What is Algonot, LLC?

Algonot, LLC is a company based in Sarasota, Florida, where science and natural remedies come together. This is why the company trademarked the slogan "Let Nature Ease Your Pain". The company was formed to produce and distribute dietary supplements based on the research of a distinguished group of physician scientists. You can learn more about the members of the Algonot Scientific Advisory Board by visiting the web site Algonot.com. Research is the cornerstone of everything the company does, and a portion of the profits will always be devoted to support more research. The Advisory Committee members are:

· Philip W. Askenase, M.D.-Yale University School of Medicine/Yale New Haven Hospital
· Jeffrey Gelfant, M.D.-Harvard Medical School/Massachusetts General Hospital
· Grannum R. Sant, M.D.-Tufts University School of Medicine/New England Medical Center
· Egilius Spierings, M.D., Ph.D.-Harvard Medical School/Brigham & Womens Hospital
· Theoharis C. Theoharides, Ph.D., M.D.-Tufts Univ. School of Medicine/New England Med. Center

What does Algonot mean?

The word Algonot comes from the ancient Greek word for pain Algos +not=no pain. This Greek word is found in the English word analgesic (an-alges-ic) which means a painkiller. The difference between Algonot and analgesic is that Algonot addresses and corrects the underlying problem that leads to pain, while analgesics reduce the pain temporarily.

How was Algonot-Plus developed?

Algonot-Plus was developed by Dr. Theoharis Theoharides. He received all his training at Yale University and is now a Professor of Pharmacology and Internal Medicine, at Tufts Medical School. Dr. Theoharides has also been the Clinical Pharmacologist of the Drug Formulary Commission continuously since 1986. Algonot-Plus is a natural, synergistic formula designed to block the advancement of arthritis, build cartilage, as well as reduce inflammation and swelling.

Formulations of glucosamine have been used in the last few years, but recent publications established its usefulness in osteoarthritis:

· McAlindon TE, LaValley MP, Gulin JP and Felson DT. Glucosamine and chondroitin for treatment of osteoarthritis. J Am Med Assn 283:1469-1475, 2000.

· Reginster JY, Droisy R, Rovati LC, Lee RL, Lejeune E, Bruyere O, Giavovelli G, Henrotin Y, Dacre JE and Gossett C. Long-term effects of glucosamine sulphate on osteoarthritis progression:a randomised, placebo-controlled clinical trial. Lancet 357:247-248, 2001.

However, no one knew how glucosamine and chondroitin worked until pioneering research at Tufts University showed that chondroitin blocked a unique cell of our immune system, called mast cell, from releasing toxic substances that cause inflammation and degrade the protective cartilage in the joints. Dr. Theoharides then set out to investigate what type of chondroitin would be best to use, whether we could combine it with other natural molecules that may inhibit inflammation and may increase the absorption of these molecules.

How momentous is the recent introduction of Algonot-Plus

This is the first natural formulation ever to combine three natural ingredients that individually, and in combination, reduce the symptoms and the underlying problem in areas of tissue stress, while also increasing their absorption so that they may reach the tissues where they act. The product was introduced this past July, after over two years worth of research, by a company formed by two individuals who benefited from our research and wished to contribute back by making this and other unique natural products available to the public. Algonot-Plus does the following:

· Blocks the chain reaction that advances inflammation
· Helps the body make new connective tissue, protective lining and cartilage
· Provides key protective molecules
· Reduces inflammation
· Increases absorption of all the active substances
· Provides important antioxidants

How will this product help people?

Algonot-Plus uniquely blocks, builds and relieves. It blocks inflammation and protective tissue destruction, it builds new connective tissue and relieves the pain associated with stiff, arthritic joints. As a result, Algonot-Plus has to be taken daily for at least three months in order to have sufficient time to address the underlying processes leading to arthritis and pain. The first benefit patients will notice is a reduction of pain, pressure and stiffness of their joints.

Who should take Algonot-Plus, and for what purpose?

The main condition for which Algonot-Plus was originally developed was osteoarthritis, the most common joint disease and, because of its high absorption of the natural anti-inflammatory quercetin, for the related condition, rheumatoid arthritis. However, Dr. Theoharides discovered that the same inflammatory process that destroys the cartilage in the joints also destroys the protective glycosaminoglycan (GAG) layer of the bladder resulting in interstitial cystitis (IC). IC is a syndrome that occurs primarily in women with symptoms of urinary frequency, urgency, nocturia and suprapubic/pelvic pain. The symptoms of IC create substantial psychological, social and emotional problems for affected patients, many of whom describe their pain as "migraine of the bladder." About 10% of IC sufferers are men who are usually misdiagnosed. However, recent evidence suggests that chronic non-bacterial prostatitis and prostatodynia may be a variant of IC, with similar findings in the prostate.

