VITAMIN E KEY TO EQUINE HEALTH 2018

At the Center for Equine Health (CEH), we continually strive to bring you the latest in

equine health through this award-winning publication.

This particular issue of Horse Report is near and dear to my own research program.

My research team studies the consequences of vitamin E deficiency in the horse. In this

Horse Report issue, we focus on the importance of vitamin E as part of a well-rounded

nutritional regimen. For horses in areas with lush green pastures, vitamin E is abundant,

as the grass consumed in a normal grazing routine provides a sufficient amount. But most

of us in California know that lush green pastures are an extreme luxury due to recent

drought conditions. As a result, many of our horses require vitamin E supplementation.

This powerful antioxidant protects against cell damage from free radicals.

You may be familiar with the importance of vitamin E in human diets. Its advantages

include an increased immune system response, balanced cholesterol levels, lower

inflammation, natural repair to damaged skin, and balanced hormones. Most importantly, however, is its ability to

prevent debilitating neuromuscular disease. This also holds true for horses. In this issue, we will discuss these diseases

and give you information on how to properly supplement your horse’s diet.

With your help, CEH continues to advance the well-being of horses and educate horse owners on the latest discoveries

in horse health. At UC Davis, we are at the forefront of research into the importance of vitamin E in the equine diet.

What an exciting time to be part of our journey!

Thank you for your continued support,

Carrie J. Finno, DVM, Ph.D.

CEH Director

Due to the importance of vitamin E

in every horse’s diet, the Center for

Equine Health has invested in irrigating

its pastures for the teaching herd.

Since the best source of vitamin E is

fresh green grass, these lush pastures

at UC Davis provide an ideal

environment for the teaching herd

to graze.

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SCHOOL OF VETERINARY MEDICINE • UNIVERSITY OF CALIFORNIA, DAVIS

CENTER FOR EQUINE HEALTH – HORSE REPORT • FALL 2018

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Recovery from Vitamin E Deficiency

Meet the Scientists Behind the Discoveries

Tarnisha, a 10-year-old

Thoroughbred, came to live

at the CEH in 2012 after her

owners donated her following an

injury that forced her retirement

from racing. Three years later,

she began showing clinical signs

of muscle wasting and weakness.

The Finno Laboratory at the CEH

diagnosed her with vitamin E

deficient myopathy, confirmed via

muscle biopsy. She was started on

a treatment plan consisting of oral

vitamin E supplementation and

showed improved clinical signs

within two weeks. She continued

to make steady improvements and

has never looked back. To maintain her health, she will need to remain on oral supplementation for the rest of her life or live

on green pasture. “Tarnisha is a perfect example of how quickly some horses can improve from vitamin E deficient myopathy

simply with the proper supplementation,” said CEH Director Carrie Finno. “This is the one disease that horses can completely

recover from with appropriate treatment.”

Hadi Habib recently graduated

from UC Davis with a bachelor’s

degree in Chemistry and a master’s

degree in Forensic Science with an

analytical chemistry focus. Hadi’s

research quantified vitamin E and

vitamin E metabolite levels in horse

blood, particularly in serum and

plasma. Vitamin E actually consists of

eight compounds that can be measured

individually. To investigate how fast a

horse “uses” vitamin E and each of these

eight compounds, vitamin E metabolites

are measured. Under the mentorship

of Drs. Birgit Puschner and Ingrid

Gennity, Hadi developed a method to

measure levels of all of the components of vitamin E and its

metabolites in equine plasma and serum. Quantification was

achieved using analytical instrumentation (UHPLC-MS/MS).

The validated method determined concentrations of

these analytes in plasma and serum of horses. Assessment

of vitamin E and metabolites is a critical component of

diagnostic investigation in horses with neuromuscular

diseases. Alpha-tocopherol (isoform of

vitamin E) levels were found to range from

3-6 µg/mL, while the metabolites were found

at much lower levels, ranging from .0002 –

.0010 µg/mL in healthy horses. This work

has been pivotal in investigating the rate at

which certain horses “use,” or metabolize,

vitamin E. The team is discovering that

some horses may require higher doses of

vitamin E than others, based on a more rapid

metabolism of the vitamin.

Hadi performed his training through the

Bioanalytical Research Core, a unique

interdisciplinary analytical core that provides

method development and validation for

therapeutics and toxicants in support of

the School of Veterinary Medicine’s drug discovery efforts.

Core members have advanced training and experience

both in the pharmaceutical industry (preclinical drug

development) and academia as well as extensive experience

with pharmacokinetic modeling of drug and metabolite

concentration data in a variety of biological matrices (blood,

urine, milk, synovial fluid, tissue).

