Supplement timing

[Guest guest]

Hi All,

It may matter when supplements are taken for their effectiveness.

Science 16 December 2005: Vol. 310. no. 5755, p. 1761

News Focus

ENVIRONMENTAL EPIGENOMICS MEETING:

Supplements Restore Gene Function via Methylation

Pennisi

DURHAM, NORTH CAROLINA

--Geneticists, molecular biologists, and epidemiologists discussed epigenetics

from

2 to 4 November at the Environmental Genomics, Imprinting, and Disease

Susceptibility conference.

It has long been known that pregnant women who consume insufficient folic acid,

a B

vitamin, run an increased risk of having babies with spina bifida or similar

neural

tube defects. Yet biologists are still teasing out exactly what this vitamin

does

for the developing fetus. At the meeting, Waterland, an epigeneticist at

Baylor College of Medicine in Houston, Texas, presented evidence from mice that

methylation of DNA--a chemical modification that can shut down genes--can be

key.

Folic acid does restore gene function in mutant mice that have improper DNA

methylation patterns, the researcher reported. However, Waterland has also found

that the supplement-induced changes in DNA methylation might not be all that

predictable--they appear to occur at different points in time during embryonic

development and to affect only specific tissues, he reported.

These mouse results may have implications for supplement use in both pregnant

women

and the public at large. " People are taking massive quantities of vitamins, and

we

don't have any idea what these potential methyl donors are doing, " says Adele

Murrell, a geneticist at the University of Cambridge, U.K.

[Figure] Straighten out. Methylation stimulated by supplements helps unkink the

tails of mutant mice.

CREDIT: R. WATERLAND/BAYLOR COLLEGE OF MEDICINE

Waterland first observed the embryonic impact of folic acid and other methyl

donors

2 years ago, while working with Randy Jirtle at Duke University in Durham, North

Carolina. At that time, he examined a strain of off-colored mice that has a

defect

in a pigment gene called agouti--the gene is defective because a mobile bit of

DNA

called a transposable element had inserted itself in some of the nearby DNA that

regulates the gene's expression. The transposable element short-circuits

methylation

of this regulatory region, causing the gene to be overactive. As a result,

yellow or

mottled coats are common in these animals. But litters born to dams fed

supplements

of folic acid, a rich source of methyl groups, were primarily the typical brown.

Waterland and his colleagues subsequently found that the supplements caused an

increase in the density of methyl groups on and around the agouti gene,

overriding

the transposable element's effects.

Waterland has since investigated a gene that may be more relevant to human

disease.

The axin gene helps set up the dorsal-ventral axis in embryos and also requires

methylation to work properly. Many mice with an axin disrupted by a transposable

element embedded in it typically develop mild to tightly angled kinks in their

tails. Again, methyl donors can come to the rescue. Waterland reported that

receiving folic acid supplements during pregnancy reduced by half kinking in the

pups' tails. Taken together, " Waterland's data are the most convincing positive

finding with respect to whether diet has any effect on the methylation patterns

and

expression of a particular [gene], " says Carmen Sapienza, a geneticist at Temple

University in Philadelphia, Pennsylvania.

Folic acid supplementation altered the methylation of the two genes in different

ways, however, illustrating the complexity of the phenomenon. In the agouti

mice,

the supplements increased methylation of the gene in a variety of tissues, and

the

change was most pronounced early in pregnancy. But in the case of the axin mice,

that gene's methylation remained low early in pregnancy and only increased later

on,

as the tail formed, Waterland reported. Moreover, the increase occurred only in

the

tissue giving rise to the tail. These two observations suggest to him that DNA

methylation produced by vitamin supplementation can be tissue-specific and,

depending on the gene involved, can occur at different times over the course of

a

pregnancy.

Waterland's research may one day lead to more sophisticated timing of when to

give

vitamin supplements to pregnant women or anyone else. " If we can understand

critical

windows and when methylation is beneficial, " says Stover, a nutritional

biochemist at Cornell University, " that would totally change the concept of how

we

set dietary requirements during pregnancy and how we think about preventive

medicine. "

Al Pater, PhD; email: old542000@...

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