Tag Archives: glucosamine sulfate

Study finds chondroitin improves pain and function in patients with arthritis

A prescription-grade formulation of chondroitin sulfate (Condrosulf) helped improve pain and function in patients with osteoarthritis (OA) of the hand, according to a single-center randomized study of 162 patients who had been suffering from OA for more than six years. Continue reading

My Recommendations for Glucosamine, Chondroitin, and SAMe for Osteoarthritis

Several readers have requested that I post the advice that I both use in practice and teach other healthcare professionals when it comes to a topic on which I frequently teach, Natural Medications for Osteoarthritis: An evidence-based evaluation.

This year I’ve given this talk in several hospitals and to state and national gatherings of physicians and PAs. Let’s start with the take home recommendations:

The Bottom Line

Take Home Point #1

All patients with osteoarthritis should take part in an active exercise regimen and reduce weight (if overweight or obese). I also recommend they begin a diet high in fruits, vegetables, and low in unsaturated fats. Antioxidants in pill form probably won’t help. Instead, I advise patients to boost consumption of vegetables and fruits that provide lots of vitamin C, vitamin E, and beta-carotene as high dietary intake of foods that contain these antioxidants might slow progression of osteoarthritis and have other benefits.

Take Home Point #2

I recommend starting with a a dose of glucosamine sulfate, 1500 mg once daily; however if this dose is not tolerated, I suggest switching to 500 mg three times daily with food. I do NOT recommend glucosamine hydrochloride (glucosamine HCL) or N-acetyl glucosamine (NAG). The evidence generally supports using glucosamine SULFATE for pain and possibly slowing disease progression. But, keep in mind that glucosamine has primarily been studied for osteoarthritis of the knee.

It might not be as effective in other joints.

Take Home Point #3

You need to give the glucosamine 4-8 weeks to see if it will help or not. If not effective, or only partially effective, then change to DONA Glucosamine Sulfate or Xicil Glucosamine Sulphate (both by Rotta Pharmaceuticals). According to the Natural Medicine Comprehensive Database, “This product has been studied in clinical research. Based on this research, this product’s Effectiveness Rating is: LIKELY EFFECTIVE for osteoarthritis. You can find DONA here. (BTW, I have no financial or other ties to sites like this that I recommend to you.)

Take Home Point #4

Chondroitin sulfate appears to be effective for osteoarthritis when combined with conventional treatments (either glucosamine sulfate or glcosamine HCL – using ConsumerLab.com approved combination products such as Cosamine-DS, Spring Valley, Member’s Mark, or Elations Healthier Joints); however, there is more and better evidence for glucosamine SULFATE – and a significant cost differential. I recommend these combinations only for patients who have not responded to 8 weeks of the DONA glucosamine sulfate.

Take Home Point #5

Combination products of glucosamine plus chondroitin or glucosamine plus MSM or glucosamine plus chondroitin plus MSM are probably effective, but there is no reliable evidence that the combination is better than treatment with just glucosamine SULFATE alone.

Take Home Point #6

Based on research to date, SAMe sounds like a great alternative. But two things keep SAMe from moving into primetime: (1) poor product quality and (2) high cost.

Take Home Point #7

Other products look promising … cat’s claw, devil’s claw, stinging nettle. However, since these products work through the same antiinflam-matory mechanisms as current NSAIDs, they may not prove to offer any advantage. It’s way too soon to recommend them.

Products such as avocado-soybean unsaponifiables and cetylated fatty acids also look interesting and appear to hold some promise for improving symptoms. But, I think it’s still a bit premature to recommend them. I’ll be watching closely for more solid evidence.

Now, here are some of the details that I share with healthcare professionals. Thanks to the Natural Medicines Comprehensive Database and ConsumerLab.com for their websites which provide great information for me to share.


This presentation will discuss an evidence-based evaluation supporting or refuting the use of a variety of natural medications (herbs, vitamins, and supplements) for joint symptoms, joint health, and bone health. In addition, we’ll review clinically useful and evidence-based sources of information for natural medications, as well as how to find and recommend quality substances.

