Fish Rich in Omega-3s Associated with Moderate Reduction in Cerebrovascular Events

Objective:

To clarify associations of fish consumption and long chain omega 3 fatty acids with risk of cerebrovascular disease for primary and secondary prevention.

Design:

Systematic review and meta-analysis.

Data sources:

Studies published before September 2012 identified through electronic searches using Medline, Embase, BIOSIS, and Science Citation Index databases.

Eligibility criteria:

Prospective cohort studies and randomised controlled trials reporting on associations of fish consumption and long chain omega 3 fatty acids (based on dietary self report), omega 3 fatty acids biomarkers, or supplementations with cerebrovascular disease (defined as any fatal or non-fatal ischaemic stroke, haemorrhagic stroke, cerebrovascular accident, or transient ischaemic attack). Both primary and secondary prevention studies (comprising participants with or without cardiovascular disease at baseline) were eligible.

Results:

26 prospective cohort studies and 12 randomised controlled trials with aggregate data on 794 000 non-overlapping people and 34 817 cerebrovascular outcomes were included. In cohort studies comparing categories of fish intake the pooled relative risk for cerebrovascular disease for 2-4 servings a week versus ≤1 servings a week was 0.94 (95% confidence intervals 0.90 to 0.98) and for ≥5 servings a week versus 1 serving a week was 0.88 (0.81 to 0.96). The relative risk for cerebrovascular disease comparing the top thirds of baseline long chain omega 3 fatty acids with the bottom thirds for circulating biomarkers was 1.04 (0.90 to 1.20) and for dietary exposures was 0.90 (0.80 to 1.01). In the randomised controlled trials the relative risk for cerebrovascular disease in the long chain omega 3 supplement compared with the control group in primary prevention trials was 0.98 (0.89 to 1.08) and in secondary prevention trials was 1.17 (0.99 to 1.38). For fish or omega 3 fatty acids the estimates for ischaemic and haemorrhagic cerebrovascular events were broadly similar. Evidence was lacking of heterogeneity and publication bias across studies or within subgroups.

Conclusions:

Available observational data indicate moderate, inverse associations of fish consumption and long chain omega 3 fatty acids with cerebrovascular risk. Long chain omega 3 fatty acids measured as circulating biomarkers in observational studies or supplements in primary and secondary prevention trials were not associated with cerebrovascular disease. The beneficial effect of fish intake on cerebrovascular risk is likely to be mediated through the interplay of a wide range of nutrients abundant in fish.

BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e6698

Smoking Shaves 11 Years Off Women's Lives

Background:

Women born around 1940 in countries such as the UK and USA were the first generation in which many smoked substantial numbers of cigarettes throughout adult life. Hence, only in the 21st century can we observe directly the full effects of prolonged smoking, and of prolonged cessation, on mortality among women in the UK.

Methods:

For this prospective study, 1·3 million UK women were recruited in 1996—2001 and resurveyed postally about 3 and 8 years later. All were followed to Jan 1, 2011, through national mortality records (mean 12 woman-years, SD 2). Participants were asked at entry whether they were current or ex-smokers, and how many cigarettes they currently smoked. Those who were ex-smokers at both entry and the 3-year resurvey and had stopped before the age of 55 years were categorised by the age they had stopped smoking. We used Cox regression models to obtain adjusted relative risks that compared categories of smokers or ex-smokers with otherwise similar never-smokers.

Findings:

After excluding 0·1 million women with previous disease, 1·2 million women remained, with median birth year 1943 (IQR 1938—46) and age 55 years (IQR 52—60). Overall, 6% (66 489/1 180 652) died, at mean age 65 years (SD 6). At baseline, 20% (232 461) were current smokers, 28% (328 417) were ex-smokers, and 52% (619 774) were never-smokers. For 12-year mortality, those smoking at baseline had a mortality rate ratio of 2·76 (95% CI 2·71—2·81) compared with never-smokers, even though 44% (37 240/85 256) of the baseline smokers who responded to the 8-year resurvey had by then stopped smoking. Mortality was tripled, largely irrespective of age, in those still smoking at the 3-year resurvey (rate ratio 2·97, 2·88—3·07). Even for women smoking fewer than ten cigarettes per day at baseline, 12-year mortality was doubled (rate ratio 1·98, 1·91—2·04). Of the 30 most common causes of death, 23 were increased significantly in smokers; for lung cancer, the rate ratio was 21·4 (19·7—23·2). The excess mortality among smokers (in comparison with never-smokers) was mainly from diseases that, like lung cancer, can be caused by smoking. Among ex-smokers who had stopped permanently at ages 25—34 years or at ages 35—44 years, the respective relative risks were 1·05 (95% CI 1·00—1·11) and 1·20 (1·14—1·26) for all-cause mortality and 1·84 (1·45—2·34) and 3·34 (2·76—4·03) for lung cancer mortality. Thus, although some excess mortality remains among these long-term ex-smokers, it is only 3% and 10% of the excess mortality among continuing smokers. If combined with 2010 UK national death rates, tripled mortality rates among smokers indicate 53% of smokers and 22% of never-smokers dying before age 80 years, and an 11-year lifespan difference.

Interpretation:

Among UK women, two-thirds of all deaths of smokers in their 50s, 60s, and 70s are caused by smoking; smokers lose at least 10 years of lifespan. Although the hazards of smoking until age 40 years and then stopping are substantial, the hazards of continuing are ten times greater. Stopping before age 40 years (and preferably well before age 40 years) avoids more than 90% of the excess mortality caused by continuing smoking; stopping before age 30 years avoids more than 97% of it.

Funding by Cancer Research UK, Medical Research Council.

Smoking Cuts Life Span by About a Decade

Objective:

To investigate the impact of smoking on overall mortality and life expectancy in a large Japanese population, including some who smoked throughout adult life.

Design:

The Life Span Study, a population-based prospective study, initiated in 1950.

Setting Hiroshima and Nagasaki, Japan.

Participants:

Smoking status for 27 311 men and 40 662 women was obtained during 1963-92. Mortality from one year after first ascertainment of smoking status until 1 January 2008 has been analysed.

Main outcome measures:

Mortality from all causes in current, former, and never smokers.

Results:

Smokers born in later decades tended to smoke more cigarettes per day than those born earlier, and to have started smoking at a younger age. Among those born during 1920-45 (median 1933) and who started smoking before age 20 years, men smoked on average 23 cigarettes/day, while women smoked 17 cigarettes/day, and, for those who continued smoking, overall mortality was more than doubled in both sexes (rate ratios versus never smokers: men 2.21 (95% confidence interval 1.97 to 2.48), women 2.61 (1.98 to 3.44)) and life expectancy was reduced by almost a decade (8 years for men, 10 years for women). Those who stopped smoking before age 35 avoided almost all of the excess risk among continuing smokers, while those who stopped smoking before age 45 avoided most of it.

Conclusions:

The lower smoking related hazards reported previously in Japan may have been due to earlier birth cohorts starting to smoke when older and smoking fewer cigarettes per day. In Japan, as elsewhere, those who start smoking in early adult life and continue smoking lose on average about a decade of life. Much of the risk can, however, be avoided by giving up smoking before age 35, and preferably well before age 35.

BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e7093

Legumes Associated with Better Glycemic Control in Type 2 Diabetes

Background:

Legumes, including beans, chickpeas, and lentils, are among the lowest glycemic index (GI) foods and have been recommended in national diabetes mellitus (DM) guidelines. Yet, to our knowledge, they have never been used specifically to lower the GI of the diet. We have therefore undertaken a study of low-GI foods in type 2 DM with a focus on legumes in the intervention.

Methods:

A total of 121 participants with type 2 DM were randomized to either a low-GI legume diet that encouraged participants to increase legume intake by at least 1 cup per day, or to increase insoluble fiber by consumption of whole wheat products, for 3 months. The primary outcome was change in hemoglobin A1c (HbA1c) values with calculated coronary heart disease (CHD) risk score as a secondary outcome.

