Effects of Vitamin D, Omega-3 Fatty Acids and a Home Exercise Program on Prevention of Pre-Frailty in Older Adults: The DO-HEALTH Randomized Clinical Trial.

BACKGROUND: The benefits of supplemental vitamin D3, marine omega-3 fatty acids, and a simple home exercise program (SHEP) on frailty prevention in generally healthy community-dwelling older adults are unclear. OBJECTIVE: To test the effect of vitamin D3, omega-3s, and a SHEP, alone or in combination on incident pre-frailty and frailty in robust older adults over a follow-up of 36 months. METHODS: DO-HEALTH is a multi-center, double-blind, placebo-controlled, 2x2x2 factorial randomized clinical trial among generally healthy European adults aged 70 years or older, who had no major health events in the 5 years prior to enrollment, sufficient mobility and intact cognitive function. As a secondary outcome of the DO-HEALTH trial, among the subset of participants who were robust at baseline, we tested the individual and combined benefits of supplemental 2,000 IU/day of vitamin D3, 1 g/day of marine omega-3s, and a SHEP on the odds of being pre-frail and frail over 3 years of follow-up. RESULTS: At baseline, 1,137 out of 2,157 participants were robust (mean age 74.3 years, 56.5% women, mean gait speed 1.18 m/s). Over a median follow-up time of 2.9 years, 696 (61.2%) became pre-frail and 29 (2.6%) frail. Odds ratios for becoming pre-frail were not significantly lower for vitamin D3, or omega 3-s, or SHEP, individually, compared to control (placebo for the supplements and control exercise). However, the three treatments combined showed significantly decreased odds (OR 0.61 [95% CI 0.38-0.98; p=0.04) of becoming pre-frail compared to control. None of the individual treatments or their combination significantly reduced the odds of becoming frail. CONCLUSION: Robust, generally healthy and active older adults without major comorbidities, may benefit from a combination of high-dose, supplemental vitamin D3, marine omega-3s, and SHEP with regard to the risk of becoming pre-frail over 3 years.

Issues of trial selection and subgroup considerations in the recent meta-analysis of Zhao and colleagues on fracture reduction by calcium and vitamin D supplementation in community-dwelling older adults.

Zhao and colleagues are addressing an important question about the efficacy of calcium and vitamin D on fracture risk reduction among community-dwelling adults age 50+. However, we are concerned about four aspects of their approach, which may affect the validity of their conclusions and implications for public health. INTRODUCTION: We discuss the recent meta-analysis by Zhao and colleagues on the primary prevention of fractures of calcium and vitamin D as well as their combination among community-dwelling adults age 50+. METHODS: Zhao and colleagues included 33 trials that recruited a total of 51,145 community-dwelling participants age 50 years and older, including any randomized clinical trial with a placebo or no treatment in the control group. RESULTS: The authors found no significant association of calcium and/or vitamin D with risk of hip fracture compared with placebo or no treatment and concluded that the routine use of calcium, vitamin D, and the combination in community-dwelling older people is not supported by their findings. We discuss four concerns regarding this meta-analysis, including the target population, the selection of trials with regard to blinding and duration of follow-up, and the lack of adjustment for adherence to the interventions and subgroup analysis by bolus versus daily dosing for vitamin D. CONCLUSION: Based on the four concerns raised in this letter and the fact that there will be a manyfold increase in the data on vitamin D supplementation in community-dwelling senior adults from large ongoing trials, we believe that it is too early to recommend the cessation of vitamin D with or without calcium for the prevention of fractures among community-dwelling adults.

Milk and other dairy foods and risk of hip fracture in men and women.