Learning Objectives

After this discussion, attendees should be able to:

  1. Describe the natural medications used for osteoarthritis symptoms,
  2. Describe an evidence-based, trustworthy source of information for natural medications,
  3. Describe a independent quality testing lab of natural medications that can be used to recommend safe products, and
  4. Describe the evidence supporting or refuting the use of several natural medications for arthritis.


Osteoarthritis can be very frustrating for patients because it can significantly interfere with an active lifestyle. Treatment choices are limited in range of options and in effectiveness. Ideally, non-drug therapies should be implemented first, when disease severity is mild.

These therapies can include:

  • exercise and weight loss,
  • dietary changes, and
  • physical therapy, braces, wraps/rubs, and other orthopedic devices.

Drug therapy should be considered for patients with moderate to severe symptoms or multi-joint disease.

Commonly Used Medicines for Osteoarthritis

Conventional Medicines

  • Acetaminophen (Tylenol)
  • Non-steroidal Anti-inflammatory Drugs (NSAIDs) — prescription and OTC (such as ibuprofen [Advil] or naproxen [Aleve])
  • Prescription COX-2 Inhibitors such as celecoxib (Celebrex)

Despite treatment with these agents, most patients often only achieve partial pain relief. And these approaches do nothing to slow down the disease process.

Some patients also worry about potential side effects related to taking these drugs, particularly after all the press generated by the COX-2 inhibitors and cardiovascular disease risk.

As a result, many patients turn to natural medicines with the hope of finding something that might:

  • relieve their pain,
  • be safe, and
  • help slow down the disease process.
  • In short … improve their condition.

As such, osteoarthritis is the most common condition for which patients turn to alternative medicines.

Commonly Used Natural Medicines for Osteoarthritis

  • Capsicum
  • Capsicum species
  • Cat’s claw
  • Uncaria guianensis
  • Devil’s claw
  • Harpagophytum procumbens
  • Ginger
  • Zingiber officinale
  • Indian frankincense
  • Boswellia serrata

Commonly Used Structure Modifying Agents for Osteoarthritis

  • Chondroitin sulfate
  • Glucosamine hydrochloride
  • Glucosamine sulfate
  • N-acetyl glucosamine

Commonly Used Natural Medicines containing Antioxidants for Osteoarthritis

  • Beta-carotene (supplements/foods)
  • Superoxide dismutase (SOD)
  • Vitamin C (supplements or foods)
  • Vitamin E (supplements or foods)

Commonly Used Miscellaneous Natural Medicines for Osteoarthritis

  • Avocado (Persea americana)
  • Cetylated fatty acids
  • Methylsulfonylmethane (MSM)
  • S-adenosylmethionine (SAMe)
  • Soybean oil (Glycine max)

Balancing Safety and Effectiveness — My Recommendations for Various Products

Recommend Against — Possibly Ineffective, even though likely safe

  • Vitamin E

Recommend Against — Insufficient Evidence of Safety or Effectiveness

  • N-acetyl glucosamine
  • Phellodendron

Don’t Recommend — Likely or possibly safe, but in-sufficient evidence of effectiveness

  • Ginger
  • Indian frankincense
  • Limbrel
  • MSM
  • Stinging nettle
  • Turmeric
  • Willow bark

Don’t Recommend — Possibly Safe and Possibly Effective

  • Avocado (with soybean oil)
  • Cetylated fatty acids
  • Beta-carotene containing foods
  • Cat’s claw
  • Devil’s claw
  • Glucosamine hydrochloride
  • SOD (injectable)

Caution — Likely Safe and Possibly Effective

  • Chondroitin sulfate
  • Vitamin C  containing foods

Recommend — Effective and likely safe

  • Capsicum (topical)
  • Glucosamine sulfate
  • SAMe

Now, for more details on these products.

Capsicum (topical)

Capsicum peppers contain the constituent “capsaicin.” It’s this compound that makes the peppers fiery hot. Capsaicin is approved by FDA and Health Canada as an OTC drug. Capsaicin is the active ingredient in Zostrix and other OTC products used topically for pain. Topical capsaicin is effective for temporary symptom relief of pain related to osteoarthritis

Repeated use of capsaicin works as a counterirritant, depleting and inhibiting the reaccumulation of substance P (associated with the process of pain transmission in OA) in sensory nerves.

