European Journal of Nutrition

, Volume 55, Issue 6, pp 2163–2176 | Cite as

The effect of vitamin D supplementation on selected inflammatory biomarkers in obese and overweight subjects: a systematic review with meta-analysis

  • Małgorzata Jamka
  • Małgorzata Woźniewicz
  • Jarosław Walkowiak
  • Paweł Bogdański
  • Jan Jeszka
  • Marta Stelmach-Mardas
Original Contribution



The objective of this systematic review was to assess the effect of vitamin D supplementation on selected inflammatory biomarkers in obese and overweight subjects.


The search process was based on the selection of publications (DB-RCT and RCT) listed in the following databases: PubMed, Web of Knowledge, Scopus, the Cochrane Library and Embase. To assess the study quality, a nine-point scoring system according to the Newcastle–Ottawa scale was used, and a high-quality study was defined by a threshold of ≥7 points. Thirteen randomized controlled trials were included. The analysed population consisted of 1955 overweight and obese subjects. The mean age ranged from 13.6 to 71.7 years. Changes in the concentration of 25-hydroxycholecalciferol (25(OH)D), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were assessed. To combine individual study results, a meta-analysis was performed.


The baseline levels of 25(OH)D suggested vitamin D deficiency or insufficiency in the analysed population. The vitamin D supplementation did not influence on CRP (std. mean differences −0.11; 95 % CI −0.27–0.04; p = 0.15), TNF-α (std. mean differences −0.13; 95 % CI −0.38–0.12; p = 0.31) and IL-6 concentrations (std. mean differences 0.1; 95 % CI −0.43–0.63; p = 0.71).


This meta-analysis suggests that supplementation with vitamin D does not have a significant influence on changes in the concentration of selected inflammatory biomarkers in the obese and overweight subjects.


Vitamin D Adipokines C-reactive protein Cytokines Dietary supplements Obesity 


Author contributions

MJ and MSM designed the study, searched databases, performed the selection of studies and wrote the manuscript. MSM analysed the data; JW contributed to writing the manuscript and commented on it. MW and PB searched databases and commented on the manuscript. JJ commented on the manuscript. All authors reviewed and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

The manuscript does not contain clinical studies or patient data.

Supplementary material

394_2015_1089_MOESM1_ESM.pdf (1.2 mb)
Supplementary material 1 (PDF 1251 kb)


