Clin Nutr Res.  2020 Jan;9(1):20-31. 10.7762/cnr.2020.9.1.20.

An Empirical Study on the Effect of Short-Term Regular Vitamin D3 Supplement Therapy on Blood Pressure and Exercise Tolerance in Heart Failure Patients

• Hosseinzadeh F
• Oskouei NJ
• Ghavamzadeh S

• KMID: 2468661
• DOI: http://doi.org/10.7762/cnr.2020.9.1.20

Abstract

The receptor of vitamin D is expressed in almost all body cells, including vascular endothelial cells and cardiomyocytes. Vitamin D deficiency has been observed widespread amongst heart failure (HF) patients, which could have harmful effects on their health condition. This study aims to investigate the effect of vitamin D supplements on blood pressure (BP) and physical activity of HF patients. Thirty-nine systolic HF patients with low ejection fraction (EF) < 50% and class III of New York Heart Association functional classification were randomly divided into 2 groups including intervention and placebo to enroll in an 8 weeks double-blind clinical trial. During the trial 6-minute walk test (6MWT), 25-hydroxyvitamin D (25[OH]D) level, BP, sodium and potassium intakes were assessed. The mean 25(OH)D level increased to 28.9 ± 11.7 ng/mL (p < 0.001) in the intervention group. There was a poor but non-significant reduction in systolic BP (−0.033 ± 4.71 mmHg, p = 0.531) in the intervention group. The BP also did not change in the placebo group at the end of the trial. A negligible decrease of 6MWT was observed in the intervention group (−6.6 ± 29.2 m) compared to the placebo (−14.1 ± 40.5 m). However, differences between the 2 groups were not statistically significant (p = 0.325). The results solely showed a slight positive correlation between 25(OH)D level and 6MWT. No significant improvements in BP and 6MWT were observed after vitamin D3 supplementation. TRIAL REGISTRATION: Iranian Registry of Clinical Trials Identifier: IRCT2016102113678N13

Keyword

Vitamin D; Heart failure; Blood pressure; Exercise test

MeSH Terms

Blood Pressure*
Cholecalciferol*
Classification
Endothelial Cells
Exercise Test
Exercise Tolerance*
Heart Failure*
Heart*
Humans
Motor Activity
Myocytes, Cardiac
Potassium
Sodium
Vitamin D
Vitamin D Deficiency
Vitamins*
Cholecalciferol
Potassium
Sodium
Vitamin D
Vitamins

Figure

• 

  Figure 1 Flowchart of sampling method and randomization. NHYA, New York Heart Association; EF, ejection fraction; HF, heart failure; 25(OH)D, 25-hydroxyvitamin D.

Reference

1. Don-Wauchope AC, McKelvie RS. Evidence based application of BNP/NT-proBNP testing in heart failure. Clin Biochem. 2015; 48:236–246.

2. Mosterd A, Hoes AW. Clinical epidemiology of heart failure. Heart. 2007; 93:1137–1146.

3. 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.

4. Writing Committee Members. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL. American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013; 128:e240–327.

5. Hill SA, Booth RA, Santaguida PL, Don-Wauchope A, Brown JA, Oremus M, Ali U, Bustamam A, Sohel N, McKelvie R, Balion C, Raina P. Use of BNP and NT-proBNP for the diagnosis of heart failure in the emergency department: a systematic review of the evidence. Heart Fail Rev. 2014; 19:421–438.

6. Hatmi ZN, Tahvildari S, Gafarzadeh Motlag A, Sabouri Kashani A. Prevalence of coronary artery disease risk factors in Iran: a population based survey. BMC Cardiovasc Disord. 2007; 7:32.

7. Shahla A, Charehsaz S, Talebi R, Omrani M. Vitamin D deficiency in young females with musculoskeletal complaints in Urmia, Northwest of Iran. Iran J Med Sci. 2005; 30:88–90.

8. Heshmat R, Mohammad K, Majdzadeh S, Forouzanfar M, Bahrami A, Ranjbar Omrani G, Nabipour I, Rajabian R, Hossein-Nezhad A, Rezaei Hemami M, Keshtkar A, Pajouhi M. Vitamin D deficiency in Iran: a multi-center study among different urban areas. Iran J Public Health. 2008; 37:72–78.

9. Hashemipour S, Larijani B, Adibi H, Javadi E, Sedaghat M, Pajouhi M, Soltani A, Shafaei AR, Hamidi Z, Fard AR, Hossein-Nezhad A, Booya F. Vitamin D deficiency and causative factors in the population of Tehran. BMC Public Health. 2004; 4:38.

10. GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015; 385:117–171.

11. Donneyong MM. Vitamin D plus calcium supplementation among postmenopausal women: effect on risk of heart failure in the Women's Health Initiative [dissertation]. Louisville (KY): University of Louisville;2013. DOI: 10.18297/etd/365.

12. Villareal DT, Miller BV 3rd, Banks M, Fontana L, Sinacore DR, Klein S. Effect of lifestyle intervention on metabolic coronary heart disease risk factors in obese older adults. Am J Clin Nutr. 2006; 84:1317–1323.

13. Stampfer MJ, Hu FB, Manson JE, Rimm EB, Willett WC. Primary prevention of coronary heart disease in women through diet and lifestyle. N Engl J Med. 2000; 343:16–22.

14. Ross AC. Modern nutrition in health and disease. 11th ed. Philadelphia (PA): Wolters Kluwer Health/Lippincott Williams & Wilkins;2014.

15. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008; 87:1080S–6S.

16. Robbins J, Petrone AB, Gaziano JM, Djoussé L. Dietary vitamin D and risk of heart failure in the Physicians' Health Study. Clin Nutr. 2016; 35:650–653.

17. Mozos I, Marginean O. Links between vitamin D deficiency and cardiovascular diseases. BioMed Res Int. 2015; 2015:109275.

18. Norman PE, Powell JT. Vitamin D and cardiovascular disease. Circ Res. 2014; 114:379–393.

19. Beveridge LA, Struthers AD, Khan F, Jorde R, Scragg R, Macdonald HM, Alvarez JA, Boxer RS, Dalbeni A, Gepner AD, Isbel NM, Larsen T, Nagpal J, Petchey WG, Stricker H, Strobel F, Tangpricha V, Toxqui L, Vaquero MP, Wamberg L, Zittermann A, Witham MD. D-PRESSURE Collaboration. 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.

20. Francis R, Aspray T, Fraser W, Gittoes N, Javaid K, MacDonald H, Patel S, Selby P, Tanna N, Bowring C. Vitamin D and bone health: a practical clinical guideline for patient management. Scotland: National Osteoporosis Society;2013.

21. Witham MD, Nadir MA, Struthers AD. Effect of vitamin D on blood pressure: a systematic review and meta-analysis. J Hypertens. 2009; 27:1948–1954.

22. Vacek JL, Vanga SR, Good M, Lai SM, Lakkireddy D, Howard PA. Vitamin D deficiency and supplementation and relation to cardiovascular health. Am J Cardiol. 2012; 109:359–363.

23. Boxer R, Kleppinger A, Ahmad A, Annis K, Hager D, Kenny A. The 6-minute walk is associated with frailty and predicts mortality in older adults with heart failure. Congest Heart Fail. 2010; 16:208–213.

24. Arslan S, Erol MK, Gundogdu F, Sevimli S, Aksakal E, Senocak H, Alp N. Prognostic value of 6-minute walk test in stable outpatients with heart failure. Tex Heart Inst J. 2007; 34:166–169.

25. Amin A, Minaee S, Chitsazan M, Naderi N, Taghavi S, Ardeshiri M. Can vitamin D supplementation improve the severity of congestive heart failure? Congest Heart Fail. 2013; 19:E22–E28.

26. Majeed Babar MZ, Haider SS, Mustafa G. Effects of vitamin D supplementation on physical activity of patients with Heart Failure. Pak J Med Sci. 2016; 32:1430–1433.

27. 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.

28. Turrini F, Scarlini S, Giovanardi P, Messora R, Roli L, Chester J, Mussi C, Bertolotti M, Trenti T, Bondi M. Effects of Cholecalciferol Supplementation in Patients with stable heart failure and LOw vITamin D levels (ECSPLOIT-D): a double-blind, randomized, placebo-controlled pilot study. Minerva Cardioangiol. 2017; 65:553–562.

29. Pilz S, Gaksch M, Kienreich K, Grübler M, Verheyen N, Fahrleitner-Pammer A, Treiber G, Drechsler C, Ó Hartaigh 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.

30. Wamberg L, Kampmann U, Stødkilde-Jørgensen H, Rejnmark L, Pedersen SB, Richelsen B. 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.

31. Hsia J, Heiss G, Ren H, Allison M, Dolan NC, Greenland P, Heckbert SR, Johnson KC, Manson JE, Sidney S, Trevisan M. Women's Health Initiative Investigators. Calcium/vitamin D supplementation and cardiovascular events. Circulation. 2007; 115:846–854.

