Chemistry - Vitamin E is a lipid soluble vitamin that can be found in either liquid or solid forms. The liquid forms occur as clear, yellow to brownish red, viscous oils that are insoluble in water, soluble in alcohol and miscible with vegetable oils. Solid forms occur as white to tan-white granular powders that disperse in water to form cloudy suspensions. Vitamin E may also be known as alpha tocopherol . Selenium in commercially available veterinary injections is found as sodium selenite. Each mg of sodium selenite contains approximately 460 micrograms (46%) of selenium.
Storage/Stability/Compatibility - Vitamin E/Selenium for injection should be stored at temperatures less than 25°C (77°F).
Pharmacology - Both vitamin E and selenium are involved with cellular metabolism of sulfur. Vitamin E has antioxidant properties and, with selenium, it protects against red blood cell hemolysis and prevents the action of peroxidase on unsaturated bonds in cell membranes.
Uses/Indications - Depending on the actual product and species, vitamin E/selenium is indicated for the treatment or prophylaxis of selenium-tocopheral deficiency (STD) syndromes in ewes and lambs (white muscle disease), sows, weanling and baby pigs (hepatic necrosis, mulberry heart disease, white muscle disease), calves and breeding cows (white muscle disease), and horses (myositis associated with STD).
A vitamin E/selenium product (Seletoc® —Schering) is also indicated for the adjunctive treatment of acute symptoms of arthritic conditions in dogs, but its efficacy for this indication has been questioned.
Pharmacokinetics - After absorption, vitamin E is transported in the circulatory system via beta-lipoproteins. It is distributed to all tissues and is stored in adipose tissue. Vitamin E is only marginally transported across the placenta. Vitamin E is metabolized in the liver and excreted primarily into the bile. Pharmacokinetic parameters for selenium were not located.
Contraindications/Precautions/Reproductive Safety - Vitamin E/selenium products should only be used in the species in which they are approved. Because selenium can be extremely toxic, the use of these products promiscuously cannot be condoned.
When administering intravenously to horses, give slowly.
Adverse Effects/Warnings - Anaphylactoid reactions have been reported. Intramuscular injections may be associated with transient muscle soreness. Other adverse effects are generally associated with overdoses of selenium (see below).
Overdosage/Acute Toxicity - Selenium is quite toxic in overdose quantities, but has a fairly wide safety margin. Cattle have tolerated chronic doses of 0.6 mg/kg/day with no adverse effects (approximate therapeutic dose is 0.06 mg/kg). Symptoms of selenium toxicity include depression, ataxia, dyspnea, blindness, diarrhea, muscle weakness, and a “garlic” odor on the breath. Horses suffering from selenium toxicity may become blind, paralyzed, slough their hooves, and lose hair from the tail and mane. Dogs may exhibit symptoms of anorexia, vomiting, and diarrhea at high dosages.
Drug Interactions - Vitamin A absorption, utilization and storage may be enhanced by vitamin E. Large doses of vitamin E may delay the hematologic response to iron therapy in patients with iron deficiency anemia. Mineral oil may reduce the absorption of orally administered vitamin E.
Elephants: Consult references listed below.
