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Effect of vitamin D supplementation on selected inflammatory biomarkers in older adults: a secondary analysis of data from a randomised, placebo-controlled trial

  • Mary Waterhouse (a1) (a2), Bich Tran (a3), Peter R. Ebeling (a2) (a4), Dallas R. English (a5) (a6), Robyn M. Lucas (a7) (a8), Alison J. Venn (a9), Penelope M. Webb (a1), David C. Whiteman (a1) (a2) and Rachel E. Neale (a1) (a2)...

Abstract

Observational studies have suggested that 25-hydroxyvitamin D (25(OH)D) levels are associated with inflammatory markers. Most trials reporting significant associations between vitamin D intake and inflammatory markers used specific patient groups. Thus, we aimed to determine the effect of supplementary vitamin D using secondary data from a population-based, randomised, placebo-controlled, double-blind trial (Pilot D-Health trial 2010/0423). Participants were 60- to 84-year-old residents of one of the four eastern states of Australia. They were randomly selected from the electoral roll and were randomised to one of three trial arms: placebo (n 214), 750 μg (n 215) or 1500 μg (n 215) vitamin D3, each taken once per month for 12 months. Post-intervention blood samples for the analysis of C-reactive protein (CRP), IL-6, IL-10, leptin and adiponectin levels were available for 613 participants. Associations between intervention group and biomarker levels were evaluated using quantile regression. There were no statistically significant differences in distributions of CRP, leptin, adiponectin, leptin:adiponectin ratio or IL-10 levels between the placebo group and either supplemented group. The 75th percentile IL-6 level was 2·8 pg/ml higher (95 % CI 0·4, 5·8 pg/ml) in the 1500 μg group than in the placebo group (75th percentiles:11·0 v. 8·2 pg/ml), with a somewhat smaller, non-significant difference in 75th percentiles between the 750 μg and placebo groups. Despite large differences in serum 25(OH)D levels between the three groups after 12 months of supplementation, we found little evidence of an effect of vitamin D supplementation on cytokine or adipokine levels, with the possible exception of IL-6.

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Copyright

Corresponding author

* Corresponding author: Dr R. E. Neale, fax +61 7 3845 3502, email rachel.neale@qimrberghofer.edu.au

Footnotes

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These authors contributed equally to this work.

