Recently in Prenatal Choline Research Study Category

More good news about taking choline during pregnancy.  A new research study out of Cornell University showed that in a mouse model of down syndrome (a mouse that is genetically designed to develop downs syndrome like disease) the pregnant and lactating mice that received additional choline had babies that fared much better than those whose mother's did no receive choline. 

More choline during pregnancy and nursing could provide lasting cognitive and emotional benefits to individuals with Down syndrome and protect against neurodegenerative conditions such as Alzheimer's disease, suggests a new Cornell study of mice.

The findings, published June 2 in Behavioral Neuroscience, could help lead to increasing the maternal dietary recommendations for choline (currently 450 milligrams a day during pregnancy, 550 milligrams for lactation), a nutrient found in egg yolks, liver, nuts and such vegetables as broccoli and cauliflower.

"We found that supplementing the maternal diet with additional choline resulted in dramatic improvements in attention and some normalization of emotion regulation in a mouse model of Down syndrome," said lead author Barbara Strupp, professor of nutritional sciences and of psychology. The researchers also found evidence for "subtle, but statistically significant, improvement in learning ability in the non-Down syndrome littermates."

In addition to mental retardation, Down syndrome individuals often experience dementia in middle age as a result of brain neuron atrophy similar to that suffered by people with Alzheimer's disease. Strupp noted that the improved mental abilities found in the Down syndrome mice following maternal choline supplements could indicate protection from such neurodegeneration "in the population at large."

Strupp and her co-authors tested Down syndrome model mice born from mothers fed a normal diet and those given choline supplements during their three-week pregnancy and three-week lactation period, as well as normal mice born from mothers with and without additional choline. The choline-supplemented mothers received approximately 4.5 times more choline (roughly comparable to levels at the higher range of human intake) than unsupplemented mothers.

At six months of age, the mice performed a series of behavioral tasks for about six months to assess their impulsivity, attention span, emotion control and other mental abilities.  

In addition to dramatic improvements in attention, the researchers found that the unsupplemented Down syndrome model mice became more agitated after a mistake than normal mice, jumping repeatedly and taking longer to initiate the next trial, whereas the choline-supplemented Down syndrome model mice showed partial improvement in these areas.

"I'm impressed by the magnitude of the cognitive benefits seen in the Down syndrome model mice," Strupp said. "Moreover, these are clearly lasting cognitive improvements, seen many months after the period of choline supplementation."

Strupp noted that the results are consistent with studies by other researchers that found increased maternal choline intake improves offspring cognitive abilities in rats. However, this is the first study to evaluate the effects of maternal choline supplementation in a rodent model of downs syndrome.  This is also one of the few studies that has evaluated offspring attentional function and effects in mice, rather than rats, Strupp noted.

Previous studies of humans and laboratory animals have shown that supplementing the diets of adults with choline has proven to be largely ineffective in improving cognition. "Although the precise mechanism is unknown, these lasting beneficial effects of choline observed in the present study are likely to be limited to increased intake during very early development," Strupp said.

Source: Cornell University

Choline is being increasingly identified as a key nutrian for a child's healthy brain development during pregnancy. 

A newborn's risk for brain and spinal-cord defects rises if the mother has low blood levels of the nutrient choline during pregnancy, researchers at the Stanford University School of Medicine have discovered.

The scientists used a collection of 180,000 blood samples from pregnant California women to look for risk factors for two neural tube birth defects: anencephaly, a lethal condition in which the brain and skull do not develop, and spina bifida, a spinal-cord malformation that causes paralysis and lifelong disability. Neural tube defects have become less common since the 1996 decision to fortify the U.S. food supply with folic acid, a B-vitamin shown to prevent the defects, but they have not disappeared.

"Families whose infants die or suffer permanent disability from NTDs still feel the burden of these defects," said Gary Shaw, DrPH, professor of neonatology and primary author of the new research, which will appear Aug. 14 in Epidemiology.

About 500 pregnancies per year are affected by neural tube defects in California alone, noted Shaw. "We're keen on understanding what risk factors explain the continued disease."

Shaw's study targeted a group of nutrients suspected to promote brain and spinal-cord development. In early pregnancy, a sealed tube forms along the embryo's back that later grows into the brain and spinal cord. Neural tube defects occur if the tube does not seal correctly. Based on prior research on folic acid, scientists believe that development of the neural tube may depend on a specific biochemical pathway that requires several vitamins and essential nutrients to operate properly. Shaw's team measured blood levels of 13 of these nutrients in two groups of women who participated in California's prenatal birth-defect screening program.

From 180,000 pregnant women screened between 2003 and 2005, the researchers identified 80 whose pregnancies were affected by neural tube defects. Their blood samples were compared to 409 samples randomly selected from among the women whose infants had no structural birth defects.

Choline, an essential nutrient found in egg yolks, soy, wheat germ and meats, was the only nutrient measured whose blood levels were linked to risk of neural tube defects.

"As choline levels went up, risk went down," Shaw said. Risk for neural tube defects was 2.4 times higher in women with the lowest blood choline levels compared to women with average blood choline levels. The highest blood choline levels were associated with the lowest risk. A previous study by Shaw's group showed that consumption of choline-rich foods was associated with lower risk for neural tube defects, but this is the first study to evaluate blood levels of choline and NTD risk.

Shaw's work provides a promising target for future clinical trials on neural tube defect prevention, said Louanne Hudgins, MD, division chief of medical genetics at Lucile Packard Children's Hospital, who did not participate in the study. Hudgins, who is also a professor of pediatric genetics at the medical school, regularly counsels families facing prenatal diagnoses of neural tube defects. "You can't change an individual's genetic predisposition to these defects. But nutrition components to NTD risk are ripe for therapy," she said.

Shaw cautioned that the blood samples tested were obtained between the 15th and 18th week of pregnancy, well after formation of the neural tube, which seals around the sixth week of pregnancy. Future research will be needed to examine blood choline levels in early pregnancy, he said. Researchers also need to test whether choline supplements given in early pregnancy reduce the rates of neural tube defects. Right now, prenatal multivitamins contain little or no choline.

For women who want to become pregnant, "the best source for choline is still eating a variety of foods," Shaw concluded. Women of reproductive age should also follow U.S. Public Health Service recommendations to take a multivitamin containing other nutrients previously shown to promote healthy pregnancies, he said.

The study was funded by grants from the U.S. Centers for Disease Control and Prevention, theNational Institute of Neurological Disorders and Stroke, and the Foundation to Promote Research into Functional Vitamin B12 Deficiency.

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

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