Consumption of olive oil and risk of breast cancer in U.S. women: results from the Nurses' Health Studies.

BACKGROUND: Olive oil consumption may reduce breast cancer risk, but it is unclear whether olive oil is beneficial for breast cancer prevention in populations outside of Mediterranean regions, namely in the U.S., where the average consumption of olive oil is low compared with Mediterranean populations. We examined whether olive oil intake was associated with breast cancer risk in two prospective cohorts of U.S. women. METHODS: We used multivariable-adjusted time-varying Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence interval (CI) for breast cancer among 71,330 (Nurses' Health Study, 1990-2016) and 93,295 women (Nurses' Health Study II, 1991-2017) who were free of cancer at baseline. Diet was assessed by a validated semi-quantitative food frequency questionnaire every 4 years. RESULTS: During 3,744,068 person-years of follow-up, 9,638 women developed invasive breast cancer. The multivariable-adjusted HR (95% CI) for breast cancer among women who had the highest consumption of olive oil (>1/2 tablespoon/d or >7 g/d) compared with those who never or rarely consumed olive oil, was 1.01 (0.93, 1.09). Higher olive oil consumption was not associated with any subtype of breast cancer. CONCLUSION: We did not observe an association between higher olive oil intake and breast cancer risk in two large prospective cohorts of U.S. women, whose average olive oil consumption was low. Prospective studies are needed to confirm these findings and to further investigate whether different varieties of olive oil (e.g., virgin and extra virgin olive oil) may play a role in breast cancer risk.

A prospective analysis of red blood cell membrane polyunsaturated fatty acid levels and risk of non-Hodgkin lymphoma.

Published studies report inconsistent associations of polyunsaturated fatty acid (PUFA) intake with non-Hodgkin lymphoma (NHL) risk. We conducted a nested case-control study in Nurses' Health Study and Health Professionals Follow-Up Study participants to evaluate a hypothesis of inverse association of pre-diagnosis red blood cell (RBC) membrane PUFA levels with risk of NHL endpoints. We confirmed 583 NHL cases and matched 583 controls by cohort/sex, age, race and blood draw date/time. We estimated odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL endpoints using logistic regression. RBC PUFA levels were not associated with all NHL risk; cis 20:2n-6 was associated with follicular lymphoma risk (OR [95% CI] per one standard deviation increase: 1.35 [1.03-1.77]), and the omega-6/omega-3 PUFA ratio was associated with diffuse large B-cell lymphoma risk (2.33 [1.23-4.43]). Overall, PUFA did not demonstrate a role in NHL etiology; the two unexpected positive associations lack clear biologic explanations.

Dietary and Supplemental Vitamin C Intake and Risk of Breast Cancer: Results from the Nurses' Health Studies.

BACKGROUND: Some previous studies suggested that high supplemental vitamin C intake may be associated with an increased risk of breast cancer, although evidence is inconsistent. OBJECTIVES: Our objective was to study the association between vitamin C intake and breast cancer risks using regularly updated assessments of intake over a long follow-up. METHODS: We prospectively followed 88,041 women aged 33 to 60 years from the Nurses' Health Study (1980-2014) and 93,372 women aged 26 to 45 years from the Nurses' Health Study II (1991-2013). A total of 11,258 incident invasive breast cancers among 181,413 women were diagnosed. Data on vitamin C intake were collected every 2-4 years via a validated FFQ and specific questions on dietary supplement use. Multivariate HRs and 95% CIs for incident invasive breast cancer were estimated with Cox models. RESULTS: During follow-up, 82% of participants ever used supplements containing vitamin C, including multivitamins. Cumulative total vitamin C intake (HR for quintiles 5 compared with 1 = 0.97; 95% CI: 0.91-1.03; Ptrend = 0.81), dietary vitamin C intake (HR for quintiles 5 compared with 1 = 0.98; 95% CI: 0.92-1.04; Ptrend = 0.57), and supplemental vitamin C intake (HR for quintiles 5 compared with 1 in users = 1.02; 95% CI: 0.94-1.09; Ptrend = 0.77) were not associated with breast cancer risks. Results were unchanged when different exposure latencies were considered. The results did not differ by menopausal status, postmenopausal hormone therapy use, or BMI. No differences were observed by estrogen receptor status of the tumor. CONCLUSIONS: Our results do not support any important association between total, dietary, or supplemental vitamin C intake and breast cancer risks.

