nucleotides in erythrocytes, weight loss, and alopecia, which were reversed by injection of 40 mg of niacin.
Data are insufficient to estimate niacin requirements of nonhuman primates with confidence. It is probable that the dietary niacin requirement of rhesus monkeys with minimal synthesis from tryptophan is 16-56 mg·kg-1 of DM.
Vitamin B6 occurs as pyridoxine, pyridoxal, and pyridoxamine. These compounds function metabolically as the coenzymes pyridoxal phosphate and pyridoxamine phosphate. The vitamin B6 coenzymes are important cofactors in amino acid metabolism and in glycogen and lipid metabolism. Vitamin B6 coenzymes also can be involved in the synthesis of niacin from tryptophan (Leklem, 1996, 1999). The bioavailability of vitamin B6 in a mixed human diet is about 75% (Tarr et al., 1981). That in foods used for laboratory animals has been reported to be as low as 40-60% under some conditions (Baker, 1995). Supplemental vitamin B6 is usually added to feeds as pyridoxine hydrochloride, with a vitamin B6 potency of 92%.
Vitamin B6 deficiency has been produced in rhesus monkeys (Macaca mulatta) by a number of investigators, beginning with McCall et al. (1946), who described the resulting syndrome as consisting of weight loss, hypochromic anemia, and ataxia. Clinical improvement was noted in 2 weeks after provision of 1 mg of pyridoxine per day to 1.5- to 2-kg monkeys. Others have confirmed those clinical signs and modified the description of the deficiency to include widespread arteriosclerosis, leukopenia, anemia, liver cirrhosis, decreased plasma albumin, and increased plasma globulin, dental caries, and neural degeneration of the cerebral cortex (Rinehart and Greenberg, 1949a, 1951, 1956; Greenberg et al., 1952; Poppen et al., 1952; Mushett and Emerson, 1956; Victor and Adams, 1956; Greenberg et al., 1958; Greenberg, 1964; Wizgird et al., 1965). Arteriosclerosis involving many tissues and organs, anemia, leukopenia, alopecia, and dermatitis are the most frequently reported signs.
The interrelationship between essential fatty acids and vitamin B6 has been investigated because it was thought that vitamin B6 might be required for the conversion of linoleic acid to arachidonic acid. In turn, a deficiency of arachidonic acid might be responsible for atherosclerosis in primates. The vascular lesions of animals with a combined deficiency of essential fatty acids and vitamin B6 were no more severe than those seen in animals with simple vitamin B6 deficiency. The fatty acid patterns in plasma and erythrocytes of control and vitamin B6-deficient animals were similar and unlike those of animals deficient in essential fatty acids. The conclusion was that no metabolic interrelationship exists between the two nutrients (Greenberg and Moon, 1959, 1961; Greenberg 1964), although the role of vitamin B6 in lipid metabolism remains controversial (Leklem, 1999).
Arteriosclerosis develops in vitamin B6-deficient cynomolgus monkeys (Macaca fascicularis) and rhesus monkeys (Kuzuya. 1993). At least partial regression of the lesions occurs upon refeeding vitamin B6 (Yamada et al., 1965).
Vitamin B6 requirements were investigated in several studies, which are summarized in Table 7-4.
Rinehart and Greenberg (1956) tested graded levels of pyridoxine hydrochloride and measured growth of rhesus monkeys weighing 1.3-3.0 kg. They concluded that the requirement was 62 µg·BWkg-1·d-1 for optimal growth. But Emerson et al. (1960) fed pyridoxine hydrochloride at 50-2,000 µg·d-1 to rhesus monkeys weighing 4.1 kg. Ataxia and alopecia persisted in animals receiving 500 µg·d-1 or less, and higher dosages were required to alleviate deficiency signs. A dosage of 1.0-2.0 mg·d-1 (244-488 µg·BWkg-1·d-1) was required for optimal growth. Specific reasons for the difference in observed requirements reported by these investigators are not apparent, but the low requirement reported by Rinehart and Greenberg (1956) was observed in animals fed diets that were lower in protein than those fed by Emerson et al. (1960). In a number of studies of vitamin B6 deficiency, administration of 3.5 mg of vitamin B6 two times per week or 1.0 mg·d-1 has been sufficient to prevent signs of deficiency (Rinehart and Greenberg, 1949b, 1956; Poppen et al., 1952; Victor and Adams, 1956; Wizgard et al., 1965).
Mann (1968) described a vitamin B6 deficiency in capuchin monkeys (Cebus albifrons) that consisted of weight loss, profound hypochromic microcytic anemia, hair loss, dermatitis (especially about the hands and toes), and, rarely, convulsions. The livers were mildly fatty, but no cirrhosis was observed. In contrast with vitamin B6 deficiency in rhesus monkeys, cardiovascular changes and arteriosclerosis were not observed. A minimal therapeutic dose of vitamin B6 at 50-100 µg·BWkg-1·d-1 was required to promote optimal weight gain. Although it was not summarized in tabular form, inspection of a graph of hematocrit vs pyridoxine dose suggests that a level of about 175-200 µg·BWkg-1·d-1 was required for an optimal hematocrit response (Mann, 1969).
Vitamin B6 deficiency also has been produced in male baboons (Papio anubis) weighing 7-15 kg. The deficient animals became apathetic and anorexic and had occasional bloody diarrhea for a day or two. Some animals’ genitalia remained juvenile. Nervous tremors were sometimes observed. The baboons died after 6-8 months unless they were given pyridoxine parenterally. Some animals were kept on intermittent pyridoxine administration to sustain a concentration of serum pyridoxine known to be compatible with life. After 2 or more years of chronic deprivation, fatty degeneration of the liver was seen with hyperplastic nodules similar to premalignant or neoplastic lesions,