Would you like a side of science to go with your horse’s supplements?

Every year equine nutritional supplements continue to increase in popularity. Verified Market Research reported that the global nutritional supplement market for horses was valued at $73.61 million in 2018. The data used to generate that report projected a steady increase in supplement sales, potentially reaching $96.18 million by 2026.

As we’ve reported in previous years, science continues to lag behind the popularity of nutritional supplements … but not for want of trying.

“While the amount of scientific information on veterinary pet supplements and nutraceuticals is increasing, there remains a paucity of quality control, safety, and efficacy data for the majority of both the substances marketed in pet supplements and the resulting products for purchase currently available,” Carrie J. Finno, DVM, PhD, Dipl. ACVIM, of the University of California, Davis, (UC Davis) School of Veterinary Medicine, wrote in a 2020 edition of Nutrition Today. “Despite this lack of evidence, the use of veterinary supplements and nutraceuticals continues to increase.”

Rest assured the importance of research in this field is not falling on deaf ears. Veterinary science teams are generating data on the safety, efficacy, mechanisms of action, and pharmacokinetics of various nutritional supplements. A PubMed search shows that within the past year or so, the bulk of equine nutritional supplement research focused on cannabidiol (CBD), followed by omega-3 supplements, gastrointestinal products, and antioxidants.

In this article we’ll provide a brief rundown of the data from those studies, as well as information on maximizing equine safety when offering supplements.

Cannabidiol (CBD)

Horse owners widely believe CBD products have anti-inflammatory, analgesic (pain-relieving), and calming effects (Williams, 2022), making them a catchall, go-to supplement. To align popularity with evidence-based medicine, researchers recently published four studies looking at CBD and its ­pharmacokinetics—how the drug is absorbed, metabolized, and excreted. First, Heather Knych, DVM, PhD, Dipl. ACVCP, a professor at UC Davis in the K.L. Maddy Equine Analytical Pharmacology Laboratory, looked at the pharmacokinetics of CBD powder obtained from the National Institutes of Health. Her team administered a single dose of CBD mixed with sesame oil to 12 Thoroughbreds. Doses of CBD were 0.5, 1, or 2 mg/kg of the horse’s body weight.

“We found the maximum circulating concentration of CBD increased with increasing dose, ranging from 1.69 ng/mL in the 0.5 mg/kg group to 6.14 ng/mL in the 2 mg/kg group,” says Knych. “Our results suggest that absorption is not saturated within the dose range studied here. Based on the results of our study, though, I cannot comment on whether saturation would or would not occur at any dose higher than 2 mg/kg, as we did not study higher doses.”

Knych’s group also looked at CBD’s effects on inflammation. “Previous studies have theorized that CBD may, at least in part, exert its anti-inflammatory effects by inhibiting COX and LOX enzymes, which are responsible for the production of inflammatory mediators,” she says.

To test this hypothesis in horses, Knych used an ex vivo (outside the horse’s body) model of inflammation to assess CBD’s effects on COX and LOX enzymes.

“Even though inhibition was not appreciated at the doses studied, we recommend further study of the ­concentration-effect relationship for CBD and its metabolites, in addition to characterizing the pharmacokinetics following administration of higher doses,” says Knych.

Next, in a 2021 study Turner et al. evaluated the anti-inflammatory properties of a 99.9% CBD powder in a laboratory setting.

The group collected and incubated white blood cells from senior horses with a range of CBD concentrations. They subsequently measured various inflammatory markers after “stimulating” those white blood cells to mimic an inflammatory insult. CBD significantly reduced the production of various pro-inflammatory mediators (interferon γ and tumor necrosis factor α). Thus, the researchers concluded that CBD shows promise as an anti-inflammatory for chronic inflammation in horses.

Third, Williams et al. (2022) administered either 0.35 mg/kg or 2 mg/kg oral CBD in the form of commercially available hemp pellets for seven days. CBD was rapidly absorbed, reaching a peak concentration in the study horses’ blood approximately two hours after administration. The CBD was metabolized slowly, clearing the bloodstream in approximately 10 hours.

