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Horm Metab Res 2018; 50(08): 587-596
DOI: 10.1055/a-0651-4842
Review
© Georg Thieme Verlag KG Stuttgart · New York

The Effects of Vitamin D Supplementation on Markers Related to Endothelial Function Among Patients with Metabolic Syndrome and Related Disorders: A Systematic Review and Meta-Analysis of Clinical Trials

Authors

  • Reza Tabrizi

    1   Health Policy Research Center, Institute of Health, Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran

  • Sina Vakili

    2   Department of Biochemistry, Shiraz University of Medical Sciences, Shiraz, Iran

  • Kamran B. Lankarani

    3   Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran

  • Maryam Akbari

    1   Health Policy Research Center, Institute of Health, Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran

  • Mehri Jamilian

    4   Endocrinology and Metabolism Research Center, Department of Gynecology and Obstetrics, School of Medicine, Arak University of Medical Sciences, Arak, Iran

  • Zahra Mahdizadeh

    5   Department of Gynecology and Obstetrics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

  • Naghmeh Mirhosseini

    6   Pure North S’Energy Foundation, Calgary, AB, Canada

  • Zatollah Asemi

    7   Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
Further Information

Publication History

received 31 May 2018

accepted 28 June 2018

Publication Date:
06 August 2018 (online)

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Abstract

This systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to summarize the effect of vitamin D supplementation on endothelial function among people with metabolic syndrome and related disorders. Cochrane library, Embase, PubMed, and Web of Science database were searched to identify related RCTs published up 20th May 2018. To check heterogeneity a Q-test and I2 statistics were used. Data were pooled by using the random-effect model and standardized mean difference (SMD) was considered as summary effect size. Twenty-two trials of 931 potential citations were found to be eligible for current meta-analysis. The pooled findings by using random effects model indicated that vitamin D supplementation to individuals with MetS and related disorders significantly increased flow-mediated dilatation (FMD) (SMD=1.10; 95% CI, 0.38, 1.81, p=0.003). However, it did not affect pulse-wave velocity (PWV) (SMD=0.04; 95% CI, –0.25, 0.33, p=0.80) and augmentation index (AI) (SMD=0.07; 95% CI, –0.25, 0.40; p=0.65). Overall, this meta-analysis demonstrated that vitamin D supplementation to patients with metabolic syndrome and related disorders resulted in an improvement in FMD, but did not influence PWV and AI.

Key words

vitamin D supplementation - endothelial function - metabolic syndrome - meta-analysis

Supplementary Material

 