Most IC patients appear to be young and middle aged women who usually have periods of symptomatic flares and remissions. IC also occurs in adolescents and children. The symptoms worsen periodically in 40-50% of pre-menopausal women and common triggers include psychological or physical stress. Many women with IC have gynecologic symptoms such as chronic pelvic pain (CPP), dyspareunia or endometriosis and IC should be suspected in women with CPP who have negative laparoscopic evaluations. Over 50% of IC patients have symptoms or history of allergic problems and about 30% have concurrent diagnosis of irritable bowel syndrome (IBS). Due to these findings, IC has been considered a neuroimmunoendocrine condition.

Diagnosis of IC is usually based on a history of irritative voiding symptoms (polyuria, nocturia), pain and negative urine cultures. NIH criteria for research studies require confirmation by cytoscopy and hydrodistension under anesthesia. The potassium sensitivity test is a marker of epithelial permeability and has been reported to be positive in 70% of IC patients. Bladder biopsy is not essential for diagnosis, but excludes other bladder pathology (such as tuberculosis or cancer). The more common non-ulcer variety is found in almost 90% of IC patients and is characterized by petechial bladder mucosal hemorrhages ("glomerulations") without ulceration. Patients with non-ulcer disease have minimal evidence of chronic inflammation on biopsy. IC patients have recently been grouped in two subcategories, those with inflammation on biopsy and those without; the former group usually presents with more pronounced symptoms who, however, reported better relief with bladder distention. In those patients with bladder inflammation, the urine has been reported to have increased levels of the mast cell molecule tryptase, which is like a meat tenderizer, and the pro-inflammatory cytokine, inteleukin-6 (IL-6).

The treatment of IC presents a challenge for clinicians since the cause of the disease is unknown {9103}. However, this condition is felt to be multifactorial in origin. Various etiologies have been postulated, but the prevailing hypotheses are (a) altered bladder permeability through some damage to the bladder protective glycosaminaglycan (GAG) layer leading to "leaky epithelium" and (b) an increase in the numbers and activation of bladder mast cells and (c) IC sensory nerve sensitization with tachykinin release. Because of this lack of knowledge of the pathophysiology of IC, treatment is frequently empirical. A variety of systemic, intravesical, cystoscopic and surgical treatments have been used. The goal of treatment is to control or ameliorate symptoms while providing support and understanding to the patient. Some patients note that their IC symptoms are provoked by certain items in the diet such as caffeine, alcohol or acidic foods {8142}. Dietary provocation of symptoms is patient-specific, and when noted, patients fair well when they avoid these items. The passive bladder hydrodistension at the time of diagnostic cystoscopy provides temporary (usually 2-3 months) symptomatic relief in 20-25% of patients and may be repeated as an elective "therapeutic" procedure. Intravesical dimethylsulfoxide (DMSO) has been the main course of treatment until recently. Patients usually prefer oral therapy to intravesical therapy as the first approach to treatment.

Pentosan polysulfate (Elmiron) is approved for oral use and has also been used intravesically. Urine hyaluronic acid was higher in IC patients, as compared to controls. Total urine GAGs were also increased in the urine of IC patients. As a result, a Canadian company has recently marketed intravesical sodium hyaluronate alone, or together with chondroitin sulfate, for IC. The beneficial effect of the therapeutically administered glycosaminoglycans may derive from inhibition of bladder mast cell activation, since mast cell proliferation and activation had been amply documented in IC.

Chondroitin sulfate is one of the most common natural proteoglycans. Chondroitin sulfate has been used, together with its building block glucosamine for the treatment of osteoarthritis. Dr. Theoharides recently showed that chondroitin sulfate is also a potent inhibitor of mast cell secretion.
There are a number of problems, however, with the presently available chondroitin sulfate preparations: (a) there is no standardization in their content of chondroitin sulfate D or E which vary in their size and degree of sulfation; (b) the absorbance is extremely low (<5%) making it unlikely that sufficiently therapeutic levels will be reached; and (c) the most common source is cow's trachea with its inherent risk of "mad cows disease" or spongiform encephalopathy (BSE). In fact, the recent report of the Independent Panel commissioned by the British government to investigate the BSE outbreak, concluded that the problem was way underestimated.

