ACA Journal of Chiropractic/November 1990 ~ FULL TEXT
Luke R. Bucci, Ph.D.
Research from rheumatology and orthopedic clinics
from Europe on the ability to reverse osteoarthritis has been
accumulating for the last 25 years. Based on these results, this
article will describe a nutritional program, that in conjunction
with standard therapies used for osteoarthritis, can actually
reverse the course of osteoarthritis.
Osteoarthritis is a collection of ill-defined joint diseases
with cartilage degeneration being a central feature. [1-3] Usually, deficient cartilage repair, joint
bone remodeling, and later, synovial inflammatory processes promote
extensive de-generation and erosion. [1-3] Osteoarthritis has the highest morbidity (incidence) of
all diseases, with almost universal occurrence after 50 years
of age, although not all cases are severe. However, 5 million
Americans per year are disabled by osteoarthritis, which is still
the primary cause of lost time from work.
Even now, osteoarthritis is thought to be a
normal consequence of aging, caused by routine "wear and
tear" on joints. Also, it is thought that cartilage cannot
heal itself, which is not completely true. [1-6] Of foremost importance is
the notion that osteoarthritis is associated with an inevitable
progression to disability, and nothing can stop or reverse the
process. These concepts have been overturned by recent research
Evidence for Reversibility of Osteoarthritis
There is substantial evidence that osteoarthritis
can be reversible. [4-7] Spontaneous remissions in humans have been recorded
and reported. Juvenile chronic arthritis can be halted by long-term,
intense physical therapy and drugs. Chronic passive joint mobilization
in animals has reversed osteoarthritis. Redistribution of joint
loads by surgical techniques, polio, paralysis, and strokes has
led to cessation of osteoarthritic progression. The proper types
of electrical and mechanical stimulation of chondrocytes (the
cells responsible for cartilage upkeep and repair) are currently
being investigated. Thus, cartilage has the innate ability to
repair itself if given the correct conditions.
A new term introduced from Europe describes
the actions of two categories of nutrients found to aid in reversal
of osteoarthritis. Chondroprotective agents promote repair of
cartilage by stimulating anabolic metabolism of chondrocytes and/or
inhibiting catabolic processes found in osteoarthritis.  This concept
of helping chondrocytes to heal cartilage, rather than reliance
on palliative analgesics, is a relatively new concept that gets
more to the actual causes of osteoarthritis, as well as treating
The two major categories of chondroprotective nutrients are:
glycosaminoglycans and antioxidants. Glycosaminoglycans (GAGs)
were formerly named mucopolysaccharides, and are major structural
components of cartilage and connective tissues.  GAGs are long polymers of repeating two-sugar
units, usually with sulfate groups on one type of sugar. The most
common GAG is chondroitin sulfate, composed of glucuronic acid
and N-acetyl galactosamine sulfate.
Chondroitin sulfate forms the bulk of GAG products previously
tested and currently available. In Europe, purified chondroitin
sulfate is available as both nutrient and drug. Two pharmaceutical
products contain mostly chondroitin sulfates: Arteparon is synthetically
sulfated purified chodroitin sulfate; Rumalon is semipurified
GAGs from bovine cartilage sources. Glucosamine sulfate is another
nutrient/pharmaceutical in European use, and is a single sugar
precursor for chondroitin sulfate.
All GAG supplements share these common features:
precursors for GAG synthesis;
inhibition of degradative enzymes (elastase, collagenase, chondroitinases);
stimulation of anabolic metabolism of chondrocytes; and
of corticosteroid and NSAID side effects.
Antioxidants with known chondroprotective abilities
are ascorbate (vitamin C), tocopherol (vitamin E), superoxide
dismutase (SOD), and catalase, and other antioxidant nutritents
have shown in vitro protection. Antioxidants share common properties
of inhibition of free radical damage to cartilage, modulation
of immune functions to resist auto-immunity, decrease of pro-inflammatory
prostaglandins, inhibition of degradative enzymes, and for vitamin
C, direct anabolic stimulation of chondrocytes.
Clinical Results of Chondroprotective Nutrients
For over 30 years, these chondroitin sulfate
forms have been used in animal and human trials against osteoarthritis.  In fact, over
40 million dose units per year of Rumalon are given. Most of these
trials have been summarized in two recent English-language reviews. [9,10] However,
most of the original articles are in foreign languages in journals
not readily accessible in the United States.
