I've reviewed this research quickly - and actually spoke (via email) with one of the lead researchers a few weeks ago who participated in this research - and its increasingly looking like prenatal choline has a number of benefits in addition to enhancing brain function.  In this new research it is suggested that prenatal choline will prevent, or lower the risk of aggressive breast cancer in the babies of mothers that took higher levels of choline (in eggs) during their pregnancy.  Here is the full report from the researcher's press release:

Eating eggs when pregnant Reduces Risk of Aggressive breast cancer in offspring

New research shows that the 'genetic impact' of a pregnant woman's diet has a profound effect on her child

A stunning discovery based on epigenetics (the inheritance of propensities acquired in the womb) reveals that consuming choline--a nutrient found in eggs and other foods--during pregnancy may significantly affect breast cancer outcomes for a mother's offspring. This finding by a team of biologists at Boston University is the first to link choline consumption during pregnancy to breast cancer. It also is the first to identify possible choline-related genetic changes that affect breast cancer survival rates.

"We've known for a long time that some agents taken by pregnant women, such as diethylstibesterol, have adverse consequences for their daughters," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "But there's an upside. The emerging science of epigenetics has yielded a breakthrough. For the first time, we've learned that we might be able to prevent breast cancer as early as a mother's pregnancy."

The researchers made the discovery in rats by studying females whose mothers were fed varying amounts of choline during pregnancy. Different groups of pregnant rats received diets containing standard amounts of choline, no choline at all, or extra choline. Then the researchers treated the female offspring with a chemical that causes cancer of the mammary gland (breast cancer). Although animals in all groups developed mammary cancer, the daughters of mothers that had received extra choline during pregnancy had slow growing tumors while daughters of mothers that had no choline during pregnancy had fast growing tumors.

"Our study provides additional support for the notion that choline is an important nutrient that has to be considered when dietary guidelines are developed," said Krzysztof Blusztajn, Ph.D., Professor of Pathology at Boston University and the study's senior researcher. "We hope it will be possible to develop nutritional guidelines for pregnant women that ensure the good health of their offspring well into old age."

The researchers also found multiple genetic and molecular changes in the rats' tumors that correlated with survival outcomes. For example, the slow growing tumors in rats had a genetic pattern similar to those seen in breast cancers of women who are considered to have a good prognosis. The fast growing tumors in mice had a pattern of genetic changes similar to those seen in women with a more aggressive disease. The researchers also found evidence that these genetic changes may result from the way that choline affects modifications of the DNA within the mammary gland of fetuses as they develop in the womb.

The National Cancer Institute estimates that there will be more than 184,000 new cases of breast cancer in 2008 and more than 40,000 deaths. Treatments for women suffering from breat cancer range from hormone therapy to surgery.

Research Source:

Raising gestational choline intake alters gene expression in DMBA-evoked mammary tumors and prolongs survival 
(December 1, 2008, The FASEB Journal)

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.

Folic acid is essential for pregnant women to combat neural tube defects in the brains of their children, but so are other nutrients like choline, betaine, and methionine.

"Periconceptional intake of folic acid prevents some neural tube defects (NTDs). Other nutrients may also contribute to NTD etiologies; a likely candidate is choline," said G.M. Shaw and associates at the March of Dimes Birth Defects Foundation. "Similar to folic acid, choline is involved in one-carbon metabolism for methylation of homocysteine to methionine."

Shaw and team "investigated whether maternal periconceptional dietary intakes of choline and its metabolite betaine influence NTD risk."

They obtained their data "from a case-control study of fetuses and infants with NTDs among 1989-1991 California births. In-person interviews were conducted with mothers of 424 NTD cases and with mothers of 440 non-malformed controls. A standard 100-item food frequency questionnaire was used to assess nutrient intake," the scientists said.

Their analysis revealed that "[d]ietary intakes of choline were associated with reduced NTD risks. Controlling for intake of supplemental folic acid, dietary folate, dietary methionine, and other covariates did not substantially influence risk estimates for choline."

