increased into the normal range but decreased back to baseline when choline supplementation was discontinued. Fatty liver was resolved completely during choline supplementation but steatosis (fatty liver) recurred in one patient after 10 weeks of return to choline-free TPN. The available data support the provisional conclusion that de novo synthesis of choline is not always sufficient to meet human requirements for choline.

Supporting animal studies (in many species, such as the baboon) also found that a choline-deficient diet resulted in decreased choline stores and liver dysfunction (Hoffbauer and Zaki, 1965; Sheard et al., 1986; Tayek et al., 1990; Yao and Vance, 1990). The following animals fed a choline-deficient diet may be susceptible to developing growth retardation, renal dysfunction and hemorrhage, or bone abnormalities: baboon (Hoffbauer and Zaki, 1965), chicken (Blair et al., 1973; Ketola and Nesheim, 1974), dog (Best and Huntsman, 1932; Hershey, 1931), guinea pig (Tani et al., 1967), hamster (Handler, 1949), pig (Blair and Newsome, 1985; Fairbanks and Krider, 1945), quail (Ketola and Young, 1973), rat (Newberne and Rogers, 1986), and trout (Ketola, 1976).

The liver is damaged when humans consume an otherwise adequate diet that is deficient in choline, resulting in elevated alanine aminotransferase levels in blood (Burt et al., 1980; Tayek et al., 1990; Zeisel et al., 1991). Fatty infiltration of liver also occurs in choline deficiency but is difficult to use as a functional marker without special liver imaging techniques (Buchman et al., 1992).

Hepatic choline and choline metabolite concentrations have been shown to decrease during choline deficiency in the rat (Zeisel et al., 1989). Phosphocholine concentration in liver is highly correlated with dietary choline intake, decreasing to 10 to 20 percent of control values after 2 weeks on a diet sufficient in methionine, folate, and vitamin B₁₂ but deficient in choline (Pomfret et al., 1990). Hepatic phosphocholine concentration was most sensitive to modest dietary choline deficiency, decreasing to 10 to 20 percent of control values after 2 weeks of a deficient diet (Pomfret et al., 1990). This