Joints: The Painful Truth (Advanced Research Series)


By Dr. Doug Kalman, Nutrition Editor

As we age, many of us notice that our joints ache a tad more than they used to. In addition, muscles ache that never used to ache before. Some would say that these symptoms are just part of the natural fabric of aging (for anyone older than 30), but could they also be consistent with osteoarthritis? Osteoarthritis (OA) often manifests itself with joint pain and inflammation, especially in the knees or hips. We can also develop OA in other areas of the body, such as the hands, shoulders or minor joints like the ankle, but those are less common than OA of the knee or hip. You can’t read a newspaper or watch television, especially during a sporting event, without seeing an advertisement for an over-the-counter medicine (such as Tylenol or Advil) or a prescription medication for reducing the symptoms of OA (such as Vioxx or Celebrex). Even so, your doctor and the folks at the health food store are aware of mounting evidence that certain natural extracts may work as well as prescription agents.

Shellfish extract anyone?

We started to eat fish because our mothers told us that it is brain food (they were partially right). Now, we consume fish because it is heart healthy (especially the fatty fish that comes from cold waters, like Pacific salmon), and people take fish oil extracts to promote heart health. But did you ever wonder about the health effects of shellfish? For the most part, if you eat shrimp, lobster or the like, it will have an equivocal effect on your cholesterol profile and heart disease risk—as long as you already have normal cholesterol values1. While Americans consume a lot of shrimp, we often throw out the shells—that is, until recently, when it was realized that certain medicines and natural agents could be extracted from those shells. One specific extract is the popular dietary supplement glucosamine. That’s right, glucosamine is a crustacean-shell extract.

The evidence for glucosamine’s effectiveness

With osteoarthritis, one of the reasons that the joints begin to ache and cause pain is that the cartilage lining—the cushion between the joints—is either worn away or is of subnormal padding. The loss of padding between the joints produces joint space narrowing. One of the objective measurements used by scientists to see if an OA medicine or natural adjunctive agent works is to examine its effects on joint space of an affected joint. If glucosamine has an effect on the joint spacing, it is thought to be a structural effect, which may also reduce the symptoms of OA.

A recent meta-analysis conducted by the Faculty of Medicine at the University of Liege in Belgium evaluated whether glucosamine sulfate had any structural or symptomatic effects in previously published OA clinical trials. Most of the better clinical studies that evaluate any potential medicine or adjunctive agent for OA use the subjective Western Ontario MacMaster University Osteoarthritis Index (WOMAC), which is known as the gold standard in OA research. It assesses how the disease or its treatment intervention (which could be glucosamine or another natural substance or a medicine) works at reducing pain and stiffing and improving the activities of daily living. For many, the OA discomfort they experience is painful, makes walking stiff and interferes with their abilities to do normal everyday things. This 2003 meta-analysis looked at all published research studies from 1980 to 2002 that assessed the effects of glucosamine on arthritis. The results showed that glucosamine had a highly significant effect on every imaginable aspect measured—joint space narrowing, quality of life as assessed by the WOMAC—as well as being considered safe and having a pain-reducing effect2. To put it in perspective, an analysis of 22 years of research found that without doubt, glucosamine works in people with osteoarthritis. The conclusion of this meta-analysis was supported by a secondary review of complementary and alternative medications for those with osteoarthritis, in which University of Maryland researchers determined that there was good evidence to support the claims made on glucosamine, as well as some other substances, for OA 3. What is even more startling is that glucosamine has equal apparent effectiveness as ibuprofen for pain relief without the same gastrointestinal side effects that are possible with ibuprofen 4.

Can glucosamine be good for pain in people who do not have OA?

It appears so, but before any blanket endorsement is decided upon, a review of the non-OA research with glucosamine is warranted. The Department of Human Movement and Exercise Sciences at the University of Western Australia took 46 people who complained of having regular knee pain (with no definitive diagnosis of OA) and split them into two groups to see if glucosamine as compared to a placebo makes any discernable difference on the amount of pain they experienced. The group that was randomized to receive the glucosamine was given a high dose of 2,000 mg per day, while the placebo group got a sugar pill. The study participants answered various standardized questionnaires and performed physical tests. When the statistical analysis was complete, the researchers found that those taking glucosamine had some degree of pain relief and improved function in their knee. It was also noted that the researchers did not detect a difference until the eight-week mark 5. In short, glucosamine appears to have a positive effect on the quality of life in those who have knee pain but do not yet know if they have definitive OA.

What about chondroitin?

Most of us are familiar with the old television show, “Laverne and Shirley,” and perhaps the humor of Abbott and Costello as well Lewis and Martin. The theme here is pairs. The pair that is pertinent to those with OA or knee pain is glucosamine and chrondroitin. Many of the published studies focus on the glucosamine fraction; however, chrondroitin is perhaps underestimated, as is Robin in Batman’s life. The chrondroitin moiety is one that is chiefly derived from cows. In fact, it is typically extracted from the trachea, although a Kosher, vegetarian source is now also available.