  1. 1.
    World Health Organization (2015) Obesity and overweight. Fact sheet No. 311 Accessed 24 January 2015
  2. 2.
    Lai YH, Fang TC (2013) The pleiotropic effect of vitamin D. ISRN Nephrol 2013:898125. doi: 10.5402/2013/898125 CrossRefGoogle Scholar
  3. 3.
    Soares MJ, Pathak K, Calton EK (2014) Calcium and vitamin D in the regulation of energy balance: where do we stand? Int J Mol Sci 15(3):4938–4945. doi: 10.3390/ijms15034938 CrossRefGoogle Scholar
  4. 4.
    Lumeng CN, Saltiel AR (2011) Inflammatory links between obesity and metabolic disease. J Clin Invest 121(6):2111–2117. doi: 10.1172/JCI57132 CrossRefGoogle Scholar
  5. 5.
    Lee BC, Lee J (2014) Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance. Biochim Biophys Acta 1842(3):446–462. doi: 10.1016/j.bbadis.2013.05.017 CrossRefGoogle Scholar
  6. 6.
    Stelmach-Mardas M, Mardas M, Warchoł W, Jamka M, Walkowiak J (2014) Successful maintenance of body weight reduction after individualized dietary counseling in obese subjects. Sci Rep 4:6620. doi: 10.1038/srep06620 CrossRefGoogle Scholar
  7. 7.
    Stelmach-Mardas M, Mardas M, Walkowiak J, Boeing H (2014) Long-term weight status in regainers after weight loss by lifestyle intervention: status and challenges. Proc Nutr Soc 739(4):509–518. doi: 10.1017/S0029665114000718 CrossRefGoogle Scholar
  8. 8.
    Pathak K, Soares MJ, Calton EK, Zhao Y, Hallett J (2014) Vitamin D supplementation and body weight status: a systematic review and meta-analysis of randomized controlled trials. Obes Rev 15(6):528–537. doi: 10.1111/obr.12162 CrossRefGoogle Scholar
  9. 9.
    Chen N, Wan Z, Han SF, Li BY, Zhang ZL, Qin LQ (2014) Effect of vitamin D supplementation on the level of circulating high-sensitivity C-reactive protein: a meta-analysis of randomized controlled trials. Nutrients 6(6):2206–2216. doi: 10.3390/nu6062206 CrossRefGoogle Scholar
  10. 10.
    Laird E, McNulty H, Ward M, Hoey L, McSorley E, Wallace JM et al (2014) Vitamin D deficiency is associated with inflammation in older Irish adults. J Clin Endocrinol Metab 99(5):1807–1815. doi: 10.1210/jc.2013-3507 CrossRefGoogle Scholar
  11. 11.
    Zanetti M, Harris SS, Dawson-Hughes B (2014) Ability of vitamin D to reduce inflammation in adults without acute illness. Nutr Rev 72(2):95–98. doi: 10.1111/nure.12095 CrossRefGoogle Scholar
  12. 12.
    Bellia A, Garcovich C, D’Adamo M, Lombardo M, Tesauro M, Donadel G et al (2013) Serum 25-hydroxyvitamin D levels are inversely associated with systemic inflammation in severe obese subjects. Intern Emerg Med 8(1):33–40. doi: 10.1007/s11739-011-0559-x CrossRefGoogle Scholar
  13. 13.
    Svoren BM, Volkening LK, Wood JR, Laffel LM (2009) Significant vitamin D deficiency in youth with type 1 diabetes mellitus. J Pediatr 154(1):132–134. doi: 10.1016/j.jpeds.2008.07.015 CrossRefGoogle Scholar
  14. 14.
    Ulitsky A, Ananthakrishnan AN, Naik A, Skaros S, Zadvornova Y, Binion DG et al (2011) Vitamin D deficiency in patients with inflammatory bowel disease: association with disease activity and quality of life. JPEN J Parenter Enteral Nutr 35(3):308–316. doi: 10.1177/0148607110381267 CrossRefGoogle Scholar
  15. 15.
    Brock K, Huang WY, Fraser DR, Ke L, Tseng M, Stolzenberg-Solomon R et al (2010) Low vitamin D status is associated with physical inactivity, obesity and low vitamin D intake in a large US sample of healthy middle-aged men and women. J Steroid Biochem Mol Biol 121(1–2):462–466. doi: 10.1016/j.jsbmb.2010.03.091 CrossRefGoogle Scholar
  16. 16.
    Turer CB, Lin H, Flores G (2013) Prevalence of vitamin D deficiency among overweight and obese US children. Pediatrics 131(1):e152–e161. doi: 10.1542/peds.2012-1711 CrossRefGoogle Scholar
  17. 17.
    Nimitphong H, Chanprasertyothin S, Jong-Jaroenprasert W, Ongphiphadhanakul B (2009) The association between vitamin D status and circulating adiponectin independent of adiposity in subjects with abnormal glucose tolerance. Endocrine 36(2):205–210. doi: 10.1007/s12020-009-9216-9 CrossRefGoogle Scholar