Post-diagnostic coffee and tea consumption and breast cancer survival.

BACKGROUND: We examined the role of post-diagnostic coffee and tea consumption in relation to breast cancer-specific and all-cause mortality among women with breast cancer in prospective cohort studies. METHODS: We identified 8900 women with stage I-III breast cancer from 1980 through 2010 in the Nurses' Health Study (NHS) and from 1991 through 2011 in the NHSII. Post-diagnostic coffee and tea consumption was assessed by a validated food frequency questionnaire every 4 years after diagnosis. RESULTS: During up to 30 years of follow-up, we documented 1054 breast cancer-specific deaths and 2501 total deaths. Higher post-diagnostic coffee consumption was associated with a lower breast cancer-specific mortality: compared with non-drinkers, >3 cups/day of coffee was associated with a 25% lower risk (hazard ratio (HR) = 0.75, 95% confidence interval (CI) = 0.59-0.96; Ptrend = 0.002). We also observed a lower all-cause mortality with coffee consumption: compared with non-drinkers, >2 to 3 cups/day was associated with a 24% lower risk (HR = 0.76, 95% CI = 0.66-0.87) and >3 cups/day was associated with a 26% lower risk (HR = 0.74, 95% CI = 0.63-0.87, Ptrend < 0.0001). Post-diagnostic tea consumption was associated with a lower all-cause mortality: compared with non-drinkers, >3 cups/day was associated with a 26% lower risk (HR = 0.74, 95% CI = 0.58-0.95; Ptrend = 0.04). CONCLUSIONS: Among breast cancer survivors, higher post-diagnostic coffee consumption was associated with better breast cancer and overall survival. Higher post-diagnostic tea consumption may be related to better overall survival.

Dietary intake of α-linolenic acid and risk of age-related macular degeneration.

Background: The relation between α-linolenic acid (ALA), a plant-derived omega-3 (n-3) fatty acid, and age-related macular degeneration (AMD) is unclear. European researchers reported that ≤40% of ALA can be present as trans forms.Objective: We aimed to evaluate the associations between intake of ALA and intermediate and advanced AMD.Design: Seventy-five thousand eight hundred eighty-nine women from the Nurses' Health Study and 38,961 men from Health Professionals Follow-Up Study were followed up from 1984 to 2012 and from 1986 to 2010, respectively. We assessed dietary intake by a validated food-frequency questionnaire at baseline and every 4 y thereafter. One thousand five hundred eighty-nine incident intermediate and 1356 advanced AMD cases (primarily neovascular AMD) were confirmed by medical record review.Results: The multivariable-adjusted HR for intermediate AMD comparing ALA intake at the top quintile to the bottom quintile was 1.28 (95% CI: 1.05, 1.56; P-trend = 0.01) in the analyses combining 2 cohorts. The HR in each cohort was in the positive direction but reached statistical significance only in the women. However, the positive association was apparent only in the pre-2002 era in each cohort and not afterward (P-time interaction = 0.003). ALA intake was not associated with advanced AMD in either time period. Using gas-liquid chromatography, we identified both cis ALA (mean ± SD: 0.13% ± 0.04%) and trans ALA isomers (0.05% ± 0.01%) in 395 erythrocyte samples collected in 1989-1990. In stepwise regression models, mayonnaise was the leading predictor of erythrocyte concentrations of cis ALA and one isomer of trans ALA. We also found trans ALA in mayonnaise samples.Conclusions: A high intake of ALA was associated with an increased risk of intermediate AMD before 2002 but not afterward. The period before 2002 coincides with the same time period when trans ALA was found in food and participants' blood; this finding deserves further study.

Vitamin D and calcium intake and risk of early menopause.