A safe alternative is the new product Algonot-Plus that combines chondroitin sulfate from shark cartilage with the flavonoid quercetin. This preparation, covered by a US patent, uses olive seed oil to prepare the solution, thus improving its absorption considerably. Moreover, it combines the well known benefits of olive oil, which is rich in bioflavonoids with many cytoprotective properties.

Algonot-Plus can also be used in other conditions where there is inflammation, without infection, many of which occur with higher frequency in IC patients, such as:

· Fibromyalgia, a condition of general body aches,
· Chronic prostatitis that afflicts most males over 60 years old with pain,
· Interstitial cystitis which causes severe bladder pain and frequency of urination in about one million women
· Irritable bowel syndrome which causes pain and bloating in the intestines
· Inflammatory bowel disease, a serious condition with a lot of inflammation and pain in the large intestine.


El-Mansoury M, Boucher W, Sant GR, Theoharides TC. Increased urine histamine and methylhistamine in interstitial cystitis. J Urology 152:350-353, 1994.

Theoharides TC, Sant GR, El-Mansoury M, Letourneau RJ, Ucci A, Meares E. Activation of bladder mast cells in interstitial cystitis - a light and electron microscopic study. J Urology 153:629-636, 1995.

Pang X, Cotreau-Bibbo MM, Sant GR, Theoharides TC. Bladder mast cell expression of high affinity estrogen receptors in interstitial cystitis. Br J Urology 75:154-161, 1995.

Pang X, Marchand J, Sant GR, Kream RM, Theoharides TC. Increased number of substance P positive nerve fibers in interstitial cystitis. Br J Urology 75:744-750, 1995.

Boucher W, El-Mansoury M, Pang X, Theoharides TC. Elevated mast cell tryptase in the urine of interstitial cystitis. Br J Urol ogy 76:94-100, 1995.

Letourneau, R, Sant, GR and Theoharides TC. Intragranular activation of bladder mast cells and their association with nerve processes in interstitial cystitis. Br J Urology 77:41-54, 1996.

Spanos C, El-Mansoury M, Letourneau R, Minogiannis P, Greenwood J, Siri P, Sant GR, Theoharides TC. Carbachol-induced bladder mast cell activation. Augmentation by estradiol and implications for interstitial cystitis. Urology 48:809-816, 1996.

Pang X, Sant GR, Theoharides TC. Altered expression of bladder mast cell growth factor receptor (c-kit) expression in interstitial cystitis. Urology 51:939-944, 1998.

Theoharides TC, Pang X, , Letourneau R, Sant GR. Interstitial cystitis: a neuroimmunoendocrine disorder. Ann N Y Acad Scie 840:619-634, 1998.

Alexacos N, Pang X, Boucher W, Cochrane DE, Sant GR, Theoharides TC. Neurotensin mediates rat bladder mast cell degranulation triggered by acute psychological stress. Urology 53:1035-1040, 1999.

Chiang G, Patra P, Letourneau R, Jeudy S, Boucher W, Green M, Sant GR, Theoharides TC. Pentosanpolysulfate inhibits mast cell histamine secretion and intracellular calcium ion levels: an alternative explanation of its beneficial effect in interstitial cystitis. J Urology 164: 2119-2125, 2000.

Theoharides TC, Kempuraj D, Sant GR. Mast cell involvement in interstitial cystitis: a review of human and experimental evidence. Urology 57 Suppl 6A):47-55, 2001.

Theoharides TC, Kempuraj D, Sant GR. Massive extracellular tryptase from activated bladder mast cells in interstitial cystitis. Urology 58:605-606, 2001.

Theoharides TC, Sant GR. New agents for the treatment of interstitial cystitis. Exp. Opin. Invest. Drugs 10:521-546, 2001.

Boucher WS, Letourneau R, Huang M, Kempuraj D, Green M, Sant GR, Theoharides TC. Intravesical sodium hyaluronate inhibits the rat urinary mast cell mediator increase triggered by acute immobilization stress. J Urology 167:380-384, 2002.

What makes this product unique, when compared to others?

This is the only product that delivers enough of three active ingredients to the joints and other areas of body stress. One of these ingredients (glucosamine) helps the body synthesize new cartilage, the second (chondroitin sulfate) is readily incorporated into damaged cartilage and prevents it from further erosion, while the third ingredient (quercetin) reduces the inflammation that destroys the joint and causes stiffness and pain. In addition, the unique addition of olive seed oil, not only permits 3-5 times higher absorption of the three active ingredients, but adds its own antioxidants, such as vitamin E, that are helpful in reducing tissue damage and prolong its healthy function.

