Vitamins that may be helpful
Glucosamine sulfate (GS), a nutrient
derived from seashells, is a building block needed for the synthesis and repair of joint
cartilage. GS supplementation has significantly reduced symptoms of osteoarthritis in
uncontrolled8 9 and single-blind trials.10 11 Many
double-blind trials have also reported efficacy.12 13 14
15 16 17 One published trial has reported no effect of GS on
osteoarthritis symptoms.18 While most research trials use 500 mg GS taken three
times per day, results of a three-year, double-blind trial indicate that 1,500 mg taken once
per day produces significant reduction of symptoms and halts degenerative changes seen by
x-ray examination.19 GS does not cure people with osteoarthritis, and they
may need to take the supplement for the rest of their lives in order to maintain benefits.
Fortunately, GS appears to be virtually free of side effects, even after three or more years
of supplementation. Benefits from GS generally become evident after three to eight weeks of
treatment.
A few trials have evaluated glucosamine hydrochloride (GH), another form of glucosamine, as
a single remedy for OA. One trial found only minor benefits from 1,500 mg per day of GH for 8
weeks in people with OA of the knee.20 However, these people were also taking up to
4,000 mg per day of acetaminophen for pain
relief, and that treatment might have masked a beneficial effect of GH. In another study,
supplementing with GH (2,000 mg each morning for 12 weeks) significantly improved symptoms,
compared with a placebo, in people with knee pain due to cartilage damage or OA.21
In a four-week study from China, GH was as effective as GS in people with OA of the
knee.22 Another study found that the combination of GH and chondroitin sulfate was
more effective than a placebo in people with moderate to severe knee pain from OA, but not in
those with mild pain.23 Despite the reported beneficial effects of GH, some
investigators believe that the sulfate component of GS itself helps relieve OA, and that GS
would therefore be more effective than GH.24
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
OA. Possibly as a result, CS supplementation may help restore joint function in people with
OA.25 On the basis of preliminary evidence, researchers had believed that oral CS
was not absorbed in humans;26 as a result, early double-blind CS research was done
mostly by giving injections.27 28 This research documented clinical
benefits from CS injections. It now appears, however, that a significant amount of CS is
absorbable in humans,29 though dissolving CS in water leads to better absorption
than swallowing whole pills.30
Strong clinical evidence now supports the use of oral CS supplements for OA. 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 OA.31 32 33 34 35
36 37 38 39 40 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.41
Reduction in symptoms typically occurs within several months.
S-adenosyl methionine (SAMe) possesses
anti-inflammatory, pain-relieving, and
tissue-healing properties that may help protect the health of joints,42
43 though the primary way in which SAMe reduces OA 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 OA
sufferers.44 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 OA.45 46
47 48 49 50 51 52 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 OA 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.53 This amount was also used in a double-blind trial, but participants
first received five days of intravenous SAMe.54 A review of the clinical trials on
SAMe concluded that its efficacy against OA was similar to that of conventional drugs but that
patients tolerated it better.55
People who have OA 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.56 Of the individual antioxidants, only vitamin E has been studied as a supplement in
controlled trials. Vitamin E supplementation has reduced symptoms of OA in both
single-blind57 and double-blind research.58 59 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 OA of the knee, 500
IU per day of vitamin E was no more effective than a placebo.60
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 OA.61
62 63 In the 1990s, a double-blind trial confirmed a reduction in
symptoms from niacinamide within 12 weeks of beginning supplementation.64 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.
The effects of New Zealand green-lipped
mussel supplements have been studied in people with OA. 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.65 In a double-blind trial, 45% of people with OA who took a
green-lipped mussel extract (350 mg three times per day for three months) reportedly had
improvements in pain and stiffness.66 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.67 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.68
The therapeutic use of DMSO (dimethyl
sulfoxide) is controversial because of safety concerns, but some preliminary research shows
that diluted preparations of DMSO, applied directly to the skin, are anti-inflammatory and
alleviate pain, including pain associated with
OA.69 70 A recent double-blind trial found that a 25% concentration of
DMSO in gel form relieved OA pain significantly better than a placebo after three
weeks.71 DMSO appears to reduce pain by inhibiting the transmission of pain
messages by nerves72 rather than through a process of healing damaged joints. DMSO
comes in different strengths and different degrees of purity; in addition, certain precautions
must be taken when applying DMSO. For these reasons, DMSO should be used only with the
supervision of a doctor.
According to a small double-blind trial, 2,250 mg per day of oral methylsulfonylmethane (MSM), a variant of DMSO,
reduced OA pain after six weeks.73 In another double-blind trial, supplementation
with 3 grams of MSM twice a day for 12 weeks significantly reduced pain and improved overall
physical functioning in patients with OA of the knee.74
In a double-blind study, a group of people with painful OA 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.75 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.
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.76 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.
Boron affects calcium metabolism, and a link between boron
deficiency and arthritis has been suggested.77 Although people with OA 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 OA.78 One double-blind
trial found that 6 mg of boron per day, taken for two months, relieved symptoms of OA in five
of ten people, compared with improvement in only one of the ten people assigned to
placebo.79 This promising finding needs confirmation from larger trials.
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, OA also includes
some inflammation.80 In a 24-week controlled but preliminary trial studying people
with OA, people taking EPA had “strikingly lower” pain scores than people who took
placebo.81 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.82
Supplementation with D-phenylalanine (DPA),
a synthetic variation of the amino acid, L-phenylalanine (LPA), has reduced chronic pain due to OA in a preliminary
trial.83 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,84 but a double-blind trial found no
benefit.85 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.86
Several trials have suggested that people with OA 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.87 A ten-year study confirmed improvement
with long-term use of bovine cartilage.88 Optimal intake of bovine cartilage is not
known.
Hyaluronic acid is a normal component of
joint fluid, but its amount and molecular structure are altered in osteoarthritic
joints.89 Injection of hyaluronic acid compounds into osteoarthritic joints,
primarily the knee, has been investigated in many double-blind trials with some improvement
demonstrated.90 91 92 However, no research has been done to
determine whether oral supplementation with hyaluronic acid is an effective treatment for
osteoarthritis.
Are there any side effects or interactions?
Refer to the individual supplement for information about any side effects or interactions.
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