Natural Treatments for Osteoarthritis

by Alan R. Gaby, MD
Abstract
Osteoarthritis (OA) is the most common form of joint disease. Although OA was
previously thought to be a progressive, degenerative disorder, it is now known that
spontaneous arrest or reversal of the disease can occur. Conventional medications
are often effective for symptom relief, but they can also cause significant side effects
and do not slow the progression of the disease. Several natural substances have been
shown to be at least as effective as nonsteroidal anti-inflammatory drugs at relieving
the symptoms of OA, and preliminary evidence suggests some of these compounds
may exert a favorable influence on the course of the disease.
(Altern Med Rev 1999;4(5):330-341)

Introduction
Osteoarthritis (OA), the most common form of joint disease, is characterized by erosion
of articular cartilage. The joints most often affected by OA are the knees, hips, spine, and hands,
although other joints may be involved. OA is usually classified either as primary (idiopathic) or
secondary. In the former, no obvious predisposing factor can be identified; in the latter, the
arthritis appears be the result of trauma, repetitive joint use, congenital or developmental defects, metabolic or endocrine disorders, or other factors. Clinical manifestations of OA include
pain, stiffness, and decreased range of motion of affected joints. In more-advanced cases, significant disability may occur. It is estimated that 100,000 people in the United States are unable
to walk because of severe OA of the hip or knee.
In the past, OA was considered a degenerative disorder, in which the joint gradually
wears out. However, more-recent evidence has resulted in a change of thinking concerning
the pathogenesis and natural history of OA. It is now known that the joint cartilage of individuals with OA is highly metabolically active, engaging (at least early in the course of the disease)
in a process of remodeling and repair of damaged tissue. Arrest or reversal of the disease, once
thought to be impossible, has now been shown to occur spontaneously in some individuals with
OA.1
Conventional pharmacological treatment of OA consists primarily of nonsteroidal antiinflammatory drugs (NSAIDs) and analgesics. While these medications often relieve symptoms, they are far from ideal therapeutic agents. NSAIDs, in particular, can cause serious side
effects, including peptic ulcer and (less commonly) hepatic or renal failure. And neither of these
classes of medications prevents or delays the progression of OA. In fact, there is evidence, both
in animals with experimental OA2 and in humans,3 that administration of NSAIDs may actually
accelerate joint destruction. New approaches are therefore needed, both to increase the safety
and efficacy of symptomatic treatment and to exert a favorable influence on the course of the
disease.
Alan R. Gaby, MD Professor of Nutritional Medicine, Bastyr University; Author, The Patient's Guide to Natural Medicine.
Townsend Letter for Doctors and Patients; Contributing Editor, Alternative Medicine Review.
Correspondence address: 125 NE 61st Street, Seattle, WA 98115

Page 330
Alternative Medicine Review Volume 4, Number 5 1999
Copyright1999 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission

Niacinamide
A half-century ago, William Kaufman,
MD, described his results using niacinamide
in the treatment of several hundred patients
with OA.4-7 The dosage was 900 to 4,000 mg
per day, depending on the degree of impairment of range of motion of the joints. Treatment with niacinamide usually resulted in an
increase in joint mobility (measured objectively), as well as subjective improvements in
joint discomfort, inflammation, and pain. Improvement with niacinamide therapy usually
did not occur until after three to four weeks of
treatment. Thereafter, progressive improvement occurred for one to three years if niacinamide was continued. Some patients receiving long-term niacinamide treatment maintained improved joint function (as demonstrated by an increase in joint range index) for
as long as twenty years. However, patients who
stopped taking the vitamin gradually reverted
to their pre-treatment status.
Because Kaufmans study lacked a
control group, the possibility of a placebo effect cannot be ruled out. However, a recent
double-blind study by Jonas et al8 tended to
support Kaufmans observations. In that study,
72 patients with OA of at least five years duration were randomly assigned to receive niacinamide (500 mg six times per day) or a placebo for 12 weeks. Outcome measures included global arthritis impact, pain, joint mobility, and erythrocyte sedimentation rate

(ESR). Global arthritis impact improved by 29

percent in patients receiving niacinamide and
worsened by 10 percent in patients given placebo (p = 0.04 for difference between groups).
Although pain levels were no different in the
two groups, patients on niacinamide reduced
their anti-inflammatory medication by 13 percent, compared with a slight increase in medication in the placebo group (p = 0.014 for difference between groups). Niacinamide reduced the ESR by 22 percent compared with
placebo (p < 0.005) and increased joint mobility (as measured by the joint range index)
by 8.0 degrees, compared with 3.5 degrees in
the placebo group (p = 0.04).
Niacinamides delayed onset of action,
its capacity to induce progressive improvement, and its gradual (as opposed to abrupt)
loss of effect after treatment is discontinued,
suggest this vitamin somehow helps control
OA, rather than merely relieving symptoms.
Although its mechanism of action is not
known, niacinamide does not appear to act
merely as an anti-inflammatory agent or analgesic.
Kaufman observed niacinamide was
most effective when taken in frequent, divided
doses. Thus, 250 mg taken six times per day
was more effective than 500 mg taken three
times per day. The need for frequent dosing is
presumably related to the short half-life of the
vitamin. Sustained-release forms of niacinamide are commercially available, and some
practitioners have found them to be an acceptable alternative to more-frequent dosing with
regular niacinamide. It is not known whether
niacin (nicotinic acid) or inositol
hexanicotinate (the other available form of
vitamin B3) can be used as substitutes for niacinamide in the treatment of OA. It should
be noted, however, that niacin, particularly in
the sustained-release form, is more hepatotoxic
than niacinamide.

