Association of prenatal folate status with early childhood wheeze and atopic dermatitis.

BACKGROUND: Prenatal folic acid supplementation is recommended to prevent birth defects. Some foods are fortified in the USA to ensure sufficient intake among reproductive-aged women. However, high prenatal folate exposure may be a risk factor for childhood atopic diseases. We investigated associations between prenatal folate and early childhood wheeze and atopic dermatitis in a US cohort. METHODS: We studied 858 mother-child dyads, enrolled prenatally. Folate was measured in 2nd and 3rd trimester maternal plasma. Parents reported current wheeze (previous 12 months) and healthcare provider diagnosis of atopic dermatitis at 3 years. We examined associations using logistic regression, modeling folate continuously and dichotomously (< or ≥20 ng/mL), a level often considered supraphysiologic. RESULTS: Over half of women were African American and on Medicaid. Median (interquartile range) folate levels were 22.6 (15.9-30.0) and 23.1 (16.1-30.0) ng/mL for 2nd and 3rd trimesters, respectively. Current wheeze and atopic dermatitis were reported for 20.4% and 26.8% of children, respectively. Second trimester folate as a continuous exposure was not significantly associated with outcomes. Decreased odds of current wheeze were observed in children born to mothers who had 2nd trimester folate ≥20 ng/mL (adjusted odds ratios = 0.67, 95% confidence interval = 0.46, 0.97) compared to children with maternal levels <20 ng/mL. Third trimester folate was not associated with outcomes. CONCLUSIONS: High plasma folate in mid-pregnancy was associated with decreased odds of current wheeze at age 3. Our findings do not support harmful effects of high prenatal folate levels on childhood atopic diseases in this setting.

The associations between diet quality, Body Mass Index (BMI) and Health and Activity Limitation Index (HALex) in the Geisinger Rural Aging Study (GRAS).

OBJECTIVES: To determine the associations between diet quality, body mass index (BMI), and health-related quality of life (HRQOL) as assessed by the health and activity limitation index (HALex) in older adults. DESIGN: Multivariate linear regression models were used to analyze associations between Dietary Screening Tool (DST) scores, BMI and HALex score, after controlling for gender, age, education, living situation, smoking, disease burden and self-vs. proxy reporting. SETTING: Geisinger Rural Aging Study, Pennsylvania. PARTICIPANTS: 5,993 GRAS participants were mailed HRQOL and DST questionnaires with 4,009 (1,722 male, 2,287 female; mean age 81.5 ± 4.4) providing complete data. RESULTS: HALex scores were significantly lower for participants with dietary intakes categorized as unhealthy (<60) (0.70, 95% CI 0.69, 0.72, p<0.05) or borderline (60-75) (0.71, 95% CI 0.70, 0.73, p<0.05) compared to those scoring in the healthy range (>75) (0.75, 95% CI 0.73, 0.77) based on DST scores. HALex scores were significantly lower for underweight (0.67, 95% CI 0.63, 0.72, p<0.05), obese class II (0.68, 95% CI 0.66, 0.71, p<0.05) and class III participants (0.62 95% CI 0.57, 0.67, p<0.05) compared to those with BMI 18.5-24.9. CONCLUSIONS: Poor diet quality, as assessed by the DST, is associated with lower HRQOL in adults ≥ 74 years of age.

Nutrient displacement associated with walnut supplementation in men.

BACKGROUND: Dietary guidance issued by various global government agencies recommends nut consumption within the context of a healthy-eating pattern. Nuts are nutrient dense and may promote nutrient adequacy. As an energy-dense food, nuts must replace other foods in the diet to prevent an excess of calories. METHODS: We evaluated how recommending the inclusion of walnuts (75 g day(-1) ) in the diet affected energy and nutrient intake in men (45-75 years; mean body mass index = 27.6 kg m(-2) ; n = 19) at risk for developing prostate cancer. Guidance was provided about incorporating walnuts isocalorically in a healthy diet. Three-day food records and body weight were collected at baseline and after two 8-week diet periods (usual versus walnut supplement diets). RESULTS: Energy intake on the walnut supplement diet exceeded the usual diet, although body weight was maintained. Energy intake was lower on the actual walnut supplement diet than the calculated walnut diet [10,865 kJ (2595 kcal) versus 11,325 kJ (2705 kcal) per day, respectively] and contributed 23% less energy than 75 g of walnuts. Approximately, 86% and 85% of the total fat and saturated fatty acids from walnuts were not displaced, whereas the increase in fibre from the usual diet to the actual walnut supplement diet represented less than one-half (39%) of the fibre provided by 75 g of walnuts. Walnuts were substituted, in part, for other foods, and the nutrient profile of the diet was improved, however, the beneficial effect of walnuts on the diet quality was not optimized. CONCLUSIONS: Individuals do not optimally implement food-based guidance. Consequently, nutrition professionals play a key role in teaching the implementation of food-based recommendations.

