Weight Loss and Mortality: What Does the Evidence Show?

A study in this month's PLoS Medicine concludes that, "deliberate weight loss in overweight subjects, without known co-morbidities, may be hazardous in the long term." Stampfer questions whether the data really support such a conclusion

Vitamin intervention for stroke prevention trial: An efficacy analysis

Background and Purpose - The Vitamin Intervention for Stroke Prevention trial (VISP) intention-to-treat analysis did not show efficacy of combined vitamin therapy for recurrent vascular events in patients with nondisabling stroke. Reasons for lack of efficacy may have included folate fortification of grain products, inclusion of the recommended daily intake for B12 in the low-dose arm, treatment with parenteral B12 in patients with low B12 levels in both study arms, a dose of B12 too low for patients with malabsorption, supplementation with nonstudy vitamins, and failure of patients with significant renal impairment to respond to vitamin therapy. We conducted an efficacy analysis limited to patients most likely to benefit from the treatment, based on hypotheses arising from evidence developed since VISP was initiated. The criteria for this subgroup were defined before any data analysis. Methods - For this analysis, we excluded patients with low and very high B12 levels at baseline (\u3c250 and \u3e637 pmol/L, representing the 25th and 95th percentiles), to exclude those likely to have B12 malabsorption or to be taking B12 supplements outside the study and patients with significant renal impairment (glomerular filtration rate \u3c46.18; the 10th percentile). Results - This subgroup represents 2155 patients (37% female), with a mean age of 66±10.7 years. For the combined end point of ischemic stroke, coronary disease, or death, there was a 21% reduction in the risk of events in the high-dose group compared with the low-dose group (unadjusted P=0.049; adjusted for age, sex, blood pressure, smoking, and B12 level P=0.056). In Kaplan-Meier survival analysis comparing 4 groups, patients with a baseline B12 level at the median or higher randomized to high-dose vitamin had the best overall outcome, and those with B12 less than the median assigned to low-dose vitamin had the worst (P=0.02 for combined stroke, death, and coronary events; P=0.03 for stroke and coronary events). Conclusions - In the era of folate fortification, B12 plays a key role in vitamin therapy for total homocysteine. Higher doses of B12, and other treatments to lower total homocysteine may be needed for some patients. © 2005 American Heart Association, Inc

Cutaneous nevi and internal cancer risk: Results from two large prospective cohorts of US women

Elevated cutaneous nevus number has been linked to longer telomeres. Recently, a large systematic Mendelian randomization study identified a significant positive association between telomere length and risk of cancer. Here, we hypothesized that higher nevus count, as a phenotypic marker of longer telomere, may be associated with increased risk of internal cancer, and prospectively examined the association between nevus count and total as well as site‐specific cancer risk among participants in the Nurses’ Health Study (NHS, 1986–2012) and the Nurses’ Health Study 2 (NHS2, 1989–2013) using Cox proportional hazards models. During 3,900,264 person‐years of follow‐up, we documented a total of 23,004 internal cancer cases (15,484 in the NHS and 7,520 in the NHS2). Compared to participants who had no nevi, the multivariate hazard ratios of total cancer (excluding skin cancer) were 1.06 (95% confidence interval [CI], 1.03–1.09) for women with 1–5 nevi, 1.08 (95% CI, 1.03–1.15) for those who had 6–14 nevi and 1.19 (95% CI, 1.05–1.35) for those with 15 or more nevi (p trend <0.0001). Moreover, because nevus count has been associated with risk of breast cancer previously, we conducted a secondary analysis by excluding breast cancer from the outcomes of interest. The results were very similar to those of our primary analysis. For individual cancer, most of the associations with nevus count were positive but not statistically significant. In conclusion, we identified the number of cutaneous nevi as a phenotypic marker associated with internal cancer risk, which may be explained by telomere biology

A prospective study of plasma fish oil levels and incidence of myocardial infarction in U.S. male physicians