How is Algonot-Plus different from other supplements?

Most joint relief supplements contain only glucosamine sulfate and a lesser amount of chondroitin sulfate. Algonot-Plus contains significant and equal amounts of these two ingredients, plus a third natural ingredient - quercetin. In addition, Algonot contains more than a gram of unrefined olive seed oil imported from Crete. The makers of other compounds are aiming exclusively at rebuilding cartilage for sufferers of osteoarthritis. Algonot-Plus has all the cartilage rebuilding properties of other compounds. But in addition, the makers of Algonot-Plus are using the results of published scientific research to target the inflammation associated with arthritis, as well as other painful inflammatory conditions.

Why is Algonot-Plus superior to any other available preparations?

Algonot-Plus is a unique patented and Trademarked formula designed to give long-term relief from arthritis. It was created under the guidance of an internationally recognized Scientific Advisory Board and the contents are of select sources, and of the highest purity certified by an independent laboratory, to provide the safest product of the best possible quality. Algonot-Plus, unlike other products, has no dyes, preservatives or fillers.

Algonot-Plus uses sulfated material because our body needs sulfated glucosamine and chondroitin. Many other products use plain glucosamine or acetyl glucosamine, or chondroitin, because they are cheaper. The following chart compares Algonot-Plus to other glucosamine and/or chondroitin supplements. It has to be noted that most of the available chondroitin preparations sold derive chondroitin from cow trachea imported from Europe and one, therefore, runs the risk of possibly contracting mad cow disease. Algonot-Plus gets its chondroitin from shark cartilage from Latin America and its soft gel capsule is made of pig gelatin to avoid the usual bovine source.

Algonot-Plus gets its quercetin from the Saphfora plant from Latin America for purity and safety. Some food supplements advertise their content of "bioflavonoids" or "citrus flavonoids," while others claim pure quercetin from fava beans. Unfortunately, these preparations are likely to be detrimental rather than helpful. For instance, there are about 30,000 flavonoids all derived from plants, but we have shown that only about six are useful. Moreover, about 15% of people from the Mediterranean area Greeks, Israelis and Italians) lack a specific enzyme and could get hemolytic anemia (destruction of their blood cells) if they were to eat fava beans.

Comparison of oral food supplements for IC to Algonot-Plus
Product CystaQ Algonot-Plus
Main Ingredient Quercetin Quercetin,
Source Fava beans Sapfora plant
Amount 150 mg 300 mg

Absorption <5% >15%
Target Unknown Mast cells, bone cells
Other Ingredients Undisclosed proprietary formulation Chondroitin sulfate, glucosamine, vitamin E, olive seed oil
Additional Advantages None known Anti-allergic, anti-inflammatory, anti-oxidant, cytoprotective
Adverse Effects Ingredients not disclosed None known
Patent Protection No Yes
Targeted Conditions Osteoarthritis Osteoarthritis, rheumatoid arthritis, fibromyalgia, chronic prostatitis, irritable bowel syndrome, inflammatory bowel disease

How did Dr. Theoharides become involved with this research?

I have been studying the mechanism of allergic reactions, and the role of mast cells, for close to 20 years. During this time, I came to realize that the mast cell, which we only thought responsible for allergic reactions, is critically important in inflammation and in the pathogenesis of arthritis and the other conditions mentioned above. As a result, we focused on ways we could block the activation of this cell and its secretion of many noxious substances. Our work in this field has been published in more than 200 scientific papers.

What are mast cells?

Of the millions of cells that make up our bodies, one type known as mast cells has an important role in asthma and other allergic reactions. One way to think of a mast cell is as resembling a soccer ball filled with many ping pong balls. The real mast cell membrane, in fact, encloses many molecular sized toxins (the ping pong balls) that are secreted when mast cells are activated by a trigger, which often is some type of allergen. More recently, mast cells have become implicated in inflamed joints and in many painful inflammatory conditions such as interstitial cystitis, mastocytosis, irritable bowel syndrome, migraines and possibly multiple sclerosis.

What has Dr. Theoharides' research shown?

Dr. Theoharides' research showed that chondroitin sulfate is very effective at blocking the activation of mast cells. Specifically, when chondroitin was added to a solution containing mast cells and known mast cell triggers, it was determined that the rate of activation of the mast cells was significantly reduced. In another test, when a flavone called quercetin was added to a solution containing activated mast cells, it was found that the secretion of toxins from the mast cell was significantly blocked. Finally, when chondroitin and quercetin were both used, it was discovered that they acted synergistically to dramatically reduce the stimulation and activation of mast cells by known triggers. The overall result was that mast cells were inhibited rather than stimulated. For a graphic presentation of this data, see our website www.algonot.com.