Dietary patterns and relationship to obesity-related health outcomes and mortality in adults 75 years of age or greater.

BACKGROUND: The prevalence of obesity-related adverse health outcomes is increasing among older adults. Because it is thought that nutrition plays an important role in successful aging, there has been considerable interest in the association between dietary patterns of older adults and obesity-related health outcomes. OBJECTIVE: This study examined the association between dietary patterns and mortality and prevalence of obesity-related health outcomes, namely cardiovascular disease (CVD), type 2 diabetes mellitus, hypertension, and metabolic syndrome (MetSyn), over a 5-year follow-up period in adults aged 75 years or greater. DESIGN: A longitudinal observational study with cross-sectional dietary assessment. SETTING: Rural Central Pennsylvania. PARTICIPANTS: Community-dwelling older adults (N = 449; 76.5 years old; 57% female). MEASUREMENTS: Multiple, unannounced, 24-hour dietary recalls were used to collect dietary intake. Cluster analysis was used to derive dietary patterns. Prevalence of CVD, diabetes mellitus, hypertension, and MetSyn was extracted from outpatient electronic medical records. Logistic regression was used to examine the associations between dietary patterns and health outcomes and mortality. RESULTS: 'Sweets and Dairy', 'Health-Conscious' and 'Western' dietary patterns were identified. Compared to the 'Health-Conscious' pattern, those in the 'Sweets and Dairy' pattern had increased odds of hypertension over the follow-up period; adjusted odds ratio (95% CI) was 2.18 (1.11-4.30). No significant associations were found for CVD, diabetes mellitus, MetSyn or mortality with dietary patterns. CONCLUSIONS: These findings support the potential value of healthy dietary patterns in the management of hypertension in older adults. We did not observe any other strong associations between dietary patterns and health outcomes or mortality in persons ≥ 75 years of age; thus failing to support the use of overly restrictive diet prescriptions for older persons, especially where food intake may be inadequate.

Dietary patterns and diet quality among diverse older adults: the University of Alabama at Birmingham Study of Aging.

OBJECTIVES: To characterize dietary patterns among a diverse sample of older adults (≥ 65 years). DESIGN: Cross-sectional. SETTING: Five counties in west central Alabama. PARTICIPANTS: Community-dwelling Medicare beneficiaries (N=416; 76.8 ± 5.2 years, 56% female, 39% African American) in the University of Alabama at Birmingham (UAB) Study of Aging. MEASUREMENTS: Dietary data collected via three, unannounced 24-hour dietary recalls was used to identify dietary patterns. Foods were aggregated into 13 groups. Finite mixture modeling (FMM) was used to classify individuals into three dietary patterns. Differences across dietary patterns for nutrient intakes, sociodemographic, and anthropometric measurements were examined using chi-square and general linear models. RESULTS: Three dietary patterns were derived. A "more healthful" dietary pattern, with relatively higher intakes of fruit, vegetables, whole grains, eggs, nuts, legumes and dairy, was associated with lower energy density, higher quality diets as determined by healthy eating index (HEI)-2005 scores and higher intakes of fiber, folate, vitamins C and B6, calcium, iron, magnesium, and zinc. The "western-like" pattern was defined by an intake of starchy vegetables, refined grains, meats, fried poultry and fish, oils and fats and was associated with lower HEI-2005 scores. The "low produce, high sweets" pattern was characterized by high saturated fat, and low dietary fiber and vitamin C intakes. The strongest predictors of better diet quality were female gender and non-Hispanic white race. CONCLUSION: The dietary patterns identified may provide a useful basis on which to base dietary interventions targeted at older adults. Examination of nutrient intakes regardless of the dietary pattern suggests that older adults are not meeting nutrient recommendations and should continue to be encouraged to choose high quality diets.

