By Vanessa Aberman, DVM, DABVP (Canine/Feline)

The previous two installments in this series focused on nutraceutical use in osteoarthritis (OA) cases (Part 1 and Part 2). This third and final article will focus on nutraceuticals used for common ailments in aging pets, including cognitive dysfunction, muscle atrophy, and heart health.

For cognitive dysfunction, melatonin, valerian root, homotaurine, apoaequorin, and carnitine/α-lipoic acid will be discussed in depth. Ursolic acid, resveratrol, and α-tocopherol acetate will be discussed regarding building muscle due to sarcopenia. Coenzyme Q10 will be considered in regard to heart disease, specifically mitral valve degenerative disease.

Cognitive function

Canine cognitive dysfunction (CCD) has gained some recognition in recent years, as dogs are living longer, and this condition is most prevalent in senior dogs. There is no cure for CCD. Pathophysiology includes beta-amyloid plaque accumulation in the brains of the affected dogs. This also occurs in humans with Alzheimer's disease.¹ Most dogs affected are >8 years old, and in between 14 and 35 percent of the dog pet population.

Clinical signs include confusion, anxiety, disturbances in the sleep/wake cycle, and decreased interaction with owners.² A simple way to screen for this is using the acronym DISHAAL: disorientation, interaction changes with owners or pets, sleep–wake cycle changes, house soiling, alterations in activity and anxiety, and learning and memory changes; as well as increased vocalization for cats.³

In a recent survey of approximately 400 pet owners with age-related behavioral change, more than 50 percent of affected animals received dietary supplements. These included CBD oil, antioxidants such as vitamin E, L-carnitine, and alpha-lipoic acid.¹ There are diets that are supplemented with fatty acids, antioxidants, and/or mitochondrial cofactors that may show improvement with signs of CCD.⁴

Melatonin

Melatonin is a derivative of serotonin that acts on mood, temperature, immune system rhythms, and other metabolic pathways. It has been used to treat insomnia and anxiety.⁵ In one study of 14 dogs with sleep behavior disorders, melatonin did not improve their clinical signs. Thirteen did not show any improvement with insomnia. It is unknown if dosing or changes to frequency would show benefit.⁶

Valerian root

Valerian root has been studied for stress-related behavioral problems (14 behaviors, including auto-grooming, whining, and digging). Twenty-eight dogs with known stress-related behaviors were placed in an unfamiliar environment and were video recorded for their response in a double-blinded study. Dogs were exposed to both a placebo and a plug-in diffuser with valerian root for 30 min, with an intervening period of approximately seven days between conditions. Those exposed to the valerian root did not have a discernible effect on the behavior of dogs placed in a non-familiar environment.⁷

Homotaurine

Homotaurine acts as a potent GABA receptor agonist and may have antioxidant properties as well. One study investigated the effect of homotaurine on cognition in dogs and yielded positive results. In the one-year trial, 24 dogs aged 10-16 years old, sheltered in the same kennel, were randomly assigned into two groups: one group receiving homotaurine supplementation (500 mg once daily), and the other living in the same environment, without any supplementation. Cognitive testing was conducted using a T-maze T zero (immediately before supplementation start) and repeated after four, eight, and 12 months. The homotaurine-supplemented dogs were able to maintain a better performance in learning and memory trials. The results suggest dietary supplementation with homotaurine, together with the additional stimulation and exercise of a learning activity, seems to slow down cognitive aging in dogs.⁸ These findings are promising, but more studies are needed to confirm these results.

Apoaequorin

Apoaequorin, a calcium-buffering protein, has demonstrated cognitive benefits in learning and executive functions in two clinical trials, likely by reducing excitotoxicity and preventing ischemic cell death associated with calcium dysregulation.⁹

In a 32-day trial, apoaequorin improved learning and executive functions without affecting memory in dogs. A higher dose resulted in better cognitive outcomes, and a second trial showed greater performance compared to selegiline.¹⁰ Combinations of Acetyl-L-carnitine (ALCAR), L-carnitine, and α-lipoic acid (LA) have been investigated in terms of cognition in dogs.

Interestingly, a few studies report that L-carnitine and alpha-lipoic acid need to be supplemented together to have any positive effect on cognition. The combination of ALCAR and LA demonstrated improved cognitive outcomes, particularly in memory, in two out of three trials that tested this pairing alone. This highlights the potential synergistic effect between the two compounds.

In the three clinical trials reviewed, L-carnitine was associated with positive effects, but was always administered in combination with other compounds. In the only study using ALCAR alone (27.5 mg/kg), cognitive performance tended to be worse in the treated group.⁹ However, care should be taken when recommending antioxidant supplementation use in dogs and cats because they are not always indicated for both species. For instance, low doses of alpha-lipoic acid can be toxic to cats and should generally be avoided.³

There have been relatively few clinical trials conducted on dogs and even fewer on cats. The variability in protocols, particularly in cognitive assessment methods and the choice of supplements, has made it difficult to draw definitive conclusions.

