If you’re concerned that intense exercise might be overwhelming your horse’s natural ability to neutralize harmful oxidants in his muscles, researchers have recently reported that a new supplement that boosts the body’s own antioxidant production might prove helpful.

Daily doses of N-acetylcysteine (NAC) combined with coenzyme Q10 (CoQ10) appear to increase  concentrations of two important natural antioxidants in the place horses need them most: the skeletal muscles, said Marisa Henry, a PhD candidate and research associate in the McPhail Performance Center’s Equine Neuromuscular Diagnostic Laboratory at Michigan State University, in East Lansing.

The findings suggest owners might soon have useful alternatives to traditional antioxidants for horses, Henry said.

“I think we should broaden our view of antioxidant supplements beyond vitamin E and selenium, especially for horses that are likely to experience oxidative stress,” she said. “Additional types of antioxidants, such as N-acetylcysteine or CoQ10, may mitigate potentially negative cellular effects of strenuous exercise and appear to benefit horses with muscle diseases like myofibrillar myopathy.”

The Natural Oxidant-Antioxidant Process

During exercise, the horse’s locomotor muscles contract and relax continuously. When the energy supplied for contraction is aerobic, the muscles use oxygen pumped in from the lungs as an energy source. Oxidants—also known as reactive oxygen species (ROS)—are natural byproducts of aerobic metabolism, and they get released into the muscle and bloodstream by the muscle cells. Specifically, the mitochondria within those cells churn out both energy and oxidants.

Despite their reputation for being harmful, low levels of oxidants serve the important purpose of increasing energy produced by mitochondria, said Henry. Once the oxidants accomplish that job, they usually get neutralized by the body’s natural antioxidants, such as the most potent one, ubiquinone—also known as CoQ10—and one of the most prevalent ones, glutathione.

Boosting Natural Antioxidants, Ubiquinone/CoQ10 and Glutathione

Researchers have already determined that supplementing horses with CoQ10 leads to higher concentrations of the protein in the blood plasma as well as in the muscle cells, Henry said. But glutathione can’t be fed to horses because it is poorly absorbed, so the body must manufacture it.

Fortunately, scientists can help the body make glutathione by ensuring it has enough “ingredients.” One of the most important of those is an amino acid called cysteine, which is available in limited supply and must be manufactured in the body on an as-needed basis. When cysteine isn’t produced in large enough quantities to meet demand, glutathione production fails.

While cysteine itself is not well-absorbed as a supplement, scientists have had success getting cysteine into humans by supplementing their diets with NAC, which contains cysteine in a more stable “packaging.” When they did, the patients created more glutathione after exercise, Henry said.

Testing the NAC/CoQ10 Combo in Racehorses in Training

Curious to know how NAC combined with CoQ10 – nicknamed NACQ – would affect the amount of glutathione in horses’ skeletal muscle cells, Henry and her colleagues, in association with researchers at Kentucky Equine Research in Versailles, Kentucky, investigated the effects of NACQ supplementation.

They provided seven Thoroughbred racehorses with an electrolyte supplement (containing sodium, potassium, chloride, calcium, and magnesium) for 30 days, with or without a NACQ supplement. At the end of the 30 days, they switched the horse’s supplement so each horse had 30 days of electrolytes with and 30 days without NACQ.

The five geldings and two mares, averaging 4.7 years old, were in active, moderate-intensity race training and fed hay and concentrated feed. “We wanted to look at antioxidant capacities in the muscle of Thoroughbred horses that are in race training, because exercise could generate high levels of reactive oxygen species that could overwhelm the antioxidant capacity, leading to oxidative stress,” she explained.

On Days 30 and 60, the researchers monitored the horses’ speeds and heart rates as they were exercised under saddle at top speed for a half-mile stretch. The days before and after these two runs, the scientists took muscle biopsies from the horses’ gluteus medius muscles. They also took jugular blood samples before the run and 10 minutes, one hour, and four hours after.

Clear Antioxidant Activity in Muscle Cells

Henry said the study horses’ speeds and heart rates did not change when they received the test supplement. The glutathione concentrations in their muscle cells, however, were significantly higher after exercise when they had been supplemented with NACQ for 30 days. Through a proteomic analysis, the scientists also detected enhanced protein activity related to neutralizing oxidants and generating energy from oxygen in the mitochondria.

“It was very cool to see in our study that the pathways related to maintaining glutathione in its active form (reducing agent, reduced nicotinamide adenine dinucleotide phosphate), NADPH pathways, were upregulated because we know that NADPH is required for reducing oxidized glutathione,” she said. “This shows that the supplements had a clear effect in the muscle. It delighted us to see how much the proteomic analysis added to our understanding of the total impact of the supplements on skeletal muscle in fit horses.”

The findings point to the antioxidants’ potential to be beneficial supplements and suggest more studies on them are warranted, said Henry.

“Most previously, research on equine species has focused on the roles of vitamin E and selenium as antioxidants and measured effects in the bloodstream,” she said. “Very few studies have looked at antioxidants in equine skeletal muscle, especially those found within mitochondria, where most reactive oxygen species are generated. … This supplementation study is novel because we not only analyzed muscle antioxidant concentrations, we also integrated their impact on cellular function through proteomics.”

Despite its potential, owners should use caution with NACQ, Henry added.

“With any supplement, of course, veterinarians should be aware of potential withdrawal periods in racing and competition horses,” she said.

“The Impact of N-Acetyl Cysteine and Coenzyme Q10 Supplementation on Skeletal Muscle Antioxidants and Proteome in Fit Thoroughbred Horses“ appeared in the October 30, 2021, issue of Antioxidants.