Chondroitin has synergistic data with glucosamine and individual data supporting its use in osteoarthritis. From laboratory clinical trials indicating that it stimulates the growth of new cartilage cells (chondrocytes) to the full clinical trials in people like you and me, research shows its effectiveness for reducing the pain associated with OA2, 6. A new form of chondroitin extracted from shark cartilage has recently been tested, and the results indicate that it is well absorbed, so it, too, may too offer benefits for those with OA6.

Will glucosamine and chondroitin raise my blood sugar?

This is a great question and one that has generated a lot of buzz. Glucosamine is a combination of a sugar and an amino acid molecule. It is absorbed in the body through the hexosamine pathway, and overactivity of this pathway disrupts insulin activity7. Glucosamine can theoretically lead to an increase in blood sugar in people with diabetes. Animal research has raised the possibility that it could contribute to insulin resistance, a condition in which the body’s insulin becomes less effective at fueling the body’s cells with sugar. Some doctors speculate this may result from glucosamine’s ability to interfere with an enzyme needed to regulate blood sugar levels.

A recent study of people with type 2 diabetes showed no significant differences in the pre- and poststudy hemoglobin A1c concentrations, a measure of glucose control, in those who took glucosamine-chondroitin and those who took a placebo for 90 days8. A separate study found that these agents do not in fact affect insulin activity or sensitivity in normal adults 9. Therefore, the concern about the potential of glucosamine to impact blood sugar or even insulin negatively appears to be unwarranted.

If you do have diabetes and use these agents, there is nothing wrong with monitoring how you are affected by them and reporting the results to your physician. Glucosamine and chondroitin have no known effects on weight loss, so for those who watch their carbohydrates, there is no need to worry.

Brands tested (noninclusive):

1. Dona

2. Move Free

3. Cosamin

Did the Devil cure your ills?

Have you ever heard of Harpagophytum procumbens? Does Devil’s claw ring a bell? In Germany, Devil’s claw is used in the adjunctive treatment of rheumatoid arthritis and low-back pain. From a genus standpoint, the Devil is considered a tuber, like the lovely potato. A recent publication described a study of Devil’s claw in 75 adults who had diagnosed arthritis of the knee or hip. In order to determine if the herbal preparation offered any benefit, the WOMAC scale was used, and subjects were also asked to rate their pain over 12 weeks. The authors of this study concluded that Devil’s claw reduced pain by about 25% and enabled the subjects taking it to be more physically active. In fact, when the physicians administered a pain test, those receiving the Devil’s claw had a 45% improvement as compared to taking nothing at all. The only negative complaints were dyspepsia and a sensation of fullness10.

In another study out of Germany, the effectiveness of Devil’s claw was evaluated in both older and young adults who suffered from low-back pain or osteoarthritis of the knee or hip. The eight-week study found that by the fourth week, those getting the active product experienced improvement, which grew over time. The authors stated that 50 to 70% of the people who got the Devil’s claw had a positive response with only minor noted side effects11.

Branded Devil’s claw used in the research:

1. Doloteffin: 2,400 mg extract daily containing 50 mg harpagoside.

Other naturally occurring agents that may offer benefit

In New Zealand, an extract of the green-lipped mussel is commonly used for the relief of pain and as an anti-inflammatory agent12. It has been shown in clinical trials to have anti-inflammatory activity in both animals and humans. The evidence points to a disease activity reduction in osteoarthritis, rheumatoid arthritis, asthma and in other inflammatory conditions. In a recent study of 60 subjects who had osteoarthritis of the knee or hip, the green-lipped mussel extract led to a significant improvement in every category tested and evaluated. At the end of the eight-week study, 80% of the subjects taking the product experienced significant improvement in pain and joint function13.

The take home: the only green-lipped mussel product tested, Lyprinol, appears to be one to watch. The data for its effectiveness is accumulating and has been validated by researchers outside of New Zealand.

It is possible that omega-3 fatty acids, which are clinically used for a wide range of conditions, may offer some benefit to those with osteoarthritis. Besides the heart benefits (a daily intake of at least one-gram reduces the risk of heart disease), a recent study found that supplementation with the omega-3 fatty acids and not the omega-6s reduced degenerative and inflammatory aspects of chondrocyte metabolism while having no negative effects on the tissue. Thus, it appears that the daily intake of omega-3 fatty acids through food or dietary supplements has a beneficial effect of slowing and reducing the inflammation that occurs in the development of degenerative joint diseases.

Omega-3 fatty acids are polyunsaturated fats (PUFA). They are found in fatty fish, fish oil supplements and in flaxseed and flaxseed oil as well as other foods. The wealth of data supports the suggestion that about 10% of your fat intake should come from this type of PUFA source.