Practice Pearl: I tell patients to allow at least 3 days of multiple daily capsaicin applications to achieve significant pain relief.

Glucosamine sulfate

An optimal treatment for osteoarthritis would be one that modifies the joint structure and returns the joint to its normal, healthy state. So far, medicine has not been able to produce such a therapy. Some researchers think glucosamine might be a candidate.

There’s a lot of hype generated about supplements. In the case of glucosamine, some of it is deserved. But the research has been conflicting and confusing. Over 20 clinical studies lasting up to 3 years and enrolling over 2500 patients have been conducted, evaluating glucosamine for OA. The vast majority of these studies evaluated glucosamine SULFATE for osteoarthritis of the KNEE.

Overall, when the findings of these studies are pooled, glucosamine appears to reduce pain scores by 28% to 41%, and to improve functionality scores by 21% to 46%.

Also, for pain relief, GS 1500 mg qd appears to be comparable to

  • … ibuprofen 1200 mg daily.
  • … piroxicam (Feldene) 20 mg daily …
  • … acetaminophen 1000 mg three times daily.

The effects of GS appear to last longer than these analgesics, but the analgesics work much faster. NSAIDs relieve symptoms within 2 weeks. GS takes 4-8 weeks.

Researchers have speculated for years that GS could potentially modify joint structure and possibly reverse or slow disease progression.

  • In 2001, a study published in Lancet showed that GS might have this effect. Researchers measured joint space narrowing in patients taking glucosamine sulfate. After 3 years of treatment, these patients did not have further joint space narrowing, suggesting that GS might have slowed or stopped disease progression.
  • In 2002, a similar 3-year study published in the  Archives of Internal Medicine showed that patients taking GS did not have increased narrowing of the joint space, again suggesting that GS slows disease progression.
  • A meta-analysis of study results suggests that patients taking glucosamine sulfate 1500 mg/day have 54% reduced risk of osteoarthritis disease progression.
  • A retrospective analysis of patients who took glucosamine sulfate for 1-3 years also showed that glucosamine sulfate is associated with a 57% decreased risk of total knee replacement.

Although most of the research has been positive, especially related to glucosamine sulfate, some research findings have been negative. The reason for the discrepancies is not completely known; however, some experts suspect that different methodologies for assessing improvement, different product formulations, and perhaps different patients have contributed.

The vast majority of glucosamine sulfate research with positive outcomes has been done using a specific brand of glucosamine sulfate called Dona (Rotta Pharmaceuticals, Italy), which costs about $1 per day.

In fact, according to one analysis, when findings from studies using the Dona formulation are pooled, GS appears to be effective; however, when findings using other formulations are pooled, GS appears to be ineffective.

Practice Pearls:

  • Glucosamine does not have a significant effect on insulin sensitivity and does not seem to increase A1C in type 2 diabetes.
  • Glucosamine is derived from the exoskeletons of shrimp, lobster, and crabs, so there is concern that glucosamine products might cause allergic reactions in people who are sensitive to shellfish.
  • There are no documented reports of allergic reaction to glucosamine in shellfish allergic patients.
  • There is also some evidence that patients with shellfish allergy can safely take glucosamine products.

Chondroitin Sulfate

Like glucosamine, chondroitin appears to serve as a substrate for the formation of the joint matrix structure. Chondroitin sulfate alone seems to be effective for improving symptoms of OA when used in conjunction with analgesics.

Trials evaluating a specific blend of glucosamine hydrochloride plus chondroitin sulfate (CosaminDS, Nutramax) have also been positive.

Preliminary evidence also suggests that chondroitin might slow joint space narrowing. However, a 2006 study in the New England Journal of Medicine (GAIT) found that glucosamine HCL or chondroitin or the combination of both was ineffective for relieving symptoms of osteoarthritis.

