Recently in Choline Risks Category

I've read quite a bit of the research on how Choline and other B-vitamins (when taken during pregnancy) add methyl groups to the child's DNA - allowing over expression of some genes (thus the better memory), and reducing expression of other genes.

Some researchers I've talked to have seen in their research that when they subject pregnant rodents (mice and rat models that are predisposed to what seem to be schizophrenia and autism ) to moderate stress over multiple generations - there are very high rates of disease and disorders.  When they feed these same strains of mice and rats Choline during the pregnancy - they eliminate this risk.

I've also read about research stress demethylates genes (removes methyl groups) - and stress and poor nutrition during pregnancy could result in 5% or higher rates of demethylation - which, I hear, is a huge impact on the mammal's (mice or humans) genes.  Research I've read also suggests that rates of anxiety and fear significantly increase in mammals (animals and humans) that have experienced high rates of stress during pregnancy and during early life.  In fact I've also read that early life stresses (poverty, stressful family environment, etc.) greatly increases the risk of PTSD later in life (a fact that has been born out in studies of army vets, I believe). 

All of this I find very interesting - because in our own child we see, I believe, the positive impact of high levels of choline during pregnancy.  One of the most visible and common situations I see this in, is if our baby boy (now 17 months) stays up past his normal birthday - which happens occasionally when we are traveling, or visiting with friends on the weekend for a dinner party.  What I find very interesting - and which I suspect is in part due to the extra choline during pregnancy that my wife took - is that while after a certain time all our friend's children start "melting down" and becoming very sensitive and prone to crying  - our child just keeps on playing and exploring like it is mid-day.  As our child gets more tired - his mood doesn't change much.  We see him start rubbing his eyes a bit - but for the most part you couldn't tell if he had just woken up from a nap, or has been up for 8 hours.  He's still just a happy, playful little boy.  Its interesting because on occasion we've gone to afternoon parties with our group of friends who have young kids - and our child is always the last one standing, sometimes until 10pm at night (his usual bedtime is between 6:30pm and 7:30pm) with no crying, no increased sensitivity - and no problems.  Our other friends have to start putting their kids to bed at 7:30 or so as they start becoming more sensitive and crying more frequently. 

Now - I also suspect that the increase in Choline during pregnancy might have some downside.  One downside I suspect is that these children are less prone to fear - which in many situations might be good - but in which many situations might also be not so good. 

What got me thinking about this recently was when were visiting friends the other day and were sitting at the dinner table. I was sitting on a bench seat with my son beside me and windows immediately behind us.  While I was eating, he turned around - reached as high as he could - and proceeded to climb up on the window using his fingertips on a 1 inch ledge, and his feet on another 1 inch ledge (if you've ever rock-climbed, you'd recognize this as a classic "front-pointing" stance).  He had his little running shoes and was totally happy hanging out hanging by his finger tips and toes.  No problem, no fear.  One side of me thinks "great - he'll be a good rock climber" - but the other side of me knows that a healthy fear is a good thing.  I'm not sure yet what this experience indicates yet - but it bears more monitoring.   

A new research study suggests that there may be an increased risk of allergies for babies that are exposed to a high methyl-donor diet (vitamins like choline, folic acid and vitamin B) during pregnancy.

A press release from the researchers noted:

A pregnant mouse's diet can induce epigenetic changes that increase the risk her offspring will develop allergic asthma, according to researchers at National Jewish Health and Duke University Medical Center. Pregnant mice that consumed diets high in supplements containing methyl-donors, such as folic acid, had offspring with more severe allergic airway disease than offspring from mice that consumed diets low in methyl-containing foods. The results of the study are being published Sept. 18, 2008, in the online version of the Journal of Clinical Investigation and will appear in the October print issue.

"Our findings suggest that a mother's diet that alters DNA methylation can affect the development of the fetus's immune system, predisposing it to allergic airway disease," said David Schwartz, MD, senior author on the paper and Professor of Medicine at National Jewish Health. "It also suggests the dramatic increase in asthma during the past two decades may be related in part to recent changes in dietary supplementation among women of childbearing age."