From the medical schools of Kumamoto, Matsumoto, Nagoya, Aichi,
Tohuku, and Inatsuki, 26 orthopedic clinics participated in a
double-blind study of 120 patients with osteoarthritis of the
knee given intra-articular injections of either 1 mg arteparon
(control group), or 50 mg Arteparon.Ò
Five total injections were given at weekly intervals for five
weeks. Assessment of treatment found that 71 percent of high-dose
patients showed improvement, and that 41 percent of controls also
showed improvement, a significant difference. Thus, short-term
observations suggested that a form of chondroitin sulfate can
improve osteoarthritic conditions.
Investigators from the Internal Medicine/Rheumatology Polyclinic
of Charles University in Prague, Czechoslovakia conducted independent
com-parisons of arteparon and rumalon in osteoarthritis of the
knee in long-term studies lasting five and ten years.  Fifty patients with osteoarthritis of the
knee in each of three groups were given either intra-muscuiar
injections of vitamin B12 (controls), arteparon (ten courses of
injections at six month intervals for a total dose of 7.5 grams),
or rumalon (ten courses of injections at six month intervals for
a total dose of 250 ml).  All
patients were also given standard analgesics and NSAIDS.
Knee pain was decreased for two years in the control group,
but afterwards, became progressively worse, even with higher NSAID
doses. This is typical of standard therapy. However, knee pain
was decreased quickly (within four months) and to a much greater
degree with arteparon and rumalon, along with a decrease in analgesics,
and continued to decrease even after five years. Likewise, measures
of joint function (time to ascend and descend a 15-step staircase)
were maintained for two years in each group, but thereafter, clear
divergence was seen. The control group became progressively worse,
while the GAG groups became progressively better. Similarly, the
ability to work became worse with the control group until, after
five years, all controls were unfit for work. Conversely, after
five years, between 50 and 80 percent of GAG subjects were fit
Another measure of response was needed for tibial osteotomy
operations. For controls, 13/50 received this operation, while
only 2/ 50 for each GAG group received osteotomies. Radiologic
parameters showed that GAG subjects had only 1/2 to 1/3 of the
adverse changes seen in the control group. The grade of osteoarthritis
did not worsen in only 1/50 control subjects, but 1/3 to 1/2 of
GAG subjects did not worsen. Subjective evaluations by doctors
and patients also showed significant benefits for GAG subjects.
Thus, by both sub-jective and objective criteria, GAG treatment
significantly prevented the inevitable progression to disability,
and even slowed the physical findings of osteoarthritis.
This study was preceded by a ten-year study of rumalon on hip
arthritis on 112 matched pairs of subjects, which also showed
remarkable prevention of progression of radiologic changes, decreases
in analgesic use, and an actual decrease in lost working days
for the rumalon group, compared to a steady progression to almost
complete disability in the control group.  All differences were statistically significant.
A series of investigations on the effects of glucosamine sulfate
supplementation by oral route showed even more promising results.
Several short-term studies found significant reductions in joint
pain, analgesic use and improvements of joint function with 0.75
or 1.5 grams of daily glucosamine sulfate. [12-15] One study actually took cartilage biopsies
before and after four weeks of glucosamine sulfate oral supplementation
in a few treated subjects.  Electron
microscopy initially showed a typical picture of established osteoarthritis.
However, those given glucosamine sulfate "....showed a picture
more similar to healthy cartilage."  The results of this article strongly suggest
that reversal of osteoarthritis was being accomplished after oral
The results of short-term oral GAG supplementation are even
more dramatic than long-term injectable GAG treatment for several
high blood and cartilage levels of GAGs are possible with oral
administration, rather than cyclic injectable administration;
effects are nonexistent with oral GAG administration;
doses of GAGs can be maintained orally. Thus it is no surprise
to find that oral GAG supplementation achieved results much faster
than injectable GAG treatment.
Antioxidants as Chondroprotectors
One recent theory of osteoarthritis causation
is based on free radical formation in joints as the trigger for
disease progression. 
Several scenarios associated with osteoarthritis are
now known to cause release of free radicals in joints. 
Local ischemia in cartilage (already a hypoxic tissue) induced by chronic joint
loading, abnormal joint forces, poor circulation, overexercise,
trauma, auto-immune attack and even excess iron elevates levels
of free radicals in joints.  Free radicals directly attack and degrade
cartilage components, [17-19] triggering a synovial and immune response
that promotes further cartilage damage. Because of the slow metabolism
of chondrocytes, both injury and repair take months or years to
become fully evident. This free radical mechanism of arthritis
indicates quite logically that antioxidants may prevent or reverse
formation of arthritic symptoms.
