Vitamin B Supplementation and Homocysteine Reduction in Nigerian Children with Nephrotic Syndrome: A Randomized Controlled Trial

Bose E. Orimadegun^1, , Adebowale A. Ademola² and Adanze O. Asinobi²

¹Department of Chemical Pathology, College of Medicine, University of Ibadan, Ibadan, Nigeria

²Department of Paediatrics, College of Medicine, University of Ibadan, Ibadan, Nigeria

Cite this paper:
Bose E. Orimadegun, Adebowale A. Ademola and Adanze O. Asinobi. Vitamin B Supplementation and Homocysteine Reduction in Nigerian Children with Nephrotic Syndrome: A Randomized Controlled Trial. World Journal of Nutrition and Health. 2025; 12(1):8-15. doi: 10.12691/jnh-12-1-2

Abstract

Nephrotic syndrome (NS) in children is associated with hyperhomocysteinemia, increasing the risk of cardiovascular disease. The deficiency of vitamins B6, B12, and folate contribute to elevated homocysteine levels, yet limited interventional studies have evaluated the effects of vitamin supplementation in pediatric NS patients. This study investigated the effect of folic acid, vitamin B6, and vitamin B12 supplementation on plasma homocysteine levels in Nigerian children with NS. A single-blind, randomized controlled trial was conducted at the University College Hospital, Ibadan, Nigeria. Forty-eight children with NS and plasma homocysteine >10 μmol/L were randomly assigned to receive either daily supplementation (5 mg folic acid, 50 mg vitamin B6, and 1 mg vitamin B12) or placebo for six months. The primary outcome was homocysteine reduction, while secondary outcomes included changes in vitamin levels, renal function, and lipid profiles. At baseline, demographic and biochemical parameters were similar between groups. After six months, the intervention group showed a significant reduction in homocysteine levels (12.8 ± 1.4 µmol/L to 6.9 ± 2.1 µmol/L, p < 0.001), while the control group had minimal change (13.3 ± 1.8 µmol/L to 12.9 ± 1.9 µmol/L, p = 1.000). The intervention group also had greater reductions than the control group in total cholesterol (-13.2 mg/dL vs. -4.9 mg/dL, p < 0.001) and LDL cholesterol (-9.8 mg/dL vs. -3.6 mg/dL, p < 0.001). Renal function parameters improved similarly in both groups. No serious adverse effects were reported, and adherence was 91.7%. Vitamin B supplementation significantly reduced plasma homocysteine and improved lipid profiles in children with NS. These findings suggest potential cardiovascular benefits, warranting further research with larger cohorts and longer follow-up.

Keywords:
nephrotic syndrome homocysteine vitamin B6 vitamin B12 folic acid lipid profile pediatric nephrology cardiovascular risk

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References:

[1]	Szczuko, M., Kikut, J., Wachowska, K., Drozd, A. and Palma, J., 2023. The significance of homocysteine metabolism in cardiovascular disease prevention. Nutrients, 15(13).
[2]	Banh, T.H.M., Hussain-Shamsy, N., Patel, V., Vasilevska-Ristovska, J., Dufek, S., Bravi, C., Pinsk, M., Geier, P., Abou Khalil, C., Cattran, D. and Parekh, R.S., 2016. Ethnic differences in incidence and outcomes of childhood nephrotic syndrome. Clinical Journal of the American Society of Nephrology, 11(10), pp.1760–1768.
[3]	Eke, F.U. and Eke, N.N., 1994. Renal disorders in children: a Nigerian study. Pediatric Nephrology, 8(3), pp.383–386.
[4]	Orimadegun, B.E., Orimadegun, A.E., Ademola, A.D. and Agbedana, E.O., 2014. Plasma homocysteine and B vitamins levels in Nigerian children with nephrotic syndrome. Pan African Medical Journal, 18, p.107.
[5]	Li, J., Li, B., Qi, J. and Shen, B., 2015. Meta-analysis of clinical trials of folic acid, vitamin B12 and B6 supplementation on plasma homocysteine level and risk of cardiovascular disease. Zhonghua Xin Xue Guan Bing Za Zhi, 43(6), pp.554–561.
[6]	World Health Organization (WHO), 2021. Cardiovascular diseases (CVDs). [online] Available at: https:// www.who.int/ news-room/ fact-sheets/ detail/ cardiovascular-diseases-(cvds) [Accessed 3 Apr. 2025].
[7]	Debreceni, B. and Debreceni, L., 2012. Why do homocysteine-lowering B vitamin and antioxidant E vitamin supplementations appear to be ineffective in the prevention of cardiovascular diseases? Cardiovascular Therapeutics, 30(4), pp.227–233.
[8]	Scott, T.M., Rogers, G., Weiner, D.E., Livingston, K.A., Selhub, J., Jacques, P.F., Rosenberg, I.H. and Troen, A.M., 2017. B-vitamin therapy for kidney transplant recipients lowers homocysteine and improves selective cognitive outcomes in the randomized FAVORIT ancillary cognitive trial. The Journal of Prevention of Alzheimer’s Disease, 4(3), pp.174–182.
[9]	Schulz, K.F., Altman, D.G. and Moher, D. (2010) 'CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials', BMJ, 340, c332. Available at: https://www.equator-network.org/reporting-guidelines/consort/ (Accessed: 6 March 2025).
[10]	Sanchez Alvarez, J., Pérez Tamajón, L., Hernández, D., Álvarez González, A., Delgado, P. and Lorenzo, V. (2005) ‘Efficacy and safety of two vitamin supplement regimens on homocysteine levels in hemodialysis patients. Prospective, randomized clinical trial’, Nefrologia: Publicacion Oficial de la Sociedad Espanola Nefrologia, 25(3), pp. 288-296.
[11]	Frantzen, F., Faaren, A.L., Alfheim, I. and Nordhei, C., 1998. Enzyme conversion immunoassay for determining total homocysteine in plasma or serum. Clinical Chemistry, 44(2), pp.311-316.
[12]	Ribeiro, R., Ribeiro, D., Cota, L., Carvalho, A., & Faleiros, R., 2022. Comparison between the Direct Method and Friedewald's Formula for the Determination of Low-Density Lipoprotein Cholesterol Serum Levels in Horses. SSRN Electronic Journal.
[13]	Maruyama, K., Eshak, E.S., Kinuta, M., Nagao, M., Cui, R., Imano, H., Ohira, T. and Iso, H. (2019) ‘Association between vitamin B group supplementation with changes in % flow-mediated dilatation and plasma homocysteine levels: a randomized controlled trial’, Journal of Clinical Biochemistry and Nutrition, 64, pp. 243–249.
[14]	Keller, A., Klawitter, J., Hildreth, K.L., Christians, U., Putnam, K., Kohrt, W., Reusch, J. & Moreau, K. (2019) 'Elevated plasma homocysteine and cysteine are associated with endothelial dysfunction across menopausal stages in healthy women', Journal of Applied Physiology, 126(6), pp. 1533-1540.