Hi, i was wondering one thing.... while i was reading heartfixer since i am MTHFR 1298 hetero (and normal MTHFR 677) i did not understand this: at first it says that who has normal 677 can produce methylfolate normally because 1298 compromise just the backward reaction from methyl to THF, but.. then it says that they treat the condition with methylfolate supplement... why????? if the problme lies in the trasformation from methylfolate to THF why treat the condition with metylfolate expecially if you are MTHFR 677 normal?????? here i copied the part of hearthfixer i'm referring to: @caledonia he MTHFR C677T defect effects the “forward reaction”, the conversion of THF in to 5-methyl folate. MTHFR A1298C has no adverse affect on 5-methyl folate production, but it does compromise the “backward” reaction, whereby 5-methyl folate is converted back in to THF, in the process generating one molecule of BH4. Individuals with abnormalities in CBS and BHMT will be low in BH4, as it is being used up detoxifying ammonia that these defects have generated, so their combination with MTHFR A1298C leads to a BH4 deficiency double whammy. DHPR is the enzyme that regenerates BH4 from BH2. It is poisoned by mercury, lead, and especially aluminum. These toxins are wide spread in our environment, and individuals with Methyl Cycle abnormalities have particular trouble dealing with them. The result is a progressive drain on BH4, a progressive impairment in neurotransmitter production, and conversion of arginine not in to nitric oxide but instead in to free radicals such as superoxide and peroxynitrite. We treat MTHFR A1298C with 5-methyl folate supplementation (aiming to push the reaction backwards) and, after your other Methyl Cycle challenges have been addressed, with nutritional doses of BH4. Metal detoxification will help here and with every other biochemical function in your body, and will be part of your overall program. We will also endeavor to decrease your need for BH4. If you are COMT (-/-), we can provide nutritional support to help maintain dopamine levels, such that you will need to use less BH4 to generate more. If you are MAO A (-/-), we can do the same thing with serotonin precursors such as high tryptophan foodstuffs. The basic philosophy is to stimulate the action of still open pathways to take the stress off your impaired pathways.