BACKGROUND:Among individuals with vitamin D deficiency, daily vitamin D supplementation appears to lower risk of acute respiratory infection. However, recent trials, in different populations and using different regimens, have yielded null results. We investigated the effect of daily vitamin D supplementation (vs placebo) on risk of upper respiratory infection (URI) in older adults. METHODS:The VITamin D and OmegA-3 TriaL (VITAL) is a randomized, double-blind, placebo-controlled trial of supplemental vitamin D and/or omega-3 fatty acids in generally healthy men (age ≥50 years) and women (age ≥55 years). This prespecified analysis focuses on vitamin D3 (2000 IU/day) versus placebo in the 15 804 (61%) participants with baseline serum total 25-hydroxyvitamin D level. The primary outcome was self-report of a recent URI at 1-year follow-up. RESULTS:Participants had a mean age of 68 years and 51% were women; 76% were non-Hispanic White, 16% Black, and 8% other race/ethnicity. The mean 25-hydroxyvitamin D level at baseline was 31 (standard deviation, 10) ng/mL, with <12 ng/mL in 2.4%. The overall effect of vitamin D supplementation on recent URI was nonsignificant (odds ratio [OR], 0.96 [95% confidence interval {CI}, .86-1.06]). In the prespecified subgroup of primary interest (<12 ng/mL and denied taking concurrent vitamin D), which had only 255 participants, vitamin D supplementation was nonsignificant (OR, 0.60 [95% CI, .28-1.30]). Statistical power to assess effect modification in other subgroups was limited. CONCLUSIONS:In older adults not selected for vitamin D deficiency, supplemental vitamin D did not lower URI risk overall. Whether effects differ in subgroups requires further study. Clinical Trials Registration. NCT01169259.

Abstract A diet supplemented with vitamin D and marine omega-3 fatty acids may prevent and treat painful disorders by promoting the resolution of inflammation. However, large, randomized placebo-controlled trials evaluating the effects of supplementation with omega-3 fatty acids and vitamin D on the presence and severity of pain are lacking. VITamin D and OmegA-3 triaL—Pain (VITAL-Pain) is an ancillary study to the VITAL trial, a large randomized, double-blind, placebo-controlled trial of vitamin D (2000 IU/day) and omega-3 supplementation (1 g/day) over 5.3 years of median follow-up, among 25,871 older men and women. We assessed pain among those reaching the end of the VITAL intervention phase using questions from the 2012 National Health Interview Survey. We used ordinal logistic regression to test the effect of vitamin D and omega-3 fatty acids on the odds ratio (OR) and 95% confidence interval [CI] of reporting higher pain prevalence or severity. Overall, 19,611 participants provided complete pain information at the end of the VITAL trial. The ORs for higher pain prevalence or severity for vitamin D and omega-3 supplementation vs placebo were 0.99 ([CI] 0.94-1.05) and 0.99 ([CI] 0.94-1.04), respectively. There was no interaction between the 2 active treatments. Dietary supplementation with commonly used moderate doses of vitamin D or omega-3 fatty acids over a median of 5.3 years did not result in a lower prevalence or severity of pain in middle-aged and older U.S. adults.

