Healing by Design

by Rajgopal Nidamboor, PhD

Any effective treatment plan for osteoarthritis should be aimed to address two fundamental objectives. The first objective is to control pain per se, the second to slow down and, if possible, reverse the progression of the joint disorder.

All the same, one fact needs to be highlighted: conventional treatment offers a smorgasbord of remedial measures in the treatment of osteoarthritis today. However, for the most part, it provides only symptomatic relief, not viable or safe long-term respite. Conventional treatment may be referred to as palliative, not all-encompassing. Besides, you have the specter of a “grand” side-effect profile of the powerful drugs used.

Is there a way out – a safe, dependable, “drugless,” effective alternative option? There is. Glucosamine and chondroitin, two natural dietary supplements, meet the basic parameters for long-term, effective pain relief in the osteoarthritis treatment plan. They offer both “twinge” release and control. In addition, they provide for the recovery of cartilage function and promote healing – all without the flagrant side-effects of conventional medications. What’s more, the duo extends sustained comfort from joint pain and tenderness (sensitivity to touch) and, in the process, improves mobility – naturally and safely.

Glucosamine

Glucosamine is the basic building block for proteoglycans. Proteoglycans, a sine qua non for healthy joint function, act like natural sponge; in so doing, they retain water that is essential for vibrant joint function. In simple terms, glucose, or sugar, and an amino acid, or protein building block, combine to form glucosamine.

Nature has endowed the human body with the ability to manufacture its own glucosamine. However, in osteoarthritis, every bit of reinforcement with glucosamine could bring about a world of difference to your joint health. The reason is simple. Glucosamine helps “form” cartilage in joints; it is also needed for the formation of blood vessels, bone, ligaments, nails, skin, synovial fluid, and tendons, aside from mucous secretions of our digestive tract. More importantly, glucosamine is fundamentally needed by the body to make chondroitin.

When taken orally in capsule or tablet form, glucosamine is absorbed from the gastrointestinal (GI) tract quickly and almost fully (approximately 90%). Once absorbed, the body sends the bulk of the “wrapped-up” compound to areas of cartilage – to build new and healthy cartilage.

The growing worldwide interest in glucosamine and chondroitin is not new. That glucosamine was synthesized more than 100 years ago may be news to some of us; it may also be news that medical research first got its “clue” in the mid-1950s that the substance could play a pivotal, or adjuvant, role in the management of osteoarthritis.

The first uncontrolled studies were, of course, not meticulous – if not totally flawed. They also invited cynicism about “positive” results – as a result of “fanciful” thinking by both physicians/therapists and their patients – when no conclusive proof was verifiable or replicable.

The idea may not have changed much today, although research across the globe (aside from the US) has showed that glucosamine helps augment and improve joint health. This has spawned the “new collagen era.” What’s more, it has also given adequate impetus for further studies. By the end of the 1960s, glucosamine had been documented to relieve patients affected by osteoarthritis. However, it is only recently that sustained research has led to the development of a more stable and dependable compound with a long shelf life.

A quick recap: in the early days, glucosamine was injected to bring about relief from pain and improve mobility in patients. It was a difficult and cumbersome agenda. In the course of time, glucosamine became available in an oral pill, capsule, or tablet form; this is, obviously, the much-preferred choice, like most medications today.

Chondroitin

Chondroitin (or chondroitin sulfate, to use its technical name) is quite like glucosamine. It is made within the body. It is also an essential component of our cartilage and other connective tissues. It belongs to a group of compounds called glycosaminoglycans.

The sulfate, for the sake of convenience, is referred to as one substance; actually, it is not. There are unique, albeit structurally identical types of the compound too – the most abundant in the body being chondroitin-4-sulfate and chondroitin-6-sulfate. The numbers for each are related to the location of the sulfate molecule, next to the chondroitin sequence. It may be mentioned too that there is a marginally different structure of chondroitin sulfate molecule – with each individual structure having different weights.

