Biomarker responses to folic acid intervention in healthy adults: a meta-analysis of randomized controlled trials

BACKGROUND: The task of revising dietary folate recommendations for optimal health is complicated by a lack of data quantifying the biomarker response that reliably reflects a given folate intake.

OBJECTIVE: We conducted a dose-response meta-analysis in healthy adults to quantify the typical response of recognized folate biomarkers to a change in folic acid intake.

DESIGN: Electronic and bibliographic searches identified 19 randomized controlled trials that supplemented with folic acid and measured folate biomarkers before and after the intervention in apparently healthy adults aged ≥18 y. For each biomarker response, the regression coefficient (β) for individual studies and the overall pooled β were calculated by using random-effects meta-analysis.

RESULTS: Folate biomarkers (serum/plasma and red blood cell folate) increased in response to folic acid in a dose-response manner only up to an intake of 400 μg/d. Calculation of the overall pooled β for studies in the range of 50 to 400 μg/d indicated that a doubling of folic acid intake resulted in an increase in serum/plasma folate by 63% (71% for microbiological assay; 61% for nonmicrobiological assay) and red blood cell folate by 31% (irrespective of whether microbiological or other assay was used). Studies that used the microbiological assay indicated lower heterogeneity compared with studies using nonmicrobiological assays for determining serum/plasma (I(2) = 13.5% compared with I(2) = 77.2%) and red blood cell (I(2) = 45.9% compared with I(2) = 70.2%) folate.

CONCLUSIONS: Studies administering >400 μg folic acid/d show no dose-response relation and thus will not yield meaningful results for consideration when generating dietary folate recommendations. The calculated folate biomarker response to a given folic acid intake may be more robust with the use of a microbiological assay rather than alternative methods for blood folate measurement.

The effect of statins on intraocular pressure and on the incidence and progression of glaucoma: A Systematic Review and Meta-analysis

Purpose: We conducted a systematic review and meta-analysis of observational studies to evaluate the effect of oral statins on intraocular pressure (IOP) and the incidence and progression of glaucoma. Methods: This was a systematic review of the literature and meta-analysis. Searches of PubMed/Medline and Embase were conducted to include all types of studies. Gray literature abstracts were also considered for inclusion. Last search date was February 2016. Risk of bias was assessed using the Newcastle-Ottawa scale independently by two reviewers. Odds ratios (OR) or hazard ratios (HR) and 95% confidence intervals (CI) were extracted from each study. Pooled ORs for incidence of glaucoma were calculated using a random-effects model. Results: We identified seven cohort studies, three case–control studies, and one cross-sectional study with a total number of 583,615 participants. No randomized controlled trials were retrieved. Pooled ORs demonstrated a statistically significant association between short-term statin use (≤2 years) and reduced incidence of glaucoma (OR 0.96, 95%CI 0.94, 0.99). Pooled ORs of long-term statin use (>2 years) did not demonstrate statistically significant reduction in incidence of glaucoma (OR 0.70, 95%CI 0.46, 1.06). There was inconsistent evidence for the protective effect of statins against the progression of glaucoma, although there was no standard definition for progression across studies. There was no significant difference in IOP associated with statin use. Conclusions: Short-term statin use is associated with a reduced incidence of glaucoma. The effect of statins on glaucoma progression and IOP is uncertain.

Quantification of the smoking-associated cancer risk with rate advancement periods: meta-analysis of individual participant data from cohorts of the CHANCES consortium

BACKGROUND: Smoking is the most important individual risk factor for many cancer sites but its association with breast and prostate cancer is not entirely clear. Rate advancement periods (RAPs) may enhance communication of smoking related risk to the general population. Thus, we estimated RAPs for the association of smoking exposure (smoking status, time since smoking cessation, smoking intensity, and duration) with total and site-specific (lung, breast, colorectal, prostate, gastric, head and neck, and pancreatic) cancer incidence and mortality.

METHODS: This is a meta-analysis of 19 population-based prospective cohort studies with individual participant data for 897,021 European and American adults. For each cohort we calculated hazard ratios (HRs) for the association of smoking exposure with cancer outcomes using Cox regression adjusted for a common set of the most important potential confounding variables. RAPs (in years) were calculated as the ratio of the logarithms of the HRs for a given smoking exposure variable and age. Meta-analyses were employed to summarize cohort-specific HRs and RAPs.

RESULTS: Overall, 140,205 subjects had a first incident cancer, and 53,164 died from cancer, during an average follow-up of 12 years. Current smoking advanced the overall risk of developing and dying from cancer by eight and ten years, respectively, compared with never smokers. The greatest advancements in cancer risk and mortality were seen for lung cancer and the least for breast cancer. Smoking cessation was statistically significantly associated with delays in the risk of cancer development and mortality compared with continued smoking.

CONCLUSIONS: This investigation shows that smoking, even among older adults, considerably advances, and cessation delays, the risk of developing and dying from cancer. These findings may be helpful in more effectively communicating the harmful effects of smoking and the beneficial effect of smoking cessation.

The value of adjuvant radiotherapy on survival and recurrence in triple-negative breast cancer: a systematic review and meta-analysis of 5,507 patients

BACKGROUND: The value of adjuvant radiotherapy in triple negative breast cancer (TNBC) remains unclear. A systematic review and meta-analysis was conducted in TNBC patients to assess survival and recurrence outcomes associated with radiotherapy following either breast conserving therapy (BCT) or post-mastectomy radiotherapy (PMRT). METHODS: Four electronic databases were searched from January 2000 to November 2015 (PubMed, MEDLINE, EMBASE and Web of Science). Studies investigating overall survival and/or recurrence in TNBC patients according to radiotherapy administration were included. A random effects meta-analysis was conducted using mastectomy only patients as the reference.  RESULTS: Twelve studies were included. The pooled hazard ratio (HR) for locoregional recurrence comparing BCT and PMRT to mastectomy only was 0.61 (95% confidence interval [CI] 0.41-0.90) and 0.62 (95% CI 0.44-0.86), respectively. Adjuvant radiotherapy was not significantly associated with distant recurrence. The pooled HR for overall survival comparing BCT and PMRT to mastectomy only was 0.57 (95% CI 0.36-0.88) and HR 1.12 (95% CI 0.75, 1.69). Comparing PMRT to mastectomy only, tests for interaction were not significant for stage (p=0.98) or age at diagnosis (p=0.85). However, overall survival was improved in patients with late-stage disease (T3-4, N2-3) pooled HR 0.53 (95% CI 0.32-0.86), and women <40 years, pooled HR 0.30 (95% CI 0.11-0.82). CONCLUSIONS: Adjuvant radiotherapy was associated with a significantly lower risk of locoregional recurrence in TNBC patients, irrespective of the type of surgery. While radiotherapy was not consistently associated with an overall survival gain, benefits may be obtained in women with late-stage disease and younger patients.