthcare professionals from the centers for disease control and prevention and the American Heart Association. Circulation. 2003;107(3):499-511.

van Etten E, Mathieu C. Immunoregulation by 1, 25-dihydroxyvitamin D 3: basic concepts. The Journal of steroid biochemistry and molecular biology. 2005;97(1):93-101.

Shea MK, Booth SL, Massaro JM, Jacques PF, D'Agostino RB, Dawson-Hughes B, et al. Vitamin K and vitamin D status: associations with inflammatory markers in the Framingham Offspring Study. American journal of epidemiology. 2008;167(3):313-20.

Michos ED, Streeten EA, Ryan KA, Rampersaud E, Peyser PA, Bielak LF, et al. Serum 25-hydroxyvitamin d levels are not associated with subclinical vascular disease or C-reactive protein in the old order amish. Calcified tissue international. 2009;84(3):195-202.

Amer M, Qayyum R. Relation between serum 25-hydroxyvitamin D and C-reactive protein in asymptomatic adults (from the continuous National Health and Nutrition Examination Survey 2001 to 2006). The American journal of cardiology. 2012;109(2):226-30.

Pittas AG, Harris SS, Stark PC, Dawson-Hughes B. The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults. Diabetes Care. 2007;30(4):980-6.

Bjorkhem-Bergman L, Nylen H, Norlin AC, Lindh JD, Ekstrom L, Eliasson E, et al. Serum levels of 25-hydroxyvitamin D and the CYP3A biomarker 4beta-hydroxycholesterol in a high-dose vitamin D supplementation study. Drug Metab Dispos. 2013;41(4):704-8. Epub 2013/02/07.

Liefaard MC, Ligthart S, Vitezova A, Hofman A, Uitterlinden AG, Kiefte-de Jong JC, et al. Vitamin D and C-Reactive Protein: A Mendelian Randomization Study. PLoS ONE. 2015;10(7):e0131740.

Picot J, Hartwell D, Harris P, Mendes D, Clegg A, Takeda A. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. 2012.

Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17(1):1-12. Epub 1996/02/01.

Beilfuss J, Berg V, Sneve M, Jorde R, Kamycheva E. Effects of a 1-year supplementation with cholecalciferol on interleukin-6, tumor necrosis factor-alpha and insulin resistance in overweight and obese subjects. Cytokine. 2012;60(3):870-4.

Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr. 2005;135(2):317-22.

Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006;84(1):18-28.

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 randomised, placebo-controlled trial. British Journal of Nutrition. 2010;103(4):549-55.

Wood AD, Secombes KR, Thies F, Aucott L, Black AJ, Mavroeidi A, et al. Vitamin D 3 supplementation has no effect on conventional cardiovascular risk factors: A parallel-group, double-blind, placebo-controlled RCT. Journal of Clinical Endocrinology and Metabolism. 2012;97(10):3557-67.

Rahimi-Ardabili H, Pourghassem Gargari B, Farzadi L. Effects of vitamin D on cardiovascular disease risk factors in polycystic ovary syndrome women with vitamin D deficiency. Journal of Endocrinological Investigation. 2013;36(1):28-32.

Sadiya A, Ahmed SM, Carlsson M, Tesfa Y, George M, Ali SH, et al. Vitamin D supplementation in obese type 2 diabetes subjects in Ajman, UAE: a randomized controlled double-blinded clinical trial. European Journal of Clinical Nutrition. 2014.

Chandler PD, Scott JB, Drake BF, Ng K, Manson JE, Rifai N, et al. Impact of vitamin D supplementation on inflammatory markers in African Americans: results of a four-arm, randomized, placebo-controlled trial. Cancer Prev Res (Phila). 2014;7(2):218-25. Epub 2013/12/12.

Gepner AD, Ramamurthy R, Krueger DC, Korcarz CE, Binkley N, Stein JH. A prospective randomized controlled trial of the effects of Vitamin D supplementation on cardiovascular disease risk. PLoS ONE. 2012;7(5).

Barnes MS, Horigan G, Cashman KD, Hill TR, Forsythe LK, Lucey AJ, et al. Maintenance of wintertime vitamin D status with cholecalciferol supplementation is not associated with alterations in serum cytokine concentrations among apparently healthy younger or older adults. Journal of Nutrition. 2011;141(3):476-81.

Muldowney S, Lucey AJ, Hill TR, Seamans KM, Taylor N, Wallace JM, et al. Incremental cholecalciferol supplementation up to 15 mug/d throughout winter at 51-55 degrees N has no effect on biomarkers of cardiovascular risk in healthy young and older adults. J Nutr. 2012;142(8):1519-25. Epub 2012/06/29.

Witham MD, Dove FJ, Khan F, Lang CC, Belch JJF, Struthers AD. Effects of Vitamin D supplementation on markers of vascular function after myocardial infarction - A randomised controlled trial. International Journal of Cardiology. 2013;167(3):745-9.

Sharifi N, Amani R, Hajiani E, Cheraghian B. Does vitamin D improve liver enzymes, oxidative stress, and inflammatory biomarkers in adults with non-alcoholic fatty liver disease? A randomized clinical trial. Endocrine. 2014;47(1):70-80.

Chen N, Wan Z, Han S-F, Li B-Y, Zhang Z-L, Qin L-Q. Effect of vitamin D supplementation on the level of circulating high-sensitivity C-reactive protein: a meta-analysis of randomized controlled trials. Nutrients. 2014;6(6):2206-16.

BHALLA AK, AMENTO EP, CLEMENS TL, HOLICK MF, KRANE SM. Specific high-affinity receptors for 1, 25-dihydroxyvitamin D3 in human peripheral blood mononuclear cells: presence in monocytes and induction in T lymphocytes following activation. The Journal of Clinical Endocrinology & Metabolism. 1983;57(6):1308-10.

Cantorna MT, Zhu Y, Froicu M, Wittke A. Vitamin D status, 1, 25-dihydroxyvitamin D3, and the immune system. Am J Clin Nutr. 2004;80(6):1717S-20S.

Adorini L, Penna G, Fibbi B, Maggi M. Vitamin D receptor agonists target static, dynamic, and inflammatory components of benign prostatic hyperplasia. Annals of the New York Academy of Sciences. 2010;1193(1):146-52.

Eleftheriadis T, Antoniadi G, Liakopoulos V, Antoniadis N, Stefanidis I, Galaktidou G. Vitamin D receptor activators and response to injury in kidney diseases. J Nephrol. 2010;23(5):514-24.

Chen Y, Kong J, Sun T, Li G, Szeto FL, Liu W, et al. 1, 25-Dihydroxyvitamin D 3 suppresses inflammation-induced expression of plasminogen activator inhibitor-1 by blocking nuclear factor-κB activation. Archives of biochemistry and biophysics. 2011;507(2):241-7.

IssueVol 3, No 1 (Winter 2017) QRcode
SectionReview Article(s)
CRP inflammation meta-analysis cholecalciferol vitamin D

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Yari Z, Ebrahimof S. Effect of vitamin D supplementation on serum C-reactive protein level: a meta-analysis of randomized controlled trials. J Nutr Sci & Diet. 3(1).