The prevalence of asthma has nearly doubled in the past 25 years. Asthma currently affects about 11 percent of the US population and accounts for $9.4 billion in direct healthcare costs. Although both genes and environment are believed to play a role in the development of asthma, scientists have been unable to definitively identify specific causes of the disease or explain the rise in prevalence.

Epigenetics is the study of gene regulation. Environmental exposures can lead to modification of methyl groups (CH3) binding to certain DNA molecules, which can result in modified expression of specific genes. A variety of environmental factors, including diet, tobacco smoke, and medications, can modify methyl groups binding to DNA, particularly during periods of vulnerability. Although no changes occur in the genetic code, epigenetic effects can be passed to offspring. Emerging research has indicated that epigenetic mechanisms can affect the development of the immune system, skewing it either toward or away from a predisposition to allergies.

The research team decided to examine the potential role of epigenetics in the development of allergic asthma. They fed pregnant mice diets either high or low in methyl donors. In addition to folic acid, the high methyl-donor diets additionally contained higher levels of L-methionine, choline, and genistein.

When the researchers evaluated offspring mice using a model of allergic asthma, they found that mice, whose mothers had the high methyl-donor diets, showed greater severity of asthma; more airway hyperreactivity, more allergic inflammation in their airways, and higher levels of the IgE in their blood. They also found that T cells were more likely to be the type associated with allergy.

The male offspring also transmitted a higher predisposition to allergic airway disease to their progeny. In contrast, mice exposed to high-methyl-donor diets during lactation or adulthood showed no increased propensity to allergic sensitization.

"There seems to be a crucial stage, during development in utero, when a young mouse is susceptible to epigenetic changes that can alter its immune system," said co-author John W. Hollingsworth, Assistant Professor of Medicine at Duke University School of Medicine. "These epigenetic changes may partially explain why it has been so difficult to definitively identify genes that contribute to asthma risk; the effect of genetic variations can be masked or further complicated by epigenetic changes."

When the researchers analyzed the genomes of the mice, they identified 82 genes that were significantly more methylated in high-methyl-diet (HMD) mice. The 10 most methylated genes were biologically plausible causes of asthma. These genes were transcription factors, which control the expression of many genes, and genes associated with cellular migration and allergic airway disease. The highly methylated genes were expressed at lower levels than less-methylated genes in mice receiving the low-methyl-donor diets.

The current research suggests too much folic acid (and other dietary supplements) during pregnancy may be related to an increased risk of allergies and asthma, and may even play a role in the dramatic increase in asthma prevalence during the past two decades. The U.S. Public Health service recommended in 1992 that all women of childbearing age consume 400 micrograms of folic acid daily to reduce their risk of birth defects of the spine and brain. In 1996 the U.S. Food and Drug Administration required that folic acid be added to specific flour, breads and other grains to prevent birth defects. Research has suggested that these measures have helped reduce birth defects.

Given the important role folic acid supplementation has played in prevention of birth defects, Drs. Schwartz and Hollingsworth do not advise any changes in folic acid supplementation, but do believe the issue is worth further investigation.

Source: National Jewish Medical and Research Center

A new research study covered by Reuters suggests that a high choline diet may be linked to increased risk of developing colorectal polyps in women. Obviously, any negative side effects of taking choline need to be thoroughly researched and understood.  The Reuter's write up notes:

"Because dietary choline is a methyl-group donor, as is folate, the investigators suspected it would have folate's anti-cancer characteristics."

Dr. Cho's group hypothesizes that "once a tumor is initiated, growth into a detectable adenoma depends in part on choline availability because choline is needed to make membranes in all rapidly growing cells."

The editorialists, from the National Cancer Institute in Bethesda, Maryland, urge "caution in developing public health policy" until more data are available. "We should remember the surprises and complexities that emerged for beta-carotene, vitamin E, vitamin C, and selenium, other initially promising chemopreventive agents."

Read the full story here: High-choline diet linked to colorectal polyps in women

Journal Research source: J Natl Cancer Inst 2007;99:1214-1215,1224-1231.

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.