Research does not agree on a universal “format” on how different weights influence or promote absorption in the use of chondroitin compounds. Be that as it may, there is a general consensus that the lower the weight of the compound, the more readily it is absorbed. This, of course, does not relate to what could be defined as “ideal” structure – one that could be thoroughly recommended for use.

Chondroitin was first identified in the 1940s, as a component of cartilage. Its early research was confined to animals – to observe, or evaluate, possible results of its application in human joint health. As studies progressed, research on animals showed its supplemental ability to augment proteoglycans’ production. This culminated in clinical trials on human subjects. The results have been consistent: chondroitin relieves joint pain, improves mobility, reduces swelling in the affected part, and also one’s “reliance” on nonsteroidal anti-inflammatory drugs (NSAIDs).

Whatever the inference, the fact remains that chondroitin isn’t as absorption-friendly in the body as glucosamine is. Less than 10% of chondroitin is absorbed vis-à-vis 90% of glucosamine.

The issue is being peremptorily debated and researched, just as scientists are speculating how low-molecular mass chondroitin – available on the market – could be absorbed with better effect. While it is as yet scientific conjecture as to what happens after chondroitin is swallowed, studies, in general, have shown that the dietary supplement is more than equal to the task of providing good joint health and/or comfort.

They Help Rebuild Cartilage

Glucosamine can help rebuild cartilage affected by osteoarthritis. When a pill, capsule, or tablet of the supplement is ingested, most of it ends up in the tissues of our joints. When glucosamine enters the chondrocytes – the cartilage-building assembly line inside the cartilage tissue – it is utilized to form new proteoglycans, which are responsible for healthy joint function. This by itself is a vital contribution, because in osteoarthritis the body’s resources to manufacture adequate levels of new proteoglycans are depleted.

While ringing in the new, and ringing out the old, is nature’s own maxim in the cell-replacement process, the process is regulated and facilitated by our body’s enzymes that mortify the old cells. When such a breakdown occurs more quickly and replacement does not keep pace with it, the outcome is imminent – frail cartilage. This situation calls for supplemental glucosamine intake. Glucosamine not only stalls the “enzymatic” destruction of proteoglycans, it also provides for anti-inflammatory responses in the affected joint.

Magic Bullet

… Or?

Critics or skeptics often observe that glucosamine adherents have an ostentatious pitch: that the supplement has “the unique ability” to provide pain relief and help regenerate damaged tissue in joints. They ask, is this a well-orchestrated marketing gimmick – one that you should run after and take?

Some critics also refer to glucosamine as nothing short of the “gingko” of osteoarthritis therapy – a popular “natural” remedy. This is not without reason. In a survey of 2146 primary-care physicians and rheumatologists and 90 patients conducted by Arthritis Today, 34% with the disorder rated glucosamine as their favorite alternative to over-the-counter (OTC) conventional pain medications. As a matter of fact, physicians/therapists rated its utility higher – with 45% preferring to call glucosamine their “supplement” of choice.

However, not everyone is impressed with the beneficial effects of glucosamine. A section of rheumatologists and researchers remains unconvinced and adheres to one quip: there have been no long-term clinical studies of the supplement in human beings. They also extend their pessimism to the fact that since glucosamine is a nutritional supplement, and therefore not regulated by the Food and Drug Administration (FDA) in the US (the regulation of course may not be relevant elsewhere), there can be no certainty in quantifiable terms regarding its potency or purity.

According to Timothy E, McAlindon, MD, MPH, chief of Division of Rheumatology, professor at Tufts University School of Medicine (US), and author of a topical study reviewing the scientific evidence about glucosamine and chondroitin, “The jury is still out on whether this works.” Nevertheless, McAlindon and his colleagues agree that there is convincing evidence that “some glucosamine products” may actually help reduce inflammation and alleviate pain of osteoarthritis. What they are ambiguous about is whether glucosamine (and, chondroitin) can also “freeze” and “turn around” the disorder. Other researchers maintain that a number of documented benefits may be exaggerated – or that the conclusions of several studies were “inclined” and methodologically inconsistent. Some say that it is just the opposite. Their raison d’être: 1 of the major 15 studies was sponsored by manufacturers and/or pharmaceutical companies.

