Good/Bad Effects of Antioxidants
In a society that is trying to slow the aging process, free radicals and antioxidants are terms that are regularly tossed around. One might not realize their importance in horses, but researchers continue to pursue the details of how and why the antioxidants vitamin E and selenium are so crucial to horses. Oxidation is a metabolic process that transforms carbohydrates, fats, and proteins into energy. A normal side effect of oxidation is the creation of waste products called free radicals that damage cell membranes. The antioxidants, such as vitamin E and selenium, battle these harmful free radicals by reducing their activity.
Vitamin E is a lipid-soluble, chain-breaking antioxidant that is essential for optimum function of the reproductive, muscular, circulatory, nervous, and immune systems. It protects against exercise-induced muscle damage and improves immune response. Vitamin E helps maintain membrane integrity, and it protects cell membranes from peroxidative damage. There are eight forms of vitamin E--four tocopherols (alpha, beta, delta, and gamma) and four tocotrienols (alpha, beta, delta, and gamma). Alpha-tocopherol is the most active form and is taken up preferentially by the central nervous system.
Vitamin E is abundant (30-100 IU, or International Units, per kilogram) in green, growing pastures and fresh forages harvested at an immature state, but its content decreases with forage maturation. Harvesting also has a negative impact on quantity. One month of hay storage can decrease the amount of vitamin E by 50%.
The vitamin is high in the germ of grains and oils pressed from the germ. Most vegetable oils contain 100-300 IU/kg of vitamin E. However, Paul Siciliano, PhD, assistant professor in the Department of Animal Sciences at Colorado State University, warns that you should never assume it is there unless the oil has been analyzed. "Some refining processes remove the vitamin E from the oil," he says.
Nearly all vitamin E is lost in high-moisture feeds such as silage, haylage, and acid-treated grains. Cereal grains such as corn, oats, and barley are very low in vitamin E (20-30 IU/kg). Therefore, it is often added to "fortified" feeds, but high levels of moisture in the feed (enough to cause molding), grinding, storage, and heat all decrease vitamin E content.
Vitamin E status can be monitored in plasma, and different forms of vitamin E give different levels in the plasma. It remains to be seen what the optimal levels are for the horse, notes Joe Pagan, PhD, owner of Kentucky Equine Research in Versailles. Research has shown that natural sources of vitamin E are much more readily available to the horse than synthetic forms, some of which are not absorbed by the horse at all. (See sidebar on page ?? for results of experiments on various types and dosages of vitamin E.)
The ideal amount of vitamin E needed by the horse is not known. The National Research Council (NRC) Guidelines set in 1989 (which will be updated in the next few years) recommend 50 IU/kg of feed for horses at maintenance. It is suggested that foals, pregnant mares, lactating mares, and heavy-working horses need 80-100 IU/kg. Horses not on good pasture or which do not receive maintenance rations might need upward of 1,000 IU of vitamin E per day as a supplement. In addition, it could be helpful to supplement vitamin E in intensely exercised horses, such as endurance horses.
However, Stephanie J. Valberg, DVM, PhD, Dipl. ACVIM, of the University of Minnesota, says it is important to recognize that the vitamin E and selenium available in the diet varies throughout the country depending on the diet and soil selenium content. Therefore, it is important to check the horse's vitamin E status by measuring plasma vitamin E. If the levels are low, additional amounts can be supplemented. She warns, "Supplementation should be done using a vitamin E supplement without additional selenium, as you will feed toxic levels of selenium if you give 6,000 units of vitamin E plus the selenium in the combined supplement." After about four weeks of supplementation, another blood test should be run to see if the levels have come up to an acceptable range.
The horse can store enough vitamin E to compensate for four months of inadequate intake, but then becomes deficient. A deficiency can result in nutritional muscular dystrophy, degenerative myelopathy, or equine motor neuron disease. While not proven, it is thought that low levels of vitamin E could cause degenerative myeloencephalopathy in young horses which are predisposed to it.
Signs of vitamin E deficiency include weight loss even with a good appetite, rough haircoat, and neurologic problems. Conversely, signs of vitamin E toxicity have not been seen.
While only limited work has been done, research suggests a positive effect of supplemental vitamin E on the equine immune system. According to Siciliano, vitamin E can influence the humoral immune response, which is the part where antibodies are the primary mediator of the immune response. However, the exact amount of vitamin E needed to elicit this improvement is not known.
Equine Motor Neuron Disease
Equine motor neuron disease (EMND) is similar to Lou Gehrig's disease in humans. It is associated with, and likely caused by, vitamin E deficiency. It is a neurodegenerative disorder of the somatic (body) lower motor neurons first recognized in New York in 1990. It is typically seen in horses over two years of age. Signs include an acute onset of trembling, weight shifting, excessive lying down, muscle wasting, and weight loss. The horse might exhibit a high tail carriage and low head carriage. Muscle atrophy, which occurs because the dying motor neurons cannot send messages to the muscles, and debilitation continue over several months until, in severe cases, debilitating weakness or death occurs. In horses with EMND, the vitamin E levels are low while the selenium levels are normal. To prevent this debilitating disease, horses without access to green forage that is high in vitamin E for a prolonged period of time should receive supplemental vitamin E. Researchers feel that one daily dose of 1,000 IU would be sufficient.
