Question: Are there safety concerns in supplementing cyanocobalamin rather methylcobalamin in those with MTHFR polymorphisms? If you're concerned about methylation-related issues, you would want to be careful with methylcobalamin supplementation in a way that you would not need to be careful about hydroxocobalamin supplementation. If you don't have a specific methylation-related goal, then I think hydroxocobalamin is the default because that's the sort of like metabolically neutral B12 in that it's not predisposed to any particular system, and it's not going to affect any system in a specific way apart from just being nutritional B12. Then the second thing is “if you had MTHFR, is it dangerous to supplement with cyanocobalamin?” It doesn't matter. I don't think MTHFR has anything to do with methylcobalamin really.
If you don't have malabsorption of everything else, you should look at the specific causes of B12 malabsorption, which are pernicious anemia and gastritis, including subclinical gastritis driven by H. pylori in the stomach.
This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/09/06/ask-anything-nutrition-march-8-2019
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