One of the most common and important problem that diminishes quality of life in dogs and cats as they age is sarcopenia, the loss of muscle mass and strength. This can also occur as a result of other causes, such as osteoarthritis, primary nerve or muscle disease, and any prolonged disuse, such as following an injury or surgery. The most effective method found for combating this in humans so far has been exercise, specifically resistance training.1 There have been a number of other dietary and pharmaceutical therapies explored, but none have yet been validated to improve muscle mass or function in humans, and the current guidelines emphasize appropriate exercise and protein intake.2
In veterinary medicine, the evidence is typically less robust for diets, medications, and supplements, and the regulatory oversight less effective than for prescription drugs. As a result, products are often marketed to pet owners and veterinarians with treatment claims based on limited evidence that would not be allowed for a product intended for human use. In the case of sarcopenia and other causes of muscle loss and weakness, there are several products available claiming to be safe and effective treatments. None of these are approved prescription drugs, and none have been through high-quality clinical trials in companion animals to demonstrate these claims.
As a practical matter, we are often forced to use therapies without robust supporting evidence when the need is high and better options are unavailable. This ius certainly the case with age-related sarcopenia, so trial-and-error use of the products may sometimes be justified., However, it is important that we have an accurate understanding of what claims can and cannot legitimately be made for these treatments, and that we give full and honest disclosure about this to our clients, so I will review the current available evidence for several of these products.
Myos (fortetropin)
Fortetropin, the purported active ingredient in this supplement, is a compound derived from the yolk of fertilized eggs. It is suspected to reduce levels of the hormone myostatin, and thereby potentially increase muscle mass. However, the evidence for this proposed mechanism in rodents dogs, and humans is mixed, and some studies find no effect on myostatin.3–6 Even in those studies where myostatin levels are altered, this doesn’t necessarily correspond to a change in muscle mass or function.7 Other mechanisms have also been posited, but these have also not been convincingly shown to be true or to have significant benefits.
The clinical studies in dogs have been small and mixed, with significant limitations. For example, one study in senior companion dogs with impaired mobility found signs of improvement within the treatment group.8 However, there was no statistically significant difference between the treatment and the placebo group at any point, and the authors acknowledged that “this statistically significant difference within the treatment group may not reflect a clinically relevant change.” It may be the study was too small to detect a difference or, of course, it may be there was no real effect to detect.
Another study often cited to support the use of this product involved dogs having a TPLO surgery for a ruptured cruciate ligament. This is not the same condition as aging-associated sarcopenia at all, though disuse atrophy following injury or surgery would itself be a worthwhile target for treatment. The study found a decrease in muscle thickness in the placebo group following surgery, as would be expected, but no decrease in the treatment group. However, there was again no statistically significant difference between the groups, and both groups showed appropriate improvement in function over time, so it is unclear whether any differences were meaningful or contributed to any difference in function or wellbeing.
As is typically the case, the evidence in cats is ever thinner. One poster presentation has reported no significant adverse effects in healthy cats. Another uncontrolled study, also presented as a poster, showed a gain in both lean mass and fat mass in cats with Stage II and Stage III chronic kidney disease given fortetropin. Since there was no control group, it is uncertain whether this was a direct effect of the supplement, and no measures of function were included.
As for risks, the few studies in dogs and cats haven’t revealed any obvious, serious adverse effects. Some GI upset has occurred in subjects in these studies, though that is common enough that whether or not it is due to the fortetropin is hard to tell. Myostatin inhibitors in general have been associated with potential heart muscle problems with long-term use as well as connective tissue injuries and other undesirable effects, though whether these would appear with long-term fortetropin use is unknown.
All of the available studies have been funded by the manufacturer of the supplement product, and while this is frequently the case for supplement and drug studies, and the data from these tests is still useful, there is an increased risk of bias in any industry-funded research.