Before After

Hadi Habib

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SCHOOL OF VETERINARY MEDICINE • UNIVERSITY OF CALIFORNIA, DAVIS

Vitamin E: Key to Equine Health

uncoordinated. They may stand with forelimbs too far

apart (or too close), have difficulty navigating curbs or

hills, or lack coordination while walking and making tight

turns. Manifestations of the disease can vary among horses

with some showing mild performance issues, while others

are severely debilitated. Although there is no cure yet for

eNAD, one of most common equine neurological diseases,

researchers are closing in on how to prevent the onset of

symptoms—and early intervention is key.

Dr. Carrie Finno, director of the CEH, said studies show

that vitamin E is necessary to prevent degeneration of the

neurons and axons throughout the brain and spinal cord

during early life in many species. Axons are the part of nerve

cells that transmit impulses, so when those cells are damaged,

communication breaks down between the brain and the rest

of the body, leading to a lack of coordination.

“We still don’t understand the cause of the degeneration, but

we do know there is an interaction between genetics and

nutrition for this disease to manifest,” Finno said. “You need

the perfect storm of genetic susceptibility and a deficiency of

vitamin E during the first few years of life.”

Researchers in the Finno Laboratory are working hard to

develop a genetic test for eNAD, but until one is available, she

advises horse owners to supplement their horses, especially

pregnant mares and newborn foals. The supplement may

Proper nutrition—particularly appropriate levels of

vitamin E—is critical to equine health. This biological

antioxidant helps maintain normal neurological function

by limiting the damage caused by oxidative stress and free

radicals. The best source of this nutrient is fresh green grass.

As soon as the grass is dried for hay, the potency of vitamin E

in the forage declines dramatically.

Many research studies, including some conducted at the

Center for Equine Health (CEH), have shown that horses

without access to grazing on green grass are often deficient in

this essential mineral, which leaves them vulnerable to three

different types of neuromuscular diseases associated with

vitamin E deficiency: equine neuroaxonal dystrophy/equine

degenerative myeloencephalopathy (eNAD/EDM), equine

motor neuron disease (EMND) and vitamin E deficient

myopathy (VEM). These diseases are typically diagnosed

based on the clinical signs, exclusion of other disorders and a

low blood vitamin E concentration.

While not all animals deficient in vitamin E exhibit clinical

signs, individual genetic factors, the age of the horse during

deficiency (such as early growth phases), and the duration of

deficiency all play a part in determining whether insufficient

levels of vitamin E in a horse’s diet will impact their health.

Equine neuroaxonal dystrophy occurs in young animals

and has a genetic predilection. Affected horses appear

Cover Story

Cut grass is not a good source of vitamin E since

nutrient levels start to diminish at harvest.

Mares and foals are especially

susceptible to vitamin E deficiency.

Dr. Carrie Finno examines a case of equine motor neuron disease

displaying the abnormal stance with all four feet placed close

together underneath the horse.

not entirely eliminate the disease, but it does appear to

result in less severe neurological signs if the foal receives

supplementation during the early stages of life.

Equine motor neuron disease occurs in older horses that

have been vitamin E deficient for more than 18 months. It

affects lower motor neurons, nerves that supply the direct

neurological input into all muscles. Without these, the

associated muscles atrophy, resulting in the clinical signs

of weakness and weight loss characteristic of this disease.

Affected horses may carry their heads lower and lie down

for longer periods of time. With treatment, approximately

40 percent of horses affected by EMND improve; 40 percent

stabilize but remain disfigured; and 20 percent progress in

severity of disease.

Vitamin E deficient myopathy is typically found in horses

with a shorter duration of vitamin E deficiency and exhibit

muscle weakness, low muscle alpha-tocopherol concentration

and mitochondrial alterations (i.e. changes to the “power

house” energy storage unit of the cell) in skeletal muscle

but no evidence of neurogenic atrophy. These animals are

generally able to recover within three months with proper

supplementation.

These three diseases are the only conditions definitively

associated with vitamin E deficiency. Despite this, many

horses with neurologic disease caused by other diseases (i.e.

equine protozoal myeloencephalitis, or EPM, and cervical

compressive vertebral myelopathy, or “Wobblers”) are placed

on vitamin E supplementation.