Savage,A., Leong,K.M., Grobler,D., Lehnhardt,J., Dierenfeld,E.S., Stevens,E.F., and Aebischer,C.P. 1999. Circulating levels of alpha-tocopherol and retinol in free-ranging African elephants (Loxodonta africana). Zoo Biology 18:(4):319-323
Shrestha,S.P., Ullrey,D.E., Bernard,J.B., Wemmer,C., and Kraemer,D.C. 1998. Plasma vitamin E and other analyte levels in Nepalese camp elephants (Elephas maximus). Journal of Zoo and Wildlife Medicine 29:(3):269-278 Abstract: Plasma concentrations of a-tocopherol (vitamin E) and other analytes in Asian elephants (Elephas maximus) inn Nepal were determined during typical work camp management of the elephants. Elephants foraged for food for 4-6 hr each day under the control of mahouts and were also provided daily with cut forage and supplements of unhusked rice, cane molasses, and salt. Blood samples were taken monthly for 1 yr without chemical restraint from 26 female elephants in four camps. Elephants were 6-60+ yr of age. Mean (+/-SEM) a-tocopherol concentration was 0.77+/-0.047 mg/ml with a range of 0.23-1.57 mg/ml. Subadults had lower concentrations than did older elephants, and there were significant differences in mean concentrations from different camps and in mean monthly concentrations. Plasma a-tocopherol concentration appears to vary widely between individuals, and a single value of <0.3 mg/ml is not sufficient to diagnose incipient vitamin E deficiency. Mean (+/-SEM) plasma retinol (vitamin A) concentration was 0.0063 +/- 0.0003 mg/ml with a range of 0.01-0.12 mg/ml. Subadults had higher concentrations than did older elephants, and mean retinal values differed significantly among camps. Beta-carotene was not found in plasma. Twenty-five other analytes determined or derived were generally similar to those reported in other Asian and African (Loxodonta africana) elephants. Estimates of nutrient intake, based upon diet composition, suggested that dietary concentrations of zinc and sodium may have been marginal, but the absence of signs of any nutrient deficiencies indicates that dietary husbandry in these elephant camps was generally satisfactory.
Stuart,R.L. 1997. Vitamin E Supplementation in the Elephant. The Elephant Managers Association Proceedings of the 18th Annual EMA Workshop, Fort Worth Zoological Park, Fort Worth Texas, November 1-4, 1997. Pages: 50-53
Dierenfeld,E.S. 1994. Vitamin E in exotics: effects, evaluation and ecology. Journal of Nutrition. 124:(12 Suppl):2579S-2581S Abstract: The pathophysiology and lesions associated with vitamin E deficiency are similar between domestic and exotic species, and circulating plasma concentrations are also similar between comparable groups. However, many ecological variables must be considered for the most relevant comparisons. Tissue values of vitamin E, apart from plasma, are unknown for most exotics. Dietary vitamin E requirements of exotic species and domestics appear to differ; based on natural foodstuff analyses and clinical observations, between 50 and 200 mg vitamin E/kg DM are necessary to prevent vitamin E deficiency, 5- to 10-fold higher than current livestock recommendations.
Sadler,W.C., Hopkins,D.T., Miller,R.E., Junge,R.E., Houston,E.W., Read,B., Kuehn,G., Gonzales,B., Miller,M., Kapustin,N., and Olson,D. 1994. Vitamin E forms for elephants. Proceedings American Association of Zoo Veterinarians. Pages: 360-370
Dierenfeld,E.S. and Traber,M.G., 1993. Vitamin E status of exotic animals compared with livestock and domestics. In: Packer,L. and Fuchs,J. (Editors), Vitamin E in health and disease. Marcel Dekker, Inc., New York pp. 345-370
Dierenfeld,E.S., Traber-MG, Packer-L (ed.), and Fuchs-J, 1993. Vitamin E status of exotic animals compared with livestock and domestics. In: Vitamin E in health and disease. Marcel Dekker, Inc; New York; USA pp. 345-370 Abstract: Vitamin E deficiency has long been recognized as a health problem in zoo animals. This review focuses on 3 areas for which comparative data from livestock and domestic animals are particularly useful: pathological and clinical deficiency signs; plasma and tissue concentrations; and dietary evaluation. Comparative data for domestic horses and zoo Perissodactyla (e.g., rhinoceros, elephants), domestic ruminants and zoo Artiodactyla (e.g., camels, giraffes), domestic swine and non-human primates, domestic carnivores (dogs, cats) and exotic carnivores (e.g., lions, tigers) and domestic poultry and zoo avifauna (e.g., ostriches, parrots) are presented.
Wallace,C., Ingram,K.A., Dierenfeld,E.S., and Stuart,R.L. 1992. Serum vitamin E status of captive elephants during prolonged supplementation of micellized natural alpha-tocopherol. Proc. Amer. Assoc. Zoo Vet.