  18. 18.
    Dutta D, Mondal SA, Choudhuri S, Maisnam I, Hasanoor Reza AH, Bhattacharya B et al (2014) Vitamin-D supplementation in prediabetes reduced progression to type 2 diabetes and was associated with decreased insulin resistance and systemic inflammation: an open label randomized prospective study from Eastern India. Diabetes Res Clin Pract 103(3):e18–e23. doi: 10.1016/j.diabres.2013.12.044 CrossRefGoogle Scholar
  19. 19.
    Neyestani TR, Nikooyeh B, Alavi-Majd H, Shariatzadeh N, Kalayi A, Tayebinejad N et al (2012) Improvement of vitamin D status via daily intake of fortified yogurt drink either with or without extra calcium ameliorates systemic inflammatory biomarkers, including adipokines, in the subjects with type 2 diabetes. J Clin Endocrinol Metab 97(6):2005–2011. doi: 10.1210/jc.2011-3465 CrossRefGoogle Scholar
  20. 20.
    Jamka M, Woźniewicz M, Bogdański P, Stelmach-Mardas M (2015) Effect of vitamin D supplementation on inflammatory cytokines, adipokines and C-reactive protein in obese subjects. PROSPERO: CRD4201501641. Accessed 4 Feb 2015
  21. 21.
    World Health Organization (2004) BMI classification. Global database on body mass index. Accessed 2 Jan 2015
  22. 22.
    Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M et al (2014) The Newcastle–Ottawa Scale (NOS) for Assessing the quality of nonrandomised studies in meta-analyses. Accessed 8 June 2015
  23. 23.
    Hozo SP, Djulbegovic B, Hozo I (2005) Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 5:13CrossRefGoogle Scholar
  24. 24.
    Normand SL (1999) Meta-analysis: formulating, evaluating, combining, and reporting. Stat Med 18(3):321–359CrossRefGoogle Scholar
  25. 25.
    de Medeiros Cavalcante IG, Silva AS, Costa MJ, Persuhn DC, Issa CI, de Luna Freire TL et al (2015) Effect of vitamin D3 supplementation and influence of BsmI polymorphism of the VDR gene of the inflammatory profile and oxidative stress in elderly women with vitamin D insufficiency: vitamin D3 megadose reduces inflammatory markers. Exp Gerontol 66:10–16. doi: 10.1016/j.exger.2015.03.011 CrossRefGoogle Scholar
  26. 26.
    Duggan C, de Dieu Tapsoba J, Mason C, Imayama I, Korde L, Wang CY et al (2015) Effect of vitamin D3 supplementation in combination with weight loss on inflammatory biomarkers in postmenopausal women: a randomized controlled trial. Cancer Prev Res (Phila) 8(7):628–635. doi: 10.1158/1940-6207.CAPR-14-0449 CrossRefGoogle Scholar
  27. 27.
    Shah S, Wilson DM, Bachrach LK (2015) Large doses of vitamin D fail to increase 25-hydroxyvitamin D levels or to alter cardiovascular risk factors in obese adolescents: a pilot study. J Adolesc Health 57(1):19–23. doi: 10.1016/j.jadohealth.2015.02.006 CrossRefGoogle Scholar
  28. 28.
    Chandler PD, Scott JB, Drake BF, Ng K, Manson JE, Rifai N et al (2014) Impact of vitamin D supplementation on inflammatory markers in African Americans: results of a four-arm, randomized, placebo-controlled trial. Cancer Prev Res (Phila) 7(2):218–225. doi: 10.1158/1940-6207.CAPR-13-0338-T CrossRefGoogle Scholar
  29. 29.
    Mason C, Xiao L, Imayama I, Duggan C, Wang CY, Korde L et al (2014) Vitamin D3 supplementation during weight loss: a double-blind randomized controlled trial. Am J Clin Nutr 99(5):1015–1025. doi: 10.3945/ajcn.113.073734 CrossRefGoogle Scholar
  30. 30.
    Nader NS, Aguirre Castaneda R, Wallace J, Singh R, Weaver A, Kumar S (2014) Effect of vitamin D3 supplementation on serum 25(OH)D, lipids and markers of insulin resistance in obese adolescents: a prospective, randomized, placebo-controlled pilot trial. Horm Res Paediatr 82(2):107–112. doi: 10.1159/000362449 CrossRefGoogle Scholar
  31. 31.
    Wamberg L, Kampmann U, Stødkilde-Jørgensen H, Rejnmark L, Pedersen SB, Richelsen B (2013) 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 24(7):644–649. doi: 10.1016/j.ejim.2013.03.005 CrossRefGoogle Scholar
  32. 32.