IMPORTANCE Results of several small randomized clinical trials have suggested that supplements of marine omega-3 fatty acids may be beneficial in treating signs and symptoms of dry eye disease (DED). However, randomized clinical trial data to examine whether omega-3 fatty acid supplements can prevent DED are lacking. OBJECTIVE To evaluate whether long-term daily supplementation with marine omega-3 fatty acids prevents the development of DED. DESIGN, SETTING, AND PARTICIPANTS This was a prespecified ancillary study of the Vitamin D and Omega-3 Trial (VITAL), a nationwide randomized double-blind placebo-controlled 2 x 2 factorial trial of vitamin D and marine omega-3 fatty acids in the primary prevention of cancer and cardiovascular disease. Participants in this ancillary study were 23 523 US adults (men 50 years and older and women 55 years and older) who at study entry were free of a previous diagnosis of DED and were not experiencing severe dry eye symptoms. Participants were enrolled from November 2011 to March 2014, and treatment and follow-up ended on December 31, 2017. Data were analyzed from January 2020 to August 2021. INTERVENTIONS Marine omega-3 fatty acids, 1 g per day. MAIN OUTCOMES AND MEASURES The primary end point was incident clinically diagnosed DED confirmed by review of the medical records. The secondary end point was a composite of all confirmed incident clinically diagnosed DED cases plus all incident reports of severe DED symptoms. RESULTS The mean (SD) age of the 23 523 participants included in the analysis was 67.0 (7.0) years, and 5678 participants (48.3%) were women. The cohort included 4610 participants (20.0%) who self-identified as Black, 16 481(71.6%) who self-identified as non-Hispanic White, and 1927 (8.4%) of other racial or ethnic groups or who declined to respond, consolidated owing to small numbers, including American Indian or Alaska Native, Asian, Hispanic or Latino, and Native Hawaiian or Other Pacific Islander. During a median (range) 5.3 (3.8-6.1) years of treatment and follow-up, 472 of 23 523 participants (2.0%) experienced a medical record-confirmed diagnosis of DED. There was no difference in diagnosed DED by randomized omega-3 fatty acid assignment (232 of 11757 participants [2.0%) with end points in the treated group vs 240 of 11766 [2.0%) with end points in the placebo group; hazard ratio, 0.97; 95% CI, 0.81-1.16). Similarly, there was no difference between groups for the secondary end point of diagnosed DED plus incident severe DED symptoms (1044 participants [8.9%] with end points in the treated group vs 1074 [9.1%] with end points in the placebo group; hazard ratio, 0.97; 95% CI, 0.89-1.06). CONCLUSIONS AND RELEVANCE In this randomized clinical trial, long-term supplementation with 1g per day of marine co-3 fatty acids for a median (range) of 5.3 (3.8-6.1) years did not reduce the incidence of diagnosed DED or a combined end point of diagnosed DED or incident severe DED symptoms. These results do not support recommending marine co-3 fatty acid supplementation to reduce the incidence of DED.

Key Points Question Does supplementation with vitamin D3 and/or omega-3 fatty acids reduce the risk of frailty? Findings In this ancillary study of a randomized clinical trial including 25 871 individuals aged 50 years or older, neither vitamin D3, 2000 IU/d, nor omega-3 fatty acid, 1 g/d, supplementation, compared with placebo, significantly affected change in frailty score during 5 years of treatment. Results were unchanged using the frailty physical phenotype. Meaning The results of this ancillary study do not support the routine use of vitamin D3 or omega-3 fatty acid supplementation in community-dwelling older adults for the prevention of frailty.

PurposeThis paper describes the Women’s Health Accelerometry Collaboration, a consortium of two prospective cohort studies of women age 62 years or older, harmonised to explore the association of accelerometer-assessed physical activity and sedentary behaviour with cancer incidence and mortality.ParticipantsA total of 23 443 women (age mean 73.4, SD 6.8) living in the USA and participating in an observational study were included; 17 061 from the Women’s Health Study (WHS) and 6382 from the Women’s Health Initiative Objective Physical Activity and Cardiovascular Health (WHI/OPACH) Study.Findings to dateAccelerometry, cancer outcomes and covariate harmonisation was conducted to align the two cohort studies. Physical activity and sedentary behaviour were measured using similar procedures with an ActiGraph GT3X+ accelerometer, worn at the hip for 1 week, during 2011–2014 for WHS and 2012–2014 for WHI/OPACH. Cancer outcomes were ascertained via ongoing surveillance using physician adjudicated cancer diagnosis. Relevant covariates were measured using questionnaire or physical assessments. Among 23 443 women who wore the accelerometer for at least 10 hours on a single day, 22 868 women wore the accelerometer at least 10 hours/day on ≥4 of 7 days. The analytical sample (n=22 852) averaged 4976 (SD 2669) steps/day and engaged in an average of 80.8 (SD 46.5) min/day of moderate-to-vigorous, 105.5 (SD 33.3) min/day of light high and 182.1 (SD 46.1) min/day of light low physical activity. A mean of 8.7 (SD 1.7) hours/day were spent in sedentary behaviour. Overall, 11.8% of the cohort had a cancer diagnosis (other than non-melanoma skin cancer) at the time of accelerometry measurement. During an average of 5.9 (SD 1.6) years of follow-up, 1378 cancer events among which 414 were fatal have occurred.Future plansUsing the harmonised cohort, we will access ongoing cancer surveillance to quantify the associations of physical activity and sedentary behaviour with cancer incidence and mortality.