Moreover, supplements are often administered in combination to enhance nutrient effects and counteract the multifaceted mechanisms of cognitive decline.⁹ There is a need for more evidence-based studies to differentiate cognitive dysfunction in veterinary patients that may stem from different causes when compared with cognitive dysfunction syndrome, because prevention, treatment, and progression may differ.³

While findings on melatonin and valerian root may not strongly support their use with cognitive dysfunction in dogs, there are promising studies that point to the benefits of the use of homotaurine, apoaequorin, and carnitine/α-lipoic acid combination products.

Muscle strength

Ursolic acid

Ursolic acid has been shown, in non-canine species, to be beneficial for skeletal muscle health because it inhibits atrophy-associated mRNA expression and improves skeletal muscle health. It also generated numerous beneficial molecular changes in the skeletal muscle of older dogs, which were associated with significant improvements in exercise participation and performance.

A placebo-controlled study was done to show efficacy in older beagles with age-associated muscle atrophy.¹¹ One group was given a daily supplement of this compound for 60 days, while another was given a placebo. To assess if there were changes in mRNA expression associated with atrophy, the quadriceps muscle was biopsied.

Ursolic acid inhibited numerous mRNA expression changes that are known to promote muscle atrophy and weakness. The dogs were evaluated on exercise participation and T-maze performance as well. Those on the supplement improved exercise participation and T-maze performance. Unfortunately, the sample size was small (10 dogs per group). The study was funded by the manufacturer of the ursolic acid supplement for dogs, so there is risk of bias.¹¹ Another study was conducted investigating resveratrol and α-tocopherol acetate due to their antioxidant properties, and the authors' description that oxidative stress and chronic inflammation can contribute to sarcopenia.¹² In this trial, blood samples of CPK (creatine phosphokinase) and ALP (total alkaline phosphatase) were obtained before the trial. CPK and ALP are considered useful biomarkers for sarcopenia, bone formation and speed in bone remodeling. Twenty-two dogs were observed for two periods of 45 consecutive periods where half were supplemented with 30 mg resveratrol and 20 UI α-tocopherol acetate in their diet, and the other group was not given supplementation.

Days 45-90 were considered a washout period without supplementation. Supplementation with resveratrol and α-tocopherol acetate reduced serum concentration in CPK and ALP, indicating positive modulation of these biomarkers.

At D90, new examinations and collection of venous blood samples were performed and returned to baseline. The correlation between supplementation and effect was confirmed by the second treatment period, in which the values of the two biomarkers returned to the baseline.¹²

It appears that providing select antioxidants and ursolic acid to sarcopenic dogs may be beneficial, but more studies need to be done before recommending this.

Cardiac health

Numerous studies of the effects of CoQ10 supplementation have been conducted in humans with cardiovascular diseases, and several of them show clinical benefits.

One study investigated myocardial Q10 concentrations in tissue samples from Cavalier King Charles spaniels (CKCS) diagnosed with myxomatous mitral valve disease (MMVD) in ACVIM stages B1, B2, and C, and compared them with a group of dogs with no evidence of heart disease. The main finding of the study was reduced concentrations of myocardial Q10 in CKCS diagnosed with MMVD in stage C compared to each of the other groups. The study concluded that depleted myocardial concentration of Q10 is associated with congestive heart failure (CHF) in CKCS diagnosed with MMVD.¹³

Another study to evaluate CoQ10 effects was done on 13 dogs with stage C MMVD. The effects evaluated were preventing myocardial injury, cardiac function, and autonomic balance in dogs. CoQ10 was given at 100 mg/dog twice daily for 28 days. Systolic function (i.e. fractional shortening [FS] and ejection fraction [EF]) increased significantly by eight percent and nine percent, respectively in the group after CoQ10 supplementation.¹⁴

In another study, 43 MMVD dogs in stages ACVIM B2, C and D received coenzyme Q10 (100 mg twice daily) or placebo for three months, and 12 non-supplemented healthy dogs served as controls. All parameters were measured before and after supplementation in MMVD dogs and once in healthy dogs. CoQ10 supplementation had a positive impact on neutrophil percentage, lymphocyte percentage, and lymphocyte concentration in groups C and D. This indicates this supplement may decrease inflammation in dogs with CHF.¹⁵

Based on these studies, supplementation with CoQ10 is reasonable in patients with stage C and D MMVD.

Conclusion

Several nutritional supplements treat common conditions, especially in aging dogs and cats. Owners often need guidance on which supplements make sense for their pets. Unfortunately, there is not as much scientific data on the benefits of these supplements, and often, the studies are funded by the manufacturers of said supplements, or there are issues with the design of the studies.

However, there is support for the use of homotaurine, apoaequorin, and carnitine/α-lipoic acid combination products in dogs with cognitive dysfunction. Supplementation of resveratrol α-tocopherol acetate, and ursolic acid may benefit dogs with decreased muscle mass, but more studies need to be performed before recommending these products. Finally, there does seem to be evidence that CoQ10 is beneficial for patients that have been diagnosed with CHF secondary to MMVD.

Vanessa Aberman, DVM, DABVP (Canine/Feline), has worked in private and corporate practices as an associate veterinarian, relief veterinarian, medical director, and area medical director. Dr. Aberman's professional interests include surgery, dentistry, and pain management. She is currently the director of Medical Quality at Modern Animal, where she ensures the veterinary teams practice the latest evidence-based guidelines. She is also a regular speaker at local and national venues.

References

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