Pre-Treatment with Turmeric (C. Xanthorrhiza) Reduces the Severity of Squamous Gastric Ulceration in Feed Restricted Horses

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Sci Forschen
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Journal of Animal Science and Research
ISSN 2576-6457 | Open Access
J Anim Sci Res | JASR
1
RESEARCH ARTICLE
Pre-Treatment with Turmeric (C. Xanthorrhiza) Reduces the Severity of
Squamous Gastric Ulceraon in Feed Restricted Horses
SPS Fletcher1,2* and SL Gough1
1School of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW, Australia
2Integral Equine Nutrion, 1 Mallawa Road, Duys Forest, NSW, Australia
Received: 06 Feb, 2019 | Accepted: 26 Feb, 2019 | Published: 05 Mar, 2019
Volume 3 - Issue 1 |
are both time and nancially expensive. “Nutraceuticals” and feed
supplements are consequently used frequently by horse owners for
treatment or prevention of gastric ulcers, with limited empirical
evidence of ecacy.
Turmeric has recently become a popular supplement in horse
diets for the treatment of various ailments, including gastric ulcers
(authors’ observation). A spice traditionally used both in food and
as a medicinal treatment in southern Asia, turmeric is purported to
have a large range of healing properties. Curcuma longa is the most
commonly used and studied species; however other species such
as C. xanthorrhiza are also used. e two species have comparable
biochemical composition and biological eects [8,9]. Many of these
eects have been examined in cell-, animal- and human-based studies
over the last decade or so and have demonstrated that both turmeric
and its major bioactive component, curcumin, have antimicrobial,
antioxidant, anti-cancer, anti-inammatory and neuroprotective
eects [10,11]. Several animal model and human studies have
indicated the potential for turmeric/curcumin to prevent or treat
gastric ulcers, with minimal side eects [12-15].
*Corresponding author: Sophie Fletcher, Integral Equine Nutrion, 1 Mallawa Road, Duys Forest, NSW, Australia, E-mail: sophie@integra-
lequine.com.au
Citaon: Fletcher SPS, Gough SL (2019) Pre-Treatment with Turmeric (C. Xanthorrhiza) Reduces the Severity of Squamous Gastric Ulceraon in Feed
Restricted Horses. J Anim Sci Res 3(1): doi doi dx.doi.org/10.16966/2576-6457.125
Copyright: © 2019 Fletcher SPS, et al. This is an open-access arcle distributed under the terms of the Creave Commons Aribuon License, which
permits unrestricted use, distribuon, and reproducon in any medium, provided the original author and source are credited.
Abstract
Domesc horses commonly suer from gastric ulcers, with potenal adverse health, welfare and performance eects. This study aimed to invesgate
the eecveness of orally administered turmeric for prevenon of gastric ulceraon in horses during stable connement and dietary manipulaon.
Ten horses were used in a 16-day randomized, placebo-controlled and blinded two-period cross-over study. All horses received a base diet with the
treatment group also receiving 20g turmeric powder in the feed once daily. Gastric ulcer scores were determined via gastroscopy on Day 0, aer
nine days in a stable (Day 9) and aer seven days of feed-fasng (Day 16). Aer a washout period of 10 weeks, treatment groups were reversed.
Squamous ulcer scores increased during connement and feed restricon in control horses (P<0.001), but not in turmeric treated horses (P=0.247),
and squamous ulceraon was more severe on Day 16 in control horses (P=0.037). Changes in glandular mucosa were less obvious in treated and
control horses. These results suggest that oral supplementaon of turmeric (C. xanthorrhiza) may be eecve in reducing the severity of squamous
ulceraon in horses.
