Dr. Joseph Cyr, M.D., L.M.C.C., practiced medicine for over 48 years and specialized in surgery for 25 years In different cities of Canada and in the U.S. namely Texas, California and Maine. He is now based in the U.S. where he is a member of the American College for Advancement in Medicine and still seeing patients. Since 1993, Dr. Cyr has witnessed several beneficial effects of different kinds of dietary supplements including liquid cartilage extract with the patients he is following up. Most commonly asked questions were collected from a HOPE popular survey about shark cartilage products and were addressed to Dr. Cyr.

1) HOPE: What is so specific to cartilage? Is there anything magic about shark cartilage?

DR. CYR: This is a very relevant question. My answer to that will be twofold. First, what is cartilage? Cartilage is a very specialized tissue found in different animal species. In adult mammals, cartilage represents less than 1% of total body weight. From a functional point of view, cartilage is what constitutes the whitish cushion that coats bone extremities. Cartilage thus plays a primordial protective role during the movement of the articulation. Cartilage is avascular, meaning that it is deprived of blood vessels. It consists mainly of collagen fibers intermingled mannered like a rope.

This arrangement of collagen fibers provides the strength and resiliency features of cartilage. Cartilage is known to contain two major biological activities:

antiangiogenic agents that prevent formation of blood vessels and inhibitors of collagenases, enzymes that digest collagen fibers. The high content of antiangiogenic agents in cartilage prompted its utilization as an ideal source of antiangiogenic molecules that can be extracted in a liquid form.

In sharks, cartilage makes up all the skeletal structures. I do not believe, however, that there is anything specific to shark in term of antiangiogenic activity. In fact, scientific literature reports molecules having antiangiogenic activity that were isolated from shark as well as from bovine species. The main reason why shark was chosen as a source resides in the fact that cartilage represents approximately 6% to 8% of its body weight. Sharks therefore represent an abundant source of cartilage in the biomass.

2) HOPE: There is a popular belief that "sharks don't get cancer". Is it related to the antiangiogenic characteristics of its cartilage?

DR. CYR: It is true that sharks have a unique ability to resist diseases and also have a low incidence of tumors. Sharks are among the oldest survivors on earth suggesting they are endowed with a very distinctive physiology. Whether or not the antiangiogenic activity of their cartilage is involved is not known. However, it is likely that the highly effective immune system of sharks plays a pivotal role in their overall health. In fact, several tissues of sharks are being investigated for their content in potentially therapeutic substances.

3) HOPE: The market of shark cartilage products seems to be overloaded by different brands of powders. What do the shark cartilage powders consist of?

DR. CYR: Most of the products on the market are powder preparations of shark cartilage. Depending upon the manufacturing method used, cartilage powder results from the drying of raw material using heat to evaporate the water that is naturally present in cartilage. .Then, the dry material is pulverized into powder, Cartilage powder can be sterilized by using

radiation or oxydizing gas, treatments potentially harmful to biological substances. Shark cartilage powder comes in bulk or in the form of capsules. Recommended daily doses for shark cartilage powder preparations can be up to 150 grams ( two hundred 750 mg capsules or more than a cup) for a 150 pound individual. Such quantities can represent up to 30 times the US recommended daily allowance in calcium.

4) HOPE: Is there alternatives to shark cartilage powders or other innovations commercially available?

DR. CYR: Yes. In fact, a Canadian company has developed a liquid extract isolated from cartilage. Liquid cartilage extract and cartilage powder are both derived from the same biological source which is shark cartilage. However, liquid cartilage extract greatly differs from powder preparations based on the manufacturing process. Liquid cartilage extract is prepared in a way by which substances always remains in their natural aqueous environment and are kept at low temperature conditions during the manufacturing process. No deleterious enzymatic or chemical treatments are used during the process. An ultrafiltration step is added to recuperate active fractions. The liquid nature of this extract allows filtration through a second set of sterile microporous membranes. On a physiological point of view, it is important to point out that liquid cartilage extract is low in calcium and contains substances that are water soluble readily assimilable by the organism.

