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

This new intervention review assessed the effects of the provision of folic acid through fortified foods or supplements, alone or plus other nutrients, in lessening the burden of arsenic-related health outcomes and reducing arsenic toxicity in arsenic-exposed populations.

Results

The review included two randomised controlled trials (RCTs), involving 822 adults who had been exposed to arsenic-contaminated drinking water in Bangladesh. One RCT compared 400 µg/d or 800 µg/d folic acid supplements, given for 12 or 24 weeks, with placebo. The other, a multi-armed trial, compared folic acid supplements (400 µg/d) plus creatine (3 g/d) to creatine alone.

The review authors judged both RCTs to be at low risk of bias in all domains. Due to differences in co-intervention, arsenic exposure, and nutritional status of participants, they did not conduct a meta-analysis but instead provided a narrative description of the data.

Folic acid supplements alone versus placebo

For this comparison, the review authors found evidence that, in arsenic-exposed individuals:

  • folic acid supplementation likely reduces blood arsenic concentrations compared to placebo (2 studies, 536 participants; moderate-certainty evidence);
  • folic acid supplementation likely reduces the proportion of total urinary arsenic excreted as inorganic arsenic (InAs) concentrations and monomethylarsonic acid (MMA) concentrations and increases the proportion excreted as dimethylarsinic acid (DMA) concentrations to a greater extent than placebo (2 studies, 546 participants; moderate-certainty evidence), suggesting that folic acid supplementation enhances arsenic methylation; and
  • folic acid supplementation (400 µg/d) likely reduces homocysteine concentrations to a greater extent than placebo (2 studies, 448 participants; moderate-certainty evidence), in a mixed folate-deficient and folate-replete population receiving arsenic-removal water filters as a co-intervention.

Folic acid supplements plus other nutrient supplements versus nutrient supplements alone

For this comparison, the review authors found evidence that, for arsenic-exposed individuals who received arsenic-removal water filters as a co-intervention, folic acid supplementation (400 µg/d) plus creatine:

  • may reduce blood arsenic concentrations more than creatine alone (1 study, 204 participants; low-certainty evidence);
  • may not change urinary arsenic methylation indices (i.e. proportion excreted as InAs, MMA, and DMA) more than creatine alone (1 study, 190 participants; low-certainty evidence); and
  • may reduce homocysteine concentrations to a greater extent than creatine alone (1 study, 204 participants; low-certainty evidence).

Neither RCT reported on cancer, all-cause mortality, neurocognitive function, or congenital anomalies.

The evidence is current to September 2020.

Conclusions

The review authors concluded that there is:

  • moderate-certainty evidence that folic acid supplements may benefit blood arsenic concentration, urinary arsenic methylation profiles, and plasma homocysteine concentration versus placebo; and
  • low-certainty evidence that folic acid supplements plus other nutrients may benefit blood arsenic and plasma homocysteine concentrations versus nutrients alone.

The review highlights the need for more studies conducted in diverse settings to assess the effects of folic acid on arsenic-related health outcomes and arsenic toxicity in arsenic-exposed adults and children.

Read the full review here on the Cochrane Library.