Objective: To examine the associations between dietary intake and tissue biomarkers of alpha linolenic acid (ALA) and risk of mortality from all causes, cardiovascular disease (CVD), and cancer.Design: Systematic review and meta-analysis of prospective cohort studies.Data sources: PubMed, Scopus, ISI Web of Science, and Google Scholar to 30 April 2021.Study selection: Prospective cohort studies that reported the risk estimates for death from all causes, CVD, and cancer.Data synthesis: Summary relative risks and 95% confidence intervals were calculated for the highest versus lowest categories of ALA intake using random effects and fixed effects models. Linear and non-linear dose-response analyses were conducted to assess the dose-response associations between ALA intake and mortality.Results: 41 articles from prospective cohort studies were included in this systematic review and meta-analysis, totalling 1 197 564 participants. During follow-up ranging from two to 32 years, 198 113 deaths from all causes, 62 773 from CVD, and 65 954 from cancer were recorded. High intake of ALA compared with low intake was significantly associated with a lower risk of deaths from all causes (pooled relative risk 0.90, 95% confidence interval 0.83 to 0.97, I²=77.8%, 15 studies), CVD (0.92, 0.86 to 0.99, I²=48.2%, n=16), and coronary heart disease (CHD) (0.89, 0.81 to 0.97, I²=5.6%, n=9), and a slightly higher risk of cancer mortality (1.06, 1.02 to 1.11, I²=3.8%, n=10). In the dose-response analysis, a 1 g/day increase in ALA intake (equivalent to one tablespoon of canola oil or 0.5 ounces of walnut) was associated with a 5% lower risk of all cause (0.95, 0.91 to 0.99, I²=76.2%, n=12) and CVD mortality (0.95, 0.91 to 0.98, I²=30.7%, n=14). The pooled relative risks for the highest compared with lowest tissue levels of ALA indicated a significant inverse association with all cause mortality (0.95, 0.90 to 0.99, I²=8.2%, n=26). Also, based on the dose-response analysis, each 1 standard deviation increment in blood concentrations of ALA was associated with a lower risk of CHD mortality (0.92, 0.86 to 0.98, I²=37.1%, n=14).Conclusions: The findings show that dietary ALA intake is associated with a reduced risk of mortality from all causes, CVD, and CHD, and a slightly higher risk of cancer mortality, whereas higher blood levels of ALA are associated with a reduced risk of all cause and CHD mortality only.Systematic review registration: PROSPERO CRD42021229487.

The previous meta-analysis of clinical trials revealed a beneficial effect of vitamin E supplementation on serum C-reactive protein (CRP) concentrations; however, it is unknown whether this vitamin has the same influence on other inflammatory biomarkers. Also, several clinical trials have been published since the release of earlier meta-analysis. Therefore, we aimed to conduct a comprehensive meta-analysis to summarize current evidence on the effects of vitamin E supplementation on inflammatory biomarkers in adults. We searched the online databases using relevant keywords up to November 2019. Randomized clinical trials (RCTs) investigating the effect of vitamin E, compared with the placebo, on serum concentrations of inflammatory cytokines were included. Overall, we included 33 trials with a total sample size of 2102 individuals, aged from 20 to 70 years. Based on 36 effect sizes from 26 RCTs on serum concentrations of CRP, we found a significant reduction following supplementation with vitamin E (− 0.52, 95% CI − 0.80, − 0.23 mg/L, P < 0.001). Although the overall effect of vitamin E supplementation on serum concentrations of interleukin-6 (IL-6) was not significant, a significant reduction in this cytokine was seen in studies that used α-tocopherol and those trials that included patients with disorders related to insulin resistance. Moreover, we found a significant reducing effect of vitamin E supplementation on tumor necrosis factor-α (TNF-α) concentrations at high dosages of vitamin E; such that based on dose–response analysis, serum TNF-α concentrations were reduced significantly at the dosages of ≥ 700 mg/day vitamin E (P_{non-linearity} = 0.001). Considering different chemical forms of vitamin E, α-tocopherol, unlike other forms, had a reducing effect on serum levels of CRP and IL-6. In conclusion, our findings revealed a beneficial effect of vitamin E supplementation, particularly in the form of α-tocopherol, on subclinical inflammation in adults. Future high-quality RCTs should be conducted to translate this anti-inflammatory effect of vitamin E to the clinical setting.

Since a 2014 meta-analysis, several randomized controlled trials (RCTs) evaluating the effect of vitamin E intake on glycemic indices and insulin resistance in adults with diabetes have reached inconsistent conclusions. Therefore, we updated the previous meta-analysis to summarize the current evidence in this regard. Online databases including PubMed, Scopus, ISI Web of Science, and Google Scholar were searched to identify relevant studies published up to September 30, 2021, using relevant keywords. Random-effects models were used to obtain overall mean difference (MD) comparing vitamin E intake with a control group. In total, 38 RCTs with a total sample size of 2171 diabetic patients (1110 in vitamin E groups and 1061 in control groups) were included. Combining the results from 28 RCTs on fasting blood glucose, 32 RCTs on HbA1c, 13 RCTs on fasting insulin, and 9 studies on homeostatic model assessment for insulin resistance (HOMA-IR) showed a summary MD of -3.35 mg/dL (95% CI: -8.10 to 1.40, P = 0.16), -0.21% (95% CI: -0.33 to -0.09, P = 0.001), -1.05 µIU/mL (95% CI: -1.53 to -0.58, P < 0.001), and -0.44 (95% CI: -0.82 to -0.05, P = 0.02), respectively. This indicates a significant lowering effect of vitamin E on HbA1c, fasting insulin and HOMA-IR, while no significant effect on fasting blood glucose in diabetic patients. However, in subgroup analyses, we found that vitamin E intake significantly reduced fasting blood glucose in studies with an intervention duration of < 10 weeks. In conclusion, vitamin E intake has a beneficial role in improving HbA1c and insulin resistance in a population with diabetes. Moreover, short-term interventions with vitamin E have resulted in lower fasting blood glucose in these patients. This meta-analysis was registered in PROSPERO with code CRD42022343118.