Agenda: Agenda Inflammation: Definition and significance
Is the presence of a “leaky gut” a major contributor to inflammation
Dietary strategies to reduce inflammation
NSAIDs: Actions and side effects
Highlight on natural anti-inflammatories
Celadrin, MicroLactin, Proteolytic Enzymes
Quick recap For my slides, go to www.doctormurray.com
What is Inflammation?: What is Inflammation? Classic definition, presence of the following five factors:
Redness (rubor)
Heat (calor)
Swelling (tumor)
Pain (dolor)
Dysfunction For my slides, go to www.doctormurray.com
“Silent Inflammation”: “Silent Inflammation” A complex scenario that is an underlying factor in many chronic degenerative diseases.
Mediated by:
Oxidants, pro-oxidants, and antioxidants
Vascular lining
Eicosanoids
Prostaglandins, thromboxanes, leukotrienes, etc.
Immune system
Slide4: Inflammation Cancer Arthritis Atherosclerosis Alzheimer’s Colitis Psoriasis Infection Diabetes Chronic inflammation plays a role in many disease conditions Eczema For my slides, go to www.doctormurray.com
C-Reactive Protein : C-Reactive Protein C-reactive protein is produced by the liver during an inflammatory response.
Those with CRP levels above 3.0 mg/L have a risk of heart attack or stroke three to eight times higher than the risk of those with a reading of less than 0.5 mg/L.
High CRP is found in those with the most severe forms of macular degeneration
Those persons with high CRP have triple the risk of developing colon cancer
Those persons with high CRP have 4 times the risk of developing Type-2 diabetes
Less than 0.5 mg/L – ideal
0.5 to 1.0 - safe
1.0 mg/L to 3.0 mg/L – danger
>3.0 - Extreme danger
Natural Approach to Inflammation FOCUS ON PHYSIOLOGY: Natural Approach to Inflammation FOCUS ON PHYSIOLOGY Identify underlying factors
Lifestyle factors
Dietary factors
Supplementation strategies For my slides, go to www.doctormurray.com
Examples of underlying factors that contribute to “silent inflammation”: Examples of underlying factors that contribute to “silent inflammation” Increased toxin exposure
Food allergies
Presence of a “leaky gut”
Chronic infections
Genetic predisposition
Insulin resistance
Slide8: Leaky gut syndrome can result in : “Leaky Gut” Food hypersensitivities
Chemical sensitivity
Fatigue / lethargy
Sleep disturbances
Hyperactivity / Irritability
Inattentiveness / poor concentration
Memory problems
Mood swings
Muscle or joint pain Cancer
Psoriasis
Liver disease
Causes of increased intestinal permeability (“leaky gut”): Causes of increased intestinal permeability (“leaky gut”) Food allergies or intolerances
direct irritation of the intestinal cells
immune system damage leading to overgrowth of harmful microbes
Antibiotics
kills the layer of friendly bacteria in the mucus layer covering the intestinal cells
promotes the growth of antibiotic resistant bacteria, fungi and protozoa
Causes of increased intestinal permeability (“leaky gut”) cont.: Causes of increased intestinal permeability (“leaky gut”) cont. High sugar intake
Overeating
Altered fats (trans fatty acids, lipid peroxides)
Excess alcohol
Causes of increased intestinal permeability (“leaky gut”) cont.: Causes of increased intestinal permeability (“leaky gut”) cont. Nutritional deficiencies.
Poor digestion and absorption.
Overgrowth of harmful microbes in the small and large intestine.
What makes RevitalX so effective in healing the Leaky Gut?: What makes RevitalX so effective in healing the Leaky Gut? Extremely low allergy potential
High quality, hypoallergenic vegetable protein
Enriched with glutamine and other “gut-critical” nutrients
High in soluble fiber
Rich in phytochemicals that reduce inflammation and promote healing
Traditional Detoxification Programs: Traditional Detoxification Programs Loss of lean body mass
Auto-intoxication – increased circulation of toxins without proper nutritional support for efficient excretion
What is a “healing crisis”?
