nutrient for humans. However, signs of choline deficiency have been described when dietary choline concentrations are low and supplies of other methyl donors, such as methionine, are inadequate. Choline usually is added to the diet as choline chloride or choline bitartrate. Choline chloride is quite hydrophilic and often is added as a liquid containing 70% choline (Chan, 1991).
Many factors influence the choline requirement. Rats fed low-protein diets or diets containing suboptimal amounts of methionine require choline supplementation, whereas rats fed diets containing 0.8% methionine show no requirement for choline (National Research Council, 1995a).
The evidence of choline need in normal primate diets is not clear. Wilgram et al. (1958) fed a diet devoid of choline to both rhesus monkeys (Macaca mulatta) and capuchin monkeys (Cebus spp.) (four animals of each species) for over a year. The diet contained about 0.16% methionine and 18% fat. Although the protein concentration of the diet was unspecified, it appeared to be 13-14%. When the diet was supplemented with 0.3% choline chloride, weight gains were greater, and one female had a baby and successfully nursed it. After a year, liver biopsies were taken by laparotomy. Liver lipid concentrations were 12-22% in unsupplemented animals and 6-9% in animals that were choline-supplemented. Liver phospholipids were lower and liver cholesterol was higher in unsupplemented animals. Histologic examination of the livers from animals fed the choline-free diet revealed lipid droplets throughout the liver, but no cirrhosis. The livers of the choline-supplemented animals were normal.
The production of fatty livers in rhesus monkeys fed a choline-free diet was confirmed, and one death from liver disease was described by Cueto et al. (1967). Patek et al. (1975) also observed cirrhosis of the liver in a rhesus monkey fed a low-protein, low-choline diet.
Studies with a low-choline diet were extended; diets were modified to contain less protein and 2% cholesterol (Wilgram, 1959; Gaisford and Zuidema, 1965; Ruebner et al., 1969; Rutherford et al., 1969). The diet was said to contain 5% protein, but the formulation indicates about 9% protein. In any event, it produced liver cirrhosis in capuchin and rhesus monkeys. It was suggested that the increased dietary cholesterol might have made the animals more susceptible to liver cirrhosis (Patek et al., 1975). Whether supplemental choline would prevent or reverse the cirrhosis seen with the low-choline, high-cholesterol diet was not tested.
In an attempt to produce choline deficiency in baboons (Papio doguera), a high-fat, low-protein diet that had been shown to produce severe choline deficiency in rats was fed (Hoffbauer and Zaki, 1965). The baboons developed mildly fatty livers after 2 months, but the degree of fat accumulation remained unchanged after 5 months. A control diet with added choline was not fed. The lesions were reversed when the animals were returned to a normal diet. The results suggest that the requirement of the adult baboon for choline, if there is one, is substantially lower than that of the rat. It should be noted that Lieber et al. (1994) were able to prevent fatty liver and fibrosis caused by ethanol ingestion when the diet of baboons was supplemented with phosphatidylcholine.
No studies have clearly established a dietary choline requirement for nonhuman primates independent of other dietary modifications. It does seem clear that a fatty liver, and occasionally cirrhosis, will result from feeding a low-protein, methionine-deficient, low-choline diet. The effect of supplemental methionine has not been investigated, but the fatty liver observed after feeding such a diet can be prevented by supplementation with 0.3% choline chloride (furnishing about 0.23% choline) (Wilgram et al., 1958). Kark et al. (1974) fed a semipurified diet containing 0.1% choline chloride (about 0.075% choline) without producing deficiency signs.
Carnitine is a required vitamin for some insects, but it is not generally recognized as an essential nutrient for mammals. Metabolically, carnitine functions in the transport of fatty acids into the mitochondria (Borum, 1991). There is no evidence that nonhuman primates require carnitine. Carnitine is found only in animal products, so presumably the control diets fed by Kark et al. (1974) and Agamanolis et al. (1976) to rhesus monkeys (Macaca mulatta) for 45 months contained no carnitine. The animals showed no signs of a deficiency disease, so it seems unlikely that there is a substantial carnitine requirement.
Inositol has occasionally been considered a vitamin, primarily on the basis of early work that suggested it was a required nutrient for mice. Later research has shown that conventionally reared mice do not require dietary inositol although gnotobiotic or antibiotic-treated mice possibly do (National Research Council, 1995b).
An inositol requirement has not been demonstrated in nonhuman primates, but there has been no attempt to do so. It is not recognized as a required nutrient for humans (Cody, 1991). In obese, insulin-resistant rhesus monkeys (Macaca mulatta), dietary myo-inositol in pharmacologic doses (1.65 g·BWkg-1·d-1) produced a mild decrease in postprandial plasma glucose concentrations without increasing postprandial insulin concentrations (Ortemyer, 1996). However, that relatively small effect of such a large dose cannot be regarded as demonstrating a nutrional requirement.