Has the Algonot-Plus research been published?

Three of the key publications appeared late last year in the most influential American and foreign Journals:

· Alexandrakis M, Singh L, Boucher W, Letourneau R, Theofilopoulos P and Theoharides TC. Differential effect of flavonoids on inhibition of secretion and accumulation of secretory granules in rat basophilic leukemia cells. International Journal of Immunopharmacology 21:379-390, 1999.

· Theoharides TC, Wang L, Pang Z, Letourneau R, Culm KE, Basu S and Correia I. Cloning and cellular localization of the rat mast cell 78-kDa protein phosphorylated in response to the mast cell "stabilizer' cromolyn. Journal of Pharmacology and Experimental Therapeutics 294:810-821, 2000.

· Theoharides TC, Patra P, Boucher W, Letourneau R, Kempuraj D, Chiang G, Jeudy S, Hesse L and Athanasiou A. Chondroitin sulphate inhibits connective tissue mast cells British Journal of Pharmacology 131:1039-1049, 2000.

· Middleton E, Kandaswami C and Theoharides TC. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease and cancer. Pharmacological Reviews 52:673-751, 2000.

How safe is the dietary supplement Algonot-Plus?

Algonot-Plus, unlike many other products, is made of entirely natural and pure ingredients. We have made sure that there is no potential danger. Glucosamine used in most of the available products sold in the USA is derived from cow trachea imported from Europe, in which case one runs the risk of possibly catching "mad cow disease." The risk of mad cow disease is so serious in Europe that bovine gelatin has been banned from all cosmetic products

· Gavaghan H. Report flags hazards of risk assessment. Science 290:911-912, 2000.

For this reason, the chondroitin sulfate in Algonot-Plus is obtained from shark cartilage imported from Latin America. For the same reason, the gelatin used for the shells of the capsules is obtained from pigs to avoid bovine material.

Can I take Algonot-Plus together with other drugs?

Algonot-Plus can be taken together with any other drug used to treat arthritis, or the other conditions mentioned. In fact, a patient should remain on the drugs they are on and start reducing them slowly only after they have being on Algonot-Plus for at least 3 months.

Can I take Algonot-Plus if I am allergic to sulfonamide antibiotics?

Glucosamine sulfate and chondroitin sulfate are unrelated to sulfonamide antibiotics and there is no evidence that the "sulfated" portions cross-react. Consequently, there is no risk of a person allergic to sulfonamides having an allergic reaction to Algonot-Plus. Moreover, Algonot-Plus is, itself, anti-allergic and would reduce the likelihood of such possibility even if it were to occur.

Is it FDA approved? If not, do you see an FDA approval in the future?

Algonot-Plus is a food supplement and does not require FDA approval. This is why the description of this product focuses on prevention and strengthening of affected joints, rather than its being a "pain killer." The label is reviewed by the FTC (Federal Trade Commission). It should, however, be pointed out that food supplements are not allowed to make any claims for treatment of any disease. This is why the label of Algonot-Plus states:

Especially formulated, based on published scientific evidence, to work together delivering more of the bioactive ingredients to the joints and other sites of body stress

Why does Algonot-Plus contain olive seed oil?

Chondroitin Sulfate is one of the most important ingredients in any of the joint relief products currently on the market. But chondroitin is composed of a very large molecule (with a molecular weight of 100,000 compared to glucose, for example, at less than 500). As a result, it is very hard to get the body to absorb chondroitin into tissues where it can do some good. Most chondroitin is flushed through the body and has no effect. Research has shown that combining this component with olive oil increases the amount absorbed by up to three times, more than 15% in many cases, compared to less than 5% of chondroitin administered in regular pill form.

· Palmieri et al. Metabolic fate of exogenous chondroitin sulfate in the experimental animal.
Arzneim.-Forsch./Drug Res. 41:768-772, 1991.

After oral administration of tritiated (3-H) chondroitin sulfate to the rat and dog, 70% of the radioactivity was absorbed. But, the high molecula weight fraction (THAT IS USEFUL) was about 10%. Additionally, if the degree of sulfation was high, the absorption WAS NEGLIGIBLE.

· Conte et al. Metabolic fate of exogenous chondroitin sulfate in man. Arzneim.-Forsch./Drug Res. 41:768-772, 1991.