The role of dairy foods for hip fracture prevention remains controversial. In this study, among US men and women, a glass of milk per day was associated with an 8% lower risk of hip fracture. This contrasts with a reported increased risk with higher milk intake in Swedish women. INTRODUCTION: The purpose of this study was to examine whether higher milk and dairy food consumption are associated with risk of hip fracture in older adults following a report of an increased risk for milk in Swedish women. METHODS: In two US cohorts, 80,600 postmenopausal women and 43,306 men over 50 years of age were followed for up to 32 years. Cox proportional hazards models were used to calculate the relative risks (RR) of hip fracture per daily serving of milk (240 mL) and other dairy foods that were assessed every 4 years, controlling for other dietary intakes, BMI, height, smoking, activity, medications, and disease diagnoses. RESULTS: Two thousand one hundred thirty-eight incident hip fractures were identified in women and 694 in men. Each serving of milk per day was associated with a significant 8% lower risk of hip fracture in men and women combined (RR = 0.92, 95% confidence interval (CI) 0.87 to 0.97). A suggestive inverse association was found for cheese in women only (RR = 0.91, CI 0.81 to 1.02). Yogurt consumption was low and not associated with risk. Total dairy food intake, of which milk contributed about half, was associated with a significant 6% lower risk of hip fracture per daily serving in men and women (RR = 0.94, CI 0.90 to 0.98). Calcium, vitamin D, and protein from non-dairy sources did not modify the association between milk and hip fracture, nor was it explained by contributions of these nutrients from milk. CONCLUSIONS: In this group of older US adults, higher milk consumption was associated with a lower risk of hip fracture.

Multivitamin use and risk of stroke incidence and mortality amongst women.

BACKGROUND AND PURPOSE: Few studies have examined the association between multivitamin use and the risk of stroke incidence and mortality, and the results remain inconclusive as to whether multivitamins are beneficial. METHODS: The associations between multivitamin use and the risk of incident stroke and stroke mortality were prospectively examined in 86 142 women in the Nurses' Health Study, aged 34-59 years and free of diagnosed cardiovascular disease at baseline. Multivitamin use and covariates were updated every 2 years and strokes were documented by review of medical records. Hazard ratios of total, ischaemic and hemorrhagic strokes were calculated across categories of multivitamin use (non-user, past, current user) and duration (years), using Cox proportional hazards models. RESULTS: During 32 years of follow-up from 1980 to 2012, 3615 incident strokes were documented, including 758 deaths from stroke. In multivariate analyses, women who were current multivitamin users did not have a lower risk of incident total stroke compared to non-users [relative risk (RR) 1.02, 95% confidence interval (CI) 0.93-1.11], even those with longer durations of 15 or more years of use (RR 1.08, 95% CI 0.97-1.20) or those with a lower quality diet (RR 0.96, 95% CI 0.80-1.15). There was also no indication of benefit from multivitamin use for incident ischaemic or hemorrhagic strokes or for total stroke mortality. CONCLUSIONS: Long-term multivitamin use was not associated with reduced risk of stroke incidence or mortality amongst women in the study population, even amongst those with a lower diet quality. An effect in a less well-nourished population cannot be ruled out.

Consumption of soy foods and isoflavones and risk of type 2 diabetes: a pooled analysis of three US cohorts.

BACKGROUND/OBJECTIVES: Evidence regarding the consumption of soy foods and isoflavones in relation to risk of type 2 diabetes (T2D) is scarce. Our study was to evaluate the association between soy food and isoflavone consumption and risk of T2D in US men and women. SUBJECTS/METHODS: We followed 63 115 women in the Nurses' Health Study (1998-2012), 79 061 women in the Nurses' Health Study II (1999-2013) and 21 281 men in the Health Professionals Follow-Up Study (2002-2010). Diet was assessed by a validated food-frequency questionnaire and was updated every 4 years. Self-reports of incident T2D were confirmed by a validated supplementary questionnaire. RESULTS: During 1 966 321 person-years of follow-up, 9185 incident T2D cases were documented. After multivariate adjustment for covariates, consumption of soy foods (tofu and soy milk) was not associated with a lower T2D risk. Compared with non-consumers of soy foods, the hazard ratio (HR) was 1.00 (95% confidence interval (CI): 0.93, 1.07) for <1 serving/week and 0.93 (95% CI: 0.83, 1.03) for ⩾1 serving/week of soy foods (P for trend=0.14). In contrast, intake of total isoflavones was inversely associated with T2D risk. Comparing extreme quintiles of isoflavones, the HR was 0.89 (95% CI: 0.83, 0.96; P for trend=0.009). Inverse associations were also found for consumption of major individual isoflavones, including daidzein and genistein, with risk of T2D. CONCLUSIONS: Intake of isoflavones was associated with a modestly lower T2D risk in US men and women who typically consumed low-to-moderate amounts of soy foods. These findings warrant replications in other populations with similar soy intake levels.

