Why ingredients for pet food supplements should be studied

Photo: RHJ/Adobe Stock

This article was originally published by Nutritional Outlook, a dvm360 sister publication.

The “humanization of pets” is a phrase that’s been used ever since animal owners began treating their pets more like equal members of the family. We want the best for our loved ones and for ourselves, so why wouldn’t we want the same for our beloved animal companions?

When it comes to food and nutrition, the “humanization” movement has pet owners buying more fresh, clean-labeled, and natural foods for their pets; foods with fewer artificial ingredients and fillers. When it comes to adding dietary supplements to the mix, pet owners seek to provide their animals with the same health benefits that they themselves gain from these functional ingredients.

But how do you know that an ingredient that benefits humans also works in animals? The answer is simple: by studying the ingredient in an animal population. It’s no surprise that fewer nutraceutical studies are conducted in animals than in humans. We spoke to some of the ingredient suppliers who are investing in pet science. As it turns out, research shows that their ingredients definitely do pose notable health perks for animals.

The Proof Is in the Pet

Why is studying pet supplement ingredients in an actual pet population so important?

“In our view, it’s simple,” said Julie Gasper, pet, equine, and lifestyle additives category lead at Cargill in Minneapolis, Minnesota. “Dogs and cats aren’t people. While humanization is driving innovation in the pet supplement category, the reality is we’re not the same. Just because a product is safe and effective in humans doesn’t mean it will be safe or effective in dogs or cats. Consider all the foods that are safe for humans but toxic to pets; we shouldn’t make assumptions without doing the testing. Any time a novel ingredient goes into a pet product, it needs to be supported by pet research, including dosage work to determine optimum inclusion levels.”

Pet supplement formulators should also consider whether an ingredient has been studied for their target species, the type of animal the supplement will be marketed for. For instance, Gasper said, “Cats are not small dogs. Felines have historically taken a backseat to canines, with the expectation that if something is good for dogs, it must be good for cats, too. We know that isn’t necessarily the case, and it’s why a big area of focus for our upcoming research will be targeted at cats.”

As Eric Anderson, managing director of NXT USA Inc. in Metuchen, New Jersey, said, “Clearly, we at NXT are in favor of human studies for humans, and animal studies for animals—whenever possible! Murine studies are great for indication and discovery, but really we need to validate in the animal—most commonly companion animals, including dogs, cats, and horses.”

In the nutraceuticals market, some ingredients have more pet studies behind them than others. “I think that the amount of quality research on pet health ingredients really varies by the ingredient,” said Margitta Dziwenka, DVM, DABT, director of preclinical and companion animal services at GRAS Associates, a Nutrasource Pharmaceutical and Nutraceutical Services company in Guelph, Ontario. “Some are well studied and have been on the market in various forms; however, there are many that still need to be researched even though they may be on the market already.” And making safety and efficacy information available to the broader scientific community as well as regulatory authorities is important, she added.

Prebiotics, Probiotics, and Postbiotics

Microbiome-health ingredients—such as prebiotics, probiotics, and postbiotics—is an ingredient category with some of the richest pet research going on today.

“Prebiotics, probiotics, and postbiotics continue to generate a significant amount of interest in both humans and animals,” Dziwenka said. “Information about the importance of a healthy gut microbiome is coming out on a regular basis, and the understanding of the link between general health and gut health in both humans and animals is expanding daily.”

Species-specific research is especially important in this ingredient class because the gut microbiome of different animals species can “vary considerably,” Dziwenka added.

Research shows that supporting the microbiome with these ingredients can yield a wide range of health benefits. “As we learn that a healthy microbiome affects more than just digestive health and comfort, we are seeing the companion animal microbiome becoming of greater interest for research in categories such as anxiety and stress, oxidative stress, immunity, skin/coat health, and much more,” said Alexis Collins, director of product and brand strategy at Stratum Nutrition in Carthage, Missouri.

