The effects of folic acid supplementation on endothelial function in adults: a systematic review and dose-response meta-analysis of randomized controlled trials.

BACKGROUND: Endothelial dysfunction serves as an early marker for the risk of cardiovascular disease (CVD); therefore, it is an attractive site of therapeutic interventions to reduce the risk of CVD. This study was conducted to investigate the effect of folic acid supplementation on endothelial function markers in randomized controlled trials (RCTs). METHODS: PubMed, ISI web of science, and Scopus databases were searched up to July 2022 for detecting eligible studies. A random-effects model was used for meta-analysis, and linear Meta-regression and non-linear dose-response analysis were performed to assess whether the effect of folic acid supplementation was affected by the dose and duration of intervention. Cochrane tools were also used to assess the risk of bias in the included studies. RESULTS: Twenty-one studies, including 2025 participants (1010 cases and 1015 controls), were included in the present meta-analysis. Folic acid supplementation significantly affected the percentage of flow-mediated dilation (FMD%) (WMD: 2.59%; 95% CI: 1.51, 3.67; P < 0.001) and flow-mediated dilation (FMD) (WMD: 24.38 µm; 95% CI: 3.08, 45.68; P = 0.025), but not end-diastolic diameter (EDD) (WMD: 0.21 mm; 95% CI: - 0.09, 0.52; P = 0.176), and intercellular adhesion molecule (ICAM) (WMD: 0.18 ng/ml; 95% CI: - 10.02, 13.81; P = 0.755). CONCLUSIONS: These findings suggest that folic acid supplementation may improve endothelial function by increasing FMD and FMD% levels. TRIAL REGISTRATION: PROSPERO registration cod: CRD42021289744.

Sun Exposure Makes no Discrimination based on Vitamin D Status and VDR-Foki Polymorphisms for Non-Melanoma Skin Cancers Risk in Iranian Subjects: A Case-Control Study.

BACKGROUND AND OBJECTIVE: Sunlight exposure, the main source of endogenous vitamin D synthesis, may increase the risk of non-melanoma skin cancers (NMSC) development. Vitamin D receptor (VDR) polymorphisms are associated with various malignancies. This study aimed to examine the associations between vitamin D status and VDR FokI polymorphisms in Iranian subjects with NMSC. MATERIALS AND METHODS: This case-control study included 73 diagnosed cases of NMSC and 72 healthy controls from dermatology clinics at Razi Hospital, Tehran, Iran. A questionnaire was used to assess sunlight exposure. The extracted DNA from whole blood samples was genotyped and serum concentrations of 25-hydroxycalciferol (25(OH)D)) and intact parathyroid hormone (iPTH) were measured. RESULTS: We found a significant higher duration of cumulative sunlight exposure in cases compared with controls (p<0.001). However, 25(OH)D and iPTH concentrations were not significantly different between cases and controls (30±15 vs. 29±15 ng/mL, p=0.78 and 46.0±20 vs. 40.5±23 pg/mL, p=0.14, respectively). We did not observe any significant increased risk of NMSC due to f allele, as compared with FF (OR =2.33, 95% CI 0.81-6.75, p=0.12). CONCLUSION: Though sunlight exposure was associated with increased NMSC risk, there were no significant associations between vitamin D status or VDR FokI polymorphisms with NMSC development in our subjects.

Metabolic Syndrome and Its Components are Linked with Increased Risk of Non-Melanoma Skin Cancers in Iranian Subjects: A Case-Control Study.

The associations between components of metabolic syndrome (MetS), insulin resistance (IR), and several malignancies have been reported. However, the possible link between IR and dermal malignancies, including non-melanoma skin cancers (NMSCs), has not been investigated to date. In this study, we aimed to examine the possible association between components of MetS, IR, adhesion molecules, and NMSC for the first time. This was a case-control study comprising 73 confirmed cases of NMSC and 72 unrelated healthy controls. Anthropometric and biochemical assessments including fasting blood lipid profile, glucose and insulin assays were performed. To evaluate IR, HOMA-IR formula was used. Though fasting serum glucose showed no significant between-group difference, serum concentrations of insulin (p = 0.048) as well as HOMA-IR (p = 0.037) were both significantly higher in NMSC group than in controls. Logistic regression analysis revealed significant associations between waist circumference (OR: 1.04, 95% CI: 1.007-1.080, p = 0.018), percent of visceral fat (OR: 1.10, 95% CI: 1.024-1.190, p = 0.01), HOMA-IR (OR: 1.169, 95% CI: 1.004-1.360, p = 0.044), circulating VCAM-1 concentrations (OR: 1.005, 95% CI: 1.003-1.007, p < 0.001) and NMSC risk. Interestingly, the occurrence of MetS was significantly higher in subjects with NMSC than in healthy controls (p = 0.038). MetS and its components were associated with increased NMSC risk.