AbstractObjectives. This study evaluated whether increased intake of fish oils (eicosapentaenoic and docosahexaenoic acids) might reduce the risk of coronary heart disease.Background.Observational and clinical studies have suggested that increased intake of fish oils, as reflected in plasma levels of fish oils, may reduce the risk of myocardial infarction.Methods.A nested case-control study was conducted among the 14,916 participants in the Physicians' Health Study with a sample of plasma before randomization. Each participant with myocardial infarction occurring during the first 5 years of follow-up was matched by smoking status and age with a randomly chosen control participant who had not developed coronary heart disease.Results.Mean levels of fish oils (with 95% confidence interval [CI] for paired differences and p values) in case and control participants, expressed as present of total fatty acids, were, for eicosapentaenoic acid, 0.26 versus 0.25 (95% CI - 0.03 to 0.05, p = 0.70) in cholesterol esters and 0.56 versus 0.54 (95% CI -0.04 to 0.09, p = 0.44) in phospholipids, and for docosahexaenoic acid, 0.23 versus 0.24 (95% CI -0.07 to 0.04, p = 0.64) in cholesterol esters and 2.22 versus 2.14 (95% CI -0.10 to 0.27, p = 0.36) in phospholipids. Results adjusted for major cardiovascular risk factors showed a very similar lack of association between fish oil levels and the incidence of myocardial infarction.Conclusions.These results indicate no beneficial effect of increased fish oil consumption on the incidence of a first myocardial infarction. However, the effect of very high levels of fish oils could not be evaluated

Muscle-Strengthening and Conditioning Activities and Risk of Type 2 Diabetes: A Prospective Study in Two Cohorts of US Women

Background: It is well established that aerobic physical activity can lower the risk of type 2 diabetes (T2D), but whether muscle-strengthening activities are beneficial for the prevention of T2D is unclear. This study examined the association of muscle-strengthening activities with the risk of T2D in women. Methods and Findings: We prospectively followed up 99,316 middle-aged and older women for 8 years from the Nurses' Health Study ([NHS] aged 53–81 years, 2000–2008) and Nurses' Health Study II ([NHSII] aged 36–55 years, 2001–2009), who were free of diabetes, cancer, and cardiovascular diseases at baseline. Participants reported weekly time spent on resistance exercise, lower intensity muscular conditioning exercises (yoga, stretching, toning), and aerobic moderate and vigorous physical activity (MVPA) at baseline and in 2004/2005. Cox regression with adjustment for major determinants for T2D was carried out to examine the influence of these types of activities on T2D risk. During 705,869 person years of follow-up, 3,491 incident T2D cases were documented. In multivariable adjusted models including aerobic MVPA, the pooled relative risk (RR) for T2D for women performing 1–29, 30–59, 60–150, and >150 min/week of total muscle-strengthening and conditioning activities was 0.83, 0.93, 0.75, and 0.60 compared to women reporting no muscle-strengthening and conditioning activities (p<0.001 for trend). Furthermore, resistance exercise and lower intensity muscular conditioning exercises were each independently associated with lower risk of T2D in pooled analyses. Women who engaged in at least 150 min/week of aerobic MVPA and at least 60 min/week of muscle-strengthening activities had substantial risk reduction compared with inactive women (pooled RR = 0.33 [95% CI 0.29–0.38]). Limitations to the study include that muscle-strengthening and conditioning activity and other types of physical activity were assessed by a self-administered questionnaire and that the study population consisted of registered nurses with mostly European ancestry. Conclusions: Our study suggests that engagement in muscle-strengthening and conditioning activities (resistance exercise, yoga, stretching, toning) is associated with a lower risk of T2D. Engagement in both aerobic MVPA and muscle-strengthening type activity is associated with a substantial reduction in the risk of T2D in middle-aged and older women. Please see later in the article for the Editors' Summar

Risk of a Second Primary Cancer after Non-melanoma Skin Cancer in White Men and Women: A Prospective Cohort Study