“We have learned that a balanced microbiome is important for overall health, for all living things. And, we are also starting to understand how microorganisms can convert dietary components into beneficial metabolites, such as short-chain fatty acids, that directly affect the health of both humans and canines. So, there are many, many branches of microbiome research possible, of which we are just beginning to explore,” she added.

Stratum Nutrition recently completed a study on its LBiome heat-treated Lactobacillus LB postbiotic ingredient to investigate whether the ingredient can lower stress levels in dogs that are traveling. “There are quite a few natural supplements on the market that are marketed to help relieve stress/anxiety in pets,” Collins explained. “Whether many of them are studied to show these effects specifically in canines is a bit trickier to answer. Many companion animal owners believe that what is effective for their own stress and anxiety will also be effective for their pet, but our companion animals deserve to have research on the supplements we give them showing specific benefits in their species. We have conducted our canine research on LBiome, to ensure that the microbiome health benefits in human clinical studies transcend from human to canine, while also observing canine-specific benefits, such as the higher superoxide dismutase (SOD)/antioxidative support in the face of travel-induced stress.”

In the new study on LBiome, investigators administered a 4 mg/kg dose of LBiome, or a placebo, to dogs daily for 5 weeks. The study’s patients experienced healthier bowel function and microbiome diversity, which Collins says was not surprising. They also, however, looked at whether LBiome supplementation helped reduce travel-induced oxidative stress in the dogs, because “any dog owner knows how awful a car ride can be with a stressed-out canine friend, and you can see the toll the ride can take on their bodies,” she explained.

During the travel-induced stress test, the dogs were put in pet crates and driven in a vehicle for 45 minutes. Before and after the ride, researchers took serum measurements to determine the SOD levels of the dogs, as “SOD is an antioxidant enzyme in the body that helps transform free radicals into less-damaging molecules, attenuating oxidative damage,” she said. According to Collins, the study found that the LBiome-supplemented dogs had significantly higher levels of SOD compared to the placebo subjects, “which can be interpreted as more protection from free radicals and oxidative damage incurred from travel-induced stress,” she said.

“There are not many published studies on postbiotics in companion animals at this time, but we are seeing an increase in published studies coming out now as interest in postbiotics for both humans and pets has grown substantially over the last 2 years,” Collins added.

Microbiome ingredients for pets are also under active investigation at ADM in Chicago, Illinois. “Specifically in the pet space, we are exploring multiple aspects of health,” said Gustavo Zenaide, vice president of pet and animal well-being at ADM. “ADM scientists have identified specific microbial strains that may support metabolic and gut health for dogs and cats.”

For instance, a recent unpublished canine study examined the heat-treated version of ADM’s probiotic strain BPL1 (Bifidobacterium animalis subsp. lactis CECT8145; trademarked as BPL1 for Biopolis S.L. in the EU and other countries). Investigators concluded that this postbiotic ingredient may increase beneficial bacteria in the gut of dogs, as well as help increase production of propionate, a short-chain fatty acid.

Zenaide said that BPL1 has also shown weight-management benefits in obese human adults by reducing visceral fat and maintaining a healthy waist circumference, in combination with healthy diet and exercise. He said the company is now exploring whether there are similar benefits in dogs.

In the probiotic arena, Zenaide says ADM is expecting a clinical trial in dogs to be published this September on probiotic strain Bacillus subtilis DE111 (a trademark of Deerland Probiotics & Enzymes in the U.S. and other countries). The study focused on whether DE111 produces any digestive health benefits in dogs as it has been clinically shown to do in humans. Not only that, but the company also expects to start DE111 clinical trials in cats this fall.

And, most recently, ADM announced a distribution partnership with Gnubiotics Sciences (Sweden) for Gnubiotics’ AmoBiome glycopeptide ingredient for pets. This fermentable-fiber ingredient is said to support digestive health and the growth of beneficial gut bacteria. “Scientists at Gnubiotics investigated the effect of the milk oligosaccharide biosimilar on the gut microbiome composition of dogs and have recently published intriguing data suggesting AmoBiome may provide microbiome stability during disturbance by an antibiotic,” Zenaide reported.

