Electrolyte Blood Press.  2017 Sep;15(1):1-11. 10.5049/EBP.2017.15.1.1.

Vitamin D and Hypertension

• Jeong HY
• Park KM
• Lee MJ
• Yang DH
• Kim SH
• Lee SY

• KMID: 2391006
• DOI: http://doi.org/10.5049/EBP.2017.15.1.1

Abstract

Vitamin D has the pleiotropic effects in multiple organ systems, and vitamin D deficiency was suggested to be associated with high blood pressure according to previous reports. Several interventional studies have examined the effect of vitamin D supplementation on high blood pressure patients, but the results have been inconsistent. In this article, we examined the literature that have proposed a mechanism involving vitamin D in the regulation of blood pressure and review previous observational and interventional studies that have shown the relationship between vitamin D and hypertension among various populations.

Keyword

Hypertension; Mechanism; Physiology; Supplement; Vitamin D

MeSH Terms

Blood Pressure
Humans
Hypertension*
Physiology
Vitamin D Deficiency
Vitamin D*
Vitamins*
Vitamin D
Vitamins

Reference

1. Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. 2006; 81:353–373. PMID: 16529140.

2. Holick MF. Vitamin D deficiency. N Engl J Med. 2007; 357:266–281. PMID: 17634462.

3. Lackland DT, Weber MA. Global burden of cardiovascular disease and stroke: hypertension at the core. Can J Cardiol. 2015; 31:569–571. PMID: 25795106.

4. Forman JP, Giovannucci E, Holmes MD, et al. Plasma 25-hydroxyvitamin D levels and risk of incident hypertension. Hypertension. 2007; 49:1063–1069. PMID: 17372031.

5. Wang TJ, Pencina MJ, Booth SL, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008; 117:503–511. PMID: 18180395.

6. Forman JP, Curhan GC, Taylor EN. Plasma 25-hydroxyvitamin D levels and risk of incident hypertension among young women. Hypertension. 2008; 52:828–832. PMID: 18838623.

7. Judd SE, Nanes MS, Ziegler TR, Wilson PW, Tangpricha V. Optimal vitamin D status attenuates the age-associated increase in systolic blood pressure in white Americans: results from the third National Health and Nutrition Examination Survey. Am J Clin Nutr. 2008; 87:136–141. PMID: 18175747.

8. Scragg R, Sowers M, Bell C. Serum 25-hydroxyvitamin D, ethnicity, and blood pressure in the Third National Health and Nutrition Examination Survey. Am J Hypertens. 2007; 20:713–719. PMID: 17586404.

9. Sypniewska G, Pollak J, Strozecki P, et al. 25-hydroxyvitamin D, biomarkers of endothelial dysfunction and subclinical organ damage in adults with hypertension. Am J Hypertens. 2014; 27:114–121. PMID: 24042165.

10. Lind L, Wengle B, Ljunghall S. Blood pressure is lowered by vitamin D (alphacalcidol) during long-term treatment of patients with intermittent hypercalcaemia. A double-blind, placebo-controlled study. Acta Med Scand. 1987; 222:423–427. PMID: 3321926.

11. Lind L, Wengle B, Wide L, Sorensen OH, Ljunghall S. Hypertension in primary hyperparathyroidism--reduction of blood pressure by long-term treatment with vitamin D(alphacalcidol). A double-blind, placebo-controlled study. Am J Hypertens. 1988; 1:397–402. PMID: 3063290.

12. Lind L, Wengle B, Wide L, Ljunghall S. Reduction of blood pressure during long-term treatment with active vitamin D (alphacalcidol) is dependent on plasma renin activity and calcium status. A double-blind, placebo-controlled study. Am J Hypertens. 1989; 2:20–25. PMID: 2643969.

13. Scragg R, Khaw KT, Murphy S. Effect of winter oral vitamin D3 supplementation on cardiovascular risk factors in elderly adults. Eur J Clin Nutr. 1995; 49:640–646. PMID: 7498100.

14. Pfeifer M, Begerow B, Minne HW, Nachtigall D, Hansen C. Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women. J Clin Endocrinol Metab. 2001; 86:1633–1637. PMID: 11297596.

