VITAMIN E DEFICIENCY. What does that mean? A great article.

Thursday, May 4th, 2017 | Filed under Medical

Our Bucket Fund horses this month are severely depleted in Vitamin E.

Now, what we don’t know is if these horses have a condition that makes them genetically predisposed to not metabolize Vitamin E well.

Or… were they fed feeds deficient in Vitamin E.

This we still don’t know.

But, many of you have questions about Vitamin E deficiency so Darla from Strawberry Mountain Morgans, who is caring for our May Bucket Fund horses, Chatterbox and Blue, sent this article to me.

Click image to go to the original article.

Vitamin E Supplementation in Horses with Neuromuscular Disorders

  1. What is vitamin E?
  2. What equine diseases are directly affected by a deficiency of vitamin E?
  3. What types of vitamin E are there?
  4. How can I tell if my horse is deficient in vitamin E?
  5. Do all horses with an alpha-tocopherol deficiency develop clinical signs of disease?
  6. What are some diseases associated with vitamin E deficiency?
  7. What types of vitamin E supplements are there?
  8. What are current recommendations for supplementation?

1. What is vitamin E?

Vitamin E functions as a biological antioxidant, preventing the oxidation of unsaturated lipids within cellular and subcellular membranes by neutralizing production of free radicals. Through this mechanism, and potentially other mechanisms yet to be elucidated, vitamin E serves to maintain normal neuromuscular function.

2. What equine diseases are directly affected by a deficiency of vitamin E?

Equine diseases that develop in the face of vitamin E deficiency in young animals include nutritional myodegeneration, neuroaxonal dystrophy in horses and equine degenerative myeloencephalopathy. Adult horses deficient in vitamin E may develop a vitamin E deficient myopathy or equine motor neuron disease.

3. What types of vitamin E are there?

Most vitamin E supplements consist of natural or synthetic forms of alpha-tocopherol because alpha-tocopherol is the most biologically available and well researched isoform of vitamin E. Vitamin E, however is a complex nutrient consisting of eight closely-related fat-soluble naturally occurring compounds that form two groups; tocopherols (saturated) and tocotrienols (unsaturated). Within each group, there are four individual isoforms (?, ?, ? and ?).

4. How can I tell if my horse is deficient in vitamin E?

When a vitamin E sample is evaluated, it is actually the concentration of ?-tocopherol that is being measured. A blood sample using serum or plasma is the most readily available sample for determination of ?-tocopherol deficiency. Blood should be chilled as soon as possible after obtaining a sample and protected from light by wrapping in tin foil. Blood samples should be centrifuged at 4°C and plasma/serum separated as soon as possible. If analysis is delayed, serum/plasma samples should be stored frozen (- 21° F, – 70° C) as vitamin E deteriorates rapidly. Normal reference ranges for plasma/serum concentrations of ?-tocopherol in the horse are;

>2 ?g/mL Adequate
1.5-2 ?g/mL Marginal
<1.5 ?g/mL Deficient

Serum versus tissue ?-tocopherol concentrations: Significant correlations exist between serum ?-tocopherol concentrations and adipose tissue, liver, muscle and CSF in healthy horses. This correlation, however, is not consistently evident in horses with vitamin E deficient myopathy (Figure 1). In cases of vitamin E deficient myopathy, a discrepancy between serum and tissue levels of ?-tocopherol may indicate that an abnormality exists in uptake of ?-tocopherol into muscle tissues.

5. Do all horses with an alpha-tocopherol deficiency develop clinical signs of disease?

No; only certain animals demonstrate clinical signs of neuromuscular disease even if the alpha-tocopherol deficiency exists in an entire herd of horses. Development of neuromuscular disease appears to depend upon the age of the animal when deficiency develops, the duration of alpha-tocopherol deficiency, the genetic make-up of the individual and other concurrent dietary deficiencies or excesses. In many horses, there are no apparent ill effects of an alpha-tocopherol deficiency. Therefore, diagnosis of the neuromuscular disorders described below requires not only determination of alpha-tocopherol status but also the appropriate clinical signs, supporting clinical pathology and/or muscle biopsy results and elimination of other possible diseases.

6. What are some diseases associated with vitamin E deficiency?

Nutritional myodegeneration
Nutritional myodegeneration (NMD), also referred to as white muscle disease, affects skeletal or cardiac muscle of rapidly growing, active foals and is primarily due to a dietary deficiency of selenium beginning in utero.11-12 In some, but not all cases, there may also be a deficiency of vitamin E. Whereas vitamin E scavenges free radicals within the cell membrane to prevent formation of lipid hydroperoxides, selenium acts to destroy cytosolic peroxides that have already been formed through its incorporation into glutathione peroxidase.13

Clinical signs: Foals with NMD often present with signs of muscle weakness, difficulty rising trembling of the limbs, stiffness, prolonged recumbency, firm painful muscles and potentially aspiration pneumonia. Depression, rapid heart rate, difficulty breathing and foamy nasal discharge or sudden death may indicate cardiac involvement.

