Homocysteine as a biomarker for predicting alcohol withdrawal syndromes: Insight from a retrospective cohort study

Main Article Content




The alcohol withdrawal syndrome is a group of symptoms and signs that usually arise within 24 -48 hours of abrupt alcohol cessation or significant reduction in consumption in alcohol dependent individuals. The most severe complication of alcohol withdrawal syndrome is alcohol withdrawal delirium (delirium tremens), which may be preceded or complicated by seizures. In recent years there is a growing interest in the role of serum homocysteine levels in chronic alcohol dependent patients undergoing withdrawal. A number of studies have shown that alcohol dependent patients have elevated serum homocysteine levels and that it can be considered to be a risk factor for severe withdrawal states. The purpose of this study was to evaluate the serum homocysteine levels in alcohol withdrawal syndromes.


It was a retrospective cohort study of alcohol dependent patients (N=49) admitted with a diagnosis of delirium tremens (DT) (n=28) and simple alcohol withdrawal (SW) (n=21) as per the ICD-10 classification. A semi-structured pro-forma was used to gather information from the file records covering both socio-demographic, clinical and biochemical variables. The historical variables included proposed risk factors like amount of daily consumption of alcohol, duration of abstinence and past history of complicated withdrawal. The serum homocysteine, vitamin B12 and folate levels of all patients sent within 24 hours of admission were also collected. Comparisons between clinical and biochemical variables were made between the two groups using Chi-square test and Student’s T test.


The mean age of patients of DT was 33.07 ± 8.24 years while that of patients with SW was 37.19 ±7.60 years. The mean duration of alcohol use in dependent pattern was 10.00 ±3.00 years in DT compared to 8.66 ±4.76 years in SW. The laboratory investigations revealed a mean serum homocysteine level of 21.09 ± 12.81 in patients presenting with DT as compared with 15.06 ± 6.17 in patients having SW and this difference was statistically significant (p<0.05). The serum folate levels differed significantly in the two groups with patients in DT having a lower mean value of 6.30 ± 3.67 as compared to patients with SW 10.23 ± 7.04. Patients with DT with withdrawal seizures (n=18) had statistically non significant rise in their mean homocysteine levels as compared to patients with DT without withdrawal seizures (n=10) [21.72±13.26 vs 19.96±12.58].


The results of this study highlight the potential role of homocysteine as a new biomarker to predict the severity of alcohol withdrawal syndromes. However there is need for further research to prove whether targeting homocysteine levels will be of benefit with respect to alcohol related disorders.


Article Details

How to Cite
SINHA, PALLAVI et al. Homocysteine as a biomarker for predicting alcohol withdrawal syndromes: Insight from a retrospective cohort study. Medical Research Archives, [S.l.], v. 4, n. 6, oct. 2016. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/701>. Date accessed: 25 june 2024.
Research Articles


Bayerlein, K., Hillemacher, T., Reulbach, U., Mugele, B., Sperling, W., Kornhuber, J., &Bleich, S. (2005).Alcoholism-associated hyperhomocysteinemia and previous withdrawal seizures.Biological Psychiatry, 57(12), 1590–1593. http://doi.org/10.1016/j.biopsych.2005.01.046

Berggren, U., Fahlke, C., Berglund, K. J., Blennow, K., Zetterberg, H., &Balldin, J. (2009). Thrombocytopenia in early alcohol withdrawal is associated with development of delirium tremens or seizures. Alcohol and Alcoholism (Oxford, Oxfordshire), 44(4), 382–386. http://doi.org/10.1093/alcalc/agp012

Bleich, S., Carl, M., Bayerlein, K., Reulbach, U., Biermann, T., Hillemacher, T., Bonsch, D., Kornhuber, J. (2005). Evidence of increased homocysteine levels in alcoholism: the Franconian alcoholism research studies (FARS). Alcoholism, Clinical and Experimental Research, 29(3), 334–336.

Bleich, S., Degner, D., Bandelow, B., Ahsen, N. von, Rüther, E., &Kornhuber, J. (2000). Plasma homocysteine is a predictor of alcohol withdrawal seizures. Neuroreport, 11(12), 2749–2752.
Bleich, S., Degner, D., Wiltfang, J., Maler, J. M., Niedmann, P., Cohrs, S., et al. (2000). Elevated homocysteine levels in alcohol withdrawal. Alcohol and Alcoholism (Oxford, Oxfordshire), 35(4), 351–354.

