Health  Vol.6 No.12 , June 2014
The Effect of Short Term Vitamin D Supplementation on the Inflammatory and Oxidative Mediators of Arterial Stiffness
Abstract: Background: Vitamin D deficiency has been implicated as a potential risk factor for cardiovascular disease. The high rate of vitamin D deficiency (<30 ng/ml) exhibited by African Americans may account for some of the excess prevalence of cardiovascular morbidity and mortality in this vulnerable US population. Vitamin D supplementation may reduce the risk of cardiovascular disease by ameliorating the onset and progression of arterial stiffness, a strong predictor of cardiovascular mortality, usually assessed by pulse wave velocity and augmentation index. Very few prospective studies have evaluated the effect of vitamin D supplementation on the inflammatory and oxidative stress mediators of arterial stiffness. Method: In a double blind randomized placebo controlled study we evaluated the effect of a monthly dose of 100,000IU of vitamin D3 for three months on the level of serum 25(OH)D, intact parathyroid hormone (PTH), urinary isoprostane, adipocyte cytokine expression and arterial stiffness among 130 overweight and obese (BMI > 25) African Americans with elevated blood pressure (130 - 150/85 - 100 mmHg) and low serum vitamin D level (10 - 25 ng/ml). Results: There was a significant increase in the serum 25(OH)D levels to a mean level of 34.5 ng/ml (SD = 7.1) with the intervention (p < 0.001). The increase in 25(OH)D levels was associated with a significant decrease in the serum level of intact PTH (p = 0.02), mean urinary isoprostane (p = 0.02) and adipocyte cytokine expression. Although the increase in the 25(OH)D levels was not associated with any significant change in the Pulse Wave Velocity (PWV) in the overall study sample, it was associated with a significant decrease in the augmentation index among the participants with the highest tertile of urinary isoprostane (p = 0.007). Conclusion: We concluded that vitamin D supplementation increased serum 25(OH)D levels, decreased intact PTH level and the levels of select inflammatory and oxidative stress mediators of arterial stiffness. Longer term prospective studies are warranted to evaluate the effect of high dose vitamin D supplementation on arterial stiffness.
Cite this paper: Martins, D. , Meng, Y. , Tareen, N. , Artaza, J. , Lee, J. , Farodolu, C. , Gibbons, G. and Norris, K. (2014) The Effect of Short Term Vitamin D Supplementation on the Inflammatory and Oxidative Mediators of Arterial Stiffness. Health, 6, 1503-1511. doi: 10.4236/health.2014.612185.

[1]   Elamin, M.B., Abu Elnour, N.O., Elamin, K.B., Fatourechi, M.M., Alkatib, A.A., Almandoz, J.P., Liu, H., Lane, M.A., Mullan, R.J., Hazem, A., Erwin, P.J., Hensrud, D.D., Murad, M.H. and Montori, V.M. (2011) Vitamin D and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis. The Journal of Clinical Endocrinology & Metabolism, 96, 1931-1942.

[2]   Holick, M.F., Binkley, N.C., Bischoff-Ferrari, H.A., Gordon, C.M., Hanley, D.A., Heaney, R.P., et al. (2011) Evaluation, Treatment, and Prevention of Vitamin D Deficiency: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism, 96, 1911-1930.

[3]   Zadshir, A., Tareen, N., Pan, D., Norris, K.C. and Martins, D. (2005) The Prevalence of Hypovitaminosis D among US Adults: Data from the NHANES III. Ethnicity & Disease, 15, S5-97-101.

[4]   Hansen, T.W., Staessen, J.A., Torp-Pedersen, C., et al. (2006) Ambulatory Arterial Stiffness Index Predicts Stroke in a General Population. Journal of Hypertension, 24, 2247-2253.

[5]   Dong, Y., Pollock, N., Stallmann-Jorgensen, I.S., Gutin, B., Lan, L., Chen, T.C., et al. (2010) Low 25-Hydroxyvitamin D Levels in Adolescents: Race, Season, Adiposity, Physical Activity, and Fitness. Pediatrics, 125, 1104-1111.

[6]   Zadshir, A., Tareen, N., Pan, D., Norris, K. and Martins, D. (2005) The Prevalence of Hypovitaminosis D among US Adults: Data from the NHANES III. Ethnicity & Disease, 15, S5-97-S5-101.

[7]   Henn, V., et al. (1998) CD40 Ligand on Activated Platelets Triggers Inflammatory Reaction of Endothelial Cells. Nature, 39, 591-594.

[8]   Geiser, T., et al. (1993) The Interleukin-8-Related Chemotactic Cytokines GRO Alpha, GRO Beta, and GRO Gamma Activate Human Neutrophil and Basophil Leukocytes. Journal of Biological Chemistry, 268, 15419-15424.

[9]   Chakraborty, H. and Gu, H. (2009) A Mixed Model Approach for Intent-to-Treat Analysis in Longitudinal Clinical Trials with Missing Values. RTI Press Publication. No. MR-0009-0903. RTI International, Research Triangle Park.

[10]   Ginde, A.A., Liu, M.C. and Camargo, C.A. (2009) Demographic Differences and Trends of Vitamin D Insufficiency in the US Population, 1988-2004. Archives of Internal Medicine, 169, 626-632.

