Choline

BACKGROUND

Choline is a precursor for a number of compounds including the neurotransmitter acetylcholine and the membrane constituents phospholipid and sphingomyelin, platelet activating factor and betaine, which is required by kidney cells and plays a role in donating methyl groups to homocysteine to form methionine. It is also important for lipid and cholesterol transport and metabolism if methyl groups. There is some evidence that choline may improve cognitive function and memory at all ages and, by extension, choline deficiency has been implicated in poor performance for groups such as the institutionalised elderly (fioravanti &Yanagi 2004, McDaniel et al 2003). There is also evidence that choline may reduce serum and urinary carnitine (Hongu & Sachan 2003).

Choline can be made in the body, but the ability of the body to produce enough depends on the methyl-exchange relationships between choline and folate, Vitamin B 12 and methionine (Zeisel & Blusztajn 1994). The dietary essentiality of choline was demonstrated in a study of healthy men with normal folate and vitamin B 12 status who developed liver damage with lower plasma choline and phosphatidylcholine concentrations when fed a choline-deficient diet (Zeisel et al 1991). However, few countries have included choline in their nutrient intake recommendations.

There is little information about requirements for most age and gender groups. Evidence from animal studies suggests that females may have a lower requirement than males. Female rats are less sensitive to choline deficiency than male rats, perhaps because of an enhanced capacity to form choline de novo (Tessitore et al 1995). If this is true for women, it is possible that the enhanced capacity may decrease after menopause (Lindblad & Schersten 1976) as animal experiments again have shown that oestrogens increase hepatic phosphatidyl-ethanolamine-N-methyltransferase activity (Drouva et al 1986, Young 1971).

Choline is widely distributed throughout the food supply, mostly in the form of phosphatidylcholine in membranes. Milk, liver, eggs and peanuts are particularly good sources. Vegetarians consuming significant quantities of refined products have a risk of becoming choline deficient. Wheat germ and dried soybeans are good sources of choline for this group (Zeisel et al 2003). Endogenous biosynthesis of choline does not meet physiological requirements and chronic deficiency leads to hepatic dysfunction.

Choline is absorbed in the small intestine both intact and after bacterial metabolism to betaine. Some betaine is also formed by oxidation of choline in liver and kidney (Bianchi & Azzone 1964, Weinhold & Sanders 1973). There appear to be no competitors for the choline transporter mechanism in the gut. The tissues of the body accumulate choline by diffusion and mediated transport (Zeisel 1981) and a specific carrier mechanism allows transport across the blood-brain barrier. This carrier has very high capacity in the neonate.

Although choline is essential, there appear to have been no reports of deficiency in the general population. Deficiencies have been seen in experimental situations and also in total parenteral nutrition (Buchman et al 1992, 1993, 1995, Chalwa et al 1989, Shapira et al 1986, Sheard et al 1986). Individuals with obesity, insulin resistance or diabetes, and middle-aged women have a propensity to develop fatty liver syndrome. This may in part be due to deficiencies of nutrients such as carnitine, essential fatty acids or choline, but there is little evidence. Given the propensity of visceral obesity in western countries including Australia and New Zealand, consideration of choline intake, amongst other nutrients, needs to be further explored.

Markers of liver dysfunction and plasma concentrations have been used to assess choline requirements, but both have limitations. Animal experiments show that hepatic choline and choline metabolites in liver decrease in choline deficiency (Zeisel et al 1989). Phosphocholine concentration in liver correlates highly with dietary choline and is also sensitive to modest changes in dietary intake. However, it is not easy to measure (Cohen et al 1995).

Plasma concentration of choline varies in response to diet (Buchman et al 1993, Burt et al 1980, Chalwa et al 1989, Sheard et al 1986, Zeisel et al 1991). The disadvantage of using it as a functional marker is that concentrations do not decline to less than 50% of normal, possibly due to hydrolysis of membrane phospholipids to maintain plasma levels (Savendahl et al 1997). Plasma phosphatidylcholine concentrations also decrease in choline deficiency, but phosphocholine concentrations are also influenced by factors that change plasma lipoprotein levels, so it is not a specific marker for choline deficiency (Zeisel et al 1991).