Additionally, Shaw and colleagues reported, "NTD risk estimates were lowest for women whose diets were rich in choline, betaine, and methionine. That is, for women whose intake was above the 75th percentile compared with below the 25th percentile for all three nutrients, the odds ratio was 0.17

"Study findings for dietary components other than folic acid offer additional clues about the complex etiologies of NTDs," they concluded.

Shaw and colleagues published their study in the American Journal of Epidemiology (Periconceptional dietary intake of choline and betaine and neural tube defects in offspring. Am J Epidemiol, 2004;160(2):102-109).

Source:  March of Dimes Birth Defects Foundation, California Birth Defects Monitoring Program, 1917 5th Street., Berkeley, CA 94710 USA.

Two compounds found in some shampoos, diethanolamine (DEA) and triethanolamine (TEA), may seep through the skin, into the brain, and block the ability of neurons to take up choline. Steven H. Zeisel, M.D., Ph.D and colleagues at University of North Carolina at Chapel Hill believe the reduction in choline update may reduce neural cell replication.

The research in animals centers around diethanolamine (DEA), a chemical used in shampoos, lotions, creams and other cosmetics. DEA is used widely because it provides a rich lather in shampoos and keeps a favorable consistency in lotions and creams, but there's also some research that shows it may rob the brain of its ability to make memory cells.

"Depending on the treatment, some mice are stupid, some are not," said researcher Dr. Steven Zeisel.

In the modern scientific telling of the ancient story Samson was shampooed by Delilah and he became so dumb she was able to manipulate him to do her bidding without cutting off his hair.

The risk from this effect is much greater for fetuses and babies than for adult humans.

Dr. Zeisel says if the dea-hypothesis holds true, the memory impact would probably be minimal in adults. But it could have a bigger effect on the developing brain, during pregnancy and the first few years of life.

Dr. Zeisel is investigating whether choline supplementation can counteract the effect of DEA and TEA.

The US National Institutes of Health National Library of Medicine happens to have an online database of household products and their ingredients. Check out the lists of Shampoo/Conditioner and Shampoo products and what each contains. It doesn't appear that all products are listed. Also, the ingredient lists look like what you find by reading the side of the bottle anyway. Still, if you want to check a number of different products while still remembering the names of these chemicals it is pretty quick to do.

Now, working with nerve tissue derived from a human cancer known as a neuroblastoma, the UNC researchers have discovered why more choline causes stem cells -- the parents of brain cells -- to reproduce more than they would if insufficient choline were available.

A report on the findings will appear in the April issue of the Journal of Neurochemistry. Authors are doctoral student Mihai D. Niculescu and Dr. Steven H. Zeisel, professor and chair of nutrition at the UNC schools of public health and medicine. Dr. Yutaka Yamamuro, a former postdoctoral fellow in Zeisel's laboratory now with Nihon University in Japan, was a key contributor.

"We found that if we provided them with less choline, those nerve cells divided less and multiplied less," Zeisel said. "We then went on to try to explain why by looking at genes known to regulate cell division."

Scientists focused on cyclin-dependent kinase inhibitor 3 genes, which keep cells from dividing until a biochemical message turns the genes off, he said. They found exactly what they expected.

"We showed that choline donates a piece of its molecule called a methyl group and that gets put on the DNA for those genes," Zeisel said. "When the gene is methylated, its expression is shut down."

But when the gene is under-methylated -- such as when there's not enough choline in the diet -- then it's turned on -- halting or slowing nerve cell division, he said.

"Nature has built a remarkable switch into these genes something like the switches we have on the walls at home and at work," Zeisel said. "In this very complicated study, we've discovered that the diet during pregnancy turns on or turns off division of stem cells that form the memory areas of the brain. Once you have changed formation of the memory areas, we can see it later in how the babies perform on memory testing once they are born. And the deficits can last a lifetime."

The next step, Zeisel said, will be confirm that the same things happen in living mouse fetuses when the mothers receive either high or low doses of choline.

Dr. Zeisel and other collaborators at UNC Chapel Hill and Tufts University have recently shown that insufficient folic acid even in later pregnancy results in lifelong reduction in cognitive ability in rats and mice.

Five years ago, University of North Carolina (UNC) at Chapel Hill researchers first reported finding that the nutrient choline played a critical role in memory and brain function by positively affecting the brain's physical development.

