Osteoarthritis

Boswellia has anti-inflammatory properties that have been compared to those of the NSAIDs used by many for inflammatory conditions.¹ Clinical trials have found that boswellia is more effective than a placebo for relieving pain and swelling and preventing loss of function in people with osteoarthritis.² Boswellia has also been found to be as effective as the anti-inflammatory drug valdecoxib (Bextra). In addition, while the improvements occurred more slowly in the boswellia group than in the valdecoxib group, they persisted for a longer period of time after treatment was discontinued.³ One clinical trial found that a combination of boswellia, ashwagandha, turmeric, and zinc effectively treated pain and stiffness associated with OA but did not improve joint health, according to X-rays of the affected joint.⁴ Unlike NSAIDs, long-term use of boswellia does not lead to irritation or ulceration of the stomach.

Chondroitin sulfate (CS) is a major component of the lining of joints. The structure of CS includes molecules related to glucosamine sulfate. CS levels have been reported to be reduced in joint cartilage affected by osteoarthritis. Possibly as a result, CS supplementation may help restore joint function in people with osteoarthritis.¹¹ On the basis of preliminary evidence, researchers had believed that oral CS was not absorbed in humans;¹² as a result, early double-blind CS research was done mostly by giving injections.^11,14 This research documented clinical benefits from CS injections. It now appears, however, that a significant amount of CS is absorbable in humans,¹⁵ though dissolving CS in water leads to better absorption than swallowing whole pills.¹⁶

Strong clinical evidence now supports the use of oral CS supplements for osteoarthritis. Many double-blind trials have shown that CS supplementation consistently reduces pain, increases joint mobility, and/or shows evidence (including X-ray changes) of healing within joints of people with osteoarthritis.^{17,18,19,20,21,22,23,24,25,26,27} Most trials have used 400 mg of CS taken two to three times per day. One trial found that taking the full daily amount (1,200 mg) at one time was as effective as taking 400 mg three times per day.²⁰ Reduction in symptoms typically occurs within several months.

SAMe (S-adenosyl methionine) possesses anti-inflammatory, pain-relieving, and tissue-healing properties that may help protect the health of joints,^43,44 though the primary way in which SAMe reduces osteoarthritis symptoms is not known. A very large, though uncontrolled, trial (meaning that there was no comparison with placebo) demonstrated “very good” or “good” clinical effect of SAMe in 71% of over 20,000 osteoarthritis sufferers.⁴⁵ In addition to this preliminary research, many double-blind trials have shown that SAMe reduces pain, stiffness, and swelling better than placebo and equal to drugs such as ibuprofen and naproxen in people with osteoarthritis.^{46,47,48,49,50,51,52,53} These double-blind trials all used 1,200 mg of SAMe per day.

Lower amounts of oral SAMe have also produced reductions in the severity of osteoarthritis symptoms in preliminary clinical trials. A two-year, uncontrolled trial showed significant improvement of symptoms after two weeks at 600 mg SAMe daily, followed by 400 mg daily thereafter.⁵⁴ This amount was also used in a double-blind trial, but participants first received five days of intravenous SAMe.⁵⁵ A review of the clinical trials on SAMe concluded that its efficacy against osteoarthritis was similar to that of conventional drugs but that patients tolerated it better.⁵⁶

In the 1940s and 1950s, one doctor reported that supplemental niacinamide (a form of vitamin B3) increased joint mobility, improved muscle strength, and decreased fatigue in people with osteoarthritis.^57,58,59 In the 1990s, a double-blind trial confirmed a reduction in symptoms from niacinamide within 12 weeks of beginning supplementation.⁶⁰ Although amounts used have varied from trial to trial, many doctors recommend 250 to 500 mg of niacinamide four or more times per day (with the higher amounts reserved for people with more advanced arthritis). The mechanism by which niacinamide reduces symptoms is not known.

