• Mild early-morning stiffness, stiffness following periods of rest, pain that worsens on joint use, loss of joint function
• Local tenderness, soft tissue swelling, joint crepitus (crackling sound), bony swelling, and restricted mobility
• X-ray findings (narrowed joint spaces, cartilage erosion, bone spurs, etc.)
Arthritis is inflammation of the joints. The most common form of arthritis is osteoarthritis, which is also known as degenerative joint disease because it is characterized by joint degeneration and loss of cartilage, the shock-absorbing gel-like material between joints.
The percentage of people who have osteoarthritis increases dramatically with age. Surveys have indicated that more than 40 million Americans have osteoarthritis, including 80% of those over the age of 50. Under age 45, osteoarthritis is much more common in men; after 45, it is a little more common in women.1,2 The hands and the weight-bearing joints—knees, hips, and spine—are most often affected by the degenerative changes of osteoarthritis. These joints are under greater stress because of weight and use.
Osteoarthritis is divided into two categories: primary and secondary. In primary osteoarthritis, the degenerative wear-and-tear process occurs after the fifth or sixth decade of life, with no apparent predisposing abnormalities. The cumulative effects of decades of use leads to the degenerative changes by stressing the collagen matrix, the support structure of the cartilage. Damage to the cartilage results in the release of enzymes that destroy cartilage components. With aging, the ability to restore and synthesize normal cartilage structures decreases. The incidence of osteoarthritis increases dramatically with age and body mass index for weight-bearing joints.1–3
Secondary osteoarthritis is associated with some predisposing factor that is responsible for the degenerative changes.4 Predisposing factors for secondary osteoarthritis include inherited abnormalities in joint structure or function, trauma (fractures along joint surfaces, surgery, etc.), presence of abnormal cartilage, and previous inflammatory disease of joints (rheumatoid arthritis, gout, septic arthritis, etc.).
Contributors to Osteoarthritis
Age-related changes in collagen-matrix repair mechanisms
Altered biochemistry
Fractures and mechanical damage
Genetic predisposition
Hormonal and sex factors
Hypermobility/joint instability
Inflammation
Inflammatory joint disease
Other factors
One of the most interesting clinical features of osteoarthritis is the lack of correlation between its severity as determined by X-rays and the degree of pain. In some cases the joint appears essentially normal, with little if any joint space narrowing, yet the pain can be excruciating. On the other hand, there are cases where there is tremendous deformity, yet little if any pain. In fact, about 40% of individuals with the worst X-ray classification for osteoarthritis are pain free.5 Depression and anxiety appear to increase the perception of pain from osteoarthritis.
Therapeutic Considerations
Normally the body deals with damage to cartilage by attempting to repair itself. This damage can be halted and sometimes reversed. The major therapeutic goal should be to decrease the rate of damage and enhance the repair and regeneration of the collagen matrix.6,7
One group of researchers studied people with osteoarthritis of the hip over a 10-year period without treatment. All subjects had X-ray changes suggestive of advanced osteoarthritis, yet the researchers reported marked clinical improvement and X-ray evidence of repair in 14 of 31 hips over time.8
Nonsteroidal anti-inflammatory drugs (NSAIDs) have become the main treatment of osteoarthritis in conventional medicine. Although these drugs provide short-term symptomatic relief, they do not address the cause of the problem and may actually increase the rate of degeneration of the joint cartilage. Experimental studies have shown that aspirin and other NSAIDs inhibit collagen matrix synthesis and accelerate cartilage destruction.9 Some retrospective clinical studies have shown that NSAID use is associated with acceleration of osteoarthritis and increased joint destruction.10–13
A patient is unlikely to die from osteoarthritis, but NSAID use is associated with significant risk for mortality. With older NSAIDs the risk is primarily related to gastrointestinal bleeding, while newer cyclooxygenase-2 (COX-2) inhibitors such as celecoxib (Celebrex) are associated with an increase in deaths due to heart disease.
The key dietary focus in the prevention and treatment of osteoarthritis is the achievement of normal body weight and improvement in insulin sensitivity. Excess weight means increased stress on weight-bearing joints, and there is also considerable evidence linking osteoarthritis to insulin resistance (see the chapter “Obesity and Weight Management”). Insulin resistance not only increases inflammation but also impairs cartilage regeneration.14 Proper sensitivity to insulin is required to signal cartilage cells to increase the synthesis and assembly of structural molecules known as proteoglycans, and the most prominent early change seen in the articular cartilage in osteoarthritis is a decrease in both proteoglycan content and structure.
Weight reduction, possibly due to a combination of mechanical and physiological factors, reduces the risk for osteoarthritis and has also been shown to reduce pain and improve cartilage function in existing osteoarthritis, especially when combined with exercise.3,15,16 Lack of exercise decreases the hydration of the joint cartilage and retards diffusion of nutrients into the affected area. When arthritis pain develops, sufferers often tend to reduce activity, and inactivity in turn decreases muscle strength. Muscle weakness increases joint wear, and the inactivity can lead to weight gain, which can worsen osteoarthritis, causing this cycle to repeat itself. In addition, patients with diabetes and cardiovascular concerns who limit their exercise may also increase their risk related to these illnesses. Weight loss and exercise independently decrease the causative factors of osteoarthritis and produce clinical improvement, but the best results are achieved by a combined approach. One study involved 252 obese elderly patients with a body mass index greater than 28 and X-ray-confirmed osteoarthritis who were randomized into healthful-lifestyle (control), diet-only, exercise-only, and diet-plus-exercise groups.16 The exercise program involved hour-long sessions that focused on aerobics and resistance training three times a week. The dietary interventions were intended to produce an average weight loss of 5% during the 18-month period. The most benefit was demonstrated in the diet-plus-exercise group. Compared with control patients and the diet-only group, subjects in the diet-plus-exercise group gained a significant improvement in self-reported physical function, six-minute walking distance, stair-climb times, and knee pain scores. Improvements in the exercise-only group were limited to the six-minute walking distance.
