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Exercise Therapeutics Update and Commentary

by Anna MacIntosh, PhD, ND
Professor of Nutrition & Exercise Therapy
National College of Naturopathic Medicine
P.O. Box 644 -- Beavercreek, Oregon 97004 USA

Keeping Joints Healthy with Exercise and Supplements

 

Ankle, knee, shoulder or hip pain - which have you experienced? Most Americans over 35 can probably tell you they have suffered through joint pain sometime in their life. Painful joints can severely impact an individual's quality of life and mobility. In the elderly, joint pain is undoubtedly the number one cause of losing the possibility of independent living. The most common reasons for joint pain are the well-known diseases of rheumatoid arthritis and osteoarthritis. Many active individuals and certainly most competitive athletes must deal with joint pain or disability on almost a constant basis. Maintaining or rebuilding joint tissue is crucial for individuals of all ages if they are to enjoy long lasting freedom from joint pain.

Composition of joint tissue

Ligaments and cartilage are forms of dense connective tissue which provide both stability and cushioning to joints. The macromolecules of which dense connective tissue is composed includes proteins (collagen and elastin) and proteoglycans. Proteoglycans are composed of a protein core with glycosaminoglycans (GAGs) attached. The synthesis of these macromolecules is well studied and known to require a number of important micronutrients.1 The specific micronutrients requirements will be discussed later under "supplements."

Collagen is the most abundant protein in the body and is a component of all types of connective tissue. Since connective tissue is pervasive in the body, producing and maintaining healthy collagen is tantamount to maintaining health. Collagen has a triple helix configuration which gives it tremendous strength. This special biochemical configuration is highly dependent on the incorporation of the amino acid proline during the synthesis of collagen. The production of normal proline requires vitamin C.2 Some of the earliest manifestations of scurvy, the vitamin C deficiency disease, are weakened connective tissue, i.e. easy bleeding of the gums. Although scurvy is considered a rarity in this country, inadequate intakes of vitamin C could still manifest in weakened connective tissue. Weakened connective tissue could allow joints to be vulnerable to injury.

GAGs are a major component of cartilage, hence smooth operation of joints is highly dependent on healthy GAGs.3 Within cartilage there are two main types of GAGs, chondroitin-4-sulphate and chondroitin-6-sulphate. GAGs are composed of repeat disaccharide (two) units. These units are composed of sugar amine compounds (i.e. glucosamine  or galactosamine) bound together as a polymer.4 All GAGs also contain sulfate ester moieties, i.e. the element sulfur is required for normal GAG synthesis.5

The dangers of standard treatments for joint pain

The standard approach to treating joint pain has been and remains anti-inflammatory medications. Both steroidal and non-steroidal drugs are typically used. Medications such as aspirin, ibuprofen and other non-steroidal anti-inflammatory drugs (most over-the-counter pain relievers are non-steroidal anti-inflammatory drugs - NSAIDs) can block the production of the inflammatory chemicals, prostaglandins. The possible long term cost to joint integrity for short term pain relief offered by these types of drugs needs to be elucidated.

At least six studies conducted in the United States and Europe have reported that NSAIDs can lead to destruction of joints.6-11 In fact, two of the studies actually showed that NSAIDs can interfere with the normal production of GAGs in cartilage.7,8 Presumably joint destruction will not occur with NSAIDs unless "high," chronic use of NSAIDs is being employed. At this time, it is not clear what is meant by a "high" dose or for how long someone can ingest NSAIDs before joint destruction begins. People with rheumatoid or osteo-arthritis and athletes who freely use NSAIDs to continue their athletic endeavors despite joint pain, would undoubtedly be the individuals at greatest risk for NSAIDs - caused joint destruction.

Athletes are also vulnerable to kidney problems, maybe even kidney failure, with high NSAID use combined with heavy sweating during workouts. Prostaglandins, the compounds whose synthesis is blocked by NSAIDs, are extremely important for normal kidney function. In order for the kidneys to filter the blood properly and help maintain normal water balance they must receive plenty of blood. Prostaglandins play a role in dilating kidney blood vessels and thereby ensuring adequate blood flow to the kidneys. Less blood to the kidneys combined with high fluid loss during sweating could be a deadly combination.

