Glucosamine Dominates Joint Health Market
in Spite of Shaky Studies

Patients Love Safe Supplement

What's up, doc? Arthritis patients taking glucosamine are clamoring, “yes, I want more”, in spite of clinical studies that warn, “no, it doesn't work”. This natural substance forms more than 50% of the joint health supplement market (1). It remains a consumer favorite in spite of 2010 and 2011 research that question its ability to relieve pain or rebuild damaged joint structures significantly better than placebo.

In the 1990's, glucosamine was welcomed onto the scene as the first authentic natural helper to appear in arthritis treatment in years. It was safe. Doctors recommended it and patients loved it. Its sales have increased from 1 million dollars a year in 1995 to $1.2 billion projected by 2020, according to research by Grand View Research as reported in New Hope Network November 13, 2014. The industry compound annual growth rate is expected at 14 per cent from 2014-2020 with the U.S. and Japan leading in sales. (2).

The growth is expected due to the ageing population and its demand for this joint supplement, as well as larger numbers of vegans, vegetarians and individuals with shellfish allergies who will drive demand in vegetarian glucosamine.

What does it mean when studies say glucosamine is not significantly better than placebo? Over and over, medical journals and textbooks asserted that placebo effects were so powerful that, on average, 35 percent of patients would improve simply if they were told that a dummy treatment was real.(3)

According to a Harvard Medical School Health Letter, "Arriving at a tidy definition of the placebo effect is difficult, but here's a try: it's a favorable response to a medical intervention — a pill, a procedure, a counseling session, you name it — that doesn't have a direct physiological effect. (Note the emphasis on direct, because there do seem to be indirect effects.) The classic example is when people enrolled in a study experience some improvement in their condition even though they have been assigned, for comparison purposes, to take "dummy" pills that don't contain any active ingredients."(4)

Safety well-documented

Glucosamine has been studied extensively yet the evidence for its effectiveness has never been strong. But its safety is clinically well documented and convincing.

In contrast, the safety of painkiller drugs (the typical intervention for joint issues) has come under fire because of harmful side effects. Long-term use of non-steroidal anti-inflammatory drugs (NSAIDS) is associated with stomach and heart problems.(5)

The clincher, as far as prescribers are concerned, may be good old patient choice. That is to say, patients believe in it. They want it. Studies show it does no harm: why not give it a three-month trial?.

2011 study results not impressive for efficacy

A published literature review entitled, Arthritis Pain? These Supplements Provide Little Relief, appeared in The Journal of Family Practice October, 2011. The authors concluded that glucosamine and chondroitin provide little benefit in terms of pain relief of osteoarthritis of the knee or hip compared with placebo and that doctors should recommend against patients buying them.

The study found that all 3 interventions (glucosamine alone, chondroitin alone, and a combination) were statistically better than placebo but with very little difference in outcomes over time. All of these improvements in pain were less than the authors’ defined minimum clinically significant improvement of 0.9 cm on a 10-cm scale. (6, 6A)

This meta-analysis used more sophisticated comparison techniques and used only larger (and probably better quality) studies than previous meta-analyses. However, inclusion and exclusion were not based on any study quality criteria.

The conclusion is consistent with the American Academy of Orthopedic Surgeons 2008 guideline that also recommended not using the two supplements for knee osteoarthritis.(6B)

2006-2010 GAIT study results beneficial but not significant except for moderate to severe pain

The Glucosamine/chondroitin Arthritis Invervention Trial (GAIT) was a large, randomized, placebo-controlled trial conducted across the United States using glucosamine-hydrochloride with results published in three different journals in 2006, 2008 and 2010. It was sponsored by the National Institutes of Health (NIH) and funded by the National Center for Complementary and Alternative Medicine (NCCAM). (7)

Two-Year GAIT Study Results: June 2010

New data from a long-term study of the dietary supplements glucosamine and chondroitin for knee osteoarthritis pain reveal that patients who took the supplements (alone or in combination) had beneficial but not significant outcomes similar to those experienced by patients who took celecoxib or placebo pills. Previous studies have examined the effects of the supplements on pain associated with osteoarthritis of the knee over a short duration—24 weeks. This study, published in the Annals of Rheumatic Diseases, is the first to assess the safety and effectiveness of the supplements over two years.

