Doctors at the University Of Colorado Are Testing Choline (taken during pregnancy by the mother) to Prevent Mental Illness in the children.

A popular word at the University of Colorado Denver's Department of Psychiatry is "choline," a nutrient found in many of our foods, but not prenatal supplements.

Researchers believe choline may be a missing link when it comes to preventing mental illness in the womb, helping developing brain cells become stable and properly communicate with one another.

"We've looked at it specifically for its ability to help a brain develop resistance to mental illness," said Dr. Randy Ross, the study's lead investigator.

In this new study Moms-to-be take three capsules of choline two times a day during pregnancy. After birth, children are observed for 18 months to document motor skill, problem solving and language development.

This same group of researchers has already published research on animals that demonstrated that Choline during pregnancy seemed to prevent many of the brain changes that are common in young rodents that are predisposed to "mental illness" (see links below for this research). 

Source: University of Denver Choline during Pregnancy Study, ClinicalTrials.gov

Animal Studies that have shown how choline during pregnancy may prevent mental illness:

Permanent improvement in deficient sensory inhibition in DBA/2 mice with increased perinatal choline.

Perinatal choline deficiency produces abnormal sensory inhibition in Sprague-Dawley rats.

Research into choline and epigenetics is expanding rapidly.  Today there was an announcement by the Welcome Trust in the UK of a new study on how dietary factors (including choline) during pregnancy, impact the long term health of the baby.  I'm sure we'll see a lot more of these over the coming decade. 

Here is the news release:

Experiment of nature' examines how mother's diet may impact on child's health

Could our mother's diet at the time we are conceived set the course for our future health? This intriguing question is at the heart of a new study based on an "experiment of nature" being conducted by Wellcome Trust-funded researchers.

We inherit our DNA the genetic blueprint that determines our make-up from our parents: 50% of our DNA from our mothers and 50% from our fathers. Apart from the occasional mutation, deletion or duplication of information, this DNA remains unchanged between generations.

The environment, for example our diet, whether we smoke, and the toxins that we encounter in our daily life, can cause changes in how our genes are expressed in other words, how they function and these changes can be inherited, even when the DNA sequence itself does not change. These so-called "epigenetic" effects can occur through a process known as DNA methylation, where methyl caps bind to our DNA and act like dimmer switches on our genes.

Now, Dr Branwen Hennig and colleagues from the Medical Research Council (MRC) International Nutrition Group based at the London School of Hygiene and Tropical Medicine have been awarded 360,000 from the Wellcome Trust to look at whether a mother's diet during pregnancy can influence these epigenetic effects.

The study will be conducted at the MRC Laboratories in Keneba, The Gambia, where the seasonal variability of food provides the ideal environment to conduct an "experiment of nature".

"During the 'hungry season' people eat mainly what they have in store, such as cereals and dried food," explains Ms Paula Dominguez-Salas, who will conduct the fieldwork in The Gambia. "They are working in the fields and have a very high energy expenditure, but their intake is very low. The 'harvest season' is the other way round and food, including fresh foods, is in relatively plentiful supply."

The researchers will measure the diets of women in early pregnancy for nutrients which affect methylation, such as folate and choline, and some B vitamins which are essential co-factors in methylation. They will compare these to levels of the nutrients in the women's blood and once the children have been born, the researchers will measure methylation patterns of the babies' DNA. This will help the researchers assess whether there is a correlation between the mother's diet and her nutritional status, and whether there are differences in methylation patterns in babies conceived during the harvest or hungry seasons.

If a mother's diet does affect her offspring's methylation patterns, this could prove very important as epigenetic changes mediated by DNA methylation are likely to have long term effects on the health and physical characteristics of offspring. Animal studies have shown that supplementing the diet of pregnant mice can lead to very marked differences in their offspring with mice fed a folate-depleted diet producing litter with different coat colour or "kinked" tails compared to those fed a diet rich in folate.

"Alterations in DNA methylation are thought to increase the risk of a child developing chronic conditions later in life, such as cardiovascular disease, cancers and type II diabetes," says Dr Hennig. "We think these epigenetic changes are established very early on in the womb."

This will be the first time that the effects of a mother's diet on epigenetic alterations of her children will be studied so extensively. A study published recently in the Proceedings of the National Academy of Sciences looked at the effect of wartime blockades in the Netherlands on the nutritional intake of mothers and whether this affected their children's expression of the IGF2 gene, which is involved in growth, as adults. It found that the IGF2 gene had 5 per cent fewer methyl caps in "famine babies" than in their siblings born outside this period. However, the study by Dr Hennig and colleagues will enable the researchers to accurately measure maternal nutritional intake and compare this to methylation patterns in their children.

The study has been welcomed by Dr Alan Schafer, Head of Molecular and Physiological Sciences at the Wellcome Trust.

"This is a very interesting and exciting area of research," says Dr Schafer. "Finding a link between these women's diet and epigenetic changes could ultimately have important implications for our understanding of long term health effects and advice on healthy eating."

Source; Welcome Trust

At a talk at the Oregon Health Sciences University in May, 2007 - one of the top researchers who is focused on Choline (Dr. Steven Zeisel, University of North Carolina) spoke. 