    Beilfuss J, Berg V, Sneve M, Jorde R, Kamycheva E (2012) Effects of a 1-year supplementation with cholecalciferol on interleukin-6, tumor necrosis factor-alpha and insulin resistance in overweight and obese subjects. Cytokine 60(3):870–874. doi: 10.1016/j.cyto.2012.07.032 CrossRefGoogle Scholar
  33. 33.
    Carrillo AE, Flynn MG, Pinkston C, Markofski MM, Jiang Y, Donkin SS et al (2012) Vitamin D supplementation during exercise training does not alter inflammatory biomarkers in overweight and obese subjects. Eur J Appl Physiol 112(8):3045–3052. doi: 10.1007/s00421-011-2279-3 CrossRefGoogle Scholar
  34. 34.
    Jorde R, Sneve M, Torjesen PA, Figenschau Y, Gøransson LG, Omdal R (2010) No effect of supplementation with cholecalciferol on cytokines and markers of inflammation in overweight and obese subjects. Cytokine 50(2):175–180. doi: 10.1016/j.cyto.2009.12.006 CrossRefGoogle Scholar
  35. 35.
    von Hurst PR, Stonehouse W, Coad J (2010) 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. Br J Nutr 103(4):549–555. doi: 10.1017/S0007114509992017 CrossRefGoogle Scholar
  36. 36.
    Zittermann A, Frisch S, Berthold HK, Götting C, Kuhn J, Kleesiek K et al (2009) Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers. Am J Clin Nutr 89(5):1321–1327. doi: 10.3945/ajcn.2008.27004 CrossRefGoogle Scholar
  37. 37.
    Pittas AG, Harris SS, Stark PC, Dawson-Hughes B (2007) The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults. Diabetes Care 30(4):980–986CrossRefGoogle Scholar
  38. 38.
    International Diabetes Federation (2006) The IDF consensus worldwide definition of the metabolic syndrome. Accessed 9 Mar 2015
  39. 39.
    Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP et al (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 96(7):1911–1930. doi: 10.1210/jc.2011-0385 CrossRefGoogle Scholar
  40. 40.
    Chandler PD, Wang L, Zhang X, Sesso HD, Moorthy MV, Obi O et al (2015) Effect of vitamin D supplementation alone or with calcium on adiposity measures: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev 73(9):577–593. doi: 10.1093/nutrit/nuv012 CrossRefGoogle Scholar
  41. 41.
    Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H et al (2006) Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 17(1):4–12Google Scholar
  42. 42.
    Park HS, Park JY, Yu R (2005) Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-alpha and IL-6. Diabetes Res Clin Pract 69(1):29–35CrossRefGoogle Scholar
  43. 43.
    Colin EM, Asmawidjaja PS, van Hamburg JP, Mus AM, van Driel M, Hazes JM et al (2010) 1,25-Dihydroxyvitamin D3 modulates Th17 polarization and interleukin-22 expression by memory T cells from patients with early rheumatoid arthritis. Arthritis Rheum 62(1):132–142. doi: 10.1002/art.25043 CrossRefGoogle Scholar
  44. 44.
    Khoo AL, Chai LY, Koenen HJ, Sweep FC, Joosten I, Netea MG et al (2011) Regulation of cytokine responses by seasonality of vitamin D status in healthy individuals. Clin Exp Immunol 164(1):72–79. doi: 10.1111/j.1365-2249.2010.04315.x CrossRefGoogle Scholar
  45. 45.
    Müller K, Diamant M, Bendtzen K (1991) Inhibition of production and function of interleukin-6 by 1,25-dihydroxyvitamin D3. Immunol Lett 28(2):115–120CrossRefGoogle Scholar
  46. 46.
    Al-Rasheed NM, Al-Rasheed NM, Bassiouni YA, Hasan IH, Al-Amin MA, Al-Ajmi HN et al (2015) Vitamin D attenuates pro-inflammatory TNF-α cytokine expression by inhibiting NF-кB/p65 signaling in hypertrophied rat hearts. J Physiol Biochem. 71(2):289–299CrossRefGoogle Scholar
  47. 47.
    Zhu Y, Mahon BD, Froicu M, Cantorna MT (2004) Calcium and 1α,25-dihydroxyvitamin D3 target the TNF-α pathway to suppress experimental inflammatory bowel disease. Eur J Immunol 35(1):217–224CrossRefGoogle Scholar
  48. 48.
    Malek HA, Shata A (2014) Effect of a high dose of vitamin D on a rabbit model of atherosclerosis. Int J Immunopathol Pharmacol 27(2):195–201Google Scholar
  49. 49.
    Shea MK, Booth SL, Massaro JM, Jacques PF, D’Agostino RB Sr, Dawson-Hughes B et al (2008) Vitamin K and vitamin D status: associations with inflammatory markers in the Framingham Offspring Study. Am J Epidemiol 167(3):313–320CrossRefGoogle Scholar