Other future areas of clinical study for ADM in the biotics pet space include skin health, mental well-being, and oral health in dogs. These ingredients have reportedly shown promise in preclinical pet studies or in humans.

Cargill’s EpiCor postbiotic ingredient has long been known in the human-supplements industry as a clinically studied immune and digestive health ingredient. The company’s version of the ingredient for pets, EpiCor Pets, is also studied for its target population.

The company recently completed a 60-day study on EpiCor Pets in nearly 350 dogs in the US. The in-home, blinded trial, not published, gave dogs either a placebo or the EpiCor Pets postbiotic supplement. The dogs’ owners observed effects and completed questionnaires before the study’s start and again at 15, 30, 45, and 60 days into the study. Invetigators also analyzed the dogs’ fecal samples at the beginning, middle, and end of the study to track any gut microbiome changes.

“This in-home study affirmed the health benefits we’d previously noted through our extensive controlled research. We expected pet parents would note improvements related to immunity and digestive health, and they did. Pet owners who fed the supplement that included EpiCor Pets were 95% more likely to give it high marks for improving their dog’s immunity as compared to those in the control group. We also saw a significant jump in pet owners’ assessment of their dog’s overall health—one of the most important considerations when consumers choose a pet food or supplement. Further, at the same time pet parents were observing improvements in their pet’s health, the fecal samples they collected were registering similar benefits in the lab. All those findings aligned with our previous clinical trials,” said Cargill’s Gasper.

But the study results also turned up an unexpected benefit. Gasper reported that owners of pets who were given EpiCor Pets were 211% more likely to rate their pet as having better breath after supplementation compared to the control group. “While this result was unexpected, it made sense,” Gasper says. “When you influence a pet’s gut microbiome, you may also influence other systems—in this case, oral health and, subsequently, a dog’s breath odor.”

Gasper says Cargill remains committed to conducting pet-specific studies on the postbiotic ingredients it offers, and that the company has so far conducted about a dozen of these studies, “including third-party research that evaluated the microbiological and immunological responses of postbiotics in dogs and cats. This work continues,” she said, “as we aim to better understand the benefits of EpiCor Pets and our other pet-specific postbiotic solutions, as well as the nutritional needs of dogs, cats, and other companion animals.”

Moreover, Gasper said that the company believes that conducting the in-home EpiCor Pets study was important in order to add to the data the company already had from in vitro and controlled studies. “In real life, pets can get into all kinds of things that influence their gut microbiome, from last night’s table scraps to a new treat,” she said. “Additionally, we wanted to understand what pet parents actually see—and how soon they notice results—when their animals are offered supplements that include EpiCor Pets. While we had a solid grasp of how EpiCor Pets positively influences the gut microbiome based on lab results and clinical trials, if a pet parent doesn’t notice a difference in their dog’s overall health and vitality, we know they may switch to a different supplement as they seek visual results.” Thus, she said, even though conducting the in-home study was a “massive undertaking,” the company felt it was important in order to add data to its bank on how pets actually respond to EpiCor Pets in a home setting.

Botanical Formulation for Joint Health

Last year, a study¹ published in Veterinary Medicine and Science studied NXT USA’s TamaFlex joint-health ingredient in working horses. TamaFlex is a blend of tamarind seed and turmeric root extract that has been shown to improve joint health, stiffness, and mobility. As NXT USA’s Anderson pointed out, “Lameness is one of the major causes of reduced physical performance and early retirement in working horses.”

In the 12-week, single-center, randomized, blinded, placebo-controlled study, investigators administered either a placebo or TamaFlex (2.5 g/day) to 22 horses that showed lameness grades of 2-4 on the American Association of Equine Practitioners (AAEP) scale. The primary endpoint was an improvement in lameness. The researchers also measured secondary-endpoint changes in rheumatoid factor (RF), anti-nuclear antibody (ANA), and anti-cyclic citrullinated peptide (ACC-peptide), as well as pro-inflammatory cytokines like interleukin (IL-1β and IL-6), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) in serum and synovial fluid.

