Advances in pet nutrition and
veterinary care have resulted in increased
longevity of companion animals. This
increased life expectancy brings with it
increased wear and tear on the body,
including the musculoskeletal system, and
can result in an increased risk of disorders
involving joints and joint capsules. Thus,
with advancing age, the risk for
development of chronic, progressive
diseases affecting, in particular, weightbearing
joints such as the knees, hips,
back, and feet appears to be on the
upswing in both human and pet
populations.
Circulatory Shock, types and stages, compensatory mechanisms
Hartz Companion Animal - Nutraceuticals and Joint Health
1. A NEWSLETTER OF PRACTICAL MEDICINE FOR VETERINARY PROFESSIONALS
MAY 2005 VOLUME 3, NUMBER 2
Nutraceuticals and
Joint Health
John E. Bauer, DVM, PhD, DACVN
Comparative Nutrition Laboratory
Department of Small Animal Clinical Sciences
College of Veterinary Medicine
Texas A&M University
College Station, Texas
Advances in pet nutrition and of articular cartilage. OA can range materials and promote their effects as
veterinary care have resulted in increased from mild to severe and results in pain, synergistic. However, it is more difficult
longevity of companion animals. This swelling, stiffness, and, over time, loss of (and costly) to scientifically prove that
increased life expectancy brings with it joint mobility. one particular substance is efficacious
increased wear and tear on the body, Several drugs have been developed and when it is combined with other
including the musculoskeletal system, and used to treat the pain and swelling of ingredients in a proprietary formula.
can result in an increased risk of disorders OA-affected joints, but none has been Some evidence exists in the veterinary
involving joints and joint capsules. Thus, able to remedy the underlying loss of literature that such combination products
with advancing age, the risk for cartilage that progressively occurs with have a beneficial effect on joint health,
development of chronic, progressive this disorder. This is a major reason why yet conflicting results with the same
diseases affecting, in particular, weight- dietary chondroprotective supplements, nutrients have been reported in other
bearing joints such as the knees, hips, which may help mitigate the loss of studies.
back, and feet appears to be on the cartilage, continue to gain popularity as
upswing in both human and pet being beneficial for OA.
populations. Although most attention has been
Most notable in this regard is directed to glucosamine and chondroitin IN THIS ISSUE:
osteoarthritis (OA). OA is the most sulfate, other products containing green- Nutraceuticals and
common form of arthritis. It is a lipped mussel, methylsulfonylmethane Joint Health ............................... 1
progressive, degenerative joint disease (MSM), and trace minerals such as zinc,
characterized by changes in the synovial copper, and manganese are often also
Dangerous Foods........................ 4
membrane, including periarticular found in joint health supplements. Many Ask the Vet ................................ 7
osteophyte production and degeneration products use combinations of these
3. continues to be high, especially because supplementation did not result in lipped mussel extracts. A purported
the number of individuals with arthritis clinically significant alterations in glucose benefit of MSM is that it is a bioavailable
appears to be increasing. It is expected metabolism in these diabetic patients in source of sulfur, which is a component of
that similar interest in these supplements this single study. Clearly, additional several structural compounds found in
will exist for companion animals as well. studies are needed to help confirm these joints.18 The use of MSM in dogs or cats
However, no long-term safety studies of findings. has yet to be evaluated. One human trial
the chondroprotective agents in dogs or In dogs, an anecdotal report using an administered a combination of 500 mg
cats have been reported in the literature. oral dose of glucosamine (1,000 mg/day, glucosamine and 500 mg MSM for 12
The continued interest in these duration unspecified) in an 11-year-old weeks and concluded that this particular
supplements awaits the publication of Labrador retriever noted urinary combination therapy showed better
results from an ongoing study supported incontinence, polyuria, and polydipsia, all efficacy in reducing pain and swelling
by the National Institutes of Health of which abruptly returned to normal than either alone.19 An extract of green-
called the Glucosamine/Chondroitin when the dose was reduced to 500 lipped mussel combined with a mixture of
Arthritis Intervention Trial (GAIT), mg/day.12 However, serum glucose GAGs, n-3 fatty acids, and possibly other
scheduled for completion in November concentration tested using a midday, compounds has been shown to benefit
2005. This study is a 24-week, placebo- nonfasted sample was normal, and dogs exhibiting chronic lameness.20
controlled, parallel, double-blinded trial follow-up tests were not conducted. By However, another dog study was unable
with 1,588 subjects evaluated at 13 contrast, one study in rats was unable to to confirm this finding.21 Additional
clinical centers. The efficacy of demonstrate adverse effects of proprietary combinations have also been
glucosamine alone, chondroitin alone, and glucosamine or chondroitin sulfate on evaluated. 22,23 In these cases, potential
the two in combination will be compared glucose metabolism.13 Until more usage benefits of glucosamine may be further
with placebo in treating OA knee pain. data are obtained, caution is advised and enhanced by the addition of other known
more frequent monitoring in cases of collagen-matrix components or even
Effects on Glucose Metabolism diabetes or possibly even obese animals antiinflammatory agents.