Alternative Medicine Review Volume 4, Number 5 1999

Page 331

Copyright1999 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission

Osteoarthritis

A number of substances that occur

naturally in the body may have value for the
prevention and/or treatment of OA. Some of
these compounds have been shown to provide
symptomatic relief, and preliminary evidence
suggests some may positively affect the progression of the disease. Although much of the
research is in its early stages, the possibility
that natural substances can be used to prevent
the degradation, or enhance the repair, of joint
cartilage is intriguing.

Niacinamide is generally well tolerated

number of clinical trials, at least three of which
and appears to be relatively safe for long-term
have been double-blind and placebo-conuse. During several thousand patient-years of
trolled. In one such study, eighty patients with
clinical experience with this vitamin, Kaufman
OA affecting various parts of the body were
did not observe any serious adverse reactions.
randomly assigned to receive GS (500 mg
In the study by Jonas et al, the mean SGOT
three times per day) or a placebo for thirty
(AST) level increased by 20 percent over
days.9 Articular pain, joint tenderness and
baseline in the niacinamide group, but none
swelling, and range of motion improved to a
of the values rose to a level considered
significantly greater extent in the GS group
dangerous or of concern. However, there are
than in the placebo group. Samples of articuoccasional reports of large doses of
lar cartilage were obtained from two patients
niacinamide causing clinically significant
in each group at the end of the treatment peelevations of liver enzymes (serum
riod. Scanning electron microscopy performed
transaminases) and, rarely,
chemical hepatitis. Patients
taking large amounts of this
Figure 1. Glucosamine Sulfate
vitamin (such as 1,500 mg
per day or more) should
CH2OH
therefore have periodic tests
to monitor liver function.
O
Therapeutic doses of
H
H
niacinamide should be used
H
with caution, if at all, in
2Na(or K) + SO4 = 2CIindividuals who have or are
OH
H
at risk of developing liver
HO
OH
disease.

H
Glucosamine Sulfate
Articular cartilage
contains a group of large
protein molecules called
proteoglycans. These proteins make up the
ground substance of cartilage the material
that gives joints strength and resilience. Glucosamine, which is produced in the body from
glucose, is a precursor molecule in the synthesis of proteoglycans. Glucosamine has been
reported to stimulate proteoglycan synthesis
in vitro, to inhibit its degradation, and to rebuild experimentally damaged cartilage; effects which might be useful for the prevention
and treatment of OA.
The efficacy of glucosamineas glucosamine sulfate (GS; see Figure 1)in the
treatment of OA has been investigated in a

NH3+
2
on the cartilage obtained from patients receiving placebo showed a typical picture of established OA, whereas the tissue from those who
received GS showed a picture more similar to
healthy cartilage.
In another double-blind investigation,
twenty patients with OA of the knee received
GS (500 mg, three times per day) or a placebo
for six to eight weeks. GS was significantly
superior to placebo, as determined by improvements in pain, joint tenderness, and swelling.
The results were rated as excellent in all ten
patients receiving GS, whereas all ten patients
receiving the placebo rated the results as fair
or poor.10

Page 332
Alternative Medicine Review Volume 4, Number 5 1999
Copyright1999 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission

3
Glucosamine

Symptom Score

Ibuprofen

0
*p<0.05

1
**p<0.001

4
Time (weeks)

In a separate investigation, 252 patients

with osteoarthritis of the knee were randomly
assigned to receive placebo or GS (500 mg
three times per day) for four weeks.11 A positive response to treatment was defined as a reduction of at least three points in the
Lequesnes index, plus a positive overall assessment by the investigator. The mean
Lequesnes index, which was 10.6 points in
both groups at the start of the study, decreased
by 3.2 points in the GS group, compared with
2.2 points in the placebo group (p < 0.05). On
intention-to-treat analysis, the responder rate
was 52 percent in the glucosamine sulfate
group and 37 percent in the placebo group (p
= 0.016).
Several studies have compared the efficacy of GS with ibuprofen. Forty patients
with unilateral osteoarthritis of the knee received GS (500 mg three times per day), or
ibuprofen (1,200 mg per day), in double-blind

fashion for eight

weeks. Although the
rate of improvement
was slower in the
GS group than in the
ibuprofen group, the
improvement became progressively
more pronounced in
the former as the
study progressed.
By the eighth week,
pain relief was significantly more pronounced in the GS
group than in the
ibuprofen group
(see Figure 2).12