Brustolin, S., Giugliani, R., & Félix, T. M. (2010).Genetics of homocysteine metabolism and associated disorders. Brazilian Journal of Medical and Biological Research, 43(1), 1–7.

Cravo, M. L., Glória, L. M., Selhub, J., Nadeau, M. R., Camilo, M. E., Resende, M. P., et al. (1996). Hyperhomocysteinemia in chronic alcoholism: correlation with folate, vitamin B-12, and vitamin B-6 status. The American Journal of Clinical Nutrition, 63(2), 220–224.

Cylwik, B., Czygier, M., Daniluk, M., Chrostek, L., &Szmitkowski, M. (2010). [Vitamin B12 concentration in the blood of alcoholics].Polski Merkuriusz Lekarski, 28(164), 122–125.

Desouza, C., Keebler, M., McNamara, D. B., & Fonseca, V. (2012).Drugs Affecting Homocysteine Metabolism.Drugs, 62(4), 605–616. http://doi.org/10.2165/00003495-200262040-00005

Eyer, F., Schuster, T., Felgenhauer, N., Pfab, R., Strubel, T., Saugel, B., &Zilker, T. (2011). Risk assessment of moderate to severe alcohol withdrawal--predictors for seizures and delirium tremens in the course of withdrawal. Alcohol and Alcoholism (Oxford, Oxfordshire), 46(4), 427–433. http://doi.org/10.1093/alcalc/agr053

Goodson, C. M., Clark, B. J., & Douglas, I. S. (2014). Predictors of severe alcohol withdrawal syndrome: a systematic review and meta-analysis. Alcoholism, Clinical and Experimental Research, 38(10), 2664–2677. http://doi.org/10.1111/acer.12529

Halsted, C. H., Villanueva, J. A., Devlin, A. M., & Chandler, C. J. (2002). Metabolic interactions of alcohol and folate.The Journal of Nutrition, 132(8 Suppl), 2367S–2372S.
Jacques, P. F., Bostom, A. G., Williams, R. R., Ellison, R. C., Eckfeldt, J. H., Rosenberg, I. H., et al. (1996). Relation between folate status, a common mutation in methylenetetrahydrofolatereductase, and plasma homocysteine concentrations.Circulation, 93(1), 7–9.

Kang, S. S., Wong, P. W., &Norusis, M. (1987). Homocysteinemia due to folate deficiency.Metabolism: Clinical and Experimental, 36(5), 458–462.

Kim, D. W., Kim, H. K., Bae, E. K., Park, S. H., & Kim, K. K. (2015). Clinical predictors for delirium tremens in patients with alcohol withdrawal seizures.The American Journal of Emergency Medicine, 33(5), 701–704. http://doi.org/10.1016/j.ajem.2015.02.030

Lee, J. H., Jang, M. K., Lee, J. Y., Kim, S. M., Kim, K. H., Park, J. Y., et al. (2005).Clinical predictors for delirium tremens in alcohol dependence.Journal of Gastroenterology and Hepatology, 20(12), 1833–1837. http://doi.org/10.1111/j.1440-1746.2005.03932.x

Lingford-Hughes, A., & Nutt, D. (2003).Neurobiology of addiction and implications for treatment.The British Journal of Psychiatry: The Journal of Mental Science, 182, 97–100.

Lipton, S. A., Kim, W. K., Choi, Y. B., Kumar, S., Emilia, D. M. D’, Rayudu, P. V., et al. (1997). Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor. Proceedings of the National Academy of Sciences of the United States of America, 94(11), 5923–5928.

Mainerova, B., Prasko, J., Latalova, K., Axmann, K., Cerna, M., Horacek, R., &Bradacova, R. (2015).Alcohol withdrawal delirium - diagnosis, course and treatment.Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia, 159(1), 44–52. http://doi.org/10.5507/bp.2013.089

Qiang, M., Denny, A. D., &Ticku, M. K. (2007). Chronic intermittent ethanol treatment selectively alters N-methyl-D-aspartate receptor subunit surface expression in cultured cortical neurons. Molecular Pharmacology, 72(1), 95–102. http://doi.org/10.1124/mol.106.033043

Refsum, H., Ueland, P. M., Nygård, O., &Vollset, S. E. (1998).Homocysteine and cardiovascular disease.Annual Review of Medicine, 49, 31–62. http://doi.org/10.1146/annurev.med.49.1.31

World Health Organization. (1992). The ICD-10 classification of mental and behavioural disorders: Clinical descriptions and diagnostic guidelines. Geneva: World Health Organization.