Results:

The low-GI legume diet reduced HbA1c values by −0.5% (95% CI, −0.6% to −0.4%) and the high wheat fiber diet reduced HbA1c values by −0.3% (95% CI, −0.4% to −0.2%). The relative reduction in HbA1c values after the low-GI legume diet was greater than after the high wheat fiber diet by −0.2% (95% CI, −0.3% to −0.1%; P < .001). The respective CHD risk reduction on the low-GI legume diet was −0.8% (95% CI, −1.4% to −0.3%; P = .003), largely owing to a greater relative reduction in systolic blood pressure on the low-GI legume diet compared with the high wheat fiber diet (−4.5 mm Hg; 95% CI, −7.0 to −2.1 mm Hg; P < .001).

Conclusion:

Incorporation of legumes as part of a low-GI diet improved both glycemic control and reduced calculated CHD risk score in type 2 DM.

Arch Intern Med. 2012;():1-8. doi:10.1001/2013.jamainternmed.70.

Multivitamins May Confer a Small, but Significant, Cancer Risk Reduction in Men

Context:

Multivitamin preparations are the most common dietary supplement, taken by at least one-third of all US adults. Observational studies have not provided evidence regarding associations of multivitamin use with total and site-specific cancer incidence or mortality.

Objective:

To determine whether long-term multivitamin supplementation decreases the risk of total and site-specific cancer events among men.

Design, Setting, and Participants:

A large-scale, randomized, double-blind, placebo-controlled trial (Physicians' Health Study II) of 14 641 male US physicians initially aged 50 years or older (mean [SD] age, 64.3 [9.2] years), including 1312 men with a history of cancer at randomization, enrolled in a common multivitamin study that began in 1997 with treatment and follow-up through June 1, 2011.

Intervention:

Daily multivitamin or placebo.

Main Outcome Measures:

Total cancer (excluding nonmelanoma skin cancer), with prostate, colorectal, and other site-specific cancers among the secondary end points.

Results:

During a median (interquartile range) follow-up of 11.2 (10.7-13.3) years, there were 2669 men with confirmed cancer, including 1373 cases of prostate cancer and 210 cases of colorectal cancer. Compared with placebo, men taking a daily multivitamin had a statistically significant reduction in the incidence of total cancer (multivitamin and placebo groups, 17.0 and 18.3 events, respectively, per 1000 person-years; hazard ratio [HR], 0.92; 95% CI, 0.86-0.998; P = .04). There was no significant effect of a daily multivitamin on prostate cancer (multivitamin and placebo groups, 9.1 and 9.2 events, respectively, per 1000 person-years; HR, 0.98; 95% CI, 0.88-1.09; P = .76), colorectal cancer (multivitamin and placebo groups, 1.2 and 1.4 events, respectively, per 1000 person-years; HR, 0.89; 95% CI, 0.68-1.17; P = .39), or other site-specific cancers. There was no significant difference in the risk of cancer mortality (multivitamin and placebo groups, 4.9 and 5.6 events, respectively, per 1000 person-years; HR, 0.88; 95% CI, 0.77-1.01; P = .07). Daily multivitamin use was associated with a reduction in total cancer among 1312 men with a baseline history of cancer (HR, 0.73; 95% CI, 0.56-0.96; P = .02), but this did not differ significantly from that among 13 329 men initially without cancer (HR, 0.94; 95% CI, 0.87-1.02; P = .15; P for interaction = .07).

Conclusion:

In this large prevention trial of male physicians, daily multivitamin supplementation modestly but significantly reduced the risk of total cancer.

JAMA. 2012;():1-10. doi:10.1001/jama.2012.14641

High-Dose Multivitamins Not Helpful, Possibly Harmful in Patients on Antiretroviral Therapy

Context:

Large randomized trials have previously shown that high-dose micronutrient supplementation can increase CD4 counts and reduce human immunodeficiency virus (HIV) disease progression and mortality among individuals not receiving highly active antiretroviral therapy (HAART); however, the safety and efficacy of such supplementation has not been established in the context of HAART.

