Recently in Prenatal Choline News Category

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

A new study by researchers from three of America's top universities suggests U.S. women aren't getting adequate amounts of a nutrient thought to promote normal fetal brain development.

Sponsored by the National Institute of Health, researchers found the average American consumes just 314 milligrams of choline each day -- much less than the 425 milligrams (women) and 550 milligrams (men) recommended by government health officials.

Choline is a nutrient essential for human brain development, normal memory function and fertility, and is thought to be particularly important during pregnancy. Foods rich in choline include soy lecithin, beef liver and egg yolks, although soy lecithin delivers one of the most bioactive and natural sources of the nutrient without cholesterol or saturated fat.

Accurately estimating per capita choline intake has been difficult because a food composition database was only recently made available to the research community. In this analysis, researchers studied the diets of some 2,000 subjects by comparing data from a food frequency questionnaire against a new U.S. Department of Agriculture choline database.

"Our research suggests the typical American diet is lower in choline than recommended," said Steven H. Zeisel, M.D., one of the study's researchers. "When corrected for energy intake, daily choline levels were significantly below the recommended daily intake for both men and women. Although we cannot be sure from this study, Americans may not understand the importance of choline in their diets, or may not know which foods are rich in the nutrient."

- New Poll Finds a Public Confused about Choline -

Most Americans can't say how much choline they consume each day and don't understand its role in the human diet, according to an August poll of U.S. adults.

Nearly three-quarters of respondents don't understand or don't know if they understand what function choline plays in a person's diet, and only 14 percent said they knew how much of the nutrient they consume in a day. Respondents over the age of 65 and between the ages of 25 and 34 were least able to estimate their daily intake.

Nutritionist Greg Paul, Ph.D., thinks choline consumption would improve if more food manufacturers used a recent Food and Drug Administration ruling to advertise "Good" or "Excellent" sources of choline on package labels.

"The small amount of choline found in most of today's processed foods makes it difficult for the average consumer to meet the nutrient's recommended daily intake," Paul said. "In 2001, the FDA ruled that food manufacturers could make certain claims about choline on product packages. Increasing the amount of choline in processed foods and better promoting those products that are good or excellent sources of choline are positive steps to help address this public health issue."

Paul said one of the easiest and cost-effective ways to boost choline levels in processed foods is to add extra amounts of soybean lecithin, a naturally occurring emulsifier long used as a functional food ingredient.

The study, "Choline Awareness in America," was conducted by Opinion Research Corporation's CARAVAN(R) among a nationally representative sample of 1,020 adults 18 years of age and older between August 24 and 27, 2006. Findings have a margin of error of plus or minus three percentage points at the 95 percent confidence level.

Cholesterol may have hurt its reputation, but choline could redeem the egg. Steven Zeisel of the University of North Carolina at Chapel Hill helped break the news at the First International Scientific Symposium on Eggs and Human Health in Washington, D.C.

"An egg contains a lot of good things. It's a good source of protein and it's cheap," he said. "It's not a good idea to cut them out of the diet entirely. Nothing is all bad or all good."

Zeisel and other experts pointed to a battery of new studies that have shown an array of benefits. For example, pregnant women can improve their children's memory function by eating more choline-rich foods, according to the studies. Eggs are second only to beef liver in choline content.

The American Heart Association has updated its guidelines to do away with its prior recommendation limiting the number of egg yolks to be consumed in a week's time to three or four. Wake Forest University Professor Stephen Kritchevsky presented scientific findings at the symposium that debunk the specific association of eggs with coronary heart disease or stroke.

However, the AHA does not advise at-risk individuals to scramble to the omelet bar. Foods rich in saturated fat are still on the list of things to avoid for heart patients.

While eggs contain only 70 calories each, they derive most of their calories from fat and are high in dietary cholesterol. But for most people, the choline advantage could outweigh the cholesterol risk.

Zeisel explained that choline is a required nutrient in the body, especially during gestation when the brain's memory center -- the hippocampus -- is formed. He said laboratory animals given extra choline during the latter part of pregnancy gave birth to offspring with improved memory skills. Spatial memory, he said, would be enhanced for life. "That's the memory used when you go to find your car at the airport."

