Safety and metabolic outcomes of resveratrol supplementation in older adults: results of a twelve-week, placebo-controlled pilot study.

Resveratrol has been found to have potent antioxidant, anti-inflammatory, and anticarcinogenic effects. The safety and efficacy of resveratrol supplementation in older adults are currently unknown. We conducted a double-blind, randomized, placebo-controlled trial to examine the safety and metabolic outcomes in 32 overweight, older adults (mean age, 73±7years). Participants were randomized into one of three treatment groups: (1) placebo, (2) moderate dose resveratrol (300mg/day), and (3) high dose resveratrol (1000mg/day). Both resveratrol and placebo were orally ingested in capsule form twice daily for 90days. Blood chemistry values remained within the normal range, and there were no significant differences in the number of participants reporting adverse events across conditions. Compared to placebo, glucose levels were significantly lower at post-treatment among participants randomized to both resveratrol conditions, with and without adjustment for the corresponding baseline values (ps<0.05). Glucose values of participants in the treatment groups, however, were not significantly different from baseline levels. These findings suggest that short-term resveratrol supplementation at doses of 300mg/day and 1000mg/day does not adversely affect blood chemistries and is well tolerated in overweight, older individuals. These findings support the study of resveratrol for improving cardio-metabolic health in older adults in larger clinical trials.

Polymorphisms associated with asthma are inversely related to glioblastoma multiforme.

A reduced risk of primary malignant adult brain tumors is observed among people reporting asthma, hay fever, and other allergic conditions; however, findings may be attributed to prediagnostic effects of tumors or recall bias. To determine whether asthma and allergic condition polymorphisms are inversely related to glioblastoma multiforme (GBM) risk, we conducted a population-based case-control study of 111 GBM patients and 422 controls. We identified five single nucleotide polymorphisms on three genes previously associated with asthma [interleukin (IL)-4RA, IL-13, ADAM33] and one gene associated with inflammation (cyclooxygenase-2). Confirming previous literature, we found that self-reported asthma, eczema, and fever are inversely related to GBM [e.g., asthma odds ratio (OR), 0.64; 95% confidence interval (CI), 0.33-1.25]. In addition, IL-4RA Ser478Pro TC, CC, and IL-4RA Gln551Arg AG, AA are positively associated with GBM (OR, 1.64; 95% CI, 1.05-2.55; 1.61; 95% CI, 1.05-2.47), whereas IL-13 -1,112 CT, TT is negatively associated with GBM (0.56; 95% CI, 0.33-0.96). Each of these polymorphism-GBM associations is in the opposite direction of a corresponding polymorphism-asthma association, consistent with previous findings that self-reported asthmatics and people with allergic conditions are less likely to have GBM than are people who do not report these conditions. Because we used germ line polymorphisms as biomarkers of susceptibility to asthma and allergic conditions, our results cannot be attributed to recall bias or effects of GBM on the immune system. However, our findings are also consistent with associations between IL-4RA, IL-13, and GBM that are independent of their role in allergic conditions.

Aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs in cancer prevention: a critical review of non-selective COX-2 blockade (review).

We comprehensively reviewed the published scientific literature on non-steroidal anti-inflammatory drugs (NSAIDs) and cancer and evaluated results based upon epidemiologic criteria of judgment: consistency of results, strength of association, dose response, molecular specificity, and biological plausibility. Sufficient data from 91 epidemiologic studies were available to examine the dose response of relative risk and level of NSAID intake for ten human malignancies. Dose response curves were fitted by exponential regression. Results showed a significant exponential decline in the risk with increasing intake of NSAIDs (primarily aspirin or ibuprofen) for 7-10 malignancies including the four major types: colon, breast, lung, and prostate cancer. Daily intake of NSAIDs, primarily aspirin, produced risk reductions of 63% for colon, 39% for breast, 36% for lung, and 39% for prostate cancer. Significant risk reductions were also observed for esophageal (73%), stomach (62%), and ovarian cancer (47%). NSAID effects became apparent after five or more years of use and were stronger with longer duration. Observed protective effects were also consistently stronger for gastrointestinal malignancies (esophagus, stomach, and colon). Results for pancreatic, urinary bladder, and renal cancer were inconsistent. Initial epidemiologic studies of malignant melanoma, Hodgkin's disease, and adult leukemia also found that NSAIDs are protective. A few studies suggest that ibuprofen has stronger anticancer effects than aspirin, particularly against breast and lung cancer. Overexpression of cyclooxygenase-2 (COX-2) and increased prostaglandin biosynthesis correlates with carcinogenesis and metastasis at most anatomic sites. Preclinical investigations provide consistent evidence that both selective and non-selective NSAIDs effectively inhibit chemically-induced carcinogenesis of epithelial tumors. This review provides compelling and converging evidence that regular intake of NSAIDs that non-selectively block COX-2 protects against the development of many types of cancer.