Case where methylation protocol (-ish) didn't raise glutathione

[Vance]

Hi All,

I’m hoping for some insight from the folks here. I also know Rich has some interest in cases where the protocol didn’t work, and I wanted to provide that feedback.

I've been gearing up to try the simplified methylation protocol. But after going through my notes, I realized I actually did something similar in 2010 (Jan-June), and then after five months of that, did testing. The testing showed low pyroglutamate (29 ug/mg). Rich has said this is a fairly reliable indicator for glutathione depletion.

So it would appear that the treatment didn’t accomplish its primarily goal – raising glutathione? (Even though I don’t have a baseline measurement, I’m presuming it wasn’t much below 29 in January because, compared to a lot of PWC’s, my symptoms aren’t that bad. To be <<29 seems pretty severe.)

This deviates quite a bit from the protocol, but Rich says the essence of the protocol is taking healthy doses of folate (5-MTHF) and B12:
* 1mg 5-MTHF
* 1mg sublingual methylcobalamin
* 50-100mg B6 (P5P). (Bear in mind that I think I may have the CBS upregulation, based on my urine amino acid results and Dr. Yasko's comments on this. B6 may not have been a good idea.)
* 30mg B3 (it looks like these are the only B’s I took – no B1/B2)
* Mg, Zn, Mo, Mn, and Li
* Betaine HCl
* Herbals for dysbiosis (garlic, uva ursi, grapeseed extract)
* And some other things that are doubtful to be related

My test results are attached. The urine/plasma amino acids were taken on the same day; organic acids three weeks later.

Symptom-wise, during that time, my notes show a variety of uncomfortable symptoms, but allergy season messes me up anyway. Mostly I think I was OK.

My question is, why did my glutathione seem to not rise?
* Deviations from the protocol (too much / too little / different types)
* Insufficient B1/B2? (I’m sure my food was providing some, but not enough?)
* Can overmethylation cause glutathione to stay low?
* Can aggravation of a CBS upregulation (via B6) cause glutathione to stay low?
* Are metals interfering?
* Dysbiosis? (But I think I have too many plasma amino acids showing good absorption, for this to be the case)

Or even with my low pyroglutamate, maybe glutathione really did come up a little?

A month ago, my serum B12, B6, and “folic acid” were tested. The B12/B6 were low but in the lab's range -- I hadn’t been supplementing at all since 2010. My “folic acid” was fairly normal.

I’m planning to do these tests in the next couple weeks:
* organic acids
* plasma amino acids
* methylation panel
* 23andme

But I’m debating whether I should try the methylation protocol (exactly, this time), or first work on metals via Cutler. (I was hoping to let glutathione do that work naturally instead...)

Anyone have thoughts?

Thank you -
Vance

 

[richvank]

Hi, Vance.

I'm sorry to hear that the treatment didn't help you.

I'm not able to make your attachments large enough to be readable. Would you be willing to email them to me at richvank at aol dot com?

Thanks.

Rich

 

[richvank]

Hi, Vance.

Thanks for sending me your lab results.

It looks to me as though you were low in B2, B5 (pantothenate), C, and intracellular magnesium.

I understand that you took P5P, but the phosphate is removed in the gut, so that there must be enough B2 present to put the phosphate back on, first in the liver, and then later in the cells, when the P5P loses its phosphate again before it enters the cells. In the Organix panel, it is not possible to separate deficiencies in B6 and B2, because both are needed to make P5P in the cells. There are several markers indicating lack of activity of P5P. Since you were supplementing lots of B6, I think that B2 must have been the one that went low.

B5 is necessary to make coenzyme A, which is necessary for feeding the Krebs cycle. It's also necessary for the conversion of alpha ketoglutarate to succinate, and there is a big drop between them.

Generally speaking, it's a good idea to supplement the B-complex vitamins together, because they work together in the energy metabolism, and if some are supplemented and others are not, the ones that are not tend to go low and be the "weak links" in the energy metabolism.

The methyl B12 dosage may not have been high enough, also. When glutathione is very low, as it appears to have been in your case, the B12 dosage needs to be higher in order to overcome the functional B12 deficiency.

Vitamin C usually goes low when glutathione is low, because glutathione normally recycles vitamin C.

I understand that you were supplementing magnesium, but it looks as though not enough was maintained inside the cells. That is common in ME/CFS, and it seems to be associated with low glutathione. It's difficult to get enough magnesium to stay in the cells until glutathione gets higher, but magnesium is necessary, together with ATP, to put the glutathione molecules together, so it's sort of a catch-22. But by raising the intake of Mg and using a form that is absorbed well, such as magnesium glycinate or magnesium "oil" on the skin, it seems possible to boost it some.

