Transcript Name of presentation

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
– 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 being
NOT Nutraceuticals
•Whole herbs
•Unprocessed (raw) natural products
•Cartilage powders
•Applied topically or injected
Four Nutraceuticals
Your 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
•USP
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
•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
•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 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
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 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
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 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 Sep
McNamara PS ; Barr SC ; Erb HN
Hematologic, Hemostatic, and Biochemical Effects in Cats
Receiving an Oral Chondroprotective Agent for 30 Days
Vet 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
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 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 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
•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 – Chondroitin
•2 types of chondroitin sulfate
•Chondroitin-4-sulfate - mammalian
•Chondroitin-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
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-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
•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
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 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 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
•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
•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 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 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
• 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
•No studies in dogs and cats
•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 – ASU
Avocado 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 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
•No studies in dogs and cats
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.
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 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 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 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 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 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 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.
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
•Perna
•GAGs
•Etodolac
•Boswellia
•Cosequin
•Pentosan
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 - 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 - 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
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) oil
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-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-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-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-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-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-3
•Renal effects
•Slows progression of glomerular disease in
people
•Undefined effect on chronic tubular renal failure
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-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-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-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-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
•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-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-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-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
•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 omega3’s needed for therapeutic effect
•Presence of excessive omega-3’s can suppress
omega-6 production and vice versa
????
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 Thistle
Dose
• Dried herb: 15-20mg/lb SID (1.5-3%
silymarin)
• Concentrated extract: 2-5 mg/lb BID (7080%)
• Alcohol concentrated extract: 2-5 mg/lb
BID-TID
(70-80%)
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
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 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
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.
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
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 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 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
•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 - 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 Control
•SAMe comes in different forms, according to the
stabilizer used
•Tosylate
•disulfate tosylate
•disulfate ditosylate
•1,4-butanedisulfonate (Actimet™)
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
•GI upset mentioned previously
•Enteric coating can help
•Give with food if necessary
•No toxicity every reported – no LD50 can be reached