Cachexia in Dogs and Cats
Cachexia or muscle wasting is usually associated with cancer in dogs and cats. Even if our dog or cat eats you witness the dog or cat losing body fast and muscle tissue. The body's metabolism is turned upside down by cachexia. You may be accused of not feeding your dog or cat. Your company may reach the stage when he/she stops eating and suffers from anorexia. You just feel helpless.
Cachexia can also occur for instance with chronic renal failure, diabetes and advanced dilated dardiomyopathy.
My littermate schnauzers Hammy and Morgy both had cachexia. Morgy had cachexia from cancer and Hammy had cachexia from renal failure.
My Morgy had osteosarcoma and the first year he lost 20 percent of his weight but regained most of the weight the next year and a half. My Hammy was 15 1/2 when he was put to sleep. I was stunned when the vet told me he weighed 19 pounds when he always weighed 24 pounds. I had the vet weigh him again. Call it denial. Sure enough when Hammy had the blood test, it showed that his kidneys were shot. He had only been vomiting and dry heaving for two days before. I carelessly assumed that he looked thinner because he was older. His appetite was always great until the last few days of his life.
Nutrition and Cancer by Gregory K. Ogilvie, DVM, Diplomate ACVIM (Internal Medicine, Oncology)
Professor and Head of Medical Oncology, Animal Cancer Center, Colorado State University
Ft. Collins, CO, USA
" Cancer cachexia is the most common paraneoplastic syndrome in veterinary medicine. This paraneoplastic syndrome of dogs and cats with a wide variety of malignancies results in profound alterations in carbohydrate, protein and lipid metabolism that subsequently results in anorexia, fatigue, impaired immune function, poor performance and weight loss in the face of adequate nutritional intake."
J Nutr Biochem. 2004 Jun;15(6):358-65. :
Fish oil supplementation in F1 generation associated with naproxen, clenbuterol, and insulin administration reduce tumor growth and cachexia in Walker 256 tumor-bearing rats.
Pinto JA Jr, Folador A, Bonato SJ, Aikawa J, Yamazaki RK, Pizato N, Facin M, Grohs H, de Oliveira HH, Naliwaiko K, Ferraz AC, Nishiyama A, Fernandez R, Curi R, Fernandes LC.
Department of Physiology, Biological Sciences Building, Federal University of Parana, 81530-990, Curitiba PR, Brazil.
Weanling female Wistar rats were supplemented with fish oil (1 g/kg body weight) for one generation. The male offspring received the same supplementation until to adult age. Rats supplemented with coconut fat were used as reference. Some rats were inoculated subcutaneously with a suspension (2 x 10(7) cells/mL) of Walker 256 tumor. At day 3, when the tumor was palpable, rats were treated with naproxen (N) (0.1 mg/mL), clenbuterol (Cb) (0.15 mg/kg body weight), and insulin (I) (10 U/kg body weight). At day 14 after tumor inoculation, the animals were killed. Tumor was removed and weighed. Blood, liver, and skeletal muscles were also collected for measurements of metabolites and insulin. In both tumor-bearing untreated rats and tumor-bearing rats supplemented with coconut fat, tumor growth, triacylglycerol, and blood lactate levels were higher, and glycogen content of the liver, blood glucose, cholesterol and HDL-cholesterol levels were lower as compared with the non-tumor-bearing and fish oil supplemented groups. Fish oil supplementation of tumor-bearing rats led to a partial recovery of the glycogen content in the liver and a full reversion of blood glucose, lactate, cholesterol, and HDL-cholesterol levels. The treatment with N plus Cb plus I attenuated cancer cachexia and decreased tumor growth in both coconut fat and fish oil supplemented rats. In conclusion, chronic fish oil supplementation decreased tumor growth and partially recovered cachexia. This beneficial effect of fish oil supplementation was potentiated by treatment with naproxen plus clenbuterol plus insulin.
Nutr Cancer. 2003;46(1):52-8. :
Cancer cachexia and tumor growth reduction in Walker 256 tumor-bearing rats supplemented with N-3 polyunsaturated fatty acids for one generation.
Togni V, Ota CC, Folador A, Junior OT, Aikawa J, Yamazaki RK, Freitas FA, Longo R, Martins EF, Calder PC, Curi R, Fernandes LC.
Departamento de Fisiologia, Universidade Federal do Parana, 81531-971 Curitiba, Pr, Brazil.
