Effects of alcohol consumption on plasma and urinary hormone concentrations in premenopausal women.

BACKGROUND: Most epidemiologic studies of the relationship between alcohol consumption and breast cancer risk over the past decade have shown that persons who consume a moderate amount of alcohol are at 40%-100% greater risk of breast cancer than those who do not consume alcohol. Dose-response effects have been observed, but no causal relationship has been established. PURPOSE: This study examines the hypothesis that alcohol consumption affects levels of reproductive hormones. METHODS: A controlled-diet study lasting for six consecutive menstrual cycles was conducted. Participants were randomly assigned to two groups, and a crossover design was used. During the last three menstrual cycles, alcohol consumption of the two groups was reversed. Thirty-four premenopausal women, aged 21-40 years, with a history of regular menstrual cycles, consumed 30 g of ethanol (equivalent to approximately two average drinks) per day for three menstrual cycles and no alcohol for the other three. All food and alcohol consumed were provided by the study. Caloric intake was monitored to ensure that each woman would maintain body weight at approximately the baseline level. Hormone assays were performed on pooled plasma or 24-hour urine specimens collected during the follicular (days 5-7), peri-ovulatory (days 12-15), and mid-luteal (days 21-23) phases of the third menstrual cycle for subjects on each diet. RESULTS: Alcohol consumption was associated with statistically significant increases in levels of several hormones. Plasma dehydroepiandrosterone sulfate levels were 7.0% higher in the follicular phase (P = .05). In the peri-ovulatory phase, there were increases of 21.2% (P = .01) in plasma estrone levels, 27.5% (P = .01) in plasma estradiol levels, and 31.9% (P = .009) in urinary estradiol levels. In the luteal phase, urinary estrone levels rose 15.2% (P = .05), estradiol levels increased 21.6% (P = .02), and estriol levels rose 29.1% (P = .03). No changes were found in the percent of bioavailable estradiol, defined by the sum of percent free estradiol and percent albumin-bound estradiol. However, increased total estradiol levels in the peri-ovulatory phase suggest elevated absolute amounts of bioavailable estradiol. CONCLUSION: This study has shown increases in total estrogen levels and amount of bioavailable estrogens in association with alcohol consumption in premenopausal women. IMPLICATION: This possible explanatory mechanism for a positive association between alcohol consumption and breast cancer risk merits further investigation.

Serum hormones and the alcohol-breast cancer association in postmenopausal women.

BACKGROUND: Alcohol ingestion is associated with an increased risk of breast cancer in most epidemiologic studies. Results, however, are heterogeneous at lower levels of alcohol intake, and a biologic mechanism for the association has not been clearly identified. To determine whether alcohol consumption by postmenopausal women elevates serum levels of hormones associated with an increased risk of breast cancer, we performed a controlled feeding study. METHODS: Participants were 51 healthy postmenopausal women not using hormone replacement therapy. Each participant rotated through three 8-week dietary periods in which she consumed 15 or 30 g of alcohol per day or an alcohol-free placebo beverage. The order of assignment to the three alcohol levels was random. During the dietary periods, all food and beverages were supplied by the study, and energy intake was adjusted to keep body weight constant. Levels of estradiol, estrone, estrone sulfate, testosterone, androstenedione, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and androstenediol were measured by radioimmunoassays in serum collected at the end of each dietary period. All statistical tests are two-sided. RESULTS: When women consumed 15 or 30 g of alcohol per day, respectively, estrone sulfate concentrations increased by 7.5% (95% confidence interval [CI] = -0.3% to 15.9%; P =.06) and 10.7% (95% CI = 2.7% to 19.3%; P =.009) and DHEAS concentrations increased by 5.1% (95% CI = 1.4% to 9.0%; P =.008) and 7.5% (95% CI = 3.7% to 11.5%; P<.001) relative to levels when women consumed placebo. None of the other hormones measured changed statistically significantly when women consumed alcohol. CONCLUSIONS: Results suggest a possible mechanism by which consumption of one or two alcoholic drinks per day by postmenopausal women could increase their risk of breast cancer.

Moderate alcohol consumption and levels of antioxidant vitamins and isoprostanes in postmenopausal women.