Horses that supplemented with TamaFlex experienced significant relief from lameness in a time-dependent manner, the researchers found. TamaFlex supplementation also resulted in reduced levels of ANA, PGE2, IL-β, TNF-α, and IL-6.

Anderson said NXT USA would now like to extend the study to dogs and cats to determine if these species experience any joint-health benefits from TamaFlex. Meanwhile, he reported that several companies are now exploring the use of TamaFlex in horse products.

“We are actively working on new research with animals,” he added. “Traditionally, pet owners would recognize some health issue with their pet and then look at supplements the owner is using and give it to the pet. ‘Aw, Fluffy can’t jump on the bed anymore; let’s give her supplement X, Y, or Z.’ Hopefully, the supplement was safe for the animal. However, it is best practice to show the benefit in the pet, at the correct dosage level, with good evidence of safety, to help validate the use of the supplement. We look forward to industry continuing to develop the scientific validation.”

Palm Phytonutrients

Some studies have been published showing that palm phytonutrients may benefit pet health. Ingredient supplier PhytoGaia in Malaysia recently introduced a new natural palm phytonutrient–complex ingredient for pets called PetGaia containing full-spectrum tocotrienols (alpha-, beta-, gamma-, and delta-) as well as plant phytosterols and squalene.

Ariati Aris, PhD, PhytoGaia’s scientific affairs specialist, said there have been “several new research/publications that have emerged in the field of animal nutrition specifically to study palm phytonutrients and their potential benefits for pet health. Interestingly, these studies were conducted and published on young puppies and adult canines.”

The first study Aris pointed to was published in 2017 and evaluated how supplementing with palm phytonutrients could aid in the growth and health of young German Shepherd dogs.² The second study, meanwhile, tested palm phytonutrients in adult golden retrievers.³ “Both studies found that palm phytonutrient–complex supplementation was associated with significant improvements in a range of health outcomes, including improved growth, increased muscle mass, and better overall health. These findings suggest that palm phytonutrient complexes such as PetGaia…could be an important dietary supplement for pet owners looking to optimize the health and well-being of their furry companions," Aris said.

Some of the hottest areas of palm phytonutrient research in pets include skin and fur health, she reported. She said that PhytoGaia’s research on PetGaia is ongoing. “However,” she added, “in addition to the published articles mentioned above, there are numerous studies on tocotrienol and squalene that give a positive impact on pet health. Individually, squalene and tocotrienols are natural, potent antioxidants with proven scientific evidence for maintaining cardiovascular health, immune enhancement, liver health, brain health, and neuroprotection, as well as keeping the skin young, soft, and supple.” She said that PetGaia’s “natural plant extract combination—tocotrienol, squalene, and phytosterols—will have a tremendous synergistic effect on a pet’s health by offering a unique solution, providing antioxidant protection against harmful free radicals while also moisturizing and safeguarding the skin.”

Pet Research on the Rise

There are many ingredient suppliers investing in pet-specific research, and reputable pet-supplement companies are looking for those proven, clinically studied ingredients. For instance, in April 2023, NOW Pets introduced a new supplement for dog and cat joint health, UC-II Advanced Joint Mobility Supplement, featuring Lonza’s (Basel, Switzerland) UC-II branded undenatured type II collagen ingredient, as well as ingredients like glucosamine hydrochloride (HCl), methylsufonylmethane (MSM), and Boswellia serrata extract.

According to a NOW press release, UC-II has been studied in dogs. One study⁴ showed that UC-II supplementation in dogs resulted in a 66% reduction in dogs’ overall occasional stiffness within 60 days and a 91% reduction in overall occasional stiffness after 120 days of supplementation, compared to baseline. Another study⁵ showed a gradual reduction of overall occasional stiffness in dogs taking UC-II over time—improvements that ceased once the dogs stopped UC-II supplementation.

