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The spore-forming single strain Clostridium butyricum (CBM588) improved progression-free survival and yielded higher response rates when added to nivolumab/ipilimumab in a randomized phase I study of metastatic renal cell carcinoma, and showed a further clinical activity signal when combined with nivolumab plus cabozantinib as first-line therapy, supporting a plausible immunomodulatory contribution of microbiome tuning to ICI outcomes [267, 268]

Nutrients for Optimisation The most important nutrients for the optimisation of the methylation cycle are: Vitamin B12 (as hydroxo- or methylcobalamin) Methylfolate (as 5-MTHF, Quatrefolic) Vitamin B6 (as pyridoxal-5-phosphate) Magnesium Nutrients for Therapy The following substances are administered for genetic mutations: Methylfolate (as 5-MTHF, Quatrefolic) Bypasses the MTHFR mutations Methionine Bypasses problems with MTHFR SAM Bypasses problems with MTHFR and MAT 5-HTP Bypasses BH4 deficiency or TPH mutations Nutrient Combinations for Certain Symptoms The following nutrient combinations are possible for certain symptoms: Nutrients for MTHFR Mutation MTHFR mutation is by far the most common genetic mutation

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