The last in the category of other naturally occurring agents worthy of mention is a product that has not received much notice in the popular media but perhaps should. Active absorbable algal calcium (AAA-Ca) in one recent study was found to reduce pain. The dose of AAA-Ca used was 900 mg. The weakness in the 80-subject study, however, was that the product was not tested alone; it was combined with collagen (3.5 grams in fact)14. Since the data do appear to support the need for future studies, this form of calcium may be one to watch as you add to your armament in the fight against aging, joint pain and osteoarthritis.

To recap

Researchers across the world have found a plethora of natural agents that may offer some benefit against joint pain and osteoarthritis. As we age, issues surrounding quality of life become more important. For some, being as physically active as they were when they were younger results in a greater duration of muscle soreness, joint pain and sometimes the onset of osteoarthritis.

As shown here, the strongest data appear in support of glucosamine and chondroitin, while a specific type of Devil’s claw also has mounting evidence of its worthiness. You should be getting omega-3 fatty acids in your diet for their many health benefits; for those with joint pain or osteoarthritis, there’s a long list of reasons for you to add omega-3 fatty acids to your supplement routine. Lyprinol and algal-calcium also appear to be of interest in the fight against osteoarthritis.

If any of these natural products interest you, take the time to learn more about them. Being proactive in your own healthcare is the best way to take your health back from today’s world of toxicity. For those of you with osteoarthritis or who are looking to prevent it, the argument for incorporating any of these therapies into your life seems to be a no-brainer.


1) De Oliveira e Silva ER, Seidman CE, Tian JJ, Hudgins LC, Sacks FM, Breslow JL. Effects of shrimp consumption on plasma lipoproteins. Am J Clin Nutr. 1996;64(5):712-7.

2) Richy F, Bruyere O, Ethgen O, et al. Structural and symptomatic efficacy of glucosamine and chrondroitin in knee osteoarthritis: a comprehensive meta-analysis. Arch Intern Med 2003;14:163(13):1514-1522.

3) Socken KL. Selected CAM therapies for arthritis-related pain: the evidence from systematic reviews. Clin J Pain 2004;20(1):13-18.

4) Ruane R, Griffiths P. Glucosamine therapy compared to ibuprofen for joint pain. Br J Community Nurs 2002;7(3):148-152.

5) Braham R, Dawson B, Goodman C. The effect of glucosamine supplementation on people experiencing regular knee pain. Br J Sports Med 2003;37(1):45-49.

6) Volpi N. Oral absorption and bioavailability of icthyic origin chondroitin sulfate in healthy male volunteers. Osteoarthritis Cartilage 2003;11(6):433-441.

7) Pang Y, Bounelis P, Chatham JC, Marchese RB. Hexosamine pathway is responsible for inhibition by diabetes of phenylephrine-induced inotropy. Diabetes 2004;53(4):1074-1081.

8) Scroggie DA, Albright A, Harris MD. The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type II diabetes mellitus: a placebo-controlled, double blinded, randomized clinical trial. Arch Intern Med 2003;163(13):1587-1590.

9) Pouwels MJ, Jacobs JR, Span PN, Lutterman JA, Smits P, Tack CJ. Short-term glucosamine infusion does not affect insulin sensitivity in humans. J Clin Endocrinol Metab. 2001;86(5):2099-103.

10) Wegener T, Lupke NP. Treatment of patients with arthritis of hip or knee with an aqueous extract of devil’s claw. Phytother Res 2003;17(10):1165-1172.

11) Chrubasik S, Thanner J, Kunzel O, Conradt C, Black A, Pollak S. Comparison of outcome measures during treatment with the proprietary Harpagophytum extract Doloteffin in patients with pain in the lower back, knee or hip. Phytomedicine 2002;9(3):181-194.

12) Halpern GM. Anti-inflammatory effects of a stabilized lipid extract of Perna canalicus (Lyprinol). Allerg Immunol 2000;32(7):272-278.

13) Cho SH, Jung YB, Scong SC, Park HB, Byun KY, Lee DC, Song EK, Son JH. Clinical efficacy and safety of Lyprinol,a patented extract from New Zealand green-lipped mussel (Perna Canaliculus) in patients with osteoarthritis of the hip and knee: a multicenter 2-month clinical study. Allerg Immunol 2003’35(6):212-216.

14) Fujita T, Ohue M, Fujii Y, Miyauchi A, Takagi Y. The effect of active absorbable algal calcium (AAA Ca) with collagen and other matrix compoenents on back pain as measured by skin impedance. J Bone Miner Metab 2002;20(5):298-302.

Dr. Kalman has been involved in over 100 clinical trials within the pharmaceutical, medical and nutrition fields, having published over 50 abstracts & more than 25 peer-reviewed manuscripts. Dr. Kalman earned a Doctorate in exercise and nutritional biochemistry and is an active member or spokesperson with many organizations (ISSN, NSCA, APS, ACSM, etc.) and a co-founder of The International Society of Sports Nutrition.