Plasma Concentrations of Long Chain N-3 Fatty Acids in Early and Mid-Pregnancy and Risk of Early Preterm Birth.

BACKGROUND: Fish oil supplementation has been shown to delay spontaneous delivery, but the levels and clinical significance remain uncertain. We examined the association between plasma fatty acids quantified in pregnancy and subsequent risk of early preterm birth. METHODS: In a case-control design nested in the Danish National Birth Cohort, we identified 376 early preterm cases (<34 gestational weeks, excluding preeclampsia cases) and 348 random controls. Plasma eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA% of total fatty acids), were measured twice in pregnancy, at gestation weeks 9 and 25 (medians). Odds ratios and 95% confidence intervals (CI's) for associations between EPA+DHA and early preterm risk were estimated by logistic regression, adjusted for the woman's age, height, pre-pregnancy BMI, parity, smoking, and socioeconomic factors. Hypotheses and analytical plan were defined and archived a priori. FINDINGS: Analysis using restricted cubic splines of the mean of 1st and 2nd sample measurements showed a strong and significant non-linear association (p < 0.0001) in which the risk of early preterm birth steeply increased when EPA+DHA concentrations were lower than 2% and flattened out at higher levels. Women in the lowest quintile (EPA+DHA < 1.6%) had 10.27 times (95% confidence interval 6.80-15.79, p < 0.0001) increased risk, and women in the second lowest quintile had 2.86 (95% CI 1.79-4.59, p < 0.0001) times increased risk, when compared to women in the three aggregated highest quintiles (EPA+DHA ≥ 1.8%). INTERPRETATION: Low plasma concentration of EPA and DHA during pregnancy is a strong risk factor for subsequent early preterm birth in Danish women.

Predicted vitamin D status and colon cancer recurrence and mortality in CALGB 89803 (Alliance).

BACKGROUND: Observational studies suggest that higher levels of 25-hydroxyvitamin D3 (25(OH)D) are associated with a reduced risk of colorectal cancer and improved survival of colorectal cancer patients. However, the influence of vitamin D status on cancer recurrence and survival of patients with stage III colon cancer is unknown. PATIENTS AND METHODS: We prospectively examined the influence of post-diagnosis predicted plasma 25(OH)D on outcome among 1016 patients with stage III colon cancer who were enrolled in a National Cancer Institute-sponsored adjuvant therapy trial (CALGB 89803). Predicted 25(OH)D scores were computed using validated regression models. We examined the influence of predicted 25(OH)D scores on cancer recurrence and mortality (disease-free survival; DFS) using Cox proportional hazards. RESULTS: Patients in the highest quintile of predicted 25(OH)D score had an adjusted hazard ratio (HR) for colon cancer recurrence or mortality (DFS) of 0.62 (95% confidence interval [CI], 0.44-0.86), compared with those in the lowest quintile (Ptrend = 0.005). Higher predicted 25(OH)D score was also associated with a significant improvement in recurrence-free survival and overall survival (Ptrend = 0.01 and 0.0004, respectively). The benefit associated with higher predicted 25(OH)D score appeared consistent across predictors of cancer outcome and strata of molecular tumor characteristics, including microsatellite instability and KRAS, BRAF, PIK3CA, and TP53 mutation status. CONCLUSION: Higher predicted 25(OH)D levels after a diagnosis of stage III colon cancer may be associated with decreased recurrence and improved survival. Clinical trials assessing the benefit of vitamin D supplementation in the adjuvant setting are warranted. CLINICALTRIALS.GOV IDENTIFIER: NCT00003835.

Impact of vitamin D supplementation on adiposity in African-Americans.

BACKGROUND: African-Americans have higher rates of obesity-associated chronic diseases. Serum 25-hydroxyvitamin D (25(OH)D) shows an inverse association with obesity status. We investigated whether vitamin D supplementation changes body mass index (BMI). SUBJECTS: In total, 328 overweight African-Americans were enrolled over three consecutive winter periods (2007-2010) into a randomized, double-blind, placebo-controlled trial to receive cholecalciferol supplementation (0, 1000 international units (IU), 2000 IU or 4000 IU per day) for 3 months. Plasma concentrations of 25(OH)D and anthropometric measurements were done at baseline, 3 and 6 months. RESULTS: At 3 months, vitamin D supplementation in three dose groups (1000 IU, 2000 IU or 4000 IU per day) did not cause any significant changes in BMI as compared with placebo group 3-month change in BMI per 1000 IU per day estimate (SE): 0.01 (0.039); P=0.78. CONCLUSIONS: In overweight African-Americans, short-term high-dose vitamin D supplementation did not alter BMI.