  • References

  • 1 Cohn JN, Quyyumi AA, Hollenberg NK, Jamerson KA. Surrogate markers for cardiovascular disease: Functional markers. Circulation 2004; 109: Iv31-Iv46
    CrossrefPubMedSearch in Google Scholar
  • 2 Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: The role of oxidant stress. Circ Res 2000; 87: 840-844
    CrossrefPubMedSearch in Google Scholar
  • 3 Benedini S, Dalle Carbonare L, Albiger N, Scanarini M, Bilora F, Petrobelli F, Giannini S, Mantero F, Scaroni C. Effect of short-term therapy with recombinant human growth hormone (GH) on metabolic parameters and preclinical atherosclerotic markers in hypopituitary patients with growth hormone deficiency. Horm Metab Res 2006; 38: 16-21
    Thieme ConnectPubMedSearch in Google Scholar
  • 4 Rudofsky G, Roeder E, Merle T, Hildebrand M, Nawroth PP, Wolfrum C. Weight loss improves endothelial function independently of ADMA reduction in severe obesity. Horm Metab Res 2011; 43: 343-348
    Thieme ConnectPubMedSearch in Google Scholar
  • 5 London GM, Guerin AP, Verbeke FH, Pannier B, Boutouyrie P, Marchais SJ, Metivier F. Mineral metabolism and arterial functions in end-stage renal disease: Potential role of 25-hydroxyvitamin D deficiency. J Am Soc Nephrol 2007; 18: 613-620
    CrossrefPubMedSearch in Google Scholar
  • 6 Wang YQ, Yang PT, Yuan H, Cao X, Zhu XL, Xu G, Mo ZH, Chen ZH. Low bone mineral density is associated with increased arterial stiffness in participants of a health records based study. J Thorac Dis 2015; 7: 790-798
    PubMedSearch in Google Scholar
  • 7 Kidher E, Harling L, Nihoyannopoulos P, Shenker N, Ashrafian H, Francis DP, Mayet J, Athanasiou T. High aortic pulse wave velocity is associated with poor quality of life in surgical aortic valve stenosis patients. Interact Cardiovasc Thorac Surg 2014; 19: 189-197
    CrossrefPubMedSearch in Google Scholar
  • 8 Sugden JA, Davies JI, Witham MD, Morris AD, Struthers AD. Vitamin D improves endothelial function in patients with type 2 diabetes mellitus and low vitamin D levels. Diabet Med 2008; 25: 320-325
    CrossrefPubMedSearch in Google Scholar
  • 9 Tarcin O, Yavuz DG, Ozben B, Telli A, Ogunc AV, Yuksel M, Toprak A, Yazici D, Sancak S, Deyneli O, Akalin S. Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects. J Clin Endocrinol Metab 2009; 94: 4023-4030
    CrossrefPubMedSearch in Google Scholar
  • 10 Stojanovic M, Radenkovic M. Vitamin D versus placebo in improvement of endothelial dysfunction: A meta-analysis of randomized clinical trials. Cardiovasc Ther 2015; 33: 145-154
    CrossrefPubMedSearch in Google Scholar
  • 11 Mazidi M, Karimi E, Rezaie P, Vatanparast H. The impact of vitamin D supplement intake on vascular endothelial function; A systematic review and meta-analysis of randomized controlled trials. Food Nutr Res 2017; 61: 1273574
    PubMedSearch in Google Scholar
  • 12 Rodriguez AJ, Scott D, Srikanth V, Ebeling P. Effect of vitamin D supplementation on measures of arterial stiffness: A systematic review and meta-analysis of randomized controlled trials. Clin Endocrinol (Oxf) 2016; 84: 645-657
    CrossrefPubMedSearch in Google Scholar
  • 13 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177-188
    CrossrefPubMedSearch in Google Scholar
  • 14 Kumar V, Yadav AK, Lal A, Kumar V, Singhal M, Billot L, Gupta KL, Banerjee D, Jha V. A Randomized Trial of Vitamin D Supplementation on Vascular Function in CKD. J Am Soc Nephrol 2017; 28: 3100-3108
    CrossrefPubMedSearch in Google Scholar
  • 15 Barchetta I, Del Ben M, Angelico F, Di Martino M, Fraioli A, La Torre G, Saulle R, Perri L, Morini S, Tiberti C, Bertoccini L, Cimini FA, Panimolle F, Catalano C, Baroni MG, Cavallo MG. No effects of oral vitamin D supplementation on non-alcoholic fatty liver disease in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. BMC Med 2016; 14: 92
    CrossrefPubMedSearch in Google Scholar
