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Methylation cycle hypothesis
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==Evidence== There is little direct evidence to support the popular methylation protocols. However, numerous patients have reported benefit while others have reported no benefit. Indirect evidence supporting a possible benefit of methylation cycle supplements include findings of increased [[homocysteine]] in the [[cerebrospinal fluid]] of CFS and [[fibromyalgia]] patients.<ref name="Regland1997">{{Cite journal | last1 = Regland | first1 = B | authorlink1 = B Regland | last2 = Andersson | first2 = M | authorlink2 = M Andersson | last3 = Abrahamsson | first3 = L | authorlink3 = L Abrahamsson | last4 = Bagby | first4 = J | authorlink4 = J Bagby | last5 =Dyrehag | first5 = LE | authorlink5 = LE Dyrehag | last6 = Gottfries | first6 = CG | authorlink6 = Carl-Gerhard Gottfries | title = Increased Concentrations of Homocysteine in the Cerebrospinal Fluid in Patients with Fibromyalgia and Chronic Fatigue Syndrome | journal = Scandinavian Journal of Rheumatology | volume = 26 | issue = 4 | pages = 301-307 | date = 1997 | pmid = 9310111 | doi = 10.3109/03009749709105320 | url = http://www.tandfonline.com/doi/abs/10.3109/03009749709105320#.Vlc19N-rTMU }}</ref> There is compelling evidence that some ME/CFS patients are low in [[methylation cycle]] metabolites, and there are some studies that provide direct evidence of methylation cycle dysregulation in ME/CFS. However, it is important to note that there are limited studies on either protocol’s effect on methylation, and no studies on Yasko’s utilization of SNP data to drive decision-making about supplements. There is a great deal of anecdotal evidence to support these therapies. However, the longer a therapy continues, the higher and higher the likelihood of improvement regardless of circumstance, especially in an illness with as much natural variability as ME/CFS. ===Evidence=== Evidence that CFS/ME patients are low in methylation cycle metabolites: ===B vitamin evidence=== {{Main article|B vitamin}} *In a small study of 58 chronic fatigue syndrome patients with a history of Epstein-Barr infection and [[B cell|B-cell]] immunodeficiency, 81% responded to folinic acid. <ref name="Lundell">{{Cite journal | last1 = Lundell | first1 = K | authorlink1 = Kathleen Lundell | last2 = Qazi | first2 = S | authorlink2 = Sanjive Qazi | last3 = Eddy | first3 = L | authorlink3 = Linda Eddy | last4 = Uckun | first4 = FM | authorlink4 = Fatih Uckun | title = Clinical activity of folinic acid in patients with chronic fatigue syndrome | journal = Arzneimittel-Forschung | volume = 56 | issue = 6 | pages = 399-404 | date = 2006 | pmid = 16889122 | doi = 10.1055/s-0031-1296741}}</ref> *Folate was found to be clinically low in approximately 50% of people with CFS in a study by Jacobson et al. 1993.<ref name="Jacobson">{{Cite journal | last1 = Jacobson | first1 = W | authorlink1 = W Jacobson | last2 = Saich | first2 = T | authorlink2 = T Saich | last3 = Borysiewicz | first3 = LK | authorlink3 = LK Borysiewicz | last4 = Behan | first4 = WMH | authorlink4 = Wilhelmina Behan | last5 =Behan | first5 = PO | authorlink5 = Peter Behan | last6 = Wreghitt | first6 = TG | authorlink6 = TG Wreghitt | title = Serum folate and chronic fatigue syndrome | journal = Neurology | volume = 43 | issue = 12 | pages = 2645 | date = Dec 1993 | pmid = 8255470 | doi = 10.1212/WNL.43.12.2645}}</ref> ===SAM-e evidence=== {{Main article|SAM-e}} ===Glutathione depletion=== {{Main article|Glutathione}}
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