Diagnosis: Foals with NMD have elevated serum creatine kinase (CK) and aspartate transaminase (AST) activities, whole blood selenium < 0.07 ?g/ml and serum vitamin E may or may not be < 2 ?g/ml.

Treatment: The cardiac form of NMD is usually not incompatible with life. Foals with skeletal muscle signs often show significant improvement within 3 to 5 days of treatment with injectable selenium products as well as general supportive care. Injectable selenium products contain 50 mg/ml (68 IU) of vitamin E as dl-alpha-tocopheryl acetate (all-rac-alpha-tocopheryl acetate) which acts a preservative for the solution and is, therefore, insufficient for alpha-tocopherol supplementation.14 Therefore, additional oral alpha-tocopherol is suggested to quickly increase antioxidant levels (see below for dosages).

Neuroaxonal Dystrophy / Equine Degenerative Myeloencephalopathy
Equine neuroaxonal dystrophy (NAD) and equine degenerative myeloencephalopathy (EDM) are closely related disorders distinguished largely by the location of axonal or neuronal degeneration in the central nervous system. NAD/EDM occurs in multiple breeds with most cases demonstrating clinical signs by six to twelve months of age. Although the pathophysiology is not completely defined, there is strong evidence of a genetic component whose expression is highly influenced by alpha-tocopherol deficiency during the first year of life. Low serum alpha-tocopherol has been described in most, but not all, affected foals.

Clinical signs: Clinical signs include symmetric ataxia that is often more severe in the pelvic limbs than the thoracic limbs, abnormal base-wide stance at rest, and proprioceptive deficits. In some reports, hyporeflexia of the cervicofacial and cutaneous trunci is described in addition to an absent laryngeal adductor reflex.15 Horses with NAD/EDM that survive to 2-3 years of age commonly exhibit lifelong, stable neurologic deficits.16

Diagnosis: An antemortem diagnosis of NAD/EDM is based solely upon clinical signs, the elimination of other causes of neurologic disease, and a possible association with a low serum ?-tocopherol concentration. A definitive diagnosis is only available upon histopathologic evaluation of spinal cord and brainstem tissue at post-mortem. There is no treatment for NAD/EDM and there have been no reports of spontaneous resolution.17

Treatment: Suspected cases are often treated empirically with alpha-tocopherol supplementation (see below for dosages). Unfortunately, there is strong evidence that alpha-tocopherol supplementation of affected horses does not lead to neurologic improvement.18-19 However, supplementation of dams with alpha-tocopherol during pregnancy may lead to a decreased incidence of NAD/EDM during the next foaling season.15,17

Vitamin E deficient myopathy
A subset of horses with alpha-tocopherol deficiency may develop clinical signs solely related to muscle atrophy and weakness without evidence of damage to motor nerves. These horses of a wide variety of breeds have been diagnosed with a vitamin E deficient myopathy (VEM).20

Whether VEM is an entity unto itself or a predecessor to development of equine motor neuron disease is not yet known.

Clinical signs: Horses present with loss of muscle mass, toe dragging, poor performance, weakness and muscle fasciculations.

Diagnosis: The most specific diagnosis of this disease is the histopathologic finding in fresh (not formalin-fixed) sacrocaudalis dorsalis muscle of an abnormal moth eaten mitochondrial staining pattern in the absence of neurogenic angular atrophy of myofibers. In many, but not all cases of VEM, serum ?-tocopherol is low. In all affected cases assessed to date, muscle ?-tocopherol concentrations have been below normal (Figure 1). This represents an unusual lack of linear correlation between serum and muscle ?-tocopherol and may indicate deficient skeletal muscle uptake or excessive muscle consumption.

Treatment: Horses with VEM are remarkably responsive to appropriate alpha-tocopherol supplementation (see below for dosages) and show a complete recovery.

Equine Motor Neuron Disease
Equine Motor Neuron Disease (EMND) is an acquired neurodegenerative disorder affecting motor nerves supplying highly oxidative type 1 muscle fibers. EMND is associated with low plasma concentrations of alpha-tocopherol21 and a dietary deficiency of alpha-tocopherol of at least 18 months duration.22

Clinical signs: Horses with EMND show signs of generalized muscle wasting, muscle fasciculations, shifting of weight between hindlimbs, low head carriage in some cases and prolonged recumbency.21

Diagnosis: Antemortem diagnosis of EMND is based upon either histopathologic evidence of the degeneration of myelinated axons upon biopsy of the ventral branch of the spinal accessory nerve or the finding of neurogenic atrophy of predominantly type 1 muscle fibers in sacrocaudalis dorsalis medialis muscle biopsy.23-24

Treatment: Treatment with relatively high doses of 5000-7000 IU ?-tocopherol/day is reported to produce clinical improvement in about 40% of cases within 6 weeks and some may horses appear normal within 3 months.25 It should be noted, however, that return to performance may result in deterioration. Divers25 reports that approximately 40% of cases will stabilize but remain permanently disfigured while 20% will have continual progression of clinical signs.