Background: Early menopause, defined as the cessation of ovarian function before the age of 45 y, affects ∼10% of women and is associated with higher risk of cardiovascular disease, osteoporosis, and other conditions. Few modifiable risk factors for early menopause have been identified, but emerging data suggest that high vitamin D intake may reduce risk.Objective: We evaluated how intakes of vitamin D and calcium are associated with the incidence of early menopause in the prospective Nurses' Health Study II (NHS2).Design: Intakes of vitamin D and calcium from foods and supplements were measured every 4 y with the use of a food-frequency questionnaire. Cases of incident early menopause were identified from all participants who were premenopausal at baseline in 1991; over 1.13 million person-years, 2041 women reported having natural menopause before the age of 45 y. We used Cox proportional hazards regression to evaluate relations between intakes of vitamin D and calcium and incident early menopause while accounting for potential confounding factors.Results: After adjustment for age, smoking, and other factors, women with the highest intake of dietary vitamin D (quintile median: 528 IU/d) had a significant 17% lower risk of early menopause than women with the lowest intake [quintile median: 148 IU/d; HR: 0.83 (95% CI: 0.72, 0.95); P-trend = 0.03]. Dietary calcium intake in the highest quintile (median: 1246 mg/d) compared with the lowest (median: 556 mg/d) was associated with a borderline significantly lower risk of early menopause (HR: 0.87; 95% CI: 0.76, 1.00; P-trend = 0.03). Associations were stronger for vitamin D and calcium from dairy sources than from nondairy dietary sources, whereas high supplement use was not associated with lower risk.Conclusions: Findings suggest that high intakes of dietary vitamin D and calcium may be modestly associated with a lower risk of early menopause. Further studies evaluating 25-hydroxyvitamin D concentrations, other dairy constituents, and early menopause are warranted.

Dietary Intakes of Eicosapentaenoic Acid and Docosahexaenoic Acid and Risk of Age-Related Macular Degeneration.

PURPOSE: To evaluate the associations between intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the intermediate and advanced stages of age-related macular degeneration (AMD). DESIGN: Prospective cohort study. PARTICIPANTS: We followed 75 889 women from the Nurses' Health Study and 38 961 men from the Health Professionals Follow-Up Study who were at least 50 years old, from 1984 to 2012 and 1986 to 2010, respectively. Cohort participants are mostly white (≥95%). METHODS: We assessed dietary intake by a validated food frequency questionnaire (FFQ) at baseline and every 4 years. We calculated cumulative average intakes of EPA and DHA from FFQs and also computed predicted erythrocyte and plasma scores directly from food intake using regression models. Cox proportional hazards models were used to compute the associations with AMD outcomes. MAIN OUTCOME MEASURES: We confirmed 1589 incident intermediate and 1356 advanced AMD cases (primarily neovascular AMD) with a visual acuity of 20/30 or worse, owing primarily to AMD, by medical record review. RESULTS: For intermediate AMD, the pooled hazard ratio (HR) between the 2 cohorts for DHA comparing the extreme quintiles of intake was 0.78 (95% confidence interval [CI], 0.66-0.92; P trend, 0.008) and for EPA + DHA was 0.83 (95% CI, 0.71-0.98; P trend, 0.03). The pooled HR for fatty fish, comparing ≥5 servings per week to almost never, was 0.61 (95% CI, 0.46-0.81; P trend, <0.001). For advanced AMD, the pooled HR for DHA was 1.01 (95% CI, 0.84-1.21; P trend, 0.75) and for fatty fish was 0.80 (95% CI, 0.59-1.08; P trend, 0.11). Secondary analyses using predicted erythrocyte and plasma scores of EPA and DHA yielded slightly stronger inverse associations for intermediate AMD and similar results for advanced AMD. CONCLUSIONS: Higher intakes of EPA and DHA may prevent or delay the occurrence of visually significant intermediate AMD. However, the totality of current evidence for EPA and DHA and advanced AMD is discordant, though there was no association with advanced AMD in the present study.

Surrogates of long-term vitamin d exposure and ovarian cancer risk in two prospective cohort studies.

Experimental evidence and ecologic studies suggest a protective role of vitamin D in ovarian carcinogenesis. However, epidemiologic studies using individual level data have been inconsistent. We evaluated ultraviolet (UV)-B radiation, vitamin D intake, and predicted plasma 25-hydroxyvitamin D [25(OH)D] levels as long-term surrogates of vitamin D exposure within the Nurses' Health Study (NHS) and NHSII. We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) for risk of overall ovarian cancer and by histologic subtype using Cox proportional hazards models. Between 1976 and 2010 in NHS and 1989 and 2011 in NHSII, we identified a total of 1,225 incident epithelial ovarian cancer cases (NHS: 970, NHSII: 255) over 4,628,648 person-years of follow-up. Cumulative average UV-B exposure was not associated with ovarian cancer risk in NHS (Ptrend = 0.08), but was associated with reduced risk in NHSII (highest vs. lowest category RR = 0.67; 95% CI: 0.50, 0.89; Ptrend < 0.01). When stratified by histologic subtype, UV-B flux was positively associated with risk of serous tumors in NHS (Ptrend < 0.01), but inversely associated in NHSII (Ptrend = 0.01). Adjusted for confounders, ovarian cancer risk was not associated with vitamin D intake from food or supplements or with predicted 25(OH)D levels. Our study does not strongly support a protective role for vitamin D in ovarian cancer risk.

