scholarly journals Effects of Folic Acid Supplementation on Inflammatory Markers: A Grade-Assessed Systematic Review and Dose–Response Meta-Analysis of Randomized Controlled Trials

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2327
Author(s):  
Omid Asbaghi ◽  
Damoon Ashtary-Larky ◽  
Reza Bagheri ◽  
Parisa Moosavian ◽  
Behzad Nazarian ◽  
...  

It has been theorized that folic acid supplementation improves inflammation. However, its proven effects on inflammatory markers are unclear as clinical studies on this topic have produced inconsistent results. To bridge this knowledge gap, this systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of folic acid supplementation on serum concentrations of the inflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Methods: To identify eligible RCTs, a systematic search up to April 2021 was completed in PubMed/Medline, Scopus, Web of Science, EMBASE, Cochrane databases, and Google Scholar using relevant keywords. A fix or random-effects model was utilized to estimate the weighted mean difference (WMD) and 95% confidence interval (95% CI). Results: Twelve RCTs were included in the present meta-analysis. The pooled analysis revealed that serum concentrations of CRP (WMD: −0.59 mg/L, 95% CI −0.85 to −0.33, p < 0.001) were significantly reduced following folic acid supplementation compared to placebo, but did not affect serum concentrations of IL-6 (WMD: −0.12, 95% CI −0.95 to 0.72 pg/mL, p = 0.780) or TNF-α (WMD: −0.18, 95% CI −0.86 to 0.49 pg/mL, p = 0.594). The dose–response analysis demonstrated a significant relationship between an elevated dosage of folic acid supplementation and lower CRP concentrations (p = 0.002). Conclusions: We found that folic acid supplementation may improve inflammation by attenuating serum concentrations of CRP but without significant effects on IL-6 and TNF-α. Future RCTs including a larger number of participants and more diverse populations are needed to confirm and expand our findings.

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 871
Author(s):  
Omid Asbaghi ◽  
Matin Ghanavati ◽  
Damoon Ashtary-Larky ◽  
Reza Bagheri ◽  
Mahnaz Rezaei Kelishadi ◽  
...  

(1) Background: This systematic review and meta-analysis aimed to assess the effects of folic acid supplementation on oxidative stress markers. (2) Methods: Online database including PubMed, Scopus, Web of Science, and Cochrane were searched up to January 2021, to retrieve randomized controlled trials (RCTs) which examined the effect of folic acid supplementation on markers of oxidative stress. Meta-analyses were carried out using a random-effects model. I2 index was used to evaluate the heterogeneity of RCTs. (3) Results: Among the initial 2322 studies that were identified from electronic databases search, 13 studies involving 1013 participants were eligible. Pooled effect size from 13 studies indicated that folic acid supplementation elicits a significant rise in serum concentrations of glutathione (GSH) (WMD: 219.01 umol/L, 95% CI 59.30 to 378.71, p = 0.007) and total antioxidant capacity (TAC) (WMD: 91.70 umol/L, 95% CI 40.52 to 142.88, p < 0.001) but has no effect on serum concentrations of nitric oxide (NO) (WMD: 2.61 umol/L, 95% CI −3.48 to 8.72, p = 0.400). In addition, folic acid supplementation significantly reduced serum concentrations of malondialdehyde (MDA) (WMD: −0.13 umol/L, 95% CI −0.24 to −0.02, p = 0.020). (4) Conclusions: This meta-analysis study suggests that folic acid supplementation may significantly improve markers within the antioxidative defense system by increasing serum concentrations of GSH and TAC and decreasing serum concentrations of MDA.


2014 ◽  
Vol 18 (8) ◽  
pp. 1514-1521 ◽  
Author(s):  
Rui Zeng ◽  
Chun-Hua Xu ◽  
Yuan-Ning Xu ◽  
Ya-Li Wang ◽  
Mian Wang

