Version 1.0 -- This protocol uses sustained-release formulas of B12 and methylfolate to provide steady support for the methylation cycle -- without having to pop pills and suck sublinguals all day. It helps my body produce more glutathione without causing over-stimulation or electrolyte imbalance symptoms. These supplements support my MAO A R297R +/+ (requires B2), MTR A66G (requires a steady supply of B12 & some B2), and MTHFR mutations... as well as my basic nutritional needs. I am sharing my protocol only to help inspire you to find supplements that work for your own unique SNPs and sensitivities. Working with a qualified, nutritionally informed practitioner is strongly recommended. The following is for informational purposes only, it is not medical advice. The Supplements (which I added on in numerical order): Nature Made B-complex with C - 1 tablet / A.M. All in One Multi-vitamin/Mineral (Holistic Health / Yasko) - 1 capsule per day, or more Pic-Mins Multimineral (Thorne) - 1 capsule / P.M. NT Factor EnergyLipids powder - 1 scoop A.M. / 1 scoop P.M. (start with 1/4 scoop and increase gradually) B12 Oils transdermal B12 spray sustained-release - 1 to 2 squirts per day Jigsaw Magnesium with sustained-release methylfolate & P5P - 2 tablets A.M, 2 tablets P.M. or more Support for my MAO A R297R +/+ mutation: In addition to the Nature Made B-complex (with 10.2mg of B2) listed above, I took 1/4 of a Solgar B2 50mg tablet (12.5mg) before lunch and 1/4 tablet before dinner for about one month before starting the B12 Oil and Jigsaw methylfolate. And I continue to take B2. Here's why: The most common reason for people to respond poorly to methylfolate is vitamin B2 deficiency. Lack of B2 in combination with MAO +/+ means that your ability to turn off your neuronal stimulus is greatly reduced, thus leading to 'apparent' over-stimulation of nerves MAO requires FAD (derived from vitamin B2) to be present when the enzyme is synthesized. It normally takes 2-4 weeks of high dose B2 (e.g. 3x daily) supplementation to normalize activity of MAO. This is provided that you have normal thyroid function. Be aware that starting up methylation when MAO A is still not functioning well can cause reactions that are quite similar to the side effects of MAO inhibitor drugs, and that are also confusingly similar to the symptoms of low potassium and/ or B12 deficiency. I experienced dry mouth, insomnia, muscle jerking, tingling in arms and legs. I found these symptoms resolved with continued B2 supplementation. Nutrient Dosages for the basic package -- 1 All in One + 1 B-Complex + 1 PIC-MINS + 4 Jigsaw magnesium tabs + 1 B12 Oils spray: B1 - 15mg B2 - 13.3mg B3 - 59.5mg B5 - 22.5mg B6 - 13.1mg Folate - 226.4mcg B12 - 2.506mg Biotin - 37.5mcg A - 1250 I.U. C - 370mg D - 100 I.U. K - 10mcg Zinc - 18.75mg Copper - 0mg Selenium - 125mcg Maganese - 2.75mg Chromium - 125mcg Magnesium - 500mg Rationale for the supplements: Low dose B-vitamin support may prevent electrolyte imbalance and over-driving the methylation cycle. Aims to provide enough enough minerals (Zinc, manganese, etc.) without triggering metal detox. Nutrient levels can easily be titrated by splitting tablets or adding additional capsules. Lower dose, time-release methylfolate reduces the likelihood of low potassium problems and overcomes the short serum half-life of standard methylfolate - which caused me to experience mood swings & extremely confusing "paradoxical reactions." The Jigsaw Magnesium seems to provide a steady trickle of methylfolate that lasts for about 8 hours, keeping the folate cycle steadily humming along. Sustained-release transdermal B12 Oils are highly preferred due to the low absorption & very short (1 to 2 hour) effect of B12 sublinguals and the corrosive effects of sugar and acids on tooth enamel. The spray seems to last for at least 6 to 8 hours, or more. I like Adenosylcobalmin/Methylcobalmin mix or the B12 Ice (AdCbl + MeCbl with Vitamin D3 and a curcumin derivative). Lipid replacement therapy (NT Factor EnergyLipids) is used to help repair cellular membranes from the oxidative stress that very often occurs with CFS/ME. I use some "proprietary supplements" that are only available from one source or are more expensive than common brands or generics - Jigsaw Magnesium w/ Methylfolate, All in One Multivitamin/Mineral, NT Factor EnergyLipids, and B12 Oils - but I believe that the quality and delivery technology of these products justify the cost. I use some low cost supplements like Nature Made B-complex and Pic-Mins to boost the overall dose of vitamins and minerals in order to reduce the number of capsules of the (not cheap but excellent) All in One Multivitamin. 1 or 2 caps per day is more affordable than taking the full dose of 4 per day ($33/month). Additional Co-factors - optional / if needed:Riboflavin (B2), Vitamin C, Vitamin D3, curcumin, liposomal glutathione, Extramel SOD extract, D-ribose, Coenzymated B6(sublingual P5P) or regular B6, NADH, thyroid glandular, and additional Metafolin (methylfolate). Potassium: There is a lot of online discussion about low potassium on methylation protocols. I supplement magnesium & try to eat a higher potassium diet to support the increased cell division & nutrient requirements that occurs with increased methylation. So far, I only seem to need extra potassiumwhen I do strenuous exercise that makes me lose electrolytes through sweat & leaves my muscles sore. After serious exertion I may go for some potato chips, coconut water or Optimal Electrolyte drink. The lower doses of methylfolate I'm using seems don't seem to cause symptoms of low potassium in my normal day-to-day activities. Your mileage may vary.