At Tufts University in Boston, guinea pigs were fed a normal
or high intake of vitamin C before, during and after surgery to
induce knee osteoarthritis.  The guinea pigs fed a standard RDA amount of vitamin C
(2.4 mg daily) developed osteoarthritis, but the guinea pigs fed
150 mg of vitamin C daily developed only very minor changes.  This in vivo work is supported
by in vitro studies that showed vitamin C is chondroprotective
by stimulating anabolism in cartilage cultures, and by inhibiting
degradative enzymes in cartilage. [20,21]
Researchers in Israel gave 32 subjects with osteoarthritis
600 mg daily of vitamine E (d-alpha tocopherol acetate) for only
10 days.  Even with this
very short experimental period, significant improvements in functional
assessment, pain and analgesic use were seen with vitamin E, but
not with a placebo.
At Konstanz University in Hannover, West Germany, 50 subjects
were given either a placebo or 400 IU of d-alpha tocopherol acetate
daily for six weeks in a double-blind study.  Significant decreases in pain and analgesic
use were seen for the vitamin E group. Functional improvements
were noted, but had not reached significance when the study ended.
In vitro investigations have also shown that vitamin E can
inhibit effects of degradative enzymes in cartilage.  Thus, simple studies have shown that even
a single antioxidant can improve osteoarthritis symptoms without
side effects. Combinations of antioxidants have yet to be investigated,
and longer experimental periods are needed to confirm the effectiveness
of antioxidants as chondroprotective agents, but the hypothetical
and preliminary evidence is strongly suggestive that antioxidants
are potent chondroprotective agents.
Nutrient Combination and Low Back Pain
One recent report examined the effects of several
nutritional supplements on chronic low back pain in a chiropractic
setting.  Objective assessment of low back function was accomplished
by a computerized testing device. Groups of six patients each
were given no supplements (controls), manganese sulfate (900 mg
daily), purified chondroitin sulfates (600 mg daily), or purified
chondroitin sulfates with a comprehensive multiple vitamin/mineral
without iron, including vitamin C and vitamin E. Improvements
in strength, range of motion and pain were greatest in the combination
group, and moderate in the chondroitin sulfate group, but minimal
in the control and manganese sulfate groups.  This pilot study is the first
to suggest that use of chondroprotective nutrients may benefit
chronic low back pain patients.
Osteoarthritis can be reversible by chondroprotective
agents if the following conditions are met:
remains intact over joint surfaces;
bone is intact;
changes to reduce pressure on affected joint are followed;
use is kept to a minimum or ideally, not used;
time is given to properly evaluate effects, and;
daily supplementation of chondroprotective nutrients is accompanied
by a diet providing all essential nutrients.
One important variable not considered here
is the use of analgesics, most of which impair synthesis of cartilage
components. [25,26] While chondroprotective nutrients can counteract analgesic
side effects, it is likely that reversal would be more apparent
without analgesic use.
Thus, a growing body of clinical evidence, along with a vast
literature on hypothetical mechanisms, supports the long-term
use of chondroprotective nutrients (GAGs and antioxidants) for
cessation or reversal of osteoarthritis, and possibly other degenerative
joint diseases. Although results may or may not be noticeable
within a month, lack of side effects and ability to attack the
cause of arthritis are prime reasons to consider their use in
routine clinical settings.
1. Hamerman, D. The biology of
osteoarthritis. N Engl J Med 1989;320(20):1322-1329.
2. Mankin, H.J. Biochemical and
metabolic aspects of osteoarthritis. Orthop Clin N Am 1971;2(1):19-31.
3. Brandt, K.D. Pathogenesis of
4. Reimann, I., Christensen, S.B.,
Diemer, N.H. Observations of reversibility of glycosaminoglycan
depletion in articular cartilage. Clin Orthop 1982;168:258-261.
5. Radin, E.L., Burr, D.B. Hypothesis:
joints can heal. Sem Arth Rheum 1984;13(3):293-302.
6. Bland, J.H., Cooper, S.M. Osteoarthritis:
a review of the cell biology involved and evidence for reversibility.
Management rationally related to known genesis and pathophysiology.
Sem Arth Rheum 1984; 14(2):106-133.
