• Mahdi Khaleel Fattah KBMS Trainee of Dermatology, Sulaimani Dermatology Teaching Center. Kurdistan Region, Iraq.
  • Mohammad Y. Saeed College of Medicine, University of Sulaimani, Kurdistan Region, Iraq.



Vitiligo, Homocysteine, Hyperhomocysteinemia, B12, Folate



Vitiligo is an acquired depigmentation disorder that significantly impacts a patient’s quality of life. Its precise etiology is yet unknown, but it appears to be complex. Many studies have been conducted in the last decade to determine the role of hyperhomocysteinemia, vitamin B12, and folate deficiency in the etiology of vitiligo. Studying part of the aforementioned conditions may give insight into vitiligo pathogenesis.


To assess the contribution of homocysteine, vitamin B12, and folate in the pathogenesis of vitiligo by measuring homocysteine (Hcy), B12, and folate levels in the sera of patients and controls. as well as to see if there are a link between them and the degree of severity and duration of the vitiligo.

Patients and Methods

In the current study, 50 vitiligo patients of both sexes and 50 age and sex-matched healthy persons were recruited for six months at the Sulaimani center for skin disease treatment. Serum B12 & folate were measured using electrochemiluminescence (ECL), while serum Hcy level was measured by colorimetric technique.


The mean serum levels of Hcy, B12, and folate in the healthy controls did not differ significantly from those in the patient group. (13.75- ±2.32 vs. 14.31±6.14 μmol/l; P > 0.05), (324.01±131.93 vs 311.57±110.55 pg/ml; P > 0.05), and (8.82±3.09 vs. 8.70±3.20 ng/ml P > 0.05) respectively.

Furthermore, no link was discovered between the serum levels of these parameters and the clinical types, the activity of the disease, and the duration of vitiligo. 


The findings don’t support the theory that homocysteine, B12, and folate are contributing factors in vitiligo etiology. Thus, screening the importance of the above mentioned factors cannot be recommended.


Krüger C, Schallreuter KU. A review of the worldwide prevalence of vitiligo in children/adolescents and adults. Int J Dermatol. 2012;51(10):1206–12. DOI:

Alikhan A, Felsten LM, Daly M, Petronic-Rosic V. Vitiligo: A comprehensive overview: Part I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up. J Am Acad Dermatol [Internet]. 2011;65(3):473–91. Available from: DOI:

Blom HJ, Smulders Y. Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects. J Inherit Metab Dis. 2011;34(1):75–81. DOI:

Kumar A, Palfrey HA, Pathak R, Kadowitz PJ, Gettys TW, Murthy SN. The metabolism and significance of homocysteine in nutrition and health. Nutr Metab. 2017;14(1):1–12. DOI:

Juhlin L OM. Improvement of vitiligo after oral treatment with vitamin B12 and folic acid and the importance of sun exposure. Acta dermato-venereologica. 1997;1;77(6):460–2. DOI:

Guilland JC, Favier A, Potier de Courcy G, Galan P HS. Hyperhomocysteinemia: an independent risk factor or a simple marker of vascular disease?. 1. Basic data. Pathol Biol (Paris). 2003;2(1;51):101-10. DOI:

Reish O, Townsend D, Berry SA, Tsai MY, King RA. Tyrosinase inhibition due to interaction of homocyst(e)ine with copper: The mechanism for reversible hypopigmentation in homocystinuria due to cystathionine β-synthase deficiency. Am J Hum Genet. 1995;57(1):127–32.

Bagheri Hamidi A, Namazi N, Mohammad Amoli M, Amani M, Gholami M, Youssefian L, et al. Association of MTHFR C677T polymorphism with elevated homocysteine level and disease development in vitiligo. Int J Immunogenet. 2020;47(4):342–50. DOI:

Tang XF, Zhang Z, Hu DY, Xu AE, Zhou HS, Sun LD, et al. Association analyses identify three susceptibility loci for vitiligo in the chinese han population. J Invest Dermatol. 2013;133(2):403–10. DOI:

Testai FD, Gorelick PB. Inherited metabolic disorders and stroke part 2: Homocystinuria, organic acidurias, and urea cycle disorders. Arch Neurol. 2010;67(2):148–53. DOI:

Góth L, Rass P, Páy A. Catalase enzyme mutations and their association with diseases. Mol Diagnosis. 2004;8(3):141–9. DOI:

Shaker OG, El-Tahlawi SMR. Is there a relationship between homocysteine and vitiligo? A pilot study. Br J Dermatol. 2008;159(3):720–4. DOI:

Singh S, Singh U, Pandey SS. Increased level of serum Homocysteine in vitiligo. J Clin Lab Anal. 2011;25(2):110–2. DOI:

Karadag AS, Tutal E, Ertugrul DT, Akin KO, Bilgili SG. Serum holotranscobalamine, vitamin B12, folic acid and homocysteine levels in patients with vitiligo. Clin Exp Dermatol. 2012;37(1):62–4. DOI:

Singh S, Singh U, Pandey S. Serum folic acid, vitamin B12 and homocysteine levels in Indian vitiligo patients. Egypt Dermatol Online J. 2012;8(1):1–7. DOI:

Salman MN, Alshalah HH, Alhattab MK. Effect of serum homocysteine in pathogenesis and activity of vitiligo. Res J Pharm Biol Chem Sci. 2016;7(6):1158–64.