Dietary fats and coronary heart disease.

The relation of dietary fat to risk of coronary heart disease (CHD) has been studied extensively using many approaches, including controlled feeding studies with surrogate end-points such as plasma lipids, limited randomized trials and large cohort studies. All lines of evidence indicate that specific dietary fatty acids play important roles in the cause and the prevention of CHD, but total fat as a percent of energy is unimportant. Trans fatty acids from partially hydrogenated vegetable oils have clear adverse effects and should be eliminated. Modest reductions in CHD rates by further decreases in saturated fat are possible if saturated fat is replaced by a combination of poly- and mono-unsaturated fat, and the benefits of polyunsaturated fat appear strongest. However, little or no benefit is likely if saturated fat is replaced by carbohydrate, but this will in part depend on the form of carbohydrate. Because both N-6 and N-3 polyunsaturated fatty acids are essential and reduce risk of heart disease, the ratio of N-6 to N-3 is not useful and can be misleading. In practice, reducing red meat and dairy products in a food supply and increasing intakes of nuts, fish, soy products and nonhydrogenated vegetable oils will improve the mix of fatty acids and have a markedly beneficial effect on rates of CHD.

Dietary intake of polyunsaturated fatty acids and risk of hip fracture in men and women.

UNLABELLED: Data on the impact of polyunsaturated fatty acid intake on hip fracture risk are inconsistent. We investigated this association in 75,878 women and 46,476 men and did not find a significant role for polyunsaturated fatty acid intake in the prevention of hip fractures. INTRODUCTION: Polyunsaturated fatty acids (PUFA) are important in the prevention of chronic diseases, but studies of bone health report inconsistent results. Our aim was to investigate the association between dietary PUFA intake and risk of hip fracture in two large prospective cohorts of men and women with long follow-up times and frequently updated dietary data. METHODS: The study population included 75,878 women and 46,476 men free of osteoporosis at baseline. Dietary intakes were assessed by a food frequency questionnaire at baseline and several times during the follow-up. Multivariable-adjusted Cox proportional hazards models were used to estimate relative risks (RR). RESULTS: During 24 years of follow-up, we identified 1,051 hip fracture cases due to low or moderate trauma among the women and 529 cases among the men. In the pooled analyses, no statistically significant associations were found between intakes of total PUFA [RR in the highest vs. lowest quintile: 0.99, 95% confidence interval (CI) 0.69, 1.43; p value for trend is =0.83], total n-3 PUFA (RR 0.89, 95% CI 0.75, 1.06; p value for trend is =0.26), total n-6 PUFA (RR 0.99, 95% CI 0.71, 1.38; p value for trend is =0.82), n-6/n-3 PUFA ratio or individual PUFAs, and hip fracture risk. However, in women low intakes of total PUFA, total n-6 PUFA, and linoleic acid were associated with higher risk. CONCLUSIONS: This study does not support a significant role for PUFA intake in the prevention of hip fractures, although low total PUFA, n-6 PUFA, or linoleic acid intakes may increase the risk in women.

Preventing chronic diseases by promoting healthy diet and lifestyle: public policy implications for China.