Many people end up more exhausted and increasingly hypersensitive
A quick way to experience a leaky gut?
Effective Detoxification Requires an Unbroken Chain of Events: Effective Detoxification Requires an Unbroken Chain of Events
Indications for continued use: Indications for continued use RevitalX
Food allergies
Inflammatory bowel disease
Irritation or ulceration of GI
Psoriasis
Leaky gut
Candidiasis
Fibromyalgia, CFS, MCS DetoxiTech
Chronic exposure to environmental toxins
Heavy metal toxicity
Hepatitis
Impaired liver function
Fibromyalgia, CFS, MCS
Key Lifestyle Strategies to Reduce Inflammation : Key Lifestyle Strategies to Reduce Inflammation Don’t Smoke!!!
Develop a positive mental attitude.
Negative emotions cripple the immune response.
Depression reduces activity of DNA repair mechanisms.
Deal with stress effectively.
Regular exposure to stress actually reduces cancer risk
Get enough sleep each night.
Follow a regular exercise program.
Do not drink excessive amounts of alcohol.
Laugh often!!!
Key Dietary Strategies to Reduce Inflammation : Key Dietary Strategies to Reduce Inflammation Identify and eliminate food allergies.
Eat a “rainbow” assortment of fruits and vegetables.
Reduce exposure to pesticides, and eat to enhance detoxification reactions and elimination
Reduce the intake of meat and other animal foods.
Eat the right types of fats .
Eat to improve insulin sensitivity, eat a low glycemic load diet.
Keep salt intake low, potassium intake high.
Dietary Therapy in Rheumatoid Arthritis: Dietary Therapy in Rheumatoid Arthritis Summary:
The treatment group began by fasting for 7-10 days. Dietary intake during the fast consisted of herbal teas, garlic, vegetable broth, decoction of potatoes and parsley and the following juices: carrots, beets, and celery. After the fast the patients followed a vegetarian diet with careful food reintroduction. Long-term follow-up indicated "a substantial reduction in disease activity" in many patients. Improvements correlated with changes in gut flora.
Scand J Rheumatol. 30(1):1-10, 2001; Clinical Rheumatology 13:475-82, 1994; Lancet 338:899-902, 1991
Dietary Therapy in Rheumatoid Arthritis: Dietary Therapy in Rheumatoid Arthritis SUMMARY
The dietary treatment group followed an anti-inflammatory diet (AID) providing an arachidonic acid intake of less than 90 mg/day. Patients in both groups were allocated to receive placebo or fish oil capsules (30 mg/kg body weight) for 3 months in a double-blind crossover study. In AID patients, the numbers of tender and swollen joints decreased by 14% during placebo treatment. In AID patients, fish oil led to a significant reduction in the numbers of tender (28% vs 11%) and swollen (34% vs 22%) joints (P<0.01).
CONCLUSION: A diet low in arachidonic acid ameliorates clinical signs of inflammation in patients with RA and augments the beneficial effect of fish oil supplementation.
Rheumatol Int. 2003 Jan;23(1):27-36.
Superfoods to decrease inflammation: Superfoods to decrease inflammation BEANS
Pinto, navy, Great Northern, lima, garbanzo(chickpeas), black beans, lentils, green beans, sugar snap peas, and green peas
FLAVONOID-RICH BERRIES
Purple grapes, cranberries, boysenberries, raspberries, strawberries, currants, blackberries, cherries, and all other varieties of fresh, frozen, or dried berries
CRUCIFEROUS VEGETABLES
Brussel sprouts, cabbage, kale, turnips, cauliflower, collards, bok choy, mustard green, Swiss chard
LOW GLUTEN WHOLE GRAINS
Brown rice, barley, buckwheat, millet, amaranth, quinoa, triticale, kamut, yellow corn, wild rice, spelt, couscous
CITRUS FRUITS
Lemons, white, and pink grapefruit, kumquats, tangerines, limes
HIGH-CAROTENE VEGETABLES
Pumpkins, carrots, butternut squash, sweet potatoes, orange bell peppers
Superfoods to decrease inflammation: Superfoods to decrease inflammation SALMON
Wild Alaskan salmon
SOY
Tofu, soymilk, soy nuts, edamame, tempeh, miso
GREEN LEAFY VEGETABLES
Kale, collard, Swiss chard, mustard greens, turnip greens, bok choy, romaine lettuce LYCOPENE SOURCES
Tomatoes, watermelon, pink grapefruit, Japanese persimmons, red-fleshed papaya, strawberry, guava
NUTS AND SEEDS
Walnuts, almonds, pistachios, macadamia nuts, pecans, hazelnuts cashews; sesame pumpkin and sunflower seeds
HERBS and SPICES
Turmeric (curcumin), capsicum, ginger, garlic, onions, dill, rosemary, etc.