Although most clinical trials have prone to type 2 diabetes should be
found the safety of glucosamine and employed when glucosamine is being IN SUMMARY
chondroitin supplements to be excellent, used for OA or related problems in such Chondroprotective agents such as
some concerns related to glucose patients. GAG precursors are often derived from
metabolism exist. Glucosamine infusions various animal species. As such, they may
in both ducks and dogs have been COMBINATION PRODUCTS contain other proteins that carry a
reported to cause hyperglycemia due to With respect to other potential for allergic reactions. As
the release of glucagon immunoreactivity chondroprotective agents, data exist that additional findings of both proprietary
and possible insulin suppression.3,8 The support an interactive, or synergistic, mixtures and single substances are
dose used in this instance may have been effect between glucosamine and reported, further confidence in the safe
higher than that generally used as a chondroitin sulfate in helping maintain and efficacious use of chondroprotective
dietary supplement. Nonetheless, in joint health. Combinations of materials, in certain clinical cases, will
humans, glucosamine infusions produced glucosamine with other products develop. However, at present, caution is
acute insulin resistance,9 and glucosamine containing mucopolysaccharides or other advised with the use of these agents in
may also induce or exacerbate insulin substances may also help alleviate joint dogs and cats, especially in the absence of
resistance.10 problems or rebuild degenerating related long-term safety data. It appears
By comparison, a recent placebo- cartilage. One proprietary product in that initial relief of some signs associated
controlled, double-blinded, randomized particular that combines glucosamine with OA may exist. However, long-term
clinical trial looked at the effects of with chondroitin sulfate and manganese benefits of their use to minimize painful
glucosamine–chondroitin sulfate ascorbate has been subjected to several flare-ups await further study.
supplementation for 90 days on glycemic cell culture and animal studies in dogs
control in human outpatients with type 2 and other target species.14–17 Survey data References
diabetes mellitus. Although a small of practicing veterinarians have provided 1. Setikar I, Giacchetti C, Zanolo G:
Pharmacokinetics of glucosamine in the dog and in
number of patients were excluded because information that pain relief as well as man. Arzneimittelforschung 36:729–735, 1986.
of comorbidities, adverse effects and mobility was good to excellent with this 2. Meininger CJ, Kelly KA, Li H, et al: Glucosamine
changes in diabetes management were type of combination product.15 inhibits inducible nitric oxide synthesis. Biochem
Biophys Res Commun 279:234–239, 2000.