Differences in development influenced action, the scientists and their colleagues found. In animal experiments conducted at Duke University, both young and old rats performed significantly better on memory tasks if they received enough choline before birth compared with same-age rats whose mothers were fed choline-deficient diets. The latter showed deficits in the hippocampus and septums of their brains.

Because humans and rodents are so similar biologically, something comparable probably happens in humans, the investigators believe.

Now, working with nerve tissue derived from a human cancer known as a neuroblastoma, the UNC researchers have discovered why more choline causes stem cells - the parents of brain cells - to reproduce more than they would if insufficient choline were available.

A report on the findings appears in the April 2004 issue of the Journal of Neurochemistry. Authors are doctoral student Mihai D. Niculescu and Dr. Steven H. Zeisel, professor and chair of nutrition at the UNC schools of public health and medicine. Dr. Yutaka Yamamuro, a former postdoctoral fellow in Zeisel's laboratory now with Nihon University in Japan, was a key contributor.

"We found that if we provided them with less choline, those nerve cells divided less and multiplied less," Zeisel said. "We then went on to try to explain why by looking at genes known to regulate cell division."

Scientists focused on cyclin-dependent kinase inhibitor 3 genes, which keep cells from dividing until a biochemical message turns the genes off, he said. They found exactly what they expected.

"We showed that choline donates a piece of its molecule called a methyl group and that gets put on the DNA for those genes," Zeisel said. "When the gene is methylated, its expression is shut down."

But when the gene is under-methylated - such as when there's not enough choline in the diet - then it's turned on, halting or slowing nerve cell division, he said.

"Nature has built a remarkable switch into these genes something like the switches we have on the walls at home and at work," Zeisel said. "In this very complicated study, we've discovered that the diet during pregnancy turns on or turns off division of stem cells that form the memory areas of the brain. Once you have changed formation of the memory areas, we can see it later in how the babies perform on memory testing once they are born. And the deficits can last a lifetime."

The next step, Zeisel said, will be confirm that the same things happen in living mouse fetuses when the mothers receive either high or low doses of choline.

Developing babies get choline from their mothers during pregnancy and from breast milk after they are born, he said. Other foods rich in choline include eggs, meat, peanuts and dietary supplements. Breast milk contains much more of this nutrient than many infant formulas.

Pregnancy and nursing make female rats - and presumably women - especially susceptible to becoming choline deficient, the scientist said. The months before and immediately after childbirth appear to be special times when women need more in their diets.

Choline is a vitamin-like substance that is sometimes treated like B vitamins and folic acid in dietary recommendations. The body uses it in making the nerve messenger chemical known as acetylcholine and in building cell membrane - the biological "wrapper" that keeps cells from leaking.

A paper Zeisel's laboratory published in January in the Journal of Nutrition also showed that the nutrient folic acid is not just critical for brain development in embryos during the earliest stages of pregnancy, but it's a key to healthy brain growth and function late in pregnancy too.

Humans and other mammals lacking sufficient folic acid shortly before they are born can suffer lifelong brain impairment, the earlier UNC animal studies indicated. Such research can never be done directly in growing human fetuses for obvious reasons.

"In the past few years, folic acid has been the single greatest success story in nutrition and in preventing birth defects," Zeisel said. "Spina bifida, the early birth defect in which the spinal cord doesn't close, and anencephaly, a condition in which the brain doesn't form normally, can be eliminated between 50% and 85% of the time if women get sufficient folic acid before they become pregnant."

A new study by Scott Swartzwelder and other researchers at Duke University Medical Center suggests that choline taken during pregnancy can result in "supercharged" brains for the infant.  The new study shows this is due to having bigger brain cells in key segments of the brain.

Choline, is found in egg yolks, liver and other meats - "exactly the kind of things people were told not to eat" due to their high cholesterol content, says Swartzwelder.

Dr. Shartzwelder believes their results in the rats could translate to humans, and indeed the US Institute of Medicine added choline to the list of essential nutrients, particularly for pregnant women, in its 2003 recommendations.

