Cats that don’t eat for long periods can develop an array of serious secondary health problems. Defining and understanding feline cachexia can be complicated, but the use of nutraceuticals can help manage the condition.

While some animal species can go for long periods without eating, cats are not among them. Laboratory studies have shown that the feline species can survive two weeks without food; however, due to the cat’s metabolic pathways, many secondary problems can occur within a few days of not eating. The most common fall into an intertwining group of disease conditions known as Feline Triaditis, which includes pancreatitis, inflammatory bowel disease, and cholangitis. Other concurrent conditions such as hepatic lipidosis (fatty liver disease), inflammatory liver disease, and vitamin deficiencies can also occur.³ This article looks at feline cachexia and how nutraceuticals can be used to manage it.

Cats are a unique species. They are strict carnivores and require a much higher protein intake than omnivores.¹ For optimal health and nutrition, special dietary factors must be taken into consideration within the feline diet. It must also include some vitamins and amino acids that cats cannot produce naturally, such as taurine, arginine, and vitamin A.^1 2Cats can also become very “set in their ways”, often stubborn at times. Once a cat has quit eating, it can be difficult to coax them back to food, especially if it created a feeling of nausea the last time it was eaten. An integrative approach may be most beneficial, and one such option for treating cachexia is nutraceuticals.

THE ROLE OF NUTRACEUTICALS

A nutraceutical can be defined as “a food (or part of a food)that provides medical or health benefits, including the prevention and/or treatment of a disease.”^{7 8} The term was coined in 1989 by Stephen DeFelice and is the combination of the words “nutrition” and “pharmaceutical.”⁷ In the United States, it is estimated that 10% to 33% of dogs and cats are fed a pet supplement or nutraceutical.⁹ The most common of these include joint and digestive health supplements, followed by those that aid cognition, skin and coat, and heart health.⁹

The pathophysiological process of cachexia can be multifactorial, and specific characteristics may revolve around the form of cachexia involved. However, inflammation and oxidative stress are at the center of this process. These alter anabolic and catabolic signaling pathways, leading to muscle depletion.⁸ In human studies, it has been estimated that muscle catabolism increases by 40% to 60% during cachexia.⁸

DEFINING CACHEXIA

So what is cachexia? The truth is, there is still some debate around finding a single definition. In human medicine, the literature gives at least 11 definitions of cachexia.⁴ One of the more popular working definitions states that cachexia is a complex metabolic syndrome associated with underlying illness, and characterized by muscle loss with or without loss of fat mass.5 In veterinary medicine, cachexia is often defined as the loss of lean body mass in an animal with a chronic disease such as congestive heart failure (CHF), chronic kidney disease (CKD), or cancer.⁶ Table 1 summarizes the specific forms of cachexia.

Sarcopenia is a very similar condition that also causes a loss of lean body mass, but it is important to differentiate the two. While cachexia involves the loss of lean body mass concurrent with a disease process, sarcopenia is defined as the loss of lean body mass without the presence of disease, and is considered part of the aging process.⁶ As with cachexia, there is still some debate about the definition of sarcopenia. Table 2 highlights the similarities and differences within these two disease processes.

Treating exact parameters within the specific forms of cachexia would be ideal. However, this is not always achievable. Therefore, the broader use of nutraceuticals should aim to decrease inflammation, reduce oxidative stress on the body, and help increase appetite. Here are a few choices that maybe beneficial in treating feline cachexia.

1. Omega-3 Fatty Acids are polyunsaturated fatty acids(PUFAs). Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are mainly sourced from marine fish and fish oil. Both EPA and DHA partly restrain inflammation by limiting the production of highly inflammatory eicosanoids, such as prostaglandins and leukotrienes derived from the n-6 fatty acid arachidonic acid (AA)⁸ Recent human studies include a discussion of the possible mechanisms creating the protective effects seen in cancer cachexia. At this time, the consensus involves the acute phase response reduction, with lower serum levels of C-reactive protein, TNF alpha, and IL-6, as the main effect underlying cancer cachexia prevention.⁸
2. Glutamine is an amino acid that is helpful for reducing the diarrhea common with both chemotherapy and radiation.¹⁰ It provides fuel for rapidly dividing cells(particularly lymphocytes and enterocytes) as well as the epithelial cells of the intestines. Glutamine maintains gut barrier function and is a precursor for the endogenous antioxidant glutathione.¹¹ With cachexia, myocytes prefer glutamine as a metabolic fuel source.¹⁰ Supplementation during cachexia can be very beneficial.
   