15. 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. PMID: 18279409.

16. Margolis KL, Ray RM, Van Horn L, et al. Effect of calcium and vitamin D supplementation on blood pressure: the Women's Health Initiative Randomized Trial. Hypertension. 2008; 52:847–855. PMID: 18824662.

17. Nagpal J, Pande JN, Bhartia A. A double-blind, randomized, placebo-controlled trial of the short-term effect of vitamin D3 supplementation on insulin sensitivity in apparently healthy, middle-aged, centrally obese men. Diabet Med. 2009; 26:19–27. PMID: 19125756.

18. Zittermann A, Frisch S, Berthold HK, et al. Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers. Am J Clin Nutr. 2009; 89:1321–1327. PMID: 19321573.

19. de Zeeuw D, Agarwal R, Amdahl M, et al. Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomised controlled trial. Lancet. 2010; 376:1543–1551. PMID: 21055801.

20. Witham MD, Crighton LJ, Gillespie ND, Struthers AD, McMurdo ME. The effects of vitamin D supplementation on physical function and quality of life in older patients with heart failure: a randomized controlled trial. Circ Heart Fail. 2010; 3:195–201. PMID: 20103775.

21. Witham MD, Dove FJ, Dryburgh M, et al. 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. PMID: 20596692.

22. Shab-Bidar S, Neyestani TR, Djazayery A, et al. Regular consumption of vitamin D-fortified yogurt drink (Doogh) improved endothelial biomarkers in subjects with type 2 diabetes: a randomized double-blind clinical trial. BMC Med. 2011; 9:125. PMID: 22114787.

23. Alvarez JA, Law J, Coakley KE, et al. High-dose cholecalciferol reduces parathyroid hormone in patients with early chronic kidney disease: a pilot, randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2012; 96:672–679. PMID: 22854402.

24. Gepner AD, Ramamurthy R, Krueger DC, et al. A prospective randomized controlled trial of the effects of vitamin D supplementation on cardiovascular disease risk. PLoS One. 2012; 7:e36617. PMID: 22586483.

25. Heshmat R, Tabatabaei-Malazy O, Abbaszadeh-Ahranjani S, et al. Effect of vitamin D on insulin resistance and anthropometric parameters in Type 2 diabetes; a randomized double-blind clinical trial. Daru. 2012; 20:10. PMID: 23351271.

26. Muldowney S, Lucey AJ, Hill TR, et al. Incremental cholecalciferol supplementation up to 15mug/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; 142:1519–1525. PMID: 22739371.

27. Salehpour A, Shidfar F, Hosseinpanah F, et al. Vitamin D3 and the risk of CVD in overweight and obese women: a randomised controlled trial. Br J Nutr. 2012; 108:1866–1873. PMID: 22317756.

28. 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. PMID: 22831874.

29. Witham MD, Dove FJ, Sugden JA, Doney AS, Struthers AD. 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. PMID: 21194910.

30. Wood AD, Secombes KR, Thies F, et al. Vitamin D3 supplementation has no effect on conventional cardiovascular risk factors: a parallel-group, double-blind, placebo-controlled RCT. J Clin Endocrinol Metab. 2012; 97:3557–3568. PMID: 22865902.

31. Breslavsky A, Frand J, Matas Z, et al. 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. PMID: 23561637.

32. Chai W, Cooney RV, Franke AA, Bostick RM. Effects of calcium and vitamin D supplementation on blood pressure and serum lipids and carotenoids: a randomized, double-blind, placebo-controlled, clinical trial. Ann Epidemiol. 2013; 23:564–570. PMID: 23958407.

33. Forman JP, Scott JB, Ng K, et al. Effect of vitamin D supplementation on blood pressure in blacks. Hypertension. 2013; 61:779–785. PMID: 23487599.

34. Larsen T, Mose FH, Bech JN, Pedersen EB. Effect of paricalcitol on renin and albuminuria in non-diabetic stage III-IV chronic kidney disease: a randomized placebo-controlled trial. BMC Nephrol. 2013; 14:163. PMID: 23889806.

