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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.

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Background Sunlight exposure, the main source of endogenous vitamin D synthesis, may increase the risk of non-melanoma skin cancer (NMSC) development. Vitamin D receptor (VDR) polymorphisms are associated with 25(OH)D levels, cancer development and insulin resistance. Objective This study aimed to examine the associations among vitamin D status, VDR FokI polymorphism, insulin resistance and NMSC. 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 were genotyped. Fasting serum 25-hydroxyvitaminD (25(OH)D)), lipid profile, glucose, and insulin were measured. To evaluate insulin resistance, HOMA-IR formula was used. Results We found a significant higher duration of cumulative sunlight exposure in cases compared with controls (p<0.001). However, 25(OH)D concentrations were not significantly different between cases and controls (30±15 vs. 29±15 ng/mL, p=0.78). Higher levels of insulin (p = 0.004) and HOMA-IR score (p= 0.019) were observed in Ff and ff genotype of FokI. 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). The components of lipid profile, fasting serum glucose, iPTH and anthropometric measures did not differ significantly across VDR genotypes. Conclusion In conclusion, sunlight exposure was associated with NMSC risk. VDR FokI polymorphisms appears to influence insulin resistance in the NMSC patients.

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.

Background: Sunlight exposure, the main source of endogenous vitamin D synthesis, may increase the risk of non-melanoma skin cancer (NMSC) development. Vitamin D receptor (VDR) polymorphisms are associated with 25(OH)D levels, cancer development and insulin resistance. This study was aimed to examine the associations among vitamin D status, VDR FokI polymorphism, insulin resistance and NMSC. 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 were genotyped. Fasting serum 25-hydroxyvitaminD (25(OH)D)), lipid profile, glucose, and insulin were measured. To evaluate insulin resistance, HOMA-IR formula was used. Results: We found a significant higher duration of cumulative sunlight exposure in cases compared with controls (p<0.001). However, 25(OH)D concentrations were not significantly different between cases and controls (30±15 vs. 29±15 ng/mL, p=0.78). Higher levels of insulin (p = 0.004) and HOMA-IR score (p= 0.019) were observed in Ff and ff genotype of FokI. 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). The components of lipid profile, fasting serum glucose, iPTH and anthropometric measures did not differ significantly across VDR genotypes. Conclusion: In conclusion, sunlight exposure was associated with NMSC risk. VDR FokI polymorphisms appears to influence insulin resistance in the NMSC patients. Keywords: sun exposure; non-melanoma skin cancer; polymorphisms; insulin resistance