Lipid-soluble vitamins A, D, and E in HIV-infected pregnant women in Tanzania.

BACKGROUND/OBJECTIVES: There is limited published research examining lipid-soluble vitamins in human immunodeficiency virus (HIV)-infected pregnant women, particularly in resource-limited settings. SUBJECTS/METHODS: This is an observational analysis of 1078 HIV-infected pregnant women enrolled in a trial of vitamin supplementation in Tanzania. Baseline data on sociodemographic and anthropometric characteristics, clinical signs and symptoms, and laboratory parameters were used to identify correlates of low plasma vitamin A (<0.7 micromol/l), vitamin D (<80 nmol/l) and vitamin E (<9.7 micromol/l) status. Binomial regression was used to estimate risk ratios and 95% confidence intervals. RESULTS: Approximately 35, 39 and 51% of the women had low levels of vitamins A, D and E, respectively. Severe anemia (hemoglobin <85 g/l; P<0.01), plasma vitamin E (P=0.02), selenium (P=0.01) and vitamin D (P=0.02) concentrations were significant correlates of low vitamin A status in multivariate models. Erythrocyte Sedimentation Rate (ESR) was independently related to low vitamin A status in a nonlinear manner (P=0.01). The correlates of low vitamin D status were CD8 cell count (P=0.01), high ESR (ESR >81 mm/h; P<0.01), gestational age at enrollment (nonlinear; P=0.03) and plasma vitamins A (P=0.02) and E (P=0.01). For low vitamin E status, the correlates were money spent on food per household per day (P<0.01), plasma vitamin A concentration (nonlinear; P<0.01) and a gestational age <16 weeks at enrollment (P<0.01). CONCLUSIONS: Low concentrations of lipid-soluble vitamins are widely prevalent among HIV-infected women in Tanzania and are correlated with other nutritional insufficiencies. Identifying HIV-infected persons at greater risk of poor nutritional status and infections may help inform design and implementation of appropriate interventions.

Vitamin supplement use and the risk of non-Hodgkin's lymphoma among women and men.

The authors examined use of individual supplements of vitamins A, C, and E only and multivitamins in relation to risk of non-Hodgkin's lymphoma in prospective cohorts of 88,410 women in the Nurses' Health Study (1980-1996), with 261 incident cases during 16 years of follow-up, and of 47,336 men in the Health Professionals Follow-Up Study (1986-1996), with 111 incident cases during 10 years of follow-up. Multivitamin use was associated with a higher risk of non-Hodgkin's lymphoma among women but not among men; the multivariate relative risks for long-term duration (10 or more years) were 1.48 (95% confidence interval (CI): 1.01, 2.16) for women and 0.85 (95% CI: 0.45, 1.58) for men. The pooled multivariate relative risk from the two cohorts was 1.18 (95% CI: 0.70, 2.02). Use of individual supplements of vitamins A, C, and E only was not associated with risk among men. An increased risk associated with the use of individual supplements of vitamins A, C, and E only among women appeared to be secondary to the use of multivitamins by the same persons. Because an elevated risk among multivitamin users was not observed consistently in the two cohorts and the pooled data were not significant, the elevated risk among women may be the result of chance.

Supplemental vitamin E intake and prostate cancer risk in a large cohort of men in the United States.

A clinical trial of vitamin E and beta-carotene supplementation for lung cancer prevention among male smokers in Finland recently reported an unexpected, strong protective effect of vitamin E against prostate cancer incidence and mortality. Our objective was to prospectively examine supplemental vitamin E intake and prostate cancer risk in a distinct U.S. population. In 1986, we identified 47,780 U.S. male health professionals, free from diagnosed cancer, who completed a dietary and lifestyle questionnaire; supplemental vitamin E and prostate cancer incidence were updated biennially through 1996. We estimated relative risks (RRs) from multivariate pooled logistic regression models. There were 1896 total (non-stage A1), 522 extraprostatic, and 232 metastatic or fatal incident prostate cancer cases diagnosed between 1986-1996. Men consuming at least 100 IU of supplemental vitamin E daily had multivariate RRs of 1.07 (95% confidence interval [CI], 0.95-1.20) for total and 1.14 (95% CI, 0.82-1.59) for metastatic or fatal prostate cancer compared with those consuming none. Current use, dosage, and total duration of use of specific vitamin E supplements or multivitamins were not associated with risk. However, among current smokers and recent quitters, those who consumed at least 100 IU of supplemental vitamin E per day had a RR of 0.44 (95% CI, 0.18-1.07) for metastatic or fatal prostate cancer compared with nonusers. Thus, supplemental vitamin E was not associated with prostate cancer risk generally, but a suggestive inverse association between supplemental vitamin E and risk of metastatic or fatal prostate cancer among current smokers and recent quitters was consistent with the Finnish trial among smokers and warrants further investigation.