35. Toxqui L, Blanco-Rojo R, Wright I, Perez-Granados AM, Vaquero MP. Changes in blood pressure and lipid levels in young women consuming a vitamin D-fortified skimmed milk: a randomised controlled trial. Nutrients. 2013; 5:4966–4977. PMID: 24317556.

36. Wamberg L, Kampmann U, Stodkilde-Jorgensen H, et al. 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. 2013; 24:644–649. PMID: 23566943.

37. Witham MD, Adams F, Kabir G, et al. Effect of shortterm vitamin D supplementation on markers of vascular health in South Asian women living in the UK--a randomised controlled trial. Atherosclerosis. 2013; 230:293–299. PMID: 24075759.

38. Witham MD, Dove FJ, Khan F, et al. Effects of vitamin D supplementation on markers of vascular function after myocardial infarction--a randomised controlled trial. Int J Cardiol. 2013; 167:745–749. PMID: 22459388.

39. Yiu YF, Yiu KH, Siu CW, et al. Randomized controlled trial of vitamin D supplement on endothelial function in patients with type 2 diabetes. Atherosclerosis. 2013; 227:140–146. PMID: 23298824.

40. Dalbeni A, Scaturro G, Degan M, Minuz P, Delva P. Effects of six months of vitamin D supplementation in patients with heart failure: a randomized double-blind controlled trial. Nutr Metab Cardiovasc Dis. 2014; 24:861–868. PMID: 24787908.

41. Scragg R, Slow S, Stewart AW, et al. Long-term high-dose vitamin D3 supplementation and blood pressure in healthy adults: a randomized controlled trial. Hypertension. 2014; 64:725–730. PMID: 24980662.

42. Strobel F, Reusch J, Penna-Martinez M, et al. Effect of a randomised controlled vitamin D trial on insulin resistance and glucose metabolism in patients with type 2 diabetes mellitus. Horm Metab Res. 2014; 46:54–58. PMID: 24198221.

43. Sollid ST, Hutchinson MY, Fuskevag OM, et al. No effect of high-dose vitamin D supplementation on glycemic status or cardiovascular risk factors in subjects with prediabetes. Diabetes Care. 2014; 37:2123–2131. PMID: 24947792.

44. Wang AY, Fang F, Chan J, et al. Effect of paricalcitol on left ventricular mass and function in CKD--the OPERA trial. J Am Soc Nephrol. 2014; 25:175–186. PMID: 24052631.

45. Witham MD, Ireland S, Houston JG, et al. Vitamin D therapy to reduce blood pressure and left ventricular hypertrophy in resistant hypertension: randomized, controlled trial. Hypertension. 2014; 63:706–712. PMID: 24420547.

46. Jo I, Ahn Y, Lee J, et al. Prevalence, awareness, treatment, control and risk factors of hypertension in Korea: the Ansan study. J Hypertens. 2001; 19:1523–1532. PMID: 11564970.

47. Norman AW. From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr. 2008; 88:491s–499s. PMID: 18689389.

48. Calvo MS, Whiting SJ, Barton CN. Vitamin D intake: a global perspective of current status. J Nutr. 2005; 135:310–316. PMID: 15671233.

49. Lips P, Hosking D, Lippuner K, et al. The prevalence of vitamin D inadequacy amongst women with osteoporosis: an international epidemiological investigation. J Intern Med. 2006; 260:245–254. PMID: 16918822.

50. Heaney RP. Functional indices of vitamin D status and ramifications of vitamin D deficiency. Am J Clin Nutr. 2004; 80:1706s–1709s. PMID: 15585791.

51. Holick MF, Siris ES, Binkley N, et al. Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab. 2005; 90:3215–3224. PMID: 15797954.

52. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007; 85:1586–1591. PMID: 17556697.

53. Chun RF. New perspectives on the vitamin D binding protein. Cell Biochem Funct. 2012; 30:445–456. PMID: 22528806.

54. Cooke NE, Haddad JG. Vitamin D binding protein (Gcglobulin). Endocr Rev. 1989; 10:294–307. PMID: 2476303.

55. Tanaka Y, Deluca HF. The control of 25-hydroxyvitamin D metabolism by inorganic phosphorus. Arch Biochem Biophys. 1973; 154:566–574. PMID: 4691503.