The maximum CBD level in circulation, however, was quite low in this study and, therefore, the researchers suggested the doses they used would be unlikely to result in clinical benefits. Williams et al. suggested dose escalation trials to achieve drug levels likely to have clinical efficacy for conditions such as osteoarthritis (OA).

Finally, Erin Contino, MS, DVM, Dipl. ACVSMR, of Colorado State University’s Orthopaedic Research Center, in Fort Collins, and colleagues evaluated CBD’s pharmacokinetics and synovial fluid concentrations. Oral administration of 1-3 mg/kg of CBD to horses resulted in measurable CBD in the blood, reaching peak levels in approximately four hours. Absorption, however, varied greatly among horses.

After administering 0.5-1.5 mg/kg CBD to study horses twice daily for five weeks, the researchers found measurable CBD in the synovial fluid of 66.7% of them. Taken together, the available pharmacokinetic data show circulating levels of CBD after oral administration are low and the anti-inflammatory effect is inconsistent. That said, having alternatives to non-steroidal anti-inflammatory drugs, which can have adverse effects, would be beneficial for horses with chronic inflammatory conditions such as OA.

Omega-3 Fatty Acids

Omega-3 fatty acids can modulate the inflammatory response in tissues. “Fish oil or algae-derived supplements containing the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have become increasingly popular,” says Undine Christmann, DVM, MSc, MPH, PhD, Dipl. ACVIM, professor of equine internal medicine at Lincoln Memorial University College of Veterinary Medicine, in Harrogate, Tennessee. “To date, studies have explored the effect of these supplements on general behavior, performance, skin, asthma, joint disease, metabolic syndrome, tying-up, various reproductive parameters, and even learning ability in young horses.”

Similar to CBD, data on omega-3 fatty acid pharmacokinetics are lagging behind their popularity. Addressing the need for basic science, Pearson et al. (2022) offered 50 study horses, split into two groups, low doses (7.5 g or 15 g) of a marine-derived omega-3 supplement containing 1.11 g of EPA and 0.69 g of DHA and 2.22 g of EPA and 1.38 g of DHA, respectively, for 12 weeks. The team’s goal was to ascertain if this level of supplementation could alter the fatty acid profile in a horse’s bloodstream. They noted a significant increase in all omega-3 fatty acids, including EPA and DHA, in the horses’ blood at six and 12 weeks of supplementation. Horses supplemented with the 15-g dose had a significantly higher level of omega-3s in circulation than horses receiving the 7.5-g dose.

“The study showed that administration of low doses of DHA and EPA resulted in a dose-dependent increase in omega-3s in the blood of horses,” Christmann says.

Pearson et al. reported circulating levels of omega-6 fatty acids decreased significantly after six weeks of supplementation.

“This further increases the omega-3 to omega-6 ratio, shifting it away from a pro-inflammatory state,” says ­Christmann.

In a 2021 study she and colleagues demonstrated that orally administered EPA and DHA were incorporated into glycerophospholipids (GPLs), which are the body’s reservoirs for those fatty acids. In turn, EPA and DHA are precursors for oxylipins, which are anti-inflammatory mediators.

“Our goal was to look at the potential of DHA and EPA supplementation to increase oxylipin precursor pools in the joints and lungs of horses, because osteoarthritis and asthma are frequent issues in horses,” Christmann says.

Her team divided 20 study horses into two groups: The treatment group received 8.82 g EPA and 5.35 g DHA once daily for 90 days, and control horses received the same diet without supplementation. The researchers collected plasma, synovial fluid, and surfactant (lung fluid collected on bronchoalveolar wash) from all horses at baseline and Days 30, 60, and 90.

“We found that omega-3 supplementation led to increases of key omega-3 fatty acids (EPA, DHA, and docosapentaenoic acid) contained in GPLs in the joints (synovial fluid) and lungs (surfactant) of horses,” Christmann says. “Peak incorporation of these fatty acids in GPLs was reached after 60 days of ­supplementation.”

“Horses with osteoarthritis or asthma potentially benefit from increased GPL storage pools that can produce ­inflammation-resolving lipids,” she adds.