Background: Previous studies suggest a positive association between history of non-melanoma skin cancer (NMSC) and risk of subsequent cancer at other sites. The purpose of this study is to prospectively examine the risk of primary cancer according to personal history of NMSC. Methods and Findings: In two large US cohorts, the Health Professionals Follow-up Study (HPFS) and the Nurses' Health Study (NHS), we prospectively investigated this association in self-identified white men and women. In the HPFS, we followed 46,237 men from June 1986 to June 2008 (833,496 person-years). In the NHS, we followed 107,339 women from June 1984 to June 2008 (2,116,178 person-years). We documented 29,447 incident cancer cases other than NMSC. Cox proportional hazard models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs). A personal history of NMSC was significantly associated with a higher risk of other primary cancers excluding melanoma in men (RR = 1.11; 95% CI 1.05–1.18), and in women (RR = 1.20; 95% CI 1.15–1.25). Age-standardized absolute risk (AR) was 176 in men and 182 in women per 100,000 person-years. For individual cancer sites, after the Bonferroni correction for multiple comparisons (n = 28), in men, a personal history of NMSC was significantly associated with an increased risk of melanoma (RR = 1.99, AR = 116 per 100,000 person-years). In women, a personal history of NMSC was significantly associated with an increased risk of breast (RR = 1.19, AR = 87 per 100,000 person-years), lung (RR = 1.32, AR = 22 per 100,000 person-years), and melanoma (RR = 2.58, AR = 79 per 100,000 person-years). Conclusion: This prospective study found a modestly increased risk of subsequent malignancies among individuals with a history of NMSC, specifically breast and lung cancer in women and melanoma in both men and women. Please see later in the article for the Editors' Summar

The Effect of Weight-Loss Interventions on Cervical and Chin Subcutaneous Fat Depots; the CENTRAL Randomized Controlled Trial

Accumulation of cervical and chin subcutaneous adipose tissues (SAT) represent known phenotypes of obesity. We aimed to evaluate the sensitivity of these fat storages to long-term weight-loss directed lifestyle-intervention and to assess their relations to bodily-adiposity, insulin-resistance, and cardiometabolic risk; We randomly assigned 278 participants with abdominal-obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate diets +/− physical-activity. All participants underwent an 18 month whole-body magnetic resonance imaging follow-up, from which we assessed cervical and chin SAT-areas; Participants (age = 48 years; 90% men; body-mass-index = 30.9 kg/m2) had an 18-month adherence-rate of 86%. Cervical-SAT and chin-SAT decreased after 6-months (−13.1% and −5.3%, respectively, p < 0.001). After 18-months only cervical-SAT remained decreased compared to baseline (−5%, p < 0.001). Cervical and chin-SAT 18-month changes were associated with changes in weight (r = 0.70, r = 0.66 respectively; <0.001 for both) and visceral-adipose-tissue (VAT; r = 0.35, r = 0.42 respectively; <0.001 for both). After adjustment to VAT, waist-circumference, or weight-changes, chin-SAT 18-month reduction was associated with favorable changes in fasting-glucose (β = 0.10; p = 0.05), HbA1c (β = 0.12; p = 0.03), and homeostasis-model-assessment-of-insulin-resistance (β = 0.12; p = 0.03). Cervical-SAT 18-month reduction was associated with decreased triglycerides (β = 0.16; p = 0.02) and leptin (β = 0.19; p = 0.01) independent of VAT; Cervical and chin-SATs are dynamic fat depots that correspond with weight-loss and are associated with changes in cardiometabolic profile. In long-term, chin-SAT displays a larger rebound compared with cervical-SAT. Chin-SAT accumulation is associated with in insulin-resistance, independent of central obesity. (ClinicalTrials identifier NCT01530724