Relative validity of the Geisinger Rural Aging Study food frequency questionnaire.

OBJECTIVE: To determine the relative validity of a population specific food frequency questionnaire (FFQ) and evaluate the effectiveness of the instrument for assessing nutritional risk in older adults. DESIGN: A cross-over design with participants completing two different dietary assessment instruments in random order. SETTING: The Geisinger Rural Aging Study (GRAS), a longitudinal study of over 20,000 adults living in the central, northern and eastern counties of Pennsylvania. PARTICIPANTS: A subset of GRAS consisting of 245 older adults (60% women) ranging in age from 70 to 95 years. MEASUREMENTS: Energy and nutrient intakes were assessed from two instruments: a population specific food frequency questionnaire (FFQ) and four 24-hour dietary recalls conducted over a two week period. RESULTS: Pearson correlation coefficients between the FFQ and dietary recalls for most nutrients were 0.5 or higher which suggests that the FFQ provided relatively valid estimates of macro and micronutrient intakes examined. Bland-Altman plots were generated to examine the agreement between instruments. Data are shown for energy, folate and zinc with close agreement at lower intakes indicative of risk for folate and zinc. Sensitivity results also showed that the FFQ was able to correctly classify individuals adequately at risk for most nutrients examined. CONCLUSION: This population specific FFQ appears to be a valid instrument for use in in evaluating risk for many nutrients that are of particular concern in older adults residing throughout many predominately rural counties in Pennsylvania.

Administration of omega-3 fatty acids and Raloxifene to women at high risk of breast cancer: interim feasibility and biomarkers analysis from a clinical trial.

BACKGROUND/OBJECTIVES: The antiestrogen, Raloxifene (Ral) is an effective breast cancer chemopreventive agent. Omega-3 fatty acids (n-3FA) may inhibit mammary carcinogenesis. On the basis of their mechanisms of action, we test the hypothesis that a combination of n-3FA and Ral may be superior in reducing select biomarkers of breast cancer risk in women. SUBJECTS/METHODS: Postmenopausal women at increased risk for breast cancer (breast density ≥ 25%) were randomized to: (1) no intervention; (2) Ral 60 mg; (3) Ral 30 mg; (4) n-3FA (Lovaza) 4 g and (5) Lovaza 4 g+Ral 30 mg for 2 years. Reduction in breast density is the primary end point of the study. We report preliminary data on feasibility, compliance and changes in secondary end points related to IGF-I signaling, estrogen metabolism, oxidative stress and inflammation in the first group of 46 women who completed 1 year of the study. RESULTS: All interventions were well tolerated with excellent compliance (96 ± 1% overall) by pill count and also supported by the expected rise in both serum n-3FA and n-3FA/Omega-6 fatty acids (n-6FA) ratio in women randomized to groups 4 and 5 (P<0.05). Lovaza decreased serum triglycerides and increased high-density lipoprotein (HDL) cholesterol compared with control (P<0.05 for both). Ral reduced serum IGF-1 in a dose-dependent manner (P<0.05) while Lovaza did not. Lovaza had no effect on IGF-1 or IGFBP-3. None of the other biomarkers were affected by our treatment. CONCLUSION: The combination of Lovaza and Ral is a feasible strategy that may be recommended in future breast cancer chemoprevention trials.

Moderate alcohol consumption and 24-hour urinary levels of melatonin in postmenopausal women.

