.:: Sustained-release Methylation Protocol ::. -- Version 1.0 -- This protocol uses sustained-release formulas of B12 and methylfolate to provide steady support for the methylation cycle and neurotransmitter production. It does not require taking dozens of pills or sucking on sublingual B12 lozenges all day. These supplements help my body produce more glutathione with less chance of over-stimulation, confusing "paradoxical" reactions or electrolyte imbalance problems. These supplements support my MAO A R297R +/+ (requires B2), MTRR A66G (requires a steady supply of B12 & some B2), and MTHFR (requires B2 and folate) mutations... as well as my basic nutritional needs. I am sharing my personal protocol to 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, slowly, in numerical order): Nature Made B-complex with C - 1 tablet / A.M. All in One Multi-vitamin (Holistic Health / Dr. 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 as tolerated) 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 Magnesium w/ methylfolate. 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 a metabolite of B2 called FAD to be present when the enzyme is synthesized. It normally takes 2-4 weeks of regular B2 supplementation (e.g. 5mg or more, 3x daily) 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, sudden awakening at night (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 - 13mg B3 - 60mg B5 - 23mg B6 - 13mg Folate - 226mcg B12 - 2.5mg Biotin - 38mcg 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 (*Note: some values were rounded to the nearest milligram) Rationale for the supplements: Nutrient levels can easily be titrated by splitting tablets or adding additional capsules - as low or high as you want! Lower dose B-vitamin support may prevent electrolyte imbalance and over-driving the methylation cycle. I want enough minerals (Zinc, manganese, etc.) to prevent insufficiency without going too high & triggering metal detox. Lower dose, time-release methylfolate reduces the likelihood of electrolyte (potassium) imbalances 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 provide full B12 coverage at least 6 to 8 hours, or more. I like Adenosylcobalmin/Methylcobalmin mix or the B12 Ice (AdCbl + MeCbl with Vitamin D3 and THC, 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 believe NT Factor helped me heal and tolerate methylation supplements better after a couple months. It was very stimulating at first, so I started with small amount and gradually increased to the recommended dose. Ignore what the product label says about a double "loading dose" if you are at all sensitive to supplements. 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 All in One Multivitamin (w/ methylation cofactors). 1 or 2 caps per day is more affordable than taking the full dose of 4 per day ($33/month). Additional Co-factors - as required: Riboflavin (B2), regular B6 or coenzymated B6 (sublingual P5P), Vitamin C, Vitamin D3, curcumin, Doctor's Best L-carnitine Fumarate, Extramel SOD extract, D-ribose, NADH, thyroid glandular, and additional Metafolin (methylfolate). Potassium: There is a lot of online discussion about low potassium on methylation protocols. In my opinion, low potassium (hypokalemia) is sometimes over-diagnosed by sick people on web forums... who assume any unusual symptom or reaction must be low potassium. I misdiagnosed other symptoms as "low potassium" and ended up taking too much potassium (when I didn't need any at all) and messed up my electrolyte balance and caused myself discomfort and setback. On the other hand, ignoring actual low potassium levels can be dangerous. It's tricky to figure out! Therefore, I believe that its better for me not to take supplements at doses that commonly disrupt electrolyte balance... unless I was under expert medical care and monitoring. I supplement magnesium & try to eat a higher potassium diet to support the increased cell division & growth that occurs with increased methylation. So far, I only seem to need extra potassium when I do strenuous exercise that makes me lose electrolytes through sweat. After serious exertion I may go for some potato chips, coconut water or Optimal Electrolyte drink. The lower doses of methylfolate (less than RDA of 400 - 800mcg) I'm using have not caused me any low potassium issues in my normal, day-to-day life.