In general, the principles detailed in the chapter “A Health-Promoting Diet” are appropriate for osteoarthritis. As with other degenerative health conditions, the Mediterranean diet may show positive effects in arthritis. The Mediterranean diet includes abundant plant foods (fruits, vegetables, whole grains, beans, nuts and seeds); minimally processed, seasonal, locally grown foods; fish and poultry; olive oil as the main source of fat; and dairy products, red meat, and wine in low to moderate amounts. Thus the diet is rich in monounsaturated fatty acids, long-chain polyunsaturated fatty acids, antioxidants, and unrefined carbohydrates. The Mediterranean diet has shown significant effects in rheumatoid arthritis in two recent studies and may show similar benefit in osteoarthritis.17,18
One popular dietary practice in the treatment of osteoarthritis is eliminating foods from the family Solanaceae (nightshade family). A horticulturist, Norman Childers, arrived at this method after finding that this simple dietary elimination cured his own arthritis.19 His theory is that genetically susceptible individuals might develop arthritis and other complaints from long-term, low-level consumption of the alkaloids found in tomatoes, potatoes, eggplant, peppers, and pimento. Presumably these alkaloids inhibit normal collagen repair in the joints or promote inflammatory degeneration of the joint. Although as yet unproved, this diet has been of benefit to some individuals.
Glucosamine
Glucosamine sulfate has emerged as the most popular nutritional approach to osteoarthritis. It is a simple molecule composed of glucose and an amine. Its main physiological function in joints is to stimulate the manufacture of glycosaminoglycans (GAGs)—molecules that provide the structural framework of cartilage and attract water to provide the gel-like nature of cartilage. Glucosamine also promotes the incorporation of sulfur into cartilage. It appears that as some people age, they lose the ability to manufacture sufficient levels of glucosamine. The result is that cartilage loses its gel-like nature and consequently its ability to act as a shock absorber. Extensive preclinical and clinical research, including long-term double-blind studies, supports a potential role for glucosamine as a primary treatment for arthritis.
Numerous double-blind studies have shown glucosamine to produce much better results compared with NSAIDs, placebos, or acetaminophen in relieving the pain and inflammation of osteoarthritis. While some of the studies comparing glucosamine with NSAIDs or acetaminophen show similar reductions in pain and symptom scores, only glucosamine improves indicators of joint function and markers showing improvement in cartilage structure. Typically the advantages of glucosamine over these other treatments are seen after two to four weeks of use, but there is some evidence that the longer glucosamine is used, the greater the therapeutic benefit.20–37
Not all studies have shown clear positive results; a few have shown no greater benefit for glucosamine over a placebo in improving symptom scores.38–41 However, it must be kept in mind that the placebo response in osteoarthritis is quite high and may confound the true benefit of glucosamine and other approaches to osteoarthritis. Fortunately, there have been several studies showing objective improvements. The results from the two longest placebo-controlled trials show quite convincingly that glucosamine slows down the progression of osteoarthritis and in many cases produces regression of the disease, as noted by X-ray improvements, and significantly reduces the incidence of total joint replacement even as much as five years after glucosamine treatment is discontinued.26–30
In the first long-term study, 212 patients with knee osteoarthritis were randomly assigned 1,500 mg oral glucosamine or a placebo once per day for three years. X-rays were taken of weight-bearing joints at enrollment and after one and three years. Average joint-space width was assessed along with symptoms of pain, stiffness, and functionality.26 The 106 patients on the placebo had progressive joint-space narrowing, with a mean joint-space loss after three years of 0.31 mm. In the glucosamine group, no significant joint-space loss occurred. Furthermore, among patients with a greater joint-space width (over 6.2 mm), those in the placebo group demonstrated a 14.9% narrowing of joint space, while patients from the glucosamine group experienced a narrowing of only 6%.28
In the second long-term study, 202 patients with knee osteoarthritis were randomly assigned to receive glucosamine (1,500 mg once per day) or a placebo.27 Changes in CAT scan and symptom scores were used to judge efficacy. Symptoms improved more significantly in the glucosamine group, but the most telling result was the fact that joint space narrowed 0.19 mm with placebo use, while there was as actually an 0.04-mm increase in joint space with glucosamine use.
Of 414 participants in the two long-term studies, 319 were postmenopausal women. After three years, postmenopausal participants in the glucosamine group showed no joint space narrowing, whereas participants in the placebo group experienced a narrowing of 0.33 mm.29 After three years, the glucosamine group showed a 14.1% improvement in symptom scores, while the placebo group actually worsened by 5.4%. These results may indicate that postmenopausal women may be especially responsive to glucosamine.28
Several head-to-head, double-blind studies have shown glucosamine to produce much better results compared with NSAIDs and analgesics in relieving the pain and inflammation of osteoarthritis, despite the fact that glucosamine exhibits little direct anti-inflammatory effect and no direct analgesic or pain-relieving effects.31–37 As we have noted, NSAIDs and analgesics such as acetaminophen offer purely symptomatic relief, and NSAIDs may actually promote the disease process; by contrast, glucosamine appears to address the cause of osteoarthritis by promoting joint repair, thus relieving symptoms. The clinical effect is impressive, especially when glucosamine’s safety and lack of side effects are considered.