However, in an article published in Osteoarthritis and Cartilage, principal investigator Amal K. Das, MD, found that glucosamine/chondroitin sulfate dietary supplement (Cosamin DS) was effective in the management of joint pain in the knee. The randomized, placebo-controlled, peer-reviewed, clinical study was conducted in a group of patients, with a combination of glucosamine and chondroitin sulfate, while using a standardized index to measure joint pain. In the study, participants on glucosamine/chondroitin supplements showed significant improvement in the management of joint pain in the knee. The response rate was 52% in comparison with 28% in the placebo group.

Glucosamine

• increases the lubricating pattern in the joints

• increases hydration of joints and tissues and, in so doing, reduces stiffness

• stimulates the production of sugars that support the cartilage matrix

• reduces the action of degradative enzymes that breakdown cartilage

• activates anti-inflammatory responses

Chondroitin

• protects the health of joints, muscles, cartilage, ligaments and tendons

• helps relieve inflamed joints associated with aging and osteoarthritis

• promotes elasticity

• shields the body against joint destruction

• improves the body’s natural ability to heal itself

• acts as a shock-absorber for the joints

Glucosamine Sulfate versus NSAIDs (Ibuprofen)

Clinical studies suggest that a definitive decrease in the intensity of osteoarthritis is almost a norm during the first week with the use of ibuprofen, but not with glucosamine sulfate. However, by the second week, as reported in most clinical trials, the glucosamine group holds on to its own – the result in terms of pain relief and osteoarthritic symptoms is apparent. Yet the most important difference between NSAIDs and glucosamine is reflected by way of the former’s side-effect profile. In one study, one in three of the ibuprofen users complained of tummy upset; there were no reported side-effect symptoms from patients taking glucosamine sulfate. The supposition is relevant, although most of the studies were not extensive, the longest trial lasting just 2 months. However, the overall pattern of results certainly shows ample promise in the use of glucosamine for the reduction of “reported” pain levels.

Oral Glucosamine Sulfate versus Placebo

In clinical trials, patients in the oral glucosamine sulfate group have often reported a significant decrease in pain and inflammation compared with the placebo (dummy pill) group. No adverse reactions were reported by patients, treated with glucosamine sulfate. This, as some clinicians opine, makes it an effective treatment option for osteoarthritis.

Glucosamine Sulfate versus NSAIDs and Placebo

In studies conducted on both NSAIDs and glucosamine sulfate groups of patients, each symptom of osteoarthritis improved, but to a much quicker and greater extent in the group treated with glucosamine. No placebo group has ever shown such results or improvement.

Side Effects of NSAIDs

• tummy ache, heartburn, and nausea

• cartilage degeneration

• leaky gut syndrome; gastrointestinal bleeding

• cramps and diarrhea

• fluid retention and weight gain

• drowsiness, dizziness, mental confusion

• wounds bleed easily; they heal slowly

• adverse reaction with alcohol

• ringing in ears, or tinnitus

• lowered melatonin (a regulatory hormone) levels at night and body temperature

Aspirin

Millions of people are taking the wonder drug, aspirin, on a daily basis. Aspirin has shown its efficacy to significantly reduce the risk of heart attack and stroke, and quell osteoarthritis pain. For some of its adherents, aspirin is a miracle remedy. But one fact remains: for all its benefits, aspirin can also damage the lining of the gastrointestinal tract.

To alleviate the difficulty, a recent, more stomach-friendly aspirin called NCX-4016, which also encompasses the cyclooxygenase-2 (COX-2) inhibitor celecoxib, is sold under the brand name Celebrex, with promising results. The new aspirin, unlike its “old” model, releases nitric oxide, which increases the blood flow in different parts of the body. Research suggests that traditional aspirin probably damages the stomach, because it may reduce blood flow to the lining of the stomach. Studies reckon that the dissipation of nitric oxide, triggered by the “new” drug, which has run into rough weather due to its deleterious effects on patients with heart afflictions, opens up the blood flow and may protect the stomach lining. The jury is out.