I'm somewhat puzzled by the comparison between your plasma amino acids and your urine amino acids from samples taken on the same day. The plasma levels of the essential amino acids are pretty good, but the urine levels are quite low. This suggests that you were not absorbing amino acids at a very high rate, either because you had a low-protein diet, or because your digestive system was not working so well. It appears that your kidneys were doing their job by not dumping much of several of the amino acids, so as to conserve them and keep their levels up in the blood, but taking in more would give you more wiggle room.

I can't tell from these data whether you had elevated levels of toxic metals or not. They could have influenced the results of the organic acids test, but it would require independent measurements of them in blood or urine to say for sure.

If you decide to go ahead with trying a methylation protocol again, I hope it works out better for you next time.

It will be interesting to see how your new lab reports come out.

Best regards,

Rich

 

[Vance]

Rich, thanks much for your time and insight. Maybe there's reason to believe that my deviations from the protocol contributed to the lack of glutathione progress. I think I'll try it again, simultaneously supporting my gut, before doing any active chelation.

I didn’t realize the Organix markers couldn’t distinguish B2/B6 – I’ve always interpreted this as lack of B6, which didn’t make any sense. Since I wasn’t supplementing B2, this makes more sense.

After these tests in 2010, I added a B complex, and this is when I learned that something in B vitamins gives me anxiety, or sometimes kind of a racing-brain feeling. Interestingly, after some isolation, it seemed it might be B2. So it’s interesting you identified B2 as perhaps my rate-limiter. The anxiety suggests B2 enables something, even if not pleasant...

Because of the anxiety, I never stuck it out -- I just quit taking the B complex. But in retrospect, I should've started at a lower dose and worked my way up, slowly.

For a couple weeks before starting the protocol again, I intend to take curcumin. Given my possible CBS upregulation, and high levels of taurine, this seems important. PubMed studies indicate curcumin directly stimulates gamma-glutamylcysteine synthetase (GCL), which it seems to me ought to help it compete better for my cysteine. It should also help prevent an initial “dip” in glutathione upon methylation startup, which I believe you’ve said is common.

My diet wasn’t low-protein at all, so I guess my lukewarm amino acids suggest mild dysbiosis or gut damage. In the months before testing, I’d even run a rotation course of herbs intended to help with dysbiosis, as well as supplementing HCl and pancreatic enzymes with a lot of my meals. Hmm. This time, I’ll use lemon juice (rather than betaine), pancreatic enzymes, berberine for gut flora (great results on PubMed), and I suppose maybe glutamine or something else for gut healing. (Given my high glutamate, the glutamine concerns me a little...)

I’ve had a couple blood and/or urine tests for metals, plus hair tests. They didn’t show much. But this doesn’t mean they aren’t entrenched somewhere, especially if I have low glutathione.

One more question... I’d wanted to use levels of reduced glutathione as my primary indicator of success. Whether I feel better or not, this seems like a major problem to be corrected, and I like that it's objective. Unfortunately I’m having some trouble finding a doctor who will order the methylation panel for me – the HDRI doesn’t seem as accessible as other labs. DirectLabs has a “Glutathione, Erythrocytes” test, and LEF has a “total glutathione” test. Or, I was going to do the Organix test again anyway, which has pyroglutamate. Although these won’t show “reduced glutathione”; are any of them adequate substitutes to at least show progress with the methylation protocol?

 

[richvank]

HI, Vance.

The other glutathione tests that are offered are total glutathione (reduced plus oxidized), and they are dominated by red blood cell glutathione. These tests are not very reflective of tissue cell reduced glutathione levels. If your glutathione status is quite low, it will show up on these tests, but if it isn't too bad, it may not show up at all. The reason is that red blood cells are normally producers and net exporters of glutathione. Their glutathione status will generally be better than that of the cells affected in ME/CFS, such as the skeletal muscle cells.

Pyroglutamate on the urine organic acids tests mainly reflects the reduced glutathione status of the kidneys, and to some degree, the intestine. The drop between citrate and the next two Krebs metabolites mostly reflects the skeletal muscle reduced glutathione status, I think, but this marker can be masked by other things that affect the early part of the Krebs cycle.

If you start out low on one of these tests, then I think it would be an indicator of progress, at least for a while. When the test got up to normal, though, it wouldn't necessarily mean that your tissue cell reduced glutathione was up to normal.