By putting rats through a maze, scientists at UNC, Duke University and Boston University were able to detect a 30 percent increase in spatial memory function in rats that were treated to extra choline while developing in the womb. "Even older animals that were ready to die could still be distinguished from those whose mothers were deprived of choline," Zeisel said. Conversely, the deficient rats performed poorly throughout life.

The Duke study reported that the "normal" -- non-Alzheimer's-related -- memory loss associated with aging was reduced or eliminated in subjects who received increased doses of choline. The numerous experiments revealed that the severity of cognitive impairment as well as when it sets in can be preset by the levels of choline consumed early on.

Zeisel added that breast milk is also rich in choline, so nursing infants would also enjoy the benefits of improved memory. As food preferences change during pregnancy, he said, the mother's appetite for certain foods should lead her to those that are needed at the various stages of development.

In recent years scientists have discovered that new nerve cells are generated in the brain well into adulthood and old age, a theory previously rejected by the scientific community.

"Stem cells for this [memory-related] area of the brain divide more and die more slowly," he said, with an increase in choline consumption before birth. New studies will aim to harness the mechanism to accelerate memory function at any age.

Biomedical researchers are exploring the effects of choline in various arenas. In fact, for several years there has been clear evidence that lack of choline can harm an individual's liver.

But more recent experiments in animals suggest that the compound can have more subtle benefits. A few scientists are, for example, investigating hints that extra choline in the adult diet boosts brainpower.

Generating far more excitement is evidence that supplemental choline given to a pregnant female can offer her offspring a wealth of life-long benefits. A growing number of rat studies indicate that choline enrichment in the womb can alter brain development in ways that facilitate learning later in life.

Prenatal choline may even guard the brain against toxic assaults and disease, not to mention senility and other neurodegenerative changes, notes Christina L. Williams, who heads the department of psychological and brain sciences at Duke University in Durham, North Carolina.

This may explain why the National Institute on Aging has been a major sponsor of studies investigating effects of prenatal choline enrichment. "After all," quips neuropsychologist H. Scott Swartzwelder of the Durham Veterans Affairs Medical Center, "aging begins at conception."

A chemical building block of every cell, choline plays an integral role throughout the body and throughout life. It's an ingredient of the membranes surrounding cells. It also transports a cholesterol carrier out of the liver and helps rid the blood of homocysteine, an amino acid that at high concentrations increases the risk of heart disease. Furthermore, choline is a precursor to molecules that relay signals between nerve cells, including those in the brain.

Though the liver synthesizes choline, it may not produce adequate amounts, at least from the food that some people in the United States eat. Recognizing that a shortage of choline in the diet causes liver damage, the Institute of Medicine (IOM) in Washington, D.C., established the first choline recommendations three years ago. This organization, which develops daily intake guidelines for vitamins and other nutrients, advocates eating about 0.5 grams per day.

Meeting the IOM's dietary-intake goals, however, can be a hit-or-miss proposition since there is a dearth of data on how much choline most foods contain. Steven H. Zeisel's laboratory at the University of North Carolina in Chapel Hill has just begun a systematic assay to quantify the choline in commonly eaten U.S. foods. Performed for the Agriculture Department, the tests should yield data on 300 of the most popular items by January 2002 and 2,700 more over the following year.

New studies show, too, that prenatal nutrition may influence how much of the nutrient an individual requires. Moreover, the IOM's nutrition guidelines were developed to prevent liver damage, whereas optimum health may require more choline.

More than a decade ago, Williams and her husband, Warren H. Meck, also at Duke, began their studies of choline's impacts on rat brains.

Meck, a neuroscientist, had been enriching the diets of adult rats with choline in hopes that it might improve their performance in certain memory tests. He knew that choline was a building block of acetylcholine. A chemical that nerve cells use in signaling, it plays an important role in memory.

Recalls Williams, "I asked if he had considered administering choline early in development," when the brain structures central to memory were forming. He hadn't.

So, Meck and Williams launched a study in which they gave pregnant female rats water laced with choline. This supplementation roughly quadrupled the animals' normal choline intake. For a few weeks after birth, the pups received injections of additional choline.

The scientists then tested these offspring throughout their short lives on their recall of locations in a maze where the researchers had hidden food. The experiment measured whether the rats could remember--and not revisit--sites they had already emptied as they sought out the remaining food during the day.

