Vztah metylace, CFS a lyme

Loni na podzim zemrel vyznamny vedec Rich van Konynenburg, ktery se dlouhodobe zabyval metylacnimi bloky jako pricinami CFS. Nez se tak stalo, zanechal CFS komunite velky odkaz ve forme mnoha svych uvah a praci. Tohle je jedna dle meho nazoru z klicovych. Kopiruju ji sem takhle, protoze tak ji mam ulozenou. Prosim nepiste mi, abych to prelozila, nemam na to kapacity, pokud nevladnnete aj, zkuste vlozit do prekladace. Myslim, ze tohle by melo byt povinne cteni pro vsechny, neb osvetluje zakladni vztah geneticke mutace-infekce a vysledku procesu, kterym se vytvari bludny kruh.

 

 

 

Richard A. Van Konynenburg, Ph.D.

9th International IACFS/ME Conference
Reno, Nevada
March 12-15, 2009

Etiology of CFS, and the Glutathione Depletion Methylation Cycle Block (GD-MCB) hypothesis for CFS

The etiology of CFS is not agreed upon. As noted above, the present author has proposed a hypothesis for CFS called the Glutathione DepletionMethylation Cycle Block hypothesis [6], which proposes that the etiology of CFS consists of genetic predisposition combined with the effects of some combination of a variety of stressors (physical, chemical, biological and/or psychological/emotional) that lead to the depletion of glutathione, which in turn causes a partial block in the methylation cycle. A updated review of the GD-MCB hypothesis follows:

An individual inherits a genomic predisposition (polymorphisms in several of certain genes) toward developing CFS. (This genomic factor is more important for the sporadic cases than for the cluster cases of CFS.)

The person then experiences some combination of a variety of possible stressors (physical, chemical, biological, and/or psychological/emotional) that place demands on glutathione. [As will be discussed later, this is the point at which Lyme disease can come into this pathogensis.]

Glutathione levels drop, producing oxidative stress, removing protection from cobalamin (vitamin B12) and allowing toxins to accumulate.

Toxins react with cobalamin, lowering the rate of formation of methylcobalamin.

Lack of sufficient methylcobalamin inhibits the activity of methionine synthase, placing a partial block in the methylation and folate cycles.

Sulfur metabolites drain excessively through the transsulfuration pathway to form cysteine.

Much of the cysteine is oxidized to cystine because of the state of high oxidative stress, and is therefore not available for the synthesis of glutathione. An alternative pathway initiated by cystathionine gamma lyase diverts the cystine into formation of hydrogen sulfide and thiosulfate, and the latter is excreted in the urine.

An interaction (vicious circle) is established between the partial block in the methylation cycle and the depletion of glutathione, and this is what causes the disorder to become chronic.

A wide range of symptoms results from these chronic abnormalities in the basic biochemistry of the cells.

The dysfunction of the detoxication system and the immune system that results from this vicious circle mechanism allows toxins and infections to accumulate over time, which increasingly produce effects of their own.

Treatment should be directed primarily at increasing the activity of methionine synthase. The resulting normalization of the methylation cycle, the folate metabolism and glutathione levels will restore function to the immune system and the detoxication system as well as to a wide range of other parts of the overall biochemistry.

It can be expected that die-off of pathogens and mobilization of stored toxins will initially produce some exacerbation of symptoms, but improvements will be experienced as the body burdens of toxins and active infections are decreased.

Included among the biological stressors that place demands on glutathione are infections, such as that produced by Borrelia burgdorferi. In other words, the possibility that Lyme disease could lead to CFS was part of the GD-MCB hypothesis as proposed. The biochemical mechanism of the proposed link between Lyme disease and CFS is elaborated in more detail below.

Hypothesis for a link between Lyme disease and CFS

The present author proposes that Lyme disease can lead to CFS in individuals who are genomically predisposed to developing glutathione depletion and a partial block in the methylation cycle under the influence of stressors. This occurs because the Borrelia burgdorferi bacterium depletes glutathione in its hosts. In such cases, Lyme disease and CFS exist together as comorbid conditions, so that CFS is a component of what has been called chronic Lyme disease. If the Lyme disease is successfully treated, the CFS continues to be present chronically unless specifically and effectively treated, because of the ongoing vicious circle interaction between glutathione depletion and the partial methylation cycle block. The resulting condition then constitutes what has been called post-Lyme disease syndrome, which falls into the category of the post-infective fatigue syndromes.