In this study we investigated the effect of lifelong supplementation of the diet with coconut oil (CO, rich in saturated fatty acids) or fish oil (FO, rich in n-3 polyunsaturated fatty acids, PUFAs) on tumor growth, animal survival, and metabolic indicators of cachexia in adult rats. Female Wistar rats were supplemented with CO or FO prior to mating and then throughout pregnancy and gestation, and then the male offspring were supplemented from weaning until 90 days of age. Then they were inoculated subcutaneously with Walker 256 tumor cells. Tumor weight at 14 days in control rats (those fed standard chow) was approximately 20 g. These animals displayed cancer cachexia, which was characterized by loss of weight, hypoglycemia, hyperlacticidemia, hypertriacylglycerolemia, and depletion of glycogen stores. Supplementation of the diet with CO did not change these parameters, except that there was a smaller decrease in serum triacylglycerol concentration. Supplementation of the diet with FO significantly decreased tumor growth (by approximately 60%), increased survival (50% at 30 days postinoculation vs. 30% in the controls and 13.5% in the CO group), and prevented the fall in body weight. Furthermore, FO supplementation partly abolished the fall in serum glucose, totally prevented the elevation in serum lactate concentrations, partly prevented the hypertriacylgylcerolemia, and preserved tissue glycogen stores. Lifelong consumption of FO, rich in n-3 PUFAs, protects against tumor growth and cancer cachexia and improves survival.
Biol Res Nurs. 2003 Jul;5(1):3-17.
Rethinking nutritional support for persons with cancer cachexia.
National Institute of Nursing Research, 31 Center Drive, Room 5B-13,
Bethesda, MD 20892-2178, USA. mccarthd@m.
Cancer cachexia is a poorly understood syndrome of anorexia, weight
loss, and muscle wasting that negatively impacts quality of life and
survival in cancer patients. Research has clearly implicated pro-
inflammatory cytokines in the biology of cancer cachexia. More
recent research implicates products of arachidonic acid and suggests
that cachexia may be a chronic inflammatory condition rather than a
nutritional aberration. To date, nutritional support to slow weight
loss has focused primarily on increasing calorie intake.
Alternatively, many foods contain factors that can modulate the
synthesis or activity of pro-inflammatory mediators, especially the
synthesis of prostaglandin E2 from arachidonic acid. These factors
and foods are sometimes called nutraceuticals, and research is
needed to evaluate their efficacy in combating cancer cachexia.
1: Biochem Biophys Res Commun. 2003 Aug 22;308(2):403-7.:
Chitosan inhibits prostaglandin E2 formation and cyclooxygenase-2
induction in lipopolysaccharide-treated RAW 264.7 macrophages.
Chou TC, Fu E, Shen EC.
Department of Physiology and Biophysics, National Defense Medical
Center, Taiwan, ROC. tcchou@m...
Chitosan, a deacetylated chitin, has been reported to accelerate the
wound healing and exert anti-inflammatory effect but the possible
mechanisms involved are still unclear. Enhanced production of
prostaglandin E2 (PGE2) and pro-inflammatory cytokines has been
shown to contribute to immunosuppression and cytotoxicity during
wound healing. In this study, we examined the effect of chitosan on
cyclooxygenase pathway and cytokines production in
lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Our results
first demonstrated that chitosans (MW=50,000, 150,000 or 300,000)
significantly inhibit the overproduction of PGE2 as well as
cyclooxygenase-2 (COX-2) protein expression and activity accompanied
by attenuation of pro-inflammatory cytokines production such as
tumor necrosis factor-alpha and interleukin-1beta formation but
increase of the anti-inflammatory cytokine, IL-10, formation in LPS-
treated RAW 264.7 macrophages. These results suggest that the
beneficial effect of chitosan on wound healing may be associated, at
least partly, with the inhibition of PGE2 production by suppressing
COX-2 induction and activity as well as attenuation of pro-
inflammatory/anti-inflammatory cytokines ratio in activated
used to treat cachexia in animals
Gut. 2003 Oct;52(10):1479-86. :
Effect of a protein and energy dense N-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial.
Fearon KC, Von Meyenfeldt MF, Moses AG, Van Geenen R, Roy A, Gouma DJ, Giacosa A, Van Gossum A, Bauer J, Barber MD, Aaronson NK, Voss AC, Tisdale MJ.
Royal Infirmary of Edinburgh, Edinburgh, UK.