A prospective study of folate intake and the risk of breast cancer.

CONTEXT: Folate is involved in DNA synthesis and methylation and may reduce breast cancer risk, particularly among women with greater alcohol consumption. OBJECTIVES: To assess the association between folate intake and risk of breast cancer and whether higher folate intake may reduce excess risk among women who consume alcohol. DESIGN: Prospective cohort study performed in 1980, with 16 years of follow-up. SETTING AND PARTICIPANTS: A total of 88818 women who completed the dietary questionnaire section of the Nurses' Health Study in 1980. MAIN OUTCOME MEASURE: Incidence of invasive breast cancer by levels of folate and alcohol intake. RESULTS: A total of 3483 cases of breast cancer were documented. Total folate intake was not associated with overall risk of breast cancer. However, among women who consumed at least 15 g/d of alcohol, the risk of breast cancer was highest among those with low folate intake. For total folate intake of at least 600 microg/d compared with 150 to 299 microg/d, the multivariate relative risk (RR) was 0.55 (95% confidence interval [CI], 0.39-0.76; P for trend = .001). This association was only slightly attenuated after additional adjustment for intake of beta carotene, lutein/zeaxanthin, preformed vitamin A, and total vitamins C and E. The risk of breast cancer associated with alcohol intake was strongest among women with total folate intake of less than 300 microg/d (for alcohol intake > or =15 g/d vs <15 g/d, multivariate RR, 1.32; 95% CI, 1.15-1.50). For women who consumed at least 300 microg/d of total folate, the multivariate RR for intake of at least 15 g/d of alcohol vs less than 15 g/d was 1.05 (95% CI, 0.92-1.20). Current use of multivitamin supplements, the major source of folate, was associated with lower breast cancer risk among women who consumed at least 15 g/d of alcohol (for current users of supplements vs never users, RR, 0.74; 95% CI, 0.59-0.93). CONCLUSIONS: Our findings suggest that the excess risk of breast cancer associated with alcohol consumption may be reduced by adequate folate intake.

Intake of potassium, magnesium, calcium, and fiber and risk of stroke among US men.

BACKGROUND: Animal experiments and epidemiological studies have suggested that high potassium intake may reduce the risk of stroke, but the evidence is inconclusive, and the role of other nutrients in potassium-rich foods remains unknown. METHODS AND RESULTS: We examined the association of potassium and related nutrients with risk of stroke among 43 738 US men, 40 to 75 years old, without diagnosed cardiovascular diseases or diabetes, who completed a semiquantitative food frequency questionnaire in 1986. During 8 years of follow-up, 328 strokes (210 ischemic, 70 hemorrhagic, 48 unspecified) were documented. The multivariate relative risk of stroke of any type for men in the top fifth of potassium intake (median intake, 4.3 g/d) versus those in the bottom (median, 2.4 g/d) was 0.62 (95% CI, 0.43, 0.88; P for trend=0.007). Results for ischemic stroke alone were similar. Intakes of cereal fiber and magnesium, but not of calcium, were also inversely associated with risk of total stroke. These inverse associations were all stronger in hypertensive than normotensive men and were not materially altered by adjustment for blood pressure levels. Use of potassium supplements was also inversely related to risk of stroke, particularly among men taking diuretics (relative risk, 0.36; 95% CI, 0.18, 0.72). CONCLUSIONS: Although these data do not prove a causal relationship, they are consistent with the hypothesis that diets rich in potassium, magnesium, and cereal fiber reduce the risk of stroke, particularly among hypertensive men. Potassium supplements may also be beneficial, but because of potential risks, use should be carefully monitored and restricted to men taking potassium-losing diuretics.