Keywords: Equine gastric ulcersyndrome; Curcuma xanthorrhiza; C.longa; Stomach; Supplement; Nutraceucal
DOI: hp://dx.doi.org/10.16966/2576-6457.125
Introduction
Equine gastric ulcer syndrome (EGUS) is a common disease within
the domestic horse population, aecting 80-100% of oroughbreds
in training and up to 59% of pleasure horses [1]. Colic, poor
condition, poor performance and behavioural changes are considered
to be major clinical signs resulting from EGUS [2,3], with adverse
eects on the health and wellbeing of the horse. Risk factors include
stress, high grain diets, intense exercise and the use of non-steroidal
anti-inammatory drugs (NSAIDS) [4,5]. Ulcerative and erosive
conditions of the squamous and glandular mucosa, now termed
equine squamous gastric disease (ESGD) and equine glandular
gastric disease (EGGD), respectively [1], likely represent distinct
clinical conditions of diering aetiology. Current pharmaceutical
treatment options are based on suppressing the production of gastric
acid and/or protecting the mucosa [1], and are oen combined with
nutritional and management changes to prevent reoccurrence [6].
e ecacy of gastric acid suppression for the treatment of lesions
of the glandular mucosa has been questioned [7]. It can be dicult to
completely eradicate risk factors for EGUS, and long term treatments

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Citaon: Fletcher SPS, Gough SL (2019) Pre-Treatment with Turmeric (C. Xanthorrhiza) Reduces the Severity of Squamous Gastric Ulceraon in
Feed Restricted Horses. J Anim Sci Res 3(1): doi doi dx.doi.org/10.16966/2576-6457.125 2
Journal of Animal Science and Research
Open Access Journal
e use of turmeric to treat or prevent gastric ulceration in horses
represents a potentially simple, cost-eective and risk free treatment
for a signicant disease, however to date there has been no scientic
investigation into this alternative. is study aims to determine if oral
supplementation of turmeric will prevent the development of gastric
ulcers in horses. Our research hypothesis was that daily administration
of turmeric would ameliorate the development of gastric ulceration
induced in horses associated with dietary modication, connement
and a previously validated feed-fasting protocol [16,17].
Materials and Methods
Horses and husbandry procedures
All horses used in this study were obtained from the Charles Sturt
University teaching herd, and were of oroughbred or Standardbred
breeding. Nine mares and one gelding (n=10) aged between 5 and
18 years old and weighing 523kg ± 51kg (mean ± sd) were used. e
study was designed as a randomized, controlled, blinded, two period
cross-over study. Prior to the experiment, and between periods 1 and
2, all horses were maintained on pasture with supplemental feeding
of lucerne hay where necessary. Horses participated in veterinary
and equine science handling and reproduction practical classes
between study periods. Upon entry to the stabling complex at the
commencement of each experimental period, horses were physically
examined to ensure they were in good health, free from injury or
illness. All procedures performed on the horses were approved by
and in accordance with the Charles Sturt University Animal Care and
Ethics Committee (A16027).
e horses were all housed within the same complex and randomly
allocated to individual stables for each period of the study. All horses
were fed 10kg ± 2kg (1.9% of their bodyweight (BW) in dry matter
(DM)) oaten/clover hay (feed analysis Supplementary table 1), divided
into two feeds at 8 am and 5 pm daily, except for during the nal 7 day
ulcer-inducing period. Immediately prior to the 5 pm meal (pre-meal
feed) each horse received 100g of oaten cha plus 50g of a powdered
coconut oil (PowerStance™, Stance Equine, Mount Ommaney,
Queensland, Australia) and 20mL molasses (to ensure palatability).
Horses in the treatment group also received 20g of powdered turmeric
daily (Curcuma xanthorrhiza, 2% curcumin; Stance Equine, Mount
Ommaney, Queensland, Australia) in the aernoon meal. Any
uneaten feed was collected, weighed and recorded to determine intake.
Horses were allowed free exercise for approximately one hour per day,
water was available ad libitum and water intake was monitored. Heart
rate (HR), rectal temperature (RT) and respiratory rate (RR) were
monitored daily throughout, and horses were weighed weekly during
the trial.
Experimental protocol
Horses were stratied on Day 0 period one according to gastric ulcer
scores and randomly assigned to either treatment (n=5) or control
(n=5) group for the rst study period. e experimental period lasted
for a total of 16 days with each animal receiving hay plus pre-meal
feed daily for the rst 9 days before commencing a 7 day intermittent
feed deprivation protocol designed to experimentally induce ulcers
[16,17]. During the ulcer induction period, all horses were deprived of
the full hay ration for 24 hours every second day, resulting in a total of
96 hours cumulative feed deprivation. Once daily feeding of the small
pre-meal was continued for both control and treatment groups during
this period. Gastric ulcers were visualized and scored on day nine
(prior to feed deprivation protocol) and again on the nal day (Day
16) of the experiment, via gastroscopy. Upon completion of period
one, horses were returned to their paddock for 10 weeks aer which
time the experimental protocol was repeated with treatments reversed.
