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Acknowledgements not applicable Abbreviations 2,3dPF2 2,3-Dinor 11-Prostaglandin F2 Anti-H1 H1-antihistamine Anti-H2 H2-antihistamine CSU Chronic spontaneous urticaria CMCD Clonal mast cell disorder CBC Complete blood count ECNM-AIM European Competence Network on Mastocytosis-American Initiative on Mast Cell Diseases GI Gastro-intestinal HT Hereditary alpha-tryptasemia IA Idiopathic anaphylaxis LTE4 Leukotriene E4 LTRA Leukotriene receptor antagonist MC Mast cell MCA Mast cell activation MCAS Mast cell activation syndrome MMAS Monoclonal mast cell activation syndrome NICAS National Institute of Health Idiopathic Clonal Anaphylaxis Analysis Score NMH N-methylhistamine NSAID Nonsteroidal anti-inflammatory drug RCT Randomized controlled trial REMA Spanish Network on Mastocytosis SM Systemic mastocytosis Author contributions EL and MP co-performed the literature review and co-wrote the manuscript

The most stable syn structures found for [s 2 Urd+H] + , TI S2 and TJ S2 , lie 1718 kJ/mol higher in energy than TA S2 with TJ S2 displaying a S2HO5 hydrogen bond

Gruijs da Silva, L

These results suggest that NNMT may also contribute to the regulation of anaerobic energy metabolism