In a subgroup of patients with more severe osteoarthritis, the combination provided modest relief, while the single agents did not. Some have interpreted this study to suggest that the COMBINATION of glucosamine hydrochloride plus chondroitin could be used for more severe osteoarthritis.


You’ve probably been asked about SAMe (s-adenosylmethionine). It’s most often considered a natural medication for depression. But it is also commonly used for joint pain and osteoarthritis.

SAMe is significantly more effective than placebo, and as effective as NSAIDs, including the COX-2 inhibitor celecoxib (Celebrex), for improving symptoms of OA.

Based on research to date, SAMe sounds like a great alternative. But two things keep SAMe from moving into primetime:

  • poor product quality and
  • high cost.

Tests on SAMe products show that many contain little or none of the active ingredient. Furthermore, patients taking the typical dose (200 mg tid) would have to pay up to $120 per month.

For patients who try SAMe, the butanedisulfonate salt has the highest bioavailability (5%) and is more stable than the tosylate salt which only has 1% bioavailability and there are concerns about stability.

Practice Pearl: SAMe has serotonergic effects. Advise caution in patients with bipolar disorder … it can cause them to convert from depression to manic state. Also, combining SAMe with other serotonergic agents such as antidepressants might lead to symptoms of serotonin syndrome.

How do you find clinically useful, evidence-based, and trustworthy information on natural medications? How do you find safe natural medications to recommend? Especially since natural medications are NOT regulated in the United States

So, how do you find product:

  • that actually contains what the label claims?
  • that is bioavailable?
  • that is NOT contaminated?

ConsumerLab.com Findings:

  • Although prior testing has shown the vast majority of glucosamine products to meet label claims, glucosamine from shellfish such as shrimp and crabs may potentially be contaminated with lead. Among the 21 glucosamine supplements ConsumerLab.com selected and tested, only 16 (64%) met quality standards and FDA labeling requirements. In other words, 36% FAILED testing.
  • Chondroitin is an ingredient with which ConsumerLab.com has found problems in the past — with products not always providing the amount claimed of this expensive ingredient.
  • Among the 19 products claiming to contain MSM, glucosamine, and/or chondroitin, 5 (26%) FAILED testing.
  • Failed for providing less ingredient than labeled, lead contamination, failure to properly break apart, or other mislabeling.
  • All eight of the SAMe supplements that CL selected for testing passed the evaluation. This is considerably better than results in 2003, in which one product was found with only 30% of its listed amount, and in 2000, when nearly half of the products were short on SAMe.


  • There are limited options for patients with osteoarthritis.
  • Many experts, including myself, now consider glucosamine SULFATE a first-line treatment. Others remain skeptical.
  • Nonetheless, the evidence generally supports using glucosamine SULFATE for pain and possibly slowing disease progression.
  • Don’t recommend glucosamine HYDROCHLORIDE or NAG.
  • Keep in mind that glucosamine has primarily been studied for osteoarthritis of the knee. It might not be as effective in other joints.
  • SAMe and perhaps chondroitin also seem to be effective. However, due to product quality control problems and high costs, they may not be as practical an option for most patients.
  • Other products look promising … cat’s claw, devil’s claw, stinging nettle. However, since these products work through the same antiinflam-matory mechanisms as current NSAIDs, they may not prove to offer any advantage. It’s way too soon to recommend them.
  • Products such as avocado-soybean unsaponifiables and cetylated fatty acids also look interesting and appear to hold some promise for improving symptoms. But, it’s still a bit premature to recommend these. I’ll be watching closely for more solid evidence.
  • Antioxidants in pill form probably won’t help. Instead, I advise patients to boost consumption of vegetables and fruits that provide lots of vitamin C, vitamin E, and beta-carotene. High dietary intake of foods that contain these antioxidants might slow progression of osteoarthritis and have other benefits.


Glucosamine and chondroitin products still popular among arthritis sufferers

The New York Times reports that although “tablets that combine glucosamine and chondroitin are popular for those seeking relief from arthritis. Elations offers the supplements in the form of a bottled eight-ounce juice drink or powder mix, and it turns out the beverage appeals to consumers who have trouble swallowing not just pills – but also the fact of aging.”

