Hyperhomocysteinemia in chronic alcoholism: relations to folic acid and vitamins B(6) and B(12) status. 2000

M L Cravo, and M E Camilo
Serviço de Gastrenterologia, Instituto Português de Oncologia Francisco Gentil, Lisbon, Portugal. mcarvo.cplancha@mail.telepac.pt

The objective of this review is to present and discuss the current perspectives of homocysteine and one carbon metabolism in chronic alcoholism. Chronic alcoholics frequently suffer from specific micronutrient deficiencies, including vitamins involved in one carbon metabolism, i.e., folate, vitamin B(6) and vitamin B(12). The possible link between homocysteine and alcoholism stems from the fact that homocysteine metabolism is closely linked to the metabolism of these three vitamins. In fact, homocysteine stands at the intersection of two pathways: methylation and transsulfuration. In methylation, homocysteine acquires a methyl group from N-5-methyltetrahydrofolate in a vitamin B(12) dependent reaction, whereas in the transsulfuration pathway, homocysteine condenses with serine to form cystathionine in an irreversible reaction catalyzed by the pyridoxal-5'-phosphate-containing enzyme, cystathionine-beta-synthase. Due to these relationships, nutritional deficiency of one of these vitamins, as a consequence of chronic alcohol intake, could lead to metabolic disruption and potentially to hyperhomocysteinemia. Consistent with an interference of alcohol in these metabolic pathways, a previous study performed in chronic alcoholics in whom hyperhomocysteinemia was observed along with disturbed vitamin status, DNA hypomethylation in peripheral lymphocytes was demonstrated as well. Because all these alterations were observed in the absence of clinically overt disease, one might speculate whether these metabolic abnormalities could be involved in the pathogenesis of organic diseases associated to chronic alcoholism.

UI MeSH Term Description Entries
D009752 Nutritional Status State of the body in relation to the consumption and utilization of nutrients. Nutrition Status,Status, Nutrition,Status, Nutritional
D005494 Folic Acid Deficiency A nutritional condition produced by a deficiency of FOLIC ACID in the diet. Many plant and animal tissues contain folic acid, abundant in green leafy vegetables, yeast, liver, and mushrooms but destroyed by long-term cooking. Alcohol interferes with its intermediate metabolism and absorption. Folic acid deficiency may develop in long-term anticonvulsant therapy or with use of oral contraceptives. This deficiency causes anemia, macrocytic anemia, and megaloblastic anemia. It is indistinguishable from vitamin B 12 deficiency in peripheral blood and bone marrow findings, but the neurologic lesions seen in B 12 deficiency do not occur. (Merck Manual, 16th ed) Deficiency, Folic Acid,Acid Deficiencies, Folic,Acid Deficiency, Folic,Deficiencies, Folic Acid,Folic Acid Deficiencies
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000437 Alcoholism A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. (Morse & Flavin for the Joint Commission of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism: in JAMA 1992;268:1012-4) Alcohol Abuse,Alcoholic Intoxication, Chronic,Ethanol Abuse,Alcohol Addiction,Alcohol Dependence,Alcohol Use Disorder,Abuse, Alcohol,Abuse, Ethanol,Addiction, Alcohol,Alcohol Use Disorders,Chronic Alcoholic Intoxication,Dependence, Alcohol,Intoxication, Chronic Alcoholic,Use Disorders, Alcohol
D014806 Vitamin B 12 Deficiency A nutritional condition produced by a deficiency of VITAMIN B 12 in the diet, characterized by megaloblastic anemia. Since vitamin B 12 is not present in plants, humans have obtained their supply from animal products, from multivitamin supplements in the form of pills, and as additives to food preparations. A wide variety of neuropsychiatric abnormalities is also seen in vitamin B 12 deficiency and appears to be due to an undefined defect involving myelin synthesis. (From Cecil Textbook of Medicine, 19th ed, p848) Deficiency, Vitamin B 12,Deficiency, Vitamin B12,Vitamin B12 Deficiency,Deficiencies, Vitamin B12,Vitamin B12 Deficiencies
D020138 Hyperhomocysteinemia Condition in which the plasma levels of homocysteine and related metabolites are elevated (>13.9 μmol/l). Hyperhomocysteinemia can be familial or acquired. Development of the acquired hyperhomocysteinemia is mostly associated with vitamins B and/or folate deficiency (e.g., PERNICIOUS ANEMIA, vitamin malabsorption). Familial hyperhomocysteinemia often results in a more severe elevation of total homocysteine and excretion into the urine, resulting in HOMOCYSTINURIA. Hyperhomocysteinemia is a risk factor for cardiovascular and neurodegenerative diseases, osteoporotic fractures and complications during pregnancy. Hyperhomocysteinemias
D026681 Vitamin B 6 Deficiency A nutritional condition produced by a deficiency of VITAMIN B 6 in the diet, characterized by dermatitis, glossitis, cheilosis, and stomatitis. Marked deficiency causes irritability, weakness, depression, dizziness, peripheral neuropathy, and seizures. In infants and children typical manifestations are diarrhea, anemia, and seizures. Deficiency can be caused by certain medications, such as isoniazid. Pyridoxine Deficiency,Deficiency, Pyridoxine,Deficiency, Vitamin B 6,Deficiency, Vitamin B6,Vitamin B6 Deficiency,Vitamin Deficiency, B6,B6 Deficiencies, Vitamin,B6 Deficiency, Vitamin,B6 Vitamin Deficiencies,B6 Vitamin Deficiency,Deficiencies, B6 Vitamin,Deficiencies, Vitamin B6,Deficiency, B6 Vitamin,Vitamin B6 Deficiencies,Vitamin Deficiencies, B6

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