four nutraceuticals your practice should not be without wendy blount, dvm

Four NutraceuticalsYour Practice Should Not Be WithoutWendy 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

– 75% Referrals – Internal Medicine and Herbal Medicine/Nutrition

– 25% General Practice

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 beingIntent is to improve health and well being

NOT Nutraceuticals

•Whole herbs

•Unprocessed (raw) natural products

•Cartilage powders

•Applied topically or injected

Four NutraceuticalsYour Practice Shouldn’t be Without

•Joint Supplements

•chondroprotectives

•Fish Oil

•Milk Thistle

•Silymarin, SilybinTM

•SAMe

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

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

•USPUSP

Quality ControlOther 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

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 supplementsEncourage research on animal supplements

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

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 labelLook for the ConsumerLabs Seal on the label

USP - United States Pharmacopeia

•Compiles a list of suppliers that have voluntarily submitted their products for USP verification and approval

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


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 trialsreduce need for NSAID therapy in clinical trials


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

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.

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

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)

Chondroprotectives - What Do They Do?•Prevent periarticular thrombi formation

•Potential Anticoagulant effectPotential 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

Chondroprotectives- GAGs, Amino Sugars, Structural Proteins -

•Glucosamine sulfate

•Glucosamine HCl

•Chondroitin sulfate

•Hyaluronic acid

•Pentosan polysulphate (Elmiron)

• Hexosamine and Hexuronic acid - Adequan

Chondroprotectives- Others -

•Animal Extracts – collagen II, Perna

•Antioxidants

•Vitamins

•Minerals

•Amino Acids and Enzymes

•Herbs

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

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


•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:CAUTION: Glucosamine can potentially disregulate diabetics


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 HOWEVER – N-acetylglucosamine less efficacious in

cell culture


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

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 ConsumberLabs found 73% of products tested contained less chondroitin than claimed on labelcontained less chondroitin than claimed on label

Glycosaminoglycans – Chondroitin

•2 types of chondroitin sulfate

•Chondroitin-4-sulfate - mammalian

•Chondroitin-6-sulfate - sharkChondroitin-6-sulfate - shark

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


•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


•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.

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

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

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

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


•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.


•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.


•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.

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 -CAUTION - High doses of single antioxidants can actually have pro-oxidant effects

•Broad spectrum combination antioxidants are probably preferred

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


•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


•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

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

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)

Antioxidants – Methylsulfonylmethane (MSM)

•No toxicity has been reported

•No studies in dogs and cats

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

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

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

Minerals - Zinc

•Positive effects probably due to antioxidant activity

•also may immobilize macrophages

•No studies on arthritis in dogs or cats

Minerals - Calcium

•Popular among breeders

•No studies on calcium supplementation and arthritis in dogs or cats

Amino Acids & Enzymes

•Do Enzymes work if Given Orally?

•Pancreatic enzymes certainly work when given orally, even if not incubated on the food

•A number of small proteins (<10kDaltons) are absorbed intact if given PO

Amino Acids & Enzymes - Creatine

•Large doses help muscle function in people

•Dose in veterinary products is typically very small

•Any potential benefit is unlikely


•In SynoviCre

AA & Enzymes – Proteolytic Enzymes•Inhibit pro-inflammatory compounds and fibrinolytic activity

•Bromelain, papain, trypsin, etc.

•People with arthritis or spinal pain showed similar pain reduction, whether they were treated with enzymes or the NSAID diclofenac

•Bromelain decreases swelling in people with sports injuries when taken in high doses every 4 hours

AA & Enzymes - Superoxide Dismutase

•An enzyme that inhibits inflammation by inactivation of superoxide radicals and possibly stabilization of lysosomes

•Forms peroxide, which in turn must be neutralized by other enzymes catalase or glutathione peroxidase

•Extracted from bovine liver cells

AA & Enzymes - Superoxide Dismutase

•Oral absorption is poor

•because of its large size, penetration to target tissues after IM injection is poor