After intravenous administration of chondroitin sulfate (16,000 daltons), more than 50% is excreted in the urine in the first 24 hours, while the absolute bioavailability (how much reaches the blood) after oral administration is 13.2%. Keep in mind that this size (16,000 daltons) has almost no protective value in laboratory experiments.

· Conte et al. Metabolic factor of partially depolymerized chondroitin sulfate administered to the rat. Drugs Exptl. Clin. Res. 17:27-33, 1991.

The major excretion of both intramuscular and oral administration is in the urine. The size of chondroitin sulfate bigger than 4000 daltons (NOTE: the bigger the more effective, preferably over 100,000 and highly sulfated) was only a few percent of the total administered. Six times more material had to be administered by mouth to reach the level administered intramuscularly.

· Baici et al. Analysis of glycosaminoglycans in human serum after oral administration of chondroitin sulfate. Rheumatology International 12:81-88, 1992.

They found NO absorption and considered the protection in the joints after oral administration an unfounded theory.

· Conte et al. Biochemical and pharmacokinetic aspects of oral treatment with chondroitin sulfate. Arzneim.-Forsch./Drug Res. 415:918-925, 1995.

A medicinal preparation of low molecular weight (14,000 daltons) chondroitin sulfate (Condrosulf, Germany) was orally administered to male healthy volunteers in a single daily dose of 800 mg or in two doses of 400 mg each per day. The highest amount of 2.5 microg/ml was achieved in the blood 4-8 hr after administration and was down by 80% at 24 hours. Keep in mind that this size (14,000 daltons) has almost no protective value in laboratory experiments.

In the studies mentioned above, chondroitin sulfate was of small molecular weight, low degree of sulfation and it was tritiated, a method that usually gives higher readings; yet, absorption ranged from 0-10% after oral administration.

When chondroitin sulfate of about double the size used in those studies (26,000 daltons) was used and was 14-C-labeled, ONLY 0.4% of the oral dose administered in rats was intact chondroitin sulfate in the blood, even though 4% was recovered intact in the urine (unpublished observations). One is, therefore, forced to conclude that at best maybe 4% of real chondroitin sulfate of molecular weight 26,000 daltons is absorbed from the intestine intact.

The companies selling chondroitin sulfate as food supplement for arthritis do not provide information on the size or the degree of sulfation of chondroitin sulfate. In other words, at best they may get 4% absorption and at worst 0%. Yet, sales of chondroitin sulfate are about $0.5 billion per year in the USA. In fact, the MERCK INDEX (10th edition, 1983, p. 2190) lists chondroitin sulfate as having an average molecular weight of 50,000 daltons depending on the source and method of preparation. It is the higher molecular weight and higher degree of sulfation that are biologically active in laboratory and clinical experiments, but it is these that are almost impossible to absorb orally in a powder form.

The innovation of Alonot-Plus is that chondroitin sulfate, together with glucosamine sulfate and quercetin, are mixed in unrefined olive seed oil, thus forming micelles that increase the absorption as the intestine is particularly suited for absorbing oils and lipids, while it excluded polarized molecules with ionic charges (sulftate).

Does the olive oil have any other benefits?

It was recently shown that polyphenols, compounds that are particularly rich in olive seed oil, have protective action against experimental arthritis:

· Martinez-Dominguez E, de la Puerta R, Ruiz-Gutierrez V. Protective effects upon experimental inflammation models of a polyphenol-supplemented virgin oil diet. Inflamm Res 50:102-106, 2001.

Actually, olive oil has also been shown to have protective action in the development and/or severity of rheumatoid arthritis:

· Alarcon de la Lasra C, Barranco md, Motilva V, Herrerias JM. Mediterranean diet and health: biological importance of olive oil. Curr Pharm Des 7: 933-950, 2001.

· Linos A, Kaklamani VG, Kaklamani E, Koumantaki Y, Giziaki E, Papazoglou S, Mantzoros CS. Dietary factors in relation to rheumatoid arthritis: a role for olive oil and cooked vegetables? Am J Clin Nutr 71: 1010, 1999.

· Brzeski M, Madhok R, Capell HA. Evening primrose oil in patients with rheumatoid arthritis and side effects of non-steroidal anti-inflammatory drugs. Br J Rheumatol 30: 370-372, 1991.

· Kremer JM, Lawrence DA, Jubiz W, DiGiacomo R, Rynes R, Bartholomew LE, Sherman M. Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Clinical and immunologic effects. Arthritis Rheum 33: 810-820, 1990.

