Effect of Alcohol on Serum Folate Level

Eichner, E. Randy; Hillman, Robert W.

doi:10.1172/jci107219

Cited by 145 publications

(42 citation statements)

References 20 publications

(26 reference statements)

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“…In addition, folate intake tended to be negatively correlated with serum folate in male students. One reason to explain a negative correlation might be high intake of beer, and alcohol intake negatively affects serum folate concentrations (Eichner & Hillman, 1973). Similar findings that men had lower mean concentrations of serum and erythrocyte folate than women have been shown by other investigators (Lim & Heo, 2002;Planells et al, 2003;Ganji & Kafai, 2003).…”

Section: Discussionsupporting

confidence: 61%

Folate intake estimated with an updated database and its association to blood folate and homocysteine in Korean college students

2004

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Objective: To measure folate content in cooked foods commonly consumed in Korea for evaluating its relation to folate nutriture of college students. Design: Folate content in 32 raw and cooked foods was measured by microbiological assay after trienzyme extraction. These values and the previously published values of 110 raw foods commonly consumed in Korea were used to update the currently available food tables to estimate dietary folate intake of 106 students based on a 3-day 24-h recall. The association of folate intake with blood folate and homocysteine concentrations was evaluated. Setting: Cheongju, Korea. Subjects: Healthy college students aged 18 to 27 y old (44 males and 62 females). Results: The average folate loss in 32 foods caused by cooking was 29%. The mean daily dietary folate intakes estimated with an updated database were 406 and 305 mg in males and females, respectively. About 10% of both male and female students showed low serum folate (o6.8 nmol/l). Folate intake was positively correlated with serum and erythrocyte folate concentrations in female students (r ¼ 0.27 and 0.29, respectively, Po0.05), and negatively correlated with serum homocysteine in male students (r ¼ À0.41, Po0.05). Conclusions: Mean dietary folate intake was higher than those of previous studies since the database was updated using values obtained with trienzyme extraction. Folate intake for the general population should be re-evaluated using reliable food folate values obtained with trienzyme extraction.

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Section: Discussionsupporting

confidence: 61%

Folate intake estimated with an updated database and its association to blood folate and homocysteine in Korean college students

2004

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“…31,32 The present finding of decreased MTHFR activity in response to both ethanol feeding and folate deficiency may constitute another explanation for low serum folate levels in chronic alcoholics. 16 However, we cannot determine whether decreased MTHFR activity resulted in selectively decreased end product 5-MTHF in the experimental groups, because folate analogs were not measured in their livers. In this regard, tetrahydrofolate, not 5-MTHF, is the major constituent of plasma folate in the pig, 33 whereas the distribution of pig liver folates is not known.…”

Section: Discussionmentioning

confidence: 97%

“…1) and prior evidence for the effects of ethanol on promoting folate deficiency and altering methionine metabolism. [3][4][5][6][7]16 We developed a micropig model for alcoholic liver disease based on 14 weeks of feeding diets that either contained ethanol or were deficient in folate, or both factors in combination. 15 Compared with the control group fed a folate-sufficient diet without ethanol, each folate-deficient diet reduced liver folate by one half, and the combined diet resulted in a fourfold elevation in plasma homocysteine.…”