•Intra-articular injections show mixed results

•Considerable quality control issues

•1998 study evaluated 6 SOD products, and found none to contain more than 5% of label claims

Herbs - Boswellia

•Boswellia serrata (frankincense)

•May reduce pain and swelling by inhibiting lipooxygenase

•Excellent quality herbal source would be crucial, as whole herbs are not standardized

•2 studies in dogs show positive effect on joint pain

Herbs – ASUAvocado Soybean Unsaponifiables

•stimulate the synthesis of matrix components by chondrocytes

•approved as a prescription drug in France

•introduced in Denmark as a food supplement

•Four randomized, double-blind, placebo-controlled clinical trials in people

•ameliorates symptoms of knee and hip osteoarthritis

Herbs – ASUAvocado Soybean Unsaponifiables

•In new product Dasuquin by Nutramax

•Early stages of research

•In vitro studies (cell culture)

•Preliminary studies in healthy dogs

•No clinical trails in dogs or cats yet

Herbs – Devil’s Claw

•Harpagophytum procumbens

•Inhibits TNF-alpha

•Few negative side effects

•Drug Doloteffin was derived from this herb


Herbs – Willow Bark•Salix alba

•A source of salicylates

•Aspirin was derived from this tree bark

•Same side effects as aspirin

•Related plants: Poplar (Poplar spp.), Sweet Birch (Betula lenta)

•A number studies supporting use of willow bark for OA in people

Herbs – Yucca

•Yucca schidigera

•Very popular, but not well studied

•Included in dog foods because of its interesting side effect – decreases odor of dog feces.

•No evidence that it affects arthritis in any way

Herbs – Yam• Wild Yam, Mexican Yam

•Contains diosgenin, which has been used as a precursor in the manufacture of commercial corticosteroids

•But does not appear to be converted to glucocorticoid by mammals

•Unstudied, and efficacy is questionable

•Concurrent use with NSAIDs could be unwise

Combination products•Combined glucosamine and chondroitin is thought to be synergistic

•Anabolic effects of glucosamine

•Anti-catabolic effects of chondroitin

•Different mechanisms of action

•Adding Manganese enhances rate limiting cofactor

Dog/Cat Clinical Studies

•Experimentally produced ruptured cruciates, followed by corrective surgery

•Post-op DJD reduced by Cosequin

Hulse DS, Hart D, Slater M, et al; The effects of Cosequin in cranial cruciate deficient and reconstructed stifle joints in dogs. Proc Vet Orthop Soc:64, 1998.


•Experimentally produced synovitis

•Pretreatment with Cosequin reduced inflammation and lameness

Canapp SO, McLaughlin RM, Hoskinson JJ, et al; Scintigraphic evaluation of Cosequin as a treatment for acute synovitis in dogs. Am J Vet Res.


•Survey of 3,000 small animal practitioners

•Perceived improved mobility, reduced pain, improved attitude

•Adverse effect - only 2% had GI upset

Anderson MA, Slater M, Hammad TA, Brawner, WR; Results of a survey of small animal practitioners on the perceived efficacy and safety of an oral chondroprotective nutraceutical. Prev Vet Med 38:65-73, 1999.


•Glucosamine for Feline Idiopathic Cystitis

•125mg mg N-acetyl glucosamine per day x 6 months

•No difference in outcome

Gunn-Moore AD, Shenoy CM. Oral glucosamine and the management of feline idiopathic cystitis. J Feline Med Surg August 2004;6(4):219-25.


•Clinical study compared carprofen, meloxicam and Synoquin for treating OA

•surgeons noted improvement with carprofen and meloxicam

•owners saw improvement only with meloxicam

•force plate analysis significantly improved by carprofen and meloxicam but not by the nutraceutical Synoquin

Dog/Cat Clinical Studies•Force plate values returned to normal only with meloxicam

•treatments well tolerated, except for a case of hepatopathy in a dog treated with carprofen.

•Synoquin (VetPlus Ltd) – chondroitin, glucosamine HCL, N-Acetyl-D glucosamine, ascorbic acid and zinc.