56. Holick MF. Resurrection of vitamin D deficiency and rickets. J Clin Invest. 2006; 116:2062–2072. PMID: 16886050.

57. DeLuca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr. 2004; 80:1689s–1696s. PMID: 15585789.

58. Henry HL. Regulation of vitamin D metabolism. Best Pract Res Clin Endocrinol Metab. 2011; 25:531–541. PMID: 21872796.

59. Coetzee M, Kruger MC. Osteoprotegerin-receptor activator of nuclear factor-kappaB ligand ratio: a new approach to osteoporosis treatment? South Med J. 2004; 97:506–511. PMID: 15180028.

60. Poole KE, Reeve J. Parathyroid hormone - a bone anabolic and catabolic agent. Curr Opin Pharmacol. 2005; 5:612–617. PMID: 16181808.

61. Blaine J, Chonchol M, Levi M. Renal control of calcium, phosphate, and magnesium homeostasis. Clin J Am Soc Nephrol. 2015; 10:1257–1272. PMID: 25287933.

62. Juppner H. Phosphate and FGF-23. Kidney Int Suppl. 2011; S24–S27. PMID: 21346724.

63. Nair R, Maseeh A. Vitamin D: The “sunshine” vitamin. J Pharmacol Pharmacother. 2012; 3:118–126. PMID: 22629085.

64. Beveridge LA, Struthers AD, Khan F, et al. Effect of Vitamin D Supplementation on Blood Pressure: A Systematic Review and Meta-analysis Incorporating Individual Patient Data. JAMA Intern Med. 2015; 175:745–754. PMID: 25775274.

65. Qi D, Nie X, Cai J. The effect of vitamin D supplementation on hypertension in non-CKD populations: A systemic review and meta-analysis. Int J Cardiol. 2017; 227:177–186. PMID: 27866065.

66. Te Riet L, van Esch JH, Roks AJ, van den Meiracker AH, Danser AH. Hypertension: renin-angiotensin-aldosterone system alterations. Circ Res. 2015; 116:960–975. PMID: 25767283.

67. Forman JP, Williams JS, Fisher ND. Plasma 25-hydroxyvitamin D and regulation of the renin-angiotensin system in humans. Hypertension. 2010; 55:1283–1288. PMID: 20351344.

68. Santoro D, Caccamo D, Lucisano S, et al. Interplay of vitamin D, erythropoiesis, and the renin-angiotensin system. Biomed Res Int. 2015; 2015:145828. PMID: 26000281.

69. Burgess ED, Hawkins RG, Watanabe M. Interaction of 1,25-dihydroxyvitamin D and plasma renin activity in high renin essential hypertension. Am J Hypertens. 1990; 3:903–905. PMID: 2081010.

70. Li YC, Kong J, Wei M, et al. 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest. 2002; 110:229–238. PMID: 12122115.

71. Zhou C, Lu F, Cao K, et al. Calcium-independent and 1,25(OH)2D3-dependent regulation of the renin-angiotensin system in 1α-hydroxylase knockout mice. Kidney Int. 2008; 74:170–179. PMID: 18385669.

72. Yuan W, Pan W, Kong J, et al. 1,25-dihydroxyvitamin D3 suppresses renin gene transcription by blocking the activity of the cyclic AMP response element in the renin gene promoter. J Biol Chem. 2007; 282:29821–29830. PMID: 17690094.

73. Harrison DG, Guzik TJ, Lob HE, et al. Inflammation, immunity, and hypertension. Hypertension. 2011; 57:132–140. PMID: 21149826.

74. Guzik TJ, Hoch NE, Brown KA, et al. Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med. 2007; 204:2449–2460. PMID: 17875676.

75. Crowley SD, Song YS, Lin EE, et al. Lymphocyte responses exacerbate angiotensin II-dependent hypertension. Am J Physiol Regul Integr Comp Physiol. 2010; 298:R1089–R1097. PMID: 20147609.

76. Tran LT, MacLeod KM, McNeill JH. Chronic etanercept treatment prevents the development of hypertension in fructose-fed rats. Mol Cell Biochem. 2009; 330:219–228. PMID: 19440659.