Finally, Rizzo de Medeiros Ferreira et al. studied omega-3 fatty acids in the reproductive arena. Their team reported improved uterine involution after supplementing the diets of pregnant mares starting 90 days prior to their expected foaling date until seven days after their first ovulation (TheHorse.com/1110322). The researchers administered a DHA-rich microalgae product once daily at 0.06 g/kg body weight. The product contained 16.12 g DHA per 100 g of product. Assuming a horse weighs 550 kg (1,200 pounds), this means an average dose of DHA was approximately 5 g.

The sooner a uterus involutes postpartum, the more successful breeders might be at achieving a pregnancy at the time of foal heat, and the better the mare’s odds of early conception, Christmann explains.

Gastrointestinal Supplements

Antiulcer products

Equine gastric ulcer syndrome (EGUS), which includes disease of both the squamous (upper) and glandular (lower) regions of the stomach due to gastric acid, is prominent and believed to contribute to poor performance, recurrent colic, weight loss, and behavior changes.

Medications typically help resolve equine squamous gastric disease (ESGD), but without implementing and maintaining management changes, ulcers in the squamous region tend to recur. The rate of EGUS is high, particularly among performance horses, making gastroprotectants popular.

Andrews et al. (2022) evaluated a nutritional supplement containing curcumin. While the research team’s primary goal was to determine if curcumin improved lameness, presumably due to the herb’s anti-inflammatory properties, their secondary goal was to evaluate its effects on gastric ulcer scores.

In the study, 10 Thoroughbreds received a supplement containing 1,050 mg curcumin extract, as well as Yucca schidigera, vitamin B12, methylsulfonylmethane (MSM), and Boswellia extract, or a control diet for 31 days. By Day 14 of supplementation, curcumin and its metabolite were measurable in 90% of the horses, demonstrating it is absorbed after oral administration.

Most of the horses had gastric ulcers at the start of the study. Gastric ulcer scores decreased in both the treatment and control groups by Day 31, showing that the curcumin supplement did not worsen gastric ulceration, and new ulcers did not form. The study authors were surprised that even the control group had reduced ulcer scores, considering stall confinement is a known risk factor. They suggested the horses had a high plane of nutrition compared to their diet on pasture prior to the start of the study, as well as less competition for feed.

One other study evaluating a nutritional supplement for EGUS found that a combination of pectin, soy lecithin, zinc oxide, and Castanea sativa Mill. (an extract of sweet chestnut) “promoted healing of mild ESGD in endurance horses.”

In that study Lo Feudo et al. (2021) randomly divided 15 endurance horses diagnosed with squamous gastric ulcers into a treatment and control group. Treated horses received the supplement for 30 days, and both groups underwent recommended management changes typical for horses diagnosed with ESGD (e.g., increased pasture turnout, access to good-quality hay, and reduced intake of nonstructural carbohydrates). Only the treatment group experienced a significant decrease in ulcer score, prompting the authors to conclude the supplement “was effective at promoting healing of mild ESGD in endurance horses.”

Mechanisms thought to contribute to the improvement in ulcer scores included:

• Pectins form a gel when exposed to the gastric juice, which protects the stomach lining.
• This gel might also stabilize mucus, increase buffering capacity, and increase gastric pH to make it less acidic.
• Lecithin forms a protective layer that reinforces the acid-repelling properties of the squamous stomach lining.
• Zinc oxide and C. sativa Mill. might exert antioxidant properties that protect the stomach lining against damaging free radicals.

Probiotics

Probiotics, prebiotics, and post- and parabiotics are popular products to support gastrointestinal health, the intestinal microbiome in particular.

“High-grain diets, abrupt changes in feed, administering medications, especially antibiotics, may all contribute to dysbiosis—an imbalance in the microbial population of the microbiome,” says C. Giselle Cooke, MB, BS, PhD (cand.), of the School of Medical Sciences at the University of Sydney, Australia. “In turn, dysbiosis can result in colic, colitis, behavior changes, laminitis/tissue inflammation, and immune dysfunction.

“Dysbiosis produces metabolic byproducts which can be noxious or even toxic, such as those that cause intestinal colic,” she adds.