•Moreau M, Dupuis J, Bonneau NH, Desnoyers M. Clinical evaluation of a nutraceutical, carprofen and meloxicam for the treatment of dogs with osteoarthritis. Vet Rec 152[11]:323-9 2003 Mar 15


•Clinical study compared carprofen, meloxicam and Cosequin effect on thyroid function in dogs with OSA

•normal thyroid function at the outset

•None of the three had any significant effect on thyroid function

Chastain CB, Panciera D. Effect of Meloxicam, Carprofen and a Nutraceutical on Thyroid function tests. SA Clin Endocrin. 2004 May-Aug;14(2):6.

Dog/Cat Clinical Studies•Pentosan PO for 12 weeks had no benefit in animals recovering from cranial cruciate surgery

•Assessed by radiographs and owner impression

Innes JF, Barr AR, Sharif M. Efficacy of oral calcium pentosan polysulphate for the treatment of osteoarthritis of the canine stifle joint secondary to cranial cruciate ligament deficiency. Vet Rec April 2000;146(15):433-7.

Dog/Cat Clinical Studies•Pentosan SC for 4 weeks had no benefit in animals recovering from cranial cruciate surgery

•Assessed by lameness, rads, force plates at 6,12, 24 and 48 weeks.

Budsberg S, Bergh MS, Reynolds LR, et al. Evaluation of pentosan polysulfate sodium in the postoperative recovery from cranial cruciate surgery in dogs; a randomized, placebo-controlled clinical trail. Vet Surg April 2007;36(3):234-44.

Dog/Cat Clinical Studies•Hyaluronan IA once a week x 5 weeks after experimental cruciate injury – no benefit

•Assessed by arthroscopy & force plates.

Smith G, Myers SL, Brandt KD, et al. Effect of intraarticular injection on vertical ground reaction force and progression of osteoarthritis after anterior cruciate ligament transection. J Rheumotol. February 1005;32(2):325-34.

Dog/Cat Clinical Studies•Collagen II given at 1 mg or 10 mg per day for 90 days, to dogs with OA.

•Lameness and pain assessed weekly for 120 days.

•Significant improvements in pain and lameness in both groups. Relapse after withdrawal for 30 days.

Deparle LA, Gupta RC, Canerdy TD, et al. Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs. J Vet Pharmacol Ther August 2005;28(4):385-90.

Dog/Cat Clinical Studies•Dogs with DJD were treated with Perna for 56 days

•Scored by owners and veterinarians

•No difference between the groups at 28 days

•Significant improvement in Perna group by day 56

Pollard B, Guilford WG, Ankenbauer-Perkins KL, et al. Clinical efficacy and tolerance of an extract of green lipped mussel extract (Perna canaliculus) in dogs presumptively diagnosed with DJD. NZ Vet June 2006;54(3):114-8.

Dog/Cat Clinical Studies•Dogs with arthritis were treated with Perna added to a dry diet for 6 weeks

•Scored by veterinarians

•Significant improvement in Perna at 6 weeks

Bui LM, Bierer TL. Influence of green lipped mussels (Perna canaliculus) in alleviating signs of arthritis in dogs. Vet Ther Winter 2—3;4(4):397-407.

Dog/Cat Clinical Studies•Boswellia 400mg/10kg body weight SID x 6 weeks

•71% of dogs with OA had improvement within 2 weeks

•Assessed by grading lameness

Innes JF, Fuller CJ, Grover ER et al. Randomised, double blind, placebo-controlled parallel group study of P54FP for the treatment of dogs with osteoarthritis. Vet Rec April 2003;152(15):457-60.

Dog/Cat Clinical Studies•Carprofen reduced progression of experimental OA, based on histology and chemistry

•No assessment of effect on lameness

Pelletier JP, Lajeunesse, Javanovic DV, et al. Carporfen simultaneously reduces morphological changes in cartilage and subchondral bone in experimental dog osteoarthritis. J Rheum Dec 2000;27(12):2893-902.


