in folic acid for reproduction in other monkey species, was not optimal for reproduction in the squirrel monkey.

Capuchin monkeys (Cebus albifrons) exhibited deficiency signs similar to those of squirrel monkeys (Rasmussen et al., 1980; Thenen et al., 1991), including megaloblastic anemia, leukopenia, increased polymorphonuclear leukocyte lobe counts, and increased urinary formiminoglutamic acid. A wide variability in the severity of deficiency signs in dams and suckling neonates fed folic acid-deficient diets has been reported (Gillet et al., 1987); megaloblastic anemia was the sign most consistently present. Pregnant animals fed folic acid sufficient to support reproduction, but apparently below the requirement, had lowered blood and liver folate concentrations, increased urinary formiminoglutamic acid excretion, and reduced milk folate (Blocker et al., 1989).

Folic acid deficiency in marmosets (Callithrix jacchus) produced the usual deficiency signs (weight loss, alopecia, diarrhea, megaloblastic anemia, leukopenia, and granulocytopenia) and lesions of the oral mucosa, described as bilateral angular cheilosis, in about half the deficient animals (Dreizen and Levy, 1969). The stomatitis seemed to be a result of interference with maturation of the epithelial cells and later ulceration and secondary infection (Dreizen et al., 1970). The folic acid deficiency was prevented by supplementing the test diet with 0.1 mg of folic acid per day for animals consuming 30 g of diet per day.

Signs of folic acid deficiency in the baboon (Papio cynocephalus) were similar to those seen in other primate species, including weight loss, anorexia, gingivitis, diarrhea, severe leukopenia and thrombocytopenia, and sometimes macrocytic anemia. The animals lost weight before becoming anorexic. Abnormalities in the white cells appeared well before the development of anemia (Siddons et al., 1974a).

The proposed association between low folate status, hyperhomocyst(e)inemia, and vascular dysfunction has led to research with nonhuman primate models. A diet-induced hyperhomocyst(e)inemia in cynomolgus monkeys resulted in decreased blood flow to the leg when platelets were activated by intraarterial infusion of collagen (Lentz et al., 1996). Supplementation of atherosclerotic cynomolgus monkeys with 5 mg folic acid, 400 µg vitamin B12, and 20 mg vitamin B6 daily reduced plasma homocyst(e)ine concentrations but plasma cholesterol remained elevated, and normal vascular function was not restored (Lentz et al., 1997).

Folic acid requirements have been studied in a number of primate species, but the conclusions have not been consistent, because different measures were used as end points in assessing folic acid status. Findings from these studies are summarized in Table 7-5. The minimal folic acid requirement for growing rhesus monkeys has been estimated to be 30-60 µg·BWkg-1·d-1 (Cooperman et al., 1946; Day and Trotter, 1947, 1948). The requirement for squirrel monkeys for weight maintenance, based on regression analysis, was estimated to be 28 µg·BWkg-1·d-1. That was furnished by folic acid at about 0.3 mg·kg-1 of air-dry diet. However, the data suggest that 0.55 mg·kg-1 of air-dry diet was needed to ensure maximal growth. To maintain normal hematologic measures and cytologic features in bone marrow, the requirement was more than 75 µg·BWkg-1·d-1, which was furnished by folic acid at 0.84 mg·kg-1 of air-dry diet (Rasmussen et al., 1979). A higher dietary concentration was required to support reproduction in squirrel monkeys. Rasmussen et al. (1979) and Rasmussen (1980) reported that a stock diet containing folic acid at 1.4 mg·kg-1 of air-dry diet did not support optimal reproduction and was improved by supplementation with crystalline folic acid; this concentration was equivalent to folic acid at 3.0 mg·kg-1 of air-dry diet. Biologic availability of folic acid in natural ingredients is poorly understood, so these authors suggested a total folic acid requirement of 450 µg·BWkg-1·d-1,onthe basis of 25% availability of food forms. Capuchin monkeys appear to have a folic acid requirement for growth and normal hematologic status of 45-75 µg·BWkg-1·d-1;this requirement is similar to that of squirrel monkeys and could be met by providing folic acid at 0.84 mg·kg-1 of air-dry diet (Rasmussen et al., 1980).

The folic acid requirement of rhesus monkeys has been estimated to be 1.5 mg·kg-1 of dietary DM, on the basis of the data discussed above. The folic acid requirement of squirrel monkeys and capuchin monkeys is estimated to be 1.5 mg·kg-1 of dietary DMfor growth and 3.3 mg·kg-1 dietary DMfor reproduction. Data are insufficient for setting quantitative requirements of other species. The above requirement estimates take no account of the reduced biologic availability of folic acid in natural diets (Institute of Medicine, 1998). If all dietary folic acid is from natural ingredients, it is suggested that the requirements be increased to 2.55 and 5.61 mg·kg-1 dietary DMfor growth and reproduction, respectively.

Vitamin B12

Vitamin B12, also known as cobalamin, contains cobalt. The two active cofactor forms are adenosylcobalamin and methylcobalamin. The two mammalian enzymes for which vitamin B12 is a coenzyme are methylmalonyl-CoA mutase and methionine synthase. The vitamin is part of a metabolic enzyme system that removes the methyl group from folacin, regenerating that vitamin. Vitamin B12 also is involved in the formation of methionine from homocysteine and in nucleic acid metabolism. It is found only in animal products and microorganisms. Vegetables and grains contain no vitamin B12 (Herbert, 1996; Weir and Scott, 1999). Microorganisms in the rumen synthesize vitamin B12 if the cobalt supply is adequate. Thus, ruminants have a nutritional requirement for cobalt but not for vitamin B12 itself. It is



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