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Methylation cycle hypothesis
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===Freddd's Protocol=== Freddd is a member of the online ME/CFS community [[Phoenix Rising]]. He developed his own version of the [[Methylation cycle|methylation]] protocol working with Dr Rich Van Konynenberg, and began posting articles descriptions of his experiences in 2011. In Freddd's protocol, supplements are started at very low doses and titrated, or increased until no effect is noted. The recommendations end with supplements at suprapharmacological levels. #Stop taking any supplements that contain hydroxycobalamin, cyanocobalamin, folic acid, glutathione, and [[glutathione#precursors|glutathione precursors]] (e.g. [[N-acetylcysteine|NAC]], [[glutamine]], and undenatured [[Whey products|whey]]). #Supplement with basic cofactors for a week. :Basic cofactors consist of: #*[[Vitamin A|Vitamins A]] and [[Vitamin D]] (11,000 IU and 3000 β 5000 IU respectively) #*[[Vitamin C]] at 4000+ mg per day #*[[Vitamin E]] #*[[B vitamin#vitamin B complex|B vitamin complex]] with [[Pyridoxal-5'-phosphate|P5P]], [[biotin]] and [[Pantothenic Acid|pantethine]] (without including cyano [[B12]] or [[Folate|folic acid]]) #*A 1:1 [[magnesium]]:[[calcium]] supplement #*[[Zinc]], 50 mg per day #*[[Omega 3 fatty acid]]s, 2-6 caps per day #*Optional Basic Cofactors include: #**[[Glycophospholipid]]s #**Additional [[Pantothenic Acid|pantethine]] #**[[Multimineral]] supplements ([[choline]], [[selenium]]) #**[[Alpha lipoic acid]] #**[[D-Ribose]] #**[[Coenzyme Q10|CoQ-10]] #Titrate B12s while adjusting methylfolate and [[potassium]] #*[[Methylcobalamin]] (MeB12) should start at 15-20 mg per day #*[[Cobalamin|Adenosylcobalamin]] (AdoB12) should start at 10 mg per ''week'' #Titrate [[methylfolate]] to sufficiency, starting at 1 mg #*Continue adjusting [[potassium]] as needed #*If unable to relieve symptoms of folate or potassium deficiency, lower vitamin B1, [[Vitamin B2|B2]] and [[Niacin|B3]] intake as needed. #*After a week on MeB12, replace MeB12 with AdoB12 for one day. #Titrate [[L-carnitine#fumarate|L-carnitine fumarate]] (LCF) to effectiveness, starting at 125 mg per day and aiming for 500-1000 mg per day, stopping when an increase of 250 mg makes no difference. #Titrate [[SAM-e]], starting with 100 mg and increasing to 200-600 mg per day. #Titrate [[Trimethylglycine|TMG]], starting with 250 mg or less. If it does nothing, discontinue. #Titrate [[biotin]] #CNS Penetration Test β the penetration test is to determine whether the B12s are entering the cerebrospinal fluid. #*[[MeB12]] β use 2 tablets, adding one each half hour to total. #*[[AdoB12]] β wait a few days after previous test; then, try 50 mg AdoB12 (2 tablets), adding one each half hour to total.
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