Antioxidant Supplementation In The Treatment Of Rheumatoid Arthritis

James Meschino DC, MS, ROHP

Rheumatoid arthritis (RA) is a chronic condition that causes joint pain and loss of mobility. Approximately three percent of the population is affected, with women out numbering men by approximately three to one.  In more severe cases it can lead to eye inflammation, neurological problems, inflamed blood vessels, disorders of the lymph   system, and cardiac complications.  The current scientific thinking views rheumatoid arthritis as an autoimmune disease, whereby the body’s immune system attacks its own tissues as if it were a foreign invader.¹ The normal white blood cell count in synovial fluid is less than 100 per ml, on average.  In osteoarthritis, this figure rises to approximately 800 per ml, and is significantly higher than this in rheumatoid arthritis.  White blood cells are known to contribute to pain and inflammation via several mechanisms, one of which involves the conversion of arachidonic acid to inflammatory leukotrienes (LTB4).  This reaction is catalyzed by the 5-lipoxygenase enzyme within leukocytes. Evidence suggests that free radicals generated by white blood cells within the synovial fluid serve to increase the rate of synthesis of certain inflammatory mediators (e.g., LTB-4, PG-2, interleukin-1, tissue necrosis factor–alpha).²  As such, investigators have recently explored the use of antioxidant vitamins and minerals as a possible means to reduce the pain and inflammatory events associated with rheumatoid arthritis.

Several important clinical trials support the use of antioxidant vitamin and mineral supplementation at specific doses, as a complementary intervention to help manage this condition.  In many cases the need for anti-inflammatory drugs can be significantly reduced, and sometimes eliminated when antioxidant supplementation is co-administered.^3,4,5,6 As long term use of anti-inflammatory drugs is associated with many adverse and life threatening side effects, any safe and effective treatment that is shown to reduce reliance upon these medications should be considered in the management of these cases.⁴ Thus, health practitioners should be aware of the research status pertaining to the use of antioxidant vitamins and minerals in the global management of patients with rheumatoid arthritis.

Vitamin E
Along with other antioxidants, Vitamin E has been shown to modulate the activity of the cyclooxygenase and lipoxygenase enzymes.  Both of these enzymes are involved in the conversion of arachidonic acid to pro-inflammatory prostaglandins and leukotrienes, respectively.  Experimental evidence demonstrates that Vitamin E and other antioxidants reduce the synthesis of pro-inflammatory prostaglandins (e.g. PG-2) and leukotrienes (LTB-4).^3,4,5 One randomized, double blind clinical study tested Vitamin E supplementation against the anti-inflammatory drug, diclofenac sodium, in hospitalized rheumatoid arthritis patients.  Patients were either given 400 mg of natural Vitamin E, three times daily, or the standard anti-inflammatory dosage of diclofenac sodium.  After three weeks of treatment both groups showed the same significant degree of improvement with respect to joint stiffness, improved grip strength, and pain reduction.  Duration of morning stiffness was reduced in the Vitamin E group from 90 to 68 minutes versus 68 to 30 minutes in the diclofenac group.  Both the physicians and patients considered both interventions to be similarly effective, and indicated that the use of Vitamin E in these cases could help to reduce the incidence of serious side effects associated with the use of anti-inflammatory drugs.⁴

Other clinical studies using Vitamin E as a treatment for rheumatoid arthritis have shown more modest improvement, however, even these researchers concluded that Vitamin E’s small but significant pain-relieving effect justifies using this vitamin as a complement to standard anti-inflammatory treatment.⁵

Vitamin C
In regards to Vitamin C and rheumatoid arthritis, a few studies show that RA patients tend to have low blood levels and white blood cell levels of Vitamin C.  It is known that white blood cells use Vitamin C at a faster rate when fighting an infection and that Vitamin C modulates the activity of cyclooxygenase and lipoxygenase enzymes within white blood cells, in a similar manner as Vitamin E.  Animal studies show that Vitamin C reduces inflammation and swelling, and demonstrate greater pain tolerance in animals with arthritis.⁷

Selenium
The mineral selenium also participates as an antioxidant by activating the enzyme glutathione peroxidase. In this role, selenium serves as the prosthetic group, attaching to four different sites on the glutathione peroxidase enzyme, and thereby activating its antioxidant capabilities.  Patients with rheumatoid arthritis have been shown to have lower blood levels of selenium.^8,9 In an important double-blind clinical trial, patients given 200 micrograms of selenium daily for three months showed fewer tender and swollen joints, and less morning stiffness.  They also required lower doses of anti-inflammatory medication than patients in the control group.⁶

In conclusion, the administration of the antioxidant vitamins, Vitamin E and Vitamin C, as well as the mineral selenium, to patients suffering from rheumatoid arthritis represents a scientifically sound complementary intervention that has been shown to enhance the reduction of joint pain, swelling and tenderness in clinical and experimental studies.  Some of the biological mechanisms through which these antioxidants act to reduce the synthesis of inflammatory mediators within the joint synovial tissues have been documented.  It is important to note that the doses of these micronutrients associated with reduction of RA signs and symptoms, are at levels well beyond what an individual can derive from food alone.  Thus, supplementation of these nutrients is required to achieve the desired results in RA cases.  As a precautionary note, Vitamin E intake above 400 IU per day may potentiate the effects of anticoagulant drugs (coumadin, warfarin, Plavix, aspirin), and possibly lead to a bleeding disorder.  Therefore, patients on these medications should not exceed a daily intake of 400 IU per day of Vitamin E from supplement sources.¹⁰ Aside from this potential adverse side effect, there are few other instances where antioxidant supplementation (at the above noted dosages) is of concern or contraindicated.

References:

1. Murray M, Pizzorno J. Encyclopedia of Natural Medicine (2^nd edition) 1998;Prima Publishing:770-1
2. Borenstein O. Osteoarthritis clinical update. American College of Rheumatology 1999;Annual Scientific Meeting, Medscape 1999
3. McAdam P. Chicken cartilage assessed in rheumatoid arthritis. Medical Tribune, Nov1993:p8
4. Wittenborg A, et al. Effectiveness of vitamin E in comparison with diclofenac sodium in treatment of patients with chronic polyarthritis. Z Rheumatol, Aug1998;57(4):215-21
5. Edmonds SE, et al. Putative analgesic activity of repeated oral doses of vitamin E in the treatment of rheumatoid arthritis. Results of a prospective placebo controlled double blind trial. Ann Rheum Dis, Nov1997;56(11):649-55
6. Heinle AK. Selenium concentration in erythrocytes of patients with RA. Clinical and laboratory chemistry infection markers during administration of selenium. Med-Klin 1997;92(suppl 3):29-31
7. Situnayake RD. Chain breaking antioxidant status in rheumatoid arthritis: clinical and laboratory correlates. Ann Rheum Dis, Feb1991;50(2):81-6
8. Kose K, et al. Plasma selenium levels in rheumatoid arthritis. Biol Trace Elem Res, 1996;53(1-3):51-6
9. Tarp U, et al. Low selenium level in severe rheumatoid arthritis. Scand J Rheumatol, 1985;14(2):97-101.
10. Corrigan JJ Jr., et al. Effect of vitamin E on prothrombin levels in warfarin-induced vitamin K deficiency. Am J Clin Nutr, Sep1981;34(9):1701-5