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Supplement Glutathione to protect supplemented b12

Adster

Senior Member
Messages
600
Location
Australia
Good point, the use of the term exitotoxicity is potentially confusing. I should say "symptoms like that of" or "often described as" exitotoxicity, as I have no proof of their origin. For me, mb12 REDUCES these symptoms, to a point. There is also the issue of flavours in the adb12 causing issues rather than the adb12 itself.

It looks very likely through my experiences with supplementation so far that I have a glutathione problem, either I'm not making enough or it's being used up by something faster than it can be replenished. Clearly there are many possible reasons for this that taking more mb12/folate than I currently am just can't fix. Mercury toxicity being one possibility.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Good point, the use of the term exitotoxicity is potentially confusing. I should say "symptoms like that of" or "often described as" exitotoxicity, as I have no proof of their origin. For me, mb12 REDUCES these symptoms, to a point. There is also the issue of flavours in the adb12 causing issues rather than the adb12 itself.

It looks very likely through my experiences with supplementation so far that I have a glutathione problem, either I'm not making enough or it's being used up by something faster than it can be replenished. Clearly there are many possible reasons for this that taking more mb12/folate than I currently am just can't fix. Mercury toxicity being one possibility.

Hi Adster,

YES. What I would prefer, as it is more clear is a paragraph you can cut and paste or something with simply a list of symptoms in order of onset and/or combinations and/or severity etc. Then perhaps we can assign a word as a suitable shorthand term so that we, and others reading it can understand exactly what is meant. I'm putting together a variety of symtoms sets with just that purpose in mind so that if I say SS1 maybe that means Symnptoms Set 1 as the set of symptoms for folate deficiencies and then we assign "induced folate deficiency" as one of the conditions that has it's characteristics of SS1 along with "paradoxical folate deficiency", "NAC Detox", "Glutathione Detox", "medication induced folate deficiency" and just plain ordinary folate deficiency. Maybe we will even be able to see which symptoms disinguish one from the other. That would allow recognition that while there are multiple causes, the effects of folate deficiency is always included in that set. We have use terms like IBS, FMS, ME, CFS, MCS and formal symptoms definitions exist for those but slicing and dicing the same symptoms sets in differrent ways because of secondary or tertiary causes makes MANY different possible sets, most of them unnamed. Included in these symptoms sets of the same universe of symptoms is "20 year pre-MS, "20 year Pre Parkinson's. "20 year Pre ALS" and so on. If we can distinguish which specific symptoms subsets points at these various things a lof of disease could be prevented and the way of treatment might become obvious.
 

Adster

Senior Member
Messages
600
Location
Australia
I think if terms like "paradoxical folate deficiency" and "induced folate deficiency" are going to be used to help diagnose and treat people, then properly designed placebo controlled studies and testing needs to be included to back them, rather than just anecdotal evidence from a small set of samples. Otherwise I think the term "potential" should be put before the conditions. There are way to many variables in individual's biochemistry and cross over of symptoms to be saying that if someone takes NAC and feels worse then they are definitely experiencing folate deficiency. Maybe you have that data from testing, and maybe that is always the case, I don't know.

And while super sensitive people with poor gut function are taking supplements with additives like fruit flavours, mannitol and xylitol etc. then you never really know what is causing what for sure without lab results. I'm also a little bit concerned that you might think that ME/CFS is DEFINITELY a subset of plain b12 deficiency illness. It may be, but until it's proven I think it's a dangerous assumption. It's the same as Andy Cutler thinking that all ME/CFS is caused by mercury poisoning. You can't both be right! :- )
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
I think if terms like "paradoxical folate deficiency" and "induced folate deficiency" are going to be used to help diagnose and treat people, then properly designed placebo controlled studies and testing needs to be included to back them, rather than just anecdotal evidence from a small set of samples. Otherwise I think the term "potential" should be put before the conditions. There are way to many variables in individual's biochemistry and cross over of symptoms to be saying that if someone takes NAC and feels worse then they are definitely experiencing folate deficiency. Maybe you have that data from testing, and maybe that is always the case, I don't know.