AIM: N-3 fatty acids, especially eicosapentaenoic acid (EPA)[ie oil from cold water fish], may possess anticachectic properties. This trial compared a protein and energy dense supplement enriched with n-3 fatty acids and antioxidants (experimental: E) with an isocaloric isonitrogenous control supplement (C) for their effects on weight, lean body mass (LBM), dietary intake, and quality of life in cachectic patients with advanced pancreatic cancer. METHODS: A total of 200 patients (95 E; 105 C) were randomised to consume two cans/day of the E or C supplement (480 ml, 620 kcal, 32 g protein +/- 2.2 g EPA) for eight weeks in a multicentre, randomised, double blind trial. RESULTS: At enrolment, patients' mean rate of weight loss was 3.3 kg/month. Intake of the supplements (E or C) was below the recommended dose (2 cans/day) and averaged 1.4 cans/day. Over eight weeks, patients in both groups stopped losing weight (delta weight E: -0.25 kg/month versus C: -0.37 kg/month; p = 0.74) and LBM (Delta LBM E: +0.27 kg/month versus C: +0.12 kg/month; p = 0.88) to an equal degree (change from baseline E and C, p<0.001). In view of evident non-compliance in both E and C groups, correlation analyses were undertaken to examine for potential dose-response relationships. E patients demonstrated significant correlations between their supplement intake and weight gain (r = 0.50, p<0.001) and increase in LBM (r = 0.33, p = 0.036). Such correlations were not statistically significant in C patients. The relationship of supplement intake with change in LBM was significantly different between E and C patients (p = 0.043). Increased plasma EPA levels in the E group were associated with weight and LBM gain (r = 0.50, p<0.001; r = 0.51, p = 0.001). Weight gain was associated with improved quality of life (p<0.01) only in the E group. CONCLUSION: Intention to treat group comparisons indicated that at the mean dose taken, enrichment with n-3 fatty acids did not provide a therapeutic advantage and that both supplements were equally effective in arresting weight loss. Post hoc dose-response analysis suggests that if taken in sufficient quantity, only the n-3 fatty acid enriched energy and protein dense supplement results in net gain of weight, lean tissue, and improved quality of life. Further trials are required to examine the potential role of n-3 enriched supplements in the treatment of cancer cachexia.
DIETARY MANAGEMENT OF RENAL AND CARDIAC DISEASE
"Advanced cases of DCM are presented with exercise intolerance and clinical signs of CHF. There can be marked weight loss and cachexia. Syncope related to ventricular arrhythmia or neurocardiogenic syncope (inappropriate bradycardia and vasodilation) may be related by the owner. Clinical signs of left-sided CHF include tachypnea, respiratory distress, and coughing related to pulmonary edema. Right-sided CHF is characterized by jugular pulses and jugular venous distension, hepatomegaly, and ascites. Biventricular failure includes the above findings along with pleural effusion. Auscultation may reveal atrial and ventricular gallops, systolic murmurs, or arrhythmias"
Chronic Renal Failure, Canine
"A veterinarian will first identify and correct any active renal disease that may exacerbate or mask chronic renal failure. A diagnosis of chronic renal failure requires a physical exam and various laboratory tests. A physical exam of a dog with this disease commonly will reveal dehydration, small and irregular kidneys, cachexia or severe weight loss, pale mucous membranes or gingiva, oral ulcers, and uremic breath odor. Laboratory tests initially may include a CBC, or complete blood count, blood chemistry analysis, and urinalysis. Other tests that may be recommended in order to diagnose completely the cause of the disease include a urine culture, x-rays, ultrasound, blood pressure measurement, and biopsy. Some of these tests may require referral to a specialist of veterinary internal medicine."
What is diabetes
"Energy shortage intracellular
increase in gluconeogenesis---->decrease in protein
synthesis-cachexia/lethargy-polyphagia-increased susceptibilty to bladder
infections--impaired wound healing--poor coat condition "
Expert Rev Anticancer Ther. 2003 Jun;3(3):381-92.:
Cancer-related cachexia and oxidative stress: beyond current therapeutic options.
Mantovani G, Maccio A, Madeddu C, Massa E.
Cattedra e Divisione di Oncologia Medica, Universita di Cagliari Policlinico Universitario, Presidio di Monserrato, Italy.
Cancer-related anorexia/cachexia syndrome is a complex phenomenon in which metabolic abnormalities, proinflammatory cytokines produced by the host immune system, circulating tumor-derived catabolic factors, decreased food intake and probably additional unknown factors all play different roles. This review examines the mechanisms of cancer-related anorexia/cachexia syndrome and the mainstays of its management. The two major options for pharmacological therapy have been progestational agents and corticosteroids. Agents currently under investigation are nonsteroidal anti-inflammatory drugs, N-3 fatty acids, branched-chain amino acids and thalidomide. On the basis of several previously published studies and clinical experience, an innovative treatment approach, which consists of an integrated nutritional and pharmacological treatment, has been developed. This approach, based upon multiple components each targeted at different factors involved, may be effective in both improving objective clinical symptoms, such as lean body mass, and subjective symptoms such as quality of life. A Phase II study has been initiated and Phase III study designed.