Papas,A.M., Cambre,R.C., Citino,S.B., and Sokol,R.J. 1991. Efficacy of absorption of various vitamin E forms by captive elephants and black rhinoceroses. Journal of Zoo and Wildlife Medicine 22:(3):309-317 Abstract: A biochemical vitamin E deficiency may exist in captive elephants (Elephas maximus and Loxodonta africana) and black rhinoceroses (Diceros bicornis) because plasma alpha-tocopherol concentrations apparently are lower in these animals than in their free-ranging counterparts. Analysis of serum or plasma from 35 elephants and 11 black rhinoceroses from 11 zoological institutions and one private owner confirmed common occurrence and persistence of low circulating alpha-tocopherol levels. Concentrations averaged <0.3 micrograms/ml despite prolonged supplementation with D,L-alpha-tocopherol acetate, the most common vitamin E supplement for animal diets. Further experimental work demonstrated that supplementing the diet with D,L- or D-alpha-tocopherol acetate or D-alpha tocopherol to provide up to 62 IU/kg body weight (BW) in elephants and 23 IU/kg BW in black rhinoceroses increased circulating blood alpha-tocopherol by <0.2 micrograms/ml. Apparently, elephants and black rhinoceroses absorbed these fat-soluble or water-dispersible forms of vitamin E poorly. In contrast, the water-soluble form, D-alpha-tocopherol polyethylene glycol 1,000 succinate (TPGS) was absorbed well, as indicated by rapid increases in circulating blood alpha-tocopherol (0.3 to 1.9 micrograms/ml) from several-fold lower TPGS doses in the diet (4.8 or 6.6 IU/kg BW in elephants and 1.5 or 3.9 IU/kg BW in black rhinoceroses). There is a marked difference in the bioavailability of TPGS versus other vitamin E forms in captive elephants and black rhinoceroses, suggesting that there are major species differences in the utilization of various forms of vitamin E.
Dolensek,E.P. and Combs,S.B. 1990. Vitamin E deficiency in zoo animals. Proc.4th Ann.Scholl Conf.Nutrition of Captive Wild Animals.
Papas,A.M., Cambre,R.V., Citino,S.B., Baer,D.J., and Wooden,G.R. 1990. Species differences in the utilization of various forms of vitamin E. Proc. Amer. Assoc. Zoo Vet. Pages: 186-190
Dierenfeld,E.S. 1989. Vitamin E in elephants -- A research update. Proc.Ann.Elephant Workshop 10. Pages: 60-63
Ullrey,D.E. 1989. Is vitamin E really the key to sexual satisfaction? Proc.8th Ann.Scholl Conf.Nutrition of Captive Wild Animals. Pages: 49-57
Dierenfeld,E.S. and Dolensek,E.P. 1988. Circulating levels of vitamin E in captive Asian elephants (Elephas maximus). Zoo Biology 7(2):165-172 Abstract: Circulating levels of alpha-tocopherol (vitamin E) were examined via high-performance liquid chromatography in four female Asian elephants (Elephas maximus) at the New York Zoological Park between 1983 and 1987. Plasma vitamin E averaged 0.08 micrograms/ml in 1983, and was considered deficient. Over a four-year period of dietary supplementation ranging from 0.7 to 3.7 IU vitamin E/kg body mass (approximately 50 to 250 IU/kg diet as fed), mean plasma alpha-tocopherol increased to 0.6 micrograms/ml. Plasma and dietary vitamin E were found to be significantly correlated (p < 0.025) in these animals. Serum of plasma vitamin E measured in an additional 20 elephants from eight other zoological institutions in the United States and Canada averaged 0.5 microgram/ml, but values were not significantly correlated (P > 0.05) with calculated dietary levels of the vitamin. To achieve the mean value for circulating alpha-tocopherol in captive elephants (0.5 micrograms/ml), feed must provide at least 1.0, and more like 2.0 to 2.5 IU vitamin E/kg body mass (approximately 130 to 167 IU/kg diet).
