four nutraceuticals your practice should not be without l.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Four Nutraceuticals Your Practice Should Not Be Without PowerPoint Presentation
Download Presentation
Four Nutraceuticals Your Practice Should Not Be Without

Loading in 2 Seconds...

play fullscreen
1 / 131

Four Nutraceuticals Your Practice Should Not Be Without - PowerPoint PPT Presentation


  • 262 Views
  • Uploaded on

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

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Four Nutraceuticals Your Practice Should Not Be Without' - libitha


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
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
    • 75% Referrals – Internal Medicine and Herbal Medicine/Nutrition
    • 25% General Practice
nutraceutical
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
not nutraceuticals
NOT Nutraceuticals
  • Whole herbs
  • Unprocessed (raw) natural products
    • Cartilage powders
  • Applied topically or injected
four nutraceuticals your practice shouldn t be without
Four NutraceuticalsYour Practice Shouldn’t be Without
  • Joint Supplements
    • chondroprotectives
  • Fish Oil
  • Milk Thistle
    • Silymarin, SilybinTM
  • SAMe
quality control
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 control7
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
quality control8
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
national animal supplement council
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

nada new animal drug application
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
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

usp united states pharmacopeia
USP - United States Pharmacopeia

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

why chondroprotectives
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
why chondroprotectives14
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
why chondroprotectives15
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
cox2 selectivity
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
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
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 do19
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
chondroprotectives gags amino sugars structural proteins
Chondroprotectives- GAGs, Amino Sugars, Structural Proteins -

Glucosamine sulfate

Glucosamine HCl

Chondroitin sulfate

Hyaluronic acid

Pentosan polysulphate (Elmiron)

Hexosamine and Hexuronic acid - Adequan

chondroprotectives others
Chondroprotectives- Others -

Animal Extracts – collagen II, Perna

Antioxidants

Vitamins

Minerals

Amino Acids and Enzymes

Herbs

chondroprotectives
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
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
glucosamine amino sugar24
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

glucosamine amino sugar25
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
glucosamine amino sugar26
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
glycosaminoglycans chondroitin
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

glycosaminoglycans chondroitin28
Glycosaminoglycans – Chondroitin
  • 2 types of chondroitin sulfate
    • Chondroitin-4-sulfate - mammalian
    • Chondroitin-6-sulfate - shark
chondroitin 4 sulfate
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
chondroitin 4 sulfate30
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
chondroitin 4 sulfate31
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.

hyaluronic acid
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
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
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
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

animal extracts collagen ii36
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.

animal extracts collagen ii37
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. 

animal extracts collagen ii38
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.

antioxidants
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

antioxidants vitamin c
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

antioxidants vitamin c41
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

antioxidants vitamin c42
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
antioxidants vitamin e
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
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 msm45
Antioxidants – Methylsulfonylmethane (MSM)

No toxicity has been reported

No studies in dogs and cats

vitamins niacinamide
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
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
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
Minerals - Zinc
  • Positive effects probably due to antioxidant activity
  • also may immobilize macrophages
  • No studies on arthritis in dogs or cats
minerals calcium
Minerals - Calcium
  • Popular among breeders
  • No studies on calcium supplementation and arthritis in dogs or cats
amino acids enzymes
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
Amino Acids & Enzymes - Creatine

Large doses help muscle function in people

Dose in veterinary products is typically very small

Any potential benefit is unlikely

No studies in dogs and cats

In SynoviCre

aa enzymes proteolytic enzymes
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
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 dismutase55
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
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 asu avocado soybean unsaponifiables
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 asu avocado soybean unsaponifiables58
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
Herbs – Devil’s Claw
  • Harpagophytum procumbens
  • Inhibits TNF-alpha
  • Few negative side effects
  • Drug Doloteffin was derived from this herb
  • No studies in dogs and cats
herbs willow bark
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
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
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
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
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.

dog cat clinical studies66
Dog/Cat Clinical Studies
  • 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.