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3. Flavonoids are bioactive polyphenol compounds that are ubiquitously abundant in food and plants.¹² They have antioxidant and anti-inflammatory properties. Flavonoids can scavenge free radicals, protect against other oxidants, chelate metal ions, and increase the activity and expression of antioxidant enzymes.¹² Quercetin is a flavonoid found in many fruits, vegetables, and seeds. It has the potential to reduce oxidative stress-induced damage by acting on the TNF alpha, AKT, PGC1 alpha, and AMPK pathways.⁸
   

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   Table 1: Specific Forms of Cachexia6

   Cardiac cachexia	• Longest recognized and most studied form. • In addition to the hemodynamic and neurohormonal alterations in CHF, the loss of LBMthat typically accompanies this disease has devastating implications for the patient. • In 1 study of dogs, over 50% of dogs with dilated cardiomyopathy (DCM) and CHF had some degree of cachexia.
   Cancer cachexia	• In one study with dogs, BCS was low in only a minority of cases; however, 35% of dogs had mild to severe muscle wasting. • A study of cats with cancer showed muscle loss in 91% of affected cats. • In addition, cats that were below optimal body condition had a significantly shorter survival time compared to those with a BCS greater than 5.9. • Very important to assess not only BCS (which assesses fat stores), but also muscle condition score (MCS) and changes in body weight to detect cancer cachexia.
   Renal cachexia	• Although the prevalence of cachexia in dogs and cats with Chronic Kidney Disease (CKD)has not specifically been measured, it appears to be relatively high and likely has negative clinical effects. • The results of a recent retrospective study in 100 dogs with CKD (International Renal InterestSociety Stages II–IV) showed that dogs classified as underweight at the time of diagnosis had a significantly shorter survival time compared to both moderate and overweight dogs
   Other forms of cachexia	• In dogs and cats with chronic respiratory diseases, clinicians often anecdotally note muscle loss.

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   Table 2: Chachexia vs. Sarcopenia: Differentiating the Two

   Cachexia	Sarcopenia
   • Loss of lean muscle mass • Occurs with chronic disease process	• Loss of lean muscle mass • Occurs with the aging process • Similar to cachexia without the disease process

4. Milk Thistle (Silymarin) is a very commonly-used supplement in veterinary medicine, with a wide variety of applications. It is well known for its antioxidant properties and for being highly hepatoprotective, demonstrated in numerous experimental models and clinical studies.¹³ Antioxidants are reported to be one of the main modulators of many physiological pathways, and the antioxidant/pro-oxidant balance (redox balance) in our diet can affect the gastrointestinal organs, blood circulation, and tissues.¹³ Milk Thistle can be a very important addition to the treatment of cachexia.
5. Probiotics are also important. The gut microbiome —more specifically, a normal microbiome — plays a key role in many physiological functions within the body. When there are alterations in the microbiome, “dis-ease” can occur, leading to increased systemic inflammation, gut barrier dysfunction, muscle wasting, and other numerous negative pathologies culminating in a full disease process.¹⁴ Prebiotics and probiotics help provide needed supplementation to strengthen the gut microbiome, thus reducing inflammation and helping bring the body back to a more homeostatic state. In studies using mice, a human commensal microbe, Lactobacillus reuteri, was sufficient to lower systemic indices of inflammation and inhibit cachexia.¹⁵

Cachexia is a very complicated, multifactorial disease process, and with their unique characteristics, feline patients can make it even more challenging. The use of nutraceuticals can help reduce inflammation, clean up free radicals, and stimulate the cat’s appetite, providing a better quality of life and ultimately helping treat the cachexia.

