Skip to main content
SpringerLink
Log in

The effects of vitamin D supplementation on proatherogenic inflammatory markers and carotid intima media thickness in subjects with metabolic syndrome: a randomized double-blind placebo-controlled clinical trial

  • Endocrine Trials
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

Metabolic syndrome may predispose to cardiovascular diseases. Since, in recent studies, vitamin D is advocated for cardioprotective roles, this study was designed to investigate the effects of vitamin D supplementation on proatherogenic inflammatory markers and common carotid intima media thickness in subjects with metabolic syndrome.

Methods

This randomized double blind clinical trial was conducted in Tabriz, Iran. Eligible subjects (n = 80) with metabolic syndrome were recruited thorough advertisement and randomized to receive either vitamin D (50,000 IU/week) or matching placebo for 16 weeks. Interlukin-6, high sensitivity C-reactive protein, vascular cell adhesion molecule-1, E-selectin, and common carotid intima media thickness were measured at the beginning and end of the study. The study was registered at http://www.irct.ir (code: IRCT201409033140N14).

Results

Sixteen weeks supplementation with vitamin D increased median of serum 25-hydroxy vitamin D [25(OH)D] and mean calcium levels (p < 0.001) in the intervention group. There was also a significant difference in parathyroid hormone level at the end of the study (p < 0.001). Vitamin D treatment reduced IL-6 level after 16 weeks (p = 0.027). Compared to baseline, vascular cell adhesion molecule-1 and E-selectin levels decreased significantly in vitamin D treated subjects; however, there were no significant differences between two groups. No effect of vitamin D supplementation was observed in either common carotid intima media thickness or high sensitivity C-reactive protein concentrations at the end of the study (p > 0.05).

Conclusions

Vitamin D supplementation improved some proatherogenic inflammatory markers in subjects with metabolic syndrome. No changes of high sensitivity C-reactive protein and carotid intima media thickness were shown after 16 weeks.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. K. Alberti, R.H. Eckel, S.M. Grundy, P.Z. Zimmet, J.I. Cleeman, K.A. Donato, J.C. Fruchart, W.P. James, C.M. Loria, S.C. Smith, Harmonizing the metabolic syndrome a joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; American heart association; world heart federation; international atherosclerosis society; and international association for the study of obesity. Circulation. 120, 1640–1645 (2009)

    Article  CAS  PubMed  Google Scholar 

  2. E. Kaperonis, C. Liapis, J. Kakisis, D. Dimitroulis, V. Papavassiliou, Inflammation and atherosclerosis. Eur. J. Vasc. Endovasc. Surg. 31, 386–393 (2006)

    Article  CAS  PubMed  Google Scholar 

  3. E. Ingelsson, J. Hulthe, L. Lind, Inflammatory markers in relation to insulin resistance and the metabolic syndrome. Eur. J. Clin. Invest. 38, 502–509 (2008)

    Article  CAS  PubMed  Google Scholar 

  4. H. Schuett, M. Luchtefeld, C. Grothusen, K. Grote, B. Schieffer, How much is too much? Interleukin-6 and its signalling in atherosclerosis. Thromb. Haemost. 102, 215–222 (2009)

    Article  CAS  PubMed  Google Scholar 

  5. U.I. Christiana, A.E. Casimir, A.A. Nicholas, M.C. Christian, A.I. Obiefuna, Plasma levels of inflammatory cytokines in adult Nigerians with the metabolic syndrome. Niger. Med. J. 57, 64–68 (2016)

    Article  PubMed  Google Scholar 

  6. T.W. Weiss, H. Arnesen, I. Seljeflot, Components of the interleukin-6 transsignalling system are associated with the metabolic syndrome, endothelial dysfunction and arterial stiffness. Metabolism. 62, 1008–1013 (2013)

    Article  CAS  PubMed  Google Scholar 

  7. J.F. Polak, M.J. Pencina, K.M. Pencina, C.J. O’Donnell, P.A. Wolf, R.B. D’Agostino Sr, Carotid-wall intima–media thickness and cardiovascular events. New.Eng. J. Med. 365, 213–221 (2011)

    Article  CAS  PubMed  Google Scholar 

  8. P.J. Touboul, D.E. Grobbee, H. den Ruijter, Assessment of subclinical atherosclerosis by carotid intima media thickness: technical issues. Eur. J. Prev. Cardiol 19, 18–24 (2012)