"We found that the prenatally supplemented animals clearly outperformed the others," Williams says. With repeated testing, scores improved for many of the animals in both the supplemented group and an unsupplemented group that served as a control. Yet even after 16 weeks of daily testing, she notes, the supplemented rats continued to make fewer errors than the others did.

One aspect of the results was even more startling, Williams notes. The more difficult the tests of memory and learning became, the bigger the apparent benefit of that prenatal enrichment. The best explanation is that the choline-supplemented offspring could "hold more information," Williams told Science News. "We know of no other treatment that increases memory size."

Her group and others have repeatedly confirmed the findings. "What's so amazing," Williams contends, is that the aptitude for learning in prenatally supplemented animals "is as good in old age as it was when they were young. They show no decline." In contrast, animals not supplemented prenatally with choline show signs of senility in old age. It appears that, with supplementation, "we're building a better brain," she says.

Nuances in choline action are showing up. By narrowing the window of prenatal supplementation, Williams and others have identified only two small periods during which extra choline boosts a rat's intelligence. The first is from days 12 to 17 in gestation. This correlates roughly with the second half of a human pregnancy. The other window runs from two to four weeks after birth--a period that corresponds loosely with human infancy and toddlerhood.

Recently, scientists have begun delving into what underlies that first malleable period. It coincides with the formation of a complex network of choline-sensitive nerve cells that sends information to a region of the brain known as the hippocampus, Williams notes. This area is active in learning and memory.

Five years ago or so, Williams and other researchers asked Swartzwelder to look for signs that early choline exposure somehow changes the brain. Dubious that a week of prenatal enrichment could smarten animals, much less trigger detectable physiological changes, he nonetheless agreed to a pilot study.

The results changed his perspective.

In a hippocampal neuron, certain patterns of incoming chemical signals can trigger a response called long-term potentiation. During this response, newly arriving signals are more effective than under other conditions. The process helps cement memories by "promoting the encoding and consolidation of new information. It's the first step in learning," Swartzwelder explains.

Compared with hippocampal tissue from unsupplemented animals, brains primed with prenatal choline showed long-term potentiation more readily, Swartzwelder found. When he then turned to brains from animals whose mothers had been choline-deficient, he found hippocampal circuits unusually resistant to the effect.

It appeared that choline is "powerful stuff," Swartzwelder recalls. But to make sure of his results, he repeated the analyses, using rats reared and treated by a different group of researchers. Again, he saw the same effect. Overall, the greater the prenatal exposure to choline, the larger the effect on the brain.

That was two years ago. Now, Swartzwelder is focusing on glutamate, a primary chemical messenger responsible for triggering long-term potentiation. Brain cells have specialized protein complexes, called NMDA receptors, that respond to glutamate. They don't promote long-term potentiation unless they receive closely timed signals from other brain cells.

Swartzwelder's team has now shown that NMDA receptors in the brains of animals that received prenatal choline enrichment are unusually responsive to signals. This finding suggests that these animals might make memories more readily than others do.

Prenatal supplementation with choline can also protect the brain later in life. That finding, to be published soon in the Journal of Neuroscience, is "the wildest thing of all," Swartzwelder says.

His group and its collaborators find evidence that choline can influence the effects of a toxic drug. Prenatal supplementation protects neurons in the brains of adolescent rats from the cell death ordinarily associated with high doses of a drug that blocks the NMDA receptors.

Last year, prenatal choline supplementation in another study prevented memory defects following drug-triggered brain lesions. The researchers used a drug that induces convulsive epileptic seizures in rodents. Epileptic seizures not only damage the brain, but they also tend to impair memory and learning.

Gregory L. Holmes of Harvard Medical School's Center for Research in Pediatric Epilepsy in Boston and his colleagues administered the neurotoxic drug to rodents--some of which had received prenatal choline supplementation--and then monitored the animals' learning skills.

Using a standard test of spatial memory, the researchers daily released each rat into a pool of milky water and waited for the animal to find a stationary platform just beneath the surface. Animals that had not experienced seizures oriented themselves more quickly every day. This learning showed up in rats whether or not they had received prenatal choline supplementation.

After the experienced rats developed epilepsy, however, the pattern changed. When tested a week after seizures, prenatally supplemented animals remembered where the platform was and in succeeding days continued to improve their performance. But rats that had received no prenatal choline supplementation acted as if they had no memory of where the platform had been and showed less improvement in finding it during the following days.