Avoid: Avoid Trans-fatty acids (VERY BAD!)
Intake of arachidonic acid (meat and dairy)
High intake of omega-6 fatty acids
Corn oil, cottonseed oil, grapeseed oil, peanut oil, safflower oil, sesame oil, soybean oil, sunflower oil
Margarine
Fried foods and high saturated fats
Any product with long shelf life (crackers, pastries, chips)
Trans Fatty Acids are Harmful: Detriments to Human Health: Trans Fatty Acids are Harmful: Detriments to Human Health Lowers “good” HDL Cholesterol
Raises atherogenic lipoprotein (a)
Lowers volume and quality of breast milk
Correlates to low birth weight in infants
Interferes with gestation
Negatively affects the immune system
Increases level of abnormal sperm
Alters cell membrane function and structure
Causes alteration in adipose cell size and fatty acid composition
Escalates the problem of essential fatty acid deficiency
Potentiates free radical formation
Causes insulin insensitivity
Promote inflammation
Functions of EFAs: Functions of EFAs Membrane Functions and Integrity
Regulation of Cell Processes
Biosynthesis of Eicosanoids
Every cell in the body uses EFAs...: Every cell in the body uses EFAs... The body is made out of cells
Cells are made out of membranes
Membranes are made out of fats
Good fat builds good membranes cell cell membrane cell membrane fatty acids
Cell membrane consequences of fatty acid structure: Cell membrane consequences of fatty acid structure Saturated and trans fatty acid chains pack tightly and form more rigid membranes.
Unsaturated chains bend and pack in a less ordered way, with greater potential for motion, elasticity, and function.
Eicosanoids: Eicosanoids Hormone-like compounds that impact virtually every system in the body
Examples:
prostaglandins (series 1, 2, and 3)
thromboxanes (TXs)
leukotrienes (LTs)
hydroxy fatty acids
Eicosanoids mediate: Eicosanoids mediate Allergic response
Blood clotting and platelet aggregation
Blood pressure
Gastrointestinal function and secretions
Heart function
Inflammation, pain, and swelling
Kidney function and fluid balance
Nerve transmission
Steroid production and hormone synthesis
The Three Eicosanoid Families: The Three Eicosanoid Families From EPA-PGE3
Anti-inflammatory
Anti-aggregatory
Dilate blood vessels From GLA- PGE1
Strong anti-inflammatory
Dilate blood vessels
Reduce blood clotting From AA-PGE2
Strong pro-inflammatory
Constrict blood vessels
Increase blood clotting Very beneficial potentially harmful very beneficial
Effects of Eicosanoid Imbalance: Effects of Eicosanoid Imbalance Inflammation
Blood vessel constriction
Increased allergic response
Impaired immune response
Abnormal cell function
Disease:
arthritis, diabetic nerve damage, heart attacks, high blood pressure, atherosclerosis, allergies, skin inflammations, and cancer
Fatty Acid Metabolism: Fatty Acid Metabolism
Inhibitors of Delta 6 Desaturase: Inhibitors of Delta 6 Desaturase Diabetes
Viral infection
Atopic disease
Cholesterol
Stress hormones
Corticosteroids
Catecholamines
Aging Alcohol
Smoking
Arachidonic acid
Saturated fat
Trans fatty acids
Nutrient deficiency
Zinc, B6, vitamin C
Long Chain Omega-3 Fatty Acids: Major Health Benefits: Long Chain Omega-3 Fatty Acids: Major Health Benefits Cancer & Cardiovascular disease
Neurological diseases
Depression, OCD, ADD
Alzheimer’s disease
Inflammatory diseases
Psoriasis, eczema
Inflammatory bowel disease (IBD)
Rheumatoid arthritis
Conner WE. Importance of n-3 fatty acids in health and disease. AJCN 2000;72:1241
What is “pharmaceutical grade?”: What is “pharmaceutical grade?” Proposed criteria:
Manufactured in a certified GMP facility approved for pharmaceutical products or by the USP.