Ursolyx (ursolic acid)
Ursolic acid is a chemical compound found in a variety of plants. There is an extensive body of research in vitro and in lab animal subjects, and some in humans, evaluating the potential effects of this compound on muscle and on other tissues and physiologic pathways. The results are quite mixed.9,10 A systematic review from 2017 found some rodent studies showing improvements in muscle mass and function but also some human studies failing to show tangible benefits.9 A more recent review of the compound and its effects on risk factors for cardiovascular disease in humans found no change in “body weight, body mass index, waist circumference, body fat percentage, lean body mass, systolic blood pressure, diastolic blood pressure, fasting blood glucose, insulin, triglyceride and high-density lipoprotein” and concluded the compound ”had no significant effect on the cardiometabolic risk factors in adults.”10
One small study in laboratory beagle dogs has been published that shows some promising change sin mRNA expression suggesting it could mitigate muscle atrophy. However, the functional measures were either highly subjective (e.g “willingness to exercise”) or showed no difference compared with placebo (e.g. latency for maze test), and there was no assessment of any change in muscle mass. While this is useful data, alone it is hardly sufficient to support widespread use of ursolic acid supplements. In cats, there is no published evidence showing meaningful clinical effects, only claims from one manufacturer that such evidence exists.
TL;DR
As is so often the case, there is plenty of marketing claiming these products can delay or even reverse muscle loss from sarcopenia or other causes, but there is no robust or independent clinical trial data to support these claims. Safety is equally unclear, and though no significant adverse effects have been reported, this inspires limited confidence given how little research exists in companion dogs and cats.
In the absence of remedies for sarcopenia that are proven safe and effective based on appropriate research evidence, the use of such supplements may be reasonable. However, history has pretty clearly shown that the majority of such products never really reach that standard of evidence or have a significant clinical impact, and it seems unlikely that these will be exceptions to that pattern.
References
1. Chen N, He X, Feng Y, Ainsworth BE, Liu Y. Effects of resistance training in healthy older people with sarcopenia: a systematic review and meta-analysis of randomized controlled trials. Eur Rev Aging Phys Act Off J Eur Group Res Elder Phys Act. 2021;18(1):23. doi:10.1186/s11556-021-00277-7
2. Dent E, Morley JE, Cruz-Jentoft AJ, et al. International Clinical Practice Guidelines for Sarcopenia (ICFSR): Screening, Diagnosis and Management. J Nutr Health Aging. 2018;22(10):1148-1161. doi:10.1007/s12603-018-1139-9
3. White DA, Harkin KR, Roush JK, Renberg WC, Biller D. Fortetropin inhibits disuse muscle atrophy in dogs after tibial plateau leveling osteotomy. PLoS ONE. 2020;15(4):e0231306. doi:10.1371/journal.pone.0231306
4. Evans W, Shankaran M, Nyangau E, et al. Effects of Fortetropin on the Rate of Muscle Protein Synthesis in Older Men and Women: A Randomized, Double-Blinded, Placebo-Controlled Study. J Gerontol A Biol Sci Med Sci. 2021;76(1):108-114. doi:10.1093/gerona/glaa162
5. Nugent Britt CC, Alvarez LX, Lamb K. In a Randomized, Placebo-Controlled Cross-Over Study, Administration of 6 and 12 G Fortetropin® Does Not Reduce Serum Myostatin in Healthy Adult Dogs Over 72-Hours. Front Vet Sci. 2021;8:680576. doi:10.3389/fvets.2021.680576
6. Sharp MH, Lowery RP, Mobley CB, et al. The Effects of Fortetropin Supplementation on Body Composition, Strength, and Power in Humans and Mechanism of Action in a Rodent Model. J Am Coll Nutr. 2016;35(8):679-691. doi:10.1080/07315724.2016.1142403
7. Lim C, McKendry J, Giacomin T, et al. Fortetropin supplementation prevents the rise in circulating myostatin but not disuse-induced muscle atrophy in young men with limb immobilization: A randomized controlled trial. PloS One. 2023;18(5):e0286222. doi:10.1371/journal.pone.0286222
8. Hetrick K, Harkin KR, Roush JK. Evaluation of Fortetropin in geriatric and senior dogs with reduced mobility. Can Vet J. 2022;63(10):1057-1060.
9. Katashima CK, Silva VR, Gomes TL, Pichard C, Pimentel GD. Ursolic acid and mechanisms of actions on adipose and muscle tissue: a systematic review. Obes Rev. 2017;18(6):700-711. doi:10.1111/obr.12523
10. Rafiee P, Rasaei N, Amini MR, et al. The effects of ursolic acid on cardiometabolic risk factors: a systematic review and meta-analysis. Future Cardiol. 2024;20(3):151-161. doi:10.1080/14796678.2024.2349476
