Omeprazole Can Have Negative Side Effects In Humans; Should Horse Owners Be Worried?

If you watch television, no doubt you've seen commercials by law groups warning users about the dangers of proton pump inhibitors in humans. Proton pump inhibitors are prescribed for the prevention and treatment of acid-reflux disease and ulcers. They work by blocking the production of stomach acid and are marketed under the brand names Prilosec, Nexium, and Prevacid. Human studies link chronic use of proton pump inhibitors to kidney disease, fracture risk, and anemia.

Included in this classification of drugs is omeprazole, a common medication also used in horses to prevent and treat gastric ulcers.

Some equine nutritionists and horsemen are concerned that omeprazole may hold the same dangers for horses. No equine studies investigating these concerns have been published, so nutritionists can only speculate how suppression of stomach acid by omeprazole might be affecting horses.

Dr. Juliet Getty of Getty Equine Nutrition in Lewisville, Texas, believes horsemen's concerns are reasonable because what happens in a horse's stomach is not that different from human digestion.

“What happens in humans is that these medications not only reduce protein digestion, but they also inhibit the absorption of key minerals and vitamins, such as magnesium, calcium, vitamin D, and vitamin B12,” Getty said.

Protein is essential for muscle development and repair, which is crucial in performance horses. Getty explained that stomach acid activates pepsin, the enzyme that breaks apart proteins into smaller chains of amino acids. Protein digestion then can be completed by other enzymes within the small intestine, down to individual amino acids that can be absorbed into the bloodstream.

She described how omeprazole affects protein digestion in humans.

“If the long amino acid chain is not broken apart initially in the stomach by pepsin, which would be inhibited by omeprazole, then that protein would not be adequately digested,” she said. “It is possible that a protein deficiency could ultimately develop, but you would definitely see a compromised protein status.”

Magnesium is important for muscle function, a healthy nervous system, sound bones, and healthy kidneys.

Calcium's primary role is to build strong bones and teeth. Constant bone turnover that occurs in racehorses creates a high demand for calcium. The mineral also helps muscles to contract and relax and nerves to send and receive signals. In the vascular system, calcium is essential for blood clotting and a steady heartbeat.

Digestibility Trial

Dr. Joe Pagan, president of Kentucky Equine Research, similarly was concerned how omeprazole's suppression of digestive acid in the horse's stomach affects digestion. In particular, he wanted to determine if omeprazole interfered with the digestibility of a calcium supplement KER developed to increase bone density. The supplement utilizes a marine-derived calcium called BMC, which is more digestible than the limestone powder (calcium carbonate) typically used as a calcium source in horse feeds.

Pagan conducted a digestion trial with four idle Thoroughbreds that evaluated how well the horses were able to digest two sources of calcium (BMC and limestone) with and without two weeks of omeprazole administration at the recommended therapeutic dose  (4 mg/kg per day).

“The source of calcium and the omeprazole both significantly affected calcium digestibility,” Pagan said.

He found the calcium in BMC was more digestible than limestone, but that omeprazole administration decreased the digestibility of both sources of calcium. Omeprazole administration decreased calcium digestibility by 20 percent in the limestone-supplemented diet, while the calcium in the BMC-supplemented diet was 15 percent less digestible.

Interestingly, omeprazole had no effect on any other nutrient that the study measured, except calcium. It did not adversely affect the digestibility of magnesium, iron, protein, fat, or fiber.

However, Pagan did find that serum gastrin was doubled in the horses on omeprazole. Gastrin is a hormone produced by the stomach to stimulate gastric-acid secretion.

“In studies with other animals and humans, increased gastrin has also led to increases in parathyroid hormone [PTH] production, and there was a trend toward increased PTH in this study,” Pagan said. “PTH causes the body to pull calcium from the skeleton to maintain blood calcium, which is essential to support muscle and nervous function. Chronically elevated PTH may lead to osteoporosis, or holes in the bone that reduce bone strength and mass.

Although this study did not directly assess bone metabolism, Pagan called this result a potential smoking gun.

“Now, this study only included four horses, and the length of omeprazole administration was just two weeks,” he said. “At this point I don't have any definitive proof that omeprazole affects bone, but I think it would be worth conducting additional studies to determine if longer-term administration of omeprazole would have an effect on PTH production that might have an effect on bone.”

Pagan said the results of KER's digestibility study indicate further research into the effects of omeprazole on calcium digestibility are needed.

“This study should not be an alarm that everyone should stop using omeprazole,” he said. “It doesn't mean that at all. It means that if you're using omeprazole, you probably should pay closer attention to the horse's calcium intake and make sure it is adequate, and preferably use available forms of calcium.

“From our previous studies of furosemide—Lasix—we found that it increases urinary calcium excretion. So if you have a horse that is on omeprazole and Lasix, for sure you need to take a pretty close look and make sure you are giving them enough calcium in their diet.”