The same doses

of GS and ibuprofen
were compared in a
four-week study involving a similar group of patients.13 Again,
clinical improvement tended to occur sooner
in the ibuprofen group than in the GS group,
but there was no difference between groups
from the second week onward.
In a four-week study of 178 patients
with osteoarthritis of the knee, both GS and
ibuprofen significantly reduced OA symptoms,
with a trend of GS being more effective.14 The
beneficial effects of both GS and ibuprofen
persisted for at least two weeks after the treatments were discontinued; however, there was
a trend toward a greater residual effect in the
GS group.
GS has also been compared with
piroxicam, another NSAID. Some 329 patients
with osteoarthritis of the knee were randomly
assigned to one of four daily treatments for 90
days: 1,500 mg of GS; 20 mg of piroxicam;
GS plus piroxicam; or placebo.15 Patients were
followed an additional sixty days after treatment was discontinued. After ninety days of

Alternative Medicine Review Volume 4, Number 5 1999

Page 333

Copyright1999 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission

Osteoarthritis

Figure 2. Changes in pain score during comparison

study of glucosamine sulfate vs. ibuprofen. Adapted

treatment, GS was significantly more effective than placebo (as determined by the
Lequesne index) and more effective than
piroxicam (statistical comparison not presented). The beneficial effect of GS was maintained during the 60 days after treatment was
discontinued, whereas the effects of piroxicam
progressively decreased after withdrawal of
treatment.
These studies indicate that GS can relieve the symptoms of OA at least as effectively as some commonly used NSAIDs. Although circumstantial evidence, i.e., residual
effects after withdrawal of treatment and positive changes seen in biopsy samples, suggests
GS may also have a favorable influence on
the disease process, long-term studies are
needed to confirm this possibility.
No serious side effects have been
reported with the use of GS and the compound
is generally well tolerated, particularly when
compared with NSAIDs. Recently, concern
has been expressed about the potential for GS
to induce insulin resistance.16 This effect has
been demonstrated with continuous
intravenous infusions of GS in
normoglycemic 17 but not hyperglycemic18
animals,
using
the
euglycemic
hyperinsulinemic clamp method. Although
insulin resistance was detectable with GS
doses as low as 0.1 mg per kg body weight
per minute, the relevance of these findings to
humans is not clear. No abnormalities of
glucose metabolism have been reported in
individuals taking GS. However, until longterm studies are done, the potential for GS to
promote insulin resistance should be kept in
mind.
Although GS is not widely accepted
by conventional physicians in the United
States, it is a mainstay of treatment in Germany and Russia.19 Doctors in these countries
usually recommend 500 mg three times per
day for six to eight weeks, then twice a day
thereafter. For flare-ups, low doses of NSAIDs

are prescribed, along with 500 mg of glucosamine once a day. The use of glucosamine
reportedly makes it possible to cut the effective dosage of NSAIDs in half.

Chondroitin Sulfate
Chondroitin sulfate (CS) is a term used
to denote a group of structurally similar
polysaccharides, typically comprised of sulfated and unsulfated residues of glucuronic
acid and N-acetylglucosamine. CS is one of
the components of proteoglycans, the macromolecules that contribute to the structural and
functional properties of joint cartilage. There
is evidence that CS stimulates the synthesis
of proteoglycans by chondrocytes.
Forty-two patients (aged 35-78 years)
with symptomatic OA of the knee were randomly assigned to receive, in double-blind
fashion, 800 mg of a proprietary product containing chondroitin 4- and 6-sulfate (CS;
Condrosulf, IBSA, Lugano, Switzerland) per
day or a placebo for one year.20 After three
months, joint pain was reduced to a significantly greater extent in the CS group than in
the placebo group. The difference in pain reduction between groups became even more
pronounced after twelve months (63% vs.
26%; p < 0.01). The increase in overall mobility capacity (assessed by a visual analogue
scale) was significantly greater at six and 12
months in the CS group than in the placebo
group (69% increase vs. 19% increase; p <
0.01). After one year, the mean width of the
medial femoro-tibial joint was unchanged
from baseline in the CS group, but had decreased significantly in the placebo group.
Although no statistical comparison was presented for the change in joint width between
the CS and placebo groups, these findings are
consistent with the possibility that CS treatment slowed the progression of OA.
In another study, 85 patients with OA
of the knee were randomly assigned to
receive, in double-blind fashion,

Page 334
Alternative Medicine Review Volume 4, Number 5 1999
Copyright1999 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission

to be safe and effective for the symptomatic

treatment of OA. Preliminary evidence
suggests CS may also have a favorable
influence on the course of the disease but
definitive studies are lacking.

Glucosamine Sulfate vs.