IMPORTANCE:Marine ω-3 fatty acid has been suggested to protect against colorectal cancer.OBJECTIVE:To assess the effect of daily marine ω-3 fatty acid supplementation on the risk of colorectal cancer precursors, including conventional adenomas and serrated polyps.DESIGN, SETTING, AND PARTICIPANTS:This study was a prespecified ancillary study of the placebo-controlled randomized clinical trial VITAL (Vitamin D and Omega-3 Trial). An intention-to-treat analysis was used to examine the effect of daily marine ω-3 supplements among 25 871 adults in the US general population (including 5106 African American persons) free of cancer and cardiovascular disease at enrollment. Randomization was from November 2011 to March 2014, and intervention ended as planned on December 31, 2017.INTERVENTIONS:Marine ω-3 fatty acid, 1 g daily (which included eicosapentaenoic acid, 460 mg, and docosahexaenoic acid, 380 mg) and vitamin D3 (2000 IU daily) supplements.MAIN OUTCOMES AND MEASURES:Risk of conventional adenomas (including tubular adenoma, tubulovillous adenoma, villous adenoma, and adenoma with high-grade dysplasia) or serrated polyps (including hyperplastic polyp, traditional serrated adenoma, and sessile serrated polyp). In a subset of participants who reported receiving a diagnosis of polyp on follow-up questionnaires, endoscopic and pathologic records were obtained to confirm the diagnosis. Odds ratios (ORs) and 95% CIs were calculated using logistic regression, after adjusting for age, sex, vitamin D treatment assignment, and use of endoscopy. Secondary analyses were performed according to polyp features and participants' characteristics.RESULTS:The demographic characteristics of participants at randomization were well balanced between the treatment and placebo groups; for example, 50.6% vs 50.5% were women, and 19.7% vs 19.8% were African American persons were included in each group. The mean (SD) age was 67.1 (7.1) years in the placebo group and 67.2 (7.1) in the ω-3 treatment group. During a median follow-up of 5.3 years (range, 3.8-6.1 years), 294 cases of conventional adenomas were documented in the ω-3 group and 301 in the control group (multivariable OR, 0.98; 95% CI, 0.83-1.15) (1:1 ratio between number of cases and number of participants). In addition, 174 cases of serrated polyps were documented in the ω-3 group and 167 in the control group (OR, 1.05; 95% CI, 0.84-1.29). Null associations were found for polyp subgroups according to size, location, multiplicity, or histology. In secondary analyses, marine ω-3 treatment appeared to be associated with lower risk of conventional adenomas among individuals with low plasma levels of ω-3 index at baseline (OR, 0.76; 95% CI, 0.57-1.02; P = .03 for interaction by ω-3 index). A beneficial association of supplementation was also noted in the African American population (OR, 0.59; 95% CI, 0.35-1.00) but not in other racial/ethnic groups (P = .11 for interaction).CONCLUSIONS AND RELEVANCE:Supplementation with marine ω-3 fatty acids, 1 g per day, was not associated with reduced risk of colorectal cancer precursors. A potential benefit of this supplementation for individuals with low baseline ω-3 levels or for African American persons requires further confirmation.TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT01169259.