BACKGROUND: Although alcohol intake has been positively associated with breast cancer risk in epidemiologic studies, the mechanisms mediating this association are speculative. OBJECTIVE: The Postmenopausal Women's Alcohol Study was designed to explore the effects of moderate alcohol consumption on potential risk factors for breast cancer. In the present analysis, we evaluated the relationship of alcohol consumption with antioxidant nutrients and a biomarker of oxidative stress. DESIGN: Participants (n=53) consumed a controlled diet plus each of three treatments (15 or 30 g alcohol/day or a no-alcohol placebo beverage), during three 8-week periods in random order. We measured the antioxidants, vitamin E (alpha (alpha)- and gamma (gamma)-tocopherols), selenium, and vitamin C in fasting blood samples which were collected at the end of diet periods, treated and frozen for assay at the end of the study. We also measured 15-F(2t)-IsoP isoprostane, produced by lipid peroxidation, which serves as an indicator of oxidative stress and may serve as a biomarker for conditions favorable to carcinogenesis. RESULTS: After adjusting for BMI (all models) and total serum cholesterol (tocopherol and isoprostane models) we observed a significant 4.6% decrease (P=0.02) in alpha-tocopherol and a marginally significant 4.9% increase (P=0.07) in isoprostane levels when women consumed 30 g alcohol/day (P=0.06 and 0.05 for overall effect of alcohol on alpha-tocopherol and isoprostanes, respectively). The other antioxidants were not significantly modified by the alcohol treatment. CONCLUSIONS: These results suggest that moderate alcohol consumption increases some biomarkers of oxidative stress in postmenopausal women.

Effect of dietary fat on length of the follicular phase of the menstrual cycle in a controlled diet setting.

The length of the follicular phase of the menstrual cycle (defined as the time from the first day of menses until the day of urinary LH peak, inclusive) was examined in 30 healthy, premenopausal women. The women consumed defined, weight maintaining diets, with a ratio of polyunsaturated to saturated fatty acids (P/S ratio) of either 0.3 or 1.0. Both P/S groups consumed a high fat diet (40% energy from fat) for 4 menstrual cycles, followed by 4 menstrual cycles of a low fat diet (20% energy from fat). There was a significant increase (P less than 0.006) in the length of the follicular phase of the menstrual cycle during consumption of the low fat diet. Two thirds of the women showed increases in follicular phase length with an average increase of 1.9 days.

Cyclic changes in lipoprotein and apolipoprotein levels during the menstrual cycle in healthy premenopausal women on a controlled diet.

Lipoprotein, apolipoprotein (apo), and hormone levels were measured in 12 healthy women over three consecutive menstrual cycles, one free-living and two under controlled dietary conditions. Serum hormone levels were measured to identify menstrual cycle phases (menses, early follicular, late follicular, and midluteal). After stabilization for one cycle on the controlled diet, ANOVA modeling of the second controlled-diet cycle revealed that low-density lipoprotein (LDL) cholesterol levels in the midluteal phase were significantly lower (by 7%) than in the early follicular phase. High-density lipoprotein (HDL) cholesterol levels during the late follicular phase were higher (by 6%) than menses levels. Differences in the HDL-cholesterol and apoA-I fluctuations resulted in a higher proportion of HDL-cholesterol to apoA-I during the late follicular phase than that during the menses phase. The ratios of LDL cholesterol/HDL cholesterol and apoB/apoA-I in the early follicular phase were greater by 5.6% and 6.0%, respectively, than those in the midluteal phase. Fluctuations in total cholesterol, triglyceride, apoA-I, and apoB did not reach significance. Thus, the cyclic fluctuations of LDL and HDL cholesterol need to be considered in the screening and medical monitoring of women with borderline lipoprotein levels, as well as in the design and the interpretation of results of studies involving premenopausal women.

Influence of caloric contribution and saturation of dietary fat on plasma lipids in premenopausal women.

Total cholesterol, HDL cholesterol, and triglycerides were measured in 31 premenopausal women randomized into one of two diet groups: one diet with a P:S ratio of 1.0 and one diet with a P:S ratio of 0.3. Both groups were fed a high-fat diet (40% of energy from fat) for four menstrual cycles per subject followed by a similar interval on a low-fat diet (20% of energy from fat). Changing from the high-fat to the low-fat diet resulted in a nonsignificant mean decrease of 7% in total cholesterol. HDL-cholesterol response to the low-fat regimen was influenced by the P:S ratio. Women in the high P:S group showed no change; mean HDL cholesterol in women in the low P:S group decreased 12%. Plasma triglycerides increased in both groups on the low-fat diet although the increase was greatest in the low P:S group.