CONTEXT: Low overnight urinary melatonin metabolite concentrations have been associated with increased risk for breast cancer among postmenopausal women. The Postmenopausal Women's Alcohol Study was a controlled feeding study to test the effects of low to moderate alcohol intake on potential risk factors for breast cancer including serum and urinary levels of hormones and other biomarkers. Previously, we observed significant increases in concentrations of serum estrone sulfate and dehydroepiandrosterone sulfate in participants after consumption of 15 or 30 g (one or two drinks) of alcohol per day. OBJECTIVE: In the present analysis, we evaluated the relationship of alcohol consumption with 24-h urinary 6-sulfatoxymelatonin (6-SMT) concentration (micrograms per 24 h). DESIGN AND PARTICIPANTS: Healthy postmenopausal women (n = 51) consumed a controlled diet plus each of three treatments (a nonalcoholic placebo beverage or 15 or 30 g alcohol/d) during three 8-wk periods in random order under conditions of weight maintenance. MEASURES: 6-SMT was measured in 24-h urine samples that were collected at entry into the study (baseline) and at the midpoint (4 wk) and end (8 wk) of each of the three diet periods. RESULTS: Concentration of 6-SMT was not significantly modified by the alcohol treatment after adjustment for body mass index, hours of sleep, daylight hours, and baseline level of 6-SMT. CONCLUSIONS: These results suggest that low to moderate daily alcohol consumption does not significantly affect 24-h urinary levels of melatonin among healthy postmenopausal women.

All-cause mortality risk of metabolically healthy obese individuals in NHANES III.

Mortality risk across metabolic health-by-BMI categories in NHANES-III was examined. Metabolic health was defined as: (1) homeostasis model assessment-insulin resistance (HOMA-IR) <2.5; (2) ≤2 Adult Treatment Panel (ATP) III metabolic syndrome criteria; (3) combined definition using ≤1 of the following: HOMA-IR ≥1.95 (or diabetes medications), triglycerides ≥1.7 mmol/L, HDL-C <1.04 mmol/L (males) or <1.30 mmol/L (females), LDL-C ≥2.6 mmol/L, and total cholesterol ≥5.2 mmol/L (or cholesterol-lowering medications). Hazard ratios (HR) for all-cause mortality were estimated with Cox regression models. Nonpregnant women and men were included (n = 4373, mean ± SD, age 37.1 ± 10.9 years, BMI 27.3 ± 5.8 kg/m², 49.4% female). Only 40 of 1160 obese individuals were identified as MHO by all definitions. MHO groups had superior levels of clinical risk factors compared to unhealthy individuals but inferior levels compared to healthy lean groups. There was increased risk of all-cause mortality in metabolically unhealthy obese participants regardless of definition (HOMA-IR HR 2.07 (CI 1.3-3.4), P < 0.01; ATP-III HR 1.98 (CI 1.4-2.9), P < 0.001; combined definition HR 2.19 (CI 1.3-3.8), P < 0.01). MHO participants were not significantly different from healthy lean individuals by any definition. While MHO individuals are not at significantly increased risk of all-cause mortality, their clinical risk profile is worse than that of metabolically healthy lean individuals.

A high-legume low-glycemic index diet reduces fasting plasma leptin in middle-aged insulin-resistant and -sensitive men.

Fasting leptin and ghrelin levels were measured in 36 insulin-sensitive (IS) and 28 insulin-resistant (IR) men who consumed a legume-enriched low-glycemic index (LG) diet or healthy American (HA) diet in a randomly ordered cross-over feeding study consisting of two 4-week periods. Weight remained stable over the entire study. Fasting plasma leptin was significantly reduced from pre-study levels by both the LG (18.8%, P < 0.001) and HA (16.1%, P < 0.001) diets, whereas fasting ghrelin did not change. By subgroup analysis according to prestudy insulin status, leptin was reduced in IR subjects after both the LG (17.1%, P < 0.01) and the HA (33.3%, P < 0.001) diets, whereas IS subjects responded only after the LG diet (23.1%, P < 0.01). Thus, a legume-rich LG index diet may be a beneficial strategy for reducing circulating leptin concentrations, even under conditions of weight maintenance.

Measures of adiposity and body fat distribution in relation to serum folate levels in postmenopausal women in a feeding study.