Endocrinology. 2003 Sep;144(9):3749-56. :
Minireview: From anorexia to obesity--the yin and yang of body weight control.
Zigman JM, Elmquist JK.
Department of Medicine and Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Over the past decade, there has been a tremendous increase in the understanding of the molecular and neural mechanisms that control food intake and body weight. Yet eating disorders and cachexia are still common, and obesity cases are rising at alarming rates. Thus, despite recent progress, an increased understanding of the molecular and neural substrates that control body weight homeostasis is a major public health goal. In this review, we discuss the mechanisms by which metabolic signals interact with key behavioral, neuroendocrine, and autonomic regulatory regions of the central nervous system. Additionally, we offer a model in which hormones such as leptin and ghrelin interact with similar central nervous system circuits and engage them in such a way as to maintain an appropriate and tight regulation of body weight and food intake. Our model predicts that overstimulation or understimulation of these central pathways can result in obesity, anorexia, or cachexia.
Osteoprotegerin (OPG)anti cachexia-also found to reduce pain in osteosarcoma
steoprotegerin prevents and reverses hypercalcemia in a murine model of humoral
hypercalcemia of malignancy.
Cancer Res; 60(4):783-7 2000 UI: 20168597
Osteoprotegerin (OPG), a novel, secreted tumor necrosis factor receptor family member that
inhibits osteoclast formation and activity was examined for its activity in a syngeneic tumor
model of humoral hypercalcemia of malignancy. Normal mice bearing Colon-26 tumors develop
increases in both parathyroid hormone-related protein (PTHrP) expression and plasma PTHrP,
marked hypercalcemia, and increased bone resorption. OPG, given either at the onset of
hypercalcemia or after it had occurred, blocked tumor-induced increases in bone resorption and
hypercalcemia and rapidly normalized blood ionized calcium. In tumor-bearing mice, OPG
treatments reduced osteoclast activity from approximately 2-fold above normal into the
subphysiological range but had no effects on tumor size, tumor-induced cachexia, or PTHrP
levels. The potent effects of OPG in this humoral hypercalcemia of malignancy model suggest a
potential therapeutic role for OPG in the prevention and treatment of this disorder.
moreHorowitz MC, Xi Y, Wilson K, Kacena MA
Control of osteoclastogenesis and bone resorption by members of the TNF family of receptors
Cytokine Growth Factor Rev; 12(1):9-18 2001 UI: 21212081
Skeletal mass is maintained by a balance between cells which resorb bone (osteoclasts) and
cells which form bone (osteoblasts). Bone development and growth is an on-going, life-long
process. Bone is formed during embryonic life, grows rapidly through childhood, and peaks
around 20 years of age (formation exceeds resorption). For humans the skeleton then enters a
long period, approximately 40 years, when bone mass remains relatively stable. Skeletal
turnover continues but the net effect of resorption and formation on bone mass is zero. For
women this ends when they enter menopause and similar bone loss occurs for men, but later in
life. These opposite functions are coupled, resorption precedes formation, and osteoblasts, or
their precursors, stromal cells, regulate osteoclast formation and activity. Until recently, the
molecular nature of this regulation, was poorly understood. However, recent observations have
identified members of the TNF family of ligands and receptors as critical regulators of
osteoclastogenesis. Osteoprotegerin (OPG) a decoy receptor was first identified. Its ligand,
receptor activator of nuclear factor-kappaB ligand (RANKL), was quickly found, and shown to
be expressed on stromal cells and osteoblasts. Its cognate receptor, RANK, was found to be
expressed in high levels on osteoclast precursors. The interaction between RANKL and RANK
was shown to be required for osteoclast formation. These observations have provided a
molecular understanding of the coupling between osteoclastic bone resorption and osteoblastic
bone formation. Moreover, they provide a framework on which to base a clear understanding of
normal (e.g. postmenopausal osteoporosis and age associated bone loss) and pathologic skeletal
changes (e.g. osteopetrosis, glucocorticoid-induced osteoporosis, periodontal disease, bone
metastases, Paget's disease, hyperparathyroidism, and rheumatoid arthritis).
bone painRecord 8
Luger NM, Honore P, Sabino MA, Schwei MJ, Rogers SD, Mach DB, Clohisy DR, Mantyh
Osteoprotegerin diminishes advanced bone cancer pain.