Aragon CL, Hofmeister EH, Budsberg SC. Systematic review of clinical trials of treatments for osteoarthritis in dogs. JAVMA, Vol 230, No. 4, February 15, 2007.

•Meloxicam most effective at managing OA

•Moderately effective:

•CarprofenCarprofen

•EtodolacEtodolac

•PentosanPentosan

•PernaPerna

•BoswelliaBoswellia

•GAGsGAGs

•CosequinCosequin

Studies - Conclusions

•Many studies are based on experimental models of OA, many on unstable knees

•Don’t know how this correlates with natural disease

•No studies on glucosamine alone (without chondroitin) in dogs and cats

•No studies comparing different joint supplements

•LD50 for GAGs extremely high - >5g/kg – non-toxic


•Cosequin, Collagen II, Perna and Boswelia seem to work for joint pain of OA.

•Synoquin does not seem to help joint pain

•Cosequin helps recovery after cruciate surgery

•Pentosan PO/SC and IA hyaluronic acid do not seem to help recovery after cruciate surgery

•N-acetyl glucosamine does not improve idiopathic cystitis


•Cosequin, Perna and Boswelia seems to work for joint pain

•Synoquin does not seem to help joint pain

•Cosequin helps recovery after cruciate surgery

•Pentosan PO/SC and IA hyaluronic acid do not seem to help recovery after cruciate surgery

•N-acetyl glucosamine does not improve idiopathic cystitis

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Fatty Acids

Also referred to as PUFAs

Omega-3 fatty acids

Omega-6 fatty acids

Omega-9 fatty acids

•oleic acid (18:1n-9)

Fatty Acids – Omega-3

•DHA - docosahexaenoic acid (22:6n-3)

•EPA- eicosapentaenoic acid (20:5n-3)

•EPA and DHA in fish oil

•DHA also in blue-green algae

•ALA - Alpha linolenic acid (18:3n-3)

•precursor to EPA & DHA

•Present in flax seed (linseed) oilPresent in flax seed (linseed) oil


•ALA Not well converted to DHA and EPA in dogs and cats

•due to lack of delta-6-dehydrogenase

•Need fish oil for EPA and DHA benefits


•Powerful antiinflammatory effects

•decrease synovial IL-1 production, which contributes to pathogenesis of arthritis

•Necessary for mitochondrial function

•Residual effects for several weeks after discontinuing therapy


Dermatologic effects

•Many studies showing benefits of EPA and DHA pruritic skin disease in dogs

•Improvement in cats with miliary dermatitis


•Antineoplastic effects

•Both fish oil and arginine increased survival time and disease free interval in dogs with LSA

•Decrease production of cytokines that mediate cancer cachexia

•Antinflammatory effects are accompanied by immunostimulant properties


•Cardiovascular effects

•Primary treatment for hyperlipidemia

•Improves cardiac cachexia in dogs

•Protects against fibrillation and ischemic renal failure in ischemic models in the dog

•Reduces myocardial infarct size in a canine model of myocardial ischemia and reperfusion


•Musculoskeletal effects

•Mediates signs of RA in people, especially early in disease

•Moderates symptoms, does not slow progression of RA in people


•Renal effects

•Slows progression of glomerular disease in people

•Undefined effect on chronic tubular renal failure


•Hematologic effects

•At very high doses, can cause coagulopathy

•Cats more sensitive to this than dogs

•Do not give 2-3 days perioperatively

•Monitor with

•Von Willebrand’s Disease or other coagulopathy

•NSAIDs or coumadin therapy (or toxicity)


•Neurologic effects

•DHA necessary for proper neurologic development in puppies, kittens and people

•Helps a number of mental disorders in people

•This includes retinal development

•DHA blood levels are low in poodles with RP (retinitis pigmentosa) and PRA


Quality Control

•Contamination with heavy metals, dioxins and PCBs is a concern

•More of a problem with eating fish than fish oil supplements (stored in tissues)