All gastroscopic examinations were performed using a 3m
endoscope of 9mm outer diameter (Olympus Medical Systems
Corporation, Tokyo, Japan). Endoscopy was performed on horses that
had been fasted overnight (16-18 hours) to ensure good visualization
of gastric mucosa. Water was not withheld. Horses were sedated
with xylazine (0.4mg/kg IV) and acetylpromazine (0.02mg/kg IV).
Two horses required additional sedation during the procedure
(butorphanol, 0.1mg/kg, IV). e stomach was insuated with air
using a manual air pump attached to the endoscopy biopsy channel
until stomach folds were absent, and adherent feed was rinsed from the
mucosa, to allow full observation of all regions. Lesions were scored on
Day 0 (pre-treatment), Day 9 (aer 8 days of stabling) and Day 16
(aer 7 days of feed-fasting, as described above) based on the gastric
ulcer scoring system currently recommended by the European College
of Equine Internal Medicine consensus statement [1], (Table 1), and
recorded as both an overall grade (0 to 4) and as the sum of scores for
squamous and glandular mucosa as previously described [18]. Scores
were assigned for each region: greater curvature of the margoplicatus
(MPGC), lesser curvature (LC), dorsal squamous fundus (FUND),
ventral glandular fundus (GLAND) and pyloric antrum (PYL), using
de-identied video recordings by one researcher (SLR) who was
blinded to treatment throughout the experiment.
Statistical methods
Within each treatment period, gastric ulcer severity was analyzed by
separate analysis of summed ulcer scores for the squamous (MPGC, LC
and FUND) and glandular (PYL and GLAND) mucosa for control and
treatment groups by one-way repeated measures analysis of variance
on ranks (ANOVA) using the Friedman test, with post-hoc multiple
pairwise comparisons using Dunn’s method. Treatment eects were
evaluated at each time point (Day 0, Day 9 and Day 16) by Wilcoxon
matched-pairs signed rank test. In all cases P<0.05 was considered
signicant and all analyses were performed using GraphPad Prism
version 7 (GraphPad Soware, San Diego, California).
Results
All horses remained well for the duration of the study, and none
demonstrated clinical signs (colic, inappetance, bruxism, cribbing)
suggestive of gastric ulceration. Daily health observations (HR, RT, RR)
Grade Squamous Mucosa Glandular Mucosa
0
The epithelium is intact and
there is no appearance of
hyperkeratosis (yellowing of the
mucosa)
The epithelium is intact and
there is no appearance of
hyperaemia
1The mucosa is intact, but there
are areas of hyperkeratosis
The mucosa is intact,
but there are areas of
hyperaemia
2Small, single or mulfocal (<5)
lesions
Small, single or mulfocal
(<5) lesions
3Large single or extensive (≥ 5)
supercial lesions
Large single or extensive (≥
5) supercial lesions
4Extensive lesions with areas of
apparent deep ulceraon
Extensive lesions with areas
of apparent deep ulceraon
Table 1: Grading system for equine gastric ulcer syndrome, adapted
from Andrews, et al. [2]. Summed scores were derived for the squamous
mucosa based on assessment of the dorsal fundus and margoplicatus at
the greater and lesser curvature. Glandular scores were determined for
the ventral glandular fundus and pyloric antrum.

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Citaon: Fletcher SPS, Gough SL (2019) Pre-Treatment with Turmeric (C. Xanthorrhiza) Reduces the Severity of Squamous Gastric Ulceraon in
Feed Restricted Horses. J Anim Sci Res 3(1): doi doi dx.doi.org/10.16966/2576-6457.125 3
Journal of Animal Science and Research
Open Access Journal
Discussion
e current study successfully induced squamous and glandular
gastric ulceration in horses via dietary modication, box connement
and intermittent feed restriction. e severity of squamous ulceration
was ameliorated in horses receiving 20g turmeric daily compared to
control animals, suggesting that turmeric administration attenuated
the development of gastric ulcers in horses. is nding supports
results from other studies which have demonstrated similar eects
in other species [12,19,20]. However, care must be exercised in
extrapolating this nding from healthy, sedentary horses with induced
disease, to horses with spontaneous disease, particularly as two horses
developed moderate-severe squamous ulceration during turmeric
administration. No treatment eect was observed on the development
of glandular lesions.
