The latest on glucosamine/chondroitin supplements

Robert H. Shmerling, MD
Robert H. Shmerling, MD, Faculty Editor, Harvard Health Publications

Follow me on Twitter  @RobShmerling

When it comes to health supplements, glucosamine and chondroitin are among the most popular. Just how popular are they? According to one estimate, about one in five Americans takes glucosamine and one in 10 takes chondroitin. The cost of these and other non-vitamin supplements and herbal remedies is close to 15 billion dollars per year. So you’d think they must be highly effective. And yet, that’s not so clear.

They are touted not only as arthritis pain relievers but also as treatments to prevent joint disease. Yet, a number of past studies have come to mixed conclusions — some small studies found that people felt better taking glucosamine and/or chondroitin, but at least as many have found no benefit. A 2010 analysis of multiple studies (called a meta-analysis) found that among more than 3,800 people with osteoarthritis of the knee or hip, treatment with glucosamine, chondroitin, or the combination was no better than placebo. The case for these supplements protecting joint health or preventing arthritis is similarly weak.

A new study of glucosamine/chondroitin

A new study of glucosamine and chondroitin enrolled 164 patients with knee pain due to osteoarthritis and gave half of them a combination of glucosamine and chondroitin; the other half received an identical placebo pill. The study was stopped early for an unusual reason — those taking the supplement actually reported worse symptoms than those taking a placebo. This raises the possibility that taking glucosamine and chondroitin might make your joints feel worse than doing nothing.

Does this spell the end of people taking glucosamine, chondroitin, or both? It’s unlikely. While the evidence of benefit is certainly not compelling, people who feel it is helping them may not care so much about individual studies. Even if a treatment is not effective on average, there may be folks who, for whatever reason, get real relief from it. And, even if the benefit is from the placebo effect, the benefit is real and that is hard to give up on. Finally, people are taking glucosamine and/or chondroitin for a number of reasons and conditions other than osteoarthritis of the knee — so this study may not apply to them.

And what about the downsides?

In general, glucosamine and chondroitin are thought to be safe. However, as with any medication, there are potential risks. In this latest trial, people taking the glucosamine-chondroitin combination reported diarrhea and abdominal pain more often than those taking the placebo did. Other reported side effects include

  • heartburn
  • drowsiness
  • headaches
  • allergic reactions (especially if you have an allergy to shellfish).

A small 2013 study found that taking glucosamine may increase the risk of glaucoma, a condition that can threaten vision if not treated. Chondroitin may act as a blood thinner, so it comes with a warning about potential bleeding. Another concern is drug interactions, a problem that can develop with any combination of medications; check with your doctor or pharmacist before taking glucosamine and/or chondroitin. Many doctors warn patients that the FDA does not regulate supplements such as glucosamine and chondroitin, so they may not contain the amounts stated on the label or there could be contaminants in them.

And, of course, there is cost to consider — health insurance usually doesn’t cover these supplements. (I found a glucosamine-chondroitin supplement online for $17.50/month at a popular online supplement chain.)

Should you give it a try?

When my patients ask me about whether they should take glucosamine and/or chondroitin, I keep an open mind. I check on reports of interactions with my patient’s current medications, let them know that the FDA does not regulate these products, and that they are considered unproven. But if a patient is interested in taking these supplements, I rarely object. And if, after a period of time, they have noticed no improvement, I might suggest they discontinue them. As long as they have the information they need and the treatment seems safe, whether to take an over-the-counter supplement for joint symptoms is a decision I leave to my patients.

The bottom line

For advocates of glucosamine and/or chondroitin, this recent study is only the latest bit of bad news. But this is not likely to be the last word. There are different types and doses available and they are taken for a number of different conditions. There may be certain situations in which they are particularly helpful. We’ll need additional research to know what they are.