Plasma lipid and lipoprotein concentrations of men consuming a low-fat, high-fiber diet.

This study assessed the influence of a low-fat, high-fiber diet on blood lipid concentrations of 42 men with desirable or moderately elevated cholesterol concentrations. A low-fat diet (19% fat, 4% saturated fatty acids, 4.6 g fiber/MJ) was compared with a high-fat diet (41% fat, 15% saturated fatty acids, 2.0 g fiber/MJ) and with subjects' self-selected diets. Substituting the low-fat for the high-fat diet decreased total, low-density-lipoprotein, and high-density-lipoprotein cholesterol by 17-20%. Lipid changes between 6 and 10 wk were minor. A reduction in plasma cholesterol of greater than 0.52 mmol/L was achieved with the low-fat diet in 59% of men changing from their self-selected diets and in 79% changing from the high-fat diet. Percent reduction was independent of subjects' cholesterol classification. Results indicate that significant reductions in plasma cholesterol can be achieved by the majority of men committing to a low-fat, high-fiber diet.

Selective responses of hormones involved in carbohydrate and lipid metabolism and properties of erythrocyte membranes during the menstrual cycle in premenopausal women consuming moderate amounts of alcohol.

The effects of chronic consumption of moderate amounts of alcohol on hormones associated with lipid and carbohydrate metabolism, plasma concentrations of triacylglycerol and cholesterol, insulin receptors on erythrocyte membranes, and erythrocyte membrane fluidity were studied during three phases of the menstrual cycle in 37 premenopausal women. Subjects were given either 30 g ethanol or an equienergetic fruit juice for three menstrual cycles in a crossover design. Blood samples were analyzed during the luteal, midcycle, and follicular phases. Administration of alcohol induced a significant rise in plasma glucagon and cortisol uniformly across the entire menstrual cycle. A similar rise in plasma growth hormone was observed at midcycle during the period when subjects consumed alcohol. A marginal effect was observed on cholesterol and somatomedin C concentrations. Insulin binding to erythrocyte ghosts was not affected by either alcohol or menstrual-cycle phase. Erythrocyte membranes were more fluid during the follicular phase than during the luteal phase of the menstrual cycle when the women were consuming the alcohol. There were no perceptible interactions between alcohol and phases of the menstrual cycle for the indexes studied, except membrane fluidity.

The fluctuation of plasma carotenoid concentrations by phase of the menstrual cycle: a controlled diet study.

This is the first controlled diet study to examine the fluctuation of plasma carotenoids, lipoproteins, and serum hormone concentrations by phase of the menstrual cycle. Nonsmoking, premenopausal women (n = 12) with confirmed ovulatory cycles were given a standard diet with 10 mg total carotenoids/d for two cycles under isoenergetic conditions. Blood was drawn for simultaneous measurement of carotenoids, lipoproteins, and hormones on menses days 1-2, 4-6, 11 through 1 d after the luteinizing hormone surge, and 7-8 d after the surge, representing the menses, early and late follicular, and midluteal phases, respectively. Regression modeling with adjustment for plasma cholesterol concentrations was used to compare mean individual and total plasma carotenoid concentrations by phase of the cycle. Plasma carotenoid concentrations were at their lowest at menses and significantly higher thereafter, except for alpha-carotene. Compared with plasma concentrations at menses, beta-carotene peaked (increased by 9%, P = 0.01) in the late follicular phase. Plasma lutein/zeaxanthin and anhydrolutein concentrations were higher by 8-11% (P < or = 0.006) and by 15-31% (P < or = 0.02), respectively, during the last three phases. Plasma lycopene and phytofluene concentrations peaked (increased by 12%, P = 0.004; and by 21%, P = 0.006, respectively) at the midluteal phase. This cyclic fluctuation may affect the estimation of the plasma carotenoid-disease relation in studies of premenopausal women.

Dietary fat and menstrual-cycle effects on the erythrocyte ghost insulin receptor in premenopausal women.