Chondroitin
There has been an ongoing debate concerning whether GS or CS is the preferable
therapeutic agent or whether these compounds
should be used in combination. Orally administered GS has been shown to be well absorbed.24 On the other hand, CS is a relatively
large molecule and is presumably hydrolyzed
in the intestinal tract prior to being absorbed.
While some CS does appear to be absorbed
intact,25 the proportion of an oral dose that is
absorbed is said to be small.26 Some have argued that CS is largely broken down in the
gastrointestinal tract and then reassembled after being absorbed. If that is true, administering CS is merely an expensive way to obtain
precursor molecules. Since GS serves as a precursor to, and appears to promote the synthesis of, CS, administering GS may be a lessexpensive method of increasing the CS content of joint cartilage. On the other hand, it is
conceivable that the small amount of CS that
does get absorbed (or perhaps one of its
byproducts of partial digestion) exerts beneficial effects that cannot be duplicated by giving GS.
To date, there have been no studies
comparing the efficacy of GS and CS, or comparing the combination to either compound by
itself. Until such studies are done the choice
of which regimen to use remains a matter of
individual preference.

Vitamin E
Twenty-nine patients with OA at various sites were randomly assigned to receive
(single blind) 600 mg of vitamin E (type not
specified) per day or a placebo for ten days,

Alternative Medicine Review Volume 4, Number 5 1999

Page 335

Copyright1999 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission

Osteoarthritis

Chondrosulf (400 mg twice a day) or a

placebo for six months.21 Lequesnes Index,
spontaneous joint pain (visual analogue
scale) and walking time (defined as the
minimum time to perform a 20-meter walk)
all decreased progressively in the CS group.
There was a significant difference in favor
of the CS group for each of these parameters
(after three months for Lequesnes Index and
spontaneous joint pain; after six months for
walking time).
In a randomized, three-year, doubleblind trial, 34 patients with OA of finger joints
received Chondrosulf (400 mg three times per
day) and 85 patients received a placebo.22
During the study, a comparable number of patients in each group developed OA in previously non-affected finger joints. However, in
the CS group compared with the placebo group
there was a significant decrease in the number
of patients with new erosive OA of finger
joints. The authors concluded administration
of CS may protect against the development of
erosive changes in patients with finger joint
OA.
In another study, 146 patients with OA
of the knee were divided into two groups.23
One group received diclofenac sodium
(Voltaren; 50 mg three times per day) for one
month, followed by a placebo for two months.
The other group received CS (400 mg three
times per day) for three months. Both groups
then received a placebo for an additional three
months. Clinical efficacy was evaluated by
assessing the Lequesnes Index, spontaneous
pain, pain on load, and acetaminophen use. CS
was significantly more effective than placebo
in all parameters measured, and the effect of
CS became more pronounced with time. The
beneficial effects of CS diminished gradually
during the three months after treatment was
discontinued.
No serious side effects were reported
in any of the studies with CS. Thus, CS appears

and then the alternate treatment for an additional ten days.27 Fifty-two percent of the patients reported a reduction in pain while receiving vitamin E, compared with only 4 percent receiving placebo (p < 0.01).
In another study, 53 patients with OA
of the hip or knee were treated for three weeks
with vitamin E (d-alpha-tocopheryl acetate 400
mg three times per day; equivalent to approximately 600 IU three times per day) or
diclofenac (50 mg three times per day).28 Both
treatments appeared to be equally effective in
reducing the circumference of knee joints and
walking time, and in increasing joint mobility.
Although the mechanism of action of
vitamin E against OA is not known, this vitamin has been reported to have anti-inflammatory activity 29 and may also inhibit prostaglandin synthesis. In addition, vitamin E may
help stabilize lysosomal membranes, thereby
inhibiting the release of enzymes believed to
play a role in the pathogenesis of osteoarthritic
joint damage.

Boron
Boron has long been recognized as an
essential trace element for plants, but has only
recently been considered to be possibly essential for humans. Boron appears to participate
in hydroxylation reactions, which play a role
in the synthesis of steroid hormones and vitamin D. In Australia, where much of the food
is grown on soil deficient in this mineral, boron supplements were popular as a treatment
for OA, and were reportedly selling at a rate
of 10,000 bottles per month before the Australian government removed the product from
the market.30
In a double-blind study, 20 Australians
with OA were randomly assigned to receive
boron (6 mg per day as sodium tetraborate
decahydrate) or a placebo for eight weeks.31
Of those receiving boron, 50 percent improved, compared with 10 percent of those

given placebo. Because of the small sample

size, this difference was not statistically significant. When the five subjects (25%) who
dropped out of the study (mostly because of
clinical deterioration) were excluded from the
analysis, 71 percent of those in the boron group
improved, compared with 12.5 percent of those
in the placebo group (p < 0.05). No side effects were seen and there were no significant
changes in common laboratory parameters.
These results suggest boron supplementation may be helpful for individuals with
OA whose diets are likely to be low in boron.
Further research is needed to confirm this preliminary study and to determine whether individuals with a higher dietary intake of boron
can benefit from supplementation.
The average American diet provides
approximately 1-2 mg of boron per day, primarily from fruits, vegetables, and nuts; however, according to German research, intake can
vary from 0.3 to 41 mg per day. While the capacity of boron to increase estrogen levels32
might raise concerns about possible cancer
risks with boron supplementation, there is no
evidence that populations with a high intake
of boron (such as the French) have an increased
incidence of hormone-related cancers.

