Published on November 17, 2007
Slide1: Welcome to Expo West What is Arthritis?: What is Arthritis? There are 127 different kinds of arthritis! Osteoarthritis: progressive degeneration of joint cartilage. Minor degree of inflammation. Rheumatoid arthritis: Severe inflammation that involves many joints and moves beyond musculoskeletal system. Gout: Very painful form of arthritis characterized by the formation of uric acid crystals and severe inflammation. Slide3: 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 Osteoarthritis: Osteoarthritis Clinical Symptoms: mild early-morning stiffness, pain that worsens with joint use, and loss of joint function Clinical Signs: local tenderness, soft tissue swelling, joint crepitus, bony swelling, restricted mobility, Heberden's nodes, and other signs of degenerative loss of articular cartilage X-Ray Findings: narrowed joint space, osteophytes, increased density of subchondral bone, subchondral sclerosis, bony cysts, soft tissue swelling, and periarticular swelling Multifactorial Etiology of Osteoarthritis: Multifactorial Etiology of Osteoarthritis Age-related changes in collagen matrix repair Hypermobility/joint instability Hormonal and sex factors Altered biochemistry and nutritional status Genetic predisposition Inflammation Fractures and mechanical damage Acromegaly Others Natural Approach to OsteoarthritisFocus on Physiology: Natural Approach to Osteoarthritis Focus on Physiology Reduce stress on joints Achieve ideal body weight Engage in regular exercise Health promoting diet Supply nutrients essential to joint function Promote cartilage repair Foundational Supplements: Foundational Supplements High Potency Multiple High Potency Greens Drink Pharmaceutical Grade Fish Oil 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). Mixtures of proteolytic enzymes Clinically proven, old-time therapy for inflammation. MicroLactin Highly purified mixture of milk peptides derived from hyper-immunized cows. Excellent documentation. Celandrin® Patented mix of cetylated, esterifed fatty acids. Fast-acting natural approach to inflammation. Excellent results with either oral or topical application. 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 Slide12: Human Cell Membrane Fatty Acid Metabolism: Fatty Acid Metabolism Slide14: Cell Membrane Phospholipids Arachidonic Acid Prostaglandin H2 Thromboxane A2 Prostaglandin E2 Prostaglandin D2 Prostacyclin (PGI2) Prostaglandin F2α Phospholipase A2 Cyclooxygenase isomerase TXA2 synthase PGI2 synthase reductase COX -1 - constitutively expressed COX -2 - inducible Slide15: 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 Slide16: Cox-1 vs. Cox-2 What the drug companies wanted us to believe. Arachidonic acid COX-2 “Inducible” Bad Prostaglandins Inflammation Pain Fever Slide17: Cox-1 vs. Cox-2 The reality. Arachidonic acid COX-2 “Inducible” Prostaglandins Pathological Physiological Inflammation Pain Fever Renal function Vascular Tissue repair Metabolic Pathways of Arachadonic Acid: Metabolic Pathways of Arachadonic Acid Membrane Phospholipids ARACHIDONIC ACID Prostaglandin H2 COX Thromboxane A2 Platelet Aggregation Vasoconstriction Prostacyclin Platelet Aggregation Vasodilation Thromboxane A2 vs. Prostacyclin: ARACHIDONIC ACID Platelet TXA2 Endothelial PGI2 (Prostacyclin) Vasoconstriction Platelet Aggregation Vasodilation Anti-Platelet Aggregation COX -1 COX -2 Thromboxane A2 vs. Prostacyclin Slide20: 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 Slide21: 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 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 Celadrin Cream & Osteoarthritis : Celadrin Cream & Osteoarthritis University of Connecticut 40 patients with osteoarthritis of the knee Topical application of Celadrin cream twice daily morning and night. Randomly assigned, placebo controlled, double-blind trial Tests were performed at baseline, once at 30 minutes and 30 days after treatment Range of motion, getting up and down from a chair, step down and extended reach were measured Compliance was 100% for both treatment and placebo groups. No side effects were noted. No arthritis drugs only lifesaving drugs Improvement on all parameters tested but especially in stair climbing and the ability to rise from a chair was substantial at 30 minutes Only treatment group had significant difference at T2 and T3 Journal of Rheumatology 2004, April 3(4):767-774. Celadrin Capsules & Osteoarthritis: Celadrin Capsules & Osteoarthritis 64 patients with osteoarthritis of the knee Evaluated for knee range of motion and function at baseline, day 30 and day 68 Randomized, double-blind, placebo controlled trial After 68 days, patients treated with soft gel Celadrin exhibited significant increase in knee flexing compared to placebo. Patient responses to pain, discomfort, walking distances and physical function indicated a significant shift towards functional improvement in the Celadrin group with OA of the knee compared to a modest improvement in the placebo group. 