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Four Nutraceuticals Your Practice Should Not Be Without

Four Nutraceuticals Your Practice Should Not Be Without. Wendy Blount, DVM. Wendy Blount, DVM. DVM TAMU 1992 Private Practice Houston 2 years Small Animal Residency TAMU 1994-1997 Small Animal Internal Medicine Private Practice Nacogdoches, TX

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Four Nutraceuticals Your Practice Should Not Be Without

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  1. Four NutraceuticalsYour Practice Should Not Be Without Wendy Blount, DVM

  2. Wendy Blount, DVM • DVM TAMU 1992 • Private Practice Houston 2 years • Small Animal • Residency TAMU 1994-1997 • Small Animal Internal Medicine • Private Practice Nacogdoches, TX • 75% Referrals – Internal Medicine and Herbal Medicine/Nutrition • 25% General Practice

  3. Nutraceutical NAVNA - North American Veterinary Nutraceutical Association • Non-drug substance • Purified and extracted • Administered orally • Provides nutritional building blocks for normal body structure and function • Intent is to improve health and well being

  4. NOT Nutraceuticals • Whole herbs • Unprocessed (raw) natural products • Cartilage powders • Applied topically or injected

  5. Four NutraceuticalsYour Practice Shouldn’t be Without • Joint Supplements • chondroprotectives • Fish Oil • Milk Thistle • Silymarin, SilybinTM • SAMe

  6. Quality Control Governmental regulation • Dietary Supplement Health and Education Act of 1994 - gives FDA power of enforcement over all dietary supplements • Nutrition Labeling and Education Act of 1990 - FTC enforces label claims on all products sold in US

  7. Quality Control • NASC Membership • NADA Number if claims on the label • Third Party Evaluation • www.consumerlab.com • Veterinary literature - clinical studies in the target species, not in vitro studies or lab animal studies • USP

  8. Quality Control Other things to look for • Price • Ingredient List - Beware “proprietary blends” • Nature of the claims • Good instructions for use • Studies provided by manufacturer are on their actual product, not ingredients

  9. National Animal Supplement Council www.nasc.cc Member companies submit themselves to rigorous independent inspections Work directly with FDA to improve best manufacturing processes and adverse event reporting Work closely with AAFCO Encourage research on animal supplements

  10. NADA - New Animal Drug Application Required by law if medical claims are on the label Often ignored NADA number means the manufacturer has bothered to abide by FDA regulations for drug manufacture

  11. ConsumerLabs www.consumerlabs.com Purchases and tests dietary supplements for potency and purity - published reports Compiles information on dietary supplements Compiles a list of recalls and FDA warning letters pertaining to dietary supplement manufacturers Look for the ConsumerLabs Seal on the label

  12. USP - United States Pharmacopeia Compiles a list of suppliers that have voluntarily submitted their products for USP verification and approval

  13. Why Chondroprotectives? NSAIDs treat symptoms powerfully, but do not address the primary disease process in any way Chondroprotectives do address disease • support joint tissue health and repair

  14. Why Chondroprotectives? NSAIDs can cause side effects • Mild, self limiting side effects are common • Serious side effects are rare, but can include death • Serious side effects can occur even when used appropriately Chondroprotectives are associated with minimal and mild side effects • reduce need for NSAID therapy in clinical trials

  15. Why Chondroprotectives? NSAIDs intervene at a single point in the inflammatory cascade • cyclooxygenase Chondroprotectives can intervene in multiple pathways that lead to arthritis • Multiple opportunities for therapeutic intervention

  16. COX2 Selectivity THEORY • COX1 is constitutive - responsible for normal activity • COX2 is induced - kicks in during inflammation • Drugs that selectively inhibit COX2 should have fewer side effects, because they don’t affect homeostasis REALITY • In vitro data do not always correlate with in vivo results • Side effects are still significant even with very COX2 selective drugs.