Manufactured according to pharmaceutical standards that include quality control steps to insure purity and potency.
Must provide at least a 60% concentration of the most active long-chain omega-3 fatty acids (EPA and DHA).
Ratio of omega-3 fatty acids to arachidonic acid must be greater than 50:1.
How much do I take?: How much do I take? For general health and prevention of cardiovascular disease:
1,000 mg of EPA/DHA daily
For other indications, especially in cancer and inflammatory states:
3,000 mg EPA/DHA daily
NSAIDs – New Sorts of Aspirin in Disguise: NSAIDs – New Sorts of Aspirin in Disguise Classes
Butypyrazolidines (eg.,kebuzone, mofebutazone)
Acetic acid & acenamide derivatives (eg.,Arthrotec®, diclofenac)
Oxicams (eg.,meloxicam, piroxicam)
Propionic acid derivatives (eg.,oxaprozin, ibuprofen, naproxen)
Fenamates (eg.,mefenamic acid)
Cox-2 inhibitors (eg.,celecoxib, rofecoxib)
Side Effects
Gastric irritation and ulcers
Kidney and liver damage
Allergic reactions, tinnitus, easy bleeding and bruising, and various minor disturbances
Inhibition of cartilage repair and promotion of osteoarthritis
Slide37: Cyclooxygenase (COX) Two isoenzymes
Cyclooxygenase-1 (COX 1): constitutive
- physiologic production of PG in gastric mucosa,
endothelium, platelet, kidney
Cyclooxygenase-2 (COX 2): inducible
- induced by mitogen, cytokine, endotoxin
- promotes synthesis of pro-inflammatory prostaglandins
Slide38: Cox-1 vs. Cox-2
What the drug companies wanted us to believe. Arachidonic acid COX-2
“Inducible” Bad Prostaglandins Inflammation
Pain
Fever
Slide39: Cox-1 vs. Cox-2
The reality. Arachidonic acid COX-2
“Inducible” Prostaglandins
Pathological Physiological Inflammation
Pain
Fever Renal function
Vascular
Tissue repair
Slide40: Aspirin COX-1 Thromboxane Prostacyclin Thromboxane COX-2 inhibitors Decreased CV events Prostacyclin Increased CV events COX-2 Why do Cox-2 inhibitors increase risk for heart disease?
#1. Because they adversely effect the ratio of thromboxane to prostacyclin
Slide41: Why do Cox-2 inhibitors increase risk for heart disease?
#2. Because they adversely effect resolvin levels Resolvin E1 is a newly discovered physiological derivative of eicosapentaenoic acid (EPA) that inhibits both the migration of inflammatory cells to sites of inflammation and the turning on of other inflammatory cells.
The synthesis of Resolvin E1 requires Cox-2.
Therefore, inhibition of vascular COX-2 blocks the synthesis of Resolvin E1 in addition to blocking the beneficial PGI3 form of prostacyclin.