The Times points out that “Glucosamine and chondroitin have their doubters among doctors, with several studies, including one published in The New England Journal of Medicine in 2006, indicating that for many people, they do not relieve pain much better than placebos.”

However, “such products remain popular with 25 percent of arthritis sufferers seeking relief with glucosamine, chondroitin, or other supplements, according to a 2009 report by Mintel, a market research firm.

You can read more about what I recommend when it comes to glucosamine and chondroitin here.

Glucosamine sulfate appears to have no effect on chronic low back pain from degenerative lumbar osteoarthritis

I’ve posting a blog on the effectiveness of glucosamine sulfate for osteoarthritis of the knee. In my practice, it’s never seemed to work well for arthritis or degenerative disc disease of the lower back. Now, there’s new data supporting my observation.

On its website, ABC News reported, “Glucosamine has looked like salvation to many people with joint pain,” and “statistics attest to the supplement’s widespread appeal.”

For example, a “2007 federal survey of Americans’ use of complementary and alternative medicine found that more than 6 million adults in the United States had taken glucosamine in the previous month.”

Meanwhile, a “study from the US Centers for Disease Control and Prevention, published in 2004, found that among women treated at New Mexico hospitals for joint and muscle pain, 25 percent of those with osteoarthritis used glucosamine.”

Nevertheless, there have been mixed study results regarding the effectiveness of the treatment, according to the Los Angeles Times “Booster Shots” blog. “Some studies have shown the supplement to be effective in treating some joint pain, but others show no benefit.” (You can read why in another of my blogs on the topic)

Now, research coming out of Norway reveals “that glucosamine was no different from a placebo in treating lower back pain.”

The study included 250 individuals with “chronic back pain and degenerative lumbar osteoarthritis” who were randomly assigned “1,500 milligrams daily of glucosamine or an inactive placebo,” HealthDay reported .

The “patients’ pain was measured using the Roland Morris Disability Questionnaire at 6 weeks, then again at 3, 6 and 12 months,” according to the paper in the Journal of the American Medical Association. “At the start of the … trial, patients taking glucosamine scored 9.2 on the pain scale while the patients taking placebo scored 9.7.”

Six months later, “the average score in both groups was 5.0,” MedPage Today reported.” At a year, the average score was 4.8 for glucosamine and 5.5 for placebo, but the difference remained nonsignificant.”

What’s more, “between the end of the intervention and the end of follow-up, there was … no significant difference in average disability score, lower back pain at rest and during activity, and quality of life.”

Still, pointed out the author of an accompanying editorial, “no one study settles any question,” WebMD reported.

But the supplement “did no harm,” explained lead author Philip Wilkens. “And some patients who improved while taking the supplement told him they were sure it helped them.”

I still think it’s worth a try. Just be sure to use one of the brands of Glucosamine Sulfate that have been shown to be most helpful. You can find their names here.

Walking Plus Glucosamine Sulfate May Improve Symptoms of Osteoarthritis

A 30-minute walk taken at least 3 days a week combined with glucosamine sulfate supplements may reduce symptoms of mild to moderate hip or knee osteoarthritis (OA), researchers report in a new study published online in the journal Arthritis Research & Therapy.

Here’s are some of the details based upon a MedScape report:

“Management of [OA] includes the use of non-pharmacologic and pharmacologic therapies,” wrote Norman T. M. Ng, MD, from the University of Queensland, Brisbane, Australia, and colleagues. “Although walking is commonly recommended for reducing pain and increasing physical function in people with OA, glucosamine sulphate has also been used to alleviate pain and slow the progression of OA.”

The main goal of this feasibility study was to evaluate the combined effects of a progressive walking program and glucosamine sulfate intake on OA symptoms and physical activity participation in people with mild to moderate OA.

In addition, the investigators compared the effectiveness of 2 frequencies of walking (3 vs 5 days per week) and 3 step levels (1500, 3000, and 6000 steps per day), combined with glucosamine sulfate supplements, and also examined compliance with supplement intake and the walking program.

