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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1997 Nov;56(11):649–655. doi: 10.1136/ard.56.11.649

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

S Edmonds 1, P Winyard 1, R Guo 1, B Kidd 1, P Merry 1, A Langrish-Smith 1, C Hansen 1, S Ramm 1, D Blake 1
PMCID: PMC1752293  PMID: 9462166

Abstract

OBJECTIVE—Vitamin E, the most potent naturally occurring lipid soluble antioxidant has been suggested to possess both anti-inflammatory and analgesic activity in humans. This double blind and randomised study used a broad spectrum of clinical and laboratory parameters to investigate whether there was any additional anti-inflammatory or analgesic effects, or both, of orally administered α-tocopherol in rheumatoid arthritis patients who were already receiving anti-rheumatic drugs.
METHODS—Forty two patients were enrolled and treated with α-tocopherol (n=20) at a dose of 600 mg twice a day (2 × 2 capsules) or with placebo (n=22) for 12 weeks. The following parameters were measured: (1) Three clinical indices of inflammation—the Ritchie articular index, the duration of morning stiffness, and the number of swollen joints; (2) three measures of pain—pain in the morning, pain in the evening, and pain after chosen activity; (3) haematological and biochemical measures of inflammatory activity; (4) assays for the oxidative modification of proteins and lipids.
RESULTS—All laboratory measures of inflammatory activity and oxidative modification were unchanged. Furthermore, the clinical indices of inflammation were not influenced by the treatment. However, the pain parameters were significantly decreased after vitamin E treatment when compared with placebo.
CONCLUSION—The results provide preliminary evidence that vitamin E may exert a small but significant analgesic activity independent of a peripheral anti-inflammatory effect, but which complements standard anti-inflammatory treatment.



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Figure 1  .

Figure 1  

Consort flow diagram. *Inclusion criteria violated by three patients in placebo arm.

Figure 2  .