Comments:

  1. Nina

    Does anyone have any information concerning the effect, if any, of glucosamine on blood sugar levels? I have read a few research papers but none seem to have provided conclusive evidence eith for or against.
    Nina

  2. Christof Faber

    Were these investigations on glucosamine/chondroitine wrong ?
    N Engl J Med 2006 Feb 23; 354 (8) : 795-808 :
    Abstract
    BACKGROUND:
    Glucosamine and chondroitin sulfate are used to treat osteoarthritis. The multicenter, double-blind, placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis.
    METHODS:
    We randomly assigned 1583 patients with symptomatic knee osteoarthritis to receive 1500 mg of glucosamine daily, 1200 mg of chondroitin sulfate daily, both glucosamine and chondroitin sulfate, 200 mg of celecoxib daily, or placebo for 24 weeks. Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia. Assignment was stratified according to the severity of knee pain (mild [N=1229] vs. moderate to severe [N=354]). The primary outcome measure was a 20 percent decrease in knee pain from baseline to week 24.
    RESULTS:
    The mean age of the patients was 59 years, and 64 percent were women. Overall, glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent. As compared with the rate of response to placebo (60.1 percent), the rate of response to glucosamine was 3.9 percentage points higher (P=0.30), the rate of response to chondroitin sulfate was 5.3 percentage points higher (P=0.17), and the rate of response to combined treatment was 6.5 percentage points higher (P=0.09). The rate of response in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group (P=0.008). For patients with moderate-to-severe pain at baseline, the rate of response was significantly higher with combined therapy than with placebo (79.2 percent vs. 54.3 percent, P=0.002). Adverse events were mild, infrequent, and evenly distributed among the groups.
    CONCLUSIONS:
    Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee. Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain. (ClinicalTrials.gov number, NCT00032890.).
    Copyright 2006 Massachusetts Medical Society.

  3. Ally

    For years I have taken glucosamine/chondroitin/MSM. When I take the pills after eating some food, I have NO problems. Occasionally, however, I forget the food – and then I have stomach burn!

    • Rita

      Hi Aly
      I have been taking supplements for the last 9 years for joints and energy. I was told and directed to take ith food or after.
      for a long while I did but when i forget it felt like I was going to throw up.
      However now when i forget I don’t feel as bad. Supplements are like food and meant to be taken’t with food so it can interact better and you won’t feel the effect with a half full stomach.
      Hope this helps

  4. Janis Kvintus

    I have taken this for years and it has helped me so much! The problem is it raises my blood pressure, even with my blood pressure medicine, so I had to stop taking it. My arthritis pain was so bad I started it again, and up went my blood pressure. So I stopped again and I take MSM for pain and optimized quercetin and bromelain , taurine and a few other supplements that help arthritis and I think I have found the answer. My blood pressure went down and no pain!

  5. Stephanie

    well, Doctor, All I know is that both my knees were in awful shape. Take in 25 years ago, Hit by a car on my bike, After flying strait up pasta 40 ft sign & all I knew to do was to place myself in a fetal position, I landed on my knees about one quarter inch above my knee caps. Then about 15 years ago I was walking my 3 65 to 90 pound Airedales when I fell in a hole about 8 inches deep at the edge of someone’s yard & my left knee went BACKWARDS three inches. Then last year I was walking fast on the deck & it was slick,( didn’t know!!!), & I went down with my right knee & ankle twisted behind me. I cannot afford to go to a doc. So I started taking Glucosamine/Chondroitin/w/MSM & my knees are almost healed!! The proof is in the pudding as the old saying goes. My sis has problems with iodine so she cannot take it. I am still trying to find a safe one for her. Thank you !!

  6. Paul Kleiber

    I replied to two of the comments made on this G&C article as I believe they hit the nail on the head. The key is in the efficacy of the brand. The ingredients used, I believe, will affect the way it is absorbed. Who knows what “brand(s)” were used in this and other studies? One comment asked if G&C was measured in the blood stream. Wouldn’t this make sense, rather than anecdotal evidence from people with varying reference points?
    I have used G&C for over 20 years and researched it carefully, actually talking to a doctor at John Hopkins University doing initial studies. They were using Cosamin DS (NutraMax Labs) as their base line. This brand has definitely worked for me – both in pain management and slowing the deterioration of cartilage. (I started after my first hip replacement having been told my other hip would be following soon. After 15 years I finally had my other hip replaced.) No study will change my mind. G&C is a naturally occurring substance, with the body producing less as it ages.