“At this time, we know nothing about vitamin E metabolism

in horses, the appropriate dosage or its actual efficacy in

preventing or treating neurological conditions other than

eNAD, EMND and VEM,” said Finno, who was appointed as

the inaugural holder of the Dr. Gregory L. Ferraro Endowed

Directorship this spring. “Supplementation with vitamin E

may alter drug metabolism and disposition, since, in humans,

the same cytochrome isoforms that metabolize vitamin E

metabolize approximately 50 percent of therapeutic drugs.”

Therefore, while vitamin E supplementation may not

necessarily be harmful for these other neurologic diseases,

it is unlikely to be beneficial. Baseline blood vitamin E

concentrations should always be assessed before initiating

any vitamin E supplementation.

Finno notes that recent droughts in California may

also contribute to the decline in forage with sufficient

vitamin E levels. Her laboratory is currently

conducting research into how both healthy horses

and horses with neuromuscular disease metabolize

vitamin E. There may be an underlying genetic variation

in certain horses that results in them having a higher

requirement of vitamin E. When these horses are then placed

in a vitamin E deficient environment, such as a dry lot in

California, neuromuscular disease may develop. If the Finno

Laboratory can identify which horses require more vitamin

E than others, supplementation could be individualized to

prevent disease in those individuals.

“Continued research into this vital nutrient is critical to

promoting equine health,” Finno said. “Especially for those

horses that live in areas where access to green pasture is

limited, like many areas in this state.”

For more information on vitamin E deficiency and suggested

supplementation, please see the accompanying article in this

issue of the Horse Report.

CENTER FOR EQUINE HEALTH – HORSE REPORT • FALL 2018

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SCHOOL OF VETERINARY MEDICINE • UNIVERSITY OF CALIFORNIA, DAVIS

Importance of Vitamin E

When it comes to horse health and

nutrition, geography can play more

of a part than most would think. With

horses achieving a significant portion of

their diet through grazing, where they

graze can make a big difference. And

most California horses are at a distinct

disadvantage when it comes to the

nutrients—especially vitamin E—they

could be getting from grazing.

Vitamin E is an essential nutrient

for horses and one that can easily be

provided with access to a lush green

pasture in which to graze. Grass is

an abundant source of vitamin E, but

most California horses don’t have this

luxury. Vitamin E from grass can only be

found in fresh grass. The nutrient levels

decrease, and eventually are lost, as soon

as the grass is harvested and stored, so

cut hay is not an option.

Much of California has a hot, dry climate with little rain.

Some desert areas of the state see less than five inches of rain

per year, and the more populated centers—the Southern

California coastal areas and the Central Valley—receive less

than 20 inches—well below the national average. With this

lack of rain comes lack of green pastures for horses to graze.

Therefore, these horses are not getting the proper amount of

vitamin E naturally, and if not supplemented, that deficiency

could have dire consequences.

Consequences of Deficiency

In short, vitamin E helps a horse’s muscles and nerves

function properly. The biological antioxidant helps maintain

normal neuromuscular function, and a lack of it can

lead to diseases such as nutritional myodegeneration in

conjunction with selenium deficiency, equine neuroaxonal

A case of eNAD/EDM displaying an

abnormal stance due to damage of the

proprioceptive tracts.

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SCHOOL OF VETERINARY MEDICINE • UNIVERSITY OF CALIFORNIA, DAVIS

dystrophy/equine degenerative

myeloencephalopathy (eNAD/EDM),

vitamin E deficient myopathy (VEM) and

equine motor neuron disease (EMND).

These diseases can be extremely

debilitating to horses, if not fatal.

EMND manifests in horses similar to

amyotrophic lateral sclerosis (aka Lou

Gehrig’s disease) in humans, ultimately

wasting away the muscles due to lack

of nourishment. Horses with eNAD

can have gait abnormalities and lose all

limb control, while EDM escalates those

conditions, resulting in a more severe

incoordination.

The Center for Equine Health (CEH)

is studying vitamin E deficiency—not

only the effects it has on horses, but

also potential correlations it may have

with humans. Research reveals a number of similarities in

how vitamin E deficient neurodegeneration takes place in the

equine and human systems. CEH Director Dr. Carrie Finno

hopes further funding will allow her team to expand on

how vitamin E deficiency contributes to neurodegenerative

diseases across species.

Supplementation

Since there is no effective treatment for most of the diseases

vitamin E deficiency can cause, it is imperative that they be

prevented from happening in the first place. If horses are

not able to access fresh pastures to graze in, vitamin E must

be supplemented in their diet. All vitamin E supplements

Vitamin E, an essential nutrient for horses, can

be acquired by grazing in lush green pastures.