If studies of people confirm an effect of prenatal choline on the brain's response to assaults after birth, Holmes' team wrote in the November 15, 2000 Journal of Neuroscience, these findings "could lead to nutrition-based preventive strategies." The authors liken the possibility to the use of folate vitamins now routinely prescribed to pregnant women to prevent neural tube defects in the fetus.

Jan Krzysztof Blusztajn of Boston University, a co-author on that paper, has been probing biochemical differences that arise from prenatal choline supplementation.

Three years ago, he showed that extra choline available during hippocampal development permanently modifies that area's efficiency in using the nutrient. When choline concentrations in the womb are low, the brain becomes "very frugal" with this nutrient, Blusztajn says, whereas the choline metabolism of animals that encounter an abundance in the womb "becomes quite wasteful." Prenatal conditions probably determine how much choline an adult requires.

His studies indicate that an overly frugal hippocampus may lead to problems. Its parsimony may leave little choline free to perform mentally demanding activities

With a low stockpile of choline, production of the neurotransmitter acetylcholine may prove insufficient to carry sustained high-throughput communications between memory neurons. They just poop out and learning slows. However, Blusztajn reports that prenatally supplemented rats "have some sort of cognitive reserve--which is probably also a biochemical reserve. It lets them sustain longer [choline-fueled] neurotransmission."

Evidence is emerging that choline supplementation in adulthood, too, may sometimes improve memory. This result comes from a study of people who, because of gastrointestinal problems, receive virtually all of their nutrition intravenously. Manufacturers don't regularly fortify with choline most nourishment that's administered intravenously.

"We now know that between 20% and 50% of patients receiving [intravenous] nutrition long-term develop liver disease," notes Alan L. Buchman of Northwestern University Medical School in Chicago. Some die; others may survive with transplants. In the September-October Journal of Parenteral and Enteral Nutrition his team reports on a pilot study of 15 volunteers with gastrointestinal problems who were receiving intravenous nutrition. Signs of liver damage disappeared in those seven who had been randomly assigned to receive supplemental choline for 24 weeks.

The researchers also administered IQ and other tests to 11 participants. These initially scored below normal on verbal, memory and visual memory tests. In the January-February Journal of Parenteral and Enteral Nutrition, the scientists reported that those scores improved "significantly" in the men and women receiving supplemental choline. This suggests, they said, that severe choline deficiency in adulthood may impair memory reversibly.

Zeisel is beginning several more human trials. In one, resembling the animal experiments, 80 pregnant women will be given specially prepared waffles and asked to eat one with each meal from about 15 weeks into their pregnancy until a month after their baby is born. Some of the women will get normal waffles, the rest will get ones fortified with either one egg or its choline equivalent in the form of soy lecithin.

When the women's babies are 10 and 12 months old, psychologists will test the infants' visual memory--the child's recall of where Mom's picture last appeared.

Zeisel has also just launched the first detailed analysis of how much choline people need for basic health. Eighty volunteers will be held, Zeisel says, for 71 days in a university metabolic ward. Everything they eat and excrete will be measured. The food--resembling heavily fortified milk shakes--will initially carry a normal range of recommended nutrients. Then, all the participants will be switched to a choline-free version.

They'll remain on that diet until enzymes indicative of liver damage begin appearing in their blood. At that point, Zeisel says, "we'll begin adding back increasing amounts of choline until we discover how much it takes to return each to normal."

Because the test will include men and women, blacks and whites, and premenopausal and postmenopausal women, it should determine whether particular groups differ in their needs.

Today, few people exhibit overt choline deficiency. Zeisel suspects, however, that at least some teeter on the brink of insufficiency. Because the best-known choline-rich foods tend to be animal products, especially ones high in fat, he worries that vegans and those who have successfully pared most fat from their diet may be vulnerable.

Don't be afraid of eating eggs despite their cholesterol, he chides. Their yolks are among the richest known natural sources of choline. A tall glass of skim milk offers as much choline as an egg does. And coming soon, predicts Gregory Paul, director of nutrition for Central Soya of Fort Wayne, Indiana, will be a host of foods--orange juice, baked goods, and pasta--fortified with choline-rich soy lecithin.

So, keep an eye out for those new choline labels, Williams says; they'll help identify "what we call food for thought."