And while super sensitive people with poor gut function are taking supplements with additives like fruit flavours, mannitol and xylitol etc. then you never really know what is causing what for sure without lab results. I'm also a little bit concerned that you might think that ME/CFS is DEFINITELY a subset of plain b12 deficiency illness. It may be, but until it's proven I think it's a dangerous assumption. It's the same as Andy Cutler thinking that all ME/CFS is caused by mercury poisoning. You can't both be right! :- )

Hi Adster,

There are way to many variables in individual's biochemistry and cross over of symptoms to be saying that if someone takes NAC and feels worse then they are definitely experiencing folate deficiency

Ten of us over at WD did an intentional trial. It wasn't just "feels worse". It was a specific set of symptoms that reversed starting within hours after stopping NAC, glutathione (precursors) or un denatured whey and taking an 8mg dose of Metafolin and 10mg each of adb12 and mb12 and continued until symptoms were gone again. All 10 had been on the active protocol with excellent results including up from a wheelchair. All had sudden return of symptoms and suddenly worsening instead of continuing to improve when starting the trial. If you go looking for Glutathione Detox and NAC detox you will find the essentially same descriptions for those two and for folate deficiency and then there is what Metafolin got rid of that also coincides.



And while super sensitive people with poor gut function are taking supplements with additives like fruit flavours, mannitol and xylitol etc. then you never really know what is causing what for sure without lab results.

Perhaps just an interesting coincidence but the whole "super sensitive" situation is precisely one of those things caused by methylfolate and/or methylb12 deficiencies.

I'm also a little bit concerned that you might think that ME/CFS is DEFINITELY a subset of plain b12 deficiency illness.

Now this "plain b12 deficiency illness" is one of the most frequent reactions against the whole idea and is a myth. However, I have absolutely no belief in a "plain b12 deficiency illness". There are 2 kinds of active b12, mb12 and adb12 and there are separately discernable complexes of symptoms for the body and the CNS for each making a total of 4 discreet b12 deficiency illnesses affecting over 600 differnt biological functions in the body and nervous sytem. There isn't anything in the entire body that isn't dependent uopn sufficient b12 of the correct variety. Every single system, without exception, of the body is dependent upon it.

It's the same as Andy Cutler thinking that all ME/CFS is caused by mercury poisoning. You can't both be right!


Actually Adster, Cutler and I might both be right. Let me explain how. Consider it this way. The model of the whole thing as I see it is basically this. For this also consider that 80% of mercury toxicity symptoms are IDENTICAL with b12/folate deficiency symptoms. It might be very difficult to tell them apart. This may be because mercury quite possibly destroys methylb12. 1 mg of mercury can destroy 7mg of methylb12. The typical total body load of b12 is estimated at 2.5-5mg. A person can have many mg of mercury in their body. A load of 30mg is not unusual. That possibly can destroy 210mg of methylb12. That would destroy all the methylb12 obtainable in the body and that will be eaten in food for the next 70 years. Now that would be a cause of b12 deficiency that keeps on taking making climbing back up out of the pit impossible on an ordinary food intake.

1 - Some percentage of people have some inborn errors within themselves that affects how they handle b12 and/or folate. This affects their immune systems and the ability of the body to remove toxins and heal fully so damage accumulates over time. This also puts their body on the knife edge of just making it by or in some cases the toxins or other stressors just plain overwhelm the system.

2- When the person is sufficiently weakened, something happens, there is a stressor. The stressors that I have seen in person, in others, in the literature, etc include vaccination, viral illnesses, bacteria illnesses, traumatic injury, toxic challange, surgery, etc. There have been endless triggers suggested because some people have had them. I've had several of them. My daughter had several a different times in her life. She got a cold at age 2 the day she said her first complete sentence, stopped talking for several years, started stimming and repeating one syllable; baaa - baaaaaa - baaa- baaaa etc. She emerged over several years after age 5. Then illness and setback, then auto crash and setback with FMS following. My history is similar in many ways. In any case the stressor tips the balance of b12 down the slope to a lower meta stable placement that can't normally be returned to the higher meta-stable position without intervention. Certain systems don't recover.

3 - The person ends up, as a result of exhausting the body load of b12 to a low point, and with possible genetic processing problems, is stuck. Even if the toxins are cleared out, or the virus is defeated or whatever, they are in a hole and can't get out. What starts out as an illness, an injury, a toxic reaction becoms something else chronic. The symptoms change from the acute onset symptoms to a somewhat larger set of slowly worsening and broadening symptoms completely independently of whatever the specific trigger(s) were.