Fuelled by rapid urbanization and changes in dietary and lifestyle choices, chronic diseases have emerged as a critical public health issue in China. The Healthy China 2020 programme recently announced by the Chinese government has set an overarching goal of promoting public health and making health care accessible and affordable for all Chinese citizens by year 2020. One of important components of the programme is to reduce chronic diseases by promoting healthy eating and active lifestyles. Chronic diseases not only affect health and quality of life, but also have economical and social consequences. With a limited infrastructure for chronic disease care, China is ill-equipped to deal with the escalating chronic disease epidemic, which threatens to reverse the gains of economic development in recent decades. Population-based intervention studies conducted in China and elsewhere have demonstrated the efficacy and effectiveness of several preventive strategies to reduce risk of chronic diseases in high-risk individuals and the general population. However, translating these findings into practice requires changes in health systems and public policies. To achieve the goals set by the Healthy China 2020 programme, prevention of chronic diseases should be elevated to a national public policy priority.

Benefit-risk assessment of vitamin D supplementation.

UNLABELLED: Current intake recommendations of 200 to 600 IU vitamin D per day may be insufficient for important disease outcomes reduced by vitamin D. INTRODUCTION: This study assessed the benefit of higher-dose and higher achieved 25-hydroxyvitamin D levels [25(OH)D] versus any associated risk. METHODS AND RESULTS: Based on double-blind randomized control trials (RCTs), eight for falls (n = 2426) and 12 for non-vertebral fractures (n = 42,279), there was a significant dose-response relationship between higher-dose and higher achieved 25(OH)D and greater fall and fracture prevention. Optimal benefits were observed at the highest dose tested to date for 700 to 1000 IU vitamin D per day or mean 25(OH)D between 75 and 110 nmol/l (30-44 ng/ml). Prospective cohort data on cardiovascular health and colorectal cancer prevention suggested increased benefits with the highest categories of 25(OH)D evaluated (median between 75 and 110 nmol/l). In 25 RCTs, mean serum calcium levels were not related to oral vitamin D up to 100,000 IU per day or achieved 25(OH)D up to 643 nmol/l. Mean levels of 75 to 110 nmol/l were reached in most RCTs with 1,800 to 4,000 IU vitamin D per day without risk. CONCLUSION: Our analysis suggests that mean serum 25(OH)D levels of about 75 to 110 nmol/l provide optimal benefits for all investigated endpoints without increasing health risks. These levels can be best obtained with oral doses in the range of 1,800 to 4,000 IU vitamin D per day; further work is needed, including subject and environment factors, to better define the doses that will achieve optimal blood levels in the large majority of the population.

Health effects of trans-fatty acids: experimental and observational evidence.

BACKGROUND/OBJECTIVES: Growing evidence indicates that trans-fatty acids (TFA) adversely affect cardiovascular health. As part of the World Health Organization (WHO) Scientific Update on TFA, we reviewed the evidence for effects of TFA consumption on coronary heart disease (CHD). SUBJECTS/METHODS: We searched Medline publications examining TFA consumption and CHD risk factors or outcomes, emphasizing results of studies in humans. We evaluated and synthesized evidence from both controlled feeding trials evaluating risk factors and long-term observational studies evaluating risk factors or clinical outcomes, each of which have complementary strengths and limitations, to enable the most robust and reliable inferences of effects. RESULTS: The effects of TFA consumption on risk factors most consistently seen in both controlled trials and observational studies included adverse lipid effects (for example [upward arrow] low-density lipoprotein cholesterol, [downward arrow] high-density lipoprotein cholesterol (HDL-C), [upward arrow] total/HDL-C ratio), proinflammatory effects (for example [upward arrow] tumor necrosis factor-alpha activity, [upward arrow] interleukin-6, [upward arrow] C-reactive protein) and endothelial dysfunction. These effects were most prominent in comparison with cis unsaturated fats; adverse effects on total/HDL-C and endothelial function were also seen in comparison with saturated fatty acids (SFA). TFA may also worsen insulin sensitivity, particularly among individuals predisposed to insulin resistance; possible effects on weight gain and diabetes incidence require further confirmation. Five retrospective case-control studies and four prospective cohort studies demonstrated positive associations between TFA consumption and CHD events. A meta-analysis of prospective studies indicated 24, 20, 27 and 32% higher risk of myocardial infarction (MI) or CHD death for every 2% energy of TFA consumption isocalorically replacing carbohydrate, SFA, cis monounsaturated fatty acids and cis polyunsaturated fatty acids, respectively. The differential effects of specific TFA isomers may be important but are less well established. The available evidence indicates that trans-18:1 and particularly trans-18:2 isomers have stronger CHD effects than trans-16:1 isomers. The limited data suggest that the experimental effects of ruminant and industrial TFA are similar when consumed in similar quantities, but very few persons consume such high levels of ruminant TFA, and observational studies do not support adverse CHD effects of ruminant TFA in amounts actually consumed. CONCLUSIONS: Controlled trials and observational studies provide concordant evidence that consumption of TFA from partially hydrogenated oils adversely affects multiple cardiovascular risk factors and contributes significantly to increased risk of CHD events. The public health implications of ruminant TFA consumption appear much more limited. The effects of specific TFA isomers require further investigation.