  17. NSAID Side Effects • suppress chondrocyte metabolism • inhibit normal collagen and proteoglycan synthesis • gastric ulceration and hemorrhage. • renal damage/failure • especially with long term use • Especially when used with ACE inhibitors, diuretics • Very rarely liver failure

  18. Chondroprotectives - What Do They Do? • GAGs line the cartilage – act as protectant and shock absorber • Supplementation enhances cartilage metabolism • Retard cartilage degradation (metalloproteinases) • Retard production of inflammatory cartilage breakdown products (anti-inflammatory)

  19. Chondroprotectives - What Do They Do? • Prevent periarticular thrombi formation • Potential Anticoagulant effect, because heparin and GAGs are chemically similar • Minor but clinically insignificant shifts in hemostatic parameters • Long term use concurrent with platelet inhibitors should be monitored (aspirin, phenylbutazone) • It can take up to 4-6 weeks to see maximum effects

  20. Chondroprotectives- GAGs, Amino Sugars, Structural Proteins - Glucosamine sulfate Glucosamine HCl Chondroitin sulfate Hyaluronic acid Pentosan polysulphate (Elmiron) Hexosamine and Hexuronic acid - Adequan

  21. Chondroprotectives- Others - Animal Extracts – collagen II, Perna Antioxidants Vitamins Minerals Amino Acids and Enzymes Herbs

  22. Chondroprotectives Safety Studies: Hematologic, hemostatic, and biochemical effects in dogs receiving an oral chondroprotective agent for thirty days.Am J Vet Res 57[9]:1390-4 1996 SepMcNamara PS ; Barr SC ; Erb HN Hematologic, Hemostatic, and Biochemical Effects in Cats Receiving an Oral Chondroprotective Agent for 30 DaysVet Ther 1[2]:108-117 Spring'00 Experimental Safety Study * PS McNamara; SC Barr; HN Erb; LL Barlow

  23. Glucosamine – Amino Sugar • Extracted from crab shells (chitin) • Can rarely cause hypersensitivities if not pharmaceutical grade • Can also be extracted from corn • Building block nutrient that is extracted from the serum by chondrocytes to form GAGs • Decreased glucosamine synthesis by chondrocytes has been observed in early OA

  24. Glucosamine – Amino Sugar Also stimulates synovial cell synthesis of hyaluronic acid May modulate joint inflammation by scavenging free radicals Recommended dose 125-250 mg per 20-25 lb daily Double the dose for the first 4-6 weeks CAUTION:Glucosamine can potentially disregulate diabetics

  25. Glucosamine – Amino Sugar Glucosamine sulfate vs Glucosamine HCl • Glucosamine HCl is better absorbed in people • Clinical studies show GS is effective despite this • Do not know if there is a difference in absorption or efficacy in dogs and cats • Both are proven efficacious • HOWEVER – N-acetylglucosamine less efficacious in cell culture

  26. Glucosamine – Amino Sugar Glucosamine for Feline Idiopathic Cystitis • GAGs line the bladder mucosa • Theory is that the GAG layer may be deficient in those dogs and cats who suffer from chronic/recurring UTI and idiopathic cystitis • No studies to support this yet

  27. Glycosaminoglycans – Chondroitin Harvested from cartilage Extensive processing required for high quality product more expensive ingredient than glucosamine Some products don’t actually contain as much chondroitin as is on the label ConsumberLabs found 73% of products tested contained less chondroitin than claimed on label

  28. Glycosaminoglycans – Chondroitin • 2 types of chondroitin sulfate • Chondroitin-4-sulfate - mammalian • Chondroitin-6-sulfate - shark

  29. Chondroitin-4-sulfate • Binds to collagen in the cartilage matrix • Contributes to resiliency and water holding properties of cartilage • As animals age, they make less C4S and more of the more brittle GAGs • Contributes to age related joint degeneration

  30. Chondroitin-4-sulfate • Like glucosamine, inhibits metalloproteinases • Decreases degradation of collagen and proteoglycans • decreases interleuken 1 and blocks complement • C4S released by platelets during normal clotting • Decreased release with disease or age causes pathologic microthrombi in subchondral bone and other tissues

  31. Chondroitin-4-sulfate Has positive effects that last long after treatment discontinued (unlike glucosamine) Many think you can wean down to the lowest effective dose after 6-8 weeks.