In one of the earlier comparative studies in which glucosamine (1,500 mg per day) was compared with ibuprofen (1,200 mg per day), pain scores decreased faster in the first two weeks in the ibuprofen group. However, by week four the group receiving glucosamine experienced a significantly better improvement than the ibuprofen group.31 Physicians rated the overall response as good in 44% of the glucosamine-treated patients as compared with only 15% of the ibuprofen group.
Additional studies designed to further evaluate the comparative effectiveness of glucosamine and NSAIDs provide even better evidence.32–37 One study consisted of 200 subjects with osteoarthritis of the knee who were given either glucosamine (500 mg three times per day) or ibuprofen (400 mg three times per day) for four weeks.32 Consistently with previous studies, the ibuprofen group experienced quicker pain relief. However, by the end of the second week, the group taking glucosamine experienced results as good as those of the ibuprofen group. In addition, although the side effects of glucosamine were mild and affected only 6% of the group, ibuprofen produced more significant side effects much more frequently, with 35% of the group experiencing them.
Glucosamine was shown to offer significant benefit in an open trial involving 1,506 patients in Portugal.42 The patients received 500 mg glucosamine three times per day over a mean period of 50 days. Symptoms of pain at rest, on standing, and during exercise, as well as in limited active and passive movements, all improved steadily throughout the treatment period. Objective therapeutic efficacy was rated by doctors as “good” in 59% of the patients and “sufficient” in a further 36%. Although this was not a controlled study, a 95% response rate is impressive. The results with glucosamine were rated by both doctors and patients as being significantly better than those obtained with previous treatment including NSAIDs, vitamin therapy, and cartilage extracts. Glucosamine produced good benefit in a significant portion of patients who had not responded to any other medical treatment. The improvement with glucosamine lasted for 6 to 12 weeks after the end of treatment. Obesity was associated with a significant shift from a “good” to a “sufficient” outcome. This finding may indicate that higher dosages may be required for obese individuals or that glucosamine is not enough to counteract the added stress of obesity on the joints. Patients with peptic ulcers and patients taking diuretics were also associated with a shift from “good” to “sufficient” in efficacy as well as tolerance. Individuals with current peptic ulcers should take glucosamine with foods. People taking diuretics may need to increase the dosage to compensate for the reduced effectiveness.
Glucosamine may also have a role as a preventive measure against the development of osteoarthritis, especially in athletes subjected to joint strain. One study to investigate the cartilage-protective action of glucosamine in athletes compared biomarkers for cartilage breakdown and manufacture in soccer players and nonathlete controls before and after they took glucosamine or a placebo. Based on the ratio of cartilage breakdown to manufacture, it was concluded that glucosamine exerts a cartilage-protective effect in athletes by preventing cartilage degradation but maintaining cartilage synthesis.43
Glucosamine only mildly affects the speed of recovery from an injury. In a study of 106 male athletes after acute knee injury who were given either glucosamine (1,500 mg per day) or a placebo for 28 days, no significant difference was found between the glucosamine group and the placebo group in pain intensity scores for resting and walking, or in degree of knee swelling, at the 7-day, 14-day, 21-day, and 28-day assessments. The only finding that placed glucosamine over the placebo was in knee flexibility after 28 days of treatment.44 For more information on natural approaches for acute sports injuries, see the chapter “Sports Injuries, Tendinitis, and Bursitis.”
Results of a Double-Blind Study of Glucosamine vs. Ibuprofen34 |
||||
TIME |
GLUCOSAMINE |
IBUPROFEN |
||
Knee Pain (Average Score) |
||||
Before treatment |
8.42 |
8.46 |
||
Week 2 |
5.54 |
5.63 |
||
Week 4 |
3.60 |
4.18 |
||
2 weeks after treatment |
3.26 |
3.84 |
||
Knee Swelling (Average Score) |
||||
Before treatment |
1.43 |
1.48 |
||
Week 2 |
0.77 |
0.89 |
||
Week 4 |
0.47 |
0.48 |
||
2 weeks after treatment |
0.36 |
0.54 |
||
Clinical Improvement |
||||
|
Glucosamine |
Ibuprofen |
||
Effectiveness |
After 4 Weeks (%) |
After 6 Weeks (%) |
After 4 Weeks (%) |
After 6 Weeks (%) |
Symptom free |
45 |
55 |
32 |
36 |
Improved |
39 |
32 |
45 |
41 |
Unchanged |
11 |
7 |
15 |
14 |
Worsened |
5 |
6 |
8 |
9 |
Side Effects |
||||
|
Glucosamine Sulfate |
Ibuprofen |
||
Side effects |
6% |
16% |
||
Dropouts |
0% |
10% |
||
The standard dosage for glucosamine is 1,500 mg per day. It may be administered as a single dose or divided doses with equal effectiveness. Obese individuals may need higher dosages, based on their body weight (e.g., 20 mg/kg per day). Also, individuals taking diuretics may need to take higher dosages. Athletes or individuals who subject their joints to greater wear and tear may need to increase the dosage to 3,000 mg to maintain positive cartilage synthesis.
Glucosamine sulfate appears to be more effective than glucosamine hydrochloride. Unfortunately several large, well-publicized studies have utilized the hydrochloride form. For example, the Glucosamine/Chondroitin Arthritis Intervention Trial involved 1,583 patients with symptomatic knee osteoarthritis.45,46 Patients were randomly assigned to receive 1,500 mg glucosamine hydrochloride per day, 1,200 mg chondroitin sulfate per day, both glucosamine hydrochloride and chondroitin sulfate, 200 mg celecoxib per day, or a placebo. Overall, glucosamine hydrochloride and chondroitin sulfate were not significantly better than the placebo in reducing knee pain by 20%.
