Nutraceutical Interventions in Arthritis
Ronald Ritchie, D.C.

    Specific nutrients that are useful for those patients with arthritis are the following. This is certainly not an exhaustive list as the constellation of nutraceutical substances that address the various aspects of arthritis is vast. All of these nutrients are not necessary for every patient so let’s try to specify which is most valuable for specific patients.


Glucosamine Sulfate
    Glucosamine is an amino sugar component of chitin, heparan sulphate, chondroitin sulphate and many complex glycosaminoglycans (mucopolysaccharides). Proteoglycans are large carbohydrate-rich molecules present in virtually all cartilage and many connective tissues. Glucosamine sulfate provides the basic building block for cartilage matrix¹. Proteoglycans are hydrophilic and provide resiliency, load distribution, shock absorption, and compressive resistance functions especially as it relates to joints. Loss of fluid content and degradation of type II collagen (the major collagen component of cartilage²) appears to be a key to the pathological process common in many forms of arthritis^3,4. Early investigations of glucosamine sulfate appeared to demonstrate the ability of the substance to actually rebuild and restore thickness to joint cartilage. More recent studies regarding disease modification⁵ demonstrate glucosamine sulfate’s ability to prevent cartilage thickness loss⁶. There also appears to be an anti-inflammatory effect⁷ of glucosamine but in clinical trials has not worked as well as NSAIDs. Individuals taking NSAIDs and glucosamine concurrently have found less benefit than with glucosamine alone. This is hypothesized to be a consequence of COX suppression and therefore decreased availability of all eicosanoids within cartilaginous tissues. Glucosamine sulfate appears to be absorbed intact with one study indicating greater than 88% absorption⁸. Glucosamine sulfate is the form which has been studied in many clinical and laboratory trials, and it is this form that has been repeatedly demonstrated as effective⁹; however, it is believed that glucosamine HCl should be equally as effective. There has been some recent debate regarding blood sugar problems when giving glucosamine sulfate to diabetics¹⁰. There is currently no definitive answer as to the effect of glucosamine on blood glucose, as it has not been a primary outcome variable of any of the glucosamine studies. It should be noted that studies have demonstrated that the sugar portion of glucosamine is not metabolized through “normal” pathways.

    With all of these concepts in mind, treatment of most types of arthritis with glucosamine sulfate is appropriate although the most effective use is in patients with osteoarthritis. Therapeutic dosage of 1500 mg daily in divided doses is appropriate.


Chondroitin Sulfate
    Chondroitin sulfate is a glycosaminoglycan that is a major component of the extracellular matrix and connective tissue of animals, found on the outside of the cell membranes of some animal cells. They are repeating polymers of glucuronic acid and sulphated Nacetyl- glucosamine residues that are highly hydrophilic and anionic. It was initially thought that chondroitin sulfate (because of its molecular size) would not be absorbed intact and therefore accounted for some of the failure in treatment. Recent studies have demonstrated chondroitin’s absorption and availability in the disaccharide form¹¹; however, it is not as well absorbed as glucosamine. Chondroitin sulfate has a similar anti-inflammatory effect to glucosamine⁹ although other studies demonstrate that it may act via a different mechanism^12,13. Many of the benefits attributed to glucosamine can also be related to chondroitin sulfate. Chondroitin appears to protect existing cartilage by decreasing water loss from the matrix and inhibiting the breakdown of cartilage by enzymatic reactions. Many recent studies have demonstrated combined glucosamine/chondroitin therapy seems to be more effective for certain individuals or types of arthritis^14,15. Although glucosamine is a precursor for chondroitin synthesis and logic would seem to indicate that administration of glucosamine would address all cartilage maintenance and repair issues, this process requires a significant amount of metabolic energy. In some individuals there are circumstances where this metabolic energy is limited or unavailable, therefore administration of chondroitin may spare this metabolic pathway and help protect cartilage better than glucosamine sulfate.

    In my practice I have found that individuals with a significant number of concurrent health conditions such as asthma, diabetes, digestive disorders, etc. will respond more favorably using a combined glucosamine/chondroitin formulation. I have also found that patients with rheumatoid arthritis have better results using chondroitin sulfate with MSM than glucosamine sulfate alone. Chondroitin sulfate should be given at 1500 mg daily in divided doses.


