Creatine and folic acid for arsenic methylation in Bangladeshi adults
What it found
In adults exposed to arsenic in drinking water, creatine supplements lowered a form of arsenic in blood called MMAs, but the effect was smaller than that of folic acid.
Folic acid also raised DMAs and improved methylation indices.
What they found
Studies in people
Blood MMAs decreased
After 12 weeks, blood MMAs decreased more in all treatment groups than in the placebo group. The decrease was about 10% for folic acid groups, 6% for creatine alone, and 8% for creatine plus folic acid, compared with 2% for placebo.
Blood DMAs increased
Blood DMAs increased by about 13% with 400 micrograms folic acid and 11% with 800 micrograms folic acid, while it barely changed with placebo. Creatine alone did not significantly raise DMAs.
Methylation indices improved
The primary methylation index (PMI) decreased and the secondary methylation index (SMI) increased more in all folic acid groups than in placebo. Creatine alone also increased SMI compared with placebo.
Creatine effect smaller
Creatine supplementation alone lowered blood MMAs and increased SMI, but the effect was smaller than that of folic acid. There were no significant changes in blood InAs, blood DMAs, or PMI with creatine alone.
Effect reversed after stopping
When participants who had been taking 800 micrograms folic acid switched to placebo for the second 12 weeks, their SMI and blood DMAs decreased, suggesting the benefits wear off without continued supplementation.
Sex difference in creatine
In exploratory analyses, creatine supplementation significantly lowered blood MMAs and increased SMI in male participants compared with placebo, but not in female participants. The authors note the study was not designed to test sex differences.
What the authors conclude
“FA supplementation lowered bMMAs and increased bDMAs in a sample of primarily folate-replete adults, whereas creatine supplementation lowered bMMAs.”
Also in their conclusions
- They conclude that folic acid supplementation increased arsenic methylation capacity, as shown by larger decreases in PMI and MMAs and increases in SMI and DMAs in blood compared with placebo.
- They state that creatine supplementation lowered blood MMAs, but the effect was small compared with folic acid.
- They suggest that sustainable improvement in arsenic methylation may require long-term interventions such as food fortification with folic acid.
How it was done
The authors wanted to see whether folic acid, creatine, or both could help the body methylate arsenic, a process that may reduce the risk of arsenic-related health problems.
They randomly assigned 622 Bangladeshi adults exposed to arsenic in well water to one of five groups: placebo, 400 micrograms folic acid daily, 800 micrograms folic acid daily, 3 grams creatine daily, or 3 grams creatine plus 400 micrograms folic acid daily, for 12 weeks. All participants received arsenic-removal water filters. Blood arsenic metabolites were measured at weeks 0, 1, 12, and 24.
What it can’t tell you
- This trial measured arsenic metabolites in blood over 24 weeks. It cannot show whether these changes lead to fewer arsenic-related diseases like cancer or skin lesions.
- The study was done in Bangladeshi adults exposed to high arsenic in drinking water. The results may not apply to other populations or to people with different folate levels.
- The trial was not designed to test differences between men and women, so the apparent sex difference in creatine response needs more research.
Who paid
- Funding
- Funded by Intramural NIH HHS; NIEHS NIH HHS; NCI NIH HHS; NIGMS NIH HHS (from the PubMed record).
- Authors work at
- Columbia University, USA; University of California, USA; Columbia University Arsenic Project in Bangladesh, Bangladesh
The paper
- Title
- The Folic Acid and Creatine Trial: Treatment Effects of Supplementation on Arsenic Methylation Indices and Metabolite Concentrations in Blood in a Bangladeshi Population
- Type
- Randomised controlled trial
- Evidence
- Studies in people
- Summarised from
- Full text
- Licence
- Public domain. Words in quotation marks are the authors’; the rest is our summary.
- Cite
- Abuawad AK, Bozack AK, Navas-Acien A, et al (2023). The Folic Acid and Creatine Trial: Treatment Effects of Supplementation on Arsenic Methylation Indices and Metabolite Concentrations in Blood in a Bangladeshi Population. Environmental health perspectives. doi:10.1289/EHP11270Free full textPubMed 36976258DOI
Summary written 29 Sep 2026. Check it against the paper before it changes what you eat. How we summarise papers · Report an error