Vitamin D
In addition to its effects on calcium metabolism, vitamin D plays a role in the normal
turnover of articular cartilage. In a prospective study of 556 participants in the
Framingham study, low dietary intake of vitamin D and low serum levels of the vitamin
were each associated with increased radiographic progression of OA of the knee, but not
with the incidence of newly diagnosed OA.33
In an eight-year prospective study of 237 individuals (aged 65 years or older), low serum
levels of 25-hydroxyvitamin D were associated with an increased risk of developing OA
of the hip, as defined by joint-space narrowing.34 These studies suggest adequate intake

Page 336
Alternative Medicine Review Volume 4, Number 5 1999
Copyright1999 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission

Ascorbic Acid
Vitamin C is required for the synthesis of collagen, an important structural protein of joint cartilage. In guinea pigs, supplementation with vitamin C had a slight protective effect on experimentally-induced cartilage
degeneration of the knee.35 In a study of participants in the Framingham Osteoarthritis
Cohort Study, a higher intake of vitamin C
(upper tertile) was associated with a reduced
risk of cartilage loss and disease progression
in individuals with OA of the knee.36 In an
uncontrolled clinical trial, 59 patients with
petechiae and either rheumatoid or osteoarthritis received ascorbic acid (300-1,000 mg per
day) plus hesperidin (a flavonoid). Abnormal
capillary fragility improved and clinical improvement also frequently occurred.37 These
observations suggest adequate intake of vitamin C may help prevent progression of OA. It
is not known whether supplementation with
pharma-cological doses of vitamin C would
provide additional benefit.

Manganese
Animal studies have shown that manganese plays a role in the synthesis of chondroitin sulfate,38 an important component of
articular cartilage. Manganese deficiency has
been found to cause a cartilage metabolism disorder in farm animals. This condition is said
to resemble Mseleni joint disease, an OA-like
disease endemic to a remote part of Zululand,
where dietary intake of manganese is believed
to be low.39
It is not known whether manganese
deficiency plays a significant role in the
pathogenesis of OA; however, one cannot rule
out the possibility of subtle manganese
deficiency in Western societies. According to
Pfeiffer, modern farming techniques deplete

manganese from the soil, resulting in lower

concentrations of manganese in food.40 In
addition, individuals who consume refined
grains (such as white bread) obtain only half
as much manganese in their diet as those who
eat whole grains.

S-Adenosylmethionine
A metabolite of the essential amino
acid methionine, S-adenosylmethionine
(SAMe) functions as a methyl donor in many
biochemical reactions. In vitro studies have
provided evidence that SAMe stimulates the
synthesis of proteoglycans by human articular chondrocytes.41 During clinical trials of
SAMe as a treatment for depression, some
patients reported marked improvement in their
OA. Subsequently, extensive clinical trials,
which enrolled approximately 22,000 patients,
suggest SAMe is as effective as NSAIDs in
the treatment of OA, but is better tolerated.
In one such study, 734 patients with
OA were randomly assigned to receive, in
double-blind fashion, placebo, SAMe (1,200
mg per day), or naproxen (750 mg per day)
for 30 days.42 The reduction in pain and improvement in function were similar in the
SAMe and naproxen groups, and both active
treatments were significantly more effective
than placebo. For most parameters measured,
naproxen was significantly more effective than
placebo by day 15, whereas statistical significance was not seen with SAMe until day 30.
SAMe was better tolerated than naproxen, both
in terms of physicians (p < 0.025) and patients
(p < 0.01) assessments, and in terms of the
number of patients with side effects (p < 0.05).
There was no difference between SAMe and
placebo in the number of side effects.
Other short-term (three to four weeks)
double-blind trials have produced similar results. In a study involving 76 patients, SAMe
(1,200 mg per day) was significantly more
effective than placebo at relieving pain.43 The
same dose of SAMe was also as effective as

Alternative Medicine Review Volume 4, Number 5 1999

Page 337

Copyright1999 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission

Osteoarthritis

of vitamin D (or, presumably, adequate sunlight exposure) may slow the progression and
possibly help prevent the development of OA.

