REVIEW ARTICLE Biomarkers of alcoholism: an updated review S. K. Das*, L. Dhanya and D. M. Vasudevan Department of Biochemistry, Amrita Institute of Medical Sciences, Kerala, India Alcoholic beverages, and the problems they engender, have been familiar in human societies since the beginning of recorded history. Among a variety of blood tests used to aid the diagnosis of alcohol consumption and related disorders, laboratory tests are particularly useful in settings where cooperativeness is suspected or when a history is not available. Biochemical and haematological tests, such as gamma-glutamyltransferase activity, aspartate aminotransferase activity and erythrocyte mean corpuscular volume, are established markers of alcohol intake. Carbohydrate-deficient transferrin is the only test approved by the FDA for the identification of heavy alcohol use. Total serum sialic acid and sialic acid index of Apolipoprotein J have the potential to be included in a combination of measurements providing an accurate, more exact, assessment of alcohol consumption in a variety of clinical and research settings. Several other markers with considerable potential for measuring recent alcohol intake include beta-hexosaminidase, acetaldehyde adducts and the urinary ratio of serotonin metabolites, 5- hydroxytryptophol and 5-hydroxyindoleacetic acid. These markers provide hope for more sensitive and specific aids to diagnosis and improved monitoring of alcohol intake. Keywords: Acetaldehyde; alcohol; aspartate aminotransferase; carbohydrate-deficient transferrin; collagen; ethanol; gamma glutamyltransferase; tumour necrosis factor Introduction Alcoholic beverages, and the problems they engender, have been familiar in human societies since the beginning of recorded history. Alcohol is no longer viewed as a threat to all people, but rather to a small subclass of ‘‘alcoholics’’ or, in today’s technical terms, people who are ‘‘alcohol-dependent’’ [1]. Measuring alcohol use and alcoholic liver disease in an individual or in a country has several limitations, and the definition of a ‘‘standard’’ drink varies significantly from country to country. Although most heavy drinkers imbibing more than 50 g per day do not develop significant liver disease, a certain amount is required to develop alcoholic liver disease (ALD) [2]. Evidence suggests that the risk is increased with ingestion of w40 g/day for males (or about 4 drinks or two-thirds of a bottle of table wine) and w20 g/ day for females [3]. This level is considered ‘‘hazar- dous’’ and ‘‘harmful’’ in medical epidemiological meta-analyses [4]. However, alcohol is causally related to more than 60 medical conditions [1]. Physicians have long sought an accurate and inexpensive means of identifying persons who con- sume excessive amounts of ethanol. It has been reported that medically diagnosed alcoholics can be differentiated from non-alcoholics using clinical laboratory tests. Moreover, distinguishing alcoholic from non-alcoholic liver disease patients has impor- tant implications for its treatment and management [5]. Despite intensive investigation, there is still no satisfactory laboratory marker for surreptitious alcohol ingestion. Chronic alcoholism is diagnosed on the basis of clinical history, questionnaires about alcohol consumption and a number of laboratory investigations [6]. The perceived difficulty of obtaining an accurate drinking history may be one reason for the wide- spread under-diagnosis of alcohol misuse and related disorders [7]. Ethanol can be easily and accurately measured in body fluids or vapours by several chemical and enzymatic methods. However, the existence of ethanol in the body is short lived and ethanol’s metabolism and distribution within the body are extremely complex. The complex distribu- tion and metabolism of ethanol and its metabolites can obscure the relationship between the ethanol concentration that is measured in body fluids or vapours and the amount that is actually taken into the body [8]. Various blood tests have been used to aid in the assessment of drinking history. More recently, laboratory tests based on urine, breath and sweat analyses have been investigated, but there has been a great deal of controversy over the usefulness of these markers. Many conventional tests have only *Correspondence author. Subir Kumar Das, Department of Biochemistry, Amrita Institute of Medical Sciences, Elamakkara P.O. Cochin 682 026, Kerala, India. Tel: +91 484 2801234. Fax: +91 484 2802051. Email: subirkumardas@aims.amrita.edu; drsubirkdas@yahoo.co.in (Received 30 March 2007; accepted 7 May 2007) The Scandinavian Journal of Clinical & Laboratory Investigation, Vol. 68, No. 2, April 2008, 81–92 ISSN 0036-5513 print/ISSN 1502-7686 online # 2008 Informa UK Ltd (Informa Healthcare, Taylor & Francis AS). DOI: 10.1080/00365510701532662 http://www.informaworld.com