Why do certain supplements/medication stop working?

[richvank]

I dont think cfs is going to be treated by a one trick wonder, i think its going to take a few different approaches at the same time as its a multi system illness. This is what i think Rich is getting at. The methylation maybe one of those tricks that we have to throw at it with a few other treatments.

cheers!!!

Hi, heapsreal.

I agree, and I think it's going to be an individual thing to figure out which additional treatments a person will need.

One physician I know gives all his patients the methylation treatment, and then watches the response. If they experience some symptoms that appear to be caused by detox, but they are able to tolerate them, he continues with this treatment. If they have intolerable symptoms that appear to be related to mobilization of toxins, then he stops the methylation treatment and works on improving the status of the gut. When that is working better, he moves on to supporting the liver. His thinking is that the toxins that were being mobilized were being reabsorbed by the gut and sent back to the liver. In order to properly process and excrete the toxins, the gut and liver must both be functioning well enough to handle them.

My guess is that when there is an inflammation response to methylation cycle treatment, there is an infection. If the inflammation continues without resolution, then my guess is that the immune system has been reactivated, but is not capable of defeating an existing infection. In such cases, I think that treating to support the immune system would be one approach. Another would be to test to determine what pathogen is causing the infection, and then treating it with an antibiotic, antiviral or antifungal, depending on the pathogen.

I think it's important to note that a healthy person would not have any reaction to the supplements used in the methylation protocols, because their methylation cycle, detox system and immune system would already be functioning normally. So the fact that there is a response, even though it may seem to be deleterious, means that the methylation cycle was partially blocked and that these supplements were needed. However, the way one should proceed from that point on probably depends on the type of response that the individual person has.

So far, I'm pretty sure that if the following are present, they will need specific treatment, in addition to treating the methylation cycle partial block: biotoxin (including mold) illness, Lyme disease and its coinfections, well-entrenched viral infections, and high body burdens of toxic heavy metals, such as mercury. There may be others of which I'm not aware, but there is some experience with these, at least, which people have reported.

Best regards,

Rich

 

[aquariusgirl]

I don't think I got an inflammatory response when I first started using supps to support methylation, but I believe I did the last time I used them. I woke up with body wide inflammation. Not pleasant.
I guess there's some connection between immune response and inflammation that gets triggered above a certain threshold.

 

[garcia]

I dont think cfs is going to be treated by a one trick wonder, i think its going to take a few different approaches at the same time as its a multi system illness. This is what i think Rich is getting at. The methylation maybe one of those tricks that we have to throw at it with a few other treatments.

cheers!!!

Hi heaps, I don't think many will disagree that it will take a few treatment approaches to cure this multi-system illness. But Rich is talking about causal models rather than treatments. I think methylation is a great adjunct treatment (providing you can tolerate it). However I don't believe that the GD-MCB is the cause of ME/CFS. Right now I think the retroviral model postulated by the WPI & others is streets ahead of any other model out there.

GD-MCB may be part of the pathology/symptomatology, but it is not the root cause IMHO.

 

[heapsreal]

Hi Garcia, i was just agreeing with rich's post about successful outcomes with methylation were usually combined with av's etc. I also think that b12 my also help with nerve regeneration etc as cfs is a neuroligical illness as well, so a side benfit to methylation as its roll is to raise glutathione through improving methylation. When u say GD i take it you a refering to gut dysbosis(spelling??) which i also dont think is a cause of cfs but a part of the multisystem break down that can happen to some with cfs, but all these multisystem dysfunction need treating i guess.

but cheers!!!

Hi heaps, I don't think many will disagree that it will take a few treatment approaches to cure this multi-system illness. But Rich is talking about causal models rather than treatments. I think methylation is a great adjunct treatment (providing you can tolerate it). However I don't believe that the GD-MCB is the cause of ME/CFS. Right now I think the retroviral model postulated by the WPI & others is streets ahead of any other model out there.

GD-MCB may be part of the pathology/symptomatology, but it is not the root cause IMHO.

 

[garcia]

Hi Garcia, i was just agreeing with rich's post about successful outcomes with methylation were usually combined with av's etc. I also think that b12 my also help with nerve regeneration etc as cfs is a neuroligical illness as well, so a side benfit to methylation as its roll is to raise glutathione through improving methylation. When u say GD i take it you a refering to gut dysbosis(spelling??) which i also dont think is a cause of cfs but a part of the multisystem break down that can happen to some with cfs, but all these multisystem dysfunction need treating i guess.

but cheers!!!

Hi heaps, again I agree totally with methylation *treatment*.

B12, methylation, raising glutathione etc. are all fantastic treatments (providing you can tolerate).

What I disagree with is Rich's GD-MCB hypothesis (Glutathione Depletion, Methylation-Cycle Block). Rich postulates this as the *root cause* of ME/CFS. I see it merely as part of the pathology/symptomatology (probably caused by a untreated gamma retroviral infection).