Vitamin D intake and incidence of multiple sclerosis.

BACKGROUND: A protective effect of vitamin D on risk of multiple sclerosis (MS) has been proposed, but no prospective studies have addressed this hypothesis. METHODS: Dietary vitamin D intake was examined directly in relation to risk of MS in two large cohorts of women: the Nurses' Health Study (NHS; 92,253 women followed from 1980 to 2000) and Nurses' Health Study II (NHS II; 95,310 women followed from 1991 to 2001). Diet was assessed at baseline and updated every 4 years thereafter. During the follow-up, 173 cases of MS with onset of symptoms after baseline were confirmed. RESULTS: The pooled age-adjusted relative risk (RR) comparing women in the highest quintile of total vitamin D intake at baseline with those in the lowest was 0.67 (95% CI = 0.40 to 1.12; p for trend = 0.03). Intake of vitamin D from supplements was also inversely associated with risk of MS; the RR comparing women with intake of >or=400 IU/day with women with no supplemental vitamin D intake was 0.59 (95% CI = 0.38 to 0.91; p for trend = 0.006). No association was found between vitamin D from food and MS incidence. CONCLUSION: These results support a protective effect of vitamin D intake on risk of developing MS.

Dietary intakes of vitamins A, C, and E and risk of melanoma in two cohorts of women.

Within the two Nurses' Health Study cohorts of US women, we examined whether higher intakes of vitamin C, vitamin E, retinol, or individual tocopherols or carotenoids are associated with a lower risk of melanoma. We confirmed 414 cases of invasive melanoma among over 162,000 Caucasian women aged 25-77 years during more than 1.6 million person-years of follow-up. Diet was measured every 4 years with a food frequency questionnaire and supplement use was reported every 2 years. Several measures of sun sensitivity were assessed and included in proportional hazards models. We found that vitamins A, C, E and their individual components were not associated with a lower risk of melanoma. Only retinol intake from foods plus supplements appeared protective within a subgroup of women who were otherwise at low risk based on nondietary factors (relative risk (RR)=0.39, 95% confidence interval (CI) 0.22-0.71 for >/=1,800 vs 400 microg day(-1), P for linear trend=0.01). Contrary to expectation, we observed higher risks of melanoma with greater intakes of vitamin C from food only (RR=1.43, 95% CI 1.01-2.00 for >/=175 vs <90 mg day(-1), P for linear trend=0.05) and a significant positive dose-response with frequency of orange juice consumption (P=0.008). Further research is needed to determine whether another component in foods such as orange juice may contribute to an increase in risk.

Intakes of vitamins E and C, carotenoids, vitamin supplements, and PD risk.