32. Sluyter JD, Camargo CA Jr, Stewart AW, Waayer D, Lawes CM, Toop L, Khaw KT, Thom SA, Hametner B, Wassertheurer S, Parker KH, Hughes AD, Scragg R. Effect of monthly, high-dose, long-term vitamin D supplementation on central blood pressure parameters: a randomized controlled trial substudy. J Am Heart Assoc. 2017; 6:e006802.

33. Witte KK, Byrom R, Gierula J, Paton MF, Jamil HA, Lowry JE, Gillott RG, Barnes SA, Chumun H, Kearney LC, Greenwood JP, Plein S, Law GR, Pavitt S, Barth JH, Cubbon RM, Kearney MT. Effects of vitamin D on cardiac function in patients with chronic HF: the VINDICATE study. J Am Coll Cardiol. 2016; 67:2593–2603.

34. Janssen HC, Samson MM, Verhaar HJ. Vitamin D deficiency, muscle function, and falls in elderly people. Am J Clin Nutr. 2002; 75:611–615.

35. Hosseinzadeh F, Jangi Oskouei N, Ghavamzadeh S. The effect of vitamin D supplementation on inflammation and markers of vascular function in heart failure patients. Crescent J Med Biol Sci. 2019; 6:285–292.

36. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011; 96:1911–1930.

37. First Databank. Nutritionist IV 4.1. San Bruno (CA): The Hearst Corporation;1995.

38. Enright PL. The six-minute walk test. Respir Care. 2003; 48:783–785.

39. Weir MR, Dzau VJ. The renin-angiotensin-aldosterone system: a specific target for hypertension management. Am J Hypertens. 1999; 12:205S–213S.

40. Ford JA, MacLennan GS, Avenell A, Bolland M, Grey A, Witham M. RECORD Trial Group. Cardiovascular disease and vitamin D supplementation: trial analysis, systematic review, and meta-analysis. Am J Clin Nutr. 2014; 100:746–755.

41. Boxer RS, Kenny AM, Cheruvu VK, Vest M, Fiutem JJ, Piña II. Serum 25-hydroxyvitamin D concentration is associated with functional capacity in older adults with heart failure. Am Heart J. 2010; 160:893–899.

42. Kong J, Qiao G, Zhang Z, Liu SQ, Li YC. Targeted vitamin D receptor expression in juxtaglomerular cells suppresses renin expression independent of parathyroid hormone and calcium. Kidney Int. 2008; 74:1577–1581.

43. 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.

44. Morimoto A, Uzu T, Fujii T, Nishimura M, Kuroda S, Nakamura S, Inenaga T, Kimura G. Sodium sensitivity and cardiovascular events in patients with essential hypertension. Lancet. 1997; 350:1734–1737.

45. Farquhar WB, Edwards DG, Jurkovitz CT, Weintraub WS. Dietary sodium and health: more than just blood pressure. J Am Coll Cardiol. 2015; 65:1042–1050.

46. Carretero OA, Oparil S. Essential hypertension. Part I: definition and etiology. Circulation. 2000; 101:329–335.

47. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, MacLaughlin EJ, Muntner P, Ovbiagele B, Smith SC Jr, Spencer CC, Stafford RS, Taler SJ, Thomas RJ, Williams KA Sr, Williamson JD, Wright JT Jr. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018; 71:e127–248.

48. Izawa KP, Watanabe S, Yokoyama H, Hiraki K, Morio Y, Oka K, Osada N, Omiya K. Muscle strength in relation to disease severity in patients with congestive heart failure. Am J Phys Med Rehabil. 2007; 86:893–900.

49. Dontje ML, van der Wal MH, Stolk RP, Brügemann J, Jaarsma T, Wijtvliet PE, van der Schans CP, de Greef MH. Daily physical activity in stable heart failure patients. J Cardiovasc Nurs. 2014; 29:218–226.

50. Ribeiro JP, Chiappa GR, Neder JA, Frankenstein L. Respiratory muscle function and exercise intolerance in heart failure. Curr Heart Fail Rep. 2009; 6:95–101.

51. Kim DH, Sabour S, Sagar UN, Adams S, Whellan DJ. Prevalence of hypovitaminosis D in cardiovascular diseases (from the National Health and Nutrition Examination Survey 2001 to 2004). Am J Cardiol. 2008; 102:1540–1544.

52. Boxer RS, Kenny AM, Schmotzer BJ, Vest M, Fiutem JJ, Piña IL. A randomized controlled trial of high dose vitamin D3 in patients with heart failure. JACC Heart Fail. 2013; 1:84–90.