Glucosamine sulfate has an excellent safety record in animal and human studies. On the basis of these studies, many experts have recommended that glucosamine be considered as a preferred treatment for osteoarthritis. Side effects, when they do appear, are generally limited to light to moderate gastrointestinal symptoms, including stomach upset, heartburn, diarrhea, nausea, and indigestion. If these symptoms occur, glucosamine should be taken with meals.
Some people are sulfur-sensitive and may worry about taking glucosamine sulfate. However, an important distinction needs to be made. When patients report that they are allergic to sulfur, what they usually mean is that they are allergic to sulfa drugs or sulfite-containing food additives. It is impossible to be allergic to sulfur, as sulfur is an essential mineral. The sulfate form of sulfur is present in human blood. In short, glucosamine is extremely well tolerated, and only a few allergic reactions have been reported, although millions of people take glucosamine.
Concern has been expressed that glucosamine may influence insulin secretion or action, or both. This concern is based primarily on in vitro studies with high concentrations of glucosamine that are impossible to achieve with oral supplementation at recommended dosages. Detailed human studies show glucosamine has no impact on insulin secretion or action in healthy subjects, those with type 2 diabetes, or those with insulin resistance.47–50 In fact, in long-term studies, glucosamine actually produced a nonsignificant lowering of fasting blood glucose concentrations in all groups of subjects.50
Glucosamine may potentiate the effect of warfarin (Coumadin). The World Health Organization adverse drug reactions database documented 21 spontaneous case reports in which glucosamine interfered with warfarin; 17 of these resolved when glucosamine was stopped. Given the widespread use of glucosamine, this potentiation does not appear to be a significant concern. Nonetheless, patients using both warfarin and glucosamine should be monitored by a physician.51
Chondroitin
Chondroitin sulfate (as well as shark cartilage, bovine cartilage extracts, and sea cucumber) contains a mixture of intact or partially hydrolyzed GAGs. Chondroitin sulfate is composed of repeating units of derivatives of glucosamine sulfate with attached sugar molecules. Although the absorption rate of glucosamine sulfate is 90% to 98%, the absorption of intact chondroitin sulfate is estimated to be much lower, anywhere from 0% to 13%.52–54 The difference in absorption is largely due to the difference in size. A molecule of chondroitin sulfate is at least 50 to 300 times larger than a molecule of glucosamine sulfate—too large to pass through the normal intact intestinal barrier or into cartilage cells. These absorption problems suggest that any direct effect of these compounds in osteoarthritis is highly unlikely. Furthermore, chondroitin sulfate levels are typically elevated in the synovial tissues in patients with osteoarthritis.55 Any clinical benefit from chondroitin sulfate is most likely due to the absorption of sulfur or smaller GAG molecules broken down by the digestive tract. However, even this is controversial, as in one human study, 1 g chondroitin sulfate failed to increase serum GAG concentration at all. These results prompted the researchers to conclude that oral chondroitin has no effect on cartilage.56,57
Despite the fact that direct action by the chondroitin molecule is unlikely, one study using 800 mg chondroitin sulfate for two separate periods of three months over the course of one year showed decreased pain and improved knee function, as well as a decrease in the progression of joint space reduction.58 This study reveals that even intermittent use of chondroitin may be effective.
The clinical studies that have been done with orally administered chondroitin sulfate demonstrate that it is less effective than glucosamine sulfate.59–64 Furthermore, there is no evidence that using glucosamine and chondroitin together is more effective than using either alone. In general, the more impressive results have been achieved with glucosamine sulfate. Nevertheless, given the safety record of chondroitin and evidence that it may modify joint space pathology, chondroitin is a reasonable addition to an osteoarthritis patient’s glucosamine regimen. Although it has no apparent direct action, chondroitin may provide a modest benefit by exerting some indirect effect on improving joint health (see next section).
Hyaluronic Acid
Hyaluronic acid is an important GAG in joints, where it provides a structural framework and affects the ability of the cartilage to hold water. By the time most people reach the age of 70, the hyaluronic acid content in their body has dropped by 80% from when they were 40, predisposing them to a decrease in connective tissue integrity, particularly in the skin and joints. Weekly injections of hyaluronic acid (Synvisc, Hyalgan, Supartz, etc.) into joints affected by osteoarthritis have been shown to be an effective treatment, with improvement noted in pain, function, and patients’ self-assessment at different postinjection periods, but especially at 5 to 13 weeks postinjection.65
Oral supplementation with hyaluronic acid has been shown to be a practical method of increasing body hyaluronic acid stores. Supplements feature hyaluronic acid derived either from animal sources or from bacterial fermentation.
Two double-blind, placebo-controlled studies have been done on the effects of hyaluronic acid in osteoarthritis. In the first, 20 patients with knee osteoarthritis were given either hyaluronic acid (80 mg per day) or a placebo for eight weeks.66 Compared with the placebo group, pain scores were significantly improved in the hyaluronic acid group. In the second study, 60 patients with osteoarthritis were randomized to receive either 200 mg hyaluronic acid, 100 mg hyaluronic acid, or a placebo for eight weeks.67 Significant reductions in pain scores and total symptom scores were seen with the 200-mg dosage but not with the 100-mg dosage.