BACKGROUND & AIMS: The effects of vitamin D on risk of colorectal cancer precursors are not clear. We examined the influence of vitamin D supplementation on risk of colorectal adenomas and serrated polyps in a prespecified ancillary study of a large-scale prevention trial (the vitamin D and omegA-3 trial, VITAL) of individuals who were free of cancer and cardiovascular disease at enrollment. METHODS: In VITAL trial, 25,871 adults with no history of cancer or cardiovascular disease (12,786 men 50 years or older and 13,085 women 55 years or older) were randomly assigned to groups given daily dietary supplements (2000 IU vitamin D-3 and 1 g marine n-3 fatty acid) or placebo. Patients were assigned to groups from November 2011 through March 2014 and the study ended on December 31, 2017. We confirmed conventional adenomas and serrated polyps by reviewing histopathology reports from participants who had reported a diagnosis of polyps and were asked by their doctors to return for a repeat colonoscopy or sigmoidoscopy in 5 years or less. We calculated the odds ratios (ORs) and 95% CIs by logistic regression, after adjusting for age, sex, n-3 treatment assignment, and history of endoscopy at time of randomization. RESULTS: During a median follow-up of 5.3 years, we documented 308 cases of conventional adenomas in 12,927 participants in the vitamin D group and 287 cases in 12,944 participants in the placebo group (OR for the association of vitamin D supplementation with adenoma, 1.08; 95% CI, 0.92-1.27). There were 172 cases of serrated polyps in the vitamin D group and 169 cases in the placebo group (OR for the association of vitamin D supplementation with serrated polyp, 1.02; 95% CI, 0.82-1.26). Supplementation was not associated with polyp size, location, multiplicity, or histologic features. We found evidence for an interaction between vitamin D supplementation and serum level of 25-hydroxyvitamin D, measured in 15,787 participants at randomization. Among individuals with serum levels of 25-hydroxyvitamin D below 30 ng/mL, the OR associated with supplementation for conventional adenoma was 0.82 (95% CI, 0.60-1.13), whereas among individuals with serum levels of 25-hydroxyvitamin D above 30 ng/mL, the OR for conventional adenoma was 1.20 (95% CI, 0.92-1.55) (P for interaction = .07). There was a significant interaction between vitamin D supplementation and serum level of 25-hydroxyvitamin D in their association with advanced adenoma (P for interaction = .04). CONCLUSIONS: Based on an ancillary study of data from the VITAL trial, daily vitamin D supplementation (2000 IU) was not associated with risk of colorectal cancer precursors in average-risk adults not selected for vitamin D insufficiency. A potential benefit for individuals with low baseline level of vitamin D requires further investigation.

Introduction: Increased psychosocial stress and obesity are both associated with elevated risk of cardiovascular disease (CVD). However, the effect of change in cumulative psychosocial stressors (s...

BACKGROUND Marine omega-3 fatty acid (MO3FA) has been suggested to protect against colorectal cancer. However, the chemopreventive effect of MO3FA on precursors of colorectal cancer remains unclear. METHODS We assessed the effect of MO3FA supplementation on risk of conventional adenomas and serrated polyps, the two distinct subtypes of precursors of colorectal cancer, within the VITamin D and OmegA-3 TriaL (VITAL), a randomized, placebo-controlled, two-by-two factorial trial of MO3FA (1 g per day [460 mg EPA and 380 mg DHA]) and vitamin D3 (2000 IU per day) supplements among 25,871 Americans aged 50 years or older (including 5,106 blacks). Although regular screening endoscopy was not protocol-mandated during the study period, prior colonoscopy/sigmoidoscopy and other risk factors were well balanced by treatment group at baseline. When participants reported a diagnosis of polyp on the annual follow-up questionnaire, we requested permission to obtain endoscopic and pathologic records to confirm the diagnosis and extract the histopathologic information. Serrated polyps included hyperplastic polyps and mixed/serrated adenomas (traditional and sessile types). We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) in relation to MO3FA treatment using logistic regression, after adjusting for age, sex, vitamin D treatment assignment, and use of endoscopy. We also performed subgroup analyses according to polyp features and participants’ characteristics. RESULTS During a median follow-up of 5.3 years, we documented 296 cases of colorectal adenomas in the intervention group and 306 in the control groups (multivariable OR=0.97, 95% CI, 0.83-1.14); and 178 and 170 cases of serrated polyps in the two groups, respectively (OR=1.05, 95% CI, 0.85-1.30). Similar null association was found for advanced adenomas (advanced histology or ≥10 mm) or high-risk serrated polyps (located in the proximal colon or ≥10 mm), or polyp subgroups according to size, location, multiplicity, or histology. When stratified by race/ethnicity, we found that MO3FA treatment was associated with lower risk of adenomas (OR=0.53, 95% CI, 0.31-0.91) and serrated polyps (OR=0.54, 95% CI, 0.27-1.10) in African Americans, whereas no association was found in non-Hispanic whites or other racial/ethnic groups (P for interaction=0.06 for adenomas and 0.15 for serrated polyps). No interaction was detected with other demographic factors, colorectal cancer risk factors, endoscopic use, baseline fish intake, or plasma MO3FA levels. CONCLUSIONS Supplementation with marine omega-3 fatty acids at a dose of 1 g per day was not associated with risk of colorectal premalignant lesions. A potential benefit among African Americans requires further confirmation. Citation Format: Mingyang Song, I-Min Lee, JoAnn E. Manson, Julie E. Buring, Rimma Dushkes, David Gordon, Joseph Walter, Kana Wu, Andrew T. Chan, Shuji Ogino, Charles S. Fuchs, Jeffrey A. Meyerhardt, Edward L. Giovannucci. Marine omega-3 fatty acid supplementation and risk of colorectal adenomas and serrated polyps: A randomized placebo-controlled trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-249.