Prospective study of diet and the risk of duodenal ulcer in men.

The authors examined the associations between dietary factors and the risk of duodenal ulcer in a prospective cohort of 47,806 men, aged 40-75 years, who were free of diagnosed gastric or duodenal ulcer or cancer. During 6 years of follow-up, they documented 138 newly diagnosed cases of duodenal ulcer. They found little evidence for an important effect of fat, type of fat, or protein intake. Higher consumption of fruits and vegetables was associated with lower risk of duodenal ulcer (relative risk (RR) = 0.67, 95% confidence interval (CI) 0.39-1.15 for > or = 7 servings per day vs. < 3 servings per day) after adjustment for age, body mass index, smoking, and use of aspirin or other nonsteroidal anti-inflammatory drugs. Total dietary fiber intake was inversely associated with the risk of duodenal ulcer (RR = 0.55, 95% CI 0.31-0.96 for men in the highest vs. the lowest quintile of dietary fiber). The soluble component of fiber was strongly associated with a decreased risk of duodenal ulcer (RR = 0.40, 95% CI 0.22-0.74 for the highest quintile). Several age- and energy-adjusted nutrients correlated with dietary fiber were also inversely related to the risk of duodenal ulcer, but vitamin A from all sources combined (including supplements and multivitamins) was the only nutrient that was statistically significant after adjustment for other risk factors (RR = 0.46, 95% CI 0.23-0.91 for men in the highest vs. the lowest quintile of vitamin A intake). These findings provide evidence that vitamin A from all sources, as well as diets high in fruits and vegetables, may reduce the development of duodenal ulcer, possibly due to their fiber content. Although the associations appeared stronger for dietary fiber and vitamin A, the authors can not exclude the possibility that other closely correlated dietary factors may be the true protective factors.

Calcium, vitamin D, and the occurrence of colorectal cancer among women.

BACKGROUND: Despite evidence from animal studies for a protective effect of higher calcium and possibly vitamin D intake against colorectal cancer, epidemiologic studies have been inconclusive. PURPOSE: We investigated the associations between the intake of calcium and vitamin D and the occurrence of colorectal cancer. METHODS: In a prospective study, 89 448 female registered nurses who were free of cancer responded to a mailed, semiquantitative food-frequency questionnaire in 1980; dietary information was updated in 1984 and 1986. Through 1992, 501 incident cases of colorectal cancer (396 colon and 105 rectal cancers) were documented. As measures of exposure, we used nutrient intake in 1980 and also two measures of long-term intake on the basis of the three questionnaires: the average of intakes from the three questionnaires and consistent intakes, which were defined as high if women were in the upper tertile on all questionnaires and low if they were in the lower tertile on all questionnaires. To further characterize long-term intake, we conducted analyses excluding women who reported a change in their consumption of milk (primary source of calcium and vitamin D) in the 10 years prior to 1980. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using the lowest quintile of intake as a reference. The Mantel extension test was used to evaluate linear trends across the categories of nutrient intake. In multivariate analyses, the trends were tested with use of the medians of the intake as a continuous variable in the logistic model. The P values for the trends were two-sided. RESULTS: On the basis of the data from the 1980 questionnaire alone, the multivariate RR for colorectal cancer for women in the upper versus the lower quintile were 0.80 (95% CI = 0.60-1.07) for dietary calcium, 0.84 (95% CI = 0.63-1.13) for dietary vitamin D (from foods only), and 0.88 (95% CI = 0.66-1.16) for total vitamin D (from foods and supplements). After the exclusion of women who reported a change in their milk intake, the RRs for colorectal cancer for the highest versus the lowest categories of average intake were 0.74 (95% CI = 0.36-1.50) for dietary calcium, 0.72 (95% CI = 0.34-1.54) for dietary vitamin D, and 0.42 (95% CI = 0.19-0.91) for total vitamin D. The corresponding RRs for the consistency analyses were 0.70 (95% CI = 0.35-1.39) for dietary calcium, 0.59 (95% CI = 0.30- 1.16) for dietary vitamin D, and 0.33 (95% CI = 0.16-0.70) for total vitamin D. CONCLUSIONS: These findings do not support a substantial inverse association between calcium intake and risk of colorectal cancer, but an inverse association between intake of total vitamin D and risk of colorectal cancer was suggested. IMPLICATIONS: Available evidence does not warrant an increase in calcium intake to prevent colon cancer, but longer-term studies of both calcium and especially vitamin D in relation to colorectal cancer risk are needed.