Cooke’s team recently published a comprehensive review of studies evaluating the safety, tolerability, and efficacy of probiotic products from 1954 to 2020. After identifying and assessing 18 studies, here’s what they found:

• The most common bacteria in probiotic supplements were Lactobacillus spp, Bifidobacteria spp, Enterococcus spp, Streptococcus spp, and Bacillus spp.
• Products containing only a single probiotic species appear less efficacious than multispecies formulations.
• Probiotic bacteria did not improve digestibility of either starches or fibers and did not provide a clear benefit in managing colic or preventing ­salmonellosis.

“In fact, our conclusion was that there were unclear and conflicting results associated with probiotic bacteria use for gastrointestinal conditions,” says Cooke. “This could be because bacteria species are ones commonly used for human consumption. In other words, the currently available commercial probiotic formulations do not contain equine-­specific species but, rather, appear to have appropriated human probiotic species without good evidence for any repurposed benefit.”

In addition, “Neither single nor ­multispecies probiotic supplementation has been shown to be efficacious in treating equine salmonellosis,” she says.

Two positive findings Cooke mentioned were that probiotics improved athletic fitness and stamina and reduced grain-induced hindgut acidosis.

Antioxidants

Svete et al. (2021) evaluated the effects of two antioxidants, coenzyme Q and vitamin E, on exercise-induced oxidative stress in untrained leisure horses. The premise of the study was that strenuous or unaccustomed exercise can lead to muscle damage, inflammation, and oxidative stress. The latter results in increased production of reactive oxygen species, which essentially flounce around cells, damaging DNA, proteins, and other cellular structures. Antioxidants that can minimize that damage following exercise would, therefore, be beneficial.

Svete’s team recruited 40 healthy client-owned leisure horses and divided them into four groups. Horses received either a paraffin control, 800 mg coenzyme Q once daily, 1.8 U/kg body weight of vitamin E once daily, or both coenzyme Q and vitamin E. Supplements were offered for 14 days before horses underwent a prescribed exercise program. The researchers collected blood samples at baseline before supplementation, after 14 days of supplementation prior to the exercise program, immediately following exercise, and again 24 hours after exercise.

Key findings of this study were that supplementation did not increase circulating levels of coenzyme Q10 or vitamin E, but vitamin E administered alone or in concert with coenzyme Q10 prevented lipid peroxidation—a consequence of reactive oxygens damaging cell membranes.

Balancing Efficacy With Safety and Quality Concerns

In an Irish industry survey by Murray et al. (2018), 93% of respondents thought feed supplements had to meet legal standards. Seventy-two percent thought each batch was analyzed for quality, and 92% were under the impression each supplement underwent testing prior to launch.

None of these assumptions are correct. Instead, production of nutritional supplements for animals is largely unregulated, with the exception of the NASC’s quality seal program. As a result, our sources say, the market is flooded with poor-quality supplements presumed, but often unproven, to be safe.

Safety was an important consideration in the studies described herein. For example, Williams said the 2 mg/kg dose of oral CBD was well-tolerated by the supplemented horses.

“We also found that CBD, at doses ranging from 0.5-2 mg/kg, was well-tolerated, with no significant behavioral, gastrointestinal, or cardiac abnormalities observed,” shares Knych.

Contino et al., however, found that liver values increased in over 65% of CBD-­supplemented horses. Those increases were neither dose-dependent nor permanent, as levels returned to normal within 10 days of supplementation. Further, no liver enzyme elevations were sufficiently high to warrant diagnostic work-up or treatment.

Another important finding Williams et al. reported was that the CBD product used in the study resulted in measurable levels of tetrahydrocannabinol (THC) in the bloodstream. “THC levels may result in a positive drug test on a competition basis or during prepurchase examination drug screening,” the study authors stated.

In a 2021 study Berreta et al. found that none of 11 probiotic products marketed for horses met their label claims in terms of the microorganisms listed. In fact, several of the products did not contain any microorganisms. By definition, a probiotic must have live microorganisms to confer a health benefit.

Take-Home Message

These are exciting times for owners keen on providing their horses with the best possible diets. With new products continuing to enter the market, safety issues persist, and many questions remain, such as what supplements to give, how much, when, and to which horse.

When recommending products, veterinarians should consider Finno’s word of caution: “A veterinarian is legally liable if he or she recommends a pet supplement or nutraceutical product that leads to adverse effects.”

This article was originally published in the July 2022 issue of The Horse.