Reference Number: 679
Year: 2010
Link: Link to original paper
Nutrition: Choline
Summary
ABSTRACT
Background: Choline is obtained from the diet and from the biosynthesis of phosphatidylcholine. Phosphatidylcholine is catalyzed by the enzyme phosphatidylethanolamine-N-methyltransferase (PEMT), which is induced by estrogen. Because they have lower estrogen concentrations, postmenopausal women are more susceptible to the risk of organ dysfunction in response to a low-choline diet. A common genetic polymorphism (rs12325817) in the PEMT gene can also increase this risk. Objective: The objective was to determine whether the risk of low choline–related organ dysfunction increases with the number of alleles of rs12325817 in premenopausal women and whether post-menopausal women (with or without rs12325817) treated with estrogen are more resistant to developing such symptoms. Design: Premenopausal women (n = 27) consumed a choline-sufficient diet followed by a very-low-choline diet until they developed organ dysfunction (or for 42 d), which was followed by a high-choline diet. Postmenopausal women (n = 22) were placed on the same diets but were first randomly assigned to receive estrogen or a placebo. The women were monitored for organ dysfunction and plasma choline metabolites and were genotyped for rs12325817. Results: A dose-response effect of rs12325817 on the risk of choline related organ dysfunction was observed in premenopausal women: 80%, 43%, and 13% of women with 2, 1, or 0 alleles, respectively, developed organ dysfunction. Among postmenopausal women, 73% who received placebo but only 18% who received estrogen developed organ dysfunction during the low choline diet. Conclusions: Because of their lower estrogen concentrations, post-menopausal women have a higher dietary requirement for choline than do premenopausal women. Choline requirements for both groups of women are further increased by rs12325817. This trial was registered at clinicaltrials.gov as NCT00065546.
Summary of Findings
This study focuses on the rs12325817 SNP on PEMT. It is a human clinical trial of pre and post menopausal women. It explored why some women develop signs of choline deficiency, such as liver or muscle damage, when their diet is low in choline, while others remain completely healthy. The researchers focused on two major factors that influence choline needs: oestrogen levels and genetic variation in the PEMT gene, which helps the liver make phosphatidylcholine, a molecule essential for exporting fats and maintaining healthy cell membranes.
The study involved premenopausal women, postmenopausal women, and postmenopausal women taking oestrogen therapy. All participants first ate a diet with enough choline, then switched to a very low choline diet until they showed early signs of organ dysfunction, and finally returned to a high choline diet to recover. The researchers also tested each woman for specific PEMT gene variants that reduce the body’s ability to make phosphatidylcholine.
The results showed a clear pattern. Premenopausal women, who naturally have higher oestrogen levels, were the most resistant to choline deficiency. Many of them could stay on the low choline diet for a long time without developing liver or muscle problems. This is because oestrogen activates the PEMT gene, allowing the liver to make more phosphatidylcholine internally, reducing the need for dietary choline.
In contrast, postmenopausal women not taking oestrogen were much more vulnerable. A large proportion developed organ dysfunction relatively quickly when choline intake was restricted. Without oestrogen, their PEMT activity was lower, so they relied far more on dietary choline to keep their liver and muscles healthy.
The study also found that genetic variation strongly influenced choline requirements. Women who carried certain PEMT variants, especially the promoter variant that reduces oestrogen responsiveness, were significantly more likely to develop organ dysfunction on a low choline diet. This was true even for some premenopausal women, showing that genetics can override the natural protection provided by oestrogen. Women with homozygous SNPs on the risk variant were the most sensitive to choline deficiency.
When postmenopausal women took oestrogen therapy, their resistance to choline deficiency improved dramatically. Oestrogen essentially “rescued” PEMT activity, allowing their bodies to make more phosphatidylcholine and reducing their reliance on dietary choline.
Overall, the study demonstrated that choline requirements vary widely among women, depending on both hormone status and genetic makeup. A single recommended intake is unlikely to meet everyone’s needs. Women with low oestrogen, such as those who are postmenopausal, have had their ovaries removed, or have certain medical conditions, and women with PEMT risk variants may require higher choline intake to maintain liver and muscle health.
The authors conclude that personalised nutrition is essential for choline, and that both genetics and hormonal status should be considered when determining optimal intake.
Significance to the Baker
For a baker cooking for postmenopausal women, this paper highlights why choline rich ingredients can make a meaningful difference in supporting their wellbeing. After menopause, oestrogen levels fall, which reduces the body’s ability to activate the PEMT gene and make choline internally. The study shows that many postmenopausal women become far more sensitive to low choline diets, especially if they also carry certain PEMT gene variants. For a baker, this means that choosing ingredients naturally higher in choline, such as eggs, soy flour, wheat germ, legumes, and certain seeds, can help create baked goods that are not only delicious but also nutritionally supportive for this group. It is a simple, food based way to help women maintain healthier liver and muscle function through everyday eating. Seeds don’t replace primary choline sources like eggs, soy, or legumes, but they add steady background intake and often come packaged with nutrients that support the same metabolic pathways, especially methionine, B vitamins, and healthy fats. The best sources of choline from seeds are flaxseeds, then sesame seeds and sunflower seeds. Putting these seeds in porridge pots for breakfast is a way to get them into a regular dietary pattern.
