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Folic acid supplements could boost DNA repair, says study

By Stephen Daniells , 21-Jun-2006

Daily folic acid supplements could improve DNA stability and reduce the risk of certain cancers linked to faults in the genetic code, suggests new research.

"To our knowledge, this is the first human study to determine the effects of folate supplementation on DNA repair. DNA repair is crucial in maintaining genomic stability and compromised DNA repair is associated with increased risk of malignancy," wrote lead author Graham Basten from the University of Sheffield.

Folate deficiency has previously been linked to an increased risk of precancerous lesions that could lead to a variety of cancers, including breast, colorectal, pancreatic, and lung.

The randomised, double-blind, placebo-controlled study, published in the British Journal of Cancer (Vol. 94, pp. 1942-1947), was carried out with 61 healthy volunteers (31 women) with an average age of 41.

Volunteers were assigned to receive daily folic acid supplements of 1.2 milligrams or a glucose placebo for 12 weeks. The folic acid dose is significantly higher than the RDI in both the UK and the US (200 micrograms), but significantly lower than the pharmacological doses used in many clinical trials.

Blood samples were taken to measure the red cell folate (RCF) levels, and all subjects had RCF levels of between 250 and 650 nanomoles per litre, meaning no-one was folate deficient (less than 200 nanomoles per litre).

The blood samples were also used to measure the stability of DNA in lymphocytes.

In agreement with previous work by the same group, the folic acid supplementation resulted in significant increases in the RCF levels, as well as the folate derivative 5-methyltetrahydrofolate (5-MeTHF). They also reported increases in S-adenosylmethionine (SAM) levels, a compound that is involved in the stability of DNA.

The researchers also made a link between RCF levels and misincorporation of the DNA base, uracil. Misincorporation of uracil is associated with the formation of DNA fragments that are said to promote cancer development.

"There was a strong correlation between the magnitude of lymphocyte total folate and reduction in lymphocyte DNA uracil misincorporation," reported the researchers.

The most significant effects were observed for those with the lowest RCF values, leading the researchers to say that the activity of DNA repair may not be altered by upping the folate intakes for people with adequate folate levels.

However, the intervention appeared to have no impact on other markers of DNA instability, namely DNA strand breaks and global DNA methylation.

"Uracil misincorporation is evidently more sensitive to improved folate status in healthy individuals than other putative biomarkers of DNA damage or repair, and may, therefore, be considered a valid and functional biomarker for the influence of folate on genomic stability in health people," concluded the researchers.

The mechanism behind the observed effects is not currently known and remains to be established, said the researchers.

Josephine Querido, science information officer at Cancer Research UK, told that although there was relatively strong eveidence that folate-rich foods were linked to a lower risk of certain cancer, it is still not clear if supplements could give the same benefits.

"Folate is a B vitamin found in green and leafy vegetables. It is needed in the body to make and repair DNA. This is important as damage to a cell's DNA can lead to cancer," she said.

Folate, the natural form of the B vitamin, can be found in foods such as liver, eggs, beans, whole grains, and green leafy vegetables. Folic acid is the synthetic form used for food fortification and in supplements.

Studies have shown that folic acid is more easily absorbed from fortified foods (85 percent) and supplements (100 percent) than the folate found naturally in foods (50 percent).

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