NOW’s pet products bear the NASC seal from the National Animal Supplement Council. “All products in the NOW Pet line use the same ingredients and strict quality assurance for dog and cat supplements as for NOW’s human products,” the company added.

A pet health ingredient with a rich body of research in pets is the ideal choice for any pet supplement maker. “One clinical study isn’t enough. You’ll see companies claim to offer a science-based ingredient, but it is supported by only a single trial. And even that may or may not have been conducted with pets; they instead might be using research in mice, pigs, and other livestock species to support their product in dogs and cats,” said Gasper.

“There’s a huge difference between having just one pet study and having a dozen studies that span both clinical and real-world, in-home settings,” she concluded. “More research gives you a much better picture of what the ingredient is, how it works, and what it is doing to support a pet’s health.”

And what if a company isn’t using a branded ingredient or conducting research on its own ingredient? Nutrasource’s Dziwenka noted that there’s still a lot you can do to vet your ingredient science.

“The gold standard is to always evaluate a specific product for safety and efficacy in the intended species; however, a company may be able to rely on data available in the published literature which has been conducted on similar products,” she advised. “How much you can rely on data from other species and other similar products may vary depending on what the supplement is and how similar the products are.”

And, Dziwenka cautioned, “A good understanding of the unique dietary requirements and metabolism of each species you are interested in is very important. You cannot assume that the supplement will be metabolized the same in cats and dogs as it is in humans, and you cannot assume the dose is the same either.” Companies looking for a cost-effective way to make more-informed formulating decisions can also design and conduct “basic proof-of-concept” studies, she added.

In conclusion, she said, “I think that a thorough literature review on the ingredient or ingredients in [your] supplement is a great place to start. This will give you a good idea of the quality and quantity of information that is available and in what species. It is very important to also remember to review the doses used in studies and then compare that to the doses of the ingredients in your own supplement. It is also important to consider the biological interactions of the various ingredients if you have a multi-ingredient formulation, not just the effect of the individual ingredients in isolation. This will allow you to identify the gaps in the data and allow you to gather data on the supplement to ensure it is both safe and efficacious in the species you are interested in.”

References

1. Jain, S.; Patil, S.G.; Chinta, G.; Alluri, K.V. TamaFlex—A Novel Nutraceutical Blend Improves Lameness and Joint Functions in Working Horses. Vet Med Sci. 2022, 8 (5), 1936-1945. DOI: https://doi.org/10.1002/vms3.894
2. Ningkun, C.; Fengxia, W.; Shuxin, Y.; Yinhui, M.; Qingji, H.; Baojian, C. Effects of Red Palm Oil on Growth and Health of Young German Shepherd Dogs. Feed Research. 2017. https://qikan.cqvip.com/Qikan/Article/Detail?id=673337666&from=Qikan_Search_Index
3. Xinyu, Y.; Ningkun, C.; Qianqian, M.; et al. Effects of Red Palm Oil Supplementation on Adult Golden Retrievers: A Study on Growth Performance, Nutrient Digestibility, and Health Status. Feed Research. 2018. http://www.cqvip.com/qk/93825x/20183/675455317.html
4. D’Altilio, M.; Peal, A.; Alvey, M.; et al. Therapeutic Efficacy and Safety of Undenatured Type II Collagen Singly or in Combination with Glucosamine and Chondroitin in Arthritic Dogs. Toxicol Mech Methods. 2007, 17 (4), 189-196. DOI: 10.1080/15376510600910469
5. Gupta, R.C.; Canerdy, T.D.; Lindley, J. Comparative Therapeutic Efficacy and Safety of Type-II Collagen (UC-II), Glucosamine and Chondroitin in Arthritic Dogs: Pain Evaluation by Ground Force Plate. J Anim Physiol Anim Nutr (Berl). 2012, 96 (5), 770-777. DOI: 10.1111/j.1439-0396.2011.01166.x