Folate and genistein cut disease risk, study finds

By Alex McNally

- Last updated on GMT

Maternal supplementation of a mixture containing folic acid and
vitamin B12 or genistein had a positive result on reducing disease
susceptibility in newborn mice, a study reports.

Researchers at Duke University Medical Centre and writing in the Proceedings of the National Academy looked at how to cut down the risk of the chemical bisphenol A (BPA), commonly used in the food packaging.

They were measuring the coat colour of infant rats from mothers which were given BPA with and without a supplementation.

The changing in coat colour indicated that a gene has been altered by BPA, without it being changed or mutated.

BPA is an additive widely used in plastic packaging and the resin linings of food cans.

It is also used in dental filling.

Other published studies have found that the chemical migrates in small amounts into food and beverages from packaging containing the substance.

This study adds not only more weight against the use of BPA but suggests a way of offsetting its negative effects.

It is of importance as some studies have found human exposure to the food packaging chemical is proportionately higher than levels found to have caused cancer in laboratory animals.

It also provides additional evidence that what a pregnant mother eats can make her offspring more susceptible to disease later in life.

The resarchers said that: "This study shows that maternal exposure to this endocrine-active compound shifted the coat color distribution of viable yellow agouti (A vy ) mouse offspring toward yellow by decreasing CpG methylation in an intracisternal A particle retrotransposon upstream of the Agouti gene… providing evidence that epigenetic patterning during early stem cell development is sensitive to BPA exposure.

"Moreover, maternal dietary supplementation, with either methyl donors like folic acid or the phytoestrogen genistein, negated the DNA hypomethylating effect of BPA.

Thus, we present compelling evidence that early developmental exposure to BPA can change offspring phenotype by stably altering the epigenome, an effect that can be counteracted by maternal dietary supplements."

The researchers found that BPA exposure in the womb caused noticeable changes in the offspring without altering any of the offspring's genes.

Additionally, the researchers discovered that administration of folic acid or genistein, an active ingredient in soy, during pregnancy protected the offspring from the negative effects of BPA.

Normally the mice used in the tests are slender and brown, the researchers found that when the mouse mothers received BPA, a statistically significant increase in the number of their offspring were born with a yellow coat.

Previous studies with these mice have shown that yellow agouti mice are at a much greater risk for diabetes, obesity and cancer.

The researchers said that as BPA is " ubiquitously present in the human population ", these findings " hold promise for reducing disease susceptibility by public health nutrition interventions."

In the tests, the researchers recorded that: "BPA-exposed offspring exhibited 27 _ 2.8% (n _ 73) methylation across the nine sites compared with 39 _ 2.6% (n _ 60) methylation in control offspring.

Thus, BPA-exposed offspring showed a significantly (P _ 0.004) decreased average percentage of cells methylated at these nine sites relative to that in control offspring."

Those on supplementation were given methyl donors with 4.3 mg of folic acid/kg diet; 0.53 g of vitamin B12/kg diet; 5 g of betaine/kg diet; 7.97 g of choline chloride/kg diet or genistein (250 mg/kg diet) two weeks before mating.

This produced an effect of negating BPA-induced DNA hypomethylation in the offspring and indicated that " maternal nutritional supplementation with methyl donors counteracted the hypomethylating effect of BPA ," they said.

However, they added that it was too early to determine what the levels of maternal BPA in humans would equal those that caused epigenetic changes seen in the mice.

The levels of BPA used in the current experiments were five times lower than that considered harmful for mice, showing that even a low exposure was able to cause noticeable effects in the offspring.

Source: Proceedings of the National Academy of Sciences Published online before print doi 10.1073/pnas.0703739104 Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development Authors: Dana Dolinoy, Dale Huang, and Randy Jirtle.

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