Figure 2  

Mean change in the visual analogue scale (VAS) for (A) pain in the morning and (B) pain after chosen activity (intention to treat population).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnett F. C., Edworthy S. M., Bloch D. A., McShane D. J., Fries J. F., Cooper N. S., Healey L. A., Kaplan S. R., Liang M. H., Luthra H. S. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. doi: 10.1002/art.1780310302. [DOI] [PubMed] [Google Scholar]
  2. Blankenhorn G. Klinische Wirksamkeit von Spondyvit (Vitamin E) bei aktivierten Arthrosen. Eine multicentrische placebokontrollierte Doppelblindstudie. Z Orthop Ihre Grenzgeb. 1986 May-Jun;124(3):340–343. doi: 10.1055/s-2008-1044572. [DOI] [PubMed] [Google Scholar]
  3. Burton G. W., Ingold K. U. Vitamin E as an in vitro and in vivo antioxidant. Ann N Y Acad Sci. 1989;570:7–22. doi: 10.1111/j.1749-6632.1989.tb14904.x. [DOI] [PubMed] [Google Scholar]
  4. Burton G. W., Joyce A., Ingold K. U. First proof that vitamin E is major lipid-soluble, chain-breaking antioxidant in human blood plasma. Lancet. 1982 Aug 7;2(8293):327–327. doi: 10.1016/s0140-6736(82)90293-8. [DOI] [PubMed] [Google Scholar]
  5. Carter B. D., Kaltschmidt C., Kaltschmidt B., Offenhäuser N., Böhm-Matthaei R., Baeuerle P. A., Barde Y. A. Selective activation of NF-kappa B by nerve growth factor through the neurotrophin receptor p75. Science. 1996 Apr 26;272(5261):542–545. doi: 10.1126/science.272.5261.542. [DOI] [PubMed] [Google Scholar]
  6. Coderre T. J. The role of excitatory amino acid receptors and intracellular messengers in persistent nociception after tissue injury in rats. Mol Neurobiol. 1993 Fall-Winter;7(3-4):229–246. doi: 10.1007/BF02769177. [DOI] [PubMed] [Google Scholar]
  7. Coderre T. J., Yashpal K. Intracellular messengers contributing to persistent nociception and hyperalgesia induced by L-glutamate and substance P in the rat formalin pain model. Eur J Neurosci. 1994 Aug 1;6(8):1328–1334. doi: 10.1111/j.1460-9568.1994.tb00323.x. [DOI] [PubMed] [Google Scholar]
  8. Douglas C. E., Chan A. C., Choy P. C. Vitamin E inhibits platelet phospholipase A2. Biochim Biophys Acta. 1986 May 21;876(3):639–645. doi: 10.1016/0005-2760(86)90053-6. [DOI] [PubMed] [Google Scholar]
  9. Fairburn K., Grootveld M., Ward R. J., Abiuka C., Kus M., Williams R. B., Winyard P. G., Blake D. R. Alpha-tocopherol, lipids and lipoproteins in knee-joint synovial fluid and serum from patients with inflammatory joint disease. Clin Sci (Lond) 1992 Dec;83(6):657–664. doi: 10.1042/cs0830657. [DOI] [PubMed] [Google Scholar]
  10. Hattori S., Hattori Y., Banba N., Kasai K., Shimoda S. Pentamethyl-hydroxychromane, vitamin E derivative, inhibits induction of nitric oxide synthase by bacterial lipopolysaccharide. Biochem Mol Biol Int. 1995 Jan;35(1):177–183. [PubMed] [Google Scholar]
  11. Ito Y., Ochiai J., Sasaki R., Suzuki S., Kusuhara Y., Morimitsu Y., Otani M., Aoki K. Serum concentrations of carotenoids, retinol, and alpha-tocopherol in healthy persons determined by high-performance liquid chromatography. Clin Chim Acta. 1990 Dec 24;194(2-3):131–144. doi: 10.1016/0009-8981(90)90128-f. [DOI] [PubMed] [Google Scholar]
  12. Jialal I., Fuller C. J., Huet B. A. The effect of alpha-tocopherol supplementation on LDL oxidation. A dose-response study. Arterioscler Thromb Vasc Biol. 1995 Feb;15(2):190–198. doi: 10.1161/01.atv.15.2.190. [DOI] [PubMed] [Google Scholar]
  13. Kidd B. L., Morris V. H., Urban L. Pathophysiology of joint pain. Ann Rheum Dis. 1996 May;55(5):276–283. doi: 10.1136/ard.55.5.276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kidd B. L. Problems with pain--is the messenger to blame? Ann Rheum Dis. 1996 May;55(5):275–275. doi: 10.1136/ard.55.5.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Levine R. L., Garland D., Oliver C. N., Amici A., Climent I., Lenz A. G., Ahn B. W., Shaltiel S., Stadtman E. R. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol. 1990;186:464–478. doi: 10.1016/0076-6879(90)86141-h. [DOI] [PubMed] [Google Scholar]
  16. Machtey I., Ouaknine L. Tocopherol in Osteoarthritis: a controlled pilot study. J Am Geriatr Soc. 1978 Jul;26(7):328–330. doi: 10.1111/j.1532-5415.1978.tb01345.x. [DOI] [PubMed] [Google Scholar]
  17. Mapp P. I., Kidd B. L., Gibson S. J., Terry J. M., Revell P. A., Ibrahim N. B., Blake D. R., Polak J. M. Substance P-, calcitonin gene-related peptide- and C-flanking peptide of neuropeptide Y-immunoreactive fibres are present in normal synovium but depleted in patients with rheumatoid arthritis. Neuroscience. 1990;37(1):143–153. doi: 10.1016/0306-4522(90)90199-e. [DOI] [PubMed] [Google Scholar]
  18. Mapp P. I., Walsh D. A., Garrett N. E., Kidd B. L., Cruwys S. C., Polak J. M., Blake D. R. Effect of three animal models of inflammation on nerve fibres in the synovium. Ann Rheum Dis. 1994 Apr;53(4):240–246. doi: 10.1136/ard.53.4.240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Moore P. K., Oluyomi A. O., Babbedge R. C., Wallace P., Hart S. L. L-NG-nitro arginine methyl ester exhibits antinociceptive activity in the mouse. Br J Pharmacol. 1991 Jan;102(1):198–202. doi: 10.1111/j.1476-5381.1991.tb12153.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Morris R., Southam E., Gittins S. R., de Vente J., Garthwaite J. The NO-cGMP pathway in neonatal rat dorsal horn. Eur J Neurosci. 1994 May 1;6(5):876–879. doi: 10.1111/j.1460-9568.1994.tb00998.x. [DOI] [PubMed] [Google Scholar]
  21. Niedbala B., Sánchez A., Feria M. Nitric oxide mediates neuropathic pain behavior in peripherally denervated rats. Neurosci Lett. 1995 Mar 16;188(1):57–60. doi: 10.1016/0304-3940(95)11394-c. [DOI] [PubMed] [Google Scholar]
  22. Reddanna P., Rao M. K., Reddy C. C. Inhibition of 5-lipoxygenase by vitamin E. FEBS Lett. 1985 Nov 25;193(1):39–43. doi: 10.1016/0014-5793(85)80075-2. [DOI] [PubMed] [Google Scholar]
  23. Scherak O., Kolarz G., Schödl C., Blankenhorn G. Hochdosierte Vitamin-E-Therapie bei Patienten mit aktivierter Arthrose. Z Rheumatol. 1990 Nov-Dec;49(6):369–373. [PubMed] [Google Scholar]
  24. Snyder S. H. Nitric oxide: first in a new class of neurotransmitters. Science. 1992 Jul 24;257(5069):494–496. doi: 10.1126/science.1353273. [DOI] [PubMed] [Google Scholar]
  25. Tasinato A., Boscoboinik D., Bartoli G. M., Maroni P., Azzi A. d-alpha-tocopherol inhibition of vascular smooth muscle cell proliferation occurs at physiological concentrations, correlates with protein kinase C inhibition, and is independent of its antioxidant properties. Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12190–12194. doi: 10.1073/pnas.92.26.12190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Zhen L. X., Ishii K., Taketa K., Ogata M. Inhibitory effect of alpha-tocopherol on methemoglobin formation by nitric oxide in normal and acatalasemic mouse hemolysates. Physiol Chem Phys Med NMR. 1993;25(4):253–260. [PubMed] [Google Scholar]
  27. de Groot H., Hegi U., Sies H. Loss of alpha-tocopherol upon exposure to nitric oxide or the sydnonimine SIN-1. FEBS Lett. 1993 Jan 4;315(2):139–142. doi: 10.1016/0014-5793(93)81150-x. [DOI] [PubMed] [Google Scholar]

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