Evidence in support of this hypothesis

Sambri and Cevenini [10] found in culture experiments that Borrelia burgdorferi (Bb) requires that cysteine be supplied exogenously, and is not able to make use of either methionine or cystine as a cysteine source. They also found that cysteine diffuses passively into Bb, i.e. there is no active transporter protein. This requirement of Bb for exogenous cysteine is important, because it means that Bb must take cysteine from its host. Cysteine is the rate-limiting amino acid for the synthesis of glutathione in human cells, and if it becomes depleted, this synthesis will be inhibited [11].

It has been found that Bb uses cysteine in the synthesis of several of its essential proteins: outer surface protein A (OspA), outer surface protein B (OspB), coenzyme A, a hemolysin and others [10,12]. Bb does not use glutathione for its control of its redox potential, as do human cells. Instead, it uses reduced coenzyme A (CoASH) [13].

Pancewicz et al. have found that Bb does in fact lower the cysteine and glutathione levels in its human host, and also inhibits the activity of glutathione peroxidase [14]. Because glutathione peroxidase, with the help of glutathione, normally converts hydrogen peroxide to water, thus eliminating its contribution to oxidative stress, low glutathione and low activity of glutathione peroxidase will allow a rise in hydrogen peroxide concentration and a rise in oxidative stress [15].

Although Bb appears to be more resistant than other bacterial pathogens to reactive oxygen species, it does incorporate unsaturated fatty acids in its membranes, and these are vulnerable to oxidative attack [16]. It has been observed that elevation of hydrogen peroxide causes Bb to assume its cyst form [17], in which it is less vulnerable to environmental threats [18], including antibiotics [19]. Perhaps this self-actuated mechanism serves to promote the survival of Bb in its host.

It is known that the immune system is dysfunctional in CFS, and the GD-MCB hypothesis [6] suggests that this results from glutathione depletion and disruption of the folate metabolism. Glutathione is particularly important for the function of the T lymphocytes [20], and folate is needed in the synthesis of DNA and RNA, necessary for the proliferation of T cells [21]. Thus, the biochemical mechanism suggested in the GD-MCB hypothesis can be expected to have a deleterious effect on the cell-mediated (Th1) immune response, which is needed to counter intracellular pathogens. Bb has been found to be able to reside intracellularly [18], and it has been shown that Th1 types of responses are required for optimum eradication of Bb [22]. Therefore, this immune dysfunction may help Bb to continue to survive in the body of the host, which is relevant to chronic Lyme disease.

The major overlap in symptoms between CFS on the one hand, and both chronic Lyme disease and post-Lyme disease syndrome on the other, as described earlier, is also evidence that supports this hypothesis.
In this regard, a study was performed by Gaudino et al. [23] that compared a group of patients judged to have post-Lyme disease syndrome (though the authors acknowledged that the possibility of ongoing infections could not be ruled out) with a group who met the research case definition for CFS [1] but did not have histories suggestive of Lyme disease. The authors found that both groups experienced severe fatigue, myalgia, headaches, and perceived cognitive problems. Eighty-four percent of the post-Lyme patients also met the research case definition for CFS. They did not find significant differences between the two groups in terms of psychiatric illness.

Despite the overlap in symptoms, they did find that some symptoms distinguished the two groups. Fever, sore throat, tender lymph nodes and unrefreshing sleep were found to be significantly more common among the patients with CFS. They also found that post-Lyme patients showed more global cognitive impairment.

It should be noted that the CFS research case definition [1] described earlier, which was used for patient selection in this study, specifically lists sore throat, tender lymph nodes and unrefreshing sleep among eight symptoms, four of which must be present to diagnose CFS. The more recent Canadian diagnostic case definition for ME/CFS [2] specifies a broader definition for sleep dysfunction and combines sore throat and tender lymph nodes together under immune manifestations. The immune manifestations are then grouped together with two other categories of symptoms, and the definition requires only that at least one symptom from two of these three categories must be present. Since there are 21 symptoms listed in these three categories, it is likely that patients in a group selected using the Canadian criteria for CFS would be less likely to exhibit sore throat, tender lymph nodes and unrefreshing sleep than a group selected using the CFS research case definition. In view of this, the differences found in this study between these symptoms in post-Lyme disease syndrome and CFS do not appear to be very robust. In addition, while this study found little cognitive deficit in the CFS patients, an earlier study in CFS reported poor performance on reaction time and attention [24], in disagreement with this study. It therefore appears that CFS and post-Lyme disease syndrome are essentially indistinguishable on the basis of comparison of symptoms.

