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.

Abstract

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

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.

SAMe

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.

Conclusion

  • 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.

Bibliography

4 thoughts on “My Recommendations for Glucosamine, Chondroitin, and SAMe for Osteoarthritis

  1. Michael Grant

    You state, “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.”

    But a contrary view from http://en.wikipedia.org/wiki/Sam-e :

    “Claims that the SAMe butanedisulfonate salt is more stable or better absorbed are not supported by the references that are usually cited as evidence. Different salts have successfully been used in clinical trials, but there is no published head-to-head comparison.[16][17][18]”

    I have found nothing supporting either view. I would appreciate it if you could provide the actual article(s) or reference on which you based your statement.

    I have severe spinal arthritis and intend to try SAMe, but want to make certain I am buying the best form of SAMe, if in fact it makes a difference.

    Thank you.

  2. waltlarimore

    Here are the comments and citations from the Natural Medicines Comprehensive Database (www.NaturalDatabase.com):

    Currently, several oral salt forms of SAMe are available: sulfate, sulfate-p-toluenesulfonate (also labeled as tosylate), and butanedisulfonate (Friedel HA, Goa KL, Benfield P. S-adenosyl-L-methionine. A review of its pharmacological properties and therapeutic potential in liver dysfunction and affective disorders in relation to its physiological role in cell metabolism. Drugs 1989;38:389-416, http://www.ncbi.nlm.nih.gov/pubmed/2680435?dopt=Abstract; and Cowley G, Underwood A. Newsweek. July 5, 1999; pp. 46-50.).

    The oral bioavailability of the tosylate salt is 1%, and the oral bioavailability of the butanedisulfonate salt is 5%, presumably due to a large first pass effect (Investigator’s Brochure: Ademetionine 1,4-butanedisulfonate. Knoll Pharmaceuticals; Stramentinoli G, Gualano M, Galli-Kienle M. Intestinal absorption of S-adenosyl-L-methionine. J Pharmacol Exp Ther 1979;209:323-6, http://www.ncbi.nlm.nih.gov/pubmed/439007?dopt=Abstract).

    Concerns about the stability of the tosylate formulation have been expressed (Czap A. Beware the son of SAMe. Altern Med Rev 1999;4:73, http://www.ncbi.nlm.nih.gov/pubmed/10231606?dopt=Abstract).

    The butanedisulfonate salt is stable for 2 years at room temperature (Investigator’s Brochure: Ademetionine 1,4-butanedisulfonate. Knoll Pharmaceuticals; Cowley G, Underwood A. Newsweek. July 5, 1999; pp. 46-50.).

    Hope this helps.

    Dr. Walt

  3. waltlarimore

    Also, this from the Natural Database on the effectiveness of SAMe for osteoarthritis:

    Multiple clinical trials show that taking SAMe orally is superior to placebo and comparable to NSAIDs, including the COX-2 inhibitor celecoxib (Celebrex), for decreasing symptoms associated with osteoarthritis.

    SAMe is associated with fewer adverse effects than NSAIDs and is comparable in reducing pain and improving functional limitation.

    Significant symptom relief with SAMe may require up to 30 days of treatment compared to only 15 days with NSAIDs.

    Some evidence suggests that intravenous loading doses of SAMe given over five days, followed by oral treatment, can speed symptom relief to 14 days.

    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. SAMe also costs a fortune.

    For example, patients taking the typical dose of 200 mg three times daily, would have to pay from $60 to $120 per month.

    Dr. Walt

  4. waltlarimore

    By the way, all eight of the SAMe supplements that ConsumerLab (www.ConsumerLab.com) selected for quality 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.

    All caplet and tablet products were able to disintegrate properly.

    You can learn which products passed at http://www.ConsumerLab.com.

    Dr. Walt

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