References:

1. Fowler M., Xie H. Chapter 15:Basic Nutrition and Food Therapy in Cats. In Integrative and TraditionalChinese Veterinary Medicine Food Therapy. Chi University Press, Reddick, Florida; 2020. 651-671.
2. Hand MS, Thatcher CD, Remillard RL, Roudebush P. Chapter 11: Normal Cats. In Small Animal ClinicalNutrition,4th ed. Walsworth Publishing Company; Marceline, Missouri; 2000. 291-347.
3. Simpson KW. Pancreatitis and triaditis in cats: causes and treatment. J Small Anim Pract.2015;56(1):40-49. doi:10.1111/jsap.12313.
4. Santiago SL, Freeman LM, Rush JE. Cardiac cachexia in cats with congestive heart failure: Prevalence and clinical, laboratory, and survival findings. J Vet Intern Med. 2020;34(1):35-44. doi:10.1111/jvim.15672.
5. Evans WJ, Morley JE, Argilés J, et al. Cachexia: a new definition. Clin Nutr. 2008;27(6):793-799.doi:10.1016/j.clnu.2008.06.013.
6. Freeman LM. Cachexia and sarcopenia: emerging syndromes of importance in dogs and cats. J VetIntern Med. 2012;26(1):3-17. doi:10.1111/j.1939-1676.2011.00838.x.
7. Kalra EK. Nutraceutical–definition and introduction. AAPS PharmSci. 2003;5(3):E25. doi:10.1208/ps050325.
8. Aquila G, Re Cecconi AD, Brault JJ, Corli O, Piccirillo R. Nutraceuticals and Exercise against MuscleWasting during Cancer Cachexia. Cells. 2020;9(12):2536. Published 2020 Nov 24. doi:10.3390/cells9122536.
9. Finno CJ. Veterinary Pet Supplements and Nutraceuticals.Nutr Today.2020;55(2):97-101. doi:10.1097/nt.0000000000000399.
10. Dressler D. Integrated approaches to canine cancer: Mitigation of treatment side effects.Inno Vet CareJournal.May 29, 2019.
11. Kim H. Glutamine as an immunonutrient. Yonsei Med J. 2011;52(6):892-897. doi:10.3349/ymj.2011.52.6.892.
12. Kim C, Hwang JK. Flavonoids: nutraceutical potential for counteracting muscle atrophy [publishedcorrection appears in Food Sci Biotechnol. 2020 Nov 20;29(12):1773].Food Sci Biotechnol.2020;29(12):1619-1640. Published 2020 Sep 16. doi:10.1007/s10068-020-00816-5.
13. Fallah M, Davoodvandi A, Nikmanzar S, et al. Silymarin (milk thistle extract) as a therapeutic agent in gastrointestinal cancer. Biomed Pharmacother. 2021;142:112024. doi:10.1016/j.biopha.2021.112024.
14. Herremans KM, Riner AN, Cameron ME, Trevino JG. The Microbiota and Cancer Cachexia. Int J Mol Sci.2019;20(24):6267. Published 2019 Dec 12. doi:10.3390/ijms20246267.
15. Varian BJ, Gourishetti S, Poutahidis T, et al. Beneficial bacteria inhibit cachexia [published correction appears in Oncotarget. 2018 Jun 29;9(50):29536. Goureshetti, Sravya [corrected to Gourishetti, Sravya]]. Oncotarget. 2016;7(11):11803-11816. doi:10.18632/oncotarget.7730.

AUTHOR PROFILE

Jared Mitchell, DVM

Dr. Jared Mitchell graduated from Mississippi State University's College of Veterinary Medicine in 2004. In 2010, he opened his practice, Mitchell Animal Clinic, in Mobile, Alabama. Wanting more for his patients, he began incorporating holistic modalities into his practice. Dr. Mitchell is currently completing certification to become a Certified Veterinary Medical Aromatherapist through the Veterinary Medical Aromatherapy Association. He plans to achieve certifications in herbal medicine, acupuncture, veterinary chiropractic and other holistic modalities.