Brush,P.J. and Anderson,P.H. 1986. Levels of plasma alpha-tocopherol (Vitamin E) in zoo animals. International Zoo Yearbook 24/25:316-321
Monitoring Parameters -
1) Clinical efficacy
2) Blood selenium levels. Normal values for selenium have been reported as: >1.14 micromol/L in calves, >0.63 micromol/L in cattle, >1.26 micromol/L in sheep, and >0.6 micromol/L in pigs. Values indicating deficiency are: <0.40 micromol/L in cattle, <0.60 micromol/L in sheep, and <0.20 micromol/L in pigs. Intermediate values may result in suboptimal production.
3) Optionally, glutathione peroxidase activity may be monitored
Dosage Forms/Preparations/FDA Approval Status/Withholding Times/Doses (per manufacturer) -
Veterinary-Approved Products: Vitamin E/Selenium Oral:
Equ-SeE (one teaspoonful contains 1 mg selenium and 228 IU vitamin E) & Equ-Se5E® (one teaspoonful contains 1 mg selenium and approximately 1100 IU vitamin E); (Vet-a-Mix) (OTC) Approved for oral use in horses.
Veterinary-Approved Products: Vitamin E/Selenium Injection:
Mu-Se® (Schering); (Rx): Each ml contains: selenium 5 mg (as sodium selenite); Vitamin E 68 IU; 100 ml vial for injection. Approved for use in non-lactating dairy cattle and beef cattle. Slaughter withdrawal = 30 days.
Dose: For weanling calves: 1 ml per 200 lbs. body weight IM or SQ.
For breeding beef cows: 1 ml per 200 lbs. body weight during middle third of pregnancy and 30 days before calving IM or SQ.
Bo-Se® (Schering); (Rx): Each ml contains selenium 1 mg (as sodium selenite) & Vitamin E 68 IU; 100 ml vial for injection. Approved for use in calves, swine and sheep. Slaughter withdrawal = 30 days (calves); 14 days (lambs, ewes, sows, and pigs).
Dose: Calves: 2.5 - 3.75 mls/100 lbs body weight (depending on severity of condition and geographical area) IM or SQ.
Lambs (2 weeks of age or older): 1 ml per 40 lbs. body weight IM or SQ (1 ml minimum).
Ewes: 2.5 mls/100 lbs. body weight IM or SQ.
Sows and weanling pigs: 1 ml/40 lbs. body weight IM or SQ (1 ml minimum). Do not use on newborn pigs.
L-Se® (Schering); (Rx): Each ml contains: selenium 0.25 mg (as sodium selenite) and Vitamin E 68 IU in 30 ml vials. Approved for use in lambs and baby pigs. Slaughter withdrawal = 14 days.
Dose:Lambs: 1 ml SQ or IM in newborns and 4 ml SQ or IM in lambs 2 weeks of age or older
Baby Pigs: 1 ml SQ or IM.
E-Se® (Schering); (Rx): Each ml contains selenium 2.5 mg (as sodium selenite) and Vitamin E 68 IU in 100 ml vials. Approved for use in horses.
Dose: Equine: 1 ml/100 lbs. body weight slow IV or deep IM (in 2 or more sites; gluteal or cervical muscles). May be repeated at 5-10 day intervals.
Seletoc® (Schering); (Rx): Each ml contains selenium 1 mg (as sodium selenite) and Vitamin E 68 IU in 10 ml vials. Approved for use in dogs.
Dose: Dogs: Initially, 1 ml per 20 pounds of body weight (minimum 0.25 ml; maximum 5 ml) SQ, or IM in divided doses in 2 or more sites. Repeat dose at 3 day intervals until satisfactory results then switch to maintenance dose. If no response in 14 days reevaluate. Maintenance dose: 1 ml per 40 lbs body weight (minimum 0.25 ml) repeat at 3-7 day intervals (or longer) to maintain.
Also available is a sustained-release selenium oral bolus (Dura Se®-120 —Schering) that provides 3 mg of selenium per day for up to 4 months.
Human-Approved Products: There are no approved vitamin E/selenium products, but there are many products that contain either vitamin E (alone, or in combination with other vitamins ±minerals) or selenium (as an injection alone or in combination with other trace elements) available.
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