77. Schrader LI, Kinzenbaw DA, Johnson AW, Faraci FM, Didion SP. IL-6 deficiency protects against angiotensin II induced endothelial dysfunction and hypertrophy. Arterioscler Thromb Vasc Biol. 2007; 27:2576–2581. PMID: 17962626.

78. Hartupee J, Liu C, Novotny M, Li X, Hamilton T. IL-17 enhances chemokine gene expression through mRNA stabilization. J Immunol. 2007; 179:4135–4141. PMID: 17785852.

79. Sakaguchi S, Ono M, Setoguchi R, et al. Foxp3+CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease. Immunol Rev. 2006; 212:8–27. PMID: 16903903.

80. Yin K, Agrawal DK. Vitamin D and inflammatory diseases. J Inflamm Res. 2014; 7:69–87. PMID: 24971027.

81. Tarcin O, Yavuz DG, Ozben B, et al. Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects. J Clin Endocrinol Metab. 2009; 94:4023–4030. PMID: 19584181.

82. Lee SY, Kim HY, Gu SW, Kim HJ, Yang DH. 25-hydroxyvitamin D levels and vascular calcification in predialysis and dialysis patients with chronic kidney disease. Kidney Blood Press Res. 2012; 35:349–354. PMID: 22487876.

83. Ko EJ, Kim BH, Jeong HY, et al. Serum 25-hydroxyvitamin D as a predictor of hospitalization-free survival in predialysis and dialysis patients with chronic kidney disease: a single-center prospective observational analysis. Kidney Res Clin Pract. 2016; 35:22–28. PMID: 27069854.

84. Chitalia N, Recio-Mayoral A, Kaski JC, Banerjee D. Vitamin D deficiency and endothelial dysfunction in non-dialysis chronic kidney disease patients. Atherosclerosis. 2012; 220:265–268. PMID: 22071357.

85. Zhang QY, Jiang CM, Sun C, et al. Hypovitaminosis D is associated with endothelial dysfunction in patients with non-dialysis chronic kidney disease. J Nephrol. 2015; 28:471–476. PMID: 25515034.

86. Andrukhova O, Slavic S, Zeitz U, et al. Vitamin D is a regulator of endothelial nitric oxide synthase and arterial stiffness in mice. Mol Endocrinol. 2014; 28:53–64. PMID: 24284821.

87. Lind L, Pollare T, Hvarfner A, et al. Long-term treatment with active vitamin D (alphacalcidol) in middle-aged men with impaired glucose tolerance. Effects on insulin secretion and sensitivity, glucose tolerance and blood pressure. Diabetes Res. 1989; 11:141–147. PMID: 2697485.

88. Krause R, Buhring M, Hopfenmuller W, Holick MF, Sharma AM. Ultraviolet B and blood pressure. Lancet. 1998; 352:709–710.

89. Pan WH, Wang CY, Li LA, Kao LS, Yeh SH. No significant effect of calcium and vitamin D supplementation on blood pressure and calcium metabolism in elderly Chinese. Chin J Physiol. 1993; 36:85–94. PMID: 8198625.

90. Salehpour A, Hosseinpanah F, Shidfar F, et al. A 12-week double-blind randomized clinical trial of vitamin D(3) supplementation on body fat mass in healthy overweight and obese women. Nutr J. 2012; 11:78. PMID: 22998754.

91. Wu SH, Ho SC, Zhong L. Effects of vitamin D supplementation on blood pressure. South Med J. 2010; 103:729–737. PMID: 20622727.

92. Kunutsor SK, Burgess S, Munroe PB, Khan H. Vitamin D and high blood pressure: causal association or epiphenomenon? Eur J Epidemiol. 2014; 29:1–14. PMID: 24374742.

93. Jorde R, Sneve M, Torjesen P, Figenschau Y. No improvement in cardiovascular risk factors in overweight and obese subjects after supplementation with vitamin D3 for 1 year. J Intern Med. 2010; 267:462–472. PMID: 20141565.

94. Witham MD, Price RJ, Struthers AD, et al. Cholecalciferol treatment to reduce blood pressure in older patients with isolated systolic hypertension: the VitDISH randomized controlled trial. JAMA Intern Med. 2013; 173:1672–1679. PMID: 23939263.