  7. Cynthia Steinberger

    Perhaps not relevant to humans, but I have one canine “double-blind” observation – A couple of years ago my 16 year old bichon was walking very slowly and stiffly, and was using his legs in an unusual way, a gait described by the (French speaking) veterinarian as an “amble”, perhaps indicating back pain – both legs on the same side moved forward together, instead of in opposition -usually one leg moves back while the one leg moves forward – the vet said, without great enthusiasm, that glucosamine might be worth a try; she agreed that clinical evidence was lacking. So I tried – and after a few weeks, I met a neighbour in the park, and as we walked back home with the dog, the neighbour commented that Mopsy was walking briskly again, like a young dog – “What happened to him? Have you discovered the fountain of youth?” she asked. I explained about the doggy glucosamine pills (and the neighbour was so very impressed with the change in Mopsy that she began taking glucosamine herself for joint stiffness).

    The dog did not know whether he was being given an active substance or a placebo – and my neighbour was also ignorant of the dog’s treatment when she commented on the improvement. So one double-blind observation, in favour of glucosamine improving agility in an old bichon. (And my neighbour reports that her knees feel much better, but she does know what she is swallowing ….)

  8. Vince

    Perhaps a little balance here a common standard treatment also does not work “A Controlled Trial of Arthroscopic Surgery for Osteoarthritis of the Knee” NEJM N Engl J Med 2002; 347:81-88 “..When medical therapy fails to relieve the pain of osteoarthritis of the knee, arthroscopic lavage or débridement is often recommended. More than 650,000 such procedures are performed each year1 at a cost of roughly $5,000 each. In uncontrolled studies of knee arthroscopy for osteoarthritis, about half the patients report relief from pain…. Results………At no point did either arthroscopic-intervention group have greater pain relief than the placebo group …………Furthermore, at no time point did either arthroscopic-intervention group have significantly greater improvement in function than the placebo group ‘” So why not complain about that.

  9. Billy Holcombe

    I have taken these supplements for 20+ years. I have thru the years ran out of them or was off my routine of taking them and I have noticed more pain not only in my joints, but also start having more pain in my leg from my sciatic nerve.
    I first started eating gummy candies at a recommendation of my brother I had complained about my ankles bothering me in the morning when I got up. I am not sure how long I had been eating them when one morning I did not have the problem. When I ran out, it came back. I would start again and it would go away. I can affirm there is relief for me by taking the supplements. I told countless people about my experience and they came back and thanked me for telling them. My wife doesn’t tolerate the supplements, so they are not for everyone. For me, however, it just plain works. Must be eating into drug manufactures profits!

  10. M.A.L. DDS

    Since G & C is not injected directly into the bloodstream or joints, what degraded form does it have after digestion and final absorption gastric or intestinally? Has anyone ever done blood analysis to see the levels of circulating G & C (the only way it could get to the joints)? Have any studies been done (animal?) to quantify the increase of G & C in joints after regimens had been administered? I have a feeling that actual scientific studies have been eclipsed by testimonials. One wonders if some may even be related to the companies manufacturing said products.

    • Paul Kleiber

      Excellent comment. I am a proponent and have been using G & C for over 20 years. BUT, before I started, I thoroughly researched brands and have concluded that the efficacy vary greatly from one to another. I believe the key is in “absorbability”. This goes to what you intimate – what exactly reaches the blood and what remains to be absorbed. If the G & C is unusually inexpensive, it is likely made with cheaper ingredients. I use Cosamin DS from NutraMax Labs. They recently came out with Cosamin ASU with different percentages of G & C and have gone back to the DS after a noticeable difference. Without using the best ingredients available, the studies will always be suspect.

      • Laura M

        My veterinarian recommended glucosamine chondroitin ASU for arthritis-associated lameness in my elderly horse. After a few weeks of supplementation he was back to his former active self. I have been giving it to him for 7 years, he is over 30 yrs old, and still active. I looked it up online and found a study in the NIH library supporting the effectiveness of GC ASU in relieving pain of arthritis in the knees in humans. I began taking the human version (same manufacturer) and it has almost eliminated the arthritis pain in my knees. I hike, climb stairs, and sleep without pain. I’m sold. GC ASU for humans is available at Costco and online.

