Methotrexate (MTX) and Caffeine

 

Recently I had written a blog post on Methotrexate (MTX) and Caffeine in German [1]. This is an offspring and not merely a translation of this article.

Klaus Krüger, a German Professor of Rheumatology based in Munich, told in an interview for BDI aktuell [a publication of the BDI, which stands for Berufsverband Deutscher Internisten - Professional Association of German Internists], that even though MTX is generally well tolerated, nausea is a common side effect. He mentioned coffee being able to alleviate this side effect.

As I've known Dr. Krüger for at least 15 years, I thought to look for the study not mentioned in BDI aktuell. He monitores, condenses and lectures on studies and won't give this kind of information without having read a study. And I've found a likely study by Dr. Anand Narayan Malaviya [2].

In his study, A.N. Malaviya examined the effect of caffeine on the symptoms of methotrexate intolerance in patients with rheumatoid arthritis. Caffeine (coffee / dark chocolate) relieved the symptoms of MTX intolerance in the majority of patients.

Let's look at some details of this study, which looked at 855 patients treated with methotrexate. 313 patiens did not have any MTX intolerance, leaving 542 patients with some degree of MTX intolerance. In 422 patients MTX intolerance did not require any intervention. 120 (14 % of the initial 855) patients had 'moderate' or 'severe' MTX intolerance. “Among these, 55 % had complete relief of symptoms and were able to continue taking the advised dose of MTX; 13.3 % had partial improvement and continued taking MTX but only with antiemetics; 7.5 % were minimally better but were somehow managing; 10 % were complete caffeine failure without any relief; 14.2 % did not like caffeine (coffee or dark chocolate) and did not want to take it.” Tea, not coffee is mostly drunk in the northern part of India.

I myself like coffee and dark chocolate, but I would have no hesitation in recommending tea drinkers to give it a try; however, precisely that was not tested. Dark chocolate and coffee contain slightly more caffeine when compared to tea. However, it is more important that the polyphenols in tea (e.g. epigallocatechin gallate) bind the caffeine and only release it in the intestine, which renders the kinetics different from those of coffee, for example. It may well be the case that the faster absorption of caffeine from coffee is more effective at preventing methotrexate nausea.

I've always been concerned about strategies to keep patients on MTX as it is very effective in itself or as a co-medication [3]. Give coffee a chance!


Links and annotations:
[1] https://rheumatologe.blogspot.com/2021/07/methotrexat-mtx-und-kaffee.html – more annotations and links to texts in German there
[2] Malaviya AN. Methotrexate intolerance in the treatment of rheumatoid arthritis (RA): effect of adding caffeine to the management regimen. Clin Rheumatol. 2017 Feb;36(2):279-285. doi: 10.1007/s10067-016-3398-3. Epub 2016 Sep 6. PMID: 27596742.  https://pubmed.ncbi.nlm.nih.gov/27596742/
[3] https://rheumatologe.blogspot.com/2015/05/methotrexate-and-hydrating.html

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