[11]   Judd, S. and Tangpricha, V. (2008) Vitamin D Deficiency and Risk for Cardiovascular Disease. Circulation, 117, 503-511.

[12]   Hollis, B.W. (2005) Circulating 25-Hydroxyvitamin D Levels Indicative of Vitamin D Sufficiency: Implications for Establishing a New Effective Dietary Intake Recommendation for Vitamin D. Journal of Nutrition, 135, 317-322.

[13]   IOM (Institute of Medicine) (2011) Dietary Reference Intakes for Calcium and Vitamin D. The National Academies Press, Washington, DC.

[14]   Priemel, M., von Domarus, C., Klatte, T.O., Kessler, S., Schlie, J., Meier, S., Proksch, N., Pastor, F., Netter, C., Streichert, T., Püschel, K. and Amling, M. (2010) Bone Mineralization Defects and Vitamin D Deficiency: Histomorphometric Analysis of Iliac Crest Bone Biopsies and Circulating 25-Hydroxyvitamin D in 675 Patients. JBMR, 25, 305-312.

[15]   Holick, M.F. (2004) Vitamin D Importance in the Prevention of Cancers, Type 1 Diabetes, Heart Disease, and Osteoporosis. The American Journal of Clinical Nutrition, 79, 362-371.

[16]   Thomas, M.K., Lloyd-Jones, D.M., Thadhani, R.I., Shaw, A.C., Deraska, D.J., Kitch, B.T., Vamvakas, E.C., Dick, I.M., Prince, R.L. and Finkelstein, J.S. (1998) Relation between Serum 25-Hydroxyvitamin D Concentrations and Mean (±SE) Serum Concentrations of Parathyroid Hormone in the Study Patients. Figure 2 in Hypovitaminosis D in Medical Inpatients by Thomas MK et al. The New England Journal of Medicine, 338, 777-783.

[17]   Hunt, S.C., Williams, R.R. and Kuida, H. (1991) Different Plasma Ionized Calcium Correlations with Blood Pressure in High and Low Renin Normotensive Adults in Utah. American Journal of Hypertension, 4, 1-8.

[18]   Jiang, B.B., Morimoto, S., Yang, J., Niinoabu, T., Fukuo, K. and Ogihara, T. (1998) Expression of Parathyroid Hormone/Parathyroid Hormone-Related Protein Receptor in Vascular Endothelial Cells. Journal of Cardiovascular Pharmacology, 31, S142-S144.

[19]   Osto, E., Fallo, F., Pelizzo, M.R., Maddalozzo, A., Sorgato, N., Corbetti, F., Montisci, R., Famoso, G., Bellu, R., Lüscher, T.F., Iliceto, S. and Tona, F. (2012) Coronary Microvascular Dysfunction Induced by Primary Hyperparathyroidism Is Restored after Parathyroidectomy. Circulation, 126, 1031-1039.

[20]   Kosch, M., Hausberg, M., Vormbrock, K., Kisters, K., Gabriels, G., Rahn, K.H. and Barenbrock, M. (2000) Impaired Flow-Mediated Vasodilation of the Brachial Artery in Patients with Primary Hyperparathyroidism Improves after Parathyroidectomy. Cardiovascular Research, 47, 813-818.

[21]   Dusso, A.S. and Brown, A.J. (1998) Mechanism of Vitamin D Actions and Its Regulation. American Journal of Kidney Diseases, 32, S13-24.

[22]   Carlberg, C., Quack, M., Herdick, M., Bury, Y., Polly, P. and Toell, A. (2001) Central Role of VDR Conformations for Understanding Selective Actions of Vitamin D(3) Analogues. Steroids, 66, 213-221.

[23]   Ebert, R., Schutze, N., Adamski, J. and Jakob, F. (2006) Vitamin D Signaling Is Modulated on Multiple Levels in Health and Disease. Molecular and Cellular Endocrinology, 248, 149-159.

[24]   Wu-Wong, J.R., Nakane, M., Ma, J., Ruan, X. and Kroeger, P.E. (2006) Effects of Vitamin D analogs on Gene Expression Profiling in Human Coronary Artery Smooth Muscle Cells. Atherosclerosis, 186, 20-28.

[25]   Jones, G., et al. (1998) Current Understanding of the Molecular Actions of Vitamin D. Physiological Reviews, 78, 1193-1231.

[26]   Seibert, E., Levin, N.W. and Kuhlmann, M.K. (2005) Immunomodulating Effects of Vitamin D Analogs in Hemodialysis Patients. Hemodialysis International, 9, S25-S29.

[27]   Luscher, T.F. and Barton, M. (2000) Endothelins and Endothelin Receptor Antagonists: Therapeutic Consideration for a Novel Class of Cardiovascular Drugs. Circulation, 102, 2434-2440.

[28]   Al Mheid, I., Patel, R., Murrow, J., Morris, A., Rahman, A., Fike, L., Kavtaradze, N., Uphoff, I., Hooper, C., Tangpricha, V., Wayne Alexander, R., Brigham, K. and Quyyumi, A.A. (2011) Vitamin D Status Is Associated With Arterial Stiffness and Vascular Dysfunction in Healthy Humans. Journal of the American College of Cardiology, 58, 186-192.