Ancillary GAIT Study Results: October 2008

GAIT researchers led by rheumatologists Allen D. Sawitzke, M.D., and Daniel O. Clegg, M.D., both of the University of Utah School of Medicine, conducted a 2-year ancillary GAIT study at nine sites with a subset of participants from the original GAIT study. The ancillary study results, published in Arthritis & Rheumatism, October 2008, showed the two supplements, together or alone, appeared to fare no better than placebo in slowing loss of cartilage in knee osteoarthritis. However, interpreting the study results is complicated because participants taking placebo had a smaller loss of cartilage, or joint space width, than predicted.

Primary GAIT Study Results: February 2006

Researchers led by rheumatologist Daniel O. Clegg, M.D., of the University of Utah School of Medicine, conducted the 4-year primary GAIT study at 16 sites. The results, published in the New England Journal of Medicine, February 22, 2006, showed that the popular dietary supplement combinations did not provide significant relief from osteoarthritis pain among all participants. However, a smaller subgroup of study participants with moderate-to-severe pain showed significant relief with the combined supplements.

The initial GAIT study evaluated the supplements efficacy and safety alone or in combination, as well as celecoxib (prescription drug Celebrex®) and placebo on 1583 patients with knee osteoarthritis. It concluded that glucosamine and chondroitin supplements are extremely safe

What is glucosamine?

Glucosamine is an amino-sugar produced naturally in the body, made from glucose and the amino acid glutamine but its production slows with aging--when people need it the most. It plays an important role in the formation, maintenance, and repair of cartilage and other body tissues. It stimulates the production of molecules glycosaminoglycans and proteoglycans. These substances are the foundation of cartilage, tendons, ligaments, collagen, synovial fluid in the joints and other tissues.

Protoglycans are proteins that make up the connective tissue of cartilage giving joints their elasticity, strength, and resilience.

Glucosamine supplements

The source of glucosamine in most dietary supplements is chitin--most often obtained from the outer skeletons of shellfish, but also from the cell walls of fungi.

The supplement is formulated in tablet, capsule, and powder preparations using glucosamine-sulfate or glucosamine-

hydrochloride both of which are easily absorbed. There is no conclusive evidence to suggest that one form is better than another, however hydrochloride has been reported to be more concentrated and better absorbed by the body.(8, 9)

Unlike the sulfate version, the hydrochloride form does not use salt as a stabilizer. Many people who need these supplements have low sodium restrictions for other conditions, such as high blood pressure. Because of this, the hydrochloride form is preferred by some supplement companies.

Four leading manufacturers--Shaklee Advanced Joint Health Complex, Osto Bi-Flex®, Nature Made® Triple Flex, and Schiff® Move Free®--all use hydrochloride in their joint supplement. Of these, Advanced Joint Health Complex is the only vegetarian-sourced form of glucosamine hydrochloride.

Dietary supplements that contain glucosamine often contain additional ingredients such as chondroitin sulfate, boswellia, MSM, shark cartilage, and trace elements such as manganese, necessary for normal bone health.

The substance is also found in liquid products and topical creams, but there are no clinical studies to evaluate these preparations.

It's also available as an injectable form that your doctor can insert directly into a joint. N-acetyl-glucosamine is also available as an enema.

Vegetarian glucosamine supplements

Glucosamine in supplements is most often sourced from shrimp, crabs or lobster, making them off limits to vegetarians. Shellfish may cause reactions in those with allergies, or a possible worsening of asthma symptoms. (10)

A growing niche market is vegetarian glucosamine supplements, sourced from corn. They target vegetarians but also individuals with shellfish allergies, and those who strictly follow Jewish food habits. They can be used by the general public as well.

If you worry about such things, The Institute for Responsible Technology in May, 2010, estimated tht 85% of commerical corn crops in the U.S. are genetically modified (GMO).(11) DNA, the material used to genetically modify corn, is present only in the protein fraction of that crop.

Since vegetarian-glucosamine is a fermented by-product from corn and contains little to no protein, it is highly unlikely that there are any detectable traces of GMO's in corn-derived glucosamine.

The vegetarian version is also produced in both the hydrochloride or sulfate forms. Glucosamine-hydrochloride may also help the body make chondroitin sulfate (another substance necessary for healthy cartilage).(12)

Who needs it?