A prospective study of alcohol, smoking, caffeine, and the risk of symptomatic diverticular disease in men.

The relationship between smoking, caffeine, and alcohol intake and the risk of symptomatic diverticular disease has not been investigated directly. We examined these associations in a prospective cohort of 47,678 US men, 40 to 75 years old. During 4 years of follow-up (1988 to 1992), we documented 382 newly diagnosed cases of symptomatic diverticular disease. After adjustments for age, physical activity, and energy-adjusted intake of dietary fiber and total fat, alcohol intake (comparing those who drink > 30 g of alcohol/d to nondrinkers) was only weakly and nonsignificantly associated with risk of symptomatic diverticular disease (relative risk (RR) = 1.36; 95 percent confidence interval (CI), 0.94 to 1.97; P for trend = 0.37). We observed no association between caffeine, specific caffeinated beverages, and decaffeinated coffee and the risk of symptomatic diverticular disease. Current smoking was not appreciably associated with risk of symptomatic diverticular disease compared to nonsmokers (RR = 1.25; 95 percent CI, 0.75 to 2.09) after adjustment for age, physical activity, and energy-adjusted intake of dietary fiber and total fat. In a subset analysis restricted to men who had undergone sigmoidoscopy or colonoscopy, a modest positive association was seen between smoking and risk of symptomatic diverticular disease. These results suggest that smoking, caffeine, and alcohol intake are not associated with any substantially increased risk of symptomatic diverticular disease.

Dietary intake of marine n-3 fatty acids, fish intake, and the risk of coronary disease among men.

BACKGROUND: It has been hypothesized that a diet containing n-3 fatty acids from fish reduces the risk of coronary heart disease, but few large epidemiologic studies have examined this question. METHODS: In 1986, 44,895 male health professionals, 40 to 75 years of age, who were free of known cardiovascular disease completed detailed and validated dietary questionnaires as part of the Health Professionals Follow-up Study. During six years of follow-up, we documented 1543 coronary events in this group: 264 deaths from coronary disease, 547 nonfatal myocardial infarctions, and 732 coronary-artery bypass or angioplasty procedures. RESULTS: After controlling for age and several coronary risk factors, we observed no significant associations between dietary intake of n-3 fatty acids or fish intake and the risk of coronary disease. For men in the top fifth of the group in terms of intake of n-3 fatty acids (median, 0.58 g per day), the multivariate relative risk of coronary heart disease was 1.12 (95 percent confidence interval, 0.96 to 1.31), as compared with the men in the bottom fifth (median, 0.07 g per day). For men who consumed six or more servings of fish per week, as compared with those who consumed one serving per month or less, the multivariate relative risk of coronary disease was 1.14 (95 percent confidence interval, 0.86 to 1.51). The risk of death due to coronary disease among men who ate any amount of fish, as compared with those who ate no fish, was 0.74 (95 percent confidence interval, 0.44 to 1.23), but the risk did not decrease as fish consumption increased. CONCLUSIONS: Although the possibility of residual confounding by unmeasured factors cannot be entirely excluded, these data suggest that increasing fish intake from one to two servings per week to five to six servings per week does not substantially reduce the risk of coronary heart disease among men who are initially free of cardiovascular disease.

Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals.

The authors assessed the reproducibility and validity of an expanded 131-item semiquantitative food frequency questionnaire used in a prospective study among 51,529 men. The form was administered by mail twice to a sample of 127 participants at a one-year interval. During this interval, men completed two one-week diet records spaced approximately 6 months apart. Mean values for intake of most nutrients assessed by the two methods were similar. Intraclass correlation coefficients for nutrient intakes assessed by questionnaires one year apart ranged from 0.47 for vitamin E without supplements to 0.80 for vitamin C with supplements. Correlation coefficients between the energy-adjusted nutrient intakes measured by diet records and the second questionnaire (which asked about diet during the year encompassing the diet records) ranged from 0.28 for iron without supplements to 0.86 for vitamin C with supplements (mean r = 0.59). These correlations were higher after adjusting for week-to-week variation in diet record intakes (mean r = 0.65). These data indicate that the expanded semiquantitative food frequency questionnaire is reproducible and provides a useful measure of intake for many nutrients over a one-year period.