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Colestipol (decrease cobalamin and folate absorption) Methotrexate (inhibits DHFR) Nitrous Oxide (inactivates MS) High Dose Niacin (depletes SAMe and limits pyridoxal kinase = active B6) Theophylline (limits pyridoxal kinase = active B6) Cyclosporin A (decreases renal function and increases Hcy) Metformin (decreases cobalamin absorption) Phenytoin (folate antagonist) Carbamazepine (folate antagonist) Oral Contraceptives (deplete folate) Antimalarials JPC-2056, Pyrimethamine, Proguanil (inhibits DHFR) Antibiotic Trimethoprim (inhibits DHFR) Ethanol Bactrim (inhibits DHFR) Sulfasalazine (inhibits DHFR) Triamterene (inhibits DHFR) Involving yourself with providers who are educated on MTHFR Take supplements that are methylation supportive L-5-MTHF Riboflavin (B2) Methylcobalamin or Hydroxocobalamin Zinc DHA Choline TMG (must be avoided in pregnancy) Magnesium Methyl- B6 NAC Vitamin E (natural forms only) Selenium Glutathione Vitamin C Vitamin D Potassium Probiotics Molybdenum Milk Thistle *****Avoid gluten as 20% of patients with MTHFR have gluten sensitivity and gluten is inflammatory

The additional GIP agonism is studied for potential synergistic metabolic effects

This educational protocol outlines a once-daily subcutaneous research approach and includes a practical dilution framework designed to support precise insulin syringe dosing in laboratory and educational settings

doi: 10.1016/j.cell.2020.09.058 180 HalimTYSteerCAMathLGoldMJMartinez-GonzalezIMcNagnyKMet al