  11. K.E.Watson

    a few years ago I fell going upstairs right on my knee cap.
    This lead to: limping around for months, doctor assessment of no break, just bruised, and NSAIDS for pain relief.
    I found glucosamine sulfate 500 mg which I took 2 times a day.
    I had relief when I took them and pain when I did not.
    After < 18 mos. I stopped and all is good. I now live never thinking about the fall and have no limp and take no meds.
    supplements have a place probably not for all.

  12. Kieran Jones L.Ac.

    I tend to recommend a collagen supplement rather than glucosamine. While the aminos in collagen are non-essential amino acids, I think it is unlikely that all people are making enough of these compounds to serve the routine needs of the skin and gut, the cofactor needs (in the case of glycine), and still have enough left over to support healing a damaged joint. I’ve personally seem encouraging anecdotes in patients I work with.

  13. Phyllis Wolfe

    Several years ago I had terrible pain in my right knee, seemingly out of the blue. I could hardly walk. I contacted the most highly rated knee surgeon in Atlanta at the time. She made an appointment, took an x-ray, and said I was losing cartilage behind my right knee cap. She immediately told me to start taking CosaminDS. It is more expensive but has the stated amount of Chondrotin, which many less expensive brands do not. She also had me do a little physical therapy, but for only a couple of weeks. My pain went away within a few days. I continued the CosaminDS for at least a year, then cut down on the dose and gradually stopped taking it

    Now, from hiking too much or doing too many stairs, I feel a some pain in that knee. Then I take the CosaminDS for a few days or a week. The pain disappears so I gradually cut back to no supplement. This has kept me pain free now for 14 years. IF CARTILAGE LOSS IS YOUR PROBLEM, I HIGHLY RECOMMEND TAKING COSAMIN DS.

    • emeterio I hurtado

      can i take glucosamine sulfate also ??

      • Phyllis Wolfe

        Sorrry, but I cannot answer that question. I would ask your doctor to research that for you. CosaminDS contains both Glucosamine and Chondroitin, so I would not think you would need more of either, but do check with your doctor .

  14. Suzanne Marilley

    I am a breast cancer survivor. After I started taking Letrozole (generic Femara), I suffered stinging pain in my ankles every morning as I rose from bed. I searched on the internet and found the Cosamin DS recommendations. I phoned my doctor who said that I could try it.

    Although this medicine does not vanquish all my joint pain, it certainly took the edge off it, especially in the morning. I take one pill in the morning and one at night. I started taking the pills almost five years ago. I certainly would have had to discontinue taking the letrozole if I had not found some form of relief.

  15. William

    Glucosamine is not independent of joint structure. I had been taking G-C/MSM for years, but finally had to have a hip replacement. It seemed to help, along with other herbal supplements, but did not prevent the loss of cartilage in the joint.

    The year after my surgery, my dog started to limp. An x-ray showed he had lost cartilage in his shoulder and neck not unlike my hip. I upgraded his Eukanuba dog food to the “senior” version “with glucosamine.” Wondering what they added, I looked at the ingredients. The glucosamine comes from “processed chicken parts.” Pretty clear that is bones and joints with lots of cartilage.

    Sure, we both take a glucosamine supplement (which has relieved his limping), but no bone leaves the house without first being subjected to 12 hours of simmering to make bone broth, for both of us. (Hint: stash bones in a ziplock bag in the freezer until you have a good lot for broth.)

    • beaux

      What about your dog? Years ago my really-old dog started limping and favoring his left rear leg. I had started taking G/L w/MSM and started giving him half a pill a day. In a period of 2 weeks he returned to “Throw-the ball-now-buster” health. I will never stop the G/L w/MSM.

      • William

        As I said, “we both take a glucosamine supplement (which has relieved his limping).” His vet-prescribed Dasuquin costs more than my glucosamine supplement, but it works! Half a pill twice a day, with peanut butter.

  16. M A Skeptic

    I am not seeing any references to the study mentioned. I wonder if the source of the supplements is known and whether it was ever tested for actual ingredients; most are never tested.

    • Paul Kleiber

      Exactly. The ingredients are key. I researched G&C before starting over 20 years ago and discovered that how the G&C gets absorbed will make a huge difference. The best, I believe, is Cosamin DS.