Things are gradually changing for glucosamine; it is no longer a question of why one has not heard about it yet. The fact is that several progressive physicians/therapists are prescribing glucosamine sulfate for osteoarthritis. But the ticklish question that we encounter is the label – glucosamine is classified as a nutritional or dietary supplement, not a drug. Hence, it may be an out-of-pocket expenditure in some countries (though not in the UK, where it is available on National Health Service).

In addition to subjective clinical studies – except for a brace of quality clinical trials that detractors point out as not being substantial, or all-embracing, it may also be mentioned that most studies offer data on the basis of animal-based clinical trials performed to evaluate how glucosamine works. It has, however, been found that in vitro, glucosamine sulfate stimulates cartilage cells to synthesize both glycosaminoglycans and proteoglycans.

Oral glucosamine sulfate has demonstrated beneficial effects on inflammation and joint pain in clinical studies. However, one question remains: how do glucosamine supplements, taken orally, really get to the “right place” in the joint to stimulate new cartilage growth, as most pro-glucosamine bodies and prescribers maintain?

In an article published in the Journal of the American Medical Association (JAMA), a group of participants was given glucosamine sulfate tagged with a radioactive dye. The objective was simple. The technique allowed investigators to follow the glucosamine “trail” through the body. The results showed that oral glucosamine sulfate became a component of cartilage – supporting all of the subjective results experienced and reported by patients, from time to time.

Growing Disenchantment with Conventional Treatment

Although the two supplements have been in vogue as a means of primary treatment in Europe, they have made their presence felt in the US and elsewhere, including India, and with good effect. The reason for such a development is not difficult to understand.

Pharmaceutical companies often spend their hefty resources, not just in terms of money, or inclination, researching and marketing drugs – such as NSAIDs – to treat illness or disease. This is also where their organized “action” bears fruit – getting patents for their drugs. Besides this, patented medicines help them to recover their enormous investments. This also helps them protect, garner, even conquer markets and/or charge prices higher than those manufactured by their competitors.

Not that the drive for patents is “bad” medicine. It is good, because it gives the lead to the development of more useful and life-saving medications. But there is a downside to the idea – nutritional supplements, such as glucosamine and chondroitin, cannot be patented. Hence, pharmaceutical companies have little interest in them. This also explains why most companies in the pharmaceutical business hanker for new (patented) drugs that bring in wealth, even if they cause adverse side effects in patients using them.

The incongruity is perceptible. Funding is a difficult word for research efforts for nutritional supplements – even if they sound as glamorous as patented medicines by their names. This isn’t all. Nutritional supplements don’t really attract a first-rate budget for their development, although this does not in any way detract from the merits of their therapeutic, sometimes incredible, healing properties. Also, the whopping investment in “adverteasements,” if not advertisements, is another “knob” to give top pharmaceutical companies a handhold toward its reach in “tapping” prospective customers, which supplements cannot match.

On the upside, things are now changing – not because enthusiasm has expanded for natural supplements, and this has led to money coming in for research. Far from it. Thanks to the ubiquity of the Internet, and disenchantment with conventional medicine, there seems to be a growing hunger for information on natural supplements, especially glucosamine and chondroitin, among patients and the public at large – besides dispassionate conventional, alternative, and integrative medicine physicians and therapists.

More on Chondroitin

Chondroitin is somewhat akin to glucosamine in its beneficial function. It also plays a similar, or complementary, role. Besides, it ushers in a new era of “crop” production – in this case, healthy, water-trapping proteoglycans.

Chondroitin has a negative charge. This explains why each of its molecules is drawn away from nearby molecules to make room for water to fill within the cartilage structure. While laboratory studies suggest that chondroitin, along with glucosamine, boosts the creation of proteoglycans, the absorption of water into the cartilage is just as important a factor. Cartilage has no blood supply of its own; it has to depend to a large extent on the movement of fluids to direct necessary nutrients into the joint. You’d call it the “shock-absorber effect,” caused during joint movement.