For severe joint pain, intra-articular (right into the painful joint) corticosteroid injections will often be given. Corticosteroids are very effective anti-inflammatory agents, but the injections themselves are often painful and corticosteroids can also lead to joint damage. Corticosteroids, in high doses, leads to connective tissue degradation. You would expect that collagen breakdown would be increased. How many injections are needed before joint destruction can occur is unclear. The question remains, is short term pain relief worth the possibility of a joint that may forever be weakened?

It may be possible, even after use of steroidal and non-steroidal anti-inflammatory agents that appropriate nutrient intake (maybe supplemental) and exercise rehabilitation could return weakened, damaged joint connective tissue back to full strength.

Nutrient supplements

There are two general approaches to treating joint pain; blocking the inflammatory response or enhancing healthy connective tissue regeneration (i.e chondroprotective agents). Natural products may be used to treat joint pain because they act as; 1) macromolecule synthesis co-factors, i.e. micronutrients, 2) precursor compounds which actually become part of connective tissue macromolecules, or 3) natural anti-inflammatory agents. Although a number of botanical medicines have been well studied for their anti-inflammatory effects, this article will focus on nutrients which are considered chondroprotective agents in that they are thought to work by one of the first two mechanisms.

Numerous animal and human studies have reported beneficial results in the treatment of osteoarthritis using glucosamine sulfate.12-19 In a number of these studies the effectiveness of glucosamine sulfate supplementation has specifically been compared to NSAIDs in patients with osteoarthritis.14,15 In both studies, glucosamine sulfate was more effective than the drugs, but it required about six weeks of supplementation before it appeared to perform better than the NSAIDs.

It is theorized that glucosamine sulfate can be used as a building block for connective tissue GAGs. A Russian study found that the benefits of glucosamine sulfate were evident even one month after stopping supplementation.19 Several animal studies report that glucosamine sulfate does not block the production of inflammatory chemicals.13,20 Together these studies provide circumstantial evidence that glucosamine sulfate acts on joints by providing the precursor materials to make healthy connective tissue. The most compelling evidence for the connective tissue building actions of glucosamine sulfate arises from cartilage tissue biopsies from patients with osteoarthritis.12 One group of patients was treated with glucosamine sulfate while the other group was treated with placebo. Microscopically, the cartilage from patients treated with glucosamine sulfate had the appearance of healthy, not damaged cartilage.

Chondroitin sulfate (CS), a type of GAG, has been tested clinically and reported to be efficacious in the treatment of osteoarthritis. Chondroitin sulfate, a very large molecule compared to glucosamine sulfate, may not be absorbed after oral supplementation.21 Three clinical studies reported successful treatment of osteoarthritis using an intramuscular injectable form of CS.22-24 The actions which could explain the clinical benefits of CS include anti-inflammatory (via inhibiting complement action), inhibition of cartilage-destroying enzymes (elastase and hyaluronidase) and rebuilding of cartilage.25

Despite the fact that there are misgivings about the oral absorption of CS, at least one French clinical trial of oral CS has reported good therapeutic benefits in an osteoarthritis population.26 Also an Italian study reported increased blood levels after a single oral dose of 0.8g of chondroitin sulfate (from 0.0 to 1.0 mcg/ml).4 Oral CS may indeed be an effective supplement for improving joint health, but the discrepancy in absorption studies of oral CS combined with unclear information as to whether C-6-S or C-4-S should be supplemented, are two reasons to consider glucosamine sulfate supplementation before CS supplementation.27