7. What types of vitamin E supplements are there?

The only equine vitamin E supplements currently available contain one form of vitamin E, alpha-tocopherol. Alpha-tocopherol can be obtained from natural or synthetic sources, but the chemical structure of each is different. Natural alpha-tocopherol is composed of one isomer (d-?-tocopherol [RRR ?-tocopherol]), and it is the most bioactive form in animal tissues. Synthetic alpha-tocopherol is a mixture of eight isomers (dl-?-tocopherol [all-rac-?-tocopherol]), of which only one is identical to the natural isomer. These eight isomers vary greatly in relative biopotency. Furthermore, when synthetic or natural alpha-tocopherol is formulated as a feed additive, it is manufactured as an esterifed form (?-tocopherol acetate) to prolong shelf life. In order for ?-tocopherol acetate to be utilized in the body, the ester has to be removed and the ?-tocopherol made water-dispersable by the action of bile salts (micellization). These additional steps may limit ?-tocopherol acetate absorption in the horse.29 It is important to realize when interpreting studies that the absorption and metabolism of alpha-tocopherol in healthy horses may differ from horses with alpha-tocopherol deficiencies.

To account for differences in biopotency, the relative strengths of different forms of alpha-tocopherol are expressed as international units (IU) in which 1 mg of synthetic acetate equals 1 IU, 1 mg of natural acetate equals 1.36 IU, and 1 mg of natural alcohol equals 1.49 IU.
Relative to synthetic vitamin E (dl-?-tocopheryl acetate)

  • -natural-source alpha-tocopherol acetate (d-?-tocopheryl acetate) is 1.97 times more potent
    -natural-source alpha-tocopherol alcohol (d-?-tocopherol) is 2.52 times more potent
    -water dispersable liquid formulations of alpha-tocopherol are about 6 times more bioavailable
  • Water dispersable forms commercially available include:
    Nano•E, Kentucky Equine Research, Versailles, KY
    Elevate WS, Kentucky Performance Products LLC, Versailles, KY
    Emcelle, Stewart Products, Bedford TX

8. What are current recommendations for supplementation?

Alpha-tocopherol deficiency: Horses with alpha-tocopherol deficient neuromuscular disorders such as EMND may have impaired intestinal absorption of glucose21 and their absorption of vitamin E may also be abnormal; although, to the authors’ knowledge, this theory has not been tested. Even with normal intestinal absorption, impaired tissue uptake may play a role in EMND and therefore require a formulation of alpha-tocopherol that has the highest bioavailability and potency. Natural-source water-dispersible forms of vitamin E at 10 IU/kg body weight seem like the obvious choice for optimal treatment as they are 5-6 times more bioavailable than synthetic vitamin E acetate, and a 5000-IU dose/horse more than doubles serum vitamin E levels within 12 hr.28 Before implementing supplementation it is important to measure serum ?-tocopherol concentrations in order to determine if there is an underlying deficiency and in order to monitor the efficacy of supplementation. The NRC has set the upper safe diet concentration at 20 IU/kg BW based on biopotency of synthetic vitamin E (10,000 IU/500 kg horse). Above this level, coagulopathy and impaired bone mineralization have been reported.32 Furthermore, in healthy exercising horses, high dosage of vitamin E supplementation (10x NRC requirements) was shown to be potentially detrimental to beta-carotene absorption and thus not recommended.35

Healthy horses: Current NRC daily recommendations for vitamin E in horses are 1 -2 IU/kg body weight, however, these NRC recommendations do not discriminate between natural or synthetic sources.32 Research-based evidence for the need for additional alpha-tocopherol supplementation above 500 IU/day is lacking in healthy young and middle-aged horses receiving adequate dietary vitamin E intake. Synthetic or natural esterified forms of alpha-tocopherol are the most cost-effective means to provide vitamin E to horses with normal alpha-tocopherol status. It is important to periodically check serum ?-tocopherol concentrations and, if an adequate response to supplementation does not occur, the dose or formulation of ?-tocopherol should be altered.

??Figure 1: The relative bioavailability of various forms of alpha-tocopherol calculated in 8 horses from 48 hr area under the curve (AUC) from a 5000 IU dose of each product indexed to synthetic acetate (bioavailability set to 1).


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