A randomized trial on folic acid supplementation and risk of recurrent colorectal adenoma.

BACKGROUND: Evidence from observational studies suggests that inadequate folate status enhances colorectal carcinogenesis, but results from some randomized trials do not support this hypothesis. OBJECTIVE: To assess the effect of folic acid supplementation on recurrent colorectal adenoma, we conducted a cost-efficient, double-blind, randomized trial among participants of 2 large prospective cohorts, the Health Professionals Follow-Up Study and the Nurses' Health Study. DESIGN: Participants were randomly assigned to receive folic acid (1 mg/d) (n = 338) or placebo (n = 334) for 3-6.5 y. The primary endpoint was any new diagnosis of adenoma during the study period (May 1996-March 2004). Secondary outcomes were adenoma by site and stage and number of recurrent adenomas. Associations were also examined by plasma folate concentrations at baseline. RESULTS: Incidence of at least one recurrent adenoma was not significantly associated with folic acid supplementation [relative risk (RR): 0.82; 95% CI: 0.59,1.13; P = 0.22]. Among participants with low plasma folate concentrations at baseline (7.5 ng/mL), supplemental folic acid had no significant effect (RR: 1.28; 95% CI: 0.82, 1.99; P = 0.27, P(interaction) = 0.01). Contrary to findings from another clinical trial, there was no evidence for an increased risk of advanced or multiple adenomas. CONCLUSIONS: Our results do not support an overall protective effect of folic acid supplementation on adenoma recurrence. Folic acid supplementation may be beneficial among those with lower folate concentrations at baseline. This trial was registered at clinical trials.gov as NCT00512850.

Mammographic screening and risk factors for breast cancer.

Screening mammography can distort estimated effects in breast cancer risk models due to associations with other risk factors. Mammography information was available in the Nurses' Health Study from 1988, and 1,815 incident breast cancers were accrued through 2000 among 55,625 women with risk factor data. Logistic models were fit for screening mammography, and inverse probability weighting was used to adjust parameters in an established breast cancer risk model. Approximately 80% of women in each 2-year follow-up period had screening mammograms, which were positively associated with history of benign breast disease, family history of breast cancer, hormone therapy, alcohol use, physical activity, multivitamins, and calcium supplements, and negatively associated with postmenopause, current smoking, and body mass index. Markers of medical attention, including hypertension, high cholesterol, and osteoarthritis, were positively associated, while cardiovascular disease was negative. Inverse probability weighting led to small changes in effects of benign breast disease, family history, and hormone therapy. An apparent reduced risk associated with current smoking in unadjusted models was eliminated after weighting. Thus, several risk factors for breast cancer and cancer diagnosis are associated with mammographic screening. Adjustment for screening had some impact on breast cancer prediction in this cohort, especially for hormone therapy and smoking.

Caffeine consumption and the risk of primary open-angle glaucoma: a prospective cohort study.