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confidence: 99%

Hepatic transmethylation reactions in micropigs with alcoholic liver disease

Villanueva

Halsted

2004

Hepatology

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Alcoholic liver disease is associated with abnormal hepatic methionine metabolism, including increased levels of homocysteine and S-adenosylhomocysteine (SAH) and reduced levels of Sadenosylmethionine (SAM) and glutathione (GSH). The concept that abnormal methionine metabolism is involved in the pathogenesis of alcoholic liver disease was strengthened by our previous findings in a micropig model where combining dietary folate deficiency with chronic ethanol feeding produced maximal changes in these metabolites together with early onset of microscopic steatohepatitis and an eightfold increase in plasma aspartate aminotransferase. The goal of the present study was to determine potential mechanisms for abnormal levels of these methionine metabolites by analyzing the transcripts and activities of transmethylation enzymes in the livers of the same micropigs. Ethanol feeding or folate deficiency, separately or in combination, decreased transcript levels of methylenetetrahydrofolate reductase (MTHFR), methionine adenosyltransferase (MAT1A), glycine-N-methyltransferase (GNMT) and S-adenosylhomocysteine hydrolase (SAHH). Ethanol feeding alone reduced the activities of methionine synthase (MS) and MATIII and increased the activity of GNMT. Each diet, separately or in combination, decreased the activities of MTHFR and SAHH. In conclusion, the observed abnormal levels of methionine metabolites in this animal model of accelerated alcoholic liver injury can be ascribed to specific effects of ethanol with or without folate deficiency on the expressions and activities of hepatic enzymes that regulate transmethylation reactions. These novel effects on transmethylation reactions may be implicated in the pathogenesis of alcoholic liver disease. ( A bnormal hepatic methionine metabolism can result from chronic exposure to ethanol or from folate deficiency. Hyperhomocysteinemia has been described in chronic alcoholics, 1,2 and decreased liver S-adenosylmethionine (SAM) levels were found in experimental animals and cultured hepatocytes exposed to ethanol. [3][4][5][6] Folate deficiency also results in abnormal methionine metabolism, because 5-methyltetrahydrofolate (5-MTHF) is substrate for the methionine synthase (MS) reaction that converts homocysteine to methionine, the substrate for SAM (Fig. 1). Furthermore, folate deficiency is frequently associated with alcoholic liver disease, in part, because chronic exposure to ethanol reduces the intestinal transport of folic acid and increases folate excretion in the urine. [7][8][9] Previous data support the concept that changes in methionine metabolism are involved in the development of alcoholic liver disease. Studies in rats and micropigs have demonstrated MS activity is reduced during chronic ethanol exposure. 10 -13 Rats that were fed ethanol by gastric tube demonstrated decreased methionine adenosyltransferase MAT1-III activity with decreased SAM and SAM/ S-adenosylhomocysteine (SAH) ratio in association with increased DNA strand breaks. 5 A MAT1A knockout mouse model developed he...

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“…The inverse association between folate status and breast cancer risk has been particularly strong among women who consumed alcohol (Sellers et al, 2001;Zhang et al, 2003). To determine whether alcohol intake is also inversely associated with the status of these vitamins, potentially bridging the gap between alcohol and breast cancer, many researchers have investigated the effects of chronic alcohol consumption on folate and vitamin B 12 status (Eichner & Hillman, 1973;Halsted et al, 1973;Paine et al, 1973;McGuffin et al, 1975;Wu et al, 1975;Bonjour, 1980;Halsted, 1980;Lindenbaum, 1980). However, these studies are limited by small sample sizes, weaknesses associated with case-control and cross-sectional designs, failure to adjust for potentially confounding nutrient intakes, and the use of unreliable measures of folate, vitamin B 12 , and alcohol intakes, all of which have high day-to-day variability (Guthrie & Crocetti, 1985;Posner et al, 1992;Firth et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Effects of moderate alcohol consumption on folate and vitamin B12 status in postmenopausal women

et al. 2004

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Background: Although alcohol intake has been positively associated with breast cancer risk in epidemiologic studies, a causal relationship has not been established, and the mechanisms mediating this association are speculative. Alcohol may act through altered status of folate and vitamin B 12 , two vitamins required for DNA methylation and nucleotide synthesis, and thus cell integrity. Although the effects of heavy alcohol intake on folate and vitamin B 12 status have been well-documented, few studies have addressed the effects of moderate alcohol intake in a controlled setting. Objective: The objective of this study was to determine the effects of moderate alcohol intake on folate and vitamin B 12 status in healthy, well-nourished, postmenopausal women. Design: The study design was a randomized, diet-controlled crossover intervention. Postmenopausal women (n ¼ 53) received three 8-week alcohol treatments in random order: 0, 15, and 30 g/day. Treatment periods were preceded by 2-5-week washout periods. Blood collected at baseline and week 8 of each treatment period was analyzed for serum folate, vitamin B 12 , homocysteine (HCY), and methylmalonic acid (MMA) concentrations. Results: After adjusting for body mass index (BMI), a significant 5% decrease was observed in mean serum vitamin B 12 concentrations from 0 to 30 g of alcohol/day (461.45730.26 vs 440.25730.24 pg/ml; P ¼ 0.03). Mean serum HCY concentrations tended to increase by 3% from 0 to 30 g of alcohol/day (9.4470.37 vs 9.7370.37 mmol/l; P ¼ 0.05). Alcohol intake had no significant effects on serum folate or MMA concentrations. Conclusions: Among healthy, well-nourished, postmenopausal women, moderate alcohol intake may diminish vitamin B 12 status. Sponsorship: NCI, NIH and ARS, USDA.

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Effect of Alcohol on Serum Folate Level

Cited by 145 publications

References 20 publications

Folate intake estimated with an updated database and its association to blood folate and homocysteine in Korean college students

Folate intake estimated with an updated database and its association to blood folate and homocysteine in Korean college students

Hepatic transmethylation reactions in micropigs with alcoholic liver disease

Effects of moderate alcohol consumption on folate and vitamin B12 status in postmenopausal women

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