BACKGROUND: Oxidative damage has been implicated in the pathogenesis of PD. Limited and mostly retrospective epidemiologic data suggest a reduction or no change in risk of PD associated with high vitamin E intake. OBJECTIVE: To examine prospectively the associations between intakes of vitamins E and C, carotenoids, vitamin supplements, and risk of PD. METHODS: The authors documented the occurrence of PD within two large cohorts of men and women who completed detailed and validated semiquantitative food frequency questionnaires. A total of 371 incident PD cases were ascertained in the Nurses' Health Study, which comprised 76,890 women who were followed for 14 years, and the Health Professionals Follow-Up Study, which comprised 47,331 men who were followed for 12 years. RESULTS: Neither intake of total vitamins E or C or use of vitamin E or vitamin C supplements or multivitamins was significantly associated with risk of PD. The risk of PD, however, was significantly reduced among men and women with high intake of dietary vitamin E (from foods only). The pooled multivariate relative risk (RR) comparing individuals in the highest quintile with those in the lowest quintile was 0.68 (95% CI, 0.49 to 0.93). Consumption of nuts was also significantly associated with a reduced risk of PD (for >or=5/week vs <1/month, pooled RR, 0.57; 95% CI, 0.34 to 0.95). Intakes of dietary vitamin C and carotenoids were not significantly associated with risk of PD. CONCLUSIONS: Use of vitamin supplements and high intake of carotenoids do not appear to reduce the risk of PD. The reduction in risk of PD associated with high dietary vitamin E intake suggests that other constituents of foods rich in vitamin E may be protective. Alternatively, moderate amounts of vitamin E may reduce risk of PD, but this benefit may be lost with higher intakes.

Alcohol consumption and risk of coronary heart disease among men with type 2 diabetes mellitus.

OBJECTIVES: The goal of this study was to examine the relationship between alcohol intake and risk of coronary heart disease (CHD) among men with type 2 diabetes. BACKGROUND: Type 2 diabetes is associated with an increased risk of CHD. Emerging evidence suggests that moderate alcohol intake is associated with an important reduction in risk of CHD in individuals with type 2 diabetes. METHODS: We studied 2,419 men who reported a diagnosis of diabetes at age 30 or older in the Health Professionals' Follow-up study (HPFS). During 11,411 person-years of follow-up after diagnosis, we documented 150 new cases of CHD (81 nonfatal myocardial infarction [MI] and 69 fatal CHD). Relative risks (RR) were estimated from pooled logistic regression adjusting for potential confounders. RESULTS: Alcohol use was inversely associated with risk of CHD in men with type 2 diabetes. The age-adjusted RRs corresponding to intakes of < or =0.5 drinks/day, 0.5 to 2 drinks/day and >2 drinks/day were 0.76 (95% confidence interval: [CI]: 0.52 to 1.12), 0.64 (95% CI: 0.40 to 1.02) and 0.59 (95% CI: 0.32 to 1.09), respectively, as compared with nondrinkers (p for trend = 0.06). When we controlled for body mass index, smoking, family history of MI, hypertension, hypercholesterolemia, duration of diabetes, physical activity level, vitamin E supplements and intake of trans fat, polyunsaturated fat, fiber and folate, RRs were 0.78 (95% CI: 0.52 to 1.15), 0.62 (95% CI: 0.40 to 1.00) and 0.48 (95% CI: 0.25 to 0.94) (p for trend = 0.03). The benefits of moderate consumption did not statistically differ by beverage type. CONCLUSIONS: Moderate alcohol consumption is associated with lower risk of CHD in men with type 2 diabetes.

Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids: a prospective analysis.