Healthy joints operate like a well-oiled machine. Cartilage and joint fluids cushion bones, allowing muscles and tendons to slide smoothly and limbs to move easily.

In osteoarthritis, cartilage—the cushion between the joints—wears away or becomes damaged from overuse or trauma. This leads to pain, swelling, stiffness and loss of joint motion. In rheumatoid arthritis, many symptoms are the same as osteoarthritis. No matter what type of arthritis, glucosamine-containing supplements are often suggested by health care professionals.

Who needs it?

  1. People with osteoarthritis (particularly knee osteoarthritis)
  2. People with rheumatoid arthritis
  3. 91 million Americans over age 45 who face age-related slowdown of cartilage rebuilding.
  4. People who participate in strenuous recreational activity.
  5. Those with job-related repetitive stress to joints—an increasingly common problem given that the incidence of repetitive joint stress has tripled in recent years.
  6. Those well above ideal weight, creating additional pressure on joints
  7. People who lift heavy objects daily (even mothers carrying babies).

Why not chondroitin?

Supplements are available with glucosamine alone and combined with chondroitin.

There's controversy regarding absorption of chondroitin—“gristle” found around joints and in leaner cuts of meat--and its value in a dietary supplement. Chondroitin is too large a molecule to be absorbed whole. It is broken down and digested as it passes through the intestinal tract. Even with the smallest molecule of purified chondroitin sulfate, less than 10% is absorbed. On the other hand, glucosamine is up to 98 percent absorbed.(7)

Most people already get chondroitin from their diet--it’s found in most animal tissue. The chondroitin most often used commercially is bovine cartilage or cow trachea. Some use chondroitin sulfate, which is a cartilage extract. Shark cartilage in a powdered form is another chondroitin source.

Some manufacturers choose to use substances other than combining chondroitin. For example, Advanced Joint Health Complex and Osteo Bi-Flex® both combine the herb boswellia with glucosamine. The Arthritis Foundation notes: “Some studies have shown that boswellia, also known as frankincense, may improve blood flow to the joints and decrease pain and increase function in those with osteoarthritis.”(13)

A 90-day 2011 manufacturer's clinical study illustrated in this short video, the boswellia extract in Advanced Joint Health Complex works in as few as five days—up to 28% faster than claimed by Osto Bi-Flex®, Nature Made® Triple Flex, and Schiff® Move Free®.(14)

Consumer beware—not all supplements are equal

When choosing any dietary supplement it is important to remember that the industry is lightly regulated by the Food and Drug Administration (FDA). This includes the current Good Manufacturing Practices (cGMP),which critics have said are too lax. Even so, FDA facilities inspections discovered nearly two-thirds of supplement companies in violation of purity and safety of the rules from 2010-2016.

Shy away from products backed only by testimonials and not scientific research. Look for manufacturers that evaluate their own products through clinical studies, even though the FDA does not require supplement makers to conduct trials to prove the efficacy of dietary supplements before marketing.

The FDA prohibits any supplement from making overt health claims, such as “cures arthritis”, “regenerates cartilage”, “renews cartilage”, “rebuilds cartilage”, “freedom from pain”, etc. Such marketing statements should be viewed with skepticism as they seldom mean that the product has been researched to make these claims.

Remember, testimonials without scientific backing are basically worthless.

Arthritis Foundation advice when choosing supplements

The Arthritis Foundation advice when choosing supplements, such as glucosamine preparations, are as follows:


Do your research first. Seek scientific studies and reliable sources of information (doctors, pharmacists) for evidence that the supplement is effective in arthritis. What are its side effects? Interaction with other supplements or drugs?

Stick with a reputable manufacturer. Choose products sold by large, well-established companies that can be held accountable (how strong is their guarantee?). How long has the company been in business? What's its reputation? If you don't recognize a brand name or manufacturer, find out how long the store has stocked the brand. Research the company.(15)

30 questions to help you find the best glucosamine supplement company

How do you find the best supplements on the market? In doing my own research, I prepared a list of 30 questions to help me find the best supplement company. The answers led me to Shaklee Corporation, founded in 1956—the number one natural nutrition company in the U.S.