  • 16 Garg G, Kachhawa G, Ramot R, Khadgawat R, Tandon N, Sreenivas V, Kriplani A, Gupta N. Effect of vitamin D supplementation on insulin kinetics and cardiovascular risk factors in polycystic ovarian syndrome: A pilot study. Endocr Connect 2015; 4: 108-116
    CrossrefPubMedSearch in Google Scholar
  • 17 Mose FH, Vase H, Larsen T, Kancir AS, Kosierkiewic R, Jonczy B, Hansen AB, Oczachowska-Kulik AE, Thomsen IM, Bech JN, Pedersen EB. Cardiovascular effects of cholecalciferol treatment in dialysis patients – a randomized controlled trial. BMC Nephrol 2014; 15: 50
    CrossrefPubMedSearch in Google Scholar
  • 18 Breslavsky A, Frand J, Matas Z, Boaz M, Barnea Z, Shargorodsky M. Effect of high doses of vitamin D on arterial properties, adiponectin, leptin and glucose homeostasis in type 2 diabetic patients. Clin Nutr 2013; 32: 970-975
    CrossrefPubMedSearch in Google Scholar
  • 19 Sharma A, de Souza Brito F, Sun JL, Thomas L, Haffner S, Holman RR, Lopes RD. Noncardiovascular deaths are more common than cardiovascular deaths in patients with cardiovascular disease or cardiovascular risk factors and impaired glucose tolerance: Insights from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. Am Heart J 2017; 186: 73-82
    CrossrefPubMedSearch in Google Scholar
  • 20 Al Mheid I, Patel R, Murrow J, Morris A, Rahman A, Fike L, Kavtaradze N, Uphoff I, Hooper C, Tangpricha V, Alexander RW, Brigham K, Quyyumi AA. Vitamin D status is associated with arterial stiffness and vascular dysfunction in healthy humans. J Am Coll Cardiol 2011; 58: 186-192
    CrossrefPubMedSearch in Google Scholar
  • 21 Dong Y, Stallmann-Jorgensen IS, Pollock NK, Harris RA, Keeton D, Huang Y, Li K, Bassali R, Guo DH, Thomas J, Pierce GL, White J, Holick MF, Zhu H. A 16-week randomized clinical trial of 2000 international units daily vitamin D3 supplementation in black youth: 25-hydroxyvitamin D, adiposity, and arterial stiffness. J Clin Endocrinol Metab 2010; 95: 4584-4591
    CrossrefPubMedSearch in Google Scholar
  • 22 Giallauria F, Milaneschi Y, Tanaka T, Maggio M, Canepa M, Elango P, Vigorito C, Lakatta EG, Ferrucci L, Strait J. Arterial stiffness and vitamin D levels: The Baltimore longitudinal study of aging. J Clin Endocrinol Metab 2012; 97: 3717-3723
    CrossrefPubMedSearch in Google Scholar
  • 23 Melamed ML, Muntner P, Michos ED, Uribarri J, Weber C, Sharma J, Raggi P. Serum 25-hydroxyvitamin D levels and the prevalence of peripheral arterial disease: Results from NHANES 2001 to 2004. Arterioscler Thromb Vasc Biol 2008; 28: 1179-1185
    CrossrefPubMedSearch in Google Scholar
  • 24 Reddy Vanga S, Good M, Howard PA, Vacek JL. Role of vitamin D in cardiovascular health. Am J Cardiol 2010; 106: 798-805
    CrossrefPubMedSearch in Google Scholar
  • 25 Zehnder D, Bland R, Chana RS, Wheeler DC, Howie AJ, Williams MC, Stewart PM, Hewison M. Synthesis of 1,25-dihydroxyvitamin D(3) by human endothelial cells is regulated by inflammatory cytokines: A novel autocrine determinant of vascular cell adhesion. J Am Soc Nephrol 2002; 13: 621-629
    PubMedSearch in Google Scholar
  • 26 Witham MD, Dove FJ, Dryburgh M, Sugden JA, Morris AD, Struthers AD. The effect of different doses of vitamin D(3) on markers of vascular health in patients with type 2 diabetes: A randomised controlled trial. Diabetologia 2010; 53: 2112-2119
    CrossrefPubMedSearch in Google Scholar
  • 27 Harris RA, Pedersen-White J, Guo DH, Stallmann-Jorgensen IS, Keeton D, Huang Y, Shah Y, Zhu H, Dong Y. Vitamin D3 supplementation for 16 weeks improves flow-mediated dilation in overweight African-American adults. Am J Hypertens 2011; 24: 557-562
    CrossrefPubMedSearch in Google Scholar
  • 28 Longenecker CT, Hileman CO, Carman TL, Ross AC, Seydafkan S, Brown TT, Labbato DE, Storer N, Tangpricha V, McComsey GA. Vitamin D supplementation and endothelial function in vitamin D deficient HIV-infected patients: A randomized placebo-controlled trial. Antiviral Ther 2012; 17: 613-621