PURPOSE: To investigate whether caffeine, which transiently increases intraocular pressure (IOP) is associated with the risk of primary open-angle glaucoma (POAG). METHODS: A total of 79,120 women from 1980 to 2004 and 42,052 men from 1986 to 2004, who were 40+ years of age, did not have POAG, and reported undergoing eye examinations, were observed. Information on caffeine consumption, potential confounders, and POAG diagnoses were repeatedly updated in validated follow-up questionnaires. One thousand eleven incident POAG cases were confirmed with medical record review. Cohort-specific and pooled analyses across cohorts were conducted to calculate multivariate rate ratios (RRs). RESULTS: Compared with daily intake of less than 150 mg, the pooled multivariate RRs were 1.05 (95% confidence interval [CI], 0.89-1.25) for consumption of 150 to 299 mg/d, 1.19 (95% CI, 0.99-1.43) for 300 to 449 mg/d, 1.13 (95% CI, 0.89-1.43) for 450 to 559 mg/d, and 1.17 (95% CI, 0.90-1.53) for 600+ mg/d (P for trend = 0.11). However, for consumption of five or more cups of caffeinated coffee daily, the RR was 1.61 (95% CI, 1.00-2.59; P for trend = 0.02); tea or caffeinated cola intake were not associated with risk. Greater caffeine intake was more adversely associated with POAG among those reporting a family history of glaucoma, particularly in relation to POAG with elevated IOP (P for trend = 0.0009; P interaction = 0.04). CONCLUSIONS: Overall caffeine intake was not associated with increased risk of POAG. However, in secondary analyses, caffeine appeared to elevate risk of high-tension POAG among those with a family history of glaucoma. This result may be due to chance, but warrants further study.

Use of multivitamins, intake of B vitamins, and risk of ovulatory infertility.

OBJECTIVE: To examine whether use of multivitamins and intake of specific nutrients in multivitamins is associated with ovulatory infertility. DESIGN: A prospective cohort study. SETTING: The Nurses' Health Study II. PATIENT(S): Eighteen thousand five hundred fifty-five married, premenopausal women without a history of infertility who attempted a pregnancy or became pregnant between 1991 and 1999. INTERVENTION(S): None, observational study. MAIN OUTCOME MEASURE(S): Incident reports of infertility caused by anovulation. RESULT(S): During 8 years of follow-up, 438 women reported infertility caused by ovulatory disorder. There was an inverse association between frequency of multivitamin use and ovulatory infertility. The multivariate-adjusted relative risk (95% confidence interval) of ovulatory infertility was 0.88 (0.60, 1.28) for women consuming two tablets per week or less, 0.69 (0.51, 0.95) for women consuming three to five tablets per week, and 0.59 (0.46, 0.75) for women consuming six or more tablets per week, when compared with women who did not use these supplements (P, trend <.001). Folic acid appeared to explain part of the association between multivitamin supplement use and risk of ovulatory infertility. CONCLUSION(S): Regular use of multivitamin supplements may decrease the risk of ovulatory infertility.

Parental characteristics as predictors of birthweight.

BACKGROUND: Previous studies provided conflicting results on the relevance of parental characteristics for offspring's size at birth. The objective of this study was to investigate parental predictors of birthweight. METHODS: In this cross-sectional study, 34,063 women in the Nurses' Mother's Cohort were queried about parental characteristics during the pregnancy with and birthweight of their nurse daughter. RESULTS: The predictive linear regression model of birthweight included 13 factors and the majority of the predictive power came from parental anthropometric factors. In the adjusted analysis, daily consumption of each additional glass of milk was associated with an increase of approximately 6 g in birthweight (P for trend = 0.01) and daily consumption of each additional cup of coffee was associated with a decrease of approximately 10 g in birthweight (P for trend < 0.0001). Drinking 1-2, 3-4 and 5+ cups of coffee daily was associated with a 28% [95% confidence interval (CI) 0.12, 0.47], 30% (95% CI 0.10, 0.55) and 63% (95% CI 0.25, 1.12) increase, respectively, in the odds of intrauterine growth restriction when compared with non-drinkers. CONCLUSIONS: The present study confirmed several previously reported determinants of birthweight. Maternal dietary intake of milk and coffee during pregnancy may influence fetal growth.

Diet and lifestyle in the prevention of ovulatory disorder infertility.

OBJECTIVE: To evaluate the relation of a dietary pattern and other lifestyle practices to risk of ovulatory disorder infertility. METHODS: We followed a cohort of 17,544 women without a history of infertility for 8 years as they tried to become pregnant or became pregnant. A dietary score based on factors previously related to lower ovulatory disorder infertility (higher consumption of monounsaturated rather than trans fats, vegetable rather than animal protein sources, low glycemic carbohydrates, high fat dairy, multivitamins, and iron from plants and supplements) and other lifestyle information was prospectively related to the incidence of infertility. RESULTS: Increasing adherence to a "fertility diet" pattern was associated with a lower risk of ovulatory disorder infertility. The multivariable-adjusted relative risk of ovulatory disorder infertility comparing women in the highest with women in the lowest quintile of the "fertility diet" pattern score was 0.34 (95% confidence interval 0.23-0.48; P for trend<.001). This inverse relation was similar in subgroups defined by women's age, parity, and body weight. A combination of five or more low-risk lifestyle factors, including diet, weight control, and physical activity was associated with a 69% lower risk of ovulatory disorder infertility and an estimated population attributable risk of 66% (95% confidence interval 29-86%). CONCLUSION: Following a "fertility diet" pattern may favorably influence fertility in otherwise healthy women. Further, the majority of infertility cases due to ovulation disorders may be preventable through modifications of diet and lifestyle. LEVEL OF EVIDENCE: II.

