Estrogen protects pregnant women from choline deficiency

August 17, 2007
Photograph of Dr. Steven Zeisel

Young women are less likely than men or post-menopausal women to suffer liver or muscle damage from a deficiency of the nutrient choline, according to a new study led by Steven H. Zeisel, MD, PhD, Kenan Distinguished University professor of nutrition in the UNC School of Public Health.

Researchers discovered that the hormone estrogen turns on a gene in the liver that produces choline, a nutrient used to form cell membranes. This means pre-menopausal women, who have high levels of estrogen, can make their own supply of the nutrient. Thus, a choline deficiency is less likely to inflict damage in younger women, the researchers found.

“This finding helps explain why a majority of young women who consume too little choline in their diet do not suffer from liver and muscle damage like men and post-menopausal women do,” said Zeisel, senior author of the study.

The results were published in the July 2007 edition of the Journal of the Federation of American Societies for Experimental Biology (FASEB). The study is the first to explore the underlying mechanism of why dietary requirements for choline vary with estrogen status in humans.

Estrogen’s effect appears to protect younger women from choline deficiency during pregnancy and lactation, when significant amounts of the nutrient are transported from mother to infant, Zeisel said.

Choline is found in eggs, meats and wheat germ, among other foods. Research in mice and rats found that the offspring of pregnant females who ate a choline-rich diet perform 30 percent better in memory tests than babies from mothers who ate a normal diet, Zeisel said. The effects lasted throughout the life of the offspring, he said.

“Choline is essential to fetal brain development. Mother Nature knew what she was doing when women were designed. Only young women have estrogen, so it is what turns on the switch on the gene needed to make a nutrient women need to make normal babies,” he said.

Zeisel’s research team is currently studying the 40 percent of young women that are susceptible to choline deficiency. The team suspects that these women have a defective response to estrogen in the gene in the liver that produces choline.

Co-authors on the FASEB study include, from the UNC School of Public Health, Mary Resseguie, doctoral student of nutrition; Jiannan Song, doctoral student of nutrition; Mihai D. Niculescu, MD, PhD, research assistant professor of nutrition; Kerry-Ann da Costa, PhD, research assistant professor of nutrition; and Thomas A. Randal, PhD, bioinformatics scientist at the UNC-Chapel Hill Center for Bioinformatics.

The research was supported by grants from the National Institutes of Health.

In a second study — published in the July 2007 issue of The American Journal of Clinical Nutrition — Zeisel uses the estrogen-choline gene example to illustrate the importance of developing technologies that will help physicians identify several thousand other gene-nutrient interactions.

Humans have approximately 3,000 small molecules from metabolism in their blood, Zeisel said. Most physicians now only measure a few, such as fat, cholesterol and blood glucose, and therefore make diagnoses based on an incomplete picture, he argues. But new technology makes it possible to measure all of these small molecules and provide diets and food based interventions customized to individual needs, Zeisel said.

“We tell everyone to avoid sodium because it’s going to hurt their blood pressure,” he said. “But only about 10 percent of the population gets higher blood pressure from eating salt. If avoiding salt won’t do anything for you, why should you eat bland food? With software to analyze your entire genetic and metabolic profile, we can say, ‘Don’t worry about salt, but you should, say, eat more choline because you have a mutation in your gene that prevents you from making your own supply.'”

Zeisel said he expects the practice of nutrition to change completely in the next 10 years as physicians acquire the technology to evaluate thousands of gene-nutrient interactions. This goal lies at the heart of the research planned for the Nutrition Research Institute, part of the School of Public Health that will be located on the North Carolina Research Campus in Kannapolis, about 30 miles northeast of Charlotte. The Nutrition Research Institute will use cutting edge genomic and metabolomic biotechnology to develop innovative approaches to understanding the role of diet and activity in normal brain development, in the prevention of cancer and in the prevention and treatment of obesity and eating disorders.


For more information:

Note: Zeisel can be reached at (919) 843-4731 or

News Services contact: Becky Oskin, (919) 962-8596 or

School of Public Health contact: Ramona DuBose, director of communications, (919) 966-7467 or