MSM (methylsulfonylmethane)
    MSM is a source of organic sulfur found naturally in the human body and in many foods. It is the major metabolite of DMSO (dimethyl sulfoxide), is 34% elemental sulfur, and is the primary component that appears to be of the greatest benefit to the body16. While sulfur supports many functions, it is well known for maintaining connective tissue health and therefore supports those tissues with significant amounts of collagen and keratin such as ligaments, tendons, arteries and cartilage. Type II collagen degradation by enzymatic action is a major component in the pathogenesis of arthritis. MSM provides additional elemental sulfur to aid the body in the repair process of these tissues. MSM may support the body in regulating insulin production, improving skin smoothness and elasticity, regulating environmental and allergic sensitivities, enhancing bowel function and liver detoxification, and enhancing respiratory function¹⁶. Some studies have demonstrated immunosupportive effects of MSM¹⁷. Lastly sulfur is a key element necessary in the detoxification processes which is highly valuable in many patients with arthritis. Given this information, MSM is very useful in the treatment of most types of arthritis but RA patients seem to respond the best. Dosages vary from 850 to 3000 mg daily. Some authorities advocate even higher amounts.


Bromelain
    Bromelain is a proteolytic enzyme complex derived from the stalk of the pineapple plant which demonstrates anti-edematous, anti-inflammatory, anti-thrombotic and fibrinolytic activities. Bromelain is absorbed intact through the GI mucosa with up to 40% being detected in the blood after consumption¹⁸. Bromelain’s therapeutic actions are only partially due to its enzymatic activity. It has several biologic effects including directly affecting bradykinin production¹⁹; selectively removing certain cell surface molecules that affect lymphocyte migration and activation^20,21; has immunomodulating properties²²; enhances T-cell responsiveness²³; stimulates increased phagocytosis, pathogen killing capacity and reactive oxygen species production²⁴; produces post-traumatic and post-surgical edema reduction²⁵; and was able to induce increased natural killer cell activity in immuno compromised individuals²⁶. Studies comparing bromelain’s anti-inflammatory effects against pharmaceuticals demonstrate greater levels of improvement and decreased dependency on analgesics²⁷ with bromelain. All of this recent elucidation of the mechanisms of action of bromelain only goes to strengthen the therapeutic value and necessity of use in inflammatory disorders such as arthritis but should also include digestive disorders²⁸, pulmonary disease, vascular disease, etc.

    The most effective dosage for bromelain is 5,000 m.c.u. (milk clotting units) - three times daily between meals. I have found that getting patients to take it twice daily is about the best they can do so I prescribe two twice daily. Bromelain must be taken on an empty stomach (two hours after or one hour before a meal) and be undenatured in order to have the desired effect for arthritis. Taken with meals bromelain is an excellent aid in protein digestion.


Omega-3 Fatty Acids
    Fish source omega-3 (n-3) fatty acids have long been known for their cytoprotective capacity. In the past 10 years over 4500 studies have been performed on these valuable fats. They are cardioprotective reducing mortality significantly, anti-arrhythmic, induce lower triglycerides, reduce joint tenderness in RA patients, are anti-inflammatory, anti-tumorogenic, and anti-thrombotic²⁹. Virtually all cell membrane phospholipids are composed of n-3 or n-6 fatty acids from which are derived the various components of the arachidonic acid cascade. Deficiency in either n-3 or n-6 fatty acids will cause imbalance in eicosanoid production³⁰. Studies have demonstrated the following functions of n-3 fatty acids. A decrease in arachidonic acid concentrations with decreased clotting times and increased fibrinolysis³¹; decrease in multiple inflammatory markers in many conditions^32,33; decrease in TNF and IL1 in chronic inflammatory diseases³⁴; down-regulation of inflammation by enhancing IL10 expression³⁵; reduced IL1 and LTB4 in many tissues³⁶; and is a potent inhibitor of leukocyte adhesion receptor expression and leukocyte-endothelium interactions³⁷. Omega-3 fatty acids exert effects outside of the eicosanoid synthesis pathways. The net effect of n-3 fatty acids is to reduce heart attack and disease risks²⁹, stabilize myocardial membranes³⁸, decrease cancer cell growth rates³⁹, have anti-depressant effects (several major medical trials under way presently), and improve chronic inflammatory disease⁴⁰. As it relates to arthritis, n-3 fatty acids will reduce inflammation and edema in joints as well as aid in the repair process of many of the damaged tissues. High doses are valuable especially in RA but also in OA during inflamed episodes.