The science behind each of their products is second to none. The Forrest C. Shaklee Innovation Center is home to their

research and development team, which develops, tests, and delivers new product innovations. The center contains state-of-the-art scientific equipment used to ensure their products meet and surpass the highest industry standards of product purity, safety and effectiveness. Products within their portfolio undergo testing in this modern facility, which includes nutritional research, ingredient development, product/process development, quality assurance, and quality control.

They’ve invested more than $250 million in clinical testing, research and development and have over 135 published research manuscripts, 100 of which are published studies in peer-reviewed scientific journals—more than any other nutritional company! Even before the cGMPs, this company voluntarily operated as if regulated the same as a pharmaceutical company—in my opinion, that’s a testament to their integrity.

In 2003, they introduced a glucosamine joint health product, reformulated in 2011 as an advanced complex that includes 1500 mg vegetarian glucosamine and 100 mg of the pain-fighting herb, boswellia.

My husband and I have successfully used the supplement for improved joint function and flexibility since 2003. We both have osteoarthritis. We used to take pharmaceuticals, but no longer use pain relief drugs of any kind. Please see our arthritis story is at this link.

Featured natural glucosamine supplement for arthritis

In clinically-proven Advanced Joint Health Complex, we believe we've found the best glucosamine supplement available. We don’t have to worry about ingredient purity and potency or side effects--we’ve chosen the right company with an ironclad guarantee (if it doesn't work, get your money back). It has certainly >worked for us.

For natural relief of osteoarthritis and rheumatoid arthritis (and a can't-miss guarantee), I confidently recommend Advanced Joint Health Complex.

Note: For information on two other products synergistically designed for pain by Shaklee scientists, click on the following link: The Pain Trio.

Sources/references

(1)Press Release, Global Glucosamine Market to Reach 46.6 Thousand Metric Tons by 2017, Global Industry Analysts, Inc., S.F. Chronicle, August 24, 2011
(2)Winter, Joysa. Article: U.S., Japan lead glucosamine sales; New Hope Network, November 13, 2014
(3)Kolata, Gina. Article: Placebo effect is more myth than science, study says, New York Times, May 24, 2001.
(4)Harvard Health Letter, Putting the placebo effect to work. Harvard Medical School; April, 2012. Putting the placebo effect to work Published: April, 2012 Harvard Health Letter, Harvard Medicals School
(5)Online Medline Plus, Health Topic: Rheumatoid Arthritis, National Institutes of Health (NIH). http://www.nlm.nih.gov/medlineplus/ency/article/000431.htm
(6)Stevermer, JJ; Rogers, N Arthritis pain? These supplements provide little relief, Priority Update from Research Literature (PURL), Journal of Family Practice, October 2011. Vol. 60, No. 10: 610-612.
(6A)Wandel S, Juni P, Tendal B, et al. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. British Medical Journal, 2010;314:c4675.
(6B)Full Guideline, Treatment of Osteoarthritis of the Knee (Non-arthroplasty), adopted by the American Academy of Orthopaedic Surgeons Board of Directors, December 6, 2008.
(7) National Institutes of Health (NIH), National Center for Complementary and Alternative Medicine (NCCAM), Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), 2006 primary and 2008/2010 ancillary study results (links to three journal abstracts) http://nccam.nih.gov/research/results/gait/
(8)Houpt JB, et al. Effect of treatment of glucosamine hydrochloride in the treatment of pain in osteoarthritic of the knee. Journal of Rheumatology 1998; 25 (supplement 52): 8
(9)Article: Glucosamine, Available Forms, Avera Health Services, 5-24-2011.
(10)Benedikt H. Chondroitin sulfate: the new arthritis therapy. Journal of Natural Pharmaceuticals, 1997;1(8):1,22.
11.GMO's in Food, Institute for Responsible Technology, May, 2010.
12. Gaber, C; Day, C., Why Do I Feel This Way?, 2nd Edition, p 146, 2005
13. Boswellia. Arthritis Foundation.FAQ: non-drug treatment OA
14 Product bulletin, New Advanced Joint Health Complex, Shaklee Corporation. A pdf. http://www.shaklee.net/pws/library/products/20281_jointhealthbulletin.pdf 15. Arthritis Foundation. Tips for Selecting and Using Supplements


Disclaimer: Health statements on this page have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease








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