Squamous ulceration is generally understood to be caused by
abnormal exposure of the un-protected mucosal cells to gastric acids
[21]. Dietary factors are thought to be involved in ESGD, with high
grain (starch) diets known to decrease gastric pH [22]. Luthersson N,
et al. [23] found that a daily starch intake exceeding 2g/kg BW could
increase the risk of moderate or severe gastric ulcers. High bre diets
and/or continuous pasture grazing are thought to reduce the risk of
EGUS (due to constant gut ll and pH buering), however research
on this is mixed (reviewed by Sykes, et al. [1]). Lucerne hay has been
shown to be protective, resulting in a higher gastric pH [24]. Horses
in this study were not fed starch concentrate, however, due to the
starch content of the oaten/clover hay fed (7.9%), daily starch intake
approached 2g/kg BW, potentially increasing the risk of EGUS and
contributing to increased ulcer scores observed on Day 9. Lucerne hay
was not fed during the study period.
Fasting has also been associated with gastric ulceration due to
reduced pH of gastric uid [17]. e intermittent fasting protocol used
in this study further increased lesion scores in the squamous region
in the control group, however the group treated with turmeric had
remained stable and within normal range for all horses throughout the
experimental treatment. ere were no feed or water refusals. Horses
maintained or increased in weight in both groups during the initial 9
day period, and body weight decreased slightly during the nal 7 day
intermittent feed deprivation period. ere was no treatment eect
on body weight. Some horses showed signs of stress (weaving, wood
chewing), which increased during the feed deprivation period but
could not be related to severity of gastric ulceration or to treatment.
Observation of meal time aggression (teeth bared, ears laid back,
lunging forward) also increased following fasted days.
Results of endoscopic grading of gastric lesions are provided in
Supplementary table 2. Median (95% CI) ulcer scores on Day 1 in
period 1 (0, 0-3) were signicantly lower than in period 2 (2, 1-5;
P=0.043); but were not dierent between treatment groups (placebo: 1,
0-3; treatment: 1, 0-5; P=0.530). Squamous ulcer scores increased over
time (P<0.001) in the control group, but no such eect was observed
in horses receiving turmeric (P=0.304, Figure 1) and median (95% CI)
squamous ulcer score on Day 16 was signicantly (P=0.031) lower
when horses received turmeric (2, 0-6) than was observed for control
animals (5, 3-6), (Figure 1). Two horses receiving turmeric evidenced
summed squamous ulceration scores >6 on Days 9 and 16.
Treatment eects on glandular mucosal scores were much less
marked. Glandular mucosal scores tended to increase with time
(P=0.025 for horses during control treatment, and P=0.049 for horses
receiving turmeric; Figure 1). Dierences in glandular mucosal
scores between control and treated horses were not signicant on
Day 0 (P=0.156) or Day 16 (P=0.242; Figure 1). At day 9, following
stable connement but prior to ulcer induction period, all horses
had developed lesions in the GLAND region ranging from grade 1
to grade 3, and a signicant eect (P=0.042) was observed in control
horses. Glandular lesions were typically multifocal or linear areas of
hyperaemia and/or supercial erosion. Lesions were more common,
and tended to be more severe, in the pyloric region. One horse
(H8), receiving turmeric during period two, had a grade 4 (deep and
bleeding) lesions in the glandular fundus, but no pyloric lesions.
Figure 1: Gastric squamous and glandular ulcer scores following administraon of turmeric (20g once daily in feed, orange) or placebo (blue).
Results are presented as median (black horizontal line) and interquarle range, with all results shown. A signicant (P<0.001) me eect was
observed for squamous scores for horses during placebo treatment, but not when turmeric was administered (P=0.304). Signicant dierences
at Day 9 and Day 16, relave to Day 0, are indicated for control horses (**, P=0.016; ***, P=0.001). Median squamous scores were signicantly
higher on Day 16 following placebo treatment than following turmeric treatment (P=0.031). Signicant me eects were observed for glandular
mucosal scores associated with control (P=0.025) and turmeric treatment (P=0.049); signicant dierences on pairwise comparison were evident
only for control horses (*, P=0.042).