Olive oil is well known for its cytoprotective, longevity-producing effects, along with possible anti-cancer properties. The Island of Crete, where Algonot obtains its olive oil, is known to have among the highest longevity rates in the world and is also a leading consumer of olive oil. The olive oil in Algonot-Plus comes from the seeds of the olive rather than the olive itself, and is unrefined. It is unsaturated and we believe it is an important part of the diet of anyone interested in the benefits of nutrition based on natural ingredients.

· Bosku D. Olive oil. World Review Nutrition Diet 87:56-77, 2000.

· Trichopoulou A, Kouris-Blazos A, Vassilakou T, Gnardellis C, Polychronopoulos E, Venizelos TM, Lagiou P, Wahlqvist ML and Trichopoulos D. Diet and survival of elderly Greeks: a link to the past. Am Journal Clinical Nutrition 61:1346S-1350S, 1995.

· Trichopoulou A, Lagiou P, Kuper H and Trihopoulos D. Cancer and Mediterranean dietary traditions. Cancer Epidemiology, Biomarker Prevention 9:869-873, 2000.

Why did you choose olive seed oil from Crete?

The people of Crete have one of the highest longevity rates (live longest) in the world. I visited Crete many times, often invited to lecture at the Medical School in Heraklion. During these visits, I made an effort to speak with some of the oldest leaving Cretans up on the hills and mountains and inquired on their diet and protection from the sun. Many of them told me that they would sell their olive oil and use the olive seed oil for their salad, as well as a sunscreen. The trick was to get the olive seed oil (what one gets from the olive skin and pits) soon after harvest from the top of the containers when it was purest and of low acidity.

After visiting and testing a number of facilities all over Greece, I chose a specific one in Crete from which we obtain the olive seed oil soon after harvest, have it filtered through miniscule filters to remove any solids, and also remove almost all of the water present to reduce the acidity to almost that of olive oil. This olive seed oil is not treated with any chemicals (unrefined) because such treatments remove most of the useful anti-oxidant and cytoprotective molecules. If you have ever seen olive seed oil, its color is deep green as compared to amber/light green for olive oil. The beneficial, protective properties of olive seed oil were recently recognized by the cosmetic industry in France, which has recently marketed beauty creams based entirely on olive seed oil.

How much Algonot-Plus should be taken and for how long?

One should start with one capsule in the morning and one in the evening with meals for one week. Two capsules should then be taken twice daily with meals for at least three months before any improvement is noticeable. Heavier individuals or those with long standing or severe symptoms would have to advance to two capsules three times per day after three months. Once the bottle is opened it should be preferably stored in the refrigerator or any other cool place.

The bottle should be shaken each time because the capsules may occasionally stick to each other when they are warm. Any "oily" smell does not mean anything other than the fact that the smell of the olive seed oil may be noticeable after a while, especially if the bottle is not kept cool.

Where can I buy Algonot-Plus?

In order to keep costs down, Algonot-Plus is not available at retail stores yet. You can order Algonot-Plus by calling the toll-free number 1-800-ALGONOT or through the website Algonot.com

What is the price of Algonot-Plus?

Each bottle of 120 capsules costs $35, but is discounted to $28/bottle for any order of 6 bottles or more. Mailing costs are additional.

Dr. Theoharides CV

Theoharis C. Theoharides, Ph.D., M.D.
Professor of Pharmacology and Internal Medicine, Tufts University School of Medicine-New England Medical Center, Boston

Place and Date of Birth
Thessaloniki, Greece on February 11, 1950

High School Education
Anatolia College, Thessaloniki, Greece

University Education Degree Year Conferred Field of Study
Yale University, New Haven, CT B.A. 1972 Biology & History of Medicine
Yale University, New Haven, CT M.S. 1975 Neuropharmacology
Yale University, New Haven, CT M.Phil. 1975 Immunopharmacology
Yale University, New Haven, CT Ph.D. 1978 Pharmacology
Yale University, New Haven, CT M.D. 1983 Medicine
Harvard University, Cambridge, MA M.P.A. 2002 Biomedical Research Policy