not seen, including mean hemoglobin Other substances that may benefit 3. Reginster JY, Deroisy R, Rovati LC, et al: Long-
A1c concentrations.11 Oral glucosamine joint health include MSM and green- term effects of glucosamine sulphate on
(continues on page 6)
HARTZ® COMPANION ANIMALSM • MAY 2005 • VOL. 3, NO. 2 3
4. Dangerous Foods
Problems Resulting from Ingestion
and Appropriate Treatments
Jill A. Richardson, DVM
Associate Director, Consumer Relations and Technical Services
Hartz Mountain Corporation
Secaucus, New Jersey
Pet owners often give table scraps to increased heart rate, hyperactivity, elimination.1 It should be noted, however,
their pets as a special treat. This seems to tremors, and potentially death. Other that the bladder wall can reabsorb
be especially true on holidays, because pet effects seen with chocolate overdose caffeine, which may increase the duration
owners often include their pets in their include diarrhea, lethargy, increased of clinical signs. Therefore, the veterinary
celebrations. Unfortunately, some types of thirst, increased urination, and vomiting. staff should take extra steps, such as
human food can be toxic to pets, so it is Although theobromine and caffeine have catheterization or frequent walking, to
important that veterinarians and their staff an LD50 of 100 to 200 mg/kg, signs can keep the patient’s bladder empty.1
be aware of these dangerous foods and how manifest well below this dose: Mild signs
to respond if a pet has consumed them. can be seen at doses higher than 20 Grapes and Raisins
The best way to avoid serious mg/kg, moderate signs above 40 mg/kg, Some types of grapes and raisins have
problems caused by pets consuming and severe signs above 60 mg/kg.1 been shown to cause kidney failure in
dangerous foods is through poison The amount of methylxanthines in dogs when consumed in large amounts.2
prevention. Veterinary staff can educate chocolate varies with the type of The basis of this kidney failure is unclear
pet owners using educational displays, chocolate. Generally, the more bitter the but is currently being studied in the
newsletter items, and on-hold chocolate is, the more toxic it can be veterinary community. The exact amount
messaging. However, if a pet eats a (Table 1). In fact, unsweetened baking of grapes or raisins that may cause renal
dangerous food item, prompt action can chocolate contains about seven times failure is not known, so any amount could
help avoid a potentially life-threatening more theobromine than milk chocolate, potentially be dangerous.
problem. while white chocolate (a combination of Recommended treatment for recent
cocoa butter, sugar, butterfat, milk solids, ingestion includes inducing emesis and
Chocolate and flavorings but no cocoa beans) administering activated charcoal.2 These
A mixture of cocoa beans and cocoa contains negligible amounts of steps should be followed by fluid diuresis
butter, chocolate contains theobromine methylxanthines. for 48 hours, during which the patient
and caffeine, which are both classified as Early treatment, including should be monitored for azotemia.2 If the
methylxanthines. Dogs are sensitive to decontamination procedures (such as animal shows signs of renal failure, fluids
the effects of methylxanthines, which inducing emesis and administering and supportive care should be continued.
competitively inhibit cellular adenosine activated charcoal), monitoring
receptors, resulting in central nervous cardiovascular health, and providing Macadamia Nuts
system (CNS) stimulation and supportive care, is extremely helpful in According to a retrospective study,
tachycardia.1 Depending on the amount cases of chocolate poisoning. In addition, clinical signs commonly reported in dogs
consumed, methylxanthines can cause fluid diuresis may help enhance ingesting macadamia nuts include ataxia,
depression, hyperthermia, tremors,
vomiting, and weakness.3 In most cases,
Table 1: Amount of Methylxanthines in Certain Types of Chocolate
dogs developed clinical signs within the
Type of Chocolate Caffeine (mg/oz) Theobromine (mg/oz) first 12 hours after ingestion.3 These signs
Milk chocolate 6 44–56 have only been seen in dogs, and the exact
Semisweet 22 138 cause for dogs’ sensitivity to macadamia
Baking chocolate (unsweetened) 33–47 393
nuts is unknown. The lowest dose reported
to cause clinical effects is 2.4 g/kg.3
4 HARTZ COMPANION ANIMAL
® SM
• MAY 2005 • VOL. 3, NO. 2
5. Treatment includes decontamination members of the Allium family is n-propyl with bread dough ingestion are associated
procedures such as inducing emesis, disulfide, which is thought to cause with ethanol toxicoses and foreign body
administering activated charcoal, and oxidative damage to erythrocytes, resulting obstruction and may include severe
administering enemas. Additional in hemolysis and potentially anemia.5 abdominal pain, bloating,
supportive care should be given as needed. In one study, dogs were given depression, incoordination, and
The prognosis in most cases is extremely 5 g of whole garlic/kg vomiting.9
good. With prompt treatment, most dogs intragastrically once a day for In cases of recent
return to normal within 24 to 48 hours.3 7 days. On days 9 to 11, the ingestion in asymptomatic
dogs had decreased dogs, emesis could be
Moldy Foods erythrocyte counts, induced. Analgesia is
Moldy foods may contain certain hematocrits, and hemoglobin important in patients
tremorgenic mycotoxins such as penitrem concentrations. Heinz bodies exhibiting signs of pain.
