Abuawad et al. 2023 - Folic acid and creatine effects on blood arsenic metabolites

Abuawad and colleagues analyzed blood arsenic metabolite outcomes from the Folic Acid and Creatine Trial in Bangladesh. Participants received folic acid, creatine, both, or placebo, and all participants also received arsenic-removal water filters at baseline. The source is intervention and exposure-biomarker evidence for arsenic methylation; it does not measure heavy-metal contamination in supplements or filter materials.

Key numbers

• Trial population: 622 recruited participants from Araihazar, Bangladesh, assigned to placebo, 400 ug folic acid/day, 800 ug folic acid/day, 3 g creatine/day, or 3 g creatine plus 400 ug folic acid/day.
• Eligibility required age 20-65 years and household well-water arsenic above 50 ug/L for at least one year.
• Baseline well-water arsenic geometric means across treatment groups ranged from 119 to 128 ug/L, about 12-15 times the WHO 10 ug/L guideline.
• Baseline folate status: 80.3% of participants were folate sufficient and 19.7% were folate deficient below 9 nmol/L plasma folate.
• Water-filter intervention: all participants received READ-F arsenic-removal filters at baseline; filters were repaired or replaced if field testing exceeded 10 ug/L arsenic or if participants reported failure. About 50 of 622 filters failed during the trial.
• Blood arsenic speciation method detection limits: 0.22 ug/L for As(III)+As(V), 0.22 ug/L for MMAs, and 0.22 ug/L for DMAs.
• Placebo example for water-filter effect: blood MMAs geometric mean +/- GSD decreased from 3.55 +/- 1.89 ug/L at baseline to 2.73 +/- 1.74 ug/L at week 1.
• Week 12 blood MMAs change from baseline: placebo -2.0% (95% CI -4.0, 0.0); 400 ug folic acid -10.3% (95% CI -11.9, -8.8); 800 ug folic acid -9.5% (95% CI -11.1, -8.0); creatine plus 400 ug folic acid -8.4% (95% CI -10.0, -6.9).
• Week 12 blood DMAs change from baseline: 400 ug folic acid +12.8% (95% CI 10.5, 15.2); 800 ug folic acid +11.3% (95% CI 8.9, 13.8); placebo -0.1% (95% CI -2.8, 2.6).
• The authors report that folic-acid groups had significantly greater decreases in primary methylation index and increases in secondary methylation index than placebo.
• In phase 2, participants switched from 800 ug folic acid to placebo had decreases in SMI of -9.0% (95% CI -3.5, -14.8) and blood DMAs of -5.9% (95% CI -1.8, -10.2), supporting reversibility after folic-acid cessation.

Methods (brief)

FACT was a randomized, double-blinded, placebo-controlled trial. In the first 12 weeks, participants received placebo, folic acid, creatine, or combined creatine plus folic acid. In the second 12 weeks, half of the folic-acid participants continued folic acid and half switched to placebo. Blood samples were collected at baseline and weeks 1, 12, and 24.

Arsenic species in blood and urine were measured by HPLC coupled to dynamic reaction cell ICP-MS. The method reports total inorganic arsenic as As(III)+As(V) because sample processing can oxidize species, and it reports total MMAs and total DMAs because it cannot differentiate reduced and oxidized forms of those metabolites.

Implications

Certification: This paper should not enter any supplement or water-filter product occurrence pool. It supports mitigation and exposure-biomarker context: folic acid and creatine altered arsenic methylation markers in exposed adults, while water filters likely reduced blood arsenic metabolites across all groups.

Courses: Useful example of a human intervention study where lower-risk interpretation depends on arsenic speciation, one-carbon metabolism, and concurrent source control through filters.

App: The source does not justify consumer-facing supplement advice by itself. It can support future educational content that arsenic exposure mitigation includes both source removal and nutritional status, under clinician/public-health context.

Microbiome: No microbiome findings.

Wiki pages this source may touch

• formulation
• remediation-evidence
• supplements-vitamin-mineral
• supplements-amino-acids-isolates
• water-filters
• arsenic-inorganic
• arsenic-total

Verification notes

• DOI, title, authors, journal, year, trial size, intervention arms, baseline water arsenic range, filter protocol, arsenic speciation method, and blood metabolite changes were transcribed from the PDF.
• The auto-fetch filename mapped this source to water filters. The PDF is mainly a folic-acid/creatine supplementation trial, with water filters provided to all arms as exposure-source control.
• The page keeps inorganic arsenic, MMAs, and DMAs as blood/urine biomarkers. It does not treat changes in blood metabolites as product contamination values.

Page history

The five most recent substantive edits to this page. The full version history lives in git; when DOI minting comes online (see schema docs), each entry below will also link to a version-pinned DataCite DOI.