Objective:

To test the hypothesis that high-dose multivitamin supplementation vs standard-dose multivitamin supplementation decreases the risk of HIV disease progression or death and improves immunological, virological, and nutritional parameters in patients with HIV initiating HAART.

Design, Setting, and Participants:

A randomized, double-blind, controlled trial of high-dose vs standard-dose multivitamin supplementation for 24 months in 3418 patients with HIV initiating HAART between November 2006 and November 2008 in 7 clinics in Dar es Salaam, Tanzania.

Intervention:

The provision of daily oral supplements of vitamin B complex, vitamin C, and vitamin E at high levels or standard levels of the recommended dietary allowance.

Main Outcome Measure:

The composite of HIV disease progression or death from any cause.

Results:

The study was stopped early in March 2009 because of evidence of increased levels of alanine transaminase (ALT) in patients receiving the high-dose multivitamin supplement. At the time of stopping, 3418 patients were enrolled (median follow-up, 15 months), and there were 2374 HIV disease progression events and 453 observed deaths (2460 total combined events). Compared with standard-dose multivitamin supplementation, high-dose supplementation did not reduce the risk of HIV disease progression or death. The absolute risk of HIV progression or death was 72% in the high-dose group vs 72% in the standard-dose group (risk ratio [RR], 1.00; 95% CI, 0.96-1.04). High-dose supplementation had no effect on CD4 count, plasma viral load, body mass index, or hemoglobin level concentration, but increased the risk of ALT elevations (1239 events per 1215 person-years vs 879 events per 1236 person-years; RR, 1.44; 95% CI, 1.11-1.87) vs standard-dose supplementation.

Conclusion:

In adults receiving HAART, use of high-dose multivitamin supplements compared with standard-dose multivitamin supplements did not result in a decrease in HIV disease progression or death but may have resulted in an increase in ALT levels

JAMA. 2012;308(15):1535-1544. doi:10.1001/jama.2012.13083

Lycopene Associated with Reduced Stroke Risk in Men

Objective:

Intake of fruits and vegetables and levels of serum carotenoids have been associated with decreased risk of stroke, but the results have been inconsistent. The aim of the present study was to examine whether serum concentrations of major carotenoids, α-tocopherol and retinol, are related to any stroke and ischemic stroke in men.

Methods:

The study population consisted of 1,031 Finnish men aged 46−65 years in the Kuopio Ischaemic Heart Disease Risk Factor cohort. Serum concentrations of carotenoids retinol and α-tocopherol were measured by high-performance liquid chromatography. The association between the serum concentrations of lycopene α-carotene, β-carotene, α-tocopherol, and retinol and the risk of strokes was studied by using Cox proportional hazards models.

Results:

A total of 67 strokes occurred, and 50 of these were ischemic strokes during a median of 12.1 follow-up years. After adjustment for age, examination year, BMI, systolic blood pressure, smoking, serum low-density lipoprotein cholesterol, diabetes, and history of stroke, men in the highest quartile of serum lycopene concentrations had 59% and 55% lower risks of ischemic stroke and any stroke, compared with men in the lowest quartile (hazard ratio [HR] = 0.45, 95% confidence interval [CI] 0.25−0.95, p = 0.036 for any stroke and HR = 0.41; 95% CI 0.17−0.97, p = 0.042 for ischemic stroke). α-Carotene, β-carotene, α-tocopherol, and retinol were not related to the risk of strokes.

Conclusions:

This prospective study shows that high serum concentrations of lycopene, as a marker of intake of tomatoes and tomato-based products, decrease the risk of any stroke and ischemic stroke in men.

doi: 10.1212/WNL.0b013e31826e26a6 Neurology October 9, 2012 vol. 79 no. 15 1540-1547

Prenatal Mercury Exposure May Be Tied to ADHD in Kids

Objective:

To investigate the association of prenatal mercury exposure and fish intake with attention-deficit/hyperactivity disorder (ADHD)–related behavior.