  17. Ian Miller

    I have had a hip problem and I tried a glucosamine/chondroitin mix, and it is hard to know whether it worked or not. I felt no adverse effects, but I am shortly going to have a titanium ball and socket to replace my hip parts – the supplements did not solve the joint problem. So, for me, no adverse effects, but no obvious beneficial ones either.

  18. B Hawkins

    Interesting. I started taking Cosamine DS when word drifted back from France about the arthritis relief the supplements were giving- I was about 40 and had a “bad” knee preventing me from doing things. It worked like a miracle, leading me to believe there are some conditions involving joint pain it relieves.
    Recently recommended it to a young friend with hip pain- same results!

  19. Georgia Raysman

    My advice–give it time to work.

    When I was undergoing chemotherapy 10 years ago for breast cancer, an assistant to my Sloan Kettering oncologist suggested that I try a glucosamine/chondroitin supplement. I’d been complaining bitterly about feeling like a veteran of the Spanish-American war when I tried to get out of a chair or walk around the block–not pain in my joints but just a general creakiness.

    I started a regimen of glucosamine/chondroitin supplement but noticed no effect after a month. I tried another combination of both ingredients and again noticed no difference. Finally I tried one more combo–Flexamin Triple Strength–and within a month I realized that gradually my joint creakiness had disappeared and I was completely without symptoms.

    It then also occurred to me, though, that it might not have been the Flexamin that did the trick–it might just have been using the product for at least three months.

    If people give up on it too soon they may be shortchanging themselves. This may just not be a product that produces instant results, something that we lay people have come to expect, but will gradually help one’s joints become healthier.

  20. Stephanie

    How about the use of glucosamine and/or chondroitin for other reasons? Is this study showing they reduced mortality (obviously, for the study time only, not forever) worth considering? Use of glucosamine and chondroitin in relation to mortality. European Journal of Epidemiology, August 2012, Volume 27, Issue 8, pp 593–603

  21. Dr. John Minatelli

    The US Government sponsored 4-year multi-center GAIT study confirms Dr. Shmerlings observations that glucosamine or chondroitin alone or in combination with each other did not show statistically significant improvement in standardized test scoring over the placebo arms in osteoarthritic patients with the exception that those experiencing the highest diseased joint severity showed some statistically significant relief (see: https://nccih.nih.gov/research/results/gait). In shorter well designed placebo controlled human clinical studies glucosamine alone or in combination with chondriotin showed no better response than the placebo arm. This is why research continues to explore new dietary supplement ingredients to find a suitable product that offers clinically effective joint health relief. The well-known side effects of the prescription drugs available on today’s market for treatment of joint pain limit their utility particularly in chronic use. These include the NSAID drug family as well as the opiates and inject-able or oral steroids. Thus there is a strong need for new safe and effective products for chronic use.

  22. Philomena Kanouse, Ph.D.

    I am a 78 year old female who has taken glucosamine and chondroitin for 38 years. I run 5 miles/day, bike, lift weights and do core exercises. I am convinced that I can still do all of these things without pain – nor any joint replacements – is due to g and c. Perhaps they have worked as a preventative measure vs. curing an existing condition.

  23. George Miller

    I have been taking both in the sulfate form. They work for me. The hydrochloride form does not. When I started, it took about 2 months for any effect. I am 79 and don’t have any joint pair but do have muscular pair.

  24. Tom mues

    I have been taking Triple-Flex for over 20 years. It contains the two mentioned ingredients plus MSM. I will be 75 years old in a few months and I have absolutely no joint pain anywhere in my body. I stopped taking it a few years ago and hard a hard time walking up my driveway. I restarted taking it and the pain disappeared. I do not care what the studies report. I will continue taking it.

  25. Richard Jacobs

    This is a useless, dithering article. Every study referred to here has a negative result. There are no references to any peer-reviewed studies with the hint of a positive impact, and yet the doctor does not dissuade his patients from taking the supplements. A little more backbone, doctor!

  26. Jung Yoon

    when i take glucosamine for my joint pain, i feel a little relief from some pain. but when i combined it with chondroitin, i felt very sick. i discontinued chondroitin. i have been taking only glucosamine for years. i f i don’t take it for a few days, the pain is more than usual–when taking glucosamine. thanks.