    Article  PubMed  Google Scholar 

  9. A.G. Panayiotou, M. Griffin, P. Kouis, T. Tyllis, N. Georgiou, D. Bond, A.N. Nicolaides, Association between presence of the metabolic syndrome and its components with carotid intima-media thickness and carotid and femoral plaque area: a population study. Diabetol. Metab. Syndr 5, 44–53 (2013)

    Article  PubMed  Google Scholar 

  10. L.H. Li, X.Y. Yin, C.Y. Yao, C.X. Zhu, X.H. Wu, Serum 25-hydroxyvitamin D, parathyroid hormone, and their association with metabolic syndrome in Chinese. Endocrine. 44, 465–472 (2013)

    Article  CAS  PubMed  Google Scholar 

  11. C. Gagnon, Z.X. Lu, D.J. Magliano, D.W. Dunstan, J.E. Shaw, P.Z. Zimmet, K. Sikaris, P.R. Ebeling, R.M. Daly, Low Serum 25-Hydroxyvitamin D is associated with increased risk of the development of the metabolic syndrome at five years: results from a national, population-based prospective study (The Australian Diabetes, Obesity and Lifestyle Study: AusDiab). J. Clin. Endocrinol. Metab. 97, 1953–1961 (2012)

    Article  CAS  PubMed  Google Scholar 

  12. G. Muscogiuri, V. Nuzzo, A. Gatti, A. Zuccoli, S. Savastano, C. Di Somma, R. Pivonello, F. Orio, A. Cola, Hypovitaminosis D: a novel risk factor for coronary heart disease in type 2 diabetes? Endocrine. 51, 268–273 (2016)

    Article  CAS  PubMed  Google Scholar 

  13. S.Y. Ju, H.S. Jeong, D.H. Kim, Blood vitamin D status and metabolic syndrome in the general adult population: a dose-response meta-analysis. J. Clin. Endocrinol. Metab. 17, 1053–1063 (2013)

    Google Scholar 

  14. R. Bouillon, L. Verlinden, Does a better vitamin D status help to reduce cardiovascular risks and events. Endocrine. 47, 662–663 (2014)

    Article  CAS  PubMed  Google Scholar 

  15. A. Di Nisio, L.D. Toni, E. D’Addato, M.R. Pizzo, P. Sabatino, C. Foresta, 25-Hydroxy vitamin D insufficiency discriminates cardiovascular risk factors accumulation in peri-pubertal boys undergoing overweight screening. Endocrine. 53, 530–537 (2016)

    Article  PubMed  Google Scholar 

  16. G. Sarno, G. Daniele, G. Tirabassi, A.O. Chavez, O.O. Ojo, F. Orio, H. Kahleova, G. Balercia, W.B. Grant, P.D. Rosa, A. Colao, G. Muscogiuri, The impact of vitamin D deficiency on patients ongoing kidney transplantation: focus on cardiovascular, metabolic, and endocrine outcomes. Endocrine. 50, 568–574 (2015)

    Article  CAS  PubMed  Google Scholar 

  17. D. Martins, M. Wolf, D. Pan, A. Zadshir, N. Tareen, R. Thadhani, A. Felsenfeld, B. Levine, R. Mehrotra, K. Norris, Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the third national health and nutrition examination survey. Arch. Intern. Med. 167, 1159–1165 (2007)

    Article  CAS  PubMed  Google Scholar 

  18. E. Giovannucci, Y. Liu, B.W. Hollis, E.B. Rimm, 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch. Intern. Med. 168, 1174–1180 (2008)

    Article  CAS  PubMed  Google Scholar 

  19. T. Skaaby, L.L.N. Husemoen, C. Pisinger, T. Jørgensen, B.H. Thuesen, M. Fenger, A. Linneberg, Vitamin D status and incident cardiovascular disease and all-cause mortality: a general population study. Endocrine. 43, 618–625 (2013)

    Article  CAS  PubMed  Google Scholar 

  20. E. Kassi, C. Adamopoulos, E.K. Basdra, A.G. Papavassiliou, Role of vitamin D in atherosclerosis. Circulation. 128, 2517–2531 (2013)