Implications for the debate concerning chronic Lyme disease vs. post-Lyme disease syndrome

In view of the hypothesized link between Lyme disease and CFS, it seems possible that either chronic Lyme disease or post-Lyme syndrome could be present in a given case that began with Lyme disease and progressed into CFS, depending on whether or not Borrelia burgdorferi had subsequently been eradicated. If Bb were still present, the condition would properly be called chronic Lyme disease. If Bb had been eradicated, the patient would still have CFS, which would persist because of the vicious circle mechanism described in the GD-MCB hypothesis. Therefore, the patient would have post-Lyme disease syndrome, which is a post-infective fatigue syndrome, a recognized category within CFS [25].

Testing this hypothesis

This hypothesis can readily be tested by means of the commercially available methylation pathways panel [26], which is increasingly being used in CFS and autism. This panel measures metabolites in the methylation cycle and the folate metabolism, as well as the reduced and oxidized forms of glutathione, and will reveal whether glutathione depletion and/or a partial block in the methylation cycle are present. This panel could be used on patients believed to have either chronic Lyme disease or post-Lyme disease syndrome, to find out whether this hypothesis is valid for these patients.

Implications for treatment

If this hypothesis is valid, it suggests that treatment of chronic Lyme disease or post-Lyme disease syndrome should include treatment to lift the partial methylation cycle block. Such treatment of patients with combined diagnoses of chronic fatigue syndrome and fibromyalgia has been subjected to a clinical research study, and the results are reported in another paper at this Conference [7].

Summary

A link has been hypothesized between Lyme disease and chronic fatigue syndrome (CFS). This link is based on the Glutathione DepletionMethylation Cycle Block (GD-MCB) hypothesis for CFS [6]. The GD-MCB hypothesis proposes that in a person who is genomically predisposed, stressors that place demands on glutathione can cause it to become depleted, and can lead to a partial block in the methylation cycle. The resulting vicious circle interaction maintains CFS as a chronic condition. The present paper suggests that Lyme disease is one of the stressors that can produce this vicious circle interaction in the body of a person who is genomically predisposed. It is suggested that this leads to chronic Lyme disease. If the Borrelia bacteria are subsequently eliminated by treatment, the patient then has post-Lyme disease syndrome. Post-Lyme disease syndrome is one of the post-infective fatigue syndromes, a category of disorders within chronic fatigue syndrome [25]. A commercial test panel is available to test this hypothesis [26], and treatment to lift the methylation cycle block and to restore glutathione is available [7] if these are found to be present.

Já tomu moc nerozumím, přitom

Já tomu moc nerozumím, přitom by to mohlo být užitečný. Znamená to, když jakožto CFS borelkář se nebudu léčit a zdlábnu Gluthathion a zlepším se, tak mám post-lyme-syndrom, když se nezlepším, tak je ve mě mrcha furt? Ve skrytu duše furt věřím v to, že aktivitu infekce (pokud nemám autoimunitu apod.) mi ukáže LTT. Myslím si, že léčit borelku je jako věštit z křišťálové koule. Vykolejí v těle kde co, i trvale a zlikviduje imunitu tak, že je třeba najednou řešit daleko víc infekcí. Pak už občas člověk neví, co je tahle mrcha a co už je jiná mrcha.

Člověk, který vzal hlavu do svých rukou a nestrká ji do cizích.

No spis je to tak, ze coby

No spis je to tak, ze coby CFSar trpim urcitou genetickou mutaci, v dusledku cehoz jsem o mnoho nachylnejsi k naruseni metylacniho cyklu (napriklad moje telo neumi neco zpracovat), takze k tomu naruseni staci mnohem mene, nez u jedince, ktery tuto mutaci nema. Jakmile se na scene objevi nejaky stresor, v tomto pripade borelka, ale muze to byt samozrejme i jina infekce, metylacni cyklus se narusi zpusobem, ktery je popsany v clanku, dochazi k metylacnim blokum, vysledkem cehoz je CFS. Abych se tohoto stavu zbavila, musim za a) lecit patogena, ale v techto pripadech jen lecit patogena nestaci, musim za b) i lecit a odblokovat metylacni cyklus. Neudelam-li to druhe,dochazi k tomu, ze rada lidi se leci dlouho a dostatecne atb, ale presto zustavaji nemocni, ne protoze by v nich stale zurila infekce, ale protoze neresi narusenou metylaci. To je to, co v clanku nazyvaji postinfekcnim syndromem. Borelka je v techto pripadech jenom spoustecem nemoci, ktera by se dala spustit i jinymi stresory a je treba resit primarni problem s metylacnim cyklem. Ruzne geneticke mutace se daji resit ruznymi doplnkovymi bypassy.