5) HOPE: You mentioned that one of the features of cartilage is the presence of inhibitors of angiogenesis. What is exactly angiogenesis?

DR. CYR: Antiogenesis is the formation of new blood vessels from preexisting ones. It is a complex process during which several cellular and molecular mechanisms are involved. Briefly, an external signal - such as inflammation -will activate collagenases, special collagen-eating enzymes we have talked about earlier, to create a breach into the wall of a mature blood vessel. Endothelial cells -the main cellular component of blood vessels - will escape from that breach and lead the angiogeneses process. This newly formed "blood vessel bud" will grow and, along its path, will enlarge its diameter and form ramifications. Eventually, a new functional blood vessel network will be established allowing blood to transport oxygen and nutrients to tissues and cells in need. Antiangiogenic products have the ability to inhibit the process ofangiogenesis thus preventing unwanted formation of blood vessels,

6) HOPE: The liquid cartilage extract clearly seems more convenient to use but does it really contain antiangiogenic activity?

DR. CYR: The antiangiogenic activity of the liquid cartilage extract has been scientifically proven. The liquid cartilage extract was tested for its antiangiogenic activity using different established experimental models. The in vitro antiangiogenic activity was verified in the laboratory using the embryonic vascularization test, an improved variant of the CAM assay. In this test, blood vessels developing externally to a chick embryo and invading the yolk bringing nutrients to the embryo are used as experimental blood vessels. Deposition of a sample of the liquid cartilage extract on a specific area at the surface of the yolk results in an inhibition of blood vessel formation. This demonstrates that the liquid cartilage extract contains an antiangiogenic activity.

Furthermore, the bioavailibility of the antiangiogenic activity contained in the liquid cartilage extract was demonstrated in a human clinical trial. The liquid extract was administered orally to healthy volunteers on a daily basis fora period of 11 days. Quantities tested were 7ml and 21m1. In this study, an inert sponge was implanted subcutaneously and acted as a matrix for endothelial cell invasion within the sponge is indicative of an antiangiogenic activity. Results obtained in this trial revealed a statistically significant reduction of endothelial cell invasion within the subcutaneous sponge thereby demonstrating the bioavailibility of the antiangiogenic activity contained in the liquid cartilage extract after oral administration.

7) HOPE: Medical reports published in newspapers or specialized magazines often associate angiogenesis to diseases such as cancer and rheumatoid arthritis. Is angiogenesis an illness?

DR. CYR: Angiogenesis is not always linked to pathological conditions. In fact, angiogenesis is predominantly a normal physiological phenomenon which occurs in response to ovulation in adulthood. However, it is now well recognized that angiogenesis can also exacerbates several diseases currently termed as angiogenesis-dependant diseases. Approximately 20 angiogenesis-dependant diseases have been identified so far. The formation of new blood vessel is observed in such diseases as cancer, rheumatoid arthritis, in psoriasis and in a form of degenerative disease affecting retina in elderly. Angiogenesis is also closely linked to the etiology of hemangioma, hypertrophic scarring, keloids, warts, periodontitis, sclerodermia, neovascularization of corneal grafts and neovascular glaucoma. In those cases, angiogenesis is very often closely associated to the severity of the diseases. For instance, a tumor will grow not bigger than a few millimeters in diameter without the support of blood supply. Tumor cells, in need for nutrients and oxygen, will emit signals to trigger the angiogenic process and attracting blood vessel formation in the direction of the weakening tumor. Tumor angiogenesis will bring nutrients and oxygen to tumor cells thereby promoting tumor growth and metastasis.

8) HOPE: Since angiogenesis is so important for the progression of the so-called angiogenesis-dependant diseases, does the pharmaceutical industry put efforts in developing drugs capable of inhibiting angiogenesis?