It may also be emphasized that certain enzymes destroy the proteoglycans to “loop” in new ones. In osteoarthritis, such enzymes are “out of bounds” with new proteoglycans. It is precisely in such a situation that chondroitin plays a significant role. It stalls and slows down the imbalance caused by the death of proteoglycans and collagen in the cartilage. A study in Italy, to cull just one example, showed the use of oral chondroitin sulfate for a period of 5 days by a group of individuals with cartilage degeneration, and another with healthy cartilage, to significantly decrease the levels of degradation.

Chondroitin, like glucosamine, has the wherewithal to decrease joint inflammation – which reaches alarming levels as the osteoarthritis disorder progresses and debilitates the affected individual. The best part is that the two supplements do not alter or harm prostaglandins, the hormonelike substances or natural chemicals, involved in inflammation, unlike NSAIDs, which alter them and cause side effects such as gastrointestinal distress.

Remodeling the Joints

The two supplements, glucosamine and chondroitin, restore the joint modeling process and elevate balance – balance holds the key to stopping osteoarthritis from running wild. Besides, they prop up the proteoglycans’ building, or rebuilding, ability, aside from chondrocytes. In a major (double-blind) study, reported in The Lancet, researchers from four countries found convincing evidence that glucosamine could prevent osteoarthritic progression in 212 study subjects. Double-blind trials are thought to produce objective results, since the researchers’ and volunteers’ expectations about the experimental substance do not affect the outcome.

The study was no quick clinical “mug shot” of glucosamine; it was based on sound scientific principles and adhered to the strictest norms. This isn’t all. Neither the patients nor medical professionals had the “ghost of an idea” as to who among the trial group was taking glucosamine and/or placebo. The study was also without bias, because there is always, paradoxically, the prospect of detracting from the merits of any benefit as having emerged due to “straight-line” thinking, or wishful contemplation.

The patients in the study were all afflicted with osteoarthritis of the knee joint. Exactly half of the individuals took 1500 mg of glucosamine sulfate per day; the other half was given placebo. The supplement “diet” went on for a period of 3 years, and the end result was encouraging. Pain dropped by 20% to 25% among the participants taking glucosamine; symptoms increased by 10% in the placebo group. X-ray studies also substantiated the progress – the glucosamine group showed no deterioration in knee-joint abnormalities, whereas the placebo group continued to experience worsening abnormalities.

This was a groundbreaking outcome – even though it did not necessarily excite researchers who had already concurred that glucosamine could help the cartilage rebuild itself with the aid of scanned electron micrographs. The experience was similar with patients taking chondroitin supplements.

In another example, when an adult group of patients, with thinning cartilage, was given oral doses of chondroitin and placebo, for a period of 1 year, the cartilage in the former not only stopped thinning but also improved in its thickness. Besides this, the group showed adequate improvement in pain and joint mobility, including other parameters.

In a review published in JAMA, which was based on (re)analysis of research conducted over a three-decade period (1966–1999), researchers concluded that the two supplements do in fact show a “moderate-to-large” effect for alleviating symptoms of osteoarthritis. The reports, published in two prestigious journals, are not just suggestive but also indicative of the fact that glucosamine and chondroitin are resolute, and fairly safe, contenders in the long-term management and treatment of osteoarthritis.

The real shot in the arm for the two supplements emerged, thanks to the “reception” that they received from Drs. Jason Theodosakis, Brian Adderly, and Barry Fox’s landmark book, The Arthritis Cure. The book clearly contended the medical fact that glucosamine and chondroitin could halt, reverse, and even cure osteoarthritis. Soon enough, the two supplements became names as big as the latest blockbuster movies from Hollywood or Bollywood.

It is, of course, quite easy for one to go overboard in view of the fact that the two supplements seem to break new ground with every realistic trial. It would also be no exaggeration to say that several highly qualified and respected researchers have gone on record, despite their usual scientific inclination for discretion, and recommend that it would be useful to try the two-supplement-option prior to the use of aspirin, NSAIDs, or surgery.