 

[heapsreal]

I agree, im not sure rich thinks that but thinks its the best treatment we got, which i think is also debateable, im with you, its helps some just like av's but it doesnt help all. I think it depends where cfs 'hits' you or what it damages in the hypothalamus, or co-infections, but then the whole retrovirus thing could prove it all wrong too, but still depends where xmrv hits you as everyone has slightly different symptoms. interesting.

cheers!!!

 

[garcia]

im not sure rich thinks that

Ask him for links to his papers on the GD-MCB hypothesis. Or google it if you have time.

 

[aquariusgirl]

That's interesting Rich that you think healthy people would not have any response to methylation supps.
I gave my healthy 50-something aunt some folapro and methyl B12 & she said she felt completely out to lunch. So she got the same reaction many of us have.
I have wondered if I should get her to do some testing...

 

[richvank]

Hi, garcia.

What I've tried to say is that I believe that the partial methylation cycle block is the pivotal abnormality in the pathogenesis and pathophysiology. With respect to the root cause or causes (etiology) of ME/CFS, I have suggested that this disorder arises from a combination of a genetic predisposition and some combination of a variety of stressors, which can be physical. chemical, biological, or psychological/emotional. I've suggested that this combination leads to glutathione depletion, which leaves B12 unprotected, which causes a decreased production of methylacobalamin, which inhibits methionine synthase, which forms a vicious circle with glutathione depletion, making ME/CFS a chronic condition. The retroviruses would fit within the biological stressors in my hypothesis, and certainly could be a root cause. If effective treatment of the retroviruses ends up bringing about recovery from ME/CFS, that will be very convincing as to its role as an etiologic agent. I hope that turns out to be the case for at least some of the PWMEs/PWCs. It may not be true for all of them, though, because this population seems to be very heterogeneous.

The reason I have included the variety of stressors as etiologic agents is that I have studied the published "risk factor" studies, and have also queried quite a few PWMEs/PWCs as to the events that preceded their onset, and I've found a variety of precursors. The common factor seems to be that they are all things that would be dealt with by the body's nonspecific stress response systems, and these in turn are known to place demands on glutathione.

In addition to this, there are now many PWMEs/PWCs who have taken the Health Diagnostics methylation pathways panel, and nearly all of them show evidence of a partial methylation cycle block or glutathione depletion, and usually both.

And when treatment was given in our clinical study that is directed toward lifting the partial methylation cycle block, we observed by testing that this does in fact occur, and that glutathione also comes up automatically. This was accompanied by improvement in symptoms in at least two-thirds of those who were treated.

Putting all of this together, I think the GD-MCB hypothesis is consistent with the observations and with known biochemistry and physiology. That doesn't mean that I believe that it is scientifically proven, which is a very high standard to meet, and requires considerable investment in time, money and effort, but that it is a valid working hypothesis. I'm hoping to interest researchers and fundors in this model so that it can be more thoroughly tested.

Best regards,

Rich

 

[richvank]

That's interesting Rich that you think healthy people would not have any response to methylation supps.
I gave my healthy 50-something aunt some folapro and methyl B12 & she said she felt completely out to lunch. So she got the same reaction many of us have.
I have wondered if I should get her to do some testing...

Hi, aquariusgirl.

Very interesting! I wonder how "healthy" she really is. I think that a lot of us become less healthy so slowly that we just attribute it to getting older, and don't realize that we could be healthier if we improved our nutrition.

Best regards,

Rich

 

[dannybex]

Hi Rich,

Another weird question from Uncle Dan:

Does the methylation cycle affect or have priority over the transulfuration pathway? Or is transulfuration downstream from methylation?

Sincerely,

(Still) Clueless in Seattle

 

[Sallysblooms]

We are sure lucky to have you here Rich! I appreciate the help you have and others too.... Thank you.

 

[richvank]

Hi Rich,

Another weird question from Uncle Dan:

Does the methylation cycle affect or have priority over the transulfuration pathway? Or is transulfuration downstream from methylation?

Sincerely,

(Still) Clueless in Seattle

Hi, Dan.

The answer is "yes" to both questions. The methylation cycle is at the beginning of the sulfur metabolism. It is fed by methionine, which comes in as part of protein in the diet. Homocysteine is produced from methionine (via SAMe and SAH) in the methylation cycle, and then methionine synthase "decides" how much should be converted back to methionine, to stay in the methylation cycle. In the liver and kidneys, the BHMT reaction also converts some homocysteine back to methionine. The rest of the homocysteine enters the transsulfuration pathway, which is downstream.