DR. CYR: Pharmaceutical research in the field of angiogenesis inhibitors is very active. Several pharmaceutical companies have developed inhibitors ofangiogenesis and some of them are already being investigated in human clinical trials to verify their efficacy in angiogenesis-dependant disease. Interestingly, several of these products are derived from natural sources like fungi, bacteria, shark liver and shark cartilage. It is expected that angiogenesis inhibitors will be used as first line therapy in diseases such as solid tumors, rheumatoid arthritis, psoriasis and other pathologies complicated by the phenomenon of angiogenesis.

9) HOPE: What is the best quantity of liquid cartilage extract to be administered for in specific situations?

DR. CYR: This question is very appropriate and justified for users of the product In a healthy body, angiogenesis (formation of blood vessels) and angiogenesis inhibition (inhibition of blood vessel formation) phenomena exist within a constant equilibrium. This angiogenesis equilibrium, or homeostasis, is tightly controlled and strictly delimited. Dr .Judah Folkman has put forward an interesting theory to explain the body's balance between factors promoting angiogenesis and angiogenesis inhibitors. This delicate angiogenesis homeostasis is obligatory to fulfill the needs for blood vessel formation in response to physiological demands while preventing uncontrolled pathological angiogenesis. When the angiogenesis equilibrium gets disturbed, it is very often in favor of uncontrolled angiogenesis.

We have discussed previously about the bioavailibility of the antiangiogenic activity of the liquid cartilage extract after oral administration of 7ml or 21ml/day. Adding the liquid cartilage extract to your diet as per the recommended dose could thus help in replenish the pool of angiogenesis inhibitor factors and re-establish the angiogenesis equilibrium. It is also believed that the severity of any angiogenesis-dependant disease is linked in some ways to the degree of the angiogenesis disequilibrium. Appropriate doses can therefore be individualized according to the specific needs and adjusted depending upon health condition.

10)HOPE: What should someone expect from adding the liquid cartilage extract to its diet?

DR. CYR: Because of its proven biological activity and its bioavailibility, the liquid cartilage extract can benefit to individuals for which the angiogenesis homeostasis is perturbed. In doing so, individuals in needs provide their organism with the weapons that can help to fight against dehabilitating conditions. During years, I have been seeing patients using the liquid cartilage extract and have documented several clinical cases for which concrete benefits were obtained after oral administration of the liquid cartilage extract. Here are some of these experiences I would like to share:

Louise a 69 year old housekeeper, was diagnosed with an advanced pancreas cancer. The cancer evolved to a stage for which her medical oncologist was not anticipating efficacy from conventional chemotherapy. She was left with pain killers. Louise then turned to the liquid cartilage extract along with a healthy natural nutrition to assist pancreatic functions and regular exercise. At the end of August '97, a monitoring scan performed by her medical oncologist revealed no sign of the tumor. I talked to her recently and she 'is in good health and keeps on her new way of life.

Dave is a clerical worker in New Brunswick and is 47 years old. Three months ago, he was diagnosed with a prostate cancer. This revelation plunged Dave in a depression state. After sharing his

health concerns with friends and relatives, he decided to supplement his diet with the liquid cartilage extract and glandular extracts to enhance his thymus immune functions. Upon his most recent visit to my office, Dave advised me he was told by his medical oncologist that the tumor had shrunk. He could not believe the way he was feeling.

NOTICE TO THE READER

DR. CYR SAID: I BELIEVE IN THE SCIENTIFIC MEDICINE AND IN ALTERNATIVE THERAPIES. I DON`T TREAT CANCER; RATHER I RECOMMEND THAT MY PATIENTS, INCLUDING THOSE WITH CANCER. MULTIPLE SCLEROSIS, OR PARKINSON'S DISEASE-TAKE THE LIVE PROTEINS OF THYMUS, PANCREAS, LIVER, MESENCHYMES OR THE LIQUID SHARK CARTILAGE AS NUTRITIONAL SUPPORT, THESE FOOD SUPPLEMENTS DEFINITELY BRING UP A PERSON'S IMMUNITY. I ALWAYS MAINTAINED THAT IF YOU HAVE AN ELEVATED IMMUNITY YOU WON'T GET SERIOUS DISEASES.