The element sulfur is absolutely required for the synthesis of normal GAGs. This sulfur requirement would answer the question as to why glucosamine sulfate is an effective chondroprotective agent, while glucosamine HCl is not. SAM is a special form of the sulfur containing amino acid methionine called S-adenosylmethionine. SAM is used as a precursor for the production of sulfated products such as phospho-adenosyl-phosphosulfate (PAP). PAP is the molecule used by connective tissue cells for sulfation of GAGs.28 SAM can have anti-inflammatory activity similar to NSAIDs.29 In a number of clinical trials with osteoarthritis patients, SAM performed at least as well as NSAIDs, and often with fewer side effects.30,31 Most importantly, SAM may have connective tissue rebuilding effects, evidenced by the maintenance of benefits one month after stopping the supplement.32 SAM has also been found to stimulate production of GAGs which, as we have seen, are the building blocks of connective tissue.28

Although 500 milligrams (mg) of glucosamine sulfate three times per day (a total of 1500 mg daily) and 400 mg per day of SAM (S-adenosylmethionine) would appear to be excellent choices of nutrients which could rebuild damaged connective tissue, a comprehensive approach to joint health includes exercise and other nutrients. While glucosamine sulfate appears to be virtually non-toxic, SAM has reportedly caused stomach pain in a few individuals.20,33

Minerals shown to be important in producing strong connective tissue are copper, zinc, manganese, and boron.1,34 The best way to obtain a complement of these minerals is to add fresh nuts, seeds, and non-citrus fruits to the diet. For repair, such as with osteoarthritis or following joint injury, supplementation may be warranted (specific studies have not been conducted). Standard supplement doses would be daily: 1-2 mg of copper, 15-30 mg of zinc, 5-15 mg of manganese and 2-6 mg of boron. Vitamin C is particularly important for connective tissue integrity.35 Vegetables and fruits are the best sources of vitamin C, but if supplementing during a time of needed repair, one to two grams (1000 mg to 2000 mg) in divided doses should be sufficient. All of these nutrient supplements should be taken with food.

Exercise for healthy joints

Healthy connective tissue needs to be both strong and supple. Regular exercise is a key to achieving both. Resistance exercises (strength training) appear to be the best form of physical activity to stimulate new growth and correctly align the collagen fibers in newly forming connective tissue.36,37 This means that joints need to be moving against some resistance, either using weights or working against body weight as in push-ups. These exercises are best done slowly and when the joint is free of pain.

The approach to take for strengthening a joint which has been injured or is arthritic should begin with isometric exercises. These are resistance exercises whereby the muscles surrounding the affected joint is contracted, but there is no movement at the joint. I often refer to this type of exercise as "holding" exercise. Specifically, correctly executed (i.e. with proper biomechanics) yoga poses are an excellent form of isometric exercises. Since these types of resistances exercises do not require movement of a painful joint, they can be started as long as the joint is stable. Once joint movement becomes pain-free, adding in isotonic resistance exercises is important. Strengthening the joint (and all the connective tissue maintaining the joint) within its full range of motion is extremely important to return the joint to full functionality. I would venture to say that the reason an injured or arthritic joint is often vulnerable to future problems is because most individuals do not take the time to fully rehabilitate the joint's connective tissue.

By imposing "passive" (stretching) forces on newly forming collagen fibers (i.e. scar tissue), cross-linking and collagen fibril disorganization can be diminished.38,39 Flexibility or stretching exercises are tantamount to maintaining and rebuilding supple connective tissue.40 Stretching of the connective tissue around the affected joint should begin as soon as the joint is relatively pain and inflammation free. Stretching exercises should include the affected joint but also the unaffected paired joint and always be within the limits of pain. Further, stretches should be held for 30 seconds to 90 seconds, at least. Please see reference #40 for more details on how to properly undertake a stretching program.

Summary

Maintaining joint health is a matter of paying attention to diet and exercise (not very original!). In the diet a sufficient intake of minerals and vitamin C is ultimately important for synthesis of healthy connective tissue. Adding in two aspects of exercise which are less publicized (strengthening and stretching) than aerobic exercise, are the key to maintaining joint health, i.e. prevent future injury.