A and roquefortine C.4 Classified as and eccentrocytes, along with an Administering cool water via a
neurotoxins, tremorgenic mycotoxins can increase in erythrocyte-reduced stomach tube or orally may stop the
induce ataxia, muscle tremors, and glutathione concentrations, were also dough from rising.9 In some cases,
convulsions that can last for several days.4 detected; however, none of the dogs surgery may be required to remove the
While the exact mechanism of action is developed hemolytic anemia.6 dough. Since ethanol can cause acidosis,
unknown, studies have shown that In another study, dogs developed it is important to monitor the acid–base
penitrem A inhibits the neurotransmitter hemolytic anemia after being fed 30 g/kg balance and correct it with sodium
glycine in mice.4 Severity of signs can vary of onions once daily for 3 days.7 Heinz bicarbonate if indicated.9
from mild to severe, depending on the body hemolytic anemia was seen in a dog
particular strength of the mycotoxin that ingested Chinese chive (Allium Tobacco
ingested. Intoxications have been reported tuberosum) and garlic (Allium sativum).8 In Tobacco products contain varying
in many species; however, dogs that roam addition, toxicoses caused by ingestion of amounts of nicotine; cigarettes contain 13
or have access to spoiled foods are more at fresh, dried, or powdered plant material to 30 mg and cigars 15 to 40 mg. Butts
risk than other pets. have been reported in dogs and cats. contain about 25% of the total nicotine
Treatment goals following tremorgenic Commercial baby food containing onion content. The minimum lethal dose in
mycotoxin ingestion include minimizing powder has also been reported to cause dogs and cats is reported as 20 to 100
absorption through decontamination toxicity in cats. Clinical signs associated mg. Signs often develop quickly (usually
procedures such as inducing emesis, with onion poisoning include hemolytic within 15 to 45 minutes) and include
performing lavage, and administering anemia, hemoglobinuria, pallor, vomiting, diarrhea, emesis, excitation, salivation,
activated charcoal; controlling tremors and weakness. and tachypnea. Cardiac arrest, collapse,
and seizures with methocarbamol; and Decontamination procedures such as coma, depression, muscle weakness,
providing supportive care.4 With early inducing emesis and administering shallow respiration, tachycardia, and
aggressive treatment, prognosis is good. activated charcoal should be considered twitching can follow the period of
Definitive diagnosis can be confirmed with recent ingestions. Afterward, the excitation. Death occurs secondary to
by mass spectrometry analysis of stomach animal should be monitored for azotemia, respiratory paralysis.10
contents.4 Veterinary diagnostic hemolysis, and/or decreased packed cell For recent ingestion in asymptomatic
laboratories (VDLs) that perform the test volume. Whole-blood transfusions or animals, emesis can be induced. Never
include Michigan State and Iowa State administration of oxygenated hemoglobin attempt emesis in stimulated animals
Universities VDL. Analysis of should be considered for critical patients. because it may trigger a seizure.
mycotoxins may take several days; Fluid diuresis is recommended in patients Activated charcoal has been shown to be
therefore, it is not advised to wait for with hemoglobinuria. Supportive care helpful in adsorbing nicotine.10 Patients
results before initiating treatment. should be administered until recovery. should be monitored closely and treated
symptomatically. Artificial respiration is
Onions Rising Bread Dough indicated in patients with respiratory
Onions (raw, powdered, or cooked) can Ingestion of rising bread dough can be paralysis.
be harmful to dogs and cats. Onions are life threatening to dogs. The animal’s body
members of the genus Allium. Other heat will cause the dough to rise in the References
members of this genus include chives, stomach. Ethanol is produced during the 1. Gwaltney-Brant S: Chocolate intoxication. Vet Med
96(2):108–111, 2001.
garlic, leeks, and shallots. The primary rising process, and the dough may expand 2. Means C: The wrath of grapes. ASPCA Anim Watch
toxic principle in onions and other to several times its original size. Signs seen 22(2), 2002.