Niacinamide
In the 1940s and 1950s Dr. William Kaufman, and later Dr. Abram Hoffer, reported good clinical results in the treatment of hundreds of patients with rheumatoid arthritis and osteoarthritis using high-dose niacinamide (900 to 4,000 mg per day in divided doses).68,69 Dr. Kaufman documented improvements in joint function, range of motion, muscle strength and endurance, and sedimentation rate. Most patients achieved noticeable benefits within one to three months of use, with peak benefits noted between one and three years of continuous use.
These clinical results were more rigorously evaluated in the 1990s in a well-designed, double-blind, placebo-controlled trial.70 Seventy-two patients with osteoarthritis were randomized for treatment with niacinamide (3,000 mg per day in divided dosages) or a placebo for 12 weeks. Outcome measures included global arthritis impact and pain, joint range of motion and flexibility, erythrocyte sedimentation rate, complete blood count, liver function tests, serum cholesterol, serum uric acid, and fasting blood sugar. The researchers found that niacinamide produced a 29% improvement in global arthritis impact, compared with a 10% worsening in the placebo group. Pain levels did not change, but those on niacinamide reduced their NSAID use. Niacinamide supplementation reduced the sedimentation rate by 22% and increased joint mobility by 4.5 degrees over controls (8 degrees vs. 3.5 degrees). There were no other changes in blood chemistry. Side effects, primarily mild gastrointestinal complaints, were more common in the niacinamide group but could be effectively managed by taking the pills with food or fluids.
Niacinamide at this high dose can result in significant side effects (e.g., glucose intolerance, liver damage) and therefore requires strict medical supervision—at the very least regular blood tests to assess liver damage.
S-adenosyl-methionine (SAM-e)
S-adenosyl-methionine (SAM-e) is an important substance that the body forms by combining the essential amino acid methionine with adenosine triphosphate. A deficiency of SAM-e in the joint tissue, just like a deficiency of glucosamine, leads to loss of the gel-like nature and shock-absorbing qualities of cartilage. A detailed analysis of 11 studies reports that SAM-e reduces pain and functional limitations in patients with osteoarthritis.71
SAM-e has been shown to be important in the manufacture of cartilage components.72 In one double-blind study, supplemental SAM-e increased cartilage formation, as determined by MRI, in 14 patients with arthritis of the hands.73 In addition to this effect, SAM-e has also demonstrated some mild pain-relieving and anti-inflammatory effects in animal studies.
In double-blind trials, SAM-e has produced reductions in pain scores and in clinical symptoms similar to the reductions seen with NSAIDs such as ibuprofen, indomethacin, naproxen, and piroxicam.71–82 All of these studies indicate that SAM-e offers significant advantages over NSAIDs. The drugs are associated with a significant risk of toxicity, side effects, and actual promotion of the disease process in osteoarthritis, while SAM-e offers similar benefits with minimal risk and minimal side effects. Side effects are uncommon but can include occasional gastrointestinal disturbances, mainly diarrhea. As with glucosamine sulfate, its major benefit is enhancing cartilage regeneration rather than simply relieving symptoms.
Vitamin C
Results from the Framingham Osteoarthritis Cohort Study indicate that a high intake of antioxidant nutrients, especially vitamin C, may reduce the risk of cartilage loss and disease progression in people with osteoarthritis.83 A threefold reduction in the risk of osteoarthritis progression was found with higher vitamin C intake. These results highlight the importance of a diet rich in plant-based antioxidant nutrients for protection against chronic degenerative diseases, including arthritis.
Low intake of vitamin C is common in the elderly, resulting in altered collagen synthesis and compromised connective tissue repair.84,85 Several test tube studies have demonstrated that vitamin C has an anabolic effect on cartilage.86,87 Research has confirmed the importance of—indeed, necessity for—vitamin C in human cartilage cell protein synthesis.87 A study showed that people who reported a history of vitamin C supplementation saw a halt in the progression of their osteoarthritis.88 Vitamins C and E appear to possess synergistic effects in osteoarthritis.84
Vitamin D
Several studies have shown that low serum levels of vitamin D appear to be associated with an increased risk for progression of osteoarthritis, especially in people under 60 years of age.89–91 In one study of people undergoing hip replacement, patients with vitamin D deficiency had lower hip function scores before surgery and were significantly less likely to see an excellent outcome after surgery.91 Low serum levels of vitamin D also predict loss of cartilage, as assessed by loss of joint space and increase in bony growths. It seems reasonable to consider that exposure to adequate amounts of sunlight, as well as sufficient intake of vitamin D in childhood and young adulthood, may help decrease the risk of osteoarthritis. It is not known, however, whether increasing vitamin D intake will help decrease or reverse already established arthritis.
Vitamins A and E, Pyridoxine, Zinc, Copper, and Boron
These nutrients are required for the synthesis of collagen and maintenance of normal cartilage structures. A deficiency of any one of these would allow accelerated joint degeneration. In addition, supplementation at appropriate levels may promote cartilage repair and synthesis.
For example, boron supplementation has been used in the treatment of osteoarthritis in Germany since the mid-1970s. This use was recently evaluated in a small, double-blind clinical study and an open trial. In the double-blind study, of the patients given 6 mg boron, 71% improved, compared with only 10% in the placebo group.92 In the open trial, boron supplementation (6 to 9 mg per day) produced effective relief in 90% of arthritis patients, including patients with osteoarthritis, juvenile arthritis, and rheumatoid arthritis.93 The preliminary indication is that boron supplements are of value in arthritis, with many osteoarthritis patients experiencing complete resolution of symptoms.
Vitamin K
Studies have shown that low vitamin K status is associated with knee osteoarthritis,94,95 so vitamin K may offer some protection against arthritis. Foods rich in vitamin K include green tea, kale, turnip greens, spinach, and other green leafy vegetables.