Iron intake and risk of ovulatory infertility.

OBJECTIVE: To evaluate whether iron supplement use or greater intake of total, heme and nonheme iron is associated with lower risk of ovulatory infertility. METHODS: We conducted a prospective cohort study among 18,555 married, premenopausal women without a history of infertility who attempted a pregnancy or became pregnant between 1991 and 1999 (mean baseline age+/-standard deviation 32.6+/-3.6). Diet was assessed twice during follow-up and prospectively related to the incidence of infertility due to ovulatory disorder. RESULTS: During the 8 years of follow-up, 438 women reported infertility due to ovulatory disorder. Women who consumed iron supplements had a significantly lower risk of ovulatory infertility than women who did not use iron supplements (relative risk 0.60, 95% confidence interval 0.39-0.92), after adjusting for potential confounders. Total nonheme iron intake, primarily consumed as multivitamins and iron supplements, was inversely associated with the risk of infertility (relative risk Quintile 1 compared with 5, 95% confidence interval 0.39-0.92; P, trend .005.) Heme iron intake was unrelated to ovulatory infertility in multivariable adjusted analyses. CONCLUSION: Consumption of iron supplements and nonheme iron from other sources may decrease the risk of ovulatory infertility. LEVEL OF EVIDENCE: II-2.

Dietary evaluation and attenuation of relative risk: multiple comparisons between blood and urinary biomarkers, food frequency, and 24-hour recall questionnaires: the DEARR study.

Estimates of diet-disease relative risks (RRs) suffer from inaccuracies introduced by dietary measurement errors. Using the "method of triads," by which the validity coefficient (VC) of the dietary assessment method and "true" long-term intake could be estimated from 3 pairwise correlations between the FFQ, the reference method, and the biomarker, the authors evaluated the performance of a newly developed FFQ. Over a period of 13 mo (September 2000 to September 2001), 161 participants completed 3 FFQs and six 24-h recalls (24HRs), and supplied 2 blood samples and three 24-h urine collections. For protein, beta-carotene, and folic acid, the VCs of the FFQ with the "true intake" (0.77, 0.65, and 0.72, respectively) were relatively higher than the VCs of 24HRs (0.68, 0.60 and 0.39, respectively). Among the biomarkers, the VCs of serum beta-carotene and folic acid with the "true intake" (0.65 and 0.65) were higher than the VCs of urinary nitrogen and alpha-tocopherol (0.44 and 0.34, respectively). The DEARR study showed that the newly developed FFQ is a valid and reproducible instrument for assessing dietary intake. The VCs obtained can be used for future adjustment of diet-disease RR estimates in this population.

Dietary fat consumption and primary open-angle glaucoma.

BACKGROUND: Prostaglandin F(2alpha) analogues are effective intraocular-pressure-lowering drugs. Dietary fatty acids affect endogenous prostaglandin F(2alpha) concentrations and may thus influence intraocular pressure. OBJECTIVE: We prospectively examined dietary fat consumption in relation to primary open-angle glaucoma (POAG). DESIGN: Women (n = 76 199 in the Nurses' Health Study) and men (n = 40 306 in the Health Professionals Follow-Up Study) free of POAG in 1980 and 1986, respectively, were followed until 1996 if they were > or =40 y old and reported receiving eye exams during follow-up. Potential confounders were assessed on biennial questionnaires, and energy-adjusted cumulative averaged fat intakes were measured by using validated food-frequency questionnaires. We analyzed 474 self-reported POAG cases confirmed by medical chart review. Cohort-specific multivariate rate ratios (RRs) were obtained by using proportional hazards models and were then pooled. RESULTS: Major fats and fat subtypes were not independently associated with POAG risk. Pooled multivariate RRs (95% CI) for POAG comparing the highest with the lowest quintile of fat intake were as follows: 0.90 (0.67, 1.21) for total fat, 1.03 (0.77, 1.38) for saturated fat, 0.76 (0.56, 1.03) for monounsaturated fat, and 0.87 (0.66, 1.16) for polyunsaturated fat, none of which were statistically significant. We found a suggestive positive association between a higher ratio of n-3 to n-6 polyunsaturated fat and risk of POAG [RR = 1.49 (1.11, 2.01); P for trend = 0.10], which was stronger for high-tension POAG [RR = 1.68 (1.18, 2.39); P for trend = 0.009]. CONCLUSION: A high ratio of n-3 to n-6 polyunsaturated fat appears to increase the risk of POAG, particularly high-tension POAG. Further studies are needed.

