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Cochrane Database of Systematic Reviews

Provision of folic acid for reducing arsenic toxicity in arsenic-exposed children and adults

Overview of attention for article published in Cochrane database of systematic reviews, October 2021
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Title
Provision of folic acid for reducing arsenic toxicity in arsenic-exposed children and adults
Published in
Cochrane database of systematic reviews, October 2021
DOI 10.1002/14651858.cd012649.pub2
Pubmed ID
Authors

Sajin Bae, Elena Kamynina, Heather M Guetterman, Adetutu F Farinola, Marie A Caudill, Robert J Berry, Patricia A Cassano, Patrick J Stover

Abstract

Arsenic is a common environmental toxin. Exposure to arsenic (particularly its inorganic form) through contaminated food and drinking water is an important public health burden worldwide, and is associated with increased risk of neurotoxicity, congenital anomalies, cancer, and adverse neurodevelopment in children. Arsenic is excreted following methylation reactions, which are mediated by folate. Provision of folate through folic acid supplements could facilitate arsenic methylation and excretion, thereby reducing arsenic toxicity. To assess the effects of provision of folic acid (through fortified foods or supplements), alone or in combination with other nutrients, in lessening the burden of arsenic-related health outcomes and reducing arsenic toxicity in arsenic-exposed populations. In September 2020, we searched CENTRAL, MEDLINE, Embase, 10 other international databases, nine regional databases, and two trials registers. Randomised controlled trials (RCTs) and quasi-RCTs comparing the provision of folic acid (at any dose or duration), alone or in combination with other nutrients or nutrient supplements, with no intervention, placebo, unfortified food, or the same nutrient or supplements without folic acid, in arsenic-exposed populations of all ages and genders. We used standard methodological procedures expected by Cochrane. We included two RCTs with 822 adults exposed to arsenic-contaminated drinking water in Bangladesh. The RCTs compared 400 µg/d (FA400) or 800 µg/d (FA800) folic acid supplements, given for 12 or 24 weeks, with placebo. One RCT, a multi-armed trial, compared FA400 plus creatine (3 g/d) to creatine alone. We judged both RCTs at low risk of bias in all domains. Due to differences in co-intervention, arsenic exposure, and participants' nutritional status, we could not conduct meta-analyses, and therefore, provide a narrative description of the data. Neither RCT reported on cancer, all-cause mortality, neurocognitive function, or congenital anomalies. Folic acid supplements alone versus placebo Blood arsenic. In arsenic-exposed individuals, FA likely reduces blood arsenic concentrations compared to placebo (2 studies, 536 participants; moderate-certainty evidence). For folate-deficient and folate-replete participants who received arsenic-removal water filters as a co-intervention, FA800 reduced blood arsenic levels more than placebo (percentage change (%change) in geometric mean (GM) FA800 -17.8%, 95% confidence intervals (CI) -25.0 to -9.8; placebo GM -9.5%, 95% CI -16.5 to -1.8; 1 study, 406 participants). In one study with 130 participants with low baseline plasma folate, FA400 reduced total blood arsenic (%change FA400 mean (M) -13.62%, standard error (SE) ± 2.87; placebo M -2.49%, SE ± 3.25), and monomethylarsonic acid (MMA) concentrations (%change FA400 M -22.24%, SE ± 2.86; placebo M -1.24%, SE ± 3.59) more than placebo. Inorganic arsenic (InAs) concentrations reduced in both groups (%change FA400 M -18.54%, SE ± 3.60; placebo M -10.61%, SE ± 3.38). There was little to no change in dimethylarsinic acid (DMA) in either group. Urinary arsenic. In arsenic-exposed individuals, FA likely reduces the proportion of total urinary arsenic excreted as InAs (%InAs) and MMA (%MMA) and increases the proportion excreted as DMA (%DMA) to a greater extent than placebo (2 studies, 546 participants; moderate-certainty evidence), suggesting that FA enhances arsenic methylation. In a mixed folate-deficient and folate-replete population (1 study, 352 participants) receiving arsenic-removal water filters as a co-intervention, groups receiving FA had a greater decrease in %InAs (within-person change FA400 M -0.09%, 95% CI -0.17 to -0.01; FA800 M -0.14%, 95% CI -0.21 to -0.06; placebo M 0.05%, 95% CI 0.00 to 0.10), a greater decrease in %MMA (within-person change FA400 M -1.80%, 95% CI -2.53 to -1.07; FA800 M -2.60%, 95% CI -3.35 to -1.85; placebo M 0.15%, 95% CI -0.37 to 0.68), and a greater increase in %DMA (within-person change FA400 M 3.25%, 95% CI 1.81 to 4.68; FA800 M 4.57%, 95% CI 3.20 to 5.95; placebo M -1.17%, 95% CI -2.18 to -0.17), compared to placebo. In 194 participants with low baseline plasma folate, FA reduced %InAs (%change FA400 M -0.31%, SE ± 0.04; placebo M -0.13%, SE ± 0.04) and %MMA (%change FA400 M -2.6%, SE ± 0.37; placebo M -0.71%, SE ± 0.43), and increased %DMA (%change FA400 M 5.9%, SE ± 0.82; placebo M 2.14%, SE ± 0.71), more than placebo. Plasma homocysteine: In arsenic-exposed individuals, FA400 likely reduces homocysteine concentrations to a greater extent than placebo (2 studies, 448 participants; moderate-certainty evidence), in the mixed folate-deficient and folate-replete population receiving arsenic-removal water filters as a co-intervention (%change in GM FA400 -23.4%, 95% CI -27.1 to -19.5; placebo -1.3%, 95% CI -5.3 to 3.1; 1 study, 254 participants), and participants with low baseline plasma folate (within-person change FA400 M -3.06 µmol/L, SE ± 3.51; placebo M -0.05 µmol/L, SE ± 4.31; 1 study, 194 participants). FA supplements plus other nutrient supplements versus nutrient supplements alone In arsenic-exposed individuals who received arsenic-removal water filters as a co-intervention, FA400 plus creatine may reduce blood arsenic concentrations more than creatine alone (%change in GM FA400 + creatine -14%, 95% CI -22.2 to -5.0; creatine -7.0%, 95% CI -14.8 to 1.5; 1 study, 204 participants; low-certainty evidence); may not change urinary arsenic methylation indices (FA400 + creatine: %InAs M 13.2%, SE ± 7.0; %MMA M 10.8, SE ± 4.1; %DMA M 76, SE ± 7.8; creatine: %InAs M 14.8, SE ± 5.5; %MMA M 12.8, SE ± 4.0; %DMA M 72.4, SE ±7.6; 1 study, 190 participants; low-certainty evidence); and may reduce homocysteine concentrations to a greater extent (%change in GM FA400 + creatinine -21%, 95% CI -25.2 to -16.4; creatine -4.3%, 95% CI -9.0 to 0.7; 1 study, 204 participants; low-certainty evidence) than creatine alone. There is moderate-certainty evidence that FA supplements may benefit blood arsenic concentration, urinary arsenic methylation profiles, and plasma homocysteine concentration versus placebo. There is low-certainty evidence that FA supplements plus other nutrients may benefit blood arsenic and plasma homocysteine concentrations versus nutrients alone. No studies reported on cancer, all-cause mortality, neurocognitive function, or congenital anomalies. Given the limited number of RCTs, more studies conducted in diverse settings are needed to assess the effects of FA on arsenic-related health outcomes and arsenic toxicity in arsenic-exposed adults and children.