indomethacin (150 mg per day) 44 and

ibuprofen (1,200 mg per day),45 as assessed
by standard scoring systems for various clinical parameters.
In a 12-week double-blind study of 48
patients with OA of the knee, SAMe (1,200
mg per day) was as effective as piroxicam (20
mg per day), as determined by improvements
in pain, mobility, morning stiffness, and painfree walking distance.46 Moreover, the improvement in pain score was maintained for
at least eight weeks after SAMe was discontinued, whereas a significant worsening was
seen in the piroxicam group 28 days after the
end of treatment.
The long-term effects of SAMe have
been evaluated in an open trial involving 108
patients with OA of the knee, hip, or spine.47
Each patient received 600 mg of SAMe per
day for two weeks, followed by 400 mg per
day for a total of two years. Clinical
improvement, as determined by symptom
score, was seen after two weeks, and there was
further continuous improvement up to the sixth
month and beyond. Eighteen (19%) of 97
patients who completed two years of treatment
experienced total remission of symptoms by
the end of the study. More than 90 percent of
the physicians and more than 85 percent of
the patients assessed the effects of treatment
as very good or good. Non-specific side
effects (mostly gastrointestinal) occurred in 20
patients, but in no case did the treatment have
to be discontinued. Most side effects
disappeared during the course of therapy.
Although SAMe has been used in Europe for many years it has only recently become commercially available in the United
States. The product is rather expensive compared with other nutritional supplements. In
addition, concerns have been raised about the
stability of most of the SAMe being sold in
this country. Crystalline SAMe degrades rapidly upon exposure to heat and/or moisture,
and some of the imported raw material has

been said to be partially decomposed upon

arrival.48 Therefore, it may be preferable to use
the enteric-coated, pharmaceutical-grade tablets imported from Europe, rather than other
preparations currently being sold in the United
States.

Avocado/Soybean Extract
An extract of unsaponifiable fractions
of avocado and soybean oil (AS) has been
shown to stimulate collagen synthesis in articular chondrocyte cultures. In a recent study,
164 patients with OA of the hip or knee were
randomly assigned to receive, in double-blind
fashion, 300 mg per day of this extract
(Piascledine 300; Pharmascience Laboratories,
Courbevoie, France; containing unsaponifiable
fractions of avocado oil [one-third] and soybean oil [two-thirds]) or a placebo, for six
months.49 The mean Lequesnes index score
and the mean pain score improved to a significantly greater extent in the AS group than
in the placebo group (p < 0.001 and p = 0.003,
respectively). Thirty-nine percent of the patients in the AS group were considered clinical successes, compared with 18 percent in the
placebo group (p < 0.01). A residual effect of
the avocado/soybean extract was evident two
months after treatment was discontinued. No
severe side effects were reported.

Herbal Remedy for OA

Forty-two patients with OA were randomly assigned to receive, in double-blind
fashion, an Ayurvedic preparation (ArticulinF) or a placebo for three months, and then the
alternate treatment for an additional three
months. Articulin-F contains (per capsule) 450
mg of Withania somnifera root, 100 mg of
Boswellia serrata stem, 50 mg of Curcuma
longa rhizome, and 50 mg of a zinc complex.
The dosage was two capsules three times per
day, after meals. Compared with placebo,
Articulin-F significantly reduced the severity
of pain and the disability score. Side effects

Page 338
Alternative Medicine Review Volume 4, Number 5 1999
Copyright1999 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission

worth comparing the effects of various combinations (such GS plus niacinamide, or GS

plus niacinamide plus trace minerals) with the
effects of each treatment by itself.

Dietary Factors
Some clinicians have observed that
identification and avoidance of allergenic
foods will relieve the symptoms of OA in some
cases. In addition, one report has implicated
foods from the genus Solanaceae
(Nightshades: tomato, potato, eggplant, bell
pepper, and tobacco) as possible triggering
agents for OA.51 The reaction to Nightshade
foods is believed to be due to solanum
glycoalkaloids present in these foods.
Although no controlled studies have been done
on the relation between diet and OA, some
patients appear to benefit from individualized
dietary modifications. Avoiding allergenic
foods typically produces results within several
weeks or less, whereas it may take a number
of months on a Nightshade-free diet before
improvement is seen.

Discussion and Conclusion

This article has reviewed a number of
promising alternatives for preventing and treating OA. Although additional research needs
to be done, some of the treatments discussed
appear to be as effective as, and better tolerated than, conventional drug therapy. In addition, preliminary evidence (such as the persistence of improvement after treatment is discontinued, and positive radiographic and biopsy findings) suggests some of these treatments may help arrest or reverse the disease
process.
There are few, if any, data on whether
the various agents described in this article
would have an additive or synergistic effect if
used in combination. However, it is not likely
that each of these compounds has the same
mechanism of action. Therefore, it would be

References
1.
2.

3.

4.

5.

6.

7.
8.

9.

10.

11.

12.