58% of Celadrin group had a reduction in pain Mechanism of action thought to be inhibition of 5-lypoxygenase pathway Journal of Rheumatology 2002 Aug; 29(8):1708-1712 Celadrin Cream & Psoriasis : Celadrin Cream & Psoriasis Double-blind, placebo controlled trial Dermatologist assigned an initial severity score for each patient using a 6 point scale (0=no psoriasis; 5=significant psoriasis). Evaluation included skin scales, patchiness, raised skin, redness, dryness and cracks. Cream was applied twice per day morning and night Each participant was evaluated at 7 and 14 days Measurable improvement was noted in all symptoms Some patients had reached a plateau in their current treatments and after 14 days of topical Celadrin application had marked improvement Anti-inflammatory benefits for skin extend to wrinkle reduction and elimination Mechanism of action thought to be inhibition of 5-lypoxygenase pathway Third party pilot trial performed by Life Management Group Celadrin Cream & Wrinkles : Celadrin Cream & Wrinkles 28 subjects between the ages of 25 and 65 average age 45 Washout period of 10 days where no moisturizing cream was used. No change in diet only a request to drink water and limit sun exposure. Cream was applied twice per day morning and night for 21 days Likert-type scale was used where the changes in skin wrinkling were noted. Each participant was evaluated after 21days of application. Measurable improvement was noted in all areas by both the subject and dermatologist Anti-inflammatory benefits for skin extend to wrinkle reduction and elimination An increase in skin permeability, improvement in roughness and thickening of the skin and it was found to be firmer and better hydrated. Third party pilot trial performed by Life Management Group, participants were staff and faculty of the University of California. Celadrin Capsules & Osteoarthritis in Dogs : Celadrin Capsules & Osteoarthritis in Dogs 20% or 53 million dogs in the U.S have osteoarthritis Standard treatments are similar to humans including NSAIDS, aspirin or acetaminophen. Side effects in animals include ulcer, diarrhea and vomiting among others. 24 dogs completed the study Dogs were evaluated prior to and 30 days after supplementation with Celadrin in a dose of 2 dog chews per 20 lbs (150mg per). 75% of owners said pets were happier, had an improved temperament, and were more energetic Vet reported improved gait and stair climbing after 30 days of supplementation Celadrin & Glucosamine : Celadrin & Glucosamine Celadrin is effective at halting the joint-damaging inflammatory process. Glucosamine can repair damage already done to affected joints. Celadrin works by providing continuous lubrication and allowing the cell membrane to repel inflammatory messengers Celadrin stops the cascade of inflammation and the assaults on the membrane, which cause stiffness. The dual action of Celadrin and glucosamine provides rapid joint cushioning, quickly alleviating inflammation, building cartilage and restoring the entire joint area. Excellent results have been reported by those individuals with OA and RA who have adopted the combination treatment of Celadrin and glucosamine. Mechanism of Action : Mechanism of Action Celadrin inhibits inflammation in endothelial cells (thin cells that line the inside of some body cavities). Celadrin reduces the production of the immune factor IL-6 and controls other immune factors responsible for inflammation. Celadrin plays a role in the lubrication of affected joints. Celadrin’s special fatty acids have been shown to reduce skin inflammation, while providing an emollient effect at the site of psoriasis. Celadrin also works by inhibiting arachidonic acid, one of the main promoters of the inflammatory cascade of immune factors, by inhibiting 5-lipoxygenase — another mediator of inflammation. It may also alter cellular membranes, protecting them from the action of inflammatory immune messengers. Slide30: Toxicology and toxicity studies show Celadrin to be exceptionally safe Celadrin is comprised of special fatty acids known to be very safe There have been no reported side effects in any study to date. Participants in the study continued their heart medications without any interactions. Safety of Celadrin Slide31: Visit www.celadrin.com for more information.