Twitter Demographics

The data shown below were collected from the profiles of 14 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 66 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 66 100%

Demographic breakdown

Readers by professional status Count As %
Unspecified 7 11%
Student > Master 6 9%
Researcher 6 9%
Student > Ph. D. Student 5 8%
Other 3 5%
Other 11 17%
Unknown 28 42%
Readers by discipline Count As %
Nursing and Health Professions 8 12%
Unspecified 7 11%
Medicine and Dentistry 5 8%
Environmental Science 4 6%
Social Sciences 3 5%
Other 9 14%
Unknown 30 45%

Attention Score in Context

This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 April 2022.
All research outputs
#4,278,558
of 22,173,707 outputs
Outputs from Cochrane database of systematic reviews
#6,631
of 12,202 outputs
Outputs of similar age
#110,524
of 425,668 outputs
Outputs of similar age from Cochrane database of systematic reviews
#41
of 51 outputs
Altmetric has tracked 22,173,707 research outputs across all sources so far. Compared to these this one has done well and is in the 80th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 12,202 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 29.9. This one is in the 45th percentile – i.e., 45% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 425,668 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 73% of its contemporaries.
We're also able to compare this research output to 51 others from the same source and published within six weeks on either side of this one. This one is in the 19th percentile – i.e., 19% of its contemporaries scored the same or lower than it.