The effect of high- and low-fat diets with different levels of fatty acid unsaturation on insulin receptors of erythrocyte ghosts was studied during different phases of the menstrual cycle in 31 healthy premenopausal women. Subjects were divided into two groups and consumed controlled diets containing 39% fat with a ratio of polyunsaturated to saturated fatty acids (P:S) of either 0.30 or 1.00 for four menstrual cycles. They were switched to 19% fat at the same P:S for another four cycles. Fasting blood samples were collected during the follicular and luteal phases. Insulin receptors were measured from right-side-out ghosts. Insulin binding was significantly lower due to fewer receptors when subjects were fed the low-fat, high-carbohydrate diet compared with the high-fat, low-carbohydrate diet. There was no significant effect of level of unsaturation or time of menstrual cycle on insulin binding. Thus, insulin receptors on erythrocytes respond to dietary lipids.

Effects of dietary fat and fiber on plasma and urine androgens and estrogens in men: a controlled feeding study.

We conducted a controlled feeding study to evaluate the effects of fat and fiber consumption on plasma and urine sex hormones in men. The study had a crossover design and included 43 healthy men aged 19-56 y. Men were initially randomly assigned to either a low-fat, high-fiber or high-fat, low-fiber diet for 10 wk and after a 2-wk washout period crossed over to the other diet. The energy content of diets was varied to maintain constant body weight but averaged approximately 13.3 MJ (3170 kcal)/d on both diets. The low-fat diet provided 18.8% of energy from fat with a ratio of polyunsaturated to saturated fat (P:S) of 1.3, whereas the high-fat diet provided 41.0% of energy from fat with a P:S of 0.6. Total dietary fiber consumption from the low- and high-fat diets averaged 4.6 and 2.0 g.MJ-1.d-1, respectively. Mean plasma concentrations of total and sex-hormone-binding-globulin (SHBG)-bound testosterone were 13% and 15% higher, respectively, on the high-fat, low-fiber diet and the difference from the low-fat, high-fiber diet was significant for the SHBG-bound fraction (P = 0.04). Men's daily urinary excretion of testosterone also was 13% higher with the high-fat, low-fiber diet than with the low-fat, high-fiber diet (P = 0.01). Conversely, their urinary excretion of estradiol and estrone and their 2-hydroxy metabolites were 12-28% lower with the high-fat, low-fiber diet (P < or = 0.01). Results of this study suggest that diet may alter endogenous sex hormone metabolism in men.

Relationship between dietary intake and plasma concentrations of carotenoids in premenopausal women: application of the USDA-NCI carotenoid food-composition database.

The diet-plasma relationships for carotenoids were examined in a group of 98 nonsmoking premenopausal women who participated in the cross-sectional phase of the National Cancer Institute (NCI)-US Department of Agriculture (USDA) diet study on alcohol-hormone metabolism, 1988-90. With use of the newly developed USDA-NCI carotenoid food-composition database, the mean daily intakes of carotenoids were significantly higher when estimated from the food-frequency questionnaire (FFQ) than from the 7-d diet records. Lycopene (mean = 0.58 mmol/L), lutein plus zeaxanthin (mean = 0.46 mmol/L), and beta-carotene (mean = 0.34 mmol/L) were the major plasma carotenoids. After adjustment for body mass index, energy and alcohol intakes, and total plasma cholesterol concentration, the following significant correlation (P < 0.05) were observed between the diet record and the FFQ-estimated carotenoid intakes and their respective plasma concentrations: alpha-carotene (r = 0.58 vs 0.49), beta-carotene (r = 0.51 vs 0.49), beta-cryptoxanthin (r = 0.49 vs 0.36), lutein plus zeaxanthin (r = 0.31 vs 0.37), lycopene (r = 0.50 vs 0.26), and total carotenoids (r = 0.57 vs 0.49). These data indicate that plasma carotenoid concentrations are reflective of dietary intake, but the magnitude of the correlation varies depending on the specific carotenoid and on the dietary assessment tool.

Hormones regulating lipid and carbohydrate metabolism in premenopausal women: modulation by dietary lipids.