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Citaon: Fletcher SPS, Gough SL (2019) Pre-Treatment with Turmeric (C. Xanthorrhiza) Reduces the Severity of Squamous Gastric Ulceraon in
Feed Restricted Horses. J Anim Sci Res 3(1): doi doi dx.doi.org/10.16966/2576-6457.125 4
Journal of Animal Science and Research
Open Access Journal
no such increase. All horses developed squamous lesions following
the seven day induction period, even when sucient roughage (1.9%
of BW in DM) was provided daily. is observation is supported by
earlier work where stall connement (with ad libitum hay) induced
ulceration within 7 days, compared to horses kept at pasture [17].
Mild to moderate squamous ulceration, more severe than was seen in
Murray and Eichorn’s study, was observed in the current study, and this
may be due to the horses not having access to ad libitum hay to ensure
optimum buering of gastric acids, fulllment of natural feeding
behaviours or increased stress due to daily connement. Whilst it is
commonly accepted that horses require a daily dry matter intake of
2% body weight to ensure adequate gut ll and digestive functioning,
this may not be sucient to protect against gastric ulcers in conditions
of stress such as connement, particularly when fed as two meals
daily. is highlights the need to ensure that good management and
husbandry is in place to prevent gastric ulcers from developing and
also during treatment.
One possible explanation for the apparent attenuation of gastric
squamous ulceration associated with turmeric administration is
reduced secretion of gastric acid, thereby reducing the extent of injury
to mucosal cells in this region during fasting. is theory is supported
by previous work in other species that shows turmeric has an
antisecretory effect. Both a reduction in total gastric fluids and
decreased acid concentration have been demonstrated following
oral administration of turmeric extracts or curcumin in rat models
of gastric ulcers [12,14]. It is possible that turmeric has an effect
on histamine-mediated acid secretion, as ex vivo studies show
turmeric has an inhibitory effect on H2R and, in vivo, this effect is
comparable to the use of the H2R inhibitor ranitidine [12]. Further
studies are required to evaluate the impact of turmeric on gastric
pH in horses.
ere was no eect of oral turmeric supplementation on lesions
in the glandular regions of the stomach. is nding correlates with
the low success rates (10-40%) of pharmaceutical treatments such
as omeprazole in treating glandular ulcers in horses, compared
to the eect on squamous lesions [25], and is also supported by
clinical trials in humans, where treatment of duodenal ulcers (which
correspond to glandular ulcers in horses) with turmeric had no eect
[15]. Despite these ndings, other research has demonstrated in vivo
properties that theoretically might be protective of glandular mucosa.
Turmeric, and its bioactive components such as curcumin, has
potent anti-inammatory and antioxidant eects in many laboratory
and animal models [11] and increase gastric mucous production
[14,20]. Specically, it has been observed that C. xanthorrhiza has
gastro protective eects in a rodent model [26]. In horses, it has been
found that oral curcumin supplementation decrease in erythrocyte
sedimentation rate, suggesting it may decrease inammation in the
body [27].
e nding that ulcer scores were greater on Day 0 in period two
than in period one was unexpected, as horses had been returned to
paddock accommodation with pasture grazing and supplementary
lucerne hay fed daily. During this ‘washout’ period, horses participated
in a number of student practicals, predominantly involving handling
or, for the mares, reproductive examination. It is possible that yarding
prior to practical classes disrupted social, dietary and water intake
habits, and thereby potentiated the development of ulceration in these
horses, or that ulcers that were induced during the original period had
not healed during the 10 week recovery. Although pasture turnout,
particularly in the company of other horses, has been associated with
reduced risk for gastric ulceration [28], squamous ulceration of grade
≥ 2 has been reported in broodmares at pasture [29]. Study design
accommodated for this eect, and no dierence was observed between
treatment and control horses on Day 0.