Best regards,

Rich

 

[caledonia]

You can get the HDRI methylation panel through Dr. Ben Lynch: http://www.seekinghealth.com/methylation-pathway-panel-vitamin-diagnostics.html

It costs a little more, but if you can't find a doc locally, this is another way to do it.

 

[Dreambirdie]

Hi Caledonia-- Are there any the differences between Ben Lynch's methylation panel and the one Rich recommends? Do they test the same exact things?

 

[August59]

Rich - Not sure if you tried this, but when you click on his attchment and it brings it up on another page where it is very small, just move your pointer back over the image and click it again and they will become much larger and readable.

 

[Vance]

Thanks Caledonia -- that's what I was looking for! I even called HDRI today and asked if there was someone that did this sort of service, like Direct Labs usually does -- they didn't seem to know of anyone.

Dreambirdie, the link says at the bottom that the methylation panel is by Vitamin Diagnostics, the former name of HDRI. So it seems they are one and the same.

Sorry for the drama in reading my labs. I tried opening them now (in Firefox) and had the same experience as August59. If anyone still can't read them and wants to, let me know and I'll post them some other way.

 

[Vance]

Rich, thanks for breaking down the value of those tests with respect to glutathione. Given the availability through Dr. Ben, I’ll probably do the panel, up front at least. But I may use Organix for monitoring -- it covers more information for less money, if not as specific.

Is there a reason HDRI can’t offer only reduced/oxidized glutathione as a separate, cheaper test? If it were offered alone at something closer to $100, I'd be likely to test it more often, for monitoring.

Suppose someone is feeling poorly two months into the protocol. They'd want to know that it's because of detox from increased glutathione and they're on the way to health, not that something is wrong. But it's another $295 test -- they just spent $295 two months ago on the same test. Do they spend the money again? Maybe instead they just decide to quit the protocol. $100 is less painful.

And so I'm wondering if a cheaper test might lead to more testing, keeping more people on the protocol and providing more data to you for whether the protocol is successful. I know test costs are unavoidable to some extent, but it seems pretty straightforward for them to isolate these as a cheaper test.

 

[richvank]

***Hi, Vance.​

Rich, thanks for breaking down the value of those tests with respect to glutathione.​

***You're welcome.​

Given the availability through Dr. Ben, I’ll probably do the panel, up front at least. But I may use Organix for monitoring -- it covers more information for less money, if not as specific.​

***O.K.

Is there a reason HDRI can’t offer only reduced/oxidized glutathione as a separate, cheaper test? If it were offered alone at something closer to $100, I'd be likely to test it more often, for monitoring.​

***I think they do offer it separately. I know that their European parent lab does this, and in fact, they don't include glutathione in their methylation panel. I don't know what it costs. You could phone and ask them. It's important to know what's happening to the methylation, too, though, because they are linked. You can tell if there is a problem with the flow through the transsulfuration pathway if you have both, and in many cases, there is. Maybe Dr. Ben could offer glutathione only by acting as the ordering physician, as he does for the complete methylation pathways panel.

Suppose someone is feeling poorly two months into the protocol. They'd want to know that it's because of detox from increased glutathione and they're on the way to health, not that something is wrong. But it's another $295 test -- they just spent $295 two months ago on the same test. Do they spend the money again? Maybe instead they just decide to quit the protocol. $100 is less painful.​

***You do have a point.​

And so I'm wondering if a cheaper test might lead to more testing, keeping more people on the protocol and providing more data to you for whether the protocol is successful. I know test costs are unavoidable to some extent, but it seems pretty straightforward for them to isolate these as a cheaper test.​

***Well, you could give it a try, but if glutathione comes out low, you wouldn't know whether it was because the methylation cycle is not coming up, or whether it is because there is low flow through transsulfuration, or whether there was another cause. If glutathione comes out higher than it was initially, that would be encouraging.​

***I do empathize with the pain of high costs, especially when resources can be slim when one is not able to work.​

***Best regards,​

***Rich​

 

[Vance]

Hmm. More information is always better, isn't it. ;-) If this stuff were free, I'd do it weekly, and assuming others did as well, we'd all know a whole lot more about CFS/ME.

It's good to know it may be possible to get glutathione separate, if that's what I decided. I'll definitely do the full panel initially, anyway. I believe I found an interpretive guide you created, somewhere. Here it is... http://forums.phoenixrising.me/index.php?threads/are-there-any-doctors-who-will-interpret-the.18332/ I'll take a stab at it myself, but may ask to run it by you if I get stuck. Meanwhile, I'll pass along anything useful I learn to the community.

Thanks again, Rich.