Footnotes

References

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1. Elinav, E, Nowarski, R, Thaiss, CA, et al. (2013) Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer 13, 759771.
2. Ross, R (1999) Atherosclerosis – an inflammatory disease. N Engl J Med 340, 115126.
3. Munoz, LE, Janko, C, Schulze, C, et al. (2010) Autoimmunity and chronic inflammation – two clearance-related steps in the etiopathogenesis of SLE. Autoimmun Rev 10, 3842.
4. van Etten, E & Mathieu, C (2005) Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol 97, 93101.
5. D’Ambrosio, D, Cippitelli, M, Cocciolo, MG, et al. (1998) Inhibition of IL-12 production by 1,25-dihydroxyvitamin D3. Involvement of NF-kappaB downregulation in transcriptional repression of the p40 gene. J Clin Invest 101, 252262.
6. Alroy, I, Towers, TL & Freedman, LP (1995) Transcriptional repression of the interleukin-2 gene by vitamin D3: direct inhibition of NFATp/AP-1 complex formation by a nuclear hormone receptor. Mol Cell Biol 15, 57895799.
7. Menendez, C, Lage, M, Peino, R, et al. (2001) Retinoic acid and vitamin D(3) powerfully inhibit in vitro leptin secretion by human adipose tissue. J Endocrinol 170, 425431.
8. Sun, X & Zemel, MB (2007) Calcium and 1,25-dihydroxyvitamin D3 regulation of adipokine expression. Obesity (Silver Spring) 15, 340348.
9. Bellia, A, Garcovich, C, D’Adamo, M, et al. (2013) Serum 25-hydroxyvitamin D levels are inversely associated with systemic inflammation in severe obese subjects. Intern Emerg Med 8, 3340.
10. van de Luijtgaarden, KM, Voute, MT, Hoeks, SE, et al. (2012) Vitamin D deficiency may be an independent risk factor for arterial disease. Eur J Vasc Endovasc Surg 44, 301306.
11. Vilarrasa, N, Vendrell, J, Maravall, J, et al. (2010) Is plasma 25(OH) D related to adipokines, inflammatory cytokines and insulin resistance in both a healthy and morbidly obese population? Endocrine 38, 235242.
12. Kim, M, Na, W & Sohn, C (2013) Correlation between vitamin D and cardiovascular disease predictors in overweight and obese Koreans. J Clin Biochem Nutr 52, 167171.
13. Vaidya, A, Williams, JS & Forman, JP (2012) The independent association between 25-hydroxyvitamin D and adiponectin and its relation with BMI in two large cohorts: the NHS and the HPFS. Obesity (Silver Spring) 20, 186191.
14. Husemoen, LL, Skaaby, T, Martinussen, T, et al. (2014) Investigating the causal effect of vitamin D on serum adiponectin using a Mendelian randomization approach. Eur J Clin Nutr 68, 189195.
15. Khoo, AL, Chai, LY, Koenen, HJ, et al. (2011) Regulation of cytokine responses by seasonality of vitamin D status in healthy individuals. Clin Exp Immunol 164, 7279.
16. Barker, T, Rogers, VE, Levy, M, et al. (2015) Supplemental vitamin D increases serum cytokines in those with initially low 25-hydroxyvitamin D: a randomized, double blind, placebo-controlled study. Cytokine 71, 132138.
17. Asemi, Z, Samimi, M, Tabassi, Z, et al. (2013) Vitamin D supplementation affects serum high-sensitivity C-reactive protein, insulin resistance, and biomarkers of oxidative stress in pregnant women. J Nutr 143, 14321438.
18. Witham, MD, Dove, FJ, Khan, F, et al. (2013) Effects of vitamin D supplementation on markers of vascular function after myocardial infarction – a randomised controlled trial. Int J Cardiol 167, 745749.
19. Abou-Raya, A, Abou-Raya, S & Helmii, M (2013) The effect of vitamin D supplementation on inflammatory and hemostatic markers and disease activity in patients with systemic lupus erythematosus: a randomized placebo-controlled trial. J Rheumatol 40, 265272.
20. Grossmann, RE, Zughaier, SM, Liu, S, et al. (2012) Impact of vitamin D supplementation on markers of inflammation in adults with cystic fibrosis hospitalized for a pulmonary exacerbation. Eur J Clin Nutr 66, 10721074.
21. Schleithoff, SS, Zittermann, A, Tenderich, G, et al. (2006) Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr 83, 754759.
22. Neyestani, TR, Nikooyeh, B, Alavi-Majd, H, 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, 20052011.
23. Barnes, MS, Horigan, G, Cashman, KD, et al. (2011) 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. J Nutr 141, 476481.
24. Pittas, AG, Harris, SS, Stark, PC, et al. (2007) The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults. Diabetes Care 30, 980986.
25. Wood, AD, Secombes, KR, Thies, F, et al. (2012) Vitamin D3 supplementation has no effect on conventional cardiovascular risk factors: a parallel-group, double-blind, placebo-controlled RCT. J Clin Endocrinol Metab 97, 35573568.