Bland JH. The reversibility of osteoarthritis: a

review. Am J Med 1983;74:16-26.
Brandt KD. Effects of nonsteroidal antiinflammatory drugs on chondrocyte metabolism in vitro and in vivo. Am J Med
1987;83:29-34.
Rashad S, Revell P, Hemingway A, et al.
Effect of non-steroidal anti-inflammatory
drugs on the course of osteoarthritis. Lancet
1989;2:519-522.
Kaufman W. The Common Form of Joint
Dysfunction: Its Incidence and Treatment.
Brattleboro, VT: E. L. Hildreth Co.; 1949.
Kaufman W. The use of vitamin therapy to
reverse certain concomitants of aging. J Am
Geriatr Soc 1955;3:927-936.
Kaufman W. Niacinamide therapy for joint
mobility. Therapeutic reversal of a common
clinical manifestation of the normal aging
process. Conn State Med J 1953;17:584-591.
Kaufman W. Niacinamide: a most neglected
vitamin. J Int Acad Prev Med 1983:8;5-25.
Jonas WB, Rapoza CP, Blair WF. The effect of
niacinamide on osteoarthritis: a pilot study.
Inflamm Res 1996;45:330-334.
Drovanti A, Bignamini AA, Rovati AL.
Therapeutic activity of oral glucosamine
sulfate in osteoarthrosis: a placebo-controlled
double-blind investigation. Clin Ther
1980;3:260-272.
Pujalte JM, Llavore EP, Ylescupidez FR.
Double-blind clinical evaluation of oral
glucosamine sulphate in the basic treatment of
osteoarthritis. Curr Med Res Opin 1980;7:110114.
Noack W, Fischer M, Forster KK, et al.
Glucosamine sulfate in osteoarthritis of the
knee. Osteoarthritis Cartilage 1994;2:51-59.
Vaz AL. Double-blind clinical evaluation of
the relative efficacy of glucosamine sulphate in
the management of osteoarthritis of the knee in
out-patients. Curr Med Res Opin 1982;8:145-149.

Alternative Medicine Review Volume 4, Number 5 1999

Page 339

Copyright1999 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission

Osteoarthritis

included nausea (n = 2), dermatitis (n = 3),

and abdominal pain (n = 3), none of which
required discontinuation of treatment.50

13.

14

15

16.
17.

18.

19.

20.

21.

22.

23.

Muller-Fassbender H, Bach GL, Haase W, et

al. Glucosamine sulfate compared to ibuprofen
in osteoarthritis of the knee. Osteoarthritis
Cartilage 1994;2:61-69.
Qiu GX, Gao SN, Giacovelli G, et al. Efficacy
and safety of glucosamine sulfate versus
ibuprofen in patients with knee osteoarthritis.
Arzneimittelforschung 1998;48:469-474.
Rovati LC, Giacovelli G, Annefeld M, et al. A
large, randomised, placebo controlled, doubleblind study of glucosamine sulfate vs
piroxicam and vs their association, on the
kinetics of the symptomatic effect in knee
osteoarthritis. Second Int Congr Osteoarthritis
Res Soc 1994;Dec:56.
Adams ME. Hype about glucosamine. Lancet
1999;354:353-354.
Baron AD, Zhu JS, Zhu JH, et al. Glucosamine
induces insulin resistance in vivo by affecting
GLUT 4 translocation in skeletal muscle.
Implications for glucose toxicity. J Clin Invest
1995;96:2792-2801.
Rossetti L, Hawkins M, Chen W, et al. In vivo
glucosamine infusion induces insulin resistance in normoglycemic but not in hyperglycemic conscious rats. J Clin Invest 1995;96:132140.
Anonymous. Meeting news: take-home tips
from the American Academy of Family
Physicians. Modern Med 1997;65:40.
Uebelhart D, Thonar EJMA, Delmas PD, et al.
Effects of oral chondroitin sulfate on the
progression of knee osteoarthritis: a pilot
study. Osteoarthritis Cartilage 1998;6:39-46.
Bucsi L, Poor G. Efficacy and tolerability of
oral chondroitin sulfate as a symptomatic
slow-acting drug for osteoarthritis
(SYSADOA) in the treatment of knee osteoarthritis. Osteoarthritis Cartilage 1998;6:31-36.
Verbruggen G, Goemaere S, Veys EM.
Chondroitin sulfate: S/DMOAD (structure/
disease modifying anti-osteoarthritis drug) in
the treatment of finger joint OA. Osteoarthritis
Cartilage 1998;6:37-38.
Morreale P, Manopulo R, Galati M, et al.
Comparison of the anti-inflammatory efficacy
of chondroitin sulfate and diclofenac sodium
in patients with knee osteoarthritis. J
Rheumatol 1996;23:1385-1391.

24.

25.

26.

27.

28.

29.

30.
31.

32.

33.

34.

35.

36.

37.

Setnikar I, Palumbo R, Canali S, Zanolo G.