Academic Appointments
1968-71 Assistant in Research, Department of Biology, Yale University
1971-78 Assistant in Research, Department of Pharmacology, Yale University
1978-83 Research Associate, Biochemistry Research Lab., Veterans Admin. Medical Center, CT
1978-83 Research Associate, Sec. Clin. Immunology, Dept. of Internal Medicine, Yale University
1983-88 Assistant Professor of Pharmacology, Biochemistry and Psychiatry, Tufts University, MA
1985-92 Director of Medical Pharmacology, Tufts University School of Medicine, Boston, MA
1989-93 House Staff, Dept. of Internal Medicine, New England Medical Center, Boston, MA
1989- Associate Professor of Pharmacology (1989-1994), Biochemistry and Psychiatry, Tufts University
1990- Professor of Pharmacology and Internal Medicine, Tufts University (tenured 11/2/91)

1971 Connecticut Commission for Undergraduate Research Award
1971 Yale College Dean's Award for senior research thesis
1972 Cum Laude & Divisional Honors for joint Bachelor of Arts, Yale College
1972 Theodore Cuyler Award "for outstanding Yale College graduates", Yale University
1975-77 Advisory Committee to the Dean, Yale University Graduate School
1977 G. Papanicolaou Graduate Research Award, Hellenic University Club of New York
1979,83 Medical Award, Hellenic Medical Society of New York
1980 Travel Award, American Society for Cell Biology
1980 Winternitz Prize "for the best work in Pathology", Yale Univ. School of Medicine
1981,82 Research Fellowship, Int'l Inst. of Cellular & Molecular Pathology, Brussels
1984 Chairman - Immunopharmacology, 9th Int'l Congress of Pharmacology, London
1984 Travel Award, American Society for Pharmacology and Experimental Therapeutics
1986 Chairman - Neuroimmunology, 2nd World Conference on Inflammation, Monte Carlo
1986 Distinguished Service Citation for faculty excellence, Tufts University
1987,88 Special Faculty Recognition Award, Tufts University School of Medicine
1987 Honorary Member, Alpha Omega Alpha National Medical Honor Fraternity, USA
1989 Chairman - Neuroimmunomodulation, 3rd World Conference on Inflammation, Monte Carlo
1989,90 Citation for Excellence in Teaching, Tufts University School of Medicine
1991,93 Advisory Committee, 4th & 5th World Conferences on Inflammation, Geneva
1991,92 Citation for Excellence in Teaching, Tufts University School of Medicine
1993,94 Citation for Excellence in Teaching, Tufts University School of Medicine
1993 Medical Awareness and Patient Support Award, Interstitial Cystitis Association, NY
1994 Diocean Award for Humanitarian Health Care, Greek Orthodox Diocese of Boston
1995,97 Advisory Committee, 6th & 7th World Conference on Inflammation, Geneva
1995 Chairman, International Committee to Upgrade Medical Education in Greece (appointed by Secretary of Health)
1996 Citation for Excellence in Teaching, Tufts University School of Medicine
1997-01 Supreme Scientific Advisory Health Council, Secretary of Health, Hellenic Republic
1998 Community Service Award, Mayor Thomas Menino of Boston
1999-02 Supreme Health Board, Institute of Social Welfare, Sec. of Labor & Human Resources, Hellenic Republic
2001-02.1 J.F. Kennedy Fellow, Harvard University, J.F. Kennedy School of Government

Am. Assoc. Adv. of Science Am. Soc. Microbiology Internl. Soc. Immunopharmacol.
Am. Assoc. Hist. Medicine Am. Soc. Pharm. Exp. Therapeutics Internl. Soc. Neuroimmunomodul.
Am. Assoc. Immunologists Conn. Acad. Arts and Sciences N.Y. Acad. Sciences
Am. Fed. Clin. Research European Acad. Allergy Immunology Sigma-Xi Honor Research Society
Am. Soc. Cell Biology Internl. Assoc. Study of Pain Soc. for Neuroscience

Public Advisory Committees
1986- Massachusetts Drug Formulary Commission 1989 NIDDKD Ad Hoc Urology Study Section
2000-01 NIH Biobehavioral & Behavioral Processes-SS2
U.S. Patents:
1. Last minute prevention of migraines #5,250,529 issued on 10/5/93
2. Treatment of painful gastrointestinal syndromes #5,648,350 issued on 7/15/97
3. Treatment of stress-induced migraines #5,855,884 issued on 1/5/99
4. Therapeutic use of histamine-3 receptor agonists #5,821,259 issued on 10/13/98
5. Hydroxyzine for the treatment of interstitial cystitis #5,994,357 issued on 11/30/99
6. Treating skin disorders with CRH antagonists #6,020,305 issued on 2/1/00
7. Proteoglycans for mast cell-related conditions #09/056,707 allowed on 2/22/99


Over 250 peer-reviewed papers, 3 books and an electronic textbook of pharmacology.