26. Yusupov, E, Li-Ng, M, Pollack, S, et al. (2010) Vitamin D and serum cytokines in a randomized clinical trial. Int J Endocrinol 2010, 305054.
27. Jorde, R, Sneve, M, Torjesen, PA, et al. (2010) No effect of supplementation with cholecalciferol on cytokines and markers of inflammation in overweight and obese subjects. Cytokine 50, 175180.
28. Wamberg, L, Kampmann, U, Stodkilde-Jorgensen, H, et al. (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, 644649.
29. Carrillo, AE, Flynn, MG, Pinkston, C, et al. (2012) Vitamin D supplementation during exercise training does not alter inflammatory biomarkers in overweight and obese subjects. Eur J Appl Physiol 112, 30453052.
30. Jorde, R, Strand Hutchinson, M, Kjaergaard, M, et al. (2013) Supplementation with high doses of vitamin D to subjects without vitamin D deficiency may have negative effects: pooled data from four intervention trials in Tromso. ISRN Endocrinol 2013, 348705.
31. Medzhitov, R (2008) Origin and physiological roles of inflammation. Nature 454, 428435.
32. Trinchieri, G (2012) Cancer and inflammation: an old intuition with rapidly evolving new concepts. Annu Rev Immunol 30, 677706.
33. Tran, B, Armstrong, BK, Carlin, JB, et al. (2012) Recruitment and results of a pilot trial of vitamin D supplementation in the general population of Australia. J Clin Endocrinol Metab 97, 44734480.
34. Satoh, N, Naruse, M, Usui, T, et al. (2004) Leptin-to-adiponectin ratio as a potential atherogenic index in obese type 2 diabetic patients. Diabetes Care 27, 24882490.
35. Institute of Medicine (2011) Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press.
36. Hoenig, JM & Heisey, DM (2001) The abuse of power: the pervasive fallacy of power calculations for data analysis. Am Stat 55, 1924.
37. Tilg, H, Dinarello, CA & Mier, JW (1997) IL-6 and APPs: anti-inflammatory and immunosuppressive mediators. Immunol Today 18, 428432.
38. Steensberg, A, Fischer, CP, Keller, C, et al. (2003) IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am J Physiol Endocrinol Metab 285, E433E437.
39. Willheim, M, Thien, R, Schrattbauer, K, et al. (1999) Regulatory effects of 1alpha,25-dihydroxyvitamin D3 on the cytokine production of human peripheral blood lymphocytes. J Clin Endocrinol Metab 84, 37393744.
40. Gepner, AD, Ramamurthy, R, Krueger, DC, et al. (2012) A prospective randomized controlled trial of the effects of vitamin D supplementation on cardiovascular disease risk. PLOS ONE 7, e36617.
41. Beilfuss, J, Berg, V, Sneve, M, et al. (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, 870874.
42. Breslavsky, A, Frand, J, Matas, Z, et al. (2013) Effect of high doses of vitamin D on arterial properties, adiponectin, leptin and glucose homeostasis in type 2 diabetic patients. Clin Nutr 32, 970975.
43. Zhang, Y, Leung, DY, Richers, BN, et al. (2012) Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J Immunol 188, 21272135.
44. Barker, T, Martins, TB, Hill, HR, et al. (2013) Circulating pro-inflammatory cytokines are elevated and peak power output correlates with 25-hydroxyvitamin D in vitamin D insufficient adults. Eur J Appl Physiol 113, 15231534.
45. Tran, B, Armstrong, BK, Ebeling, PR, et al. (2014) Effect of vitamin D supplementation on antibiotic use: a randomized controlled trial. Am J Clin Nutr 99, 156161.
46. Bergman, P, Lindh, AU, Bjorkhem-Bergman, L, et al. (2013) Vitamin D and respiratory tract infections: a systematic review and meta-analysis of randomized controlled trials. PLOS ONE 8, e65835.
47. Chel, V, Wijnhoven, HA, Smit, JH, et al. (2008) Efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents. Osteoporos Int 19, 663671.
48. Hollis, BW & Wagner, CL (2013) Clinical review: the role of the parent compound vitamin D with respect to metabolism and function: why clinical dose intervals can affect clinical outcomes. J Clin Endocrinol Metab 98, 46194628.
49. Ish-Shalom, S, Segal, E, Salganik, T, et al. (2008) Comparison of daily, weekly, and monthly vitamin D3 in ethanol dosing protocols for two months in elderly hip fracture patients. J Clin Endocrinol Metab 93, 34303435.
50. Binkley, N, Gemar, D, Engelke, J, et al. (2011) Evaluation of ergocalciferol or cholecalciferol dosing, 1,600 IU daily or 50,000 IU monthly in older adults. J Clin Endocrinol Metab 96, 981988.
51. Vieth, R (2008) Comment on Chel et al.: efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents. Osteoporos Int 19, 721722 (author reply 723).

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