(continues on page 8)
HARTZ® COMPANION ANIMALSM • MAY 2005 • VOL. 3, NO. 2 5
6. Neutraceuticals and Joint Health (continued from page 3)
osteoarthritis progression: A randomized, placebo- 11. Scroggie DA, Albright A, Harris MD: 17. McNamara PS, Barr SC, Erb HN, Barlow
controlled clinical trial. Lancet 357:251–256, 2001. The effect of glucosamine-chondroitin LL: Hematologic, hemostatic, and
4. Pavelka K, Gatterova J, Olejarova M, et al: supplementation on glycosylated hemoglobin biochemical effects in cats receiving an oral
Glucosamine sulfate use and delay of progression of levels in patients with type 2 diabetes mellitus: chondroprotective agent for thirty days. Vet
knee osteoarthritis: A 3-year, randomized, placebo- A placebo-controlled, double-blinded, Ther 1:108–117, 2000.
controlled, double-blind study. Arch Intern Med randomized clinical trial. Arch Intern Med 18. Parcell S: Sulfur in human nutrition and
162:2113–2123, 2002. 163:1587–1590, 2003. applications in medicine. Altern Med Rev
5. Braham R, Dawson B, Goodman C: The effect 12. McCoy SJ, Bryson JC: High-dose 7:22–44, 2002.
of glucosamine supplementation on people glucosamine associated with polyuria and
experiencing regular knee pain. Br J Sports Med 19. Usha PR, Naidu MU: Randomised, double-
polydipsia in a dog [letter]. JAVMA blind, parallel, placebo-controlled study of oral
37:45–49, 2003. 222:431–432, 2003. glucosamine, methylsulfonylmethane and their
6. Richy F, Bruyere O, Ethgen O, et al: Structural
13. Echard BW, Talpur NA, Funk KA, et al: combination in osteoarthritis. Clin Drug
and symptomatic efficacy of glucosamine and
Effects of oral glucosamine and chondroitin Investig 24:353–363, 2004.
chondroitin in knee osteoarthritis: A comprehensive
meta-analysis. Arch Intern Med 163:1514–1522, sulfate alone and in combination on the 20. Bui LM, Bierer TL: Influence of green lipped
2003. metabolism of SHR and SD rats. Mol Cell mussels (Perna canaliculus) in alleviating signs
Biochem 225:85–91, 2001. of arthritis in dogs. Vet Ther 4:397–407, 2003.
7. Cibere J, Kopec JA, Thorne A, et al: Randomized,
double-blind, placebo-controlled glucosamine 14. Lippiello L, Idouraine A, McNamara PS, et 21. Dobenecker B, Beetz Y, Kienzle E: A
discontinuation trial in knee osteoarthritis. Arthritis al: Cartilage stimulatory and antiproteolytic placebo-controlled double-blind study on the
Rheum 51:738–745, 2004. activity is present in sera of dogs treated with a effect of nutraceuticals (chondroitin sulfate
8. Kajinuma H, Kuzuya T, Ide T, Tyler JM: Effects chondroprotective agent. Canine Pract and mussel extract) in dogs with joint diseases
of glucosamine on insulin and glucagon secretion in 24:18–19, 1999. as perceived by their owners. J Nutr
dogs and ducks. Endocrinol Jpn 22:517–523, 1975. 15. Anderson MA, Slater MR, Hammad TA: 132(suppl):1690S–1691S, 2002.
9. Monauni T, Zenti MG, Cretti A, et al: Effects of Results of a survey of small-animal 22. Reynolds R, Wight A, Wilder H: Clinical
glucosamine infusion on insulin secretion and practitioners on the perceived clinical efficacy evaluation of Arthrotabs in dogs with mobility
insulin action in humans. Diabetes 49:926–935, and safety of an oral nutraceutical. Prev Vet problems. Vet Times 28:8, 1998.
2000. Med 38:65–73, 1999. 23. Read R, Sutherland J, Ghosh P: The matrix
10. Robinson KA, Sens DA, Buse MG: Pre- 16. Canapp SO Jr, McLaughlin RM Jr, components of the epiphyseal growth plate
exposure to glucosamine induces insulin Hoskinson JJ, et al: Scintigraphic evaluation of and articular cartilages from dogs treated with
resistance of glucose transport and glycogen dogs with acute synovitis after treatment with ammonium tetrathiomolybdate, a copper
synthesis in isolated rat skeletal muscles. glucosamine hydrochloride and chondroitin antagonist. Aust J Exp Biol Med Sci
Diabetes 42:1333–1346, 1993. sulfate. Am J Vet Res 60:1552–1557, 1999. 64:545–562, 1986.
