Risker och/eller fördelar med Melatonin till personer med autoimmuna sjukdomar

Fråga: Min fråga rör eventuella kopplingar, risker och/eller fördelar med melatonin till personer med autoimmuna sjukdomar. Mer specifikt rör min fråga oligoartrit. Jag har via egna sökningar hittat ett par artiklar rörande melatonin och RA, där utfallet verkar vara inkonklusivt om vilka risker och/eller fördelar som finns. Jag är därför framför allt intresserad av risker/nytta med melatoninpreparat vid oligoartrit och juvenal ideopatisk artrit.

Svar: Studies involving juvenile idiopathic arthritis and long-term use of melaton to evaluate its risk/benift are lacking (1).

After searching PubMed, we identified the following studies of potential interest:

One study (2) evaluated the level of early morning serum melatonin among patients with juvenile rheumatoid arthritis (JRA). Twenty-one patients with JRA (fifteen patients had polyarticular JRA, 3 had oligoarticular and 3 had systemic onset JRA) and twenty healthy age and sex matched controls were enrolled in the study. The study found that serum levels of melatonin were significantly increased in JRA patients as compared to healthy controls. A significant positive correlation could link serum melatonin levels to disease activity scores and erythrocyte sedimentation rate. The study concluded that the elevated melatonin levels and its close relation to disease activity rather than disease severity suggests that melatonin might play a promoting role in rheumatoid arthritis. Hence, inhibition of its synthesis and/or action by specific antagonists may be of therapeutic value.

The role of melatonin on rheumatoid arthritis (RA) is not clear (3, 4). Only one double blind-placebo controlled clinical trial from UK of melatonin treatment in RA has been undertaken (5). The patient groups included 38 allocated to receive placebo and 37 allocated to receive 10 mg melatonin at night in addition to ongoing medication. Melatonin plasma concentrations in patients receiving melatonin treatment were more than twofold greater than at baseline. There was an increase in the inflammatory indicators erythrocyte sedimentation rate and neopterin concentrations in melatonin-treated patients in the period between 3 and 6 months, suggesting a proinflammatory effect of melatonin. However, there were no significant effects on clinical symptoms or on the concentrations of proinflammatory cytokines such as IL-1ß, IL-6, and TNF-a in the serum of melatonin-treated patients.

Some authors have reported a positive correlation between elevated melatonin levels and disease activity scores, and an advance in the nocturnal melatonin peak in melatonin treated subjects compared to control ones (3, 4). In contrast, in one study, although morning melatonin serum levels were higher in RA patients than in healthy volunteers, melatonin and RA disease activity did not correlate (6), supporting the clinical trial results by Forrest CM et al (5). It is speculated that the higher levels of melatonin in RA patients might not be the cause of the symptoms but a consequence of the disease, because the RA is a stressor and the stress would stimulate the synthesis of melatonin to protect the further injury (3). On the other hand, other authors have reported significantly lower levels of morning serum melatonin or a wider plateau of serum melatonin than in healthy people (3, 5), consistent with the possibility that the loss of its antioxidant activity could contribute to the disease. (5).

Different studies using experimental animal models of arthritis have suggested harmful actions for both endogenous and exogenous melatonin (3, 4).

1. PubMed. US National Library of Medicine/National Institutes of Health sökning gjord 2019-02-07. http://www.ncbi.nlm.nih.gov/sites/entrez
2. Hanaa Mahmoud El-Awady, Amany Salah El-Dien El-Wakkad, Maysa Tawheed Saleh, Saadia Ibraheem Muhammad and Eiman Mahmoud Ghaniema, 2007. Serum Melatonin in Juvenile Rheumatoid Arthritis: Correlation with Disease Activity. Pakistan Journal of Biological Sciences, 10: 1471-1476.
3. J.R. Calvo and M.D. Maldonado. The role of melatonin in autoimmune and atopic diseases. AIMS Molecular Science, 3(2): 158-186. April 2016
4. Gu-Jiun Lin, Shing-Hwa Huang, Shyi-Jou Chen, Chih-Hung Wang, Deh-Ming Chang, and Huey-Kang Sytwu. Modulation by Melatonin of the Pathogenesis of Inflammatory Autoimmune Diseases. Int J Mol Sci. 2013 Jun; 14(6): 11742–11766.
5. Forrest CM, Mackay GM, Stoy N, Stone TW, Darlington LG. (2007) Inflammatory status and kynurenine metabolism in rheumatoid arthritis treated with melatonin. Br J Clin Pharmacol 64: 517–526.
6. Afkhamizadeh M, Sahebari M, Seyyed-Hoseini SR (2014) Morning melatonin serum values do not correlate with disease activity in rheumatoid arthritis: a cross-sectional study. Rheumatol Int 34: 1145–1151