Historically, many herbs have been used in the treatment of osteoarthritis.
Curcumin
Curcumin is the yellow pigment of turmeric (Curcuma longa). It may be helpful in osteoarthritis due to a variety of anti-inflammatory effects.96 One concern regarding curcumin has been absorption, but there now exist a number of methods and products that enhance absorption. One of those methods involves complexing the curcumin with soy phospholipids to produce a product sold as Meriva. Absorption studies in animals indicate that peak plasma levels of curcumin after administration of Meriva were five times higher than those after administration of regular curcumin.97 Studies with another advanced form of curcumin, Theracurmin, show even better absorption (27 times greater than regular curcumin).98
Meriva has been used in two studies of patients with osteoarthritis. In the first study, 50 patients were given 1,000 mg Meriva (providing 200 mg curcumin) for three months, after which symptom scores decreased by 58%, walking distance in the treadmill test was prolonged from 76 meters to 332 meters, and the level of an inflammatory marker (CRP) in the blood decreased from 168 to 11.3 mg/l in the subgroup of patients with high CRP.99 In the second study, 100 patients with osteoarthritis were given 1,000 mg Meriva for eight months. Just as in the previous study, symptom scores, walking distance, and blood measurements of inflammation were significantly improved.100
Boswellia
Boswellia (Boswellia serrata), a large branching tree native to India, yields a gum resin known as salai guggul that has been used for centuries for arthritic and other conditions. Newer preparations concentrated for the active components (boswellic acids) are showing significant clinical results. Initially, boswellic acid extracts demonstrated antiarthritic effects in various animal models. Among several mechanisms of action are inhibition of inflammatory mediators, prevention of decreased GAG synthesis, and improved blood supply to joint tissues.101,102 Clinical studies using herbal formulas with boswellia have yielded good results in osteoarthritis of the knee, with patients experiencing decreased knee pain, decreased swelling, and increased knee flexion and walking distance.103–106 Corroborating the improvements in pain scores and joint function were significant reductions in cartilage breakdown products, indicating improved collagen matrix stability. No side effects due to boswellic acids have been reported.
Procyanidolic Oligomers
Procyanidolic oligomers are among the most useful plant flavonoids. Grape seed and pine bark extract (e.g., Pycnogenol) are two popular commercial sources, but these compounds are also found in many foods, especially berries. Two double-blind studies have been conducted using Pycnogenol for osteoarthritis and showing very good effects. In the first study, Pycnogenol (100 mg per day) or a placebo was given for three months to 156 patients with osteoarthritis.107 Overall signs and symptoms of osteoarthritis decreased by 56% in the treatment group vs. 9.6% in the placebo group. Walking distance in the treadmill test was prolonged from 68 meters at the start to 198 meters in the Pycnogenol group, compared with an increase from 65 meters to 88 meters in the placebo group. The use of drugs decreased by 58% in the Pycnogenol group vs. 1% in the placebo group. Foot swelling decreased in 79% of the Pycnogenol patients vs. 1% of the controls. Similar results were seen in a second study when Pycnogenol was given at the same dosage.108
Ginger
Ginger (Zingiber officinalis) exerts some anti-inflammatory effects. In a six-week study of 261 patients with knee osteoarthritis given ginger extract or a placebo, a moderate effect on symptoms was seen: 63% of the ginger group found relief vs. 50% of the placebo group.109 Those in the ginger group resorted to acetaminophen less frequently and had a reduction in knee pain on standing and after walking. Patients receiving ginger extract did experience more gastrointestinal adverse events than did the placebo group (59 patients vs. 21 patients), though the problems were mild. One double-blind crossover trial found ginger (170 mg three times per day) to be effective before the crossover, but by the end of the study, there was no benefit of ginger over the placebo.110 Clearly, more studies are necessary to assess ginger’s effectiveness for osteoarthritis.
Devil’s Claw
Devil’s claw (Harpagophytum procumbens) is a South African plant that grows in regions bordering the Kalahari Desert. Extracts of the root are usually standardized for harpagosides, the principal active compound. A systematic review of the clinical efficacy of devil’s claw concluded that products providing less than 30 mg harpagosides per day were of little benefit in the treatment of knee and hip osteoarthritis, while dosages providing 60 mg harpagoside per day showed moderate evidence of efficacy in the treatment of spine, hip, and knee osteoarthritis.111 Some of the individual studies showed significant benefit. For example, in a two-month double-blind study of spine and knee osteoarthritis, 670 mg devil’s claw powder three times a day was more effective than a placebo in reducing pain scores.112 In a four-month double-blind study of hip and knee osteoarthritis, 2.6 g devil’s claw powder per day was equal in efficacy to 200 mg diacerhein per day in improving pain scores but was better tolerated than the drug.113 In a review of 28 clinical trials of devil’s claw extract, adverse events occurred at a rate of about 3% and did not exceed the rate of side effects experienced with placebos.114 Long-term use appears to be safe.