Folate, vitamin B6, and B12 intakes in relation to risk of stroke among men.

BACKGROUND AND PURPOSE: Folate, vitamin B6, and B12 deficiency are related to elevated blood homocysteine level. However, the effects of intakes of these vitamins on risk of stroke are still uncertain. This study examines intakes of folate, vitamin B6, and B12 in relation to risk of ischemic and hemorrhagic stroke. METHODS: We enrolled 43 732 men, aged 40 to 75 years, who were free of cardiovascular diseases and diabetes at baseline. Participants were followed from 1986 to 2000. Dietary information was assessed every 4 years using a detailed and validated semiquantitative food frequency questionnaire. The main outcome measures were incident ischemic and hemorrhagic strokes. RESULTS: A total of 725 incident strokes, including 455 ischemic, 125 hemorrhagic, and 145 unknown types of stroke, were documented during the 14-year follow-up. After adjustment for major lifestyle and dietary factors, intake of folate was associated with a significantly lower risk of ischemic but not hemorrhagic stroke. The multivariate relative risk of ischemic stroke was 0.71 (95% CI, 0.52 to 0.96; P for trend=0.05) for men in the highest quintile of intake compared with those who in the lowest quintile. Intake of vitamin B12, but not B6, was also inversely associated with risk of ischemic stroke. CONCLUSIONS: Our findings suggest that increased folate intake is associated with decreased risk of ischemic stroke in men.

Fish consumption and risk of stroke in men.

CONTEXT: The effect of fish consumption or long-chain omega-3 polyunsaturated fatty acid (PUFA) intake on risk of stroke remains uncertain. OBJECTIVE: To examine the relation of fish consumption and long-chain omega-3 PUFA intake and risk of stroke in men. DESIGN AND SETTING: The Health Professional Follow-up Study, a US prospective cohort study with 12 years of follow-up. PARTICIPANTS: A total of 43 671 men aged 40 to 75 years who completed a detailed and validated semiquantitative food frequency questionnaire and who were free of cardiovascular disease at baseline in 1986. MAIN OUTCOME MEASURE: Relative risk (RR) of stroke by subtype based on cumulative average fish consumption or long-chain omega-3 PUFA intake, ascertained in 1986, 1990, and 1994. RESULTS: We documented 608 strokes during the 12-year follow-up period, including 377 ischemic, 106 hemorrhagic, and 125 unclassified strokes. Compared with men who consumed fish less than once per month, the multivariate RR of ischemic stroke was significantly lower among those who ate fish 1 to 3 times per month (RR, 0.57; 95% confidence interval [CI], 0.35-0.95). However, a higher frequency of fish intake was not associated with further risk reduction; the RR was 0.54 (95% CI, 0.31-0.94) for men who consumed fish 5 or more times per week. This lack of linearity was confirmed by spline analyses. By dichotomized fish intake, the multivariate RR for men who consumed fish at least once per month compared with those who ate fish less than once per month was 0.56 (95% CI, 0.38-0.83) for ischemic stroke and 1.36 (95% CI, 0.48-3.82) for hemorrhagic stroke. The inverse association between fish intake and risk of ischemic stroke was not materially modified by use of aspirin. No significant associations were found between fish or long-chain omega-3 PUFA intake and risk of hemorrhagic stroke. CONCLUSION: Our findings suggest that eating fish once per month or more can reduce the risk of ischemic stroke in men.