  32. Hyaluronic Acid GAG Composed of glucuronic acid and glucosamine Can be injected IA or IV A few studies in dogs show no effect on recovery after experimental cruciate injury

  33. Pentosan GAG derived from a plant source (beechwood) and synthetically modified by adding sulfates Oral availability is not as good as glucosamine, chondroitin A few studies in dogs show no effect at treating experimental cruciate injuries

  34. Animal Extracts - Perna Perna canaliculus – Green Lipped Mussel Antiinflammatory lipids more powerful than fish oil and some NSAIDs Exact active ingredients and mechanism of action have not been determined 2 studies in dogs demonstrate efficacy in controlling joint pain

  35. Animal Extracts – Collagen II Hyaline cartilage is composed mostly of type II Collagen II is produced from extracts of animal cartilage some evidence that collagen II can improve clinical signs due to rheumatoid arthritis in people RA is sometimes caused by autoimmunity to collagen in the joints

  36. Animal Extracts – Collagen II • Two studies have shown autoantibodies to type II collagen in dogs with joint disease Bari SM, Carter SD, Bell SC, et al; Anti-type II collagen antibody in naturally occuring canine joint diseases. Br J Rheumatol 28:480-486,1989. Niebauer GW, Wolg B, Bashey RI, et al; Antibodies to canine collagen types I and II in dogs with spontaneous cranial curciate ligament rupture and osteoparthritis. Arthritis Rheumatol 30:319-327, 1987.

  37. Animal Extracts – Collagen II low doses PO of collagen II can produce "tolerance" to the joint collagen in some people with RA This mediates clinical signs of inflammatory arthritis Lab animal models have shown consistently good results human clinical trials have shown mixed results. 

  38. Animal Extracts – Collagen II current theory is that the secret to success is found in giving LOW doses for RA.  Giving too much collagen II antigen may actually cause flare-ups with RA in people.

  39. Antioxidants Free radical damage and oxidation play a significant role especially in immune mediated arthritis Antioxidants should in theory help to minimize pathology in inflammatory arthritides CAUTION -High doses of single antioxidants can actually have pro-oxidant effects Broad spectrum combination antioxidants are probably preferred

  40. Antioxidants – Vitamin C Important to enzymes involved in cross-linkage of collagen fibers necessary to repair joint tissues Some evidence that calcium ascorbate helps alleviate pain due to OA in people Some evidence that Vitamin C helps prevent immune mediated arthritis in people Popular Among Breeders

  41. Antioxidants – Vitamin C Since dogs make vitamin C endogenously, adding vitamin C to the diet has been questioned Unlikely to cause serious toxicity unless very high doses used GI toxicity at high doses

  42. Antioxidants – Vitamin C • So what’s the deal with Ester-C ? • Wang et al, 2001 • DOG STUDY: Compared pharmacokinetics of crystalline AA and Ester-C • no significant differences found

  43. Antioxidants – Vitamin E • Decreases proinflammatory cytokines and lipid mediators • Low vitamin E intake may be a risk for development of rheumatoid arthritis in people • No evidence that vitamin E alone ameliorates symptoms of arthritis in people • No studies in dogs or cats

  44. Antioxidants – Methylsulfonylmethane (MSM) Oxidation product of DMSO Found naturally in Horsetail, fruits, vegetables, grains upregulates the proteoglycan synthesis of chondrocytes Provides a sulfur source for methionine Thought to reduce inflammation by acting as an antioxidant (though not proven)

  45. Antioxidants – Methylsulfonylmethane (MSM) No toxicity has been reported No studies in dogs and cats

  46. Vitamins – Niacinamide • Used for many immune mediated skin diseases, along with doxycyline • Fifty years ago, Kaufman reported that high-dose niacinamide was beneficial in OA and RA • Niacinamide inhibits IL1, which contributes to pathology of arthritis • No studies on arthritis in dogs and cats

  47. Minerals - Manganese • Essential cofactor in GAG formation • Often a limiting factor in joint repair • Potentiates efficacy of glucosamine • Also has an antioxidant effect • No clinical studies in dogs and cats • In many combination joint support products • Cosequin

  48. Minerals - Selenium • selenium may down-regulate cytokine signaling which contributes to pathology of arthritis • Low selenium intake may be associated with development of immune mediated arthritis in people • No studies on arthritis in dogs and cats

  49. Minerals - Zinc • Positive effects probably due to antioxidant activity • also may immobilize macrophages • No studies on arthritis in dogs or cats

  50. Minerals - Calcium • Popular among breeders • No studies on calcium supplementation and arthritis in dogs or cats

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