Pharmacokinetics of glucosamine in man.
Arzneimittelforschung 1993;43:1109-1113.
Conte A, Volpi N, Palmieri L, et al. Biochemical and pharmacokinetic aspects of oral
treatment with chondroitin sulfate.
Arzneimittelforschung 1995;45:918-925.
Kelly GS. The role of glucosamine sulfate and
chondroitin sulfates in the treatment of
degenerative joint disease. Altern Med Rev
1998;3:27-39.
Machtey I, Ouaknine L. Tocopherol in
osteoarthritis: a controlled pilot study. J Am
Geriatr Soc 1978;26:328-330.
Scherak O, Kolarz G, Schodl C, Blankenhorn
G. High dosage vitamin E therapy in patients
with activated arthrosis. Z Rheumatol
1990;49:369-373. [Article in German].
Stuyvesant VW, Jolley WB. Anti-inflammatory
activity of d-alpha-tocopherol (vitamin E) and
linoleic acid. Nature 1967;216:585-586.
Newnham RE. The role of boron in human
nutrition. J Appl Nutr 1994;46:81-85.
Travers RL, Rennie GC, Newnham RE. Boron
and arthritis: the results of a double-blind pilot
study. J Nutr Med 1990;1:127-132.
Nielsen FH, Hunt CD, Mullen LM, Hunt JR.
Effect of dietary boron on mineral, estrogen,
and testosterone metabolism in postmenopausal women. FASEB J 1987;1:394-397.
McAlindon TE, Felson DT, Zhang Y, et al.
Relation of dietary intake and serum levels of
vitamin D to progression of osteoarthritis of
the knee among participants in the
Framingham study. Ann Intern Med
1996;125:353-359.
Lane NE, Gore LR, Cummings SR, et al.
Serum vitamin D levels and incident changes
of radiographic hip osteoarthritis: a longitudinal study. Arthritis Rheum 1999;42:854-860.
Meacock SC, Bodmer JL, Billingham ME.
Experimental osteoarthritis in guinea-pigs. J
Exp Pathol 1990;71:279-293.
McAlindon TE, Jacques P, Zhang Y, et al. Do
antioxidant micronutrients protect against the
development and progression of knee osteoarthritis? Arthritis Rheum 1996;39:648-656.
Warter PJ, Drezner HL, Donio DA, Horoschak
S. Seven-year observations on the treatment of
arthritis with hesperidin-ascorbic acid. J Am
Geriatr Soc 1956;4:592-598.

Page 340
Alternative Medicine Review Volume 4, Number 5 1999
Copyright1999 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission

Leach RM Jr, Muenster A-M, Wien EM.

Studies on the role of manganese in bone
formation. II. Effect upon chondroitin sulfate
synthesis in chick epiphyseal cartilage. Arch
Biochem Biophys 1969;133:22-28.
39. Anonymous. Mseleni joint disease - a manganese deficiency? S Afr Med J 1981;60:445-447.
40. Pfieffer CC. Zinc and Other Micronutrients.
New Canaan, CT: Keats; 1978:69.
41. Harmand M-F, Vilamitjana J, Maloche E, et al.
Effects of S-adenosylmethionine on human
articular chondrocyte differentiation. Am J
Med 1987;83:48-54.
42. Caruso I, Pietrogrande V. Italian double-blind
multicenter study comparing Sadenosylmethionine, naproxen, and placebo in
the treatment of degenerative joint disease. Am
J Med 1987;83:66-71.
43. Montrone F, Fumagalli M, Sarzi Puttini P, et
al. Double-blind study of S-adenosyl-methionine versus placebo in hip and knee arthrosis.
Clin Rheumatol 1985;4:484-485.
44. Vetter G. Double-blind comparative clinical
trial with S-adenosylmethionine and indomethacin in the treatment of osteoarthritis.
Am J Med 1987;83:78-80.
45. Muller-Fassbender H. Double-blind clinical trial
of S-adenosylmethionine versus ibuprofen in
the treatment of osteoarthritis. Am J Med
1987;83:81-83.
46. Maccagno A, Di Giorgio EE, Caston OL,
Sagasta CL. Double-blind controlled clinical
trial of oral S-adenosylmethionine versus
piroxicam in knee osteoarthritis. Am J Med
1987;83:72-77.
47. Konig B. A long-term (two years) clinical trial
with S-adenosylmethionine for the treatment
of osteoarthritis. Am J Med 1987;83:89-94.
48. Czap A. Beware the son of SAMe. Altern Med
Rev 1999;4:73.
49. Maheu E, Mazieres B, Valat JP, et al. Symptomatic efficacy of avocado/soybean
unsaponifiables in the treatment of osteoarthritis of the knee and hip: a prospective, randomized, double-blind, placebo-controlled,
multicenter clinical trial with a six-month
treatment period and a two-month followup
demonstrating a persistent effect. Arthritis
Rheum 1998;41:81-91.

50.

51.

Kulkarni RR, Patki PS, Kog VP, et al. Treatment of osteoarthritis with a herbomineral
formulation: a double-blind, placebo-controlled, cross-over study. J Ethnopharmacol
1991;33:91-95.
Childers NF, Russo GM. The Nightshades and
Health. Somerville, NJ: Horticultural Publications, Somerset Press, Inc.; 1973.

Alternative Medicine Review Volume 4, Number 5 1999

Page 341

Copyright1999 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission

Osteoarthritis

38.