OBJECTIVE: To assess the associations between serum folate concentration and measures of adiposity in postmenopausal women. DESIGN: This study was conducted as a cross-sectional analysis within the control segment of a randomized, crossover trial in which postmenopausal women (n=51) consumed 0 g (control), 15 g (one drink) and 30 g (two drinks) alcohol (ethanol)/day for 8 weeks as part of a controlled diet. Subjects in one treatment arm were crossed-over to another arm after a 2- to 5-week washout period. Body mass index (BMI) was measured, and dual energy X-ray absorptiometry (DEXA) scan administered to the women during the control (0 g alcohol) treatment, and a blood sample from this group was collected at baseline and week 8 of each diet period and analyzed for folate, B12, homocysteine and methylmalonic acid. SETTING: This study was conducted at the Beltsville Human Nutrition Research Center, MD, USA. RESULTS: In multivariate analysis, women who were overweight had a 12% lower, and obese women had a 22% lower serum folate concentrations compared to normal weight women (P-trend=0.02). Vitamin B12 also decreased with increasing BMI (P-trend=0.08). Increased BMI, percent body fat, and absolute amounts of central and peripheral fat were all significantly associated with decreased serum folate, but were unrelated to serum B12, homocysteine or methylmalonic acid. CONCLUSIONS: Our data show that adiposity is associated with lower serum folate levels in postmenopausal women. With obesity at epidemic proportions, these data, if confirmed by prospective or randomized controlled studies, have important public health implications.

Calorie intake misreporting by diet record and food frequency questionnaire compared to doubly labeled water among postmenopausal women.

OBJECTIVE: We assessed the extent of energy misreporting from the use of a self-administered 7-day diet record (7-DDR) and a widely used food frequency questionnaire (FFQ) compared to total energy expenditure from doubly labeled water (DLW) in a group of postmenopausal women. DESIGN: At baseline, 65 healthy postmenopausal women were instructed to fill out the National Cancer Institute's (NCI) FFQ and a 7-DDR. Average total energy expenditure using the DLW method was also performed at baseline. RESULTS: On average, the women underestimated total energy intake compared to total energy expenditure assessed from DLW by 37% on the 7-DDR and 42% on the FFQ. CONCLUSIONS: These findings suggest that the interpretation of findings from the 7-DDR- and FFQ-based energy-disease association studies in postmenopausal women needs further evaluation. SPONSORSHIP: This research was supported (in part) by the Intramural Program of the NIH (National Cancer Institute).

No association between alcohol supplementation and autoantibodies to DNA damage in postmenopausal women in a controlled feeding study.

Alcohol consumption is linked to increased breast cancer risk. Since oestrogens increase breast cancer risk, possibly through oxidative damage, and we have shown that alcohol consumption increases serum oestrogens, we tested whether moderate alcohol supplementation increased oxidative DNA damage among healthy postmenopausal women not on hormone replacement therapy in a randomized controlled crossover study. We used serum 5-hydroxymethyl-2-deoxyuridine (5-HMdU) autoantibodies (aAbs) as a marker of oxidative DNA damage. The results showed no evidence for increased or decreased levels of oxidative DNA damage among women who consumed 15 g or 30 g alcohol per day for 8 weeks compared with women in the 0 g alcohol group. We conclude that among healthy women, it is possible that an 8-week trial of moderate alcohol supplementation might be too short to make enough 5-HMdU aAbs to compare differences by alcohol dose. In future studies, a panel of biomarkers for DNA damage should be used.

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.

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.

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.

Association of the B-vitamins pyridoxal 5'-phosphate (B(6)), B(12), and folate with lung cancer risk in older men.

A nested case-control study was conducted within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort to test for associations between selected B-vitamins (folate, vitamin B(6), vitamin B(12)) and incident lung cancer. This trial was conducted in Finland between 1985 and 1993. Serum was analyzed for these nutrients and homocysteine among 300 lung cancer cases and matched controls (1:1). Odds ratios and 95% confidence intervals were determined in conditional and unconditional (controlling for the matching factors) logistic regression models, after adjusting for body mass index, years of smoking, and number of cigarettes smoked per day. No significant associations were seen between serum folate, vitamin B(12), or homocysteine and lung cancer risk. The authors found significantly lower risk of lung cancer among men who had higher serum vitamin B(6) levels. Compared with men with the lowest vitamin B(6) concentration, men in the fifth quintile had about one half of the risk of lung cancer (odds ratio = 0.51; 95% confidence interval: 0.23, 0.93; p-trend = 0.02). Adjusting for any of the other serum factors (folate, B(12), and homocysteine) either alone or jointly did not significantly alter these estimates. This is the first report from a prospectively conducted study to suggest a role for vitamin B(6) in lung cancer.

Physical activity in relation to cancer of the colon and rectum in a cohort of male smokers.