Research, however, asserts that this is no fail-safe start; it also cautions that this is no total solution to taking the osteoarthritic bull by its horns. However, what most studies espouse is that glucosamine and chondroitin are the most sensible options to begin with, for two reasons. Their potential to provide ample benefit to the patient is high; at the same time, they also have a relatively minimal side-effect profile. In other words, they are more than relatively safe, unlike powerful pharmaceutical drugs.

The upshot is far from determined, because it is not possible yet to predict who will win the “race.” A long scientific journey into the realms of finding out an appropriate statement to address the issue is still unfinished. The essential of the essentials in the glucosamine/chondroitin fulcrum was put to the litmus, if not ultimate, test in an US$14 million study, to cull a recent exemplar – the Glucosamine/Chondroitin Arthritis Intervention Trial [GAIT] – set up by the National Center for Complementary and Alternative Medicine and the National Institute of Arthritis and Musculoskeletal Disease, US.

The study examined whether glucosamine and chondroitin do indeed relieve the pain of osteoarthritis. It enrolled over 1600 patients, for 24 weeks, in as many as 13 different clinical centers. This was followed by a subset of participating subjects for another 18 months. The study measured, in actual terms, the efficacy of the two supplements, separately and in combination, and compared results with celecoxib (a conventional COX-2 medicine) for alleviating osteoarthritic knee pain. The results were predictable: they implied that the two supplements could “perhaps” or “possibly” work in mild-to-moderate osteoarthritis – and perchance merely or marginally improve quality of life (QoL) – nothing more than that. You be the judge.

Slow Starters, but Safe and Effective

For patients used to taking ibuprofen and experiencing relief within a week’s time, a short course on glucosamine/chondroitin isn’t going to give quick results or benefit. It is obvious that the two supplements are slow starters, but when they get into you, after 1 full month of use, the results are often good, sometimes impressive. It is rightly said that what takes time to heal, heals best. The two supplements work at a level that NSAIDs don’t; they go to the “root cause” of the osteoarthritic problem, rebuild the joint structure, and provide the platform to create new, healthy tissue – a process that has to be time consuming.

In a study led by Florent Richy, an epidemiologist with the University of Liege (Belgium), researchers analyzed data from 15 studies of glucosamine/chondroitin compounds. They found that the two “nutrients” do work on symptoms; provide mobility, pain relief, and better QoL; and are “very safe.” The studies in Richy’s analyses all focused on osteoarthritis of the knee, and found that 1775 patients – 1020 taking glucosamine and 755 taking chondroitin –showed “significant changes” in symptoms. No placebo group showed this kind of improvement.

Richy’s findings also suggested that glucosamine significantly improved joint space narrowing. In addition, two chondroitin studies showed comparable results and indicated that the two supplements significantly reduced symptoms, such as pain, stiffness, physical functioning, and joint mobility. Symptom improvement began about 2 weeks after starting the supplements.

Research also suggests that taking at least 1500 mg/day of oral glucosamine sulfate for 3 years was most effective in slowing down the degenerative process. As regards chondroitin, the findings are more or less similar, if not as clear cut. However, according to Richy, the overall safety of glucosamine and chondroitin can be considered excellent. There are, he contends, substantial beneficial effects on osteoarthritis symptoms of glucosamine and chondroitin therapy when compared with placebo.

The two supplements also reduce the swelling of the inflamed joint and morning stiffness, or when the joint has been inactive for a while. Individuals who take glucosamine and chondroitin contend that they are able to move their affected joint better; many have also reported improved walking activity.

These are some of the obvious benefits of taking the two supplements, though the decision to take them is an individual choice. However, one fact remains: osteoarthritis, if not treated early enough, is a progressive degenerative condition, which only gets worse as time rolls by. Not doing anything at all poses enormous risk, including that of deformity.

Conclusion

The use of glucosamine and chondroitin therapy in osteoarthritis is aimed at decreasing joint pain and helping to maintain or improve joint function. While the pharmacological treatment of osteoarthritis has included the use of aspirin, acetaminophen, and NSAIDs, studies in the recent past have investigated and deduced the potential role of chondroprotective (cartilage-protecting) agents, such as the two supplements, in repairing articular cartilage while slowing down the degenerative process of osteoarthritis.