The study included 28 patients aged 42 to 73 years. All patients were given 1500 mg of glucosamine sulfate per day for 6 weeks and then began a 12-week progressive walking program while continuing to take glucosamine.

Fifteen patients were randomly assigned to walk 5 days per week, and the remaining 13 were randomly assigned to walk 3 days per week. The participants received a pedometer to monitor their step counts. Step level of walking was gradually increased to 3000 steps per day during the first 6 weeks of walking and to 6000 steps per day for the next 6 weeks in both groups.

Patients were assessed at baseline and at 6-, 12-, 18-, and 24-week follow-ups.

Glucosamine Alone Was Helpful

The researchers found that during the first 6 weeks of the study, when patients were taking glucosamine supplements only, physical activity levels, physical function, and total Western Ontario and McMaster Universities scores improved (P < .05).

These outcomes continued to improve through to the final follow-up, although most improvements were seen between weeks 6 and 12, the authors report.

Compliance with the walking program was the same for both groups

Walking 5 days per week was not more effective than walking 3 days per week in reducing pain and stiffness, increasing physical function, or improving most other measures used in the study, the authors report.

Participants in the 3-day walking group walked 3 days per week, but participants in the 5-day walking group walked slightly less than 4 days per week, which suggests that it may be difficult to get people with hip or knee OA to walk more than 3 to 4 days a week, the authors write.

Increased Activity Further Improved Results

Increasing the number of steps from 1500 to 3000 steps per day, combined with glucosamine intake, resulted in a 125% increase in minutes of physical activity, a 17% reduction in pain scores, and improvements in physical function. Increasing the steps to 6000 steps per day resulted in a further 57% increase in physical activity participation and further improvements in physical function.

“Although the study included a small sample, the findings provide preliminary evidence that OA sufferers can obtain health-related benefits from the combination of glucosamine supplements and walking,” the authors conclude. “If the benefits of this program are confirmed, it could be promoted to increase physical activity among people with hip or knee OA.”

Chris Morris, MD, a practicing rheumatologist at Arthritis Associates in Kingsport, Tennessee, commented on this study for Medscape Rheumatology, saying that it supports what many rheumatologists believe — that low- to no-impact exercise can make a difference in OA of the knee.

Dr. Morris added that many patients have unrealistic expectations about the beneficial effects of exercise. “They expect immediacy in terms of results — they expect to be able to do everything they did 20 years (and often 50 pounds) earlier, and when their knees hurt, they just give up. Patients need to understand that they have to start out light and gradually work their way up — that any program takes time, and that they must commit to the activity long-term.”

The study by the Australian researchers “provides yet another study to help support the viewpoint that exercise can help arthritic symptoms and the patient’s well-being,” Dr. Morris said. “I encourage my patients to exercise and have recommended walking to those who do not have the resources or access to health clubs, wellness centers, water exercise programs. Most people live reasonably near an enclosed shopping mall, many of which are carpeted, and most of which open their doors early for walkers.”

Concerning glucosamine and/or chondroitin for osteoarthritis, here are the recommendations to physicians from the Doctors of Pharmacology at the Natural Medicine Comprehensive Database:

  • If recommending a product, suggest glucosamine SULFATE; Glucosamine Hydrochloride products might also help, but the best evidence is for glucosamine SULFATE, particularly a specific product called Dona (Rotta Pharmaceuticals, Italy).
  • Recommend a dose of 1500 mg once daily; however if this dose is not tolerated, suggest switching to 500 mg three times daily.
  • Chondroitin sulfate appears to be effective for osteoarthritis when combined with conventional treatments; however, there is more and better evidence for glucosamine SULFATE.
  • Combination products of glucosamine plus chondroitin are probably effective, but there is no reliable evidence that the combination is better than treatment with just glucosamine SULFATE.

Knee Arthritis Supplements (Glucosamine & Chondroitin) May Not Help – Why you should NOT believe this headline.

WebMD Health News, along with many other news outlets, are reporting that the results from a national study which examined whether two popular supplements (glucosamine and chondroitin) slow the progression of knee arthritis. The news stories tell you the study shows that the supplements are NOT effective. But, is that true?

My Take: Continue reading