Cancer Res; 61(10):4038-47 2001 UI: 21257704
Bone cancer pain most commonly occurs when tumors originating in breast, prostate, or lung
metastasize to long bones, spinal vertebrae, and/or pelvis. Primary and metastatic cancers
involving bone account for approximately 400,000 new cancer cases per year in the United
States alone, and >70% of patients with advanced breast or prostate cancer have skeletal
metastases. Whereas pain resulting from bone cancer can dramatically impact an individual's
quality of life, very little is known about the mechanisms that generate and maintain this pain. To
begin to define the mechanisms that give rise to advanced bone cancer pain, osteolytic 2472
sarcoma cells or media were injected into the intramedullary space of the femur of C3H/HeJ
mice, and the injection hole was sealed using dental amalgam, confining the tumor cells to the
bone. Twelve days after injection of 2472 tumor cells, animals showed advanced tumor-induced
bone destruction of the injected femur, bone cancer pain, and a stereotypic set of neurochemical
changes in the spinal cord dorsal horn that receives sensory inputs from the affected femur.
Administration of osteoprotegerin, a naturally secreted decoy receptor that inhibits osteoclast
maturation and activity and induces osteoclast apoptosis, or vehicle was begun at 12 days, when
significant bone destruction had already occurred, and administration was continued daily until
day 21. Ongoing pain behaviors, movement-evoked pain behaviors, and bone destruction were
assessed on days 10, 12, 14, 17, and 21. The neurochemistry of the spinal cord was evaluated at
days 12 and 21. Results indicated that osteoprotegerin treatment halted further bone destruction,
reduced ongoing and movement-evoked pain, and reversed several aspects of the
neurochemical reorganization of the spinal cord. Thus, even in advanced stages of bone cancer,
ongoing osteoclast activity appears to be involved in the generation and maintenance of ongoing
cachexia d and bisphosponates
"TI - Effect of combination treatment with a vitamin D analog (OCT) and a bisphosphonate (AHPrBP) in a nude
mouse model of cancer-associated hypercalcemia.
AU - Endo K; Katsumata K; Iguchi H; Kubodera N; Teramoto T; Ikeda K; Fujita T; Ogata E
SO - J Bone Miner Res 1998 Sep;13(9):1378-83
Hypercalcemia represents one of the important paraneoplastic syndromes affecting morbidity and mortality of
cancer patients. We and others have demonstrated that vitamin D analogs with little calcemic activities suppress
the transcription of the parathyroid hormone- related peptide (PTHrP) gene, a major humor responsible for cancer
hypercalcemia, and thereby prevent the development of hypercalcemic syndrome. The present study was
undertaken: to compare the therapeutic efficacy of a vitamin D analog, 22-oxa-1,25-dihydroxyvitamin D3 (OCT),
and a bisphosphonate (disodium 3-amino-1-hydroxypropylidene-1,1- bisphosphonate pentahydrate [AHPrBP]), an
inhibitor of osteoclastic bone resorption, on cancer-induced hypercalcemia; and to see if the effect could be
enhanced by combination treatment, using a nude mouse model implanted with a human pancreas carcinoma
(FA-6). After a single intravenous administration, OCT (5 microg/kg of body weight [BW]) was as effective as
AHPrBP (10 mg/kg of BW) in lowering blood ionized calcium levels in tumor-bearing nude mice, and their
combination further enhanced the therapeutic effect. Although AHPrBP lost its efficacy after repeated injections,
OCT was still effective after the third administration. The therapeutic effect of OCT in cancer hypercalcemia was
observed in four other human tumors, including another pancreas carcinoma (PAN-7), two squamous cell
carcinomas of the lung (KCC-C1 and LC-6), and a squamous carcinoma of the pharynx (PHA- 1), all of which
elaborated PTHrP into the circulation. Treatment with OCT resulted in a decrease in circulating PTHrP levels by
approximately 50% in two representative models. However, the mechanism underlying the antihypercalcemic
effect of OCT seemed complex, involving inhibition of PTHrP production, suppression of excessive bone resorption,
and an antitumor activity. OCT also markedly inhibited the body weight loss with tumor growth, while AHPrBP,
which exhibited a similar antihypercalcemic effect, was less effective than OCT in preventing cachexia. The
anticachectic activity of their combination did not exceed that of OCT alone, suggesting a
hypercalcemia-dependent as well as an independent mechanism of cancer cachexia. It is concluded that OCT may
be useful, either as a single agent or in combination with bisphosphonates, for the treatment of cancer-associated
hypercalcemia and cachexia.
Since we now know how to inhibit NF-kappa B, and we’re getting better at it
every day, this will lead to therapies for reducing cachexia, which may well lead to significant improvement in the quality
of life of patients who have chronic diseases like cancer and AIDS."