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Methylation cycle hypothesis
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===Rich's protocol=== While Yasko pioneered the methylation protocol for autism, [[Rich Van Konynenburg]], trained as a physicist, was the first to apply the methylation protocol to CFS/ME and [[fibromyalgia]]. He wrote over a dozen papers that discussed the linkage between dysregulated methylation and fatiguing disorders, beginning in 2004.<ref name="Van_Konynenburg201103a">{{Cite web | last1 = Van Konynenburg | first1 = RA | authorlink1 = Rich Van Konynenburg | title = Glutathione and the Methylation Cycle| website = Phoenix Rising | date = Mar 6, 2011 | url = http://phoenixrising.me/treating-cfs-chronic-fatigue-syndrome-me/treating-chronic-fatigue-syndrome-mecfs-glutathione-and-the-methylation-cycle }}</ref><ref name="Van_Konynenburg201103b">{{Cite web | last1 = Van Konynenburg | first1 = RA | authorlink1 = Rich Van Konynenburg | title = Simplified Treatment Approach Based on the Glutathione Depletion- Methylation Cycle Block Pathogenesis Hypothesis for Chronic Fatigue Syndrome (CFS) | journal = Phoenix Rising| date = Mar 6, 2011| url = http://phoenixrising.me/treating-cfs-chronic-fatigue-syndrome-me/treating-chronic-fatigue-syndrome-mecfs-glutathione-and-the-methylation-cycle/simplified-treatment-approach-based-on-the-glutathione-depletion-methylation-cycle-block-pathogenesis-hypothesis-for-chronic-fatigue-syndrome-cfs-by-rich-van-konynenburg-ph-d}}</ref><ref name="Van_Konynenburg201203a">{{Cite web | last1 = Van Konynenburg | first1 = RA | authorlink1 = Rich Van Konynenburg| title = Glutathione Depletion-Methylation Cycle Block: A Hypothesis For the Pathogenesis of Chronic Fatigue Syndrome| journal = Phoenix Rising | date = Mar 4, 2012 | url = http://phoenixrising.me/research-2/glutathione-depletionmethylation-blockades-in-chronic-fatigue-syndrome/is-glutathione-depletion-an-important-part-of-the-pathogenesis-of-chronic-fatigue-syndrome-by-richard-van-konynenburg-independent-researcher }}</ref><ref name="Van_Konynenburg201203b">{{Cite web | last1 = Van Konynenburg | first1 = RA | authorlink1 = Rich Van Konynenburg | title = Glutathione Depletion Methyleation Cycle Block Hypothesis for the Pathogenesis of Chronic Fatigue Syndrome | journal = Phoenix Rising | date = Mar 4, 2012 | url = http://phoenixrising.me/research-2/glutathione-depletionmethylation-blockades-in-chronic-fatigue-syndrome/glutathione-depletion-methylation-cycle-block-a-hypothesis-for-the-pathogenesis-of-chronic-fatigue-syndrome-by-richard-a-van-konynenbury-ph-d }}</ref><ref name="Van_Konynenburg201204">{{Cite web | last1 = Van Konynenburg | first1 = RA | authorlink1 = Rich Van Konynenburg | title = Interpretation of the Methylation Pathways Panel (2011) | journal = Phoenix Rising | date = Apr 21, 2012 | url = http://phoenixrising.me/treating-cfs-chronic-fatigue-syndrome-me/treating-chronic-fatigue-syndrome-mecfs-glutathione-and-the-methylation-cycle/interpretation-of-results-of-the-methylation-pathways-panel-2011 }}</ref> Rich Van Konynenburg first postulated a depletion of [[glutathione]] was at the heart of many of the symptoms of CFS/ME, but quickly added information about methylation when he realized that the two were connected.<ref name="Van_Konynenburg201203b" /> By 2006, Konynenburg had developed and presented what is now known as Rich's Protocol; in 2011, he presented the final, simplified version of the protocol. #One-quarter tablet (200 micrograms) [[Actifolate]] #One-quarter tablet Intrinsic B12/folate (200 mcg of folate as folic acid, [[Methyltetrahydrofolate|5-methyl tetrahydrofolate]], and 5-formyl tetrahydrofolate (folinic acid or [[leucovorin]]), 125 mcg of vitamin B12 as [[cyanocobalamin]], 22.5 mg of [[calcium]], 17.25 mg of [[phosphorus]], and 5 mg of [[intrinsic factor]]). #Up to two tablets General Vitamin Neurological Health Formula from Holistic Health Consultants (a multivitamin, multimineral with some [[TMG]] and supplements that help support [[sulfur metabolism]]). #One softgel capsule phosphatidyl serine Complex for [[phospholipid]]s and [[essential fatty acid]]s #Activated B12 Guard (Perque) (2,000 mcg [[hydroxocobalamin]] with some [[mannitol, sucanat]], [[magnesium]] and [[cherry extract]]) Van Konynenburg emphasized the adage ''start low, and go slow'' with these supplements, due to the potential for detoxification symptoms. Methylation support formula and SAM-e were previously included in the protocol, but are now omitted.<ref name="Van_Konynenburg201103b" /> Additionally, Rich suggested avoiding choline or TMG supplementation, as it could ''push'' the [[BHMT]] pathway at the expense of the methionine pathway, and to avoid over-supplementing with different forms of folate that would compete for absorption. Finally, Rich stated that some ME/CFSers may benefit from the addition of glutathione or molybdenum. Van Konynenburg's protocol does not rely on information about patient's SNP data, but is a more ''one size fits all'' approach.
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