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PHARMACOLOGICAL ACTIVITIES - TOXICOLOGY - DRUG INTERACTIONS

Mixed Tocopherols

Mixed tocopherols are the collective term for a family of chemical substances that are
structurally related to alpha-tocopherol. Increasing the dietary polyunsaturated fatty acid
content simultaneously increases the requirement for vitamin E (Wander et al., 1997).
Appropriate levels of fish oil and vitamin E have been shown to increase life span, improve
life quality, reduce symptoms and physical evidence of disease, and decrease mortality rates in
dogs with heart disease (Dove, 2001). A wide range of clinical signs of vitamin E deficiency
in dogs has been reported: degeneration of skeletal muscles associated with muscle weakness
and reproductive failure in male and females, subcutaneous edema, anorexia, depression,
dyspnea, and eventual coma. Vitamin E deficiency in cats has been associated with depression and
anorexia, hyperesthesia on palpation of the ventral abdomen, and nodular adipose tissue (NRC,
2006).

Toxicity for mixed tocopherols has not been documented in dogs and cats when administered orally in therapeutic
TOXICOLOGY 5 mg/kg of body weight/day of dl-α-tocopherol intramuscular or subcutaneous, but significant mortality occurred
doses. However, a study in kittens suggested that toxicity of vitamin E was dose related. No mortality occurred at

at doses equivalent to 100 to 200 mg/kg of body weight/day and a dose of 1000 mg/kg of body weight/day caused
death in all kittens in the study (NRC, 2006). The acute oral LD value of all-rac-α-tocopheryl acetate for rats,
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mice, and rabbits, has been estimated to be in excess of 2 g/kg of body weight (NRC, 1987).

DRUG Validated interactions studies do not exist for vitamin E preparations. Clinical interactions
INTERACTIONS with other drugs have not been reported. However, it has been reported that vitamin E at
doses greater than 400 IU per day may increase the effect of anticoagulant drugs, although
data are inconsistent (Kim & White, 1996; Corrigan & Marcus, 1974).
A number of medications may decrease the absorption of vitamin E, including
cholestyramine, colestipol, isoniazid, mineral oil, orlistat, sucralfate, and the fat substitute,
olestra. Anticonvulsant drugs, such as phenobarbital, phenytoin, or carbamazepine, may
decrease plasma levels of vitamin E (Hendler & Rorvik, 2001).

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