4 - The EXACT subsets of symptoms a person has from a universe of about 400, is determined by the mix of 5 basic inter-related deficiencies, four b12 and methylfolate, and another half a dozen secondary deficiencies, another dozen or more tertiary deficiencies plus whatever toxins remain in the body. This is a complex mixture of hundreds of possible different subsets that do exist, many named. The symptoms are "non-specific" precisely becasue they are included amongst so many different things of the same root or secondary causes.


I think if terms like "paradoxical folate deficiency" and "induced folate deficiency" are going to be used to help diagnose and treat people, then properly designed placebo controlled studies and testing needs to be included to back them

I agree. These studies need to be done. And they probably will be, maybe in time to save the lives and health of my great grandchildren. My only granddaughter is going on 2 years old. Now if you have the tens to hundreds of millions needed to run those studies I'm sure we could put together a research team to do the research projects. I have mapped out the ones that need to be done, approximately 10 intial studies and another 20 to validate and confirm those first 10. We could have the first set of 10 up and running in about 2 years if the money were forthcoming. Since these studies will cost the pharmaceutical companies profits they will not fund or do these studies. Such is the problem of vitamins. The medical and pharmaceutical industry don't like them one little bit. There is no real money to be made on them and no "control". Have you heard any appolgies from the medical business for the heart attack plague caused by their promotion of sticks of transfats being substitued for butter in the 50s? Or the people they bled to death in other centuries. Or all the brains and lives ruined by psychosurgery. Or all the wrong things destroying peoples lives and health they have done in the name of medicine. These diseases are man made just like pellagra and beriberi. The research establishment would rather bury it forever than see revealed how badly they screwed up.


In the identification stage of course all these things are "potential". However, as the reations to methylfolate and methylb12 and adb12 can be rather prompt often making night and day differences easily visible to the naked eye it ceases being "potential", often within hours as the deficiency is reversed.

So let's take "paradoxical folate deficiency". It doesn't exist in anything indexed in google scholar. It has only been possible to do a comparison between the effects of folic acid and methylfolate for a few years and nobody has studied it. In the Cerefolin/NAC package insert research they didn't recognize it when some people had severe side effects in the studies leading to approval of the drug. However, a simple comparison with Deplin (side effects are essentially the same as placebo) shows they saw the side effects but didn't recognize them. The side effects that they list just happen to match "NAC-detox", "gltathione detox" and of course good old fashioned folate deficiency. Nobody doing that research dared suggest that NAC with Metafolin could possibly cause a severe folate deficiency. So here we are right out on the bleeding edge. If anything is done soon enough to be useful to any of us alive right now it isn't going to be by the research establishment. The 10 studies to get to the point of what I can demonstrate right now, would take place about 1 every 5 to 10 years slowly building a case on all the little pieces from the light sensitivity of methylb12, breakdown and acne to the absorbtion rate of sublinguals and how it relates to injections to establishing the threshold for the cobalamin resistant CNS problems that are present in CFS and FMS and how many injections per day of what size actually work. Coming up with those answers blind could take 50 - 100 years. Further I have already talked to researchers. They said that the real study that needs to be done is absolutely impossible to get through an institutional review committee because there are so many different substances involved. It's too complex and has too many variables and has the potential to completely re-write nutritional understanding which right now is built on flawed foudations. They like single substance or at most simple combinations of no more than 3 substances. Historically it has taken 70 or more years to reach an understanding of a vitamin once it becomes available. So for mb12/adb12 that date is approximately 1998. For Metafolin that date is approximately 2006. So that takes us out to the neighborhood 2075 for recognizing what the deficiency syndrome of mb12, adb12 and methylfolate each looks like. Since these are the most complex deficiency syndromes 70 years might be quite an underestimation.