Objective To evaluate the association between migraine and incident cardiovascular disease and cardiovascular mortality in women. Design Prospective cohort study among Nurses’ Health Study II participants, with follow-up from 1989 and through June 2011. Setting Cohort of female nurses in United States. Participants 115 541 women aged 25-42 years at baseline and free of angina and cardiovascular disease. Cumulative follow-up rates were more than 90%. Main outcome measures The primary outcome of the study was major cardiovascular disease, a combined endpoint of myocardial infarction, stroke, or fatal cardiovascular disease. Secondary outcome measures included individual endpoints of myocardial infarction, stroke, angina/coronary revascularization procedures, and cardiovascular mortality. Results 17 531 (15.2%) women reported a physician’s diagnosis of migraine. Over 20 years of follow-up, 1329 major cardiovascular disease events occurred and 223 women died from cardiovascular disease. After adjustment for potential confounding factors, migraine was associated with an increased risk for major cardiovascular disease (hazard ratio 1.50, 95% confidence interval 1.33 to 1.69), myocardial infarction (1.39, 1.18 to 1.64), stroke (1.62, 1.37 to 1.92), and angina/coronary revascularization procedures (1.73, 1.29 to 2.32), compared with women without migraine. Furthermore, migraine was associated with a significantly increased risk for cardiovascular disease mortality (hazard ratio 1.37, 1.02 to 1.83). Associations were similar across subgroups of women, including by age (<50/≥50), smoking status (current/past/never), hypertension (yes/no), postmenopausal hormone therapy (current/not current), and oral contraceptive use (current/not current). Conclusions Results of this large, prospective cohort study in women with more than 20 years of follow-up indicate a consistent link between migraine and cardiovascular disease events, including cardiovascular mortality. Women with migraine should be evaluated for their vascular risk. Future targeted research is warranted to identify preventive strategies to reduce the risk of future cardiovascular disease among patients with migraine.

Background: Although psychosocial stressors such as negative life events predict adverse physical and mental health outcomes, significant gaps remain in the literature regarding whether such associations appear with cardiovascular disease (CVD) in middle-aged and older women, a demographic at higher risk for CVD than younger women. Hence, we investigated the relationship of cumulative negative life events and risk of myocardial infarction in the Women’s Health Study (WHS). Methods and Results: We performed a prospective, nested case-control study of apparently healthy post-menopausal women participating in the ongoing follow-up cohort of the Women’s Health Study; 26,763 women were followed for an average of 9 years to ascertain MI risk. Participants answered 12 standardized questions about negative life events within 5 years of survey completion (e.g. death/illness/accidental injury of someone close, fired from job, legal trouble, unemployment, marital infidelity, serious financial problems), and 3 questions about lifetime traumatic events (life-threatening illness, accident involving child or spouse, or victim of serious assault). Our cumulative life events score (CLES) was the count of items endorsed on all 15 questions, whereas our traumatic life events score counted positive responses to the 3 traumatic event questions. Women with a CLES score of zero were compared to women with scores >0 who were divided into tertiles; thus defining 4 categories. Among 267 women with a history of MI and 281 age and smoking matched controls, the median age of participants was 56.0 years old (Interquartile range: 51.3 - 60.6). Logistic regression analyses revealed that while increasing CLES was associated with increasing MI risk [Odds Ratio: OR unadjusted model: 1.00, 1.21, 1.52, 1.87; p-trend 0.16], the trend did not reach statistical significance. In models adjusted for CVD risk factors, there was a significant interaction with household income: CLES was associated with MI only in women with household income < $50,000 yearly (OR = 1.24, 95% CI: 1.05-1.49. The odds of MI was significantly higher in women who reported traumatic life events compared to women who did not (ORtraumatic life event score =1.65: 95% CI: 1.02, 2.68); women with traumatic life event(s) had a 65% increase in odds of MI when compared to women without, after adjusting for CVD risk factors and socio-economic status. In question specific analyses, women reporting serious financial problems as a life event had significantly higher odds of MI than women who did not (OR=2.60, 95% CI: 1.20 - 5.64). Conclusion: In this analysis among middle aged and older women, we found supportive evidence that negative cumulative life events were associated with MI risk, especially in low-income women and those suffering major traumatic life events. Further research is warranted particularly in women who also have limited socioeconomic resources.

