Folic acid supplements dramatically lower blood arsenic levels

Arsenic is a toxic element that is naturally present in some soils and water. Arsenic-contaminated drinking water is currently a significant public health problem in at least 70 countries, including several developing countries and also parts of the United States. Chronic arsenic exposure is associated with increased risk for skin, liver and bladder cancers, skin lesions, cardiovascular disease, and other adverse health outcomes. The study was funded by the National Institute of Environmental Health Sciences (NIEHS) at the National Institutes of Health (NIH).

Researchers found that treatment with 400 micrograms a day of folic acid, the U.S. Recommended Dietary Allowance, reduced total blood arsenic levels in a Bangladesh study population by 14%. Folate is a B vitamin found in leafy vegetables, citrus fruits, beans, and whole grains. Folic acid can also be taken as a vitamin supplement, and in the United States, it is added to flour and other fortified foods. The researchers found that folate deficiency is very common in Bangladesh, where the study was conducted, but is not as problematic in the United States due to folate fortification. Additional studies are needed to determine if folic acid similarly lowers blood arsenic in populations where folate deficiency is less common, such as in the United States.

Support

William Suk, Ph.D., Acting Deputy Director of the NIEHS discussed the significance of this work in Bangladesh to the U.S. He explains that arsenic contamination of groundwater is one of the five most common inorganic compounds found at Superfund sites and is present at over 70% of the sites. Because of the prevalence of arsenic, the SBRP has placed an emphasis on supporting arsenic-related research in heavily affected areas all over the world to understand and mitigate the health issues arising from arsenic exposure via drinking water. This research is already demonstrating its relevance to exposures that are occurring in the United States.

Clearly the first priority should focus on mitigation efforts to lower arsenic exposure. But this is a very exciting and significant finding, and implies that folic acid has therapeutic potential for people who have been exposed to arsenic. Said Mary Gamble, Ph.D., a researcher at Columbia University and the lead author on the study that was funded by the NIEHS. Although additional studies are needed, the results of this study suggest that a simple, low-cost nutritional intervention may help to prevent some of the long-term health consequences associated with arsenic exposure for the many populations at risk.

Folic acid supplementation enhanced the detoxification of arsenic to a form that is more readily excreted in urine, said Gamble. The study results are published in the October issue of the American Journal of Clinical Nutrition. The study is jointly supported through NIEHS and the Superfund Basic Research Program (SBRP).

Gamble explains how this detoxification process is able to lower the levels of arsenic found in the blood. She explains how the folic acid increased the methylation or detoxification of arsenic in the body, allowing the body to change some of the more toxic metabolite, or methylarsonic (MMA) acid, to a form that could more easily be excreted from the body.

Millions affected

Chronic arsenic exposure currently affects 100 million persons worldwide, including populations in Bangladesh. The arsenic levels in drinking water in some parts of Bangladesh reach as high as 100 times the World Health Organization and the US Environmental Protection Agency (EPA) guidelines, which set a limit of 10 micrograms per litre for arsenic in drinking water.

The initial supplement study included 200 folate-deficient participants drawn from a larger cohort study in Bangladesh examining the adverse health effects of arsenic. Study participants received either a daily tablet of 400 micrograms per day of folic acid or a placebo for twelve weeks. The researchers collected blood and urine samples at the beginning and end of the study. Dr. Gamble pointed out that, the technology to measure arsenic in blood, and particularly to measure the individual arsenic metabolites in blood, didn't exist when the studies were first planned. She credits the advanced technology to recent advances in other laboratories at Columbia, including work conducted by Superfund grantee Joseph H. Graziano, Ph.D., a co-author on the study.

"The work that our grantees are doing in Bangladesh is extraordinary," said Claudia Thompson, Ph.D., acting director of the SBRP. Not only is the research they are conducting improving the quality of life for the people in Bangladesh, but it can potentially help the more than 100 million people worldwide that are chronically exposed to arsenic.

Elevated risk
The authors also stress that the study results imply that folic acid supplementation may help to reduce body stores of arsenic even after exposure has been eliminated. Elevated risk for adverse health outcomes persists for decades after exposure has ceased. Additional studies are needed, the researchers add, including, for example, studies to determine the optimal dose and duration of treatment, and studies that include health outcomes.

The National Institute of Environmental Health Sciences (NIEHS), a component of the National Institutes of Health, supports research to understand the effects of the environment on human health. For more information on environmental health topics, please visit our website at http://www.niehs.nih.gov/.

Superfund Basic Research Program (SBRP) is a network of university grants that are designed to seek solutions to the complex health and environmental issues associated with the nation's hazardous waste sites. The research conducted by the SBRP is a coordinated effort with the Environmental Protection Agency, which is the federal entity charged with cleaning up the worst hazardous waste sites in the country. The SBRP is federally funded and administered by the National Institute of Environmental Health Sciences, an institute of the National Institutes of Health. http://www.niehs.nih.gov/research/supported/sbrp/index.cfm.

The SPRP will hold its 20th anniversary annual meeting, "20 Years of Success and a Vision for the Future," in Durham, North Carolina, December 3-5, 2007. Visit http://tools.niehs.nih.gov/sbrp/events/index.cfm?id=23 for more information.

The National Institutes of Health (NIH) - The Nation's Medical Research Agency - includes 27 Institutes and Centres and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov

Reference: Gamble MV, Liu X, Slavkovich V, Pilsner J, Ilievski V, Factor-Litvak P, Levy D, Alam S, Islam M, Parvez F, Ahsan H, Graziano J. Folic Acid Supplementation Lowers Blood Arsenic. Am J Clin Nutr 86:1202-1209 (2007). Supported by grants RO1 ES011601 and P42 ES10349 from the NIEHS.