erythropoiesis was characterized by the presence of multi-nucleated red-cell precursors in both bone marrow and peripheral-blood smears (Porter and Fitch, 1966; Ausman and Hayes, 1974; Fitch et al., 1980). The hemolytic anemia occurred nearly at the end stage and was initially normocytic and then macrocytic, with insufficient reticulocytosis to ameliorate the anemia. Severe anemia was characterized by segmented erythrocytes in the blood and evidence of localized folate deficiency in bone marrow (Ausman and Hayes, 1974). In addition to those observations, Morris et al. (1966) reported defective cholesterol metabolism in vitamin E-deficient monkeys—a finding that was later supported by Mickel et al. (1975).

The initial experimental diets used by the above investigators were rich in animal-based saturated fat but contained small amounts of plant or fish oils to provide essential fatty acids. Bieri and Evarts (1972) showed that RRR-α-tocopherol at 5 mg·kg−1 of diet was insufficient to return plasma α-tocopherol concentrations to normal in monkeys experimentally depleted for periods of 20-60 days, whereas 10 mg·kg−1 of diet re-established baseline plasma α-tocopherol concentrations of 12-14 mg·L−1. They calculated that the -tocopherol requirement was 0.72 mg·g−1 of linoleic acid in the diet.

Fitch and Dinning (1963) showed in the rhesus monkey and Horwitt et al. (1972) in humans that the vitamin E requirement depends on concentrations of PUFAs in the diet. In a series of long-term experiments, both cebus monkeys (Cebus albifrons) and cynomolgus monkeys (Macaca fascicularis) were fed experimental diets containing 22% by weight of either coconut oil or stripped safflower oil (Ausman and Hayes, 1974; Hayes, 1974a,b; Mickel et al., 1975). Neither species fed the diet that was nearly devoid of PUFAs developed signs of vitamin E deficiency within a 2-year period. In contrast, cebus monkeys fed the diet containing stripped safflower oil developed classic signs of vitamin E deficiency within 12 months (lethargy, weakness, muscular dystrophy, hemolytic anemia, jaundice, splenomegaly, hemosiderosis, and lipofuscin and ceroid pigments in various organs), as well as evidence of peroxidation of retinal lipids in the macula of the eye (Hayes 1974b). Cynomolgus monkeys developed the same signs after 24 months. That moderate to large amounts of PUFAs will hasten the development of vitamin E deficiency also has been observed in common marmosets (McIntosh et al., 1987; Ghebremeskel et al., 1991), African green monkeys (Parks et al., 1987, 1990), and cynomolgus monkeys (Kaasgaard et al., 1992; Thomas et al., 1994; Thomas and Rudel, 1996). Finally, in a series of experiments examining immune function in cynomolgus monkeys fed marine- and plant-derived n-3 fatty acids it was possible to ensure adequate vitamin E status by adjusting dietary tocopherol content in relation to fatty acids, according to the formula of Muggli (1989). Thus, vitamin E requirements of nonhuman primates appear to vary (in part) in relation to dietary concentrations of 18:2 and 18:3 fatty acids.


The dependent variables used most often to assess vitamin E status or to define vitamin E requirements are plasma α-tocopherol concentrations, followed by the presence or absence of clinical signs of deficiency. α-Tocopherol concentrations in the plasma of apparently normal nonhuman primates have been reported to be 5-10 mg·L−1 in chimpanzees and orangutans (Ghebremeskel and Williams, 1988; Crissey et al., 1999), 10-11.6 mg·L−1 in gorillas (McGuire et al., 1989; Crissey et al., 1999), 5-8 mg·L−1 in baboons (de La Pena et al., 1972; Slifka et al., 2000), 9-10.6 mg·L−1 in mandrills (Slifka, 1994; Crissey et al., 1999), 12-16 mg·L−1 in rhesus monkeys (Nelson et al., 1981), 5-10.5 mg·L−1 in common marmosets (Charnock et al., 1992; Flurer and Zucker, 1989; Ghebremeskel et al., 1990), and 5 mg·L−1 in Saguinus fuscicollis (Flurer and Zucker, 1989). Six free-ranging black spider monkeys (Ateles paniscus chamek) had a mean plasma α-tocopherol concentration of 3.7 mg·L−1, with a range of 2.3-4.8 mg·L−1 (Karesh et al., 1998). Animals made experimentally deficient or exhibiting frank malabsorption or other illnesses that potentially affect vitamin E status had plasma α-tocopherol concentrations ranging from undetectable to 1 mg·L−1 (Ausman and Hayes, 1974; Fitch et al., 1980; Baskin et al., 1983; Chalmers et al., 1983; McIntosh et al., 1987; McGuire et al., 1989). In studies in which plasma concentrations of both α- and γ-tocopherol were determined, γ-tocopherol concentrations were generally no more than 10% of α-tocopherol concentrations (Slifka, 1994, 2000; Crissey et al., 1999)

Aside from prevention of the classical signs of deficiency, vitamin E has been used as a supplement to help prevent a variety of chronic diseases. Marmosets given neurotoxin to induce Parkinson’s disease appeared to derive no benefit from the intramuscular injection of α-tocopherol at 1,000 mg·BWkg−1 (Perry et al., 1987), although such an injection proved beneficial in mice (Perry et al., 1985). Verlangieri and Bush (1992) were able to show that 79 mg of d-α-tocopherol per day was beneficial in prevention and reversal of aortic stenosis in long-term atherogenic studies in the cynomolgus monkey. In a series of investigations of the rhesus monkey as a model of age-related macular degeneration (ARM) in humans (Crabtree et al., 1996a, 1996b, 1997), vitamin E concentrations in the peripheral neural retina correlated with concentrations of retinal protein, plasma α-tocopherol, and dietary vitamin E. The lowest concentration of vitamin E found in the retina of rhesus monkeys was in the foveal crest, which is where ARM begins in humans.

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