The effect of high- and low-fat diets with different levels of fatty acid unsaturation on plasma hormones involved in lipid metabolism was studied during different phases of the menstrual cycle in 31 premenopausal women. Subjects were divided into two groups and were fed controlled diets containing 39% fat with a ratio of polyunsaturated to saturated fatty acids (P:S) of either 0.3 or 1.0 for four menstrual cycles and then switched to a 19% fat diet with the same P:S for another four cycles. Blood samples were analyzed during both the follicular and luteal phases. A significant direct effect of level of dietary fat was observed on plasma cortisol and dehydroepiandrosterone-sulphate whereas an inverse relationship was seen for plasma insulin. Both plasma insulin and growth hormone levels were higher during the luteal compared with the follicular phase of the menstrual cycle. None of the hormones was affected by the level of unsaturation of dietary fats.

Effect of alcohol consumption on plasma carotenoid concentrations in premenopausal women: a controlled dietary study.

This 6-mo controlled dietary study compared the effect of 30 g alcohol/d for three menstrual cycles with three alcohol-free cycles on plasma carotenoid concentrations in 18 nonsmoking, premenopausal women. Participants were randomly allocated within a crossover design to either phase and consumed approximately 6 mg total carotenoids/d under isoenergetic conditions. Blood was drawn during the third menstrual cycle of each alcohol phase. After adjustment for the mean daily specific carotenoid and energy intakes for each alcohol phase, the paired differences in mean plasma alpha- and beta-carotene concentrations were significantly higher by 19% (P = 0.027) and 13% (P = 0.034), respectively, during the alcohol-intake phase of the study. The paired difference in mean plasma lutein/zeaxanthin concentration was significantly lower by 17% (P = 0.031) when the participants consumed alcohol than when they did not. This is the first reported study in women to document the independent effect of alcohol on plasma carotenoid concentrations without the potential interaction of smoking under controlled dietary conditions.

Relation of energy, fat, and fiber intakes to plasma concentrations of estrogens and androgens in premenopausal women.

To evaluate whether diet may influence the incidence of hormone-dependent cancers through an effect on blood estrogen and androgen concentrations, we analyzed diet-blood hormone relations in a cross-sectional study. Dietary energy, fat, and fiber intakes were estimated from 7-d food records completed by 90 premenopausal women on days 14-20 of their menstrual cycles. Fasting blood specimens were collected on days 5-7, 12-15, and 21-23 of each participant's cycle and pooled to create follicular-, midcycle-, and luteal-phase samples, respectively, for analysis. Energy intake was associated inversely with plasma androstenedione and dehydroepiandrosterone sulfate (DHEAS), averaged across the three menstrual cycle phases, and directly with the probability of a luteal-phase rise in progesterone. For each additional 1 MJ (239 kcal) consumed, androstenedione decreased by 6.0% (95% CI: -8.4%, -3.6%), DHEAS decreased by 5.1% (95% CI: -9.6%, -0.4%), and the probability of a progesterone rise increased by 60% (95% CI: 5%, 145%). After energy intake was adjusted for, the ratio of polyunsaturated to saturated fat (P:S) in the diet was significantly inversely associated with plasma estradiol and estrone during the luteal phase of the menstrual cycle. For each 0.1 increment in the P:S, there was a 7.6% (95% CI: -14.3%, -0.5%) decrease in estradiol and a 6.8% (95% CI: -12.7%, -0.6%) decrease in estrone. Results of this cross-sectional study support a relation between both energy and fat ingestion and plasma sex hormone concentrations in premenopausal women.

Relationships of age and reproductive characteristics with plasma estrogens and androgens in premenopausal women.

We used data from a cross-sectional study of 107 premenopausal women to evaluate the relation of age, menarcheal age, parity, and age at first live birth with plasma estrogen and androgen levels in premenopausal women. Fasting blood specimens were collected on each of days 5-7, 12-15, and 21-23 of menstrual cycles of the participants and pooled to create follicular, midcycle, and luteal phase samples, respectively, for each woman. Age was associated significantly and positively with plasma estradiol levels during the follicular phase [percentage difference/year = 2.6; 95% confidence interval (CI) = 1.0-4.2] and midcycle (percentage difference/year = 2.7; 95% CI = 0.9-4.7) but not the luteal phase (percentage difference/year = -0.4; 95% CI = -1.9-1.3) of the menstrual cycle. The relation of age to plasma estradiol varied by parity, with significant interactions during midcycle and luteal phase. Among nulliparous women, plasma estradiol levels increased with age midcycle and during the luteal phase, but among parous women estradiol levels decreased with age during these phases of the menstrual cycle. Plasma estrone increased with age in all women during the follicular phase of the menstrual cycle (percentage difference/year = 1.5; 95% CI = 0.2-2.8). During the luteal phase there was a significant interaction with parity; estrone levels in nulliparous women varied only slightly with age, but levels in parous women decreased significantly as age increased. The androgens, androstenedione and dehydroepiandrosterone sulfate decreased, and sex hormone-binding globulin increased as age increased. The results of this cross-sectional study suggest that pregnancy may modify age-related changes in plasma estrogen levels.