•No fish oil products tested by ConsumerLab have ever been contaminated


Quality Control

•Beware of rancidity of refrigerated, pressed oils

•Cod Liver Oil is not always the best source

•High in Vitamins A & D

Fatty Acids – Omega-3Side Effects

•Inhibit platelet function

•Give with food to avoid GI upset

•Very high doses without antioxidant support can result in lipid peroxidation

•Most commercial products are preserved with antioxidants

•Anecdotal reports of pancreatitis and steatitis in cats


•LA – linoleic acid (18:2n-6)

•Precursor to omega-6 fatty acids

•GLA - gamma-linolenic acid (18:3-n-6)

•Black Currant Oil

•Borage Oil

•Evening Primrose Oil


•Arachadonic acid (20:4n-6)

•Essential for cats

•Other sources rich in omega-6’s

•Corn oil

•Safflower oil

•Soybean oil

•Canola oilCanola oil


•have some pro-inflammatory effects, as they can increase TNF & IL6

•Use of omega-6 for inflammatory diseases is controversial

•GLA leads to production of PGE1, which has less inflammatory effects than other PGEs

•Also leukotriene production is inhibited


•Omega-6 are good overall coat conditioners, and help seborrhea

•Omega-6 already plentiful in the diet

•Studies in people show some response of arthritis to EPO and Borage oil

•Study on Black Currant Oil showing no beneficial effect for arthritis in people

Fatty Acids – Omega-6:Omega-3 Ratio

•Response to omega-3 therapy is due to both omega-3 dose and omega 6:ratio in the diet

•Ideal ratio is probably between 3:1 and 9:1

•Many diets >30:1; some >50:1

•The more omega-6’s in the diet, the more omega-3’s needed for therapeutic effect

•Presence of excessive omega-3’s can suppress omega-6 production and vice versa

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Milk Thistle•Silybum marianum – Aster Family (daisies and thistles)

•Ripe seeds are used medicinally

•Silymarin is one of the active ingredients

• powerful antioxidant

• Anti-inflammatory – inhibits lipooxygenase-5

• Most commonly used as an 70-80% standard extract

Milk Thistle•Components of Silymarin (all are flavonolignans)

• silybin (silibinin) – MOST ACTIVE**

• Isosilybin (isosilibinin)

• silydianin (silidianin)

• silycrystine (silicristin)

Milk Thistle•Components of Silymarin (all are flavonolignans)

• Bioavailability depends on substances in extract

• Proliposomes increase bioavailability in dogs

• Phosphotidyl choline increases bioavailability

• PC used in Nutramax Marin and DenoMarin

Milk ThistleDose

• Dried herb: 15-20mg/lb SID (1.5-3% silymarin)

• Concentrated extract: 2-5 mg/lb BID (70-80%)

• Alcohol concentrated extract: 2-5 mg/lb BID-TID

(70-80%)

• NOTE:NOTE: some extracts are whole herb extracts

hard to dose these high enough to be hard to dose these high enough to be effectiveeffective

Milk Thistle

Hepatic Effects

•Used for liver disease since the time of the Romans

•Some studies in people show improvement in liver enzymes, liver histology and survival in people with chronic active hepatitis

•No such benefit in people with viral hepatitis

•Equivocal results in people with alcoholic hepatitis

Milk Thistle

Hepatic Effects

•Protective against Amanita mushroom toxicity in dogs

•Used as an antidote for Amanita toxicity in people

• 5 mg/kg IV over 1 hour

• then 20 mg/kg/day IV x 6 daysthen 20 mg/kg/day IV x 6 days

• IV prep not readily available in the USIV prep not readily available in the US

Milk Thistle

Hepatic Effects

•Also protective against carbon tetrachloride toxicity in dogs

•Protects against acetamenophen and phenytoin liver toxicity in people

•Many use it for hepatoprotective effects in dogs who take phenobarbital and primidone

Milk Thistle

Endocrine Effects

•Reduces insulin resistance in people with coexisting diabetes and alcoholic cirrhosis

