Alcoholism folate deficiency

Folate antagonists (eg, methotrexate and certain antiepileptics) are used ia treatment for various diseases, but their adininistration can lead to a functional folate deficiency. Folate utilization can be impaired by a depletion of ziac (see Zinc compounds). In humans, the intestinal bmsh border folate conjugase is a ziac metaHoenzyme (72). One study iadicates that the substantial consumption of alcohol, when combiaed with an iaadequate iatake of folate and methionine, may iacrease the risk of colon cancer (73). Based on this study, it is recommended to avoid excess alcohol consumption and iacrease folate iatake to lower the risk of colon cancer. 

Megaloblastic anemia results from insufficient active THF to support cell division in the bone marrow. Methotrexate inhibits DHF reductase, making it a useful antineoplastic drug. Folate deficiencies may be seen during pregnancy and in alcoholism. 

Folate deficiency Folate deficiency states may increase methotrexate toxicity. Benzyl alcohol Methotrexate sodium for injection contains the preservative benzyl alcohol and is not recommended for use in neonates. 

The gastritis and chronic pancreatitis associated with chronic alcoholism may result in a reduction of the amount of vitamin B12 absorbed but this has not been found to result in a clinical deficiency (M4). Alcohol can also cause damage to the ileum. Lindenbaum and Lieber gave alcohol to human volunteers for periods of 13—37 days and found that absorption of the vitamin was impaired in six of eight volunteers and this was not corrected by the addition of intrinsic factor or pancreatin (L10,L11). Biopsy of the ileum showed ultra-structural evidence of mitochondrial damage (Rll). It has been shown previously that folate deficiency may result in a reduction in the serum vitamin B12 level (H16) and the low serum vitamin B12 levels found in some alcoholics is probably secondary to folate depletion, which is common in this condition (L12). How folate is able to influence the serum vitamin B12 level is not clear. 

H16. Herbert, V., Zalusky, R., and Davidson, C. S., Correlation of folate deficiency with alcoholism and associated macrocytosis, anaemia, and liver disease. Ann. Intern. Med. 58, 977-988 (1963). 

Decreased metabolism with acute combination with alcohol but increased metabolism with chronic alcohol consumption increased risk of folate deficiency Increased gastrointestinal bleeding... 

In vitamin B12 deficiency, a functional folate deficiency is observed because folate is "trapped" in the form of 5-methyl-THF. Both folate and vitamin B12 deficiencies result in megaloblastic anemia. Actual folate deficiency is often observed in alcoholics and pregnant women. 

Folic acid is involved in DNA synthesis and is needed to form three of the four bases of DNA. It is absorbed in the upper small intestine, but this does not require intrinsic factor. Folate deficiency may occur in alcoholics and other chronically malnourished people. 

Dietary deficiency. Folate deficiency is extremely common in the setting of general malnutrition in developing countries and is a particular problem in childhood. In Western countries folate deficiency occurs in alcoholics, some slimming diets, the elderly, the infirm and psychiatric patients. 

Vitamin M Vitamin M is also called pteroylglutaminic add or folic acid. It was isolated from yeast extract by Wills in 1930. Its structure was described by Anger in 1946. Folic add is made up of pteridine + p-aminobenzoic add + glutamic add. There are several known derivatives, called folates, which are capable of mutual restructuring. The coenzyme tetrahydrofolic acid, which plays a role in many biochemical reactions, is formed with the help of Bi2. Around 50% of total body folate are stored in the liver. A folate-binding protein (FBP) is available for transport. Folate undergoes enterohepatic circulation. The release of folate from the liver cells is stimulated by alcohol, which increases urine excretion. Folate deficiency (e.g. in the case of alcohol abuse) is accompanied by the development of macrocytosis. 

Poor dietary habits as those of chronic alcoholics can lead to folate deficiency., ... 

The predominant causes of folate deficiency in non-alcoholics are impaired absorption or metabolism or an increased demand for the vitamin. 

Chronic alcoholism is the major cause of folate deficiency in the United States. Alcoholics generally have poor diets — for example, one liter of whiskey per day. It is not dear if the alcohol induces metabolic defects that interfere with the metabolism and function of folate. Beer docs contain folate, as this product is brewed with yeast, an organism containing high levels tif the vitamin. Wine and hard liquors, on the other hand, contain little or no folate. The elderly may also be at risk for folate deficiency. It is thought that in the elderly the deficiency is due to poor diets rather than age-related defects in the absorption and utilization of folate. 

The population thought to be nxost at risk for Bf, deficiency comprises chronic alcoholics. The deficiency arises fixim a low intakt of the vitamin as well as from alcoho[-induced impairments in the metabolism of the vitamin. An alcoholic deriving of his or her energy requirement from whiskey might be expected to be consuming only 20% of the KDA for vitamin 8, as well as for other nutrients such as protein, folate, and thiamin. 1 he symptoms of deficiency are not specific for this nutrient- They include depression, confusion, and sometimes convulsions. 

Triamterene blocks dihydrofolate reductase and can cause folate deficiency with megaloblastic anemia and pancytopenia, particularly in patients with hepatic cirrhosis, who have reduced clearance of the drug (SED-11, 431). When this has been reported, all patients were taking doses of 150-600 mg/day for ascites and all had hepatic cirrhosis, often due to alcohol abuse (SEDA-17, 269). It is advisable to use spironolactone rather than triamterene in patients with cirrhosis. 

Chronic overdrinking or binge-drinking alcoholism causes deficiencies of folate, thiamine, pyridoxine, vitamin A, and zinc, the combination of which causes multiple risks for disease, but mostly for cancer. 