A D VA N C E D C A R E ®
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Joint Maintenance ADVANCED CARE®
Hartz® Everyday
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CARE® Vitamins
Enteric-Coated
Aspirin
For Dogs
• For the temporary relief of • Vitamin enriched • Highly palatable.
everyday aches and pains. • Specially formulated with Glucosamine
• Specifically formulated to
to help support healthy joint function.
• Available for Dogs and
reduce stomach upset, • Available for both dogs and cats. Puppies and Cats and Kittens
a common side effect
of aspirin.
• Highly palatable liver flavor
• An excellent source of vitamins
and minerals that help maintain
healthy skin and a shiny coat
www.hartz.com AD-192
7. Albert Ahn, DVM, is Vice President of Corporate Communications
and Veterinary Operations at The Hartz Mountain Corporation.
ASK TH E VET
Q Can garlic cause Heinz body hemolytic
anemia in cats? If so, at what dose would
this be expected to occur?
Q
Is there a confirmed dosage for
glucosamine to prevent degenerative
joint disease (DJD)?
A Garlic, like onions, is in the genus Allium and
contains n-propyl disulfide, which can cause oxidative
damage to erythrocytes. However, there are no
A
Glucosamine is an amino-monosaccharide nutrient
and is classified as a chondroprotective agent.
Chondroprotective agents are used with the intent
published studies showing Heinz body production in of healing cartilage, stimulating cartilage matrix
cats following ingestion of garlic. There has been one synthesis, and inhibiting enzymatic degradation
published study1 that indicates a dose of 5,000 mg of cartilage. Glucosamine is a precursor to the
of garlic/kg body weight produced hematologic disaccharide unit of glycosaminoglycans, which
changes in dogs. Because cats appear to be more comprise the proteoglycan ground substance of
sensitive to oxidative changes, one would assume articular cartilage. Glucosamine acts by providing the
similar effects would also be seen in cats. regulatory stimulus and raw materials for synthesis of
glycosaminoglycans in cartilage. According to current
Reference information and research standards, there is not
1. Lee KW, Yamato O, Tajima M, et al: Hematologic changes associated with
the appearance of eccentrocytes after intragastric administration of garlic
a known preventative dosage. However, based
extract to dogs. Am J Vet Res 61(11):1446–1450, 2000. on the mechanism of action, using glucosamine
prophylactically in dog breeds that are prone
Articles found in the Hartz Companion Animal SM to DJD would be an excellent idea.
newsletter can be copied and distributed to your
colleagues, staff, and clients. Additional newsletters may
also be obtained by contacting us at feedback@hartz.com
or by phone at 800-275-1414.
WE WANT TO HEAR FROM YOU!
• Have questions or comments? Call our Consumer
Relations Department at 800-275-1414 and ask to
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• To obtain a Hartz Veterinary Catalog of products,
please call 800-999-3000 x5118 or email us at
feedback@hartz.com.
HARTZ® COMPANION ANIMALSM • MAY 2005 • VOL. 3, NO. 2 7
8. Dangerous Foods (continued from page 5)
3. Hansen SR: Macadamia nut toxicosis in dogs. Vet eccentrocytes after intragastric administration of ingestion of Chinese chive (Allium tuberosum) and
Med 97(2):274–276, 2002. garlic extract to dogs. Am J Vet Res 61(11): garlic (Allium sativum) in a dog. JAAHA
4. Schell MM: Tremorgenic mycotoxin intoxication. 1446–1450, 2000. 41(1):68–73, 2005.
Vet Med 95(4):283–286, 2000. 7. Ogawa E, Shinoki T, Akahori F, Masaoka T: 9. Means C: Bread dough toxicosis in dogs. J Vet
5. Cheeke PR: Natural Toxicants in Feeds, Forages, and Effect of onion ingestion on anti-oxidizing agents Emerg Crit Care 13(1):39–41, 2003.
Poisonous Plants, ed 2. Danville, IL, Interstate in dog erythrocytes. Jpn J Vet Sci 48(4):685–690, 10. Plumlee KH: Nicotine, in Peterson ME, Talcott
Publishers, 1998. 1986. PA (eds): Small Animal Toxicology. Philadelphia,
6. Lee KW, Yamato O, Tajima M, et al: Hematologic 8. Yamato O, Kasai E, Katsura T, et al: Heinz body WB Saunders, 2001, pp 600–602.
changes associated with the appearance of hemolytic anemia with eccentrocytosis from
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