It goes without saying that the duo has gained extensive popularity in the treatment of osteoarthritis, including usage in preventative treatment. Though some clinicians are unconvinced of its value vis-à-vis OTC supplements, numerous patients and newly validated, but not substantially diverse, evidence-based studies have turned the tide – even if they are not sizeable – in the supplements’ favor, by reporting excellent symptomatic relief, comparable to any NSAID drug, but without the latter’s harmful side-effect profile.

Notes

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3. Reginster J Y, Gillot V, Bruyere O, Henrotin Y. Evidence of Nutraceutical Effectiveness in the Treatment of Osteoarthritis. Curr Rheumatol Rep. 2000; 2:472-77.

4. Deal C L, Moskowitz R W. Nutraceuticals as Therapeutic Agents in Osteoarthritis: The Role of Glucosamine, Chondroitin sulfate, and Collagen hydrolysate. Rheum Dis Clin North Am. 1999; 25:379-95.

5. McAlindon T E, LaValley M P, Gulin J P, Felson D T. Glucosamine and Chondroitin for the Treatment of Osteoarthritis: A Systematic Quality Assessment and Meta-analysis. JAMA. 2000; 283:1469-75.

6. Reichelt et al. Efficacy and Safety of Intramuscular Glucosamine sulfate in Osteoarthritis of the Knee. Arzneimittelforschung. 1994; 444[1]:75-80,

7. Vaz et al. Double-blind Clinical Evaluation of the Relative Efficacy of Ibuprofen and Glucosamine sulphate in the Management of Osteoarthritis of the Knee in Out-patients. Curr Med Res Opin. 1982; 8[3]:145–149.

8. Noack W et al. Glucosamine sulphate in Osteoarthritis of the Knee. Osteoarthritis and Cartilage. 1994; 2:51-59.

9. Gaby A R. Natural Treatments for Osteoarthritis. Alt Med Rev. 1999: 4:330-341.

10. Nidamboor R. Herbal Coxibs, Townsend Letter, June 2014; and, Financial Chronicle, November 11, 2014.

11. McCarthy F. The Neglect of Glucosamine as a Treatment for Osteoarthritis. Medi Hypotheses. 1994; 42[5]:323-27.

12. Florent Richy, University of Liege, Belgium. Arch of Intern Med, July 14, 2003.

13. Morrison M. Therapeutic Applications of Chondroitin sulphate: Appraisal of Biologic Properties. Folia Angiol. 1977; 25:225-32.

14. Dovanti A, Bignamini A A, Rovati A L. Therapeutic Activity of Oral Glucosamine sulfate in Osteoarthritis: A Placebo-controlled Double-blind Investigation. Clin Ther. 1980; 3[4]:266-72.

15. Karel Pavelká, MD, PhD, Jindriska Gatterová, MD, Marta Olejarová, MD, Stanislav Machacek, MD, Giampaolo Giacovelli, PhD, Lucio C Rovati, MD. Glucosamine sulphate: Use and Delay of Progression of Knee Osteoarthritis: A 3-Year, Randomized, Placebo-controlled, Double-blind Study. Arch Intern Med. 2002; 162:2113-2123. 

Rajgopal Nidamboor, PhD, is a board-certified wellness physician, fellow of the College of Chest Physicians (FCCP), member of the Center of Applied Medicine (M-CAM), writer-editor, commentator, critic, columnist, author, and publisher. His special interests include natural, integrative and nutritional medicine, psychology, philosophy, and spirituality. His focus areas also encompass contemporary research and dissemination of dependable information for people concerned about their health. He believes that it is increasingly gratifying to see most individuals, including physicians, thinking outside the box – especially in areas such as natural health, where the body knows best to heal itself from the inside out. His published work includes hundreds of newspaper, magazine, Web articles, four books on natural health, two coffee-table books, a handful of e-books, and a primer on therapeutics. He lives in Navi Mumbai, India.