The mainstays of natural topical preparations for osteoarthritis are those containing menthol-related compounds, One popular combination contains 4% camphor, 10% menthol, and 30% methyl salicylate and/or capsaicin (typically creams contain 0.075% capsaicin). These time-tested and clinically proved topical analgesics can often provide significant relief in arthritis. An alternative are products containing Celadrin, a mixture of cetylated fatty acids. Celadrin has been shown to affect several key factors that contribute to inflammation. Its main action appears to be its ability to enhance cell membrane health and integrity. As a result, it halts the production of inflammatory compounds known as prostaglandins. It also reduces the production of negative immune factors such as IL-6 that play a central role in inflammation. Studies have assessed both the oral and the topical use of Celadrin. In a study with oral Celadrin, 64 patients with chronic osteoarthritis of the knee were evaluated at baseline and at 30 and 68 days. Results indicated that compared with a placebo, Celadrin improves knee range of motion.115
The effect of Celadrin cream was studied in osteoarthritis of the knees. Forty patients were randomly assigned to receive either the Celadrin cream or a placebo. Patients were tested on three occasions: baseline, 30 minutes after initial treatment, and after 30 days of treatment in which the cream was applied twice per day. Assessments included knee range of motion, timed “up-and-go” from a chair, timed stair climbing, and two other functional tests. For stair climbing ability and the up-and-go test, significant decreases in time were observed 30 minutes after the first administration and after one month of use only in the Celadrin group. Likewise, range of motion of the knees increased with Celadrin, both 30 minutes after the initial application and after one month’s use. In contrast, no difference was observed in the placebo group. The other functional tests also clearly demonstrated improvements with Celadrin, while the placebo failed to produce results.116
In another study involving patients with knee osteoarthritis, patients were assessed by having them stand on a special platform for 20 and 40 seconds to measure their ability to stand comfortably in one place for a period of time. Again, only those subjects using the Celadrin cream demonstrated improvements.117
One of the significant features of Celadrin is that, unlike many other natural approaches, it produces almost immediate results.
Joint misalignment stresses joints and increases the risk for osteoarthritis. Although this concept is relatively simple, it is only recently that it has been investigated scientifically. An 18-month study of 230 patients with osteoarthritis of the knee and at least some difficulty with activity requiring movement of the knee revealed conclusively that bowlegged patients had a fourfold increased risk of osteoarthritis progression on the inner side of the knee.118 Similarly, knock-kneed patients showed almost five times the risk of osteoarthritis progression on the outer side of the knee. Not surprisingly, the greater the misalignment, the more severe the arthritis. Individuals with misalignments may need to consider chiropractic or osteopathic treatment, as well as orthotics.
Various physical therapy modalities (e.g., exercise, heat, cold, diathermy, ultrasound) are often beneficial in improving joint mobility and reducing pain in osteoarthritis, especially when administered regularly. Much of the benefit of physical therapy is thought to be a result of achieving proper hydration within the joint capsule.
Clinical and experimental studies seem to indicate that short-wave diathermy may be of the greatest benefit.119–121 Combining short-wave diathermy therapy with periodic ice massage, rest, and appropriate exercises appears to be the most effective approach. Ultrasound and laser therapy have also been shown to be helpful.122,123
The best exercises are isometrics and swimming. These types of exercises increase circulation to the joint and strengthen surrounding muscles without placing excessive strain on joints. Increasing quadriceps strength has been shown to improve the clinical features and reduce pain in osteoarthritis of the knee.124 Walking programs help to improve functional status and relieve pain in patients with arthritis of the knee.125 Patient-specific physical therapies may also be useful. For example, four older adults with hand osteoarthritis benefited from keyboard playing for 20 minutes a day, four days a week.126
Effective Nonpharmacological Approaches to Pain in Osteoarthritis
Acupuncture
Diathermy
Exercise
Laser therapy
Magnetic therapy
Massage
Physical therapy
Psychological aids
Thermal baths
Transcutaneous nerve stimulation (TENS)
Ultrasound
Weight loss
Acupuncture and Electroacupuncture
Acupuncture has been shown to be safe and effective in reducing pain from osteoarthritis.127,128 Other studies have shown very good results with either electroacupuncture or transcutaneous electrical nerve stimulation (TENS) in relieving pain due to arthritis, but only electroacupuncture improved joint function.129 Electroacupuncture has also been tested against the NSAID diclofenac in a head-to-head, 186-patient controlled trial.130 For these knee patients, improvement of osteoarthritis symptoms was greatest in the electroacupuncture group. Unlike the diclofenac and placebo groups, most of the patients receiving electroacupuncture rated their results as “much better,” and substantially better pain management and functionality were obtained in the electroacupuncture group as well.
Magnetic therapy has been used in the treatment of a wide variety of chronic pain syndromes.131 A number of studies clearly support magnetic therapy used for knee osteoarthritis.132–135 One double-blind trial enrolled 75 patients with osteoarthritis of the knee who had previously been unable to obtain acceptable results using conventional treatments.134 Low-frequency pulsed magnetic fields produced notable improvements in pain, functionality, and physician evaluation of patients’ condition. Mean morning stiffness also decreased by 20 minutes in the group using magnetic therapy, while increasing by 2 minutes in the placebo group. A second double-blind study of 176 patients with knee osteoarthritis also showed significant results from using low-amplitude and low-frequency fields.135 Reduction in pain after a treatment session was significantly greater in the magnet-on group (46%) compared with the magnet-off group (8%). A smaller, 29-subject study of knee osteoarthritis used either high-strength magnetic or a placebo knee-sleeve treatment for four hours in a monitored setting and self-treatment six hours per day for six weeks.135 This study demonstrated a significant decrease in pain scores in the treatment group and only a minimal improvement in the placebo group after four hours of treatment, but no significant differences after six weeks of self-treatment—indicating either that monitored treatment is more effective or that the benefits subside with time. Nonetheless, there is evidence that magnetic therapies may be a useful treatment for arthritis.
QUICK REVIEW
• Osteoarthritis is the most common cause of arthritis.
• NSAIDs appear to suppress the symptoms of osteoarthritis but accelerate its progression.
• The key dietary focus in the prevention and treatment of osteoarthritis is the achievement of normal body weight and improvement in insulin sensitivity.
