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Supplementary material The Supplementary material for this article can be found online at: TNF- tumor necrosis factor- CGRP calcitonin gene related peptide COX-2 cyclooxygenase-2 iNOS inducible nitric oxide synthase ATP adenosine tri-phosphate ROS reactive oxygen species FMN flavin mononucleotide FAD flavin adenosinedinucleotide ASA acetylsalicylic acid MTHFR methylenetetrahydrofolate reductase HDR headache diary results DNA deoxyribonucleic acid DHF dihydrofolate THF tetrahydrofolic acid VPA valproic acid NO nitric oxide OHB12 Hydroxocobalamin CRPS complex regional pain syndrome ROS reactive oxygen species nVDR nuclear vitamin D receptor MR Mendelian randomization IL-6 interleukin 6 MIDAS migraine disability assessment PGs prostaglandins IL-1 interleukin 1 IFN-8 interferon 8 RBP Retinol-binding protein RBP4 retinol-binding protein-4 hs-CRP high-sensitivity C-reactive protein NHANES National Health and Nutrition Survey RCT randomized clinical trial FAs fatty acids PUFAs poly unsaturated fatty acids EPA eicosapentaenoic acid DHA docosahexaenoic acid IBD inflammatory bowel disease MS multiple sclerosis NOS nitric oxide LPS lipopolysaccharides -LA Alpha-lipoic acid RNS reactive nitrogen species MDA malondialdehyde CRP C-reactive protein DNA deoxyribonucleic acid 5-HT 5-hydroxytryptamine GI gastrointestinal CoQ10 Coenzyme Q10 AAC combination of acetaminophen, acetylsalicylic acid, and caffeine NF-B Nuclear factor-B NLRP3 NOD-Like Receptor Protein 3 BFP body fat percent HDL-c high density lipoprotein-cholesterol Glossary References 1

In addition, patients receiving placebo were noted to have worsening of their curvature

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After TMAO treatment, in tumor-associated macrophages, stimulatory markers like MHC-I, MHC-II, and CD86 are upregulated, while the anti-inflammatory marker Arg1 is downregulated (79)