Table 1.
Risk factors that can increase the susceptibility to negative health outcomes of low dietary choline intake.
| Risk Factor | Explanation |
|---|---|
| Men (vs. women) | Men are more susceptible to fatty liver under low choline intake because PEMT gene expression is induced by estrogen in women (higher PEMT-mediated choline production in women than in men) |
| Postmenopausal women (vs. pre-menopausal) | Young women have higher endogenous production of choline due to the effect of estrogen on PEMT |
| Newborns and infants | Liver PEMT activity is low at birth and the demands for choline are higher than in adults |
| Pregnancy | High demands compared to non-pregnant women and active transfer of choline to the fetus can deplete choline from the liver of the mother and predispose her for choline deficiency (e.g., fatty liver) |
| Lactation | High excretion of choline derivatives into breastmilk may deplete choline from mother’s liver and predispose her for choline deficiency (e.g., fatty liver) |
| Low vitamin B12 or folate intake or MTHFR 677 TT genotype | Adequate folate and vitamin B12 support choline endogenous production by providing S-adenosylmethionine needed for PEMT enzyme |
| High-fat diet | Triglycerides accumulate in the liver if choline intake is not proportional to fat content in the diet. Adult Wister rats fed a choline-deficient and fat-rich (40%) diet developed fatty infiltration of the liver within 21 days [11]. Supplementing the high-fat diet with 50–70 mg of choline daily reduced fat content in the liver of the animals that were previously fed a choline-deficient diet. Choline also prevented further accumulation of fat in the liver under continuous high-fat diet [11]. These results suggest that dietary fat intake could determine choline requirements |
| High sugar intake, toxins such as alcohol | These factors decrease the ability of the liver to metabolize fats and enhance fatty liver |
| Polymorphisms in PEMT gene (e.g., PEMT rs7946) | Carriers of some genotypes could have lower PEMT activity, implying higher requirements for dietary sources of choline |
| A plant-based diet | Adherence to a lacto-vegetarian or a vegan diet provides up to 50% lower dietary intake of choline compared to the adequate intake levels for pregnant and lactating women [4]. In addition, low choline and B12 intake in the same time can challenge one-carbon metabolism (e.g., hyperhomocysteinemia). Women adhering to a vegetarian or a vegan diet are at risk of insufficient choline intake and a target group for choline supplementation |
| The duration of a low-choline diet | A choline-deficient diet (e.g., contains 50 mg/d of choline) can cause liver damage (elevated liver enzymes) within 3 weeks in male subjects |