I waited 54 years for medical research to figure out my problems. It didn't. I identified methylb12 and adb12 and possibly folate as my probable deficiencies in 1979 doing old fashioned paper journal library research. It was not a testable hypothesis at that time as the substances were not available except in France to researchers with a 10mg vial costing about $1000. Methylfolate was unavaiable period. Nine years and 3 months ago I was dying and couldn't wait any longer and did it myself. I have worked in group medical at various levels of software development, plan design and consulting since 1981. I know the flaws of the system all too well. I have saved my life and restored my health and done the same for my children and thousands of others over the past 8 years. I didn't approach it from the research industry method as I did not have time for that. Instead I approached it as a systems analyst and engineer with speed being of the essence as I was trying to save my life. I have a working system here that is meant to be used in a 3 step process. I expect to have a finished prototype of the new lifetime questionaire very soon now.

Three step process -

1 - Detailed lifetime symptoms questionaire - certain patterns of symptoms map to certain nutrients and body vs cns. With this we can see the adb12,mb12, metafolin and a few other things unmet needs in the body and/or the CNS. The patterns indicate which things would probably be needed and wheter we are talking about body only doses or body and resistant CNS doses. In a questionair development project I questioned people in details about their symptoms and they took 1mg mb12 or 3 mg adb12 or both as challange doses, n = 1000 aproximately over 3 years. Most of the people sampled were at any of several campgrounds or group medical conferences or traveling to said conferences so most of them were not disabled

3 Modes of answers/responses a - about 50% had multiple symptoms from the present list b. - About 30% had essentially no symptoms or a few symtoms on or off the list c. About 10% had lots of symptoms but not from the CFS/FMS/B12/Metafolin universe d. about 10% reported no symptoms but then after have a significant response with multiple symptoms affected changed their story to "Oh yes, I forgot about those. The doctor said that they were non specific and didn't matter. I had forgotten about them."

2 - A single dose challange of adb12 and/or mb12. Evaluate for 10 minute, 1, 2, 24 hour resposes. There is also an expanded version of the challange that includes Metafolin, b-complex, magnesium and l-carnitine fumarate. These raised the response rate to 95%from 85% for those with symptoms, intially or remembered after response. Those without sympoms on the list had a zero response rate.

3 - Active b12/folate protocol for those have the symptoms and response with adjustments, titrations and fine tuning
 

Adster

Senior Member
Messages
600
Location
Australia
My point about mercury, which I realise can cause b12 deficiency, is that you don't just treat it with b12. You need to use a chelating agent. Same goes for gut problems, b12 deficiency is just one of many possibilities. I'm happy to leave this here and put it in the "respectful disagreement" box :) I will continue to experiment with low doses of glutathione, which after ceasing for a few days was clearly helping me. Cheers freddd.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
My point about mercury, which I realise can cause b12 deficiency, is that you don't just treat it with b12. You need to use a chelating agent. Same goes for gut problems, b12 deficiency is just one of many possibilities. I'm happy to leave this here and put it in the "respectful disagreement" box :) I will continue to experiment with low doses of glutathione, which after ceasing for a few days was clearly helping me. Cheers freddd.

Hi Adster,

Cutler has said that IF methylb12 actually does lose it's methyl group to mercury in the body, and he says "doubtful" or "very slowly" to that, at the rate of some micrograms per day, thereby mobilizing monomethyl mercury, that this monomethyl mercury is then removed from the body by the liver. The documented rate via research of monomethylmercury removal from the body by the liver gives it a serum halflife of about 71 days which is a 1% a day reduction, the same rate at which benzos can be safely and comfoatably tapered. Therefore, if methylb12 does combine with mercury it actually then removes this toxin from the body in a slow and effective manner, and it combines slowly enough that there is no great surge of mercury. For a lot of reasons I probably had as much mercury in my body as anybody here. If methylb12 does indeed remove it from the body I wold expect that I no longer would have much in the way of mercury left. I also have been taking selenium for about 30 years.

Same goes for gut problems, b12 deficiency is just one of many possibilities.

Yes. methylb12 deficiency causes massive gut problems, inflammation and lesions from top to bottom, literally. Methyfolate deficiency also causes similar effect and can cause onset of IBS in 5 days and can relieve it almost as quickly in the presence of sufficient mb12. Now there may be other causes of such problems as well. However, they CAN"T heal without a sufficiency of both methylb12 and methylfolate as well as zinc, a, d, e, magnesium, C etc.

As b12 deficiecnies, by very poor measures, reaches perhaps 50% of the population and unrecognized folate deficiencies perhaps as high or higher, they are an odds on favorite for at least eliminating as a cause.