The implications of the study's findings are "potentially huge" Swartzwelder believes: "If it turns out that it's true in humans and can make people smarter their whole lives and forestall age-related memory decline - that's potentially a very exciting prospect."

Hannah Theobald, a nutrition scientist at the British Nutrition Foundation, calls the study "really interesting" but cautions that more research needs to be done before any recommendations can be made in humans.

Anatomy and physiology - Behavioural studies have shown giving choline to pregnant rats improves learning and memory in their offspring. The pups also suffer significantly less from failing memories as they get old.

However, it was not known whether choline's effects were on the general brain environment or whether it fundamentally changed the brain's cells.

"Our study is the first time anyone has shown that prenatal choline supplementation actually changes the anatomy and physiology of single brain cells," Swartzwelder told New Scientist. No adverse effects could be seen in the rats, he adds.

The team gave pregnant rats three to four times their normal intake of choline for six days. Gestation lasts about 21 days in rats, and the period during which the rats were fed extra choline roughly corresponds to the start of the third trimester in women.

Electrical signals  - The pups born were raised to adulthood and then their brains were examined, in particular the hippocampus - the area of the brain critical for learning.

This part of the brain was sliced in a way that preserved its internal circuitry and kept it alive. A tiny electrode was then used to recording the behaviour of each cell. The neurons of rats born to mothers given extra choline fired electrical signals more rapidly and for longer periods, indicating a capacity to communicate more easily.

The team then injected a biological dye into the neurons to look at their shape and structure. The cells from rats receiving prenatal choline supplements were substantially bigger than those from rats that did not.

"We are looking at consistent changes in the range of 20 to 25 per cent," says Swartzwelder. "These are bigger cells with more dendrites, the areas of the cell specific to receiving incoming signals." He says the combined changes induced by choline in the physiology and anatomy of the brain cells would "hotwire" the system.

Better membranes  The team does not know exactly how choline boosts brains, but it is known to contribute to the building of cell membranes during the embryo stage of development. "My bet is it has something to do this," Swartzwelder says.

Previous work by Steven Zeiser at the University of North Carolina has shown choline alters a crucial gene by adding a methyl group on to it. This switches off the gene, CDKN-3, which usually inhibits cell division in the memory regions of the brain.

There is little information on how much choline women currently take. "But don't be afraid of eggs," Swartzwelder suggests. "I used to eat a low fat diet - I've started eating eggs and I'm not even pregnant!"

However, Theobald warns that some foods rich in choline should be avoided during pregnancy. For example, liver is also high in retinol which can cause birth defects. And certain choline-rich fish like swordfish and tuna can also have a high mercury content, which is harmful to fetuses.

Original Source of Research Study Information:  Journal of Neurophysiology (vol 91 April issue)

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."

New research is increasingly identifying Choline as a key nutrient for the brain and liver.  In the past research has shown that while 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 its first choline recommendations 3 years ago. This organization, which develops daily intake guidelines for vitamins and other nutrients, advocates eating about 0.5 gram per day.

Meeting 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, IOM's nutrition guidelines were developed to prevent liver damage, whereas optimum health may require more choline.

Enriched diet

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 is a building block of acetylcholine. A chemical that nerve cells use in signaling, it plays an important role in memory.

Recalls Christina L. Williams, who heads the Department of Psychological and Brain Sciences at Duke University , "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.

Narrow window

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 2 to 4 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 2 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 (SN: 9/4/99, p. 149: http://www.sciencenews.org/sn_arc99/9_4_99/fob3.htm).

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.

Protecting neurons

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 Nov. 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 coauthor 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 out 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."

Improving memory

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 percent 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. They 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.

Minimum requirements

Zeisel has also just launched the first detailed analysis of how much choline people need for basic health. Eighty volunteers will be held "captive, " 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 cholinefree 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 Ft. Wayne, Ind., 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."

A new study out of Duke University suggests some important benefits of supplementation during pregnancy with choline.

Pregnant rats fed extra doses of an essential nutrient called choline produced offspring whose brain circuits were "wired" to learn and remember far more efficiently than offspring without the supplement, according to a study at Duke University Medical Center.

Conversely, analysis of brain slices of the offspring of rats deprived of choline indicated a decrease in memory capability.