    A word about fatty acids. Many studies have demonstrated the need for balance in the consumption of n-3 and n-6 fatty acids. A recent NIH survey states that the average American consumes n-6/n-3 fatty acids in a 47:1 ratio whereas the proper ratio for good cellular health is 7:1. Also the source of n-3 fatty acids should be natural fish. There are many recent endeavors to prove that n-3 from vegetable or grain sources are comparable to fish oil. Most plant sources of omega-3 fatty acids do not provide EPA and DHA, the two major omega-3 fatty acids found in fish sources. While fatty acids such as alpha- linolenic acid (ALA) certainly have health benefits, it is not clear that they are metabolized by the body in a fashion similar to EPA and DHA. We do not have data to show that the data on fish oil supplementation can be completely replicated by supplementing with plant sources of omega-3 fatty acids. Also be aware of the “trans” problem which are fats mutated into the trans configuration by high temperature processing and cooking. Be sure the n-3 you and your patients consume are from a reliable source. Therapeutically valuable dose range is 2000-6000 mg daily in divided doses for arthritis²⁹.


Hyaluronic Acid
    A relatively new player in the arthritis treatment market is hyaluronic acid. Since HA is a component of the cartilage matrix, it may be valuable in the treatment for arthritis. It has been demonstrated that inflammation within joints will cause fragmentation of HA and degradation of the cartilage matrix⁴¹. The vast majority of HA administration has been by intra-articular injection, implantation of surgical films and gels, and the like. Intra-articular injections of HA have proven effective in long-term studies⁴² and have been used for many years. Studies have demonstrated that HA administration in osteoarthritis will reduce inflammation and promote fibrinolysis⁴³. Glucosamine and chondroitin sulfate have both been demonstrated to increase HA production within joints with long term administration⁴⁴. Other therapeutic uses of HA have been performed for many years mainly directed towards ligament and tendon repair, and connective tissue support. The exact dosages orally to provide the best benefit is still unclear.


Type II Collagen
    Type II collagen is a major component of connective tissues and cartilage. Conditions that generate long term inflammatory processes such as RA seem to cause a biochemical change whereby these collagen fibers are replaced with less hydrophilic and flexible material. Studies have demonstrated that type II and V collagen are those most commonly affected in those with arthritis and may even be the focus of the auto-antigens of RA. Administration of purified type II undenatured collagen will act almost like an “allergy shot” to reduce inflammation in joints of RA patients by activating the GALT system⁴⁵. This response appears to be dose dependent giving greater imuno-responsiveness at slightly higher doses⁴⁶. There may be a double benefit by decreasing inflammation through immune modulation and providing raw materials for connective tissue repair and maintenance. The dose rate of 10 mg daily appears to have the greatest clinical evidence presently⁴⁷.


Herbs/Minerals
    Arnica applied topically in a homeopathic remedy form to the site of inflammation has proven very beneficial⁴⁸. The carotenoid astaxanthin demonstrates an anti-inflammatory effect possibly by COX modulation⁴⁹. There are a number of additional plant products (Curcumin, Boswellia, Quercetin, Devil’s claw, Lignum vitae, and feverfew to note a few) with anti-inflammatory and complimentary effects that would augment any therapeutic regemin. Lastly let's not forget our minerals. Virtually all patients with arthritis will require calcium in a form most suited to their body, usually matched to urine pH. Magnesium is also a major consideration and I have found that equal portions of calcium to magnesium have the best results. With any type of bone demineralization boron is always needed. Usually 3 mg daily is adequate for most physiologic demands. Other minerals may be needed based upon the unique requirements of each patient.

    As you can see there are many alternative nutraceutical therapies that are as valuable as medical therapies and in many ways superior since they work within the body’s functions to produce improvements “naturally” instead of chemically. Many of these substances work so well that the medical community is beginning to catch on.


References
1 Setnikar I; Rovati LC Absorption, distribution, metabolism and excretion of glucosamine sulfate. A review. Arzneimittelforschung 2001 Sep;51(9):699-725 ISSN: 0004-4172

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