7. Altman, R.D., Howell, D.S.,
Gottlieb, N.L. New directions in therapy of osteoarthritis. Sem
Arth Rheum 1987;17(2, Suppl 1):1-2.
8. Varma, R.S., Varma, R. eds.
Glycosaminoglycans and proteoglycans in physiological and pathological
processes of body systems. Basel: Karger, 1982.
9. Burkhardt, D., Ghosh, P. Laboratory
evaluation of antiarthritic drugs as potential chondroprotective
agents. Sem Arth Rheum 1987;17(2)Suppl.l:3-34.
10. Rejholec, V. Long-term studies
of antiosteoarthritic drugs: an assessment. Sem Arth Rheum 1987;17(2)Suppl.l:35-53.
11. Ishikawa, K., Kitagawa, T.,
Tanaka, T., Teravama, K., Kuriya, N., Iwata, H., Niwa, S., Sakurai,
M. Clinical evaluation of the intra-articular injection of glycosaminoglycan
polysulphate for osteoarthritis of the knee joint: a multicentric
double blind controlled study. Z Orthop 1982;120:708-716.
12. Drovanti, A., Bignamini, A.A.,
Rovati, A.L. Therapeutic activity of oral glucosamine sulfate
in osteoarthritis: a placebo-controlled double-blind investigation.
Clin Ther 1980;3(4):260-272.
13. Vaz, A.L. Double-blind clinical
evaluation of the relative efficacy of ibuprofen and glucosamine
sulphate in the management of osteoarthritis of the knee in out-patients.
Curr Med Res Opin 1982;8(3):145-149.
14. D'Ambrosio, E., Casa, B.,
Bompani, P., Scali, G., Scali, M. Glucosamine sulphate: a controlled
clinical investigation in arthrosis. Pharmatherapeutica 1981;2(8):504-508.
15. Pujalte, J.M., Llavore, E.,
Ylescupidez, F.R. Double-blind clinical evaluation of oral glucosamine
sulphate in the basic treatment of osteoarthrosis. Curr Med Res
16. Swaak, A.J.G., Koster, J.F.
Free radicals and arthritic diseases. Rijswijk:Eurage, 1986.
17. Greenwald, R.A. Effect of
oxygen-derived free radicals on connective tissue macromolecules.
In: Bannister, W.H., Bannister, J.V., eds. Biological and Clinical
Aspects of Superoxide and Superoxide Dismutase. New York: Elsevier,
18. Wong, S.F., Halliwell, B.,
Richmond, P., Skowroneck, W.R. The role of superoxide and hydroxyl
radicals in the degradation of hyaluronic acid induced by metal
ions and by ascorbic acid. J Inorg Biochem 1981;14:127-134.
19. Burkhardt, H., Schwingel,
M., Menninger, H., Macarmey, H.W., Tschesche H. Oxygen radicals
as effecters of cartilage destruction. Arth Rheum 1986;29(3):379-387.
20. Schwartz, E.R. The modulation
of osteoarthritic development by vitamins C and E. Int J Vit Nutr
Res 1984; Suppl 26:141-146.
21. Krystal, G., Morris, G.M.,
Sokoloff, L. Stimulation of DNA synthesis by ascorbate in cultures
of articular chondrocytes. Arth Rheum 1982;25(3):318-325.
22. Machtey, I., Ouaknine, L.
Tocopherol in osteoarthritis: a controlled pilot study. J Am Ger
23. Blankenhorn, G. Clinical efficacy
of Spondyvit (Vitamin E) in activated arthroses. A multicenter,
placebo-controlled, double-blind study. Z Orthop Ihre Grenzgeb
24. Christensen, K.D., Bucci,
L.R. Comparison of nutritional supplement effects on functional
assessments of lower back patients measured by an objective computer-assisted
tester. In: Second Symposium on Nutrition and Chiropractic. Davenport:
Palmer College of Chiropractic, 1989, 19-22.
25. Palmoski, M.J., Brandt, K.D.
Effect of salicylate on proteoglycan metabolism in normal canine
atticular cartilage in vitro. Arth Rheum 1979;22(7):746-754,
26. Palmoski, M.J., Brandt, K.D.
Effects of some nonsteroidal antiinflammatory drugs on proteoglycan
metabolism and organization in canine articular cartilage. Arth
Return to the GLUCOSAMINE Page
Return to the CHIROPRACTIC AND DJD Page
Return to the NUTRITION ARCHIVES Section