BACKGROUND: Antioxidant vitamins may decrease risk of cancer by limiting oxidative DNA damage leading to cancer initiation. Few prospective studies have assessed relations between antioxidant vitamins and ovarian carcinoma. METHODS: The authors prospectively assessed consumption of vitamins A, C, and E and specific carotenoids, as well as fruit and vegetable intake, in relation to ovarian carcinoma risk among 80,326 participants in the Nurses' Health Study who had no history of cancer other than nonmelanoma skin carcinoma. Women reported on known and suspected ovarian carcinoma risk factors including reproductive factors, smoking, and use of vitamin supplements on biennial mailed questionnaires from 1976 to 1996. Food frequency questionnaires were included in 1980, 1984, 1986, and 1990. The authors confirmed 301 incident cases of invasive epithelial ovarian carcinoma during 16 years of dietary follow-up (1980-1996). Pooled logistic regression was used to control for age, oral contraceptive use, body mass index, smoking history, parity, and tubal ligation. RESULTS: The authors observed no association between ovarian carcinoma risk and antioxidant vitamin consumption from foods, or foods and supplements together. The multivariate relative risks (95% confidence intervals [CIs]) for ovarian carcinoma among women in the highest versus lowest quintile of intake were 1.04 (95% CI, 0.72-1.51) for vitamin A from foods and supplements; 1.01 (95% CI, 0.69-1.47) for vitamin C; 0.88 (95% CI, 0.61-1.27) for vitamin E; and 1.10 (95% CI, 0.76-1.59) for beta-carotene. Among users of vitamin supplements, the authors found no evidence of an association between dose or duration of any specific vitamin and ovarian carcinoma risk, although the authors had limited power to assess these relations. No specific fruits or vegetables were associated significantly with ovarian carcinoma risk. The authors found no association between ovarian carcinoma and consumption of total fruits or vegetables, or specific subgroups including cruciferous vegetables, green leafy vegetables, legumes, or citrus fruits. Women who consumed at least 2.5 total servings of fruits and vegetables as adolescents had a 46% reduction in ovarian carcinoma risk (relative risk, 0.54, 95% CI, 0.29-1.03; P value for trend 0.04). CONCLUSIONS: These data do not support an important relation between consumption of antioxidant vitamins from foods or supplements, or intake of fruits and vegetables, and incidence of ovarian carcinoma in this cohort. However, modest associations cannot be excluded, and the authors' finding of an inverse association for total fruit and vegetable intake during adolescence raises the possibility that the pertinent exposure period may be much earlier than formerly anticipated.

Intakes of carotenoids, vitamin C, and vitamin E and MS risk among two large cohorts of women.

BACKGROUND: Antioxidant nutrients may reduce the risk of MS. In a recent case-control study, vitamin C intake was significantly inversely associated with MS risk among women. However, no prospective data are available. OBJECTIVE: To examine prospectively the associations of intakes of carotenoids, vitamin C, and vitamin E with the risk of MS among women. METHODS: The authors documented the occurrence of definite and probable MS within two large cohorts of women who completed detailed and validated semiquantitative food frequency questionnaires. One cohort (Nurses' Health Study) comprised 81,683 women aged 38 to 63 years in 1984, who were followed for 12 years; the other (Nurses' Health Study II) comprised 95,056 women aged 27 to 44 years in 1991, who were followed for 6 years. RESULTS: The authors documented a total of 214 cases of MS. After adjustments for age, latitude of birthplace, pack-years of smoking, and total energy intake, the pooled multivariate relative risks (95% CIs) comparing women in the highest quintile with those in the lowest quintile were 1.1 (0.7 to 1.7) for alpha-carotene, 1.1 (0.7 to 1.6) for beta-carotene, 1.4 (0.8 to 2.2) for beta-cryptoxanthin, 1.0 (0.6 to 1.5) for lycopene, 1.0 (0.7 to 1.6) for lutein/zeaxanthin, 1.4 (0.9 to 2.1) for total vitamin C, 1.3 (0.9 to 2.0) for dietary vitamin C, 0.8 (0.6 to 1.3) for total vitamin E, and 0.9 (0.6 to 1.4) for dietary vitamin E. The authors found no associations between intakes of fruits and vegetables and risk of MS. Use of vitamin C, vitamin E, and multivitamin supplements was also unrelated to risk of MS. CONCLUSIONS: These findings do not support hypotheses relating higher intakes of dietary carotenoids, vitamin C, and vitamin E to reduced risk of MS in women.