Journal of Experimental Medicine 2005;201:713-722
Slide42: Osteoarthritis - The most common form of arthritis 40 Million Americans suffer from OA
75% of Americans over 50 have OA
Symptoms tend to be more severe in women
Drug sales of NSAIDs in the US for OA exceed $6.6 billion
Sales of GS and CS rank #3 in supplement sales (behind multivitamins and calcium)
OVER 400,000 joint replacements each each in the U.S. due to OA
Natural Products for Osteoarthritis: Natural Products for Osteoarthritis Glucosamine sulfate
Most useful, best clinical documentation, and cost effective
Long-term studies now document significant clinical benefit
Meta-analysis shows structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis Arch Intern Med. 2003;163:1515-22
Chondroitin sulfate
Clinical effectiveness documented in 9 double-blind clinical trials
Controversies remain over quality control issues and mechanism of action
MSM
Sulfur critically important to cartilage formation, structure and integrity
MSM + Glucosamine more effective than Glucosamine alone Clinical Drug Investigation, 2004;24:353-363.
Natural Products for Osteoarthritis (cont.): Natural Products for Osteoarthritis (cont.) Niacinamide
Under utilized, but highly effective therapy (3,000 mg daily).
Celandrin®
Patented mix of cetylated, esterifed fatty acids.
Fast-acting natural approach to inflammation.
Excellent results with either oral or topical application.
MicroLactin
Highly purified mixture of milk peptides derived from hyper-immunized cows. Excellent documentation.
Mixtures of proteolytic enzymes
Clinically proven, old-time therapy for inflammation.
What is Celadrin ® : Celadrin® is a patented combination of special cetylated, esterifed fatty acids.
Celadrin® reduces inflammation and pain quickly with no side effects. Available in cream and capsule form.
Celadrin® has been shown to be effective in double-blind clinical trials published in peer-reviewed medical journals.
Celadrin® has been shown to improve osteoarthritis and psoriasis; and lower CRP.
Celadrin® applied topically works in just 30 minutes with significant improvement. What is Celadrin ®
How does Celadrin Work?: How does Celadrin Work? Possible mechanisms:
Stabilization of phospholipid membrane pool
Structural
Reduces the availability of fatty acids for action by PLA-2
Reduces lipid peroxidation and induction of non-enzymatic cleaving of phospholipids
Enzymatic
Directly inhibits PLA-2
Indirectly inhibits PLA-1 via inhibition of cytokines
Modulation of Cox-1 and Cox-2 activity
Inhibition of lipoxygenase
Reduces formation of isoprostanes
Slide47: World Class Clinical Trial Pedigree 32 Clinical Trials Performed to date
17 Published Clinical Trials
800+ Patients Studied (MicroLactin group only)
Ohio Survey – 35 years with 8,000 case histories
Indications (patient groups) studied:
Rheumatoid & Osteoarthritis
Cholesterol
Hypertension
Osteoarthritis Study - Treatment Effect: Osteoarthritis Study - Treatment Effect MicroLactin™ has 60% greater Treatment Effect than Glucosamine
Mechanism of Action: Mechanism of Action The inflammation seen with osteoarthritis is in part neutrophil mediated.
MicroLactin produces a suppression of neutrophil migration from vascular space and through vascular “tight junctions” (75%)
MicroLactin™ Osteoarthritis Study revealed an increase in the absolute serum neutrophil count.
Mechanism of Action: Mechanism of Action
Osteoarthritis Study – Serum Neutrophils: Osteoarthritis Study – Serum Neutrophils
Proteolytic Enzymes: Proteolytic Enzymes Pancreatin – from hog pancreas
Chymotrypsin and trypsin
Papain – from unripe papaya
Bromelain – from pineapple stem
Fungal proteases
Protease I, II, and III
Serratia peptidase (Peptizyme SP™)
Proteolytic Enzymes: Proteolytic Enzymes How are they different??