Some horses can develop a syndrome called tying-up (rhabdomyolysis) that is characterized by signs of muscle stiffness and pain with exercise. If muscle cells are damaged, proteins such as creatine kinase (CK), aspartate transaminase (AST), and myoglobin leak into the horse's blood and can be picked up on a diagnostic test. If muscle damage is severe, a large amount of myoglobin is excreted in the urine and, if horses are dehydrated, this can cause acute kidney failure.
Clinical signs of tying-up develop after a variable period of exercise and can range from mild stiffness of hindlimb muscles to anxiety, profuse sweating, rapid heart and respiration rates, reluctance to move, and possible collapse. The muscles in the loin and hindquarters can be especially hard and painful.
There are a variety of suspected causes for tying-up. Some horses might develop tying-up due to inadequate training, excessive work, or nutritional imbalances, whereas other horses have inherited abnormalities in the way their muscles function that make them permanently susceptible to the condition. Known heritable causes of tying-up include polysaccharide storage myopathy (PSSM) and recurrent exertional rhabdomyolysis (RER). Nutritional factors that contribute to tying-up are excess carbohydrates, electrolyte imbalances, and vitamin E and/or selenium deficiencies.
Since vitamin E and selenium protect muscles from toxic free radicals produced as a result of exercise, it is reasonable to think that deficiencies would exacerbate tying-up signs. While it is important to make sure afflicted horses receive adequate levels of vitamin E and selenium, according to Valberg, "there is no evidence to suggest that over-supplementation prevents muscle damage in horses with tying-up."
Selenium works hand in hand with vitamin E as part of the cellular antioxidant defense system, and it is an essential component of the selenium-dependent enzyme glutathione peroxidase (a "good" enzyme). Glutathione peroxidase prevents free radicals from forming and destroys lipid peroxidases ("bad" enzymes) that otherwise would cause loss of cell membrane integrity. Further, it might improve uptake of vitamin E from the digestive tract and transport into tissues.
A blood test measures whole blood selenium. The recommended level is about 0.2 ppm, and the maximum tolerable level is about 2 ppm. Since inorganic forms are not well utilized, organic sources are recommended. Horses are extremely susceptible to selenium toxicity, which is not true for other types of livestock. The selenium content of the soil has a dramatic effect on the necessity of supplementation. California, Colorado, Idaho, Montana, Oregon, South Dakota, Utah, and Wyoming are all states that report toxic areas. However, these same states, with the exception of Wyoming, also report soils in some areas that are deficient. Most of the rest of the country has soils that are now selenium-deficient, so supplementation is common. Many commercial feeds contain 0.6 ppm with the reasoning that if the diet consisted of 50% concentrate and 50% roughage from selenium-deficient soil, the amount would dilute to about 0.3 ppm.
Selenium Deficiency and Toxicity
Selenium deficiency in young horses causes stiffness, listlessness, lung edema, and an increase in heart rate, respiration rate, and salivation. A deficiency in adult horses also causes stiffness as well as a decreased immune response and lowered fertility. "A combined oral vitamin E and selenium supplement can be used for horses with low whole blood selenium concentrations," says Valberg. "In general, the recommended amount of selenium is 0.2 mg/kg of diet dry matter or about 1 mg of selenium per 500-kg horse per day in areas with low soil selenium. The blood levels should be checked within four weeks to see if adequate whole blood selenium concentrations are achieved. In some cases, more supplementation may be required if other minerals in the diet are competing with absorption of selenium."
In addition, certain plants, such as various Astragalus species (locoweeds), require large amounts of selenium for their metabolism. Therefore, they typically grow in selenium-rich soils and concentrations in these plants might approach 15,000 ppm. Horses that eat them are at high risk of selenium toxicity, the signs of which include blind staggers, colic, very dark diarrhea, and increased heart and respiration rates. Coma and death can occur from heart failure. With chronic toxicity, you might see poor hair development (especially in the mane and tail), weight loss, listlessness, hooves cracking around the coronary band, very sore feet, and even sloughing of the hooves.
It is important to note that there is a possible fatal reaction to vitamin E/selenium injections, even if given at recommended levels. Anaphylactic (immediate hypersensitivity) shock can occur from an emulsifying agent or preservative in the injection. Therefore, supplementation via intravenous injection is not recommended. Intramuscular injections do not have the same negative effect and can be used.
White Muscle Disease
Nutritional myodegeneration (NMD), commonly known as white muscle disease, is caused by a selenium deficiency. It is more frequently seen in calves and lambs, but it does occur in foals. Signs will usually be seen from birth to seven months. A newborn foal will be unsteady with painful hind end, back, or neck muscles, and he eventually might not be able to stand. Older foals will have a sudden onset of lethargy and a stiff gait followed by an inability to stand. Pneumonia can develop, and death is possible.