Information regarding the composition of joint connective tissue and metabolism of connective tissue macromolecules has laid the groundwork to understand what natural products could be helpful for joint repair. Glucosamine sulfate, SAM, vitamin C, copper, zinc, boron, and manganese are some of the important nutrients to consider supplementing when joint repair is required. Complete joint repair would also include specific strengthening and stretching exercises for the affected and paired joint.

It is important to remember that short term, infrequent use of NSAIDs are probably not problematic for the joint tissues. However, the only effect an individual is achieving with NSAIDs is anti-inflammatory. This means that treating affected joints with NSAIDs is simply symptomatic relief. Although the cause of joint pain appears to be chemicals involved in the inflammatory response, joint inflammation is a response to damaged connective tissue. Therefore the logical, comprehensive treatment for joint pain is to deal with the underlying cause of damaged connective tissue.

 

References

1. Tinker D, Rucker R. Role of selected nutrients in synthesis, accumulation , and chemical modification of connective tissue proteins. Physiol Rev 65(3):607-653, 1985.

2. Bates CJ, Levene CI. The effect of ascorbic acid deficiency on the glycosaminoglycans and glycoproteins in connective tissue. Bibl Nutr Dieta 13:131-143, 1969.

3. Comper WD, Laurent TC. Physiological function of connective tissue polysaccharides. Physiol Rev 58:255-315, 1987.

4. Conte A, Volpi N, Palmieri L, et al. Biochemical and pharmacokinetic aspects of oral treatment with chondroitin sulfate. Arzneim Forsch 45:918-25, 1995.

5. Hascall VC, Hascall GK. Proteoglycans. In: Cell Biology of Extracellular Matrix, edited by Hay ED. New York, Plenum, 1981, p. 39-63.

6. Ronningen H, Langeland N. Indomethacin treatment in osteoarthritis of the hip joint. Acta Orthop Scand 50:169-174, 1979.

7. Palmoski MJ, Brandt KD. Effects of some nonsteroidal antiinflammatory drugs on proteoglycan metabolism and organization in canine articular cartilage. Arthrit Rheum 23(9):1010-1019, 1980.

8. Brandt KD. Effects of nonsteroidal anti-inflammatory drugs on chondrocyte metabolism in Vitro and in Vivo. Am J Med 83(suppl 5A):30-34, 1987.

9. Sheild MJ. Anti-inflammatory drugs and their effects on cartilage synthesis and renal function. European J Rheumatol Inflam 13:7-16, 1993.

10. Brooks PM, Potter SR, Buchanan WW. NSAID and osteoarthritis-help or hindrance. J Rheumatol 9:3-5, 1982.

11. Newman NM, Ling RSM. Acetabular bone destruction related to non-steroidal anti-inflammatory drugs. Lancet ii:11-13, 1985.

12. Drovanti A, Biganamini AA, Rovati AL. Therapeutic activity of oral glucosamine sulfate in osteoarthrosis: a placebo-controlled double-blind investigation. Clin Ther 3(4):260-272, 1980.

13. Setnikar I, Pacini MA, Revel L. Antiarthritic effects of glucosamine sulfate studied in animal models. Arzheim-Forsch 41:542-545, 1991a.

14. Vaz AL. Double-blind clinical evaluation of the relative efficacy of ibuprofen and glucosamine sulphate in the management of osteoarthrosis of the knee in out-patients. Curr Med Res Opin 8:145-149, 1982.

15. Crolle G, D'Este E. Glucosamine sulphate for the management of arthrosis: a controlled clinical investigation. Curr Med Res Opin 7(2):104-109, 1980.

16. D'Ambrosio E, Casa B, Bompani R, et al. Glucosamine sulphate: a controlled clinical investigation in arthrosis. Pharmatherapeutica 2:504-508, 1981.

17. Pujalte JM, Llavore EP, Ylescupidez FR. Double-blind clinical evaluation of oral glucosamine sulphate in the basic treatment of osteoarthrosis. Curr Med Res Opin 7:110-114, 1980.

18. Tapadinhas MJ, River IC, Bignamini AA. Oral glucosamine sulphate in the management of arthrosis: report on a multi-centre open investigation in Portugal. Pharmatherapeutica 3:157-168, 1982.