Methods:

For a population-based prospective birth cohort recruited in New Bedford, Massachusetts (1993-1998), we analyzed data for children examined at age 8 years with peripartum maternal hair mercury measures (n = 421) or maternal report of fish consumption during pregnancy (n = 515). Inattentive and impulsive/hyperactive behaviors were assessed using a teacher rating scale and neuropsychological testing.

Results:

The median maternal hair mercury level was 0.45 μg/g (range, 0.03-5.14 μg/g), and 52% of mothers consumed more than 2 fish servings weekly. In multivariable regression models, mercury exposure was associated with inattention and impulsivity/hyperactivity; some outcomes had an apparent threshold with associations at 1 μg/g or greater of mercury. For example, at 1 μg/g or greater, the adjusted risk ratios for mild/markedly atypical inattentive and impulsive/hyperactive behaviors were 1.4 (95% CI, 1.0-1.8) and 1.7 (95% CI, 1.2-2.4), respectively, for an interquartile range (0.5 μg/g) mercury increase; there was no confounding by fish consumption. For neuropsychological assessments, mercury and behavior associations were detected primarily for boys. There was a protective association for fish consumption (>2 servings per week) with ADHD-related behaviors, particularly impulsive/hyperactive behaviors (relative risk = 0.4; 95% CI, 0.2-0.6).

Conclusions:

Low-level prenatal mercury exposure is associated with a greater risk of ADHD-related behaviors, and fish consumption during pregnancy is protective of these behaviors. These findings underscore the difficulties of balancing the benefits of fish intake with the detriments of low-level mercury exposure in developing dietary recommendations in pregnancy.

 Arch Pediatr Adolesc Med. 2012;():1-3. doi:10.1001/archpediatrics.2012.1900

Vitamin D Does Not Prevent Colds

Context:

Observational studies have reported an inverse association between serum 25-hydroxyvitamin D (25-OHD) levels and incidence of upper respiratory tract infections (URTIs). However, results of clinical trials of vitamin D supplementation have been inconclusive.

Objective:

To determine the effect of vitamin D supplementation on incidence and severity of URTIs in healthy adults.

Design, Setting, and Participants:

Randomized, double-blind, placebo-controlled trial conducted among 322 healthy adults between February 2010 and November 2011 in Christchurch, New Zealand.

Intervention:

Participants were randomly assigned to receive an initial dose of 200 000 IU oral vitamin D3, then 200 000 IU 1 month later, then 100 000 IU monthly (n = 161), or placebo administered in an identical dosing regimen (n = 161), for a total of 18 months.

Main Outcome Measures:

The primary end point was number of URTI episodes. Secondary end points were duration of URTI episodes, severity of URTI episodes, and number of days of missed work due to URTI episodes.

Results:

The mean baseline 25-OHD level of participants was 29 (SD, 9) ng/mL. Vitamin D supplementation resulted in an increase in serum 25-OHD levels that was maintained at greater than 48 ng/mL throughout the study. There were 593 URTI episodes in the vitamin D group and 611 in the placebo group, with no statistically significant differences in the number of URTIs per participant (mean, 3.7 per person in the vitamin D group and 3.8 per person in the placebo group; risk ratio, 0.97; 95% CI, 0.85-1.11), number of days of missed work as a result of URTIs (mean, 0.76 days in each group; risk ratio, 1.03; 95% CI, 0.81-1.30), duration of symptoms per episode (mean, 12 days in each group; risk ratio, 0.96; 95% CI, 0.73-1.25), or severity of URTI episodes. These findings remained unchanged when the analysis was repeated by season and by baseline 25-OHD levels.

Conclusion:

In this trial, monthly administration of 100 000 IU of vitamin D did not reduce the incidence or severity of URTIs in healthy adults.

JAMA. 2012;308(13):1333-1339. doi:10.1001/jama.2012.12505