Background: Discrimination, a form of chronic psychological stress, is related to certain chronic health conditions such as poor physical health and hypertension. However, little is known about the associations of everyday discrimination with risk of myocardial infarction. Methods and Results: We assessed the association between everyday discrimination (discrimination) and myocardial infarction (MI) using a prospective, nested case control study of 548 women (267 cases, 281 controls), selected from 26,763 women without a history of cardiovascular disease at baseline who participated in the Women’s Heath Study (WHS). Among 267 MI cases, there was a mean follow-up of 8.8 + 4.1 years from date of WHS randomization to date of MI event. At baseline, the mean age of participants was 53.6 + 6.1 years. Cases and controls were matched for age and smoking history. Discrimination was assessed by 5 questions where women reported whether they were: 1) treated with less courtesy/respect than others; 2) treated as not being smart; 3) treated as if others were afraid of them; 4) received poorer service at restaurants/stores; or 5) felt threatened/harassed. Responses were based on a Likert scale of 1=never to 5=at least once/weekly with higher scores indicating more experiences with discrimination. In unadjusted logistic regression models of increasing tertiles of discrimination, we found no significant association between discrimination and odds of MI [Odds Ratios (OR) and 95% confidence intervals (95%CI): 1.00, 1.28 (0.85-1.94), 1.06 (0.69-1.64); p trend =0.5]. Adjustment for cardiovascular disease risk factors (lipid parameters, hsCRP, family history of MI, hypertension, body mass index, diabetes, and alcohol consumption) revealed an inverse-U-shaped relationship [OR, 95%CI: 1.00, 2.14 (1.21-3.77), 1.55 (0.87-2.78); p trend = 0.03], suggesting that these factors obscured the association in unadjusted models. Notably, addition of education and income to the crude model alone [1.00, 1.38 (0.89, 2.15), 0.97 (0.61, 1.54) p trend = 0.2] or to the model with the cardiovascular risk factors [1.00, 2.27 (1.25-4.10), 1.36 (0.73, 2.53); p trend = 0.02] had minimal impact on odds of MI in these women. Conclusion: Among women participating in the WHS follow-up cohort, higher levels of everyday discrimination were related to increased odds of myocardial infarction in an inverse-U-shaped manner, a finding that is obscured by traditional cardiovascular disease risk factors. Access to measures associated with a healthy heart might be important to myocardial infarction risk attenuation among women reporting everyday discrimination. Further research is warranted to elucidate the relationship between everyday discrimination and increased risk of MI.

Background and purposeTelomere shortening has been implicated in neurodegenerative disorders. However, available data on the association between telomere length and Parkinson's disease (PD) are inconclusive.MethodsA nested case-control design was used amongst men participating in the prospective Physicians' Health Study. A large proportion of participants provided blood samples in 1997 and they were followed through 2010. Men with self-reported PD were age-matched to controls in a 1:2 ratio. Quantitative PCR was used to determine the telomere repeat copy number to single gene copy number ratio (TSR) in genomic DNA extracted from peripheral blood leukocytes. TSR was used as a measure for relative telomere length (RTL) in our analyses. Conditional logistic regression was used to determine the risk of PD associated with RTL.ResultsData on RTL were available from 408 cases and 809 controls. Median TSR was shorter in controls than in cases (47.7 vs. 50.2; P=0.02). The age-adjusted odds ratio (OR) for PD was 0.66 [95% confidence interval (CI) 0.46-0.95; P-trend over quartiles0.02] comparing the lowest to the highest quartile. The pattern of association was unchanged when comparing RTL below versus above the median (age-adjusted OR0.75; 95% CI 0.59-0.96). Associations were similar after additional adjustment for many covariates.ConclusionContrary to what was expected, in this large nested case-control study amongst men shorter telomeres were associated with reduced PD risk. Future research on the nature of this counterintuitive association is warranted.