An extract of avocado and soybean oils, known as avocado/soybean unsaponifiables (ASU), was found in a double-blind trial to reduce joint pain and improve overall functioning in people with osteoarthritis of the knee or hip. The amount used was 300 mg per day for six months.⁶¹ In a three-month double-blind trial, 71% of people taking ASU, but only 36% of those taking a placebo, were able to decrease their pain medicine or anti-inflammatory medicine by more than 50%.⁶² In a longer-term double-blind trial (two years), ASU treatment did not improve symptoms when compared with a placebo, and did not slow the progression of osteoarthritis (as determined by the amount of joint cartilage lost). However, in the subgroup of patients with the most severe disease, ASU treatment did significantly decrease the loss of joint cartilage.⁶³ ASU is believed to work by reducing inflammation and by aiding in the repair of damaged cartilage tissue. ASU is approved as a prescription drug in France and is available over the counter in some other countries.

In a double-blind study, collagen hydrolysate was compared with gelatin and egg protein as a treatment for osteoarthritis of the hip and/or knee. When subjects took 10 grams per day either of gelatin or collagen hydrolysate for two months, they reported significantly more pain relief than when they took a similar amount of egg protein.⁶⁴ More research is needed to confirm the benefits of gelatin or collagen hydrolysate in osteoarthritis. In a double-blind trial, individuals with osteoarthritis of the knee received 40 mg per day of a particular type of collagen known as undenatured type II collagen (derived from chickens) or placebo for six months. Compared with the placebo, undenatured type II collagen significantly improved pain, stiffness, and overall functioning.⁶⁵

Cetyl myristoleate (CMO) has been proposed to act as a joint “lubricant” and anti-inflammatory agent. In a double-blind trial, people with various types of arthritis who had failed to respond to nonsteroidal anti-inflammatory drugs (NSAIDs) received CMO (540 mg per day orally for 30 days), while others received a placebo.⁶⁶ These people also applied CMO or placebo topically, according to their perceived need. A statistically significant 63.5% of those using CMO improved, compared with only 14.5% of those using placebo.

Devil’s claw extract was found in one clinical trial to reduce pain associated with osteoarthritis as effectively as the slow-acting analgesic/cartilage-protective drug diacerhein.⁶⁷ The amount of devil’s claw used in the trial was 2,610 mg per day. The results of this trial are somewhat suspect, however, as both devil’s claw and diacerhein are slow-acting and there was no placebo group included for comparison.

In a double-blind study, a group of people with painful osteoarthritis of the knee received an oral enzyme-flavonoid preparation or a nonsteroidal anti-inflammatory (NSAID) for six weeks. While both treatments relieved pain and improved joint function, the enzyme-flavonoid product appeared to be slightly more effective than the NSAID. No serious side effects were seen.⁶⁸ The enzyme-flavonoid product used in this study was Phlogenzym (Mucos Pharma, Geretsried, Germany). Each enteric-coated tablet contained 90 mg of bromelain, 48 mg of trypsin, and 100 mg of rutosid (a derivative of the flavonoid rutin); one tablet was given three times a day.

The effects of New Zealand green-lipped mussel supplements have been studied in people with osteoarthritis. In a preliminary trial, either a lipid extract (210 mg per day) or a freeze-dried powder (1,150 mg per day) of green-lipped mussel reduced joint tenderness and morning stiffness, as well as improving overall function in most participants.⁷³ In a double-blind trial, 45% of people with osteoarthritis who took a green-lipped mussel extract (350 mg three times per day for three months) reportedly had improvements in pain and stiffness.⁷⁴ Another double-blind trial reported excellent results from green-lipped mussel extract (2,100 mg per day for six months) for pain associated with arthritis of the knee.⁷⁵ Side effects, such as stomach upset, gout, skin rashes, and one case of hepatitis have been reported in people taking certain New Zealand green-lipped mussel extracts.⁷⁶

In a double-blind trial, 100 mg per day of Pycnogenol reduced pain and other osteoarthritis symptoms, improved walking performance, and reduced the use of pain-relieving medication.⁸² Another double blind trial found that 150 mg per day also improved symptoms and reduced use of pain-relieving medication.⁸³