Relation of prediagnostic serum estrogen and androgen levels to breast cancer risk.

To evaluate the relation of serum sex hormones to breast cancer risk, we conducted a prospective nested case-control study using the Breast Cancer Serum Bank (Columbia, MO). This bank included serum from 3375 postmenopausal women free of cancer and not taking replacement estrogens when they donated blood between 1977 and 1987. Of these, 71 were diagnosed subsequently with breast cancer. For each case, two women alive and free of cancer at the age of the case's diagnosis and matched to the case on age and on date and time of day of blood collection were selected as controls. The median age of subjects at blood collection was 62 years, and the time from blood collection to diagnosis ranged from less than 1 to 9.5 years, with a median of 2.9 years. Postmenopausal women with elevated serum levels of total and non-sex hormone-binding globulin-bound E2 were at an increased risk of developing breast cancer. For non-sex hormone-binding globulin-bound E2, risks were elevated 4-5 fold for women in the upper three quartiles relative to those in the lowest quartile. Although breast cancer was not related to estrone or estrone sulfate concentration, the ratio of estrone sulfate to estrone was significantly inversely associated with risk, suggesting that women who develop breast cancer may be less able to metabolize estrone to its less active form. Serum testosterone was significantly positively associated with postmenopausal breast cancer; the relative risk for women in the highest versus the lowest quartile was 6.2 (95% confidence interval, 2.0-19.0). Our results support the hypothesis that prediagnostic serum estrogens and androgens are related to the subsequent diagnosis of breast cancer in postmenopausal women.

Serum sex hormone levels are related to breast cancer risk in postmenopausal women.

We conducted a nested case-control study to prospectively evaluate the relationship of serum estrogens and androgens to risk of breast cancer in postmenopausal women. From 1977 to 1987, 3375 postmenopausal women free of cancer and not taking replacement estrogens donated blood to the Breast Cancer Serum Bank in Columbia, Missouri. Of these, 72 were subsequently diagnosed with breast cancer. For each case, two controls matched on age and date and time of day of blood collection were selected using incidence density matching. The median age of subjects at blood collection was 62 years; the time from blood collection to diagnosis ranged from less than 1 to 9.5 years with a median of 2.9 years. Risk of breast cancer was positively and significantly associated with serum levels of estrogens and androgens. Compared to women in the lowest quartile, those in the highest quartile for non-sex hormone-binding globulin (non-SHBG) bound (bioavailable) estradiol had a relative risk of 5.2 (95% confidence interval [CI] = 1.5-18.5) and those in the highest quartile for testosterone had a relative risk of 6.2 (95% CI = 2.0-19.0). Our results lend considerable support to the hypothesis that serum concentrations of estrogens and androgens are related to the subsequent diagnosis of breast cancer in postmenopausal women.

Menstrual cycle effect on plasma lipids.

In a study of 31 healthy women in which dietary intake and body weight were controlled, a significantly higher mean plasma cholesterol was observed in the follicular phase of the menstrual cycle compared to the luteal phase (mean difference of 8.4% during controlled dietary periods). Higher mean plasma triglycerides (mean difference of 7.4%) and lower HDL-cholesterol (mean difference of 5.8%) were also observed in the follicular phase of the controlled dietary study, although these differences were not consistently significant.

Effects of moderate alcohol consumption on folate and vitamin B(12) status in postmenopausal women.

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=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 (461.45+/-30.26 vs 440.25+/-30.24 pg/ml; P=0.03). Mean serum HCY concentrations tended to increase by 3% from 0 to 30 g of alcohol/day (9.44+/-0.37 vs 9.73+/-0.37 micromol/l; P=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.