e endoscopic evaluation of gastric mucosal disease is challenging,
and may not correspond to histological changes [30,31]. is problem
is further compounded by the use of dierent grading systems by
dierent authors. e gastric squamous ulceration scoring system
used in the current study is that currently recommended by the
European College for Equine Internal Medicine [1], modied to
include summation of individual scores from dierent regions of the
squamous mucosa, as previously described [18]. Summation of lesion
scores (rather than reporting of mean score) allows discrimination
of horses with more numerous or extensive lesions, as has been
advocated in other scoring systems [32], although it may numerically
equate horses with a single severe lesion with those with more mild
but extensive changes. To date there is no clinical validation of this
assumption. Indeed, the assumption that hierarchical grading systems
predict more severe disease has not been proved, although intuitively
the progression of lesion severity observed in the current study
suggests disease progression. e adaptation and application of the
squamous grading system to lesions of the glandular mucosa is not
supported by the current consensus statement, and a more descriptive
approach has been recommended [1]. e system used in the current
study included recognition of the anatomical location of glandular
lesions, as recommended, as well as descriptive results which could be
assigned to numerical descriptors (grades) to permit non-parametric
statistical analysis of results.
Previously reported dose rates for the use of turmeric vary widely,
ranging from 80-500mg/kg BW [11]. As turmeric had not previously
been experimentally studied in horses at the commencement of this
study, a low dose of 20g daily (mean 37.9 ± 3.9mg/kg) was chosen
as a conservative option for this initial study. Subsequent studies in
horses [10] have evaluated similar doses (15, 20, 25 and 30g), while
puried forms of curcumin have been trialled in horses at doses
ranging from 1.06-15g [27,33]. Turmeric is considered safe with no
toxic eects when administered orally in a number of species [34,35],
and no negative eects were observed in this study. Future studies
might consider higher and more frequent doses, or administration
for a longer period prior to induction of gastric ulceration. Curcumin
is widely acknowledged to be very poorly absorbed and rapidly
metabolized in other species, resulting in extremely low plasma
concentrations [36]. Since this study was conducted, a preliminary
pharmacokinetic study in horses has shown that curcumin metabolites
are found at low concentrations in equine plasma [33]. In this study,
a fat source (powdered coconut oil) was included in the daily meal
to assist absorption, as turmeric is lipid-soluble and absorption from
the digestive tract into the portal blood is therefore improved with a
lipophilic vehicle. However, as the mechanism of action has not been
elucidated and topical administration of curcumin aids in the healing
of oral ulcers [37], turmeric might act at a local level to similarly
protect gastric mucosa.
Conclusion
is study has shown that oral supplementation of turmeric
reduced the severity of squamous ulceration in horses induced by
box connement, change of diet and feed restriction. is nding
supports laboratory and clinical research in other species suggesting
that turmeric has antiulcer properties. As a feed supplement this may
result in improved welfare, performance and nancial outcomes for
horses by reducing reliance on medication for prevention or treatment

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Citaon: Fletcher SPS, Gough SL (2019) Pre-Treatment with Turmeric (C. Xanthorrhiza) Reduces the Severity of Squamous Gastric Ulceraon in
Feed Restricted Horses. J Anim Sci Res 3(1): doi doi dx.doi.org/10.16966/2576-6457.125 5
Journal of Animal Science and Research
Open Access Journal
of ESGD. is pilot study had a number of limitations including the
limited sample size and length of trial due to ethics considerations.
Additionally, as a novel study, there was no previous data on which
to base dose rates, and whilst the feed-deprivation model of gastric
ulcers is well documented it may not necessarily correlate with disease
in the eld. Further research is required to demonstrate ecacy in
the prevention of spontaneous disease, to optimize dose rate and
frequency, and to elucidate mechanism of action.
Appendix A: Supplementary Material
Supplementary data associated with this article can be found, in the
online version
Declaration of Interest
Power Stance™ and C. xanthorrhiza were supplied by Stance
Agriculture Pty Ltd, who also provided partial funding for the project.
Other than as acknowledged below, Stance Agriculture had no role
in study design, execution or interpretation of ndings, nor in the
decision to submit the manuscript for publication. None of the authors
has any nancial or personal relationships that could inappropriately
inuence or bias the content of the paper. Ms. Sophie Fletcher is
owner of Integral Equine Nutrition (independent equine nutrition
consulting), however this had no inuence on the study in any way.
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Sci Forschen
Open HUB for Sc ie n t i f i c R e s e a r c h
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Journal of Animal Science and Research
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