It is of paramount importance to rule out vitamin B12 deficiency when folate deficiency is detected, as symptoms are similar. Laboratory changes associated with folate deficiency are similar to those seen in vitamin Bn deficiency, except vitamin Bn levels are normal. Decreases occur in the serum folate level (<3 ng/mL) within a few days of dietary folate limitations. The RBC folate level (<150 ng/mL) also declines and may be a better indicator of deficiency, as levels remain constant throughout the life span of the erythrocyte. Serum folate levels are sensitive to short-term changes such as dietary restrictions or alcohol intake, which may result in a short-term decline in serum levels with adequate tissue stores. It should be noted that an estimated 60% of patients with pernicious anemia have falsely low RBC folate levels, in all probability due to the requirement of cobal-amin for the normal transfer of methyltetrahydrofolate from plasma to cells. Additionally, if serum or erythrocyte folate levels are borderline, serum homocysteine is usually increased with a folic acid deficiency. If serum MMA levels are also elevated, vitamin B12 deficiency needs to be ruled out. 

B. Megaloblastic anemia is caused by a decrease in the synthesis of deoxythymidylate and the purine bases usually caused by a deficiency in either THF or cobalamin or both. This results in decreased DNA synthesis, which results in abnormally large hematopoietic cells created by perturbed cell division and DNA replication and repair. This patient exhibits signs of chronic alcoholism, which often leads to a folate deficiency. This can occur due to poor dietary intake, decreased absorption of folate due to damage of the intestinal brush border cells and resulting conjugase deficiency, and poor renal resorption of folate. 

Many patients in intensive care units receive intravenous nutrition, which is a mixture of various amino acids, sorbitol, and ethanol. In a study of 30 patients with normal preoperative folate levels who were operated on for gastrointestinal disease, the serum folate fell within 48 hours by 60-95% in 20 patients receiving intravenous nutrition (W24). Seven patients had a megaloblastic bone marrow. Daily treatment with 0.5 mg of folic acid given intravenously prevented any clinical signs of folate deficiency. These patients received between 100 and 150 g of ethanol daily as part of their parenteral nutrition, and this may have played a significant role in the development of folate deficiency. However, Tennant (T12) examined this possibility and found that acute depression of the serum folate concentration occurred with both alcohol-firee and alcohol-containing preparations used for parenteral nutrition. It was also noted that only one particular brand of... 

Once absorbed, folate is transported rapidly to tissues as CH3H PteGlu. While certain plasma proteins do bind folate derivatives, they have a greater affinity for nonmethylated analogs their role in folate homeostasis is not well understood. An increase in binding capacity is detected in folate deficiency and in certain disease states (e.g., uremia, cancer, and alcoholism). 

FOLATE DEFICIENCY Folate deficiency is a common complication of diseases of the small intestine, which interfere with the absorption of dietary folate and the recirculation of folate through the enterohepatic cycle. In acute or chronic alcohohsm, daily intake of dietary folate may be severely restricted, and the enterohepatic cycle of the vitamin may be impaired by toxic effects of alcohol on hepatic parenchymal cells this is the most common cause of folate-deficient megaloblastic erythropoiesis. However, it also is the most amenable to therapy, inasmuch as the reinstitution of a normal diet is sufficient to overcome the effect of alcohol. Disease states characterized by a high rate of cell turnover, such as hemolytic anemias, also may be complicated by folate deficiency. Additionally, drugs that inhibit dihydrofolate reductase (e.g., methotrexate and trimethoprim) or that interfere with the absorption and storage of folate in tissues (e.g., certain anticonvulsants and oral contraceptives) can lower the concentration of folate in plasma and may cause a megaloblastic anemia. 

Folate deficiency has been implicated in neural tube defects, including spina bifida, encephalo-celes, and anencephaly. This is true even in the absence of folate-deficient anemia or alcoholism. An inadequate intake of folate also can result in elevations in plasma homocysteine. Since even moderate hyperhomocysteinemia is considered an independent risk factor for coronary artery and peripheral vascular disease and for venous thrombosis, the role of folate as a methyl donor in the homocysteine-to-methionine conversion is getting increased attention. Patients who are heterozygous for one or another enzymatic defect and have high normal to moderate elevations of plasma homocysteine may improve with foUc acid therapy. 

As with vitamin B deficiency, any patient with folate deficiency and a megaloblastic anemia should be evaluated carefully to determine the underlying cause of the deficiency state. This should include evaluation of the effects of medications, the amount of alcohol intake, the patient s history of travel, and the function of the GI tract. 

AST were significantly below those seen in acute viral hepatitis. In addition, the ratio of the absolute values for serum ALT and AST often differ in the two diseases, tending to be greater than 1 in acute viral hepatitis and less than 1 in chronic alcohol-induced cirrhosis. The reason for the difference in ratio of enzyme activities released is not understood, but a lower level of ALT in the serum may be attributable to an alcohol-induced deficiency of pyridoxal phosphate. In addition, serologic tests for viral hepatitis were nonreactive. Her serum folate, vitamin B12, and iron levels were also slightly suppressed, indicating impaired nutritional status. 

Folate deficiencies frequently occur in individuals with chronic alcoholism. A number of factors are involved inadequate dietary intake of folate direct damage to intestinal cells and brush border enzymes, which interferes with absorption of dietary folate a defect in the enterohepatic circulation, which reduces the absorption of folate liver damage causing decreased hepatic production of plasma proteins and interference with kidney resorption of folate. 

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