dog cat clinical studies67
Dog/Cat Clinical Studies
  • 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.

dog cat clinical studies68
Dog/Cat Clinical Studies
  • 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.

dog cat clinical studies69
Dog/Cat Clinical Studies

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 studies70
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

dog cat clinical studies71
Dog/Cat Clinical Studies
  • 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 studies72
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 studies73
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 studies74
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 studies75
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 studies76
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 studies77
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 studies78
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 studies79
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.

dog cat clinical studies80
Dog/Cat Clinical Studies

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:

Carprofen

Etodolac

Pentosan

Perna

Boswellia

GAGs

Cosequin

studies conclusions
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

studies conclusions82
Studies - Conclusions

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

studies conclusions83
Studies - Conclusions

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

fatty acids
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
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) oil
fatty acids omega 388
Fatty Acids – Omega-3
  • 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
fatty acids omega 389
Fatty Acids – Omega-3
  • 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
fatty acids omega 390
Fatty Acids – Omega-3

Dermatologic effects

  • Many studies showing benefits of EPA and DHA pruritic skin disease in dogs
  • Improvement in cats with miliary dermatitis
fatty acids omega 391
Fatty Acids – Omega-3
  • 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
fatty acids omega 392
Fatty Acids – Omega-3
  • 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
fatty acids omega 393
Fatty Acids – Omega-3
  • Musculoskeletal effects
    • Mediates signs of RA in people, especially early in disease
    • Moderates symptoms, does not slow progression of RA in people
fatty acids omega 394
Fatty Acids – Omega-3
  • Renal effects
    • Slows progression of glomerular disease in people
    • Undefined effect on chronic tubular renal failure
fatty acids omega 395
Fatty Acids – Omega-3
  • 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)
fatty acids omega 396
Fatty Acids – Omega-3
  • 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
fatty acids omega 397
Fatty Acids – Omega-3

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
fatty acids omega 398
Fatty Acids – Omega-3

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 399
Fatty Acids – Omega-3

Side 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
fatty acids omega 6
Fatty Acids – Omega-6
  • 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
fatty acids omega 6101
Fatty Acids – Omega-6
  • Arachadonic acid (20:4n-6)
    • Essential for cats
  • Other sources rich in omega-6’s
    • Corn oil
    • Safflower oil
    • Soybean oil
    • Canola oil
fatty acids omega 6102
Fatty Acids – Omega-6
  • 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
fatty acids omega 6103
Fatty Acids – Omega-6
    • 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
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
milk thistle
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 thistle107
Milk Thistle
  • Components of Silymarin (all are flavonolignans)
      • silybin (silibinin) – MOST ACTIVE**
      • Isosilybin (isosilibinin)
      • silydianin (silidianin)
      • silycrystine (silicristin)
milk thistle108
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 thistle109
Milk Thistle

Dose

  • 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: some extracts are whole herb extracts

hard to dose these high enough to be effective

milk thistle110
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 thistle111
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 days
  • IV prep not readily available in the US
milk thistle112
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 thistle113
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 thistle114
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 such protection
milk thistle115
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 thistle116
Milk Thistle

Side Effects

  • Rare GI upset in people, dogs and cats
  • Rare allergic rash in people
milk thistle117
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)
s adenosyl l methionine same
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.
s adenosyl l methionine same120
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
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
same hepatic effects122
SAMe – Hepatic Effects

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

same hepatic effects123
SAMe – Hepatic Effects

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 hepatic effects124
SAMe – Hepatic Effects

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 icterus

same musculoskeletal effects
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
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 - 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 quality control128
SAMe - Quality Control
  • 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 quality control129
SAMe - Quality Control
  • SAMe comes in different forms, according to the stabilizer used
    • Tosylate
    • disulfate tosylate
    • disulfate ditosylate
    • 1,4-butanedisulfonate (Actimet™)
same quality control130
SAMe - Quality Control

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
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