    Article  Google Scholar 

  21. M. Bozic, Á. Álvarez, C. de Pablo, M.D. Sanchez-Niño, A. Ortiz, X. Dolcet, M. Encinas, E. Fernandez, J.M. Valdivielso, Impaired vitamin D signaling in endothelial cell Leads to an enhanced leukocyte-endothelium interplay: implications for atherosclerosis development. PLoS. ONE. 10, e0136863 (2015)

    Article  PubMed  Google Scholar 

  22. H. Dobnig, S. Pilz, H. Scharnagl, W. Renner, U. Seelhorst, B. Wellnitz, J. Kinkeldei, B.O. Boehm, G. Weihrauch, W. Maerz, Independent association of low serum 25-hydroxyvitamin D and 1, 25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Arch. Intern. Med. 168, 1340–1349 (2008)

    Article  CAS  Google Scholar 

  23. X. Sun, Z.B. Cao, Y. Zhang, Y. Ishimi, I. Tabata, M. Higuchi, Association between serum 25-hydroxyvitamin D and inflammatory cytokines in healthy adults. Nutrients 6, 221–230 (2014)

    Article  PubMed  Google Scholar 

  24. J. Beilfuss, V. Berg, M. Sneve, R. Jorde, E. Kamycheva, 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, 870–874 (2012)

    Article  CAS  Google Scholar 

  25. S.J. Sokol, V. Srinivas, J.P. Crandall, M. Kim, G. Tellides, A.H. Lebastchi, Y. Yu, A.K. Gupta, M.H. Alderman, The effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease. Vasc. Med. 17, 394–404 (2012)

    Article  Google Scholar 

  26. G. Targher, L. Bertolini, R. Padovani, L. Zenari, L. Scala, M. Cigolini, G. Arcaro, Serum 25‐hydroxyvitamin D3 concentrations and carotid artery intima‐media thickness among type 2 diabetic patients. Clin. Endocrinol. 65, 593–597 (2006)

    Article  CAS  Google Scholar 

  27. A.L. Carrelli, M.D. Walker, H. Lowe, D.J. McMahon, T. Rundek, R.L. Sacco, Vitamin D deficiency is associated with subclinical carotid atherosclerosis. The Northern Manhattan study. Stroke. 42, 2240–2245 (2011)

    Article  CAS  PubMed  Google Scholar 

  28. V. Carnevale, R. Minonne, A. De Matthaeis, M.A. Annese, P. Tabacco, P. D’Arcangelo, G. D’Amico, A. Scillitani, Carotid intima-media thickness is not associated with vitamin D and PTH levels in patients admitted to an internal medicine department. Endocrine. 47, 833–838 (2014)

    Article  CAS  Google Scholar 

  29. M. Blondon, M. Sachs, A.N. Hoofnagle, J.H. Ix, E.D. Michos, C. Korcarz, A.D. Gepner, D.S. Siscovick, J.D. Kaufman, J.H. Stei, B. Kestenbaum, I.H. de Boer, 25-Hydroxyvitamin D and parathyroid hormone are not associated with carotid intima-media thickness or plaque in the multi-ethnic study of atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 33, 2639–2645 (2013)

    Article  CAS  PubMed  Google Scholar 

  30. K.M. Gurses, L. Tokgozoglu, M.U. Yalcin, D. Kocyigit, M. Dural, H. Canpinar, H. Yorgun, M.L. Sahiner, E.B. Kaya, S. Akin, A. Gurlek, D. Guc, K. Aytemir, Markers of subclinical atherosclerosis in premenopausal women with vitamin D deficiency and effect of vitamin D replacement. Atherosclerosis. 237, 784–789 (2014)

    Article  CAS  PubMed  Google Scholar 

  31. S. Salekzamani, H. Mehralizadeh, A. Ghezel, Y. Salekzamani, M.A. Jafarabadi, A.S. Bavil, B.P. Gargari, Effect of high-dose vitamin D supplementation on cardiometabolic risk factors in subjects with metabolic syndrome: a randomized controlled double-blind clinical trial. J. Endocrinol. Invest. 39, 1303–1313 (2016)