Site of action and mechanisms
Methods of potency and purity
Activity in different pH environments
Clinical documentation of effectiveness
Proteolytic Enzymes: Proteolytic Enzymes Serine Proteases Cysteine Proteases
Trypsin Bromelain
Chymotrypsin Papain
Serratia peptidase
Fungal peptidases
Proteolytic Enzymes Effects on aspects of inflammation: Proteolytic Enzymes Effects on aspects of inflammation (B=Bromelain, P=Papain, T/C=Trypsin & Chymotrypsin, SP=Serratia Peptidase)
B P T/C SP
Depletion of kininogen + - - -
Inhibiting release of bradykinin - - - +
Inhibiting release of histamine - - + +
Promotion of fibrinolysis + + + +++
Alpha-macroglobulin binding + + ++ +++
Reduction in inflammatory cytokines + + ++ +++
Modulation of prostaglandins + - - -
Blocking of adhesion molecules + + + +
Proteolytic Enzymes Effects on immune complexes: Proteolytic Enzymes Effects on immune complexes (B=Bromelain, P=Papain, T/C=Trypsin & Chymotrypsin, SP=Serratia Peptidase, IC=Immune Complex)
B P T/C SP
Reduction of IC + + - +
Inhibition of IC-formation + + - +
Reduction of C1q-binding - + + +
Examples of Immune Complex/Autoimmune Diseases: Examples of Immune Complex/Autoimmune Diseases Rheumatoid arthritis
Multiple sclerosis
Lupus
Grave’s disease
Scleroderma
AIDS
Slide58: Proteolytic Enzymes Benefits to the patient with autoimmune disease:
Promotes fibrinolysis
Reduces inflammatory cytokines
Reduces circulating immune complexes
Increases antioxidant enzymes (SOD, catalase, and glutathione peroxidase)
Proteolytic Enzymes Clinical study in rheumatoid arthritis: Proteolytic Enzymes Clinical study in rheumatoid arthritis Summary:
In a 6 month study, 156 patients with RA being treated with MTX and NSAIDs were randomly divided into two groups: a control group and a group assigned to receive enzymes. Significant improvements were noted in both clinical and laboratory assessments.
Int J Immunotherapy 1997;13:85-91.
Proteolytic Enzymes Results from a double-blind study in RA: Proteolytic Enzymes Results from a double-blind study in RA Parameter Control Enzyme
Morning stiffness (min.) 87.3 54.8
Richie index, points 20.7 15.7
Circulating immune complexes 88.1 55.6
Erythrocyte sedimentation rate 29.7 25.8
Rheumatoid factor titer 98.5 55.6 Typical dosage: 30 to 60 mg daily
What natural product to use?: What natural product to use? For silent inflammation
Always build a strong foundation:
High potency multiple, good greens drink, pharmaceutical grade fish oil (1,000 mg of EPA/DHA daily)
7-Day Total Nutritional Cleansing Program
For osteoarthritis
Begin with GS and Celadrin (oral and topical)
If less than full response add MSM, then Microlactin
For severe inflammatory conditions (e.g., RA, psoriasis, IBD)
RevitalX
Increase EPA/DHA to 3 grams daily
Curcumin – 200 to 400 mg three times daily
Proteolytic enzyme mixture
Recap of Key Points: Recap of Key Points Silent inflammation is an underlying factor in many chronic degenerative diseases
Natural treatments for inflammation offer significant advantages
Safety, effectiveness, and cost
Effective strategies to reduce inflammation:
Consume an anti-inflammatory diet
Utilize pharmaceutical grade fish oil
Use appropriate natural products
Enhance endothelial function
For my slides, go to www.doctormurray.com
Why is the Future Bright for the Natural Product Industry?: Why is the Future Bright for the Natural Product Industry? Growing need for real solutions
Aging population
Continued rise in diet related diseases
Truth will prevail
New and exciting products
Best from nature is yet to come
Effective consumer education
Common Characteristics of Successful Retailers: Common Characteristics of Successful Retailers HIGH VALUES!!
Credible
Passionate
Educated
Dedicated
Positive and adaptable
Effective communication
Strong sense of mission
5 Keys to Life : 5 Keys to Life Make a spiritual connection
Take personal responsibility
Develop a positive attitude
Find your passion
Create a vehicle for making a difference in the lives of others