Vitamin E

Vitamin E refers collectively to the antioxidant compounds known as tocopherols and tocotrienols. α-Tocopherol is the most biologically active form of vitamin E. The D stereoisomer is abundant in nature, where it is synthesized by plants. Synthetic vitamin E contains D and L stereoisomers of α-tocopherol (Matthai, 1996). Food sources of vitamin E include vegetable oils, nuts, seeds, and grains. Because the various vitamin E isomers have differing biologic activities, preparations of vitamin E are standardized to international units (IU). One IU is equivalent to the activity of 1 mg of synthetically prepared dl-α-tocopherol. Vitamin E is fat soluble and requires bile and pancreatic juice for maximal intestinal absorption. High dosages of vitamin E may interfere with absorption of other fat-soluble vitamins and may predispose to development of vitamin K–dependent coagulopathy. Vitamin E supplementation traditionally has been thought harmless; however, a recent metaanalysis of vitamin E use in humans with various diseases revealed that supplementation at dosages greater than 150 units/day was associated with increased all-cause mortality. This finding led to recommendations against vitamin E supplementation, particularly at dosages above 400 units/day (Miller et al, 2005).

In veterinary hepatology vitamin E is a commonly used antioxidant. Dosage recommendations for dogs have been reported in conference proceedings and vary from 10 units/kg every 24 hours orally to 250 or 400 units/dog every 24 hours orally. The author has used the 10-unit/kg every-24-hour oral dosage most commonly. Dosing small patients can be problematic because commonly available vitamin E preparations contain 400 or 1000 units. Controlled clinical trials evaluating efficacy and safety of vitamin E supplementation in canine and feline liver disease patients are unavailable. The author does not recommend vitamin E supplementation in liver disease patients with evidence of vitamin K deficiency. In such cases S-adenosylmethionine (SAMe) or milk thistle is a preferred antioxidant.

Milk Thistle (Silymarin)

The term silymarin refers collectively to the four flavonolignan isomers (silybin, isosilybin, silydianin, silychristin) that make up the active ingredients of the herb milk thistle (Silybum marianum). Silybin is the most biologically active isomer and makes up 50% to 70% of silymarin. These flavonolignans are found throughout the milk thistle plant but are concentrated in its fruit and seeds. Commercially available preparations of silymarin vary in content and bioavailability, a fact that makes dosage recommendations difficult and hampers use of silymarin in carefully designed, prospective clinical trials. Accordingly in 2005 the National Center for Complementary and Alternative Medicine (NCCAM) issued a request for industry collaboration to develop a well-characterized, standardized formulation of silymarin that could be used in human liver disease clinical trials. If such a standardized formulation is developed, it has the potential to benefit veterinary medicine also.

The primary effect of silymarin is thought to be as an antioxidant and free-radical scavenger, but it also is proposed to have antifibrotic, antiinflammatory, and immunomodulatory actions. In humans silymarin is used primarily to treat alcoholic liver disease, viral hepatitis, and toxin-induced liver disease. Large randomized controlled clinical trials using silymarin in specific human liver diseases are lacking; however, small clinical studies suggest some benefit in specific conditions.

In experimental animal models silymarin has been shown to ameliorate hepatic injury secondary to acetaminophen, carbon tetrachloride, radiation, iron overload, alcohol, cold ischemia, and the death cap mushroom (Amanita phalloides). Indeed, silymarin is so effective at reducing A. phalloides toxicosis by preventing hepatocyte uptake of mushroom toxins in humans and dogs that an intravenous formulation has been developed specifically for the purpose of treating mushroom poisoning in humans (Seeff et al, 2001). In veterinary medicine, clinical trials evaluating efficacy of silymarin in dogs and cats with naturally occurring hepatic disease have not been published. A silybin-phosphatidylcholine complex given to normal cats was found to be safe and demonstrate antioxidant activity (Webb et al, 2012). Dosage recommendations reported in conference proceedings vary, but 20 to 50 mg/kg every 24 hours orally (dogs and cats) commonly is recommended. A veterinary product is now available containing silybin bound to phosphatidylcholine for improved gastrointestinal absorption (Marin, 5 to 10 mg/kg every 24 hours orally).