    Article  CAS  PubMed  Google Scholar 

  32. F. Azizi, F. Hadaegh, D. Khalili, A. Esteghamati, F. Hosseinpanah, A. Delavari, B. Larijani, P. Mirmiran, A. Zabetian, Y. Mehrabi, R. Kelishadi, H. Aghajani, Appropriate definition of metabolic syndrome among Iranian adults: report of the Iranian National Committee of Obesity. Arch. Iran. Med. 13, 426–428 (2010)

    PubMed  Google Scholar 

  33. M. Saghaei, Random allocation software for parallel group randomized trials. BMC. Med. Res. Methodol. 4, 26–31 (2004)

    Article  PubMed  Google Scholar 

  34. M.F. Holick, N.C. Binkley, H.A. Bischoff-Ferrari, C.M. Gordon, D.A. Hanley, R.P. Heaney, M.H. Murad, C.M. Weaver, Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 96, 1911–1930 (2011)

    Article  CAS  PubMed  Google Scholar 

  35. R.P. Heaney, Guidelines for optimizing design and analysis of clinical studies of nutrient effects. Nutr. Rev. 72, 48–54 (2014)

    Article  PubMed  Google Scholar 

  36. A.C. Ross, J.E. Manson, S.A. Abrams, J.F. Aloia, P.M. Brannon, S.K. Clinton, R.A. Durazo-Arvizu, J.C. Gallagher, R.L. Gallo, G. Jones, C.S. Kovacs, S.T. Mayne, C.J. Rosen, S.A. Shapses, The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J. Clin. Endocrinol. Metab. 96, 53–58 (2011)

    Article  CAS  Google Scholar 

  37. IPAQ Research Committee, Guidelines for data processing and analysis of the International Physical Activity Questionnaire (IPAQ)–short and long forms. Retrieved September 17, 2008 (2005)

  38. C.L. Craig, A.L. Marshall, M. Sjostrom, A.E. Bauman, M.L. Booth, B.E. Ainsworth, M. Pratt, U. Ekelund, A. Yngve, J.F. Sallis, P. Oja, International physical activity questionnaire: 12-country reliability and validity. Med. Sci. Sports. Exerc. 195, 3508–1381 (2003)

    Google Scholar 

  39. A.G. Pittas, S.S. Harris, P.C. Stark, B. Dawson-Haghes, the effects of calcium and vitamin D supplementation on blood glugose and markers of inflammation in nondiabetic adults. Diabetes. Care. 30, 980–986 (2007)

    Article  CAS  PubMed  Google Scholar 

  40. M. Kim, W. Na, C. Sohn, Correlation between vitamin D and cardiovascular disease predictors in overweight and obese Koreans. J. Clin. Biochem. Nutr. 52, 167–171 (2013)

    Article  CAS  PubMed  Google Scholar 

  41. S. Shab‐Bidar, T.R. Neyestani, A. Djazayery, M.R. Eshragian, A. Houshiarrad, A. Kalayi, N. Shariatzadeh, N. Khalaji, A. Garavi, Improvement of vitamin D status resulted in amelioration of biomarkers of systemic inflammation in the subjects with type 2 diabetes. Diabetes. Metab. Res. Rev. 28, 424–430 (2012)

    Article  PubMed  Google Scholar 

  42. R. Jorde, M. Sneve, P.A. Torjesen, Y. Figenschau, L.G. Gøransson, R. Omdal, No effect of supplementation with cholecalciferol on cytokines and markers of inflammation in overweight and obese subjects. Cytokine. 50, 175–180 (2010)

    Article  CAS  PubMed  Google Scholar 

  43. P.D. Chandler, J.B. Scott, B.F. Drake, K. Ng, J.E. Manson, N. Rifai, A.T. Chan, G.G. Bennett, B.W. Hollis, E.L. Giovanucci, K.M. Emmons, C.S. Fuch, Impact of vitamin D supplementation on inflammatory markers in African Americans: results of a four-arm, randomized, placebo-controlled trial. Cancer. Prev. Res 7, 218–225 (2014)

    Article  CAS  Google Scholar 

  44. M. Gannage-Yared, M. Azoury, I. Mansour, R. Baddoura, G. Halaby, R. Naaman, Effects of a short-term calcium and vitamin D treatment on serum cytokines, bone markers, insulin and lipid concentrations in healthy post-menopausal women. J. Endocrinol. Invest. 26, 748–753 (2003)

