mild signs after an extended time. The monkeys in the study were consuming 200 g of air-dry food per day, so a biotin requirement of 60 g·kg-1 of air-dry diet (2.4 µg·BWkg-1·d-1) was suggested. When a biotin deficiency was produced in animals fed egg white or sulfa drugs, acute dermatitis developed around the hands, face, and feet and was accompanied by watering of the eyes, loss of fur color, and loss of weight (Lease et al., 1937; Waisman et al., 1945). Complete blood profiles of animals receiving sulfa drugs revealed no changes in hemoglobin concentration, red-cell or white-cell numbers, or differential white-cell count. Biotin at 20 µg·d-1 reversed deficiency signs in animals receiving either egg white or sulfa drugs (Waisman et al., 1945).

On the basis of the data of Waisman, biologically available biotin at 110 µg·kg-1 of dietary DMis adequate to prevent deficiency in animals fed egg white or receiving sulfa drugs. That requirement estimate assumes little or no synthesis of the vitamin by intestinal microflora and no biologic availability of biotin in natural feed ingredients.

Folacin

Folacin is the term used to refer to a family of pteroylglutamates or folates. Folic acid, which is sometimes used as an alternative name for folacin, is a pteroylmonoglutamate. In the older primate literature, folic acid is referred to as vitamin M. Folic acid is part of a coenzyme involved in receiving or donating one-carbon fragments in metabolic reactions, in much the same way that pantothenic acid is involved in metabolism of two-carbon acetyl fragments. Folic acid is involved in the metabolism of nucleotides, essential components of DNA and RNA. Folic acid coenzymes also are involved in the synthesis of serine from glycine and the synthesis of methionine from homocystine (Selhub and Rosenberg, 1996; Herbert, 1999).

Folacin in natural ingredients exists as polyglutamate conjugates. Before absorption by humans, folic acid must be released from the polyglutamate by hydrolysis to the monoglutamate form via intestinal conjugases (Selhub and Rosenberg, 1996). Humans have two intestinal conjugases, one on the brush border of intestinal cells and the other an intracellular soluble enzyme. Rhesus monkeys (Macaca mulatta) fed a nonpurified diet containing synthetic folic acid did not have a conjugase on the intestinal-cell brush border (Wang et al., 1985). Other species of monkeys appear not to have been studied in this respect. The lack of a brush-border conjugase in rhesus monkeys might be related to the predominant form of folic acid in the diet. However, complete biologic availability of polyglutamate forms to nonhuman primates in natural dietary ingredients cannot be assumed. Folic acid is the supplemental folacin form usually added to feeds.

Dietary factors can affect folic acid availability. Gyr et al. (1974) reported a decrease in folic acid absorption in patas monkeys (Erythrocebus patas) fed a protein-deficient diet (0% protein). Ethanol also has been shown to inhibit folic acid absorption (Blocker and Thenen, 1987). In humans, the bioavailability of synthetic folic acid consumed with food is estimated to be 85%, whereas the bioavailability of folic acid in natural foods is estimated to be 50%. Folic acid in natural foods is concluded to be about 60% as available as synthetic folic acid (50/85 × 100 = 59%) (Institute of Medicine, 1998).

Folic acid deficiency has been studied in macaques, marmosets, squirrel monkeys, and capuchin monkeys. The most consistent deficiency signs in all species were leukopenia and megaloblastic anemia. The anemia was characterized by lowered hemoglobin and red-cell counts and higher mean corpuscular volumes (Blocker and Thenen, 1987).

Langston et al. (1938) first demonstrated the need for folic acid (then designated vitamin M) in the rhesus (Macaca mulatta) monkey. The deficiency signs in rhesus monkeys were weight loss, anorexia, diarrhea, leukopenia, thrombocytopenia, and megaloblastic anemia (Waisman and Elvehjem, 1943; Cooperman et al., 1946). Folic acid-deficient female rhesus monkeys also had abnormalities of their reproductive system characterized by atresic and cystic ovarian follicles with loss of granulosa cells. Proliferation of the granulosa cells appeared to be associated with interruption of DNA synthesis. The normal cyclic changes in the vaginal and cervical epithelium were impaired, and multiple abnormal cells were seen (Mohanty and Das, 1982). Folic acid deficiency in cynomolgus monkeys (Macaca fascicularis) was similar to that in rhesus monkeys, with megaloblastic anemia and weight loss predominant. Folic acid-depleted animals also had lower concentrations of folic acid in red-cells, plasma, and liver. Urinary excretion of formiminoglutamic acid was increased (Blocker and Thenen, 1987).

Folic acid deficiency in the squirrel monkey (Saimiri sciureus) resulted in weight loss, alopecia, scaly dermatitis, and megaloblastic anemia with profound intramedullary hemolysis in the bone marrow. Deficient animals had reduced plasma and red-cell folic acid and increased urinary formiminoglutamic acid (Rasmussen et al., 1979). The folic acid status of pregnant squirrel monkeys fed a commercial stock diet with and without a folic acid supplement was evaluated (Rasmussen, 1979; Rasmussen et al., 1980). Females supplemented with folic acid had greater maternal weight gain during pregnancy, and infants from supplemented females had higher birth weights. Higher red-cell folic acid concentrations and somewhat lower mean cell volumes were also seen in supplemented animals. Those results indicated that the stock diet, presumably adequate



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