Background and purposeTelomere shortening has been implicated in cardiovascular disease (CVD). However, prospective data on the association between relative telomere length (RTL) and ischaemic stroke are scarce and inconclusive.MethodsWe used a nested case–control design among women participating in the prospective Nurses' Health Study. Participants provided blood samples in 1990 and were followed till 2006. Women with confirmed incident ischaemic stroke were matched to controls by age, smoking, postmenopausal status and postmenopausal hormone use. Quantitative polymerase chain reaction was used to determine RTL in genomic DNA extracted from peripheral blood leukocytes. Conditional logistic regression was used to determine the risk of ischaemic stroke associated with RTL, using RTL quartiles and as dichotomous according to the median.ResultsData on RTL were available from 504 case–control pairs. Results did not suggest an association between RTL and ischaemic stroke. The odds ratio (OR) for ischaemic stroke was 0.82 [95% confidence interval (CI) 0.52–1.32] comparing lowest with the highest RTL quartile and 0.90 (95% CI 0.65–1.24) comparing RTL below the median with RTL above the median. Associations were unchanged after additional adjustment for cardiovascular risk factors. Further analyses suggested an association between RTL and fatal ischaemic stroke (54 case–control pairs; lowest versus highest quartile OR = 1.99, 95%CI 0.26–14.9); however, results were statistically insignificant.ConclusionIn this large nested case–control study among women RTL was not associated with ischaemic stroke. In light of the varying study results in the literature on the association between telomere length and stroke, additional research is warranted.

The risk for Alzheimer disease and other forms of dementia increases with age, and there is great interest in finding ways to prevent these devastating conditions. Some studies have suggested that the overall diet or specific nutrients in the diet might play a role in preserving cognitive performance with age. However, others have not shown such an effect. Currently, many people take a daily multivitamin in the hope that this may prevent dementia.

BACKGROUND:Despite widespread use of multivitamin supplements, their effect on cognitive health-a critical issue with aging-remains inconclusive. To date, no long-term clinical trials have studied multivitamin use and cognitive decline in older persons.OBJECTIVE:To evaluate whether long-term multivitamin supplementation affects cognitive health in later life.DESIGN:Randomized, double-blind, placebo-controlled trial of a multivitamin from 1997 to 1 June 2011. The cognitive function substudy began in 1998. Up to 4 repeated cognitive assessments by telephone interview were completed over 12 years. (ClinicalTrials.gov: NCT00270647) SETTING: The Physicians' Health Study II.PATIENTS:5947 male physicians aged 65 years or older.INTERVENTION:Daily multivitamin or placebo.MEASUREMENTS:A global composite score averaging 5 tests of global cognition, verbal memory, and category fluency. The secondary end point was a verbal memory score combining 4 tests of verbal memory, which is a strong predictor of Alzheimer disease.RESULTS:No difference was found in mean cognitive change over time between the multivitamin and placebo groups or in the mean level of cognition at any of the 4 assessments. Specifically, for the global composite score, the mean difference in cognitive change over follow-up was -0.01 SU (95% CI, -0.04 to 0.02 SU) when treatment was compared with placebo. Similarly, cognitive performance did not differ between the multivitamin and placebo groups on the secondary outcome, verbal memory (mean difference in cognitive change over follow-up, -0.005 SU [CI, -0.04 to 0.03 SU]).LIMITATION:Doses of vitamins may be too low or the population may be too well-nourished to benefit from a multivitamin.CONCLUSION:In male physicians aged 65 years or older, long-term use of a daily multivitamin did not provide cognitive benefits.PRIMARY FUNDING SOURCE:National Institutes of Health, BASF, Pfizer, and DSM Nutritional Products.