    Article  CAS  PubMed  Google Scholar 

  45. M. Rohla, T. Weiss, Metabolic syndrome, inflammation and atherothrombosis. Hämostaseologie 33, 283–294 (2013)

    Article  CAS  PubMed  Google Scholar 

  46. P.M. Ridker, N. Rifai, M.J. Stampfer, C.H. Hennekens, Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation. 101, 1767–1772 (2000)

    Article  CAS  PubMed  Google Scholar 

  47. C. Langenberg, J. Bergstrom, C. Scheidt-Nave, J. Pfleischifter, E. Barret-Connor, Cardiovascular death and the metabolic syndrome–role of adiposity-signaling hormones and inflammatory markers. Diabetes. Care. 29, 1363–9136 (2006)

    Article  CAS  PubMed  Google Scholar 

  48. C.M. Matter, C. Handschin, RANTES (regulated on activation, normal T cell expressed and secreted), inflammation, obesity, and the metabolic syndrome. Circulation. 115, 946–948 (2007)

    Article  PubMed  Google Scholar 

  49. M.M. Assimon, P.V. Salenger, H.A. EL‐Fawal, D.L. Mason, Nutritional vitamin D supplementation in haemodialysis: a potential vascular benefit? Nephrology. 17, 237–242 (2012)

    Article  CAS  PubMed  Google Scholar 

  50. K. Kudo, S. Hasegawa, Y. Suzuki et al., 1α, 25-Dihydroxyvitamin D 3 inhibits vascular cellular adhesion molecule-1 expression and interleukin-8 production in human coronary arterial endothelial cells. J. Steroid. Biochem. Mol. Biol. 132, 290–294 (2012)

    Article  CAS  PubMed  Google Scholar 

  51. M. Kocijancic, Z. Cubranic, B. Vujicic, S. Racki, S. Dvornik, L. Zaputovic, Soluble intracellular adhesion molecule-1 and omentin-1 as potential biomarkers of subclinical atherosclerosis in hemodialysis patients. Int. Urol. Nephrol. 48, 1145–1154 (2016)

    Article  CAS  PubMed  Google Scholar 

  52. M. Aviram, M. Rosenblat, D. Gaitini, S. Nitecki, A. Hoffman, L. Dornfeld, N. Volkova, D. Presser, J. Attias, H. Liker, T. Hayek, Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clin. Nutr. 23, 423–433 (2004)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was funded by the Research Vice Chancellor, Tabriz University of Medical Sciences (Tabriz, Iran); Grant Number (5/71/1353). The results of this article are derived from the Ph.D. thesis of Shabnam Salekzamani (No. D/36) registered in the Tabriz University of Medical Sciences, Tabriz, Iran. The authors thank the staff of Nutrition Research center for their kindly cooperation in this study. The authors express gratitude to Dr. Navid Heydari for refining the manuscript language. The authors also appreciate all the patients for their participation in this research.

Author information

Authors and Affiliations

  1. Talented Students Center, Student Research Committee, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Shabnam Salekzamani

  2. Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Abolhassan Shakeri Bavil

  3. Student Research Committee, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Hossein Mehralizadeh

  4. Road Traffic lnjury Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Mohammad Asghari Jafarabadi

  5. Department of Statistics and Epidemiology, Faculty of Health, Tabriz University of Medical Sciences, Tabriz, Iran

    Mohammad Asghari Jafarabadi

  6. Student Research Committee, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Aymaral Ghezel

  7. Nutrition Research Center, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Bahram Pourghassem Gargari

Authors
  1. Shabnam Salekzamani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abolhassan Shakeri Bavil
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hossein Mehralizadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mohammad Asghari Jafarabadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Aymaral Ghezel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bahram Pourghassem Gargari
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bahram Pourghassem Gargari.

Ethics declarations

Conflict of interest

authors declare that they have no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Salekzamani, S., Bavil, A.S., Mehralizadeh, H. et al. The effects of vitamin D supplementation on proatherogenic inflammatory markers and carotid intima media thickness in subjects with metabolic syndrome: a randomized double-blind placebo-controlled clinical trial. Endocrine 57, 51–59 (2017). https://doi.org/10.1007/s12020-017-1317-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-017-1317-2

Keywords

Search

Navigation