• The Mediterranean diet may show positive effects in osteoarthritis.
• One popular dietary practice in the treatment of osteoarthritis is eliminating foods from the family Solanaceae (nightshade family).
• Numerous double-blind studies have shown that glucosamine produces much better results compared with NSAIDs, placebos, or acetaminophen in relieving the pain and inflammation of osteoarthritis.
• Clinical studies suggest that orally administered chondroitin is less effective than glucosamine.
• A high intake of antioxidant nutrients, especially vitamin C, may reduce the risk of cartilage loss and disease progression in people with osteoarthritis.
• Meriva, a special form of curcumin bound to phosphatidylcholine to improve absorption, has been shown in two double-blind studies to produce benefits in osteoarthritis.
• Two double-blind studies have been conducted with Pycnogenol, showing very good effects in osteoarthritis.
• Natural topical preparations for osteoarthritis (menthol, capsaicin, or Celadrin) can reduce inflammation.
• Joint misalignment stresses joints and increases the risk for osteoarthritis.
• Physical therapy (e.g., exercise, heat, cold, diathermy, ultrasound, acupuncture, TENS, and electroacupuncture) can improve joint mobility and reduce pain in osteoarthritis.
Relaxation Techniques
Relaxation techniques such as meditation, deep breathing, and guided imagery have been used for many types of pain conditions. A study of 66 elderly people suffering from chronic osteoarthritis pain evaluated the effect of daily music listening on pain levels.136 Differences in perceptions of pain were measured over 14 days in experimental subjects who listened to Mozart selections for 20 minutes per day and control subjects who sat quietly for 20 minutes per day. Those who listened to music had less pain when compared with those who sat quietly and did not listen to music. The amount of pain perceived by the Mozart group also decreased incrementally over the 14-day study period.
TREATMENT SUMMARY
The natural approach to osteoarthritis is a rational program based on reducing joint stress and trauma, promoting collagen repair mechanisms, and eliminating foods and other factors that may inhibit normal collagen repair. NSAIDs should be avoided as much as possible. If you must take NSAIDs, also take deglycyrrhizinated Glycyrrhiza glabra (DGL) to help protect the gastrointestinal tract, and discontinue use of the NSAIDs as soon as possible.
Achieving ideal body weight is the primary dietary goal; see the chapter “Obesity and Weight Management.” The general recommendations in the chapter “A Health-Promoting Diet” are appropriate here as well. In addition, some people have reported benefits by eliminating plants of the Solanaceae family (tomatoes, potatoes, eggplant, peppers, etc.). Regular consumption of flavonoid-rich berries and naturally occurring vitamin C sources such as broccoli, dark leafy greens (kale, mustard greens, spinach, etc.), and citrus fruit is important, as is consuming a Mediterranean-type diet.
• A high-potency multiple vitamin and mineral formula as described in the chapter “Supplementary Measures”
• Key individual nutrients:
Vitamin B6: 50 mg per day
Vitamin K: 100 mcg per day
Zinc: 30 to 45 mg per day
Copper: 0.5 to 1 mg per day
Boron: 6 mg per day
Vitamin C: 500 to 1,000 mg per day
Selenium: 100 to 200 mcg per day
Vitamin E (mixed tocopherols): 100 to 200 IU per day
Vitamin D3: 2,000 to 4,000 IU per day
• Fish oils: 1,000 mg EPA + DHA per day
• One of the following:
Grape seed extract (>95% procyanidolic oligomers): 100 to 300 mg per day
Pine bark extract (>95% procyanidolic oligomers): 100 to 300 mg per day
Some other flavonoid-rich extract with a similar flavonoid content, super greens formula, or another plant-based antioxidant that can provide an oxygen radical absorption capacity (ORAC) of 3,000 to 6,000 units or higher per day
• Specialty supplements (begin with glucosamine; if no benefit is seen after four to six weeks, add SAM-e, followed by hyaluronic acid, and then niacinamide):
Glucosamine sulfate: 1,500 mg per day (dosages up to 3,000 mg per day may be necessary in obese individuals, those on diuretics, and athletes or individuals who are subjecting their joints to greater wear and tear)
SAM-e: 200 to 400 mg three times per day
Hyaluronic acid: 100 to 200 mg per day
Niacinamide: 1,000 mg three times per day (under medical supervision; liver enzymes must be regularly checked)
One or more of the following:
• Curcumin:
Meriva: 500 to 1,000 mg twice daily
BCM95 Complex: 750 to 1,500 mg twice daily
Theracurmin: 300 mg one to three times daily
• Boswellia extract: equivalent of 400 mg boswellic acids three times per day
• Ginger: 8 to 10 g dried powdered ginger or ginger extracts standardized to contain 20% gingerol and shogaol at a dosage of 100 to 200 mg three times per day
• Devil’s claw:
Dried root powder (tablet or capsule): 2,000 mg three times per day
Fluid extract (1:1): 2 ml three times per day
Dry powdered extract (standardized to contain 2.5% harpagosides): 750 to 1,000 mg three times per day
One of the following, applied to affected areas twice per day:
• Menthol preparations
• Capsaicin preparations
• Cetylated fatty acid cream (Celadrin)
Physical activity that causes too much strain on affected joints should be avoided. Make sure you maintain good posture, and if you have any structural abnormalities (e.g., bowlegs, knock-knees), see an orthopedist; these measures will help limit joint strain. The best exercises are isometrics, walking, and swimming.
Various physical therapy modalities such as exercise, heat, cold, diathermy, ultrasound, acupuncture, TENS, and electro-acupuncture often improve joint mobility and reduce pain in osteoarthritis.