CENTER FOR EQUINE HEALTH – HORSE REPORT • FALL 2018

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Horses in dry pastures, especially mares

and foals, need vitamin E supplementation.

CENTER FOR EQUINE HEALTH – HORSE REPORT • FALL 2018

7

consist of alpha-tocopherol because alpha-tocopherol is the

most biologically available and well researched isoform of

vitamin E.

The National Research Council (NRC) recommends a daily

vitamin E supplement to be 1-2 international units (IU)/

kilogram of the horse’s body weight. So for a 1,000-pound

horse, 450-900 IU of supplement would be necessary daily.

“It’s important to remember that not all horses with vitamin E

deficiencies will exhibit clinical signs,”

said Finno. “And we want to prevent

those clinical signs from happening

anyway, so we don’t want to wait

around until we are certain of a vitamin

E deficiency before supplementing their

diets. Unless your horse is on a year-

round green pasture, he or she requires

supplementation.”

However, Finno stresses the importance

of testing blood vitamin E levels before

initiating a supplementation program.

“Some horses may require higher doses

of supplementation than others, and it

is difficult to tailor their dosing without

a baseline vitamin E level,” said Finno. “Healthy grazing

horses maintain a blood vitamin E level between 3-4 µg/mL,

so that should be our target.”

Historically, there was little concern associated with giving

too much vitamin E. This was mainly due to the fact that

most vitamin E supplements were not very well absorbed in

the horse and the NRC levels were based on these synthetic

vitamin E supplements. With newer formulations, however,

excessive supplementation can occur.

“Previous studies have shown that detrimental effects may

not occur until supplementation reaches 10-20 times the

recommended amount,” Finno said. “However, these studies

were performed using less bioavailable vitamin E supplements

(see below). High dosages can lead to bleeding disorders.

With the newer supplement formulations, it is critical to

repeatedly check blood vitamin E levels so as to not exceed the

recommended range.”

Not all vitamin E supplements are created equally. The first

generation of supplements were termed synthetic vitamin E,

in that they contained alpha-tocopherol, the main antioxidant

component of vitamin E, in all of its

different chemical configurations. Later

research demonstrated that only the

“natural” form of vitamin E, or the one

containing only one particular highly

bioavailable configuration, was highly

effective at increasing vitamin E levels in

the blood of horses. Since then, additional

alcohol-based vitamin E supplements,

termed “water-dispersible,” have been

developed for use in horses. These are

the most effective of all supplements in

that the water-dispersible formulation is

readily absorbed and the natural vitamin E

quickly increases blood and tissue levels in

most horses.

Horses in different conditions and different stages of life may

require varying levels of supplementation. Additionally, dosing

is based on the type of vitamin E formula used (synthetic

powder/pellet, “natural” powder/pellet or “natural” water-

dispersible). After assessing baseline blood concentrations and

identifying deficiencies, pregnant mares should be given 5,000

IU/day of the natural water-dispersible vitamin E and foals

should receive 500 IU/day (i.e. 10 IU/kg as the foal grows) of

the same product as soon as the foal is born to decrease the risk

of eNAD. Blood levels should be checked frequently to ensure

that they remain in the normal range.

Finno encourages all horse owners to discuss with their

veterinarian what level would be best for their horse before

implementing any supplements into their horse’s diet.

The Horse Report is published by the University of California, Davis, School of Veterinary

Medicine: Michael D. Lairmore, dean; Carrie Finno, CEH director; Tom Hinds, director strategic

planning and communications; Rob Warren, editor; Katie Blakewell, Don Preisler, Carolyn

Sawai, Trina Wood, contributors. The Center for Equine Health is supported with funds

provided by the State of California Pari-Mutuel Fund and contributions from private donors.

The University of California does not discriminate in any of its policies, procedures or practices.

The university is an affirmative action/equal opportunity employer.

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www.vetmed.ucdavis.edu/ceh

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Center for Equine Health

School of Veterinary Medicine

University of California

One Shields Avenue

Davis, CA 95616-8589

We are grateful to equine enthusiasts like you who share our commitment to the

well-being of horses. Thanks to generous support, we continue to make great strides

in advancing equine health to help horses like Tarnisha, highlighted in this issue of

Horse Report. Please consider joining us in our mission by becoming a partner today.

The welfare of horses depends on the improvement and advancement of equine

medicine. To make a gift to the Center for Equine Health, call our Advancement team

at 530-752-7024 or visit give.ucdavis.edu/Go/CEH.

www.vetmed.ucdavis.edu

Maria Sempe