As you appear to find mitochondrial startup and generation of ATP intolerable, and that too is a one of the major deficiency symptoms, mitochondrial failure from lack of adb12 and methylation failure from lack of sufficient methylfolate and methylb12,and these two together system failures and what results from them in the body and CNS are able to define and account for and relieve virtually every symptom of CFS and FMS and ME, you have a tough row to hoe here. Glutathione, mercury and thousands of other specific breakdowns in the body mechaniosms all apear to be secondary to these root causes. These are the fundamental breakdowns. WIth fully operational methylation there is no deficiency of glutathione. With a properly functioning detox system with good methylation there may not be an accumulation of mercury. With a properly funtioning methylation system there is not the epithelial breakdown that casues the gut problems. Without mitochondrial shutdown there is not the abnormal fatigue. Without these breakdowns in the brain all the neurological problems don't happen. If mb12, adb12. methylfoalte are taken adequately before these breakdown happen, not much is needed. An ounce of prevention beats a ton treatment. One these peoblems are created via deficiency which might happen via various challnages when a person is in a borderline condition, which becasue of the pseudo vitamins of folic acid, cyancobalamin, hydroxycoblamin giving the illusion of fullfilling the role of the real vitamins the MCV alert would be at 92 or 93 instead of 100 where it has migrated to over the past 30 years. Unfortuanately these manmade diseases are endemic because of these induced deficiencies rather than rare and confined to people with certain genes. Once damage is done it take a lot more. It is very difficult to achieve a cure by chasing down all the secondary and tertiary problems without repairing the root cause as the system never works. Certain types of damage does not appear repairable. With the CNS/CSF cobalamin deficiencies spotted in those with CFS/FMS indicating that food level doses and usual vitamin forms don't work for US here with CFS and FMS, and others with ALS, MS, Parkinson's, SupraNuclear Palsy, Alzheimer's and no doubt some others it does appear that healing is difficult if that CNS/CSF deficiency isn't corrected. As the pragmatic trial for that is 50mg sublingual doses separately of each adb12 and mb12 after the person has reached body equilibrium and body startup has returned to zero, not being able to tolerate startup of ATP generation throws a monkey wrench into healing. The only thing going for this approach is that it can work for a lot of people after decades of notjhiong else really working. Startup isn't pleasant. I had to keep telling myself that it was indeed startup and the systems raggedly trying to normalize instead of something awful. Experince with myself and a lot of people though the years has also indicated that one little hole in nutrition that becomes the new limiting factor only shifts the symptoms around and that healing only takes place after ALL necessary factors are in place. Healing can be painful and unpleasant with every change until it gets along far enough and symptoms start melting away. For me the epithelial healing was fastest except for those things affected by intermittant folate deficiency. Some thing break down very quickly, like the lining of the gut. IBS only take 5 days of folate deficiency to startup and 10 to heal significantly.

Try to find some things in yourself that demonstrate actual healing that you can then follow up on and expand upon. Playing muscical chair symptoms shifting around and around isn't that unless they go away in the shifting and are not replaced by a different form. It took me 10 days to know without a doubt as my daily nausea and vomitting cleared up, burning bladder stopped burning, burning red tongue healed and ceased being burning or red, canker sores healed, cheilitis and IBS became intermittant instead of steady (all this methylation startup with endothelial cell reprodcuction), muscle burning went away with energy startup but not enough there until adb12 9 months later to heal and grow muscles. Each increase in healing caused potassium deficiency. MCV, IBS, cheilitis hung around until the folate problem got worked out years later. Peripheral nerves healed over 9 months but CNS didn't until much higher doses 5 years later.

The thing that I found and others have found is that when you really find what works, healing can be very rapid. So follow the clues. Best of luck with your chosen hypotheses and proving them out.
 

aquariusgirl

Senior Member
Messages
1,732
Rich
thanks for this. I have had bad experiences with gluthatione recently, even though years ago I did well on IVs.

Do you have any thoughts on how much b2 & b3 one would need to recycle 600mg of glut, for example?

thanks


Hi, all.