Na Wheldonove/Strattonove protokolu od 02/2006 do 10/2011 pro tezky unavovy syndrom, fibromyalgii, bolesti kloubu, intestinalni potize a milion dalsich problemu..

    Glutathion je výsledný

 

  Glutathion je výsledný netoxický produkt metabolismu homocysteinu za předpokadu,že máš

  v těle potřebné vitamíny skup.B/B6 je nezbytná v posl.fázi .....

  z homocysteinu vzniká za přispění B6-cystathionin...dále cystein a konečný glutathion...........

  Jednoduše řečeno,jez kys.listovou,B6 a B12...................jinak se díky ateroskleroze/degen.,zánětlivý

  proces/nikam nepohneš.Díky zánětu se to pak začne hemžit mikrobama........

  Ten pitomý homocystein je klíč ke zdraví............lidstvo si už vyčerpalo ze země všechny zásoby

  vitamnů,příznaky,které dnes řešíme jsou jenom důsledkem avitaminozy.

  Acidoza je vlastně medicínsky nezjistitelná,leda by se našel nějaký slídil pan doktor,který

  by nezaujatě zhltl knihu pana Tepperweina-Pryč s kyselostí..........a jelikož neznám doktora,

  kterého by zajmaly metabolické pochody v těle,tat se tak nestane.A ři tom je to tak jednoduché,

  začít pracovat na obnově acidobazické rovnováhy.Nejsem fanatik,mám jen dlohodobé zkušenosti

  a vlastně jsem 33 let byla biochemik.

 

veraokb

http://www.life-wave.cz/2/pos

http://www.life-wave.cz/2/post/2012/03/glutathion.html

 

březen 2013 ukončení CAPu 

To je problem všech

To je problem všech američanu. Neumí mluvit česky, takže vím prd :D

To máš tak, bylo nebylo a

To máš tak, bylo nebylo a bylo jen cpnhelp, já anglicky neuměl a na jedno naučené anglické slovo jsem jich deset zapomněl...  no  třeba nám to někdo přeloží, já mu taky moc nerozumím...   

březen 2013 ukončení CAPu 

ujo nespomenul NAC je v

ujo nespomenul NAC je v podstate prekurzor glutathionu, tak nezabudajte na jeho doplnanie...ma strasne vela prospesnych vlastnosti NAC, je dost sirokospektralny doplnok. dalej MSM, nemylit s MMS. MSM obsahuje priamo sulphur.

uz v minulosto dobre poznamenala Adriana a rovnako aj ten ujo povedal, ze doplnanie glutathionu v podobe tabletoveho doplnku je zbitocne, nespracuje sa. jedine IV dokazu navysit level glutationu priamo v krvi. dodnesneho dna nevciem preco BCA nevyuziva IV glutathion...neviem ako je to v EU ale US LLMD ho pouzivaju velmi casto

mother of all antioxidants je aj tak VitC...ale urcite nie gramik, ale trosku viacej :)

 

It's not the size of the dog in the fight, it's the size of the fight in the dog./05/12parasite killing/06/12start CAP11/12vitC10g/02/13hyperthermia/07/13detox(DMPS,EDTA,DMSA)vitC50g/10/13Buhner/11/13striebro/07/14 end CAP/11/14MMS/01/15RIFE

IV glutathion Jaky je rozdil

IV glutathion Jaky je rozdil oproti glutathion? Kupujete ho kde? V googlu jsem nenasel.

ako som zistil..tak cez AT/DE

ako som zistil..tak cez AT/DE lekarne a vyrobca je v taliansku... /zdroj info BCL/

problemy od 05/2015: Borelia (EM 2012), Mpn,Cpn,Ctr,EBV,CMV,HSV,vzv,yersinia. Uzivane ATB od 09/2015:Ceftriax/14dni/, Mino+azi., Mino+Klary+Amoxi+Fluko +Tinidazol,ciplox+azi,ceftr 2 mesiace,zinnat+mino+rifa. Zasklby svalov, Karpal syndrom, artralgia ramie

IV znamená zrejme

IV znamená zrejme intravenózně nebo?

ano presnetak ...infuzka do

ano presnetak ...infuzka do zili. Glutathion IV je za 10-15 minut v zilach komplet Wink

problemy od 05/2015: Borelia (EM 2012), Mpn,Cpn,Ctr,EBV,CMV,HSV,vzv,yersinia. Uzivane ATB od 09/2015:Ceftriax/14dni/, Mino+azi., Mino+Klary+Amoxi+Fluko +Tinidazol,ciplox+azi,ceftr 2 mesiace,zinnat+mino+rifa. Zasklby svalov, Karpal syndrom, artralgia ramie

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