People who have osteoarthritis and eat large amounts of antioxidants in food have been reported to exhibit a much slower rate of joint deterioration, particularly in the knees, compared with people eating foods containing lower amounts of antioxidants.⁸⁶ Of the individual antioxidants, only vitamin E has been studied as a supplement in controlled trials. Vitamin E supplementation has reduced symptoms of osteoarthritis in both single-blind⁸⁷ and double-blind research.^88,89 In these trials, 400 to 1,600 IU of vitamin E per day was used. Clinical effects were obtained within several weeks. However, in a six-month double-blind study of patients with osteoarthritis of the knee, 500 IU per day of vitamin E was no more effective than a placebo.⁹⁰

Boron affects calcium metabolism, and a link between boron deficiency and arthritis has been suggested.⁹³ Although people with osteoarthritis have been reported to have lower stores of boron in their bones than people without the disease, other minerals also are deficient in the bones of people with osteoarthritis.⁹⁴ One double-blind trial found that 6 mg of boron per day, taken for two months, relieved symptoms of osteoarthritis in five of ten people, compared with improvement in only one of the ten people assigned to placebo.⁹⁵This promising finding needs confirmation from larger trials.

Several trials have suggested that people with osteoarthritis may benefit from supplementation with bovine cartilage, which contains a mixture of protein and molecules related to chondroitin sulfate. In one preliminary trial, use of injected and topical bovine cartilage led to symptom relief in most people studied.⁹⁶ A ten-year study confirmed improvement with long-term use of bovine cartilage.⁹⁷ Optimal intake of bovine cartilage is not known.

The omega-3 fatty acids present in fish oil, EPA and DHA, have anti-inflammatory effects and have been studied primarily for rheumatoid arthritis, which involves significant inflammation. However, osteoarthritis also includes some inflammation.⁹⁸ In a 24-week controlled but preliminary trial studying people with osteoarthritis, people taking EPA had “strikingly lower” pain scores than people who took placebo.⁹⁹ However, in a double-blind trial by the same research group, supplementation with 10 ml of cod liver oil per day was no more effective than a placebo.¹⁰⁰

Horsetail is rich in silicon, a trace mineral that plays a role in making and maintaining connective tissue. Practitioners of traditional herbal medicine believe that the anti-arthritis action of horsetail is due largely to its silicon content. The efficacy of this herb for osteoarthritis has not yet been evaluated in controlled clinical trials.

Hyaluronic acid is a normal component of joint fluid, but its amount and molecular structure are altered in osteoarthritic joints.¹⁰⁶ Injection of hyaluronic acid compounds into osteoarthritic joints, primarily the knee, has been investigated in many double-blind trials with some improvement demonstrated.^107,108,109 However, no research has been done to determine whether oral supplementation with hyaluronic acid is an effective treatment for osteoarthritis.

Supplementation with D-phenylalanine (DPA), a synthetic variation of the amino acid, L-phenylalanine (LPA), has reduced chronic pain due to osteoarthritis in a preliminary trial.¹¹¹ In that study, participants took 250 mg three to four times per day, with pain relief beginning in four to five weeks. Other preliminary trials have confirmed the effect of DPA in chronic pain control,¹¹² but a double-blind trial found no benefit.¹¹³ DPA inhibits the enzyme that breaks down some of the body’s natural painkillers, substances called enkephalins, which are similar to endorphins. An increase in the amount of enkephalins may explain the reported pain-relieving effect of DPA. If DPA is not available, a related product, D,L-phenylalanine (DLPA), may be substituted (1,500 to 2,000 mg per day). Phenylalanine should be taken between meals, because protein found in food may compete for uptake of phenylalanine into the brain, potentially reducing its effect.¹¹⁴

According to arthritis research, saponins found in the herb yucca appear to block the release of toxins from the intestines that inhibit normal formation of cartilage. A preliminary, double-blind trial found that yucca might reduce symptoms of osteoarthritis.¹¹⁹ Only limited evidence currently supports the use of yucca for people with osteoarthritis.