We examined the association between occupational and leisure physical activity and colorectal cancer in a cohort of male smokers. Among the 29,133 men aged 50-69 years in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention study,152 colon and 104 rectal cancers were documented during up to 12 years of follow-up. For colon cancer, compared with sedentary workers, men in light occupational activity had a relative risk (RR) of 0.60 [95% confidence interval (CI), 0.34-1.04], whereas those in moderate/heavy activity had an RR of 0.45 (CI, 0.26-0.78; P for trend, 0.003). Subsite analysis revealed a significant association for moderate/heavy occupational activity in the distal colon (RR, 0.21; CI, 0.09-0.51) but not in the proximal colon (RR, 0.87; CI, 0.40-1.92). There was no significant association between leisure activity and colon cancer (active versus sedentary; RR, 0.82; CI, 0.59-1.13); however, the strongest inverse association was found among those most active in both work and leisure (RR, 0.33; CI, 0.16-0.71). For rectal cancer, there were risk reductions for those in light (RR, 0.71; CI, 0.36-1.37) and moderate/heavy occupational activity (RR, 0.50; CI, 0.26-0.97; P for trend, 0.04), and no association for leisure activity. These data provide evidence for a protective role of physical activity in colon and rectal cancer.

Effects of long-term alpha-tocopherol supplementation on serum hormones in older men.

BACKGROUND: alpha-tocopherol supplementation significantly reduced risk of prostate cancer in the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study. Sex hormones are thought to be involved in the etiology of prostate cancer. We examined whether long-term supplementation with alpha-tocopherol modified serum hormone levels. METHODS: Men who were cancer-free consumed > or = 90% of the study capsules, and who had both baseline and follow-up blood available, were eligible for the study. One hundred men who received alpha-tocopherol were matched on age, study center, and length of time between blood draws to 100 men who received a placebo. Multivariate linear regression models which allowed for a separate intercept for each matched pair were used to evaluate the effect of alpha-tocopherol supplementation on follow-up hormone concentrations. RESULTS: Compared to men who received a placebo, we found significantly lower serum androstenedione (P = 0.04) and testosterone (P = 0.04) concentrations among men who received alpha-tocopherol, after controlling for baseline hormone level, follow-up serum cholesterol concentration, body mass index, smoking, and fasting time. Geometric mean (95% confidence interval; CI) androstenedione concentration among men who received alpha-tocopherol was 145 ng/dl (CI, 137-153) after adjusting for covariates, compared to 158 ng/dl (CI, 148-167) among men who received a placebo. Mean testosterone concentrations for men who received alpha-tocopherol and placebo were 539 (CI, 517-562) and 573 (CI, 549-598) ng/dl, respectively. CONCLUSIONS: These results suggest that long-term alpha-tocopherol supplementation decreases serum androgen concentrations, and could have been one of the factors contributing to the observed reduction in incidence and mortality of prostate cancer in the alpha-tocopherol treatment group of the ATBC Study.

Effects of supplemental alpha-tocopherol and beta-carotene on colorectal cancer: results from a controlled trial (Finland)

BACKGROUND: Some epidemiological investigations suggest that higher intake or biochemical status of vitamin E and beta-carotene might be associated with reduced risk of colorectal cancer. METHODS: We tested the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of colorectal cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a double-blind, placebo-controlled trial among 29,133 50-69-year-old male cigarette smokers. Participants were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or a placebo daily for 5-8 years. Incident colorectal cancers (n = 135) were identified through the nationwide cancer registry, and 99% were histologically confirmed. Intervention effects were evaluated using survival analysis and proportional hazards models. RESULTS: Colorectal cancer incidence was somewhat lower in the alpha-tocopherol arm compared to the no alpha-tocopherol arm, but this finding was not statistically significant (relative risk (RR) = 0.78, 95% confidence interval (CI) 0.55-1.09; log-rank test p = 0.15). Beta-carotene had no effect on colorectal cancer incidence (RR = 1.05, 95% CI 0.75-1.47; log-rank test p = 0.78). There was no interaction between the two substances. CONCLUSION: Our study found no evidence of a beneficial or harmful effect for beta-carotene in colorectal cancer in older male smokers, but does provide suggestive evidence that vitamin E supplementation may have had a modest preventive effect. The latter finding is in accord with previous research linking higher vitamin E status to reduced colorectal cancer risk.