•May decrease blood sugar and LDL in people with type II diabetes

Milk Thistle

Cardiovascular Effects

•Amiodarone generates free radicals that may cause toxicity

•Amiodarone used for ventricular arrhythmias in dogs

•Silymarin plus amiodarone protected against induced atrial flutter

•Silymarin and amiodarone alone provided no Silymarin and amiodarone alone provided no such protectionsuch protection

Milk Thistle

Antiprotozoal Effects

•Treatment with metronidazole and silymarin was more effective than treatment with metronidazole alone

•Treatment with silymarin alone was not effective

Milk Thistle

Side Effects

•Rare GI upset in people, dogs and cats

•Rare allergic rash in people

Milk Thistle

Quality Control

•Only 2 of 9 products tested by ConsumerLab contained the expected amounts of silymarin

•Stick with a Brand you know

•The only Nutraceutical made for pets with milk thistle in it is Marin by Nutramax

•Denamarin combines Marin with SAMe (Denosyl)

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S-adenosyl-L-methionine (SAMe)

•SAMe is an amino acid which acts as a methyl donor

•transsulfates GAGs

•Used to make neurotransmitters

•dopamine and serotonin

•Absorption is better when given after a 12-hour fast in dogs

•Giving with food can prevent stomach upset.Giving with food can prevent stomach upset.

S-adenosyl-L-methionine (SAMe)

•Present in protein rich foods

•First used to treat depression on people

•Positive side effect of treating arthritis pain in people was noted

•Promotes DNA, protein and proteoglycan synthesis

•May have antiinflammatory and analgesic properties

•May be a promising antidote for Tylenol toxicity

SAMe – Hepatic Effects

•Improves hepatocellular function

•Improves bile flow

•Increases glutathione levels to fight inflammatory liver disease

•Powerful antioxidant

•In people, low glutathione levels lead to hepatitis, arthritis and depression


•50% of dogs and 80% of cats with hepatobiliary disease have low liver glutathione

•Denosyl is proven to increase liver glutathione levels in dogs and cats

•Bloodwork improvement can take up to 1-4 months


•used to produce phosphatidyl choline, the main phospholipid in hepatocyte cell membranes

•When SAMe is depleted, hepatocyte cell membranes become less fluid

•leads to impaired bile secretion into bile canaliculi and cholestasis

•Bile acids are inflammatory, leading to chronic hepatitis


•SAMe also promotes Na-K-ATPase that drives canalicular bile flow

•Low SAMe levels can also cause cholestasis this way

•SAMe is good for hepatic icterusSAMe is good for hepatic icterus

SAMe – Musculoskeletal Effects

•Human clinical trials show SAMe effective in treating OA

•Positive results can persist for at least 2 years after treatment in people

•rabbit studies show some chondroprotective effects, by increasing proteoglycan synthesis

SAMe – Dose

•18 mg/kg/day

•Daily for 1-3 months for exposure to hepatotoxin

•Daily for 2-3 months for chronic active hepatitis

•Then QOD or twice weekly

•Twice weekly for protection against hepatotoxic therapy

SAMe - Quality Control

•SAMe is an expensive ingredient

•Nearly half of products contained less SAMe than labeled when ConsumerLab first tested in 2000

•All passed testing in April 2007

•SAMe is absorbed in the small intestine

•Should be enteric coated for better absorption and to prevent stomach upset


•SAMe can break down with exposure to air

•Each tablet should be sealed in foil blister

•Can not be compounded into suspensions

•Broken tablets should be discarded

•Doses rounded to the nearest whole tablet


•SAMe comes in different forms, according to the stabilizer used

•Tosylate

•disulfate tosylate

•disulfate ditosylate

•1,4-butanedisulfonate (Actimet™)


•added compounds weigh as much as the SAMe molecule itself

•Interpret mg on ingredient list with care

•label is not always clear how much SAMe is in the product

SAMe - Side Effects

•GI upset mentioned previously

•Enteric coating can help

•Give with food if necessary

•No toxicity every reported – no LD50 can be reached

four nutraceuticals your practice should not be without wendy blount, dvm

Documents

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