AbstractObjectiveFolate and vitamin B12 are two vital regulators in the metabolic process of homocysteine, which is a risk factor of atherothrombotic events. Low folate intake or low plasma folate concentration is associated with increased stroke risk. Previous randomized controlled trials presented discordant findings in the effect of folic acid supplementation-based homocysteine lowering on stroke risk. The aim of the present review was to perform a meta-analysis of relevant randomized controlled trials to check the how different folate fortification status might affect the effects of folic acid supplementation in lowering homocysteine and reducing stroke risk.DesignRelevant randomized controlled trials were identified through formal literature search. Homocysteine reduction was compared in subgroups stratified by folate fortification status. Relative risks with 95 % confidence intervals were used as a measure to assess the association between folic acid supplementation and stroke risk.SettingThe meta-analysis included fourteen randomized controlled trials,SubjectsA total of 39 420 patients.ResultsHomocysteine reductions were 26·99 (sd 1·91) %, 18·38 (sd 3·82) % and 21·30 (sd 1·98) %, respectively, in the subgroups without folate fortification, with folate fortification and with partial folate fortification. Significant difference was observed between the subgroups with folate fortification and without folate fortification (P=0·05). The relative risk of stroke was 0·88 (95 % CI 0·77, 1·00, P=0·05) in the subgroup without folate fortification, 0·94 (95 % CI 0·58, 1·54, P=0·82) in the subgroup with folate fortification and 0·91 (95 % CI 0·82, 1·01, P=0·09) in the subgroup with partial folate fortification.ConclusionsFolic acid supplementation might have a modest benefit on stroke prevention in regions without folate fortification.


Author(s):  
I Putu Eka Widyadharma ◽  
Eric Hartono Tedyanto ◽  
Anak Agung Ayu Putri Laksmidewi ◽  
I Made Oka Adnyana ◽  
Dewa Putu Gede Purwa Samatra

The most common type of dementia is Alzheimer’s disease (AD). AD is characterized by loss of memory and cognitive impairment. In epidemiological studies, low folate could disturb vitamin B12 absorption, which leads to the inflammatory process, and it explains the association between both vitamins and AD. Authors did a systematic search through PubMed and Embase according to the PRISMA protocol. Authors included studies published in the last 5 years (from 2015 to June 2020). Authors assess the quality of studies using JADAD Scale for randomized-controlled trials. Authors found 426 journals in their search strategy. In the end, 2 studies met the eligibility criteria and were included in this review. These two randomized controlled trials revealed that folic acid improved cognitive function in AD (p<0.05) and mild cognitive impairment (p=0.028). In this systematic review, authors found that daily folic acid supplements could improve cognitive function in patients with AD and mild cognitive impairment. The exact mechanism is unknown, but it is believed that folic acid supplementation improves cognitive function by reducing the levels of peripheral inflammatory cytokines. Daily oral folic acid supplemental (400 µg and 1.2 mg) for 6-12 months improves cognitive function in AD and mild cognitive Impairment.


Author(s):  
Mahdi Vajdi ◽  
Mahsa Mahmoudi-Nezhad ◽  
Mahdieh Abbasalizad Farhangi

Abstract. Data about the effects of alpha-lipoic acid (ALA) supplementation on inflammatory markers are inconsistent. This systematic review and dose-response meta-analysis of randomized controlled trials was performed to summarize the effects of ALA supplementation on inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in adults. A comprehensive literature search was conducted in the electronic databases of PubMed, Web of Science, ProQuest, Embase, and SCOPUS from inception to February 2020. Among all of the eligible studies, 20 articles were selected. The weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated to evaluate the pooled effect size. Between-study heterogeneity was evaluated using Cochran’s Q test and I2. Subgroup analysis was done to evaluate the potential sources of heterogeneity. The dose-response relationship was evaluated using fractional polynomial modeling. Twenty eligible studies with a total sample size of 947 participants were included in the current meta-analysis. The findings of the meta-analysis showed that ALA supplementation significantly reduced CRP (WMD: −0.69 mg/L, 95% CI: −1.13, −0.26, P=0.002), IL-6 (WMD: −1.83 pg/ml, 95% CI: −2.90, −0.76, P=0.001), and TNF-α concentrations (WMD: −0.45 pg/ml, 95% CI: −0.85, −0.04, P=0.032). No evidence of departure from linearity was observed between dose and duration of the ALA supplementation on serum CRP, IL-6 and TNF-α concentration. In subgroup analysis, ALA dosage, baseline concentrations of the parameter, sample size, and gender were considered as possible sources of heterogeneity. In summary, ALA supplementation improves inflammatory markers without any evidence of non-linear association to dose or duration of the trial.


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