    PubMedSearch in Google Scholar
  • 29 Witham M, Dove F, Sugden J, Doney A, Struthers A. The effect of vitamin D replacement on markers of vascular health in stroke patients–A randomised controlled trial. Nutr Metab Cardiovasc Dis 2012; 22: 864-870
    CrossrefPubMedSearch in Google Scholar
  • 30 Stricker H, Tosi Bianda F, Guidicelli-Nicolosi S, Limoni C, Colucci G. Effect of a single, oral, high-dose vitamin D supplementation on endothelial function in patients with peripheral arterial disease: A randomised controlled pilot study. Eur J Vasc Endovasc Surg 2012; 44: 307-312
    CrossrefPubMedSearch in Google Scholar
  • 31 Larsen T, Mose FH, Bech JN, Hansen AB, Pedersen EB. Effect of cholecalciferol supplementation during winter months in patients with hypertension: A randomized, placebo-controlled trial. Am J Hypertens 2012; 25: 1215-1222
    CrossrefPubMedSearch in Google Scholar
  • 32 Marckmann P, Agerskov H, Thineshkumar S, Bladbjerg EM, Sidelmann JJ, Jespersen J, Nybo M, Rasmussen LM, Hansen D, Scholze A. Randomized controlled trial of cholecalciferol supplementation in chronic kidney disease patients with hypovitaminosis D. Nephrol Dial Transplant 2012; 27: 3523-3531
    CrossrefPubMedSearch in Google Scholar
  • 33 Thadhani R, Appelbaum E, Pritchett Y, Chang Y, Wenger J, Tamez H, Bhan I, Agarwal R, Zoccali C, Wanner C, Lloyd-Jones D, Cannata J, Thompson BT, Andress D, Zhang W, Packham D, Singh B, Zehnder D, Shah A, Pachika A, Manning WJ, Solomon SD. Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: The PRIMO randomized controlled trial. JAMA 2012; 307: 674-684
    CrossrefPubMedSearch in Google Scholar
  • 34 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: e36617
    CrossrefPubMedSearch in Google Scholar
  • 35 Yiu YF, Yiu KH, Siu CW, Chan YH, Li SW, Wong LY, Lee SW, Tam S, Wong EW, Lau CP, Cheung BM, Tse HF. Randomized controlled trial of vitamin D supplement on endothelial function in patients with type 2 diabetes. Atherosclerosis 2013; 227: 140-146
    CrossrefPubMedSearch in Google Scholar
  • 36 Angel K, Wium C, Eriksen EF, Atar D, Birkel K. Vitamin D supplementation improves endothelial function in type 2 diabetes-A randomized controlled trial. Artery Res 2013; P15:
    PubMed
  • 37 Dreyer G, Tucker AT, Harwood SM, Pearse RM, Raftery MJ, Yaqoob MM. Ergocalciferol and microcirculatory function in chronic kidney disease and concomitant vitamin d deficiency: An exploratory, double blind, randomised controlled trial. PLoS One 2014; 9: e99461
    CrossrefPubMedSearch in Google Scholar
  • 38 Ryu OH, Chung W, Lee S, Hong KS, Choi MG, Yoo HJ. The effect of high-dose vitamin D supplementation on insulin resistance and arterial stiffness in patients with type 2 diabetes. Korean J Intern Med 2014; 29: 620-629
    CrossrefPubMedSearch in Google Scholar
  • 39 Martins D, Meng YX, Tareen N, Artaza J, Lee JE, Farodolu C, Gibbons G, Norris K. The Effect of Short Term Vitamin D Supplementation on the Inflammatory and Oxidative Mediators of Arterial Stiffness. Health (Irvine Calif) 2014; 6: 1503-1511
    CrossrefPubMedSearch in Google Scholar
  • 40 Pilz S, Gaksch M, Kienreich K, Grubler M, Verheyen N, Fahrleitner-Pammer A, Treiber G, Drechsler C, ÓHartaigh B, Obermayer-Pietsch B, Schwetz V, Aberer F, Mader J, Scharnagl H, Meinitzer A, Lerchbaum E, Dekker JM, Zittermann A, März W, Tomaschitz A. Effects of vitamin D on blood pressure and cardiovascular risk factors: A randomized controlled trial. Hypertension 2015; 65: 1195-1201
    CrossrefPubMedSearch in Google Scholar
  • 41 Dalan R, Liew H, Assam PN, Chan ES, Siddiqui FJ, Tan AW, Chew DE, Boehm BO, Leow MK. A randomised controlled trial evaluating the impact of targeted vitamin D supplementation on endothelial function in type 2 diabetes mellitus: The DIMENSION trial. Diab Vasc Dis Res 2016; 13: 192-200
    CrossrefPubMedSearch in Google Scholar