Long-term nutrient intake and early age-related nuclear lens opacities.

OBJECTIVE: To assess the relation between usual nutrient intake and subsequently diagnosed age-related nuclear lens opacities. SUBJECTS: Four hundred seventy-eight nondiabetic women aged 53 to 73 years from the Boston, Mass, area without previously diagnosed cataracts sampled from the Nurses' Health Study cohort. METHODS: Usual nutrient intake was calculated as the average intake from 5 food frequency questionnaires that were collected during a 13- to 15-year period before the evaluation of lens opacities. The duration of vitamin supplement use was determined from 7 questionnaires collected during this same period. We defined nuclear opacities as a nuclear opalescence grade of 2.5 or higher using the Lens Opacification Classification System III. RESULTS: The prevalence of nuclear opacification was significantly lower in the highest nutrient intake quintile category relative to the lowest quintile category for vitamin C (P<.001), vitamin E (P =.02), riboflavin (P =.005), folate (P =.009), beta-carotene (P =.04), and lutein/zeaxanthin (P =.03). After adjustment for other nutrients, only vitamin C intake remained significantly associated (P =.003 for trend) with the prevalence of nuclear opacities. The prevalence of nuclear opacities was significantly lower (P<.001) in the highest vitamin C intake quintile category relative to the lowest quintile category (odds ratio, 0.31; 95% confidence interval, 0.16-0.58). There were also statistically significant trends of decreasing prevalence of nuclear opacities with increasing duration of use of vitamin C (P =.004 for trend), vitamin E (P =.03 for trend), and multivitamin (P =.04 for trend) supplements, but only duration of vitamin C supplement use remained significantly associated with nuclear opacities after mutual adjustment for use of vitamin E (P =.05 for trend) or multivitamin (P =.02 for trend) supplements. The prevalence of nuclear opacities was significantly lower (P =.004) for women who used a vitamin C supplement for 10 or more years relative to women who never used vitamin C supplements (odds ratio, 0.36; 95% confidence interval, 0.18-0.72). Plasma measures of vitamins C and E taken at the eye examination were also inversely associated with the prevalence of nuclear opacities. CONCLUSION: These results provide additional evidence that antioxidant nutrients play a role in the prevention of age-related nuclear lens opacities.

Prospective study of caffeine consumption and risk of Parkinson's disease in men and women.

Results of case-control studies and of a prospective investigation in men suggest that consumption of coffee could protect against the risk of Parkinson's disease, but the active constituent is not clear. To address the hypothesis that caffeine is protective against Parkinson's disease, we examined the relationship of coffee and caffeine consumption to the risk of this disease among participants in two ongoing cohorts, the Health Professionals' Follow-Up Study (HPFS) and the Nurses' Health Study (NHS). The study population comprised 47,351 men and 88,565 women who were free of Parkinson's disease, stroke, or cancer at baseline. A comprehensive life style and dietary questionnaire was completed by the participants at baseline and updated every two to four years. During the follow-up (10 years in men, 16 years in women), we documented a total of 288 incident cases of Parkinson's disease. Among men, after adjustment for age and smoking, the relative risk of Parkinson's disease was 0.42 (95% CI: 0.23-0.78; p for trend < 0.001) for men in the top one-fifth of caffeine intake compared to those in the bottom one-fifth. An inverse association was also observed with consumption of coffee (p for trend = 0.004), caffeine from noncoffee sources (p for trend < 0.001), and tea (p for trend = 0.02) but not decaffeinated coffee. Among women, the relationship between caffeine or coffee intake and risk of Parkinson's disease was U-shaped, with the lowest risk observed at moderate intakes (1-3 cups of coffee/day, or the third quintile of caffeine consumption). These results support a possible protective effect of moderate doses of caffeine on risk of Parkinson's disease.

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.