The way that methionine synthase does its "deciding" is that the cobalt ion in the cobalamin that is its cofactor gets oxidized at a rate that depends on the state of oxidative stress in the cells. The more oxidizing this state is, the more often the cobalt ion gets oxidized, and that temporarily shuts down the methionine synthase reaction and diverts the homocysteine flow into the transsulfuration pathway, which helps to make more glutathione, which counters the oxidative stress. Unfortunately, in ME/CFS this delicate mechanism gets overwhelmed, and the oxidative stress becomes more severe, so that glutathione doesn't recover and get control of it. The result is that methionine synthase becomes partially blocked, and the sulfur metabolites drain down the transsulfuration pathway, into sulfoxidation, and get excreted too much as taurine and sulfate, which depletes methionine. The whole sulfur metabolism becomes dysfunctional, and that takes down the cell-mediated immune response as well as the detoxication system. As well, everything that depends on methylation reactions is affected, including gene expression, synthesis of several needed substances, and the neurotransmitter metabolism. Also, this drains the folates from the cells via the methyl trap mechanism, and that affects things that depend on folate, such as synthesis of new RNA and DNA. The latter is what cause the red blood cells to be too big and too few in number.

The methylation cycle is so fundamental to so many parts of the body's biochemistry that when it becomes dysfunctional, it causes a host of problems, and this is why people experience so many symptoms, involving so many body systems and organs, in this disorder.

Best regards,

Rich

 

[aquariusgirl]

Ok, that's why we all have elevated taurine to begin with.
On my first Urine Amino Acids, 3/12/2008 my taurine was 1170 (220-1300).
I'll update it with my latest result when I can find it.

 

[aquariusgirl]

Rich
This might belong on another thread..but you mentioned the large red blood cells/folate connection.

So I looked up my readings over the years & I was kind of surprised. It seems like elevated MPV or MCHC is a lagging indicator.. because I got sick in the 1990s, but I didn't get elevated readings as far as I can see until 2008.

Plus, MPV is still high on my latest bloodwork in spite of years of b12 /folate supplementation. I guess that's because I've still got a b12 deficiency?

Thanks


03/25/2005
MCV 87 (80-100)
MCH 29.4 (27-33)
MCHC 33.8 (32-36)

03/09/2006
MPV 8.7 (7.8-11.0)

03/24/2008
MPV 10.5 (7.4-10.4)

10/20/2008
MPV 10.5 H (7.4-10.4) C REACTIVE PROTEIN 0.05 (0.00-0.8)


02/24/2011
MPV 11.8 (7.4-10.4)

 

[xchocoholic]

Hi All,

Some diet changes work for awhile and stop too. I've had to change my diet several times since starting all this back in 2005. I was only GFCFSFEFCF + chemical free back in 2005-6 and I felt GREAT for about a month in Sept 2006 but that was it. I wound up on the Paleo / low carb diet and it seems to be the best so far but I still have OI, and PEM though ... oh and all those freakin food and chemical intolerances ... : (

tc ... x

 

[Dufresne]

Hi Diesel. I've found drugs and supplements to stop working for two reasons.

Any supplement that gives me a quick increase in energy is quickly shut down by my body after a day or so, it seems to be for protective reasons. If I continue with it I get worse and worse. These include CoQ10, GSH, HB12, Mb12, vitamin D, E, B5, and most antioxidents. It's counterintuitive that antioxidents should be causing oxidative stress but that seems to be what's happening. My feeling is you can go the methylation route once you've quieted the immune/cytokine flare. When Rich talks about people who've been successful on his protocol after first treating underlying conditions this is what I think is happening. Although my experience has been that when the immune system is calmed energy comes up on its own very quickly, which suggests it's an immune system problem at the root of things and not a methylation block.

The other problem for me is sensitization. At this point I can't take any drug or herb and have it work longer than a day. And like you, if I wait a month or so I'll experience the same benefits for, again, a single day. This is different from the energizing supplements above: while both help for the day, the energizers cause excitotoxicity; these others simply stop working, and in my case cause a ringing in the ears and some of the same symptoms as food sensitivity although more subtle. I once proved this to a friend by sensitizing to clonazepam with two days exposure and then eating a dozen .5 mg tabs. We went on talking into the wee hours. He was quite surprised. It's a weird phenomenon that I used to be able to block by taking a couple of ritalin an hour or so before dosing with the other medication. I think this suggests a hypersensitization caused by low adrenal output.

 

[Weathervane]

I'm gonna go with the biotoxin/environmental toxin and methylation theory. Multiple infections and adrenal imbalance as well too. Cleaning all that up takes work.

 

[Lotus97]

I've read that adaptogens especially need to be cycled or they lose their effect over time. I don't know what the right amount of time is, but what I do is take them for 8 weeks and then stop for at least 2-4 weeks. I don't start them all at the same time so I'm always taking at least a few. The main reason I'm taking adaptogens is because some of them are good for the immune system, brain fog, and adrenals. The effect is going to vary from person to person, but in general adaptogens are supposed to increase your body's ability to cope with stress.