Intakes of fruits, vegetables and carbohydrate and the risk of CVD

BACKGROUND: Low-carbohydrate diets could lead to reduced fruit and vegetable intake, which may be protective against CVD. The role of carbohydrate intake in modifying the association between fruits and vegetables and CVD has not been evaluated. OBJECTIVE: To evaluate whether carbohydrate intake affects the association between fruits and vegetables and CVD. DESIGN: We included participants from two large prospective studies, the Nurses' Health Study (NHS) and the Health Professionals' Follow-Up Study (HPFS). We followed 70870 eligible NHS females for 16 years and 38918 eligible HPFS males for 14 years. Diet was assessed from an FFQ updated every 4 years. Our primary outcome was ischaemic CVD (fatal and non-fatal myocardial infarction and ischaemic stroke). We used Cox proportional hazards models to evaluate the relationship between fruits and vegetables and ischaemic CVD within groups with low, moderate or high carbohydrate intake. RESULTS: Fruit intake was strongly related with carbohydrate intake, but vegetables showed a very small correlation. Vegetable intake showed stronger associations with ischaemic CVD among the low carbohydrate group (multivariate risk ratio (RR) = 0.82 for an increment of 3 servings/d; 95% CI 0.68, 0.99); green leafy vegetables and carotene-rich fruits and vegetables followed a similar pattern. Total fruit intake was associated with a lower risk of ischaemic CVD only among participants with moderate carbohydrate intake (RR = 0.81 comparing extreme quintiles; 95% CI 0.70, 0.94). CONCLUSIONS: Total vegetables, green leafy vegetables and carotene-rich fruits and vegetables showed stronger associations with ischaemic CVD among the low carbohydrate group. No consistent trends were observed for fruit intake

Light to moderate intake of alcohol, drinking patterns, and risk of cancer: results from two prospective US cohort studies

Objectives: To quantify risk of overall cancer across all levels of alcohol consumption among women and men separately, with a focus on light to moderate drinking and never smokers; and assess the influence of drinking patterns on overall cancer risk. Design: Two prospective cohort studies. Setting: Health professionals in the United States. Participants: 88 084 women and 47 881 men participating in the Nurses’ Health Study (from 1980) and Health Professionals Follow-up Study (from 1986), followed until 2010. Main outcomes and measures Relative risks of cancer. Results: 19 269 and 7571 (excluding non-advanced prostate cancers) incident cancers were documented among women and men, respectively, over 3 144 853 person years. Compared with non-drinkers, light to moderate drinkers had relative risks of total cancer of 1.02 (95% confidence interval 0.98 to 1.06) and 1.04 (1.00 to 1.09; Ptrend=0.12) for alcohol intake of 0.1-4.9 and 5-14.9 g/day among women, respectively. Corresponding values for men were 1.03 (0.96 to 1.11), 1.05 (0.97 to 1.12), and 1.06 (0.98 to 1.15; Ptrend=0.31) for alcohol intake of 0.1-4.9, 5-14.9, and 15-29.9 g/day, respectively. Associations for light to moderate drinking and total cancer were similar among ever or never smokers, although alcohol consumption above moderate levels (in particular ≥30 g/day) was more strongly associated with risk of total cancer among ever smokers than never smokers. For a priori defined alcohol related cancers in men, risk was not appreciably increased for light and moderate drinkers who never smoked (Ptrend=0.18). However, for women, even an alcohol consumption of 5-14.9 g/day was associated with increased risk of alcohol related cancer (relative risk 1.13 (95% confidence interval 1.06 to 1.20)), driven by breast cancer. More frequent and heavy episodic drinking was not further associated with risk of total cancer after adjusting for total alcohol intake. Conclusion: Light to moderate drinking is associated with minimally increased risk of overall cancer. For men who have never smoked, risk of alcohol related cancers is not appreciably increased for light and moderate drinking (up to two drinks per day). However, for women who have never smoked, risk of alcohol related cancers (mainly breast cancer) increases even within the range of up to one alcoholic drink a day