Makes Babies Smarter, Keeps Memory Keen and Prevents Disease, Yet Most Americans Are Missing Out

Choline was discovered in 1862, but scientists did not fully understand its importance—or what foods contained it—for another 136 years. They thought we could make our own choline, much like we make Vitamin D from sunlight and cholesterol, but only women who still produce estrogen can make enough choline—and only if they have the right genes. Forty-five percent of child-bearing women have a genetic variation called a SNP (pronounced “snip”) that prevents them from turning estrogen into choline. Women beyond their child-bearing years, boys, and men cannot make choline at all because they have no estrogen. There is another wrinkle in the choline story: Our normal gut bacteria eat what we eat, and many of them like choline. All of this adds up to a disturbing statistic: roughly 80% of Americans must obtain choline from their diet.

In the 1920s, scientists began to discover that mammals on low-choline diets develop serious liver, kidney, and pancreas diseases; they also suffer from poor memory, infertility, bony abnormalities, hypertension, and growth disorders. More recently, researchers at the Nutrition Research Institute (NRI) in Kannapolis, NC, found that humans and other mammals on low-choline diets develop fatty liver disease that would be fatal if left untreated; however, the disease can be cured simply by switching to a high-choline diet.

In 1998, the U.S. Food and Nutrition Board decided that a 154-pound adult human should eat 550 mg of choline every day. Unfortunately, the 2005 National Health and Nutrition Examination Survey found that very few Americans in any age group ate enough choline to gain any of its benefits.

 

How Choline Works

During a meal, our digestive system breaks food into pieces that are small enough to reach our cells. Each cell has factorylike production lines that break food down into even smaller building blocks: Carbs become glucose, proteins become amino acids, and fats become fatty acids. Other factory lines then convert those building blocks into products that our bodies use to grow, learn, and fight disease.

Choline plays a vital role in breaking down and “recycling” food by donating methyl groups to other molecules. (For those who remember high school chemistry, a methyl group is one carbon atom attached to three hydrogen atoms, and donating a methyl group is called “methylation.”) Choline can reach any body cell, but it must be active in five specific organs (liver, kidneys, breast tissue, placenta, and brain) to keep us healthy. By methylating other molecules in cellular factory lines, choline:

  • Makes acetylcholine, a neurotransmitter that allows brain cells to develop normally, controls muscles, and protects us against age-related memory loss
  • Allows cells to send chemical messages to each other
  • Helps kidney cells remove waste products from our blood
  • Keeps cell membranes working efficiently

The table lists the choline content of common foods, many of which are also high in fat and cholesterol. We have been told to avoid fatty, high-cholesterol foods, so it’s not surprising that our national choline levels are so low. However, the benefits of choline-rich food far outweigh the risks, especially for young women who may become pregnant.

 

choline-table2Choline’s Essential Role in Pregnancy

A baby’s brain and spinal cord start out as a tiny, flat ribbon that becomes a closed tube during the first month of pregnancy, often before a woman realizes she is pregnant. If the tube stays open, a neural tube defect occurs. About 3,000 pregnancies a year in the U.S. are affected by neural tube birth defects. The two most common are spina bifida, where part of the spinal cord is exposed, and anencephaly, where the baby’s brain does not develop at all.

Pregnant women are given prenatal vitamins containing folate because we know that a low-folate diet increases the risk of a neural tube defect. What most people don’t realize is that low levels of choline before and during early pregnancy, especially in mothers who carry a SNP that does not allow them to make choline, also increases the risk of a neural tube defect or a cleft palate.

NRI researchers have discovered some fascinating facts about choline from rat and mice experiments, some of which apply to humans.

  • High levels of choline are very important during pregnancy and lactation, but most rodent mothers (called dams) cannot produce healthy pups unless they are fed a high-choline diet before, during and after pregnancy.
      • Pups born to dams that received a good supply of choline throughout pregnancy and lactation have higher IQs and better memories than pups whose dams did not receive enough choline during pregnancy and lactation.
      • Pups that got plenty of choline from their dams are better at solving mazes, including complex 12-arm radial ones, and their memories remain sharp as they age.
      • Pups that did not get enough choline suffer from age-related memory problems.
      • These differences are related to the brain’s memory center (called the hippocampus), which is normal in the smart pups and very abnormal in the others. It also means that what the dam ate while she was pregnant determines her pups’ lifelong IQ and memory. (Folate must also be available during early pregnancy for the hippocampus to develop normally, so diet is extremely important during this time.)
      • A recent Harvard study shows that 7-year-old children whose mothers got plenty of choline during pregnancy perform better on cognitive testing.
  • Pregnant dams that do not get enough choline or folate during early pregnancy have a higher risk of producing pups with neural tube defects, just as humans do.
  • In pregnant humans and dams, the placenta concentrates and delivers choline and folate to the fetus because the brain will not develop correctly unless both essential nutrients are readily available.
  • After birth, breast milk provides large amounts of choline to both human babies and rodent pups.

 

Nutrigenetics: The New Frontier

Diet is arguably the most important environmental factor in our lives. Nutritional factors are thought to cause 30% to 60% of all cancers (similar to smoking), diabetes is a nutritional/metabolic disorder, heart disease is clearly related to cholesterol, and obesity is a nationwide issue at the root of each disease just listed. Good nutrition is clearly essential to good health.

To that end, we have established an “optimal” choline level of 550 mg per day for an average adult. We know that estrogen, gut microbes, SNPs (in about one-third of people) and how we metabolize folate (a vitamin related to choline) are roadblocks that can affect how much choline we are able to obtain from food. What we don’t fully understand yet is why people metabolize food so differently or why they require different amounts of essential nutrients.

Fortunately, a new science called nutrigenetics (the study of how genes and nutrients interact to affect metabolism) is beginning to give us answers. Nutrigenetics requires geneticists, nutritionists and bioinformatics scientists to learn each other’s languages before we will obtain meaningful results from our research. This is what we do at the UNC Nutrition Research Institute.

Soon, nutrigenetics will allow doctors to give us gene-targeted nutrition advice based on a simple blood test. For the present, women who might become pregnant should eat choline-rich foods and take prenatal vitamins containing folate before getting pregnant, during pregnancy, and while breast feeding. (If breast feeding is not an option, infant formulas have been enriched with choline supplements since 2007.)

 

At the Nutrition Research Institute scientists in the Zeisel Lab now are researching how choline is needed for normal brain, liver, muscle and sperm function.