Can we prevent schizophrenia? It may be up to choline.

Choline forms healthy brain function in pregnancy.
Choline forms healthy brain function in pregnancy.

A key point about nutrition most often misunderstood is that each nutrient we eat performs a specific action. Nutrients are most often signaling molecules that direct the creation of hormones, tissues, fluids, electrical impulses and other important metabolic functions. New research has once again demonstrated the importance of these signaling molecules during pregnancy and this time it’s choline. Often considered one of the B vitamins, choline is an essential part of acetylcholine, which supports proper brain function. Similar to the way folic acid supplementation during pregnancy promotes proper neural tube development, choline supplementation appears to signal for the proper coding of specific parts of brain neurons.

Choline metabolism in humans varies greatly by stage of life, genetic polymorphisms and gender, with an increased demand for choline during pregnancy and lactation. Most dietary choline is found in meat and eggs, generally putting Paleo eaters in good choline status, while vegetarians and vegans get optimal choline by including good plant sources of choline like quinoa, broccoli, oats, green peas, edamame, bananas, and pinto beans. Pregnant and prospective pregnant women would do well to be thoughtful about choline intake. Studies have shown that one expectant mother out of five does not get adequate choline in her diet. The recommended intake of choline in pregnancy is 450 mg/day, yet the 2010 Nurse’s Health Study indicated that a whopping 95 percent of pregnant women consumed less that 411 mg of choline each day. While ad lib diets have been found to average 8.4 mg/kg for men and 6.7 mg/kg for women, a study of pregnant women in California found that 25% of women had an intake that provided less than half this amount. For a 140-pound (63 kg) woman, that calculates to be about 213 mg/day, well below the recommended intake. For women who weigh much less, this difference can be even greater. Considering the impact of choline on the developing fetal brain, choline nutrition is of significant importance.

Research funded by the Brain Behavior Research Foundation at the University of Colorado has found that mothers with better choline intake may be able to prevent schizophrenia in their children. Dr. Robert Freedman, Chair of Psychiatry at the University of Colorado, along with Dr. Camille Hoffman and Dr. Randal Ross of the University of Colorado, School of Medicine have now completed a 9-year pre and post natal study of women and their children. This gets a little technical but stick with me. Choline is needed during fetal development to properly develop neurons in the brain that transport and exchange information that form our thoughts and actions. A deficiency in choline during fetal brain development may prevent certain genes known as CHRNA7 genes, from encoding specialized alpha-7 receptors on neurons. Alpha-7 receptors are responsible for tempering or inhibiting our behavioral response to various stimuli. If the neurons lack the ability to inhibit responses, the neurons can overreact, making us more easily agitated, anxious, and even change our thoughts to be more reactive. In other words, healthy neurons have the ability to ‘turn down the volume’ on a situation or thought so that we can respond more appropriately. This is a key issue in schizophrenia.

Choline concentrations in-utero, vary at different times during pregnancy. They are higher in early pregnancy, while in later months the uterine environment changes and choline concentrations decline. This can affect how many of these alpha-7 receptors are encoded, especially in choline deficient mothers. Patients with schizophrenia have been found to have less optimal inhibitory activity in the brain near the time of birth and this may predispose them to schizophrenia later in life. Schizophrenia isn’t usually expressed until late teen hood or early twenties, and this study will continue to follow these children, but Dr. Freedman points out an interesting fact. Children, who go on to develop schizophrenia, have recognizable motor problems in the first year of life. While motor problems alone don’t diagnose future schizophrenia, often there are other signs in early childhood that can be traced to deficits in inhibition that may be associated with schizophrenia.

Here’s the University of Colorado study in a nutshell:

A double-blind trial to compare normal choline intake with choline supplementation, the study included 100 healthy women who received either:

  • Special dietary instructions on eating a choline rich diet AND 2x the normal dietary levels of choline in supplement form during pregnancy and then to mother and newborn through 3 months after birth


  • Only received special dietary instructions on eating a diet rich in choline

The results:

  • 76% of infants whose mothers received choline supplementation + dietary instruction showed normal inhibition of alpha 7 receptors
  • 43% of infants whose mothers received dietary instruction only, showed normal inhibition of alpha 7 receptors
  • Infants of mothers who carry special genetic risk factors for schizophrenia:
    • Had better alpha 7 inhibition with choline supplementation + dietary instruction
    • Had diminished alpha 7 inhibition receiving dietary instruction alone

One of the beauties of this study is that they compared diet and supplementation to diet alone. Food should be our first line of defense in health while supplements fill in the gaps in our diet. But even though variations in dietary practices from omnivore to vegan can greatly affect choline status, it may be too early to suggest specific choline supplementation in all pregnant women. As a nutritionist, I’d like to see pregnant and prospective parents have a detailed mental health history included by their health professionals, consider genetic evaluation if they have a family history of schizophrenia, and be referred for nutrition education including advise on supplementation that may be of benefit in each pregnancy. Thoughtfulness about preconception and pregnancy nutrition can only improve pregnancy outcomes and may even provide a life free of mental illness for a child.

Use these links to learn more about choline in food, to read more about the study here and also view presentations by Drs. Hoffman and Freedman from the Brain Behavior and Research Foundation’s 2015 New York Mental Health Research Symposium .


  • Choline: Critical Role During Fetal Development and Dietary Requirements in Adults, Steven H. Zeisel
  • Shaw GM, Carmichael SL, Yang W, Selvin S, Schaffer DM. Periconceptional dietary intake of choline and betaine and neural tube defects in offspring. Am. J. Epidemiol. 2004;160:102–9.
  • Velzing-Aarts FV, Holm PI, Fokkema MR, van der Dijs FP, Ueland PM, Muskiet FA. Plasma choline and betaine and their relation to plasma homocysteine in normal pregnancy. Am. J. Clin. Nutr. 2005; 81:1383–89.
  • This link leads to a website provided by the Linus Pauling Institute at Oregon State University.  Linda Illingworth is not affiliated or endorsed by the Linus Pauling Institute or Oregon State University.