Nikan Zargarzadeh1, Juliana Soares Severo2, Ana Beatriz Pizarro3, Emma Persad4, Seyed Mohammad Mousavi5. 1. School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2. Graduate Program in Food and Nutrition. Federal University of Piauí, Teresina-PI, Brazil. 3. Clinical Research Center, Fundación Valle del Lili, Cali, Colombia. 4. Department for Evidence-based Medicine and Evaluation, Danube University Krems, Krems, Austria. 5. Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: smmousavi@razi.tums.ac.ir.
Abstract
PURPOSE: Despite extensive research, findings regarding the effects of folic acid supplementation on inflammatory mediators have been controversial and inconclusive. This study therefore aimed to summarize the findings of all available clinical trials regarding the effects of folic acid supplementation on inflammatory biomarkers in adults. METHODS: A systematic search was conducted of PubMed/MEDLINE, Scopus, Web of Science, EMBASE, and Google Scholar until April 2020. All randomized controlled trials that examined the influence of folic acid supplementation on C-reactive protein, interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were included. Pooled effect sizes were calculated based on the random effects model, and dose-response analysis was modeled by using a fractional polynomial model. FINDINGS: In total, 18 randomized controlled trials involving 2286 participants were analyzed. Folic acid supplementation significantly reduced serum levels of C-reactive protein (mean difference [MD], -0.21 mg/L; 95% CI, -0.41 to -0.01; n = 16), TNF-α (MD, -14.88 pg/mL; 95% CI, -23.68 to -6.09; n = 10), and IL-6 (MD, -0.93 pg/mL; 95% CI, -1.72 to -0.14; n = 11). Subgroup analyses suggested a significant reduction at doses ≤5 mg/d and studies longer than 12 weeks in duration. A significant nonlinear association was also found between folic acid dosage (Pnonlinearity <0.001) and duration of administration (Pnonlinearity <0.001) with serum TNF-α levels. IMPLICATIONS: This meta-analysis indicates the beneficial effects of folic acid supplementation on pro-inflammatory cytokines. Further studies with a longer duration of administration, higher doses, and larger sample sizes should be performed exclusively on patients with chronic inflammatory disorders to elucidate the favorable role of folate intake on inflammatory biomarkers. International Prospective Register of Systematic Reviews identifier: CRD42021249947.
PURPOSE: Despite extensive research, findings regarding the effects of folic acid supplementation on inflammatory mediators have been controversial and inconclusive. This study therefore aimed to summarize the findings of all available clinical trials regarding the effects of folic acid supplementation on inflammatory biomarkers in adults. METHODS: A systematic search was conducted of PubMed/MEDLINE, Scopus, Web of Science, EMBASE, and Google Scholar until April 2020. All randomized controlled trials that examined the influence of folic acid supplementation on C-reactive protein, interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were included. Pooled effect sizes were calculated based on the random effects model, and dose-response analysis was modeled by using a fractional polynomial model. FINDINGS: In total, 18 randomized controlled trials involving 2286 participants were analyzed. Folic acid supplementation significantly reduced serum levels of C-reactive protein (mean difference [MD], -0.21 mg/L; 95% CI, -0.41 to -0.01; n = 16), TNF-α (MD, -14.88 pg/mL; 95% CI, -23.68 to -6.09; n = 10), and IL-6 (MD, -0.93 pg/mL; 95% CI, -1.72 to -0.14; n = 11). Subgroup analyses suggested a significant reduction at doses ≤5 mg/d and studies longer than 12 weeks in duration. A significant nonlinear association was also found between folic acid dosage (Pnonlinearity <0.001) and duration of administration (Pnonlinearity <0.001) with serum TNF-α levels. IMPLICATIONS: This meta-analysis indicates the beneficial effects of folic acid supplementation on pro-inflammatory cytokines. Further studies with a longer duration of administration, higher doses, and larger sample sizes should be performed exclusively on patients with chronic inflammatory disorders to elucidate the favorable role of folate intake on inflammatory biomarkers. International Prospective Register of Systematic Reviews identifier: CRD42021249947.
Authors: Nikan Zargarzadeh; Kiana Tadbir Vajargah; Armin Ebrahimzadeh; Seyed Mohammad Mousavi; Hamidreza Khodaveisi; Camellia Akhgarjand; Fernando M P Toyos; Henrique S Cerqueira; Heitor O Santos; Mohsen Taghizadeh; Alireza Milajerdi Journal: Front Med (Lausanne) Date: 2022-07-19