The researchers said it is the first time that a common food nutrient has been shown to cause permanent brain changes in regions responsible for learning and memory. The findings could have important implications -- especially for pregnant women and their children -- if choline proves to have the same memory-enhancing effect in humans, a theory for which considerable evidence already exists, the researchers said.

Choline is a naturally occurring amino acid found in egg yolks, milk, nuts, liver and other meats as well as in human breast milk. It is the essential building block for a memory-forming brain chemical called acetylcholine, and it plays a vital role in the formation of cell membranes throughout the body.

The Duke researchers found that brain circuits of choline-supplemented rats were built to accept and retain new information more efficiently than rats that received normal or substandard amounts of choline prenatally. And that memory enhancement endured until the rats were 4 months old -- the equivalent of early adulthood in humans.

Specifically, the research showed that choline enhanced a brain function called long-term potentiation (LTP), in which the act of receiving an electrical stimulus or "message" actually paves a pathway allowing future messages to reach the nerve cell more easily -- similar to the way that rain water creates a furrow through soil upon repeated downpours, enabling even a small trickle to find its way more easily.

If further research confirms the findings in humans, then choline could potentially be used to ensure normal memory function in the population at large through a modest change in diet, said Scott Swartzwelder, a neuropsychologist at Duke and the Durham VA Medical Center and lead author of the study. Results of his study, funded by the National Institute on Aging, will be published in the April issue of the journal of Neurophysiology.

"The ramifications of this research could be profound, because we've found that manipulating one single nutrient for a few days during gestation has a lifelong effect on brain function," Swartzwelder said. "In theory, we could develop ways to significantly reduce age-related memory deficits."

Swartzwelder said the amount of choline the pregnant rats received was well within normal limits -- about three times more than the control group received. The only time they received additional choline was during a five-day period -- days 12 through 17 -- of their 22-day gestation period. The control group received a normal dietary amount of choline, and a third group was virtually deprived of choline.

Not surprisingly, Swartzwelder said, the brains of choline-deprived rats were slower to engage the process of LTP and required a much larger stimulus to initiate LTP than the other rats.

While Swartzwelder's research is not the first to demonstrate choline's effects on memory, his is the first study reported to pinpoint the specific brain process that choline enhances.

In previous choline studies conducted at Duke, researchers showed that rats exposed to choline prenatally were better able to learn and remember the location of food in a maze, as well as to locate and swim to safety on a hidden platform in a water-filled maze. And, their memory abilities lasted well into old age. That research, conducted by Christina Williams and Warren Meck of Duke -- both co-authors of the current study -- was among the first to show that choline has a behavioral effect on memory in animals.

But until now, there has never been a physiologic explanation as to why these behavior changes occurred, said Williams, chair of the department of psychology at Duke. So, based on her behavioral studies, Swartzwelder set out to explain how choline alters memory function. By analyzing brain slices from the offspring of rats in each group, Swartzwelder showed that rats deprived of choline prenatally did not respond to even the largest electrical stimulus applied to their brain's hippocampus -- the region where LTP occurs. But the offspring of choline-supplemented animals responded very quickly and easily to the smallest electrical stimulus, indicating their hippocampus was primed to learn.

"What this suggests is an actual change in brain circuitry brought about by added choline during a critical window of prenatal development," Swartzwelder said. "The brains of choline-supplemented rats have a greater plasticity, or an ability to change and react to stimuli more readily than other rats."

Precisely why LTP occurs more readily in the choline-supplemented rats is unclear, Swartzwelder said. But there are several likely scenarios. One hypothesis is that extra choline permanently alters the developing brain circuits so they are built with either more acetylcholine receptors, or they have a greater capacity to produce acetylcholine.

A second possibility is that something inside individual nerve cells is altered to respond to acetylcholine more readily, regardless of the amount of acetylcholine present. In yet a third scenario, researchers hypothesize that there is no significant change in acetylcholine brain circuitry. Rather, choline affects a completely different neurotransmitter system, such as glutamate.

Swartzwelder said the next step is to examine the biochemistry within the various brain circuits to see which neurotransmitter systems are likely to play a role in enhancing LTP.

Source: Duke University Medical Center