The question of whether to supplement glutathione in some way in conjuction with treatment of the partial methylation cycle block in ME/CFS often comes up. There is some recent research that appears to shed some light on this issue, so I would like to
review the status of at least my understanding of it.

As I see it currently, there are three groups of people with respect to their response to
adding glutathione to methylation treatment:

1. There is a group who benefit from this addition, in terms of their symptomatic response.
2. There is a group who benefit initially, but as time goes on, it causes their symptoms to worsen.
3. There is a group who experience immediate worsening of their symptoms.

I dont know what fraction of the ME/CFS population is in each group.

I would like to suggest what I think is going on in each of these groups.

I suggest that the first group have inherited normal genotypes of their intracellular B12 processing enzymes, and they also have normal status of vitamins B2 and B3. In this group, the glutathione can be recycled at a normal rate when it becomes oxidized by reactive oxygen species that are part of the oxidative stress in ME/CFS, by the glutathione reductase reaction, which requires both B2 and B3. Furthermore, glutathione
is able to play its normal roles with respect to the intracellular processing of vitamin B12.
In particular, the Cblc enzyme (also known as MMACHC) uses glutathione to remove the upper ligand from incoming forms of B12 (cyano-, methyl- or adenosyl-) by the formation of glutathione conjugates of these ligands (PMID: 19801555).
In addition, it appears that glutathione also reacts with the resulting aquocobalamin to form glutathionylcobalamin. Glutathionylcobalamin is chemically more stable than the other forms of B12, but Cbcl is normally able to retrieve cobalamin from glutathionylcobalamin so that the cobalamin can be used to form methylcobalamin and adenosylcobalamin in the amounts needed by the cell (PMID: 21429294).
Thus, glutathione appears to serve not only as a reactant in the metabolism of B12, but also as a protector of B12 from reactions with toxins, and a buffer to store B12 until it is needed by the cell.

I suggest that the second group have inherited normal genotypes of their intracellular B12 processing enzymes, but they have a deficiency in B2 or B3 or both, so that the rate of the
glutathione reductase reaction is too slow to keep up with the oxidation of the glutathione. As a result, though the supplemented glutathione is initially beneficial to them, over time it becomes a detriment, because the ratio of reduced to oxidized glutathione drops too low, and this worsens the oxidative stress of the cells.

I suggest that the third group has inherited an inborn error of metabolism involving the Cblc enzyme. As a result of this, when glutathione reacts with B12 to form glutathionylcobalamin, their genotype of the Cblc enzyme is unable to retrieve the cobalamin from the glutathione to use it to form methylcobalamin and adenosylcobalamin. If glutathione is supplemented, this situation is made worse for this group. In addition, this group is unable to make use of hydroxocobalamin as their B12 supplement
(PMID: 21497120), because it is converted to glutathionylcobalamin in their cells (even without supplementing glutathione) and is therefore made inaccessible. I suggest that Freddd is in this group, and this explains why he cannot tolerate supplementing glutathione, why he cannot make use of cyanocobalamin or hydroxocobalamin, and why he must use high dosages of methylcobalamin and adenosylcobalamin, applied either sublingually or by injection. This raises the concentration of these species in the blood stream, and enough of them is able to diffuse into the cells through their plasma membranes to be used directly without intracellular processing, thus supplying the need of his cells for methylcobalamin and adenosylcobalamin.

Best regards,

Rich
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Rich
thanks for this. I have had bad experiences with gluthatione recently, even though years ago I did well on IVs.

Do you have any thoughts on how much b2 & b3 one would need to recycle 600mg of glut, for example?

thanks

Hi Aquariusgril,

Can you point me at you description of that or tell me what has changed since before when you responded well to it? What occurred, what symptoms changed? How fast. I'm preparing a questionaire trying to get at these things and input from you on this could be very helptful. Would you be willing to fill it out after I post it? While I would like to have your info for preparing it, I also would like to get some of it in a standardized form. Thankyou.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
According to Rich, too much methyl B12 can actually cause excitoxicity which would result in a drop in glutathione. Also, overmethylation can cause glutamate toxicity. NAC can actually convert glutamate into glutathione. Some people have a problem taking glutathione and NAC/cystein/non denatured whey, but other people don't in which case case taking these would protect the B12. However, there are a lot of other ways to raise Glutathione besides taking the supplements I mentioned.