19. Vajaradul Y. Double-blind clinical evlauation of intra-articular glucosamine in outpatients with gonarthrosis. Clin Ther 3:336-343, 1981.

20. Setnikar I, Cereda R, Pacini MA, Revel L. Antireactive properties of glucosamine sulfate. Arzneim-Forsch 41:542-545, 1991b.

21. Baici A, Horler D, Moser B, et al. Analysis of glycosaminoglycans in human serum after oral administration of chondroitin sulfate. Rheumatol Int 12:81-88, 1992.

22. Rovetta G. Galactosaminoglycan sulfate (Matrix) in therapy of tibiofibular osteoarthritis of the knee. Drugs Exptl Clin Res 17:53-57, 1991.

23. Prudden JF, Balassa LL. The biological activity of bovine cartilage preparations. Sem Arthrit Rheum 3:287-321, 1974.

24. Kerzberg EM, Roldan EJA, Castelli G, Huberman ED. Combination of glycosaminoglycans and acetylsalicylic acid in new osteoarthrosis. Scand J Rheumatol 16:377-80, 1987.

25. Pipitone VR. Chondroprotection with chondroitin sulfate. Drugs Exp Clin Res 17(1):3-7, 1991.

26. Mazieres B, Loyau G, Menkes CJ, et al. Chondroitin sulfate in the treatment of gonarthrosis and coxarthrosis. 5-month result of a multi-center double-blind controlled prospective study using placebo. Rev Rheum Mal Osteoartic 59(7-8):466-72, 1992.

27. Austin S. The confusion over chondroitin. Quarterly Rev Nat Med Summer 97:125-126.

28. Harmand MF, Vilamitjana J, Maloche E, et al. Effects of S-adenosylmethionine on human articular chondrocyte differentiation. Am J Med 83(suppl 5A):48-53, 1987.

29. Gualano M, Stramentinoli G, Rossoni G, Berti F. Antiinflammatory activity of S-adenosyl-L-methionine:interference with the eicosanoid system. Pharmacol Res Commun 15:683-688, 1983.

30. Vetter G. Double-blind comparative clinical trial with S-adenosylmethionine and indomethacin in the treatment of osteoarthritis. Am J Med 83(suppl 5A): 78-80, 1987.

31. Muller-Fassbender H. Double-blind clinical trial of S-adenosylmethionine versus ibuprofen in the treatment of osteoarthritis. Am J Med 83(suppl 5A):81-83, 1987.

32. 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 83(suppl 5A):72-53, 1987.

33. Marcolongo R, Biordano N, Colombo B, et al. Double-blind multicentre study of the activity of S-adenosyl-methionine in hip and knee osteoarthritis. Curr Ther Res 37(1): 82-94, 1985.

34. Benderdour M, Hess K, Gadet MD, Dousset B, et al. Effect of boric acid solution on cartilage metabolism. Biochem Biophys Res Comm 234:263-268, 1997.

35. Bonnevie P, Fog M, Philip J, Riis P. The influence of ascorbic acid deficiency on connective tissues. Dan Med Bulletin 16(3): 73-76, 1969.

36. Maffulli N, King JB. Effects of physical activity on some components of the skeletal system.Sports Med 13(6):393-407, 1992.

37. Stone MH. Implications for connective tissue and bone alterations resulting from resistance exercise training. Med Sci Sports Exerc 20(5):S162-S168, 1988.

38. Donatelli R, Owens-Burkhardt H. Effects of immobilization on the extensibility of perarticular connective tissue. J Ortho Sports Phys Ther 3(2):67-72, 1984.

39. Akeson WH, Amiel D, Mechanic G, et al. Collagen crosslinking alterations in joint contractures: Changes in reducible crosslinks in perarticular connective tissue collagen after nine weeks of immobilization. Conn Tissue Res 5(1):15-20, 1977.

40. MacIntosh A. Stretching: a therapeutic exercise. Townsend Lett Apr 97:32-34.

 


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