  50. 50.
    Fisher G, Hyatt TC, Hunter GR, Oster RA, Desmond RA, Gower BA (2011) Effect of diet with and without exercise training on markers of inflammation and fat distribution in overweight women. Obesity (Silver Spring) 19(6):1131–1136. doi: 10.1038/oby.2010.310 CrossRefGoogle Scholar
  51. 51.
    Camhi SM, Bray GA, Bouchard C, Greenway FL, Johnson WD, Newton RL et al (2011) The relationship of waist circumference and BMI to visceral, subcutaneous, and total body fat: sex and race differences. Obesity (Silver Spring) 19(2):402–428. doi: 10.1038/oby.2010.248 CrossRefGoogle Scholar
  52. 52.
    Vimaleswaran KS, Berry DJ, Lu C, Tikkanen E, Pilz S, Hiraki LT et al (2013) Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Med 10(2):e1001383. doi: 10.1371/journal.pmed.1001383 CrossRefGoogle Scholar
  53. 53.
    Pereira-Santos M, Costa PR, Assis AM, Santos CA, Santos DB (2015) Obesity and vitamin D deficiency: a systematic review and meta-analysis. Obes Rev 16(4):341–349. doi: 10.1111/obr.12239 CrossRefGoogle Scholar
  54. 54.
    Slusher AL, McAllister MJ, Huang CJ (2015) A therapeutic role for vitamin D on obesity-associated inflammation and weight-loss intervention. Inflamm Res 64(8):565–575. doi: 10.1007/s00011-015-0847-4 CrossRefGoogle Scholar
  55. 55.
    Tripkovic L, Lambert H, Hart K, Smith CP, Bucca G, Penson S et al (2012) Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. Am J Clin Nutr 95(6):1357–1364. doi: 10.3945/ajcn.111.031070 CrossRefGoogle Scholar
  56. 56.
    Harris SS, Pittas AG, Palermo NJ (2012) A randomized, control-controlled trial of vitamin D supplementation to improve glycaemia in overweight and obese African Americans. Diabetes Obes Metab 14(9):789–794. doi: 10.1111/j.1463-1326.2012.01605.x CrossRefGoogle Scholar
  57. 57.
    Kull M, Kallikorm R, Lember M (2009) Body mass index determines sunbathing habits: implications on vitamin D levels. Intern Med J 39(4):256–258. doi: 10.1111/j.1445-5994.2009.01900.x CrossRefGoogle Scholar
  58. 58.
    Caballero AE, Bousquet-Santos K, Robles-Osorio L, Montagnani V, Soodini G, Porramatikul S et al (2008) Overweight Latino children and adolescents have marked endothelial dysfunction and subclinical vascular inflammation in association with excess body fat and insulin resistance. Diabetes Care 31(3):576–582CrossRefGoogle Scholar
  59. 59.
    Wei J, Xu H, Davies JL, Hemmings GP (1992) Increase of plasma IL-6 concentration with age in healthy subjects. Life Sci 51(25):1953–1956CrossRefGoogle Scholar
  60. 60.
    Hager K, Machein U, Krieger S, Platt D, Seefried G, Bauer J (1994) Interleukin-6 and selected plasma proteins in healthy persons of different ages. Neurobiol Aging 15(6):771–772CrossRefGoogle Scholar
  61. 61.
    Bruunsgaard H, Andersen-Ranberg K, Jeune B, Pedersen AN, Skinhøj P, Pedersen BK (1999) A high plasma concentration of TNF-alpha is associated with dementia in centenarians. J Gerontol A Biol Sci Med Sci 54(7):M357–M364CrossRefGoogle Scholar
  62. 62.
    Ballou SP, Lozanski FB, Hodder S et al (1996) Quantitative and qualitative alterations of acute-phase proteins in healthy elderly persons. Age Ageing 25:224–230CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Małgorzata Jamka
    • 1
  • Małgorzata Woźniewicz
    • 1
  • Jarosław Walkowiak
    • 2
  • Paweł Bogdański
    • 3
  • Jan Jeszka
    • 1
  • Marta Stelmach-Mardas
    • 2
    • 4
  1. 1.Department of Human Nutrition and HygienePoznan University of Life SciencesPoznanPoland
  2. 2.Department of Paediatric Gastroenterology and Metabolic DiseasesPoznan University of Medical SciencesPoznanPoland
  3. 3.Department of Education and Obesity Treatment and Metabolic DisordersPoznan University of Medical SciencesPoznanPoland
  4. 4.Department of EpidemiologyGerman Institute of Human Nutrition Potsdam-RehbrückeNuthetalGermany

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