Nahidi Y, Meibodi NT, Esmaili H. Serum homocysteine level in vitiligo patients. Iran J Dermatology. 2014;17(69):81–4.

Agarwal S, Mendiratta V, Chander R, Jain A, Yadav P. Study of serum levels of Vitamin B 12 , folic acid, and homocysteine in vitiligo . Pigment Int. 2015;2(2):76. DOI:

Sabry H, Sabry J, Hashim H. Serum levels of homocysteine, vitamin B12, and folic acid in vitiligo. Egypt J Dermatology Venerol. 2014;34(1):65. DOI:

Sundar PK, Chavala BM, Nagaraj SM, Reddy HK. A Study of Serum Levels of Vitamin B12, Folic Acid, and Homocysteine in Vitiligo Patients and Controls Attending a Tertiary Care Hospital in Bengaluru – An Analytical Cross-Sectional Study. J Evol Med Dent Sci. 2021;10(30):2271–5. DOI:

Tsai TY, Kuo CY, Huang YC. Serum homocysteine, folate, and vitamin B 12 levels in patients with vitiligo and their potential roles as disease activity biomarkers: A systematic review and meta-analysis. J Am Acad Dermatol [Internet]. 2019;80(3):646-654.e5. Available from: DOI:

Zaki AM, Abdo HM, Ibrahim IM, Eldin A, Ibrahim K, Ch B. Serum homocysteine and vitiligo. gulf J dermatology Venereol. 2014;21(2):15–20.

Balci DD, Yonden Z, Yenin JZ ON. Serum homocysteine, folic acid and vitamin B12 levels in vitiligo. Eur J Dermatology. 2009;1;19(4):382–3. DOI:

AlGhamdi KM, Khurrum H, Moussa NA. Is there a real relationship between serum level of homocysteine and vitiligo? A controlled study on 306 subjects. J Cutan Med Surg. 2014;18(1):5–7. DOI:

Hasibuan DRU, Putra IB, Jusuf NK. Correlation between serum homocysteine and vitiligo area scoring index. Maced J Med Sci. 2017;5(3):332–4. DOI:

Asri E, Akhyar G, Gustia R. Correlation Between Homocysteine and Vitamin B12 Serum Level with Vitiligo Severity. 2019;10–5. DOI:

Hamza A, Farid C, El-sayed E, Kadeeb H. Assessment of serum homocysteine level in patients with nonsegmental vitiligo. Egypt J Dermatology Venerol. 2015;35(2):59. DOI:

Ghiasi M, Lajevardi V, Farahbakhsh A. Serum levels of vitamin B12, folic acid, and homocysteine in patients with vitiligo. Iran J Dermatology. 2015;18(2):45–50.

Silverberg JI, Silverberg NB. Serum homocysteine as a biomarker of vitiligo vulgaris severity: A pilot study. J Am Acad Dermatol. 2011;64(2):445–7. DOI:

Abdalhafid N, Sherif E, El-dibany SA, El A, Hussein S. Serum Vitamin B12 and Folic Acid in Vitiligo Patients : A Case Control Study. Int J Clin dermatology. 2020;3(2):19–21.

Bhor U PS. Scoring systems in dermatology. Indian J Dermatology, Venereol Leprol. 2006;72(4):315–21. DOI:

Chen J, Li S, Li C. Mechanisms of melanocyte death in vitiligo. Med Res Rev. 2020;(July):1–29.

Kim J, Kim H, Roh H, Kwon Y. Causes of hyperhomocysteinemia and its pathological significance. Arch Pharm Res [Internet]. 2018;41(4):372–83. Available from: DOI:

Anbar T, Zuel-Fakkar NM, Matta MF, Arbab MMI. Elevated homocysteine levels in suction-induced blister fluid of active vitiligo lesions. Eur J Dermatology. 2016;26(1):64–7. DOI:

Park HH, Lee MH. Serum levels of vitamin B12 and folate in Korean patients with vitiligo [3]. Acta Derm Venereol. 2005;85(1):66–7. DOI:

Chen JX, Shi Q, Wang XW, Guo S, Dai W, Li K, et al. Genetic polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) and risk of vitiligo in Han Chinese populations: A genotype-phenotype correlation study. Br J Dermatol. 2014;170(5):1092–9. DOI:



How to Cite