Prevention and treatment of white muscle disease usually entails vitamin E and selenium supplementation. Limited amounts of selenium pass to the foal before birth, so mares with low selenium levels should be supplemented from late gestation through lactation or foals should be supplemented at birth.
Vitamin E and selenium are important for the health of your horse. While you can have disease from too little vitamin E, there is no known toxicity. And, supplemental vitamin E in debilitated, sick, pregnant, or stressed horses could help stimulate the immune system.
Selenium can be toxic, and horses are particularly susceptible to its effects. Therefore, consult with your veterinarian before giving any selenium, or any other vitamins. Some can interfere with absorption of other nutrients essential to the well-being of your horse.
Thomas, H. The Role of Antioxidants, The Horse, January 2004, www.TheHorse.com/ViewArticle.aspx?id=4829.
Evers, S. Antioxidants for Exercising Horses, www.TheHorse.com/ViewArticle.aspx?id=4460.
NATURAL VS. SYNTHETIC VITAMIN E
Vitamin E: The Source Matters
Recent studies by Kentucky Equine Research (KER) based in Versailles, Ky., have shown that the form and source of vitamin E do make a difference to horses. Vitamin E is one of the few nutrients that can be monitored by blood plasma, explained Joe Pagan, PhD, founder of KER. Vitamin E is known to be a potent antioxidant, and it has proven useful in treating several specific problems, such as equine motor neuron disease and wobbler's syndrome. Many veterinarians also routinely use vitamin E in treating horses which are stressed or compromised due to illness, competition, or pregnancy.
Some of the vitamins and minerals you take are more readily absorbed by your body because of the source (and some aren't absorbed at all). The same is true for horses. In nature, there is only one biologically active form of vitamin E (noted as d-alpha-tocopherol). Synthetic vitamin E contains eight different isomers rather than one single isomer found in the natural form. Only one of the eight (12.5%) isomers is the same as found in nature. Synthetic forms are noted as dl-alpha-tocopherol acetate. Synthetic vitamin E is made up of 50% l isomers and 50% d isomers. The l isomers are biologically inactive, and the synthetic d isomers can be two to five times less potent than natural d isomers.
Natural vitamin E typically comes from the refinement of soybean oil. If the vitamin E byproduct of that were to be mixed with your grain ration in its raw form, the anti-oxidants would immediately "hook up" with the free radicals in the grain and be unavailable to your horse. It is unstable. Therefore, an ester is added to stabilize the vitamin E that is added to feeds and supplements. Once in the horse's gut, there are natural enzymes that remove the esters from the vitamin E, thus making it available to the horse.
There is a way to bottle water-soluble liquid vitamin E and make it available in form that can be poured on feed and fed immediately without loss of absorption by the horse. This is a much more difficult process and therefore the product is more expensive. KER has developed a water-soluble liquid form of natural vitamin E. This type of vitamin E is even more bioavailable than the esterified natural source vitamin E. KER's water-soluble product is only sold to veterinarians because studies have shown it can increase the level of vitamin E in blood plasma quickly and to quite high levels. While there has been no evidence of toxicity at high levels of vitamin E, the problem with overfeeding any nutrient is that if you overdo one vitamin, then the gut can't free all the esters and therefore all the vitamins can't be absorbed.
KER has conducted several experiments with vitamin E. In one, natural-source vitamin E gave a much higher blood plasma level than synthetic forms (which, remember, only have 12.5% absorbable vitamin E). In fact, the plasma level in horses given natural vitamin E was much higher than the researchers thought would occur. Another study looked at 21-day supplementation of vitamin E at 5,000 IU per day. The only two forms studied were synthetic and water-soluble. The only surprise to Pagan was how quickly the blood plasma levels were increased using the water-soluble form of vitamin E.
"The next question we have to answer is what blood levels of vitamin E are optimal for various types of horses," said Pagan. "Currently, we recommend that if you have a horse getting ready for a bout of exercise extensive enough for free radical release, that you 'load' the horse with water-soluble natural source vitamin E for four days prior to the event (race, endurance ride, three-day event, etc.) and continue for three days after the event."
He said it is hard to prove whether elevated levels of vitamin E are effective in combating oxidative stress, but he is confident that veterinarians can now manipulate the levels of vitamin E using a natural source for the vitamin when it is strategically important to do so because of illness or stress.
About the Author
Stephanie J. Corum received a MS in animal science from the University of Kentucky in Lexington. She has worked in various aspects of the horse industry, including Thoroughbred and Arabian racing, for nearly 20 years. More information about her work can be found at www.theridingwriter.com. She has also published the illustrated children's story Goats With Coats. Currently she and her husband own Charisma Ridge, a small horse farm in Maryland, and she competes in dressage.