"Dr. Zeisel pointed out that choline is very important for the fetal brain, and can be obtained as a supplement as phosphatidyl choline [obtained via Lecithin].  2-4 eggs per day provide enough choline during pregnancy.  The current daily value is 450 mg, but it would be useful to set the level at 850 mg.   It is like fish oil, having lifelong effect on an infant's early brain development. "

There is an ongoing human study on choline in babies right now - where they are using 900mg doses (in the pregnant mothers).  The US Food and Nutrition Board, Institute of Medicine in 1998 came out with a report on choline that suggested the maximum tolerable limit for adults (including pregnant women) is 3.75 grams/day (which is 50% of the level (7 grams/ day) at which researchers had seen any possible negative symptoms in studies.

People I have shared this information with have supplemented their diet (during pregnancy) with between 500mg and 4 grams per day, without any obvious negative symptoms - but the children are still young.  One of the biggest risk factors in this is the quality of the supplements that people take and the risk of possible contamination of the supplements.  Because of this - the researchers I've talked to tend to recommend eggs as the best source of choline (though one researcher recommended high quality Lecithin as a good source).  

Source: (Linus Pauling Institute meeting, May 2007) Medical Doctor's Research

You can read more about Choline here at the Linus Pauling Institute web site - Choline details

This posting isn't about choline, but rather on the general topic of how vitamins consumed by children may impact intelligence.  A news item in Medscape.com last May seems to have gotten much less press than I would have thought.  The news item claims:

This month's American Journal of Clinical Nutrition had a number of new papers on the topic of pregnancy and choline consumption.

The paper seems to be an effort by Dr. Zeisel, professor at the University of North Carolina, to help increase the visibility of Choline with other researchers.

In the paper, Dr. Zeisel notes:

"Evidence is growing that optimal dietary intake of folate and choline (both involved in one-carbon transfer or methylation) is important for successful completion of fetal development. Significant portions of the population are eating diets low in one or both of these nutrients.

Folates are important for normal neural tube closure in early gestation, and the efficacy of diet fortification with folic acid in reducing the incidence of neural tube defects is a major success story for public health nutrition. Similarly, maternal dietary choline is important for normal neural tube closure in the fetus and, later in gestation, for neurogenesis in the fetal hippocampus, with effects on memory that persist in adult offspring; higher choline intake is associated with enhanced memory performance."

Importantly, he notes, there is a wide variation in the amount of choline that people have in their diet (typically a variation of 3 to 4 fold)  and that in several studies it has been shown that  25% of women got less than the 6.7 mg/kg levels that are considered minimal.  Add to this the fact that different genetic makeup of people, means that different people need different levels of choline - and as of yet, there is no way to test for these genetic variations (or SNPs) - so its impossible for a person to know if they are getting enough (or their baby is getting enough) choline.

In the paper, Dr. Zeisel notes that "Changes in dietary availability of methyl groups induces stable changes in gene methylation, altering gene expression and resulting phenotype...Many of the changes in neurogenesis (the improved memory, etc.) caused by altered availability of dietary choline or folate during pregnancy are probably mediated by altered DNA methylation."

Interestingly, recent research has shown that "stress" that mammals (including humans) is a very effective at de-methylating DNA - and this is believed to be one of the leading contributors to mental illness - because the de-methylation exposes unhealthy genes that are the ultimate cause of a significant portion of the cases of mental illness.

I expect to see much more research in the area of how choline and other methy-donor supplementation during pregnancy may help reduce the risk of mental illness later in life.  As I've mentioned elsewhere in this blog, data from rodent studies and choline are already showing that this seems to be the case.  

In a second paper in this issue of the journal, Dr. Zeisel poses the question of whether supplementation for women of key brain-related nutrients like Choline is something that should be considered more. 

As he states:

"during perinatal development in which specific nutrients are required for optimal development, and there is growing evidence that optimal dietary intake of these nutrients, which include iodine, docosahexaenoic acid, choline, and folate, is important. ... For some of the nutrients discussed, such as iodine and folate, the effects in humans are abundantly clear; for others, animal data are the most convincing. More human studies need to be conducted."

My understanding is that human studies are currently underway for choline and prenatal supplementation.  One researcher I had lunch with noted that its his belief (and he's been researching choline for the past decade) is that EVERY woman should supplement with as much choline as she can.  He thought the research (which now numbers over 40 studies on the impact of Choline on the brain, done over the past 25 years) was already that compelling (and I tend to agree with him).  He was also disappointed with the pace of research being done in this area, as it seems to be the one of the most important areas of nutritional and prenatal development today.

Other researchers are much more cautious - as Dr. Zeisel noted at the end of the paper:

"It is clear that the dietary manipulation of methyl donors (either deficiency or supplementation) can have a profound effect on reproductive outcome through epigenetic mechanisms. For this reason, it is important that expert panels carefully consider recommendations for dietary intake of methyl donors during pregnancy."

 
See the research papers here:

Importance of methyl donors during reproduction (Steven Zeisel), American Journal of Clinical Nutrition

Is maternal diet supplementation beneficial? Optimal development of infant depends on mother's diet

(Steven Zeisel), American Journal of Clinical Nutrition