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Glutathione Precursor Cross Comparison

Messages
66
Ok, I made this thread as a means to compare the pros and cons of various methods used to increased Glutathione. Now I realize that increasing methylation overall should benefit GSH production overall, but I wanted to focus on Glutathione not methylation. Also, I am concerned about potential long term side effects of any supplementation so information on that should be included, not just the short term pros/cons. Please help me with this list if you have any more information. I know that the issue of methylation is quite intricate and individualized based on our SNPs, so I am trying to find a way to increase Glutathione without effecting the methylation cycle much.

My interest in this resides in the fact that there are ongoing clinical trials of NAC as a means of reducing OCD (here:http://clinicaltrials.gov/show/nct01172275), which I have. The general theory behind NAC to help OCD is that it modulates glutamate and NMDA receptors in a beneficial way. I guess the glutamate involvement is a relatively newer developement in the OCD world, compared to serotonin deficits.

Possible Glutathione increasing agents and things I have read about them:

Cystine-
-Saftey Issues: potential for causing cystine kidney stones?
-The oxidized form of cysteine, which I guess is a common form in your brain anyways as cysteine from the liver gets auto-oxidized in the pro-oxidant environment of the brain

Glutathione-
-Pro: This is exactly what you are looking to increase. Supplementing with this means you don't have to deal with issues involved with precursors.
- Ineffectively absorbed by the body. This is a rather large molecule and is broken down in the gut, so you don't get the amount that you supplement. (However could this just be overcome by supplementing with a lot of Glutathione, ignoring the expense that would incur).

N-acetylcysteine
-very effective means of increasing liver Glutathione as well as brain GSH, proven by the fact that it is the go to antidote for acetomenophan overdose.
- Has been proven to cause pulmonary hypertenson at very high doses in rats (I understand that this might not actually be an issue, but the way I see it, if I can supplement with any of the other precursors and not have to worry about this, then that would be the way to go)
-I have read from many individual testimonials that people have reduced OCD symptoms as a result of this supplement

L-Cysteine
- Don't know much about supplementing with straight L-Cysteine. I have read on one site that they believe that L-Cysteine is more "proven" to be safe over NAC.

If anyone else has any experience with these and or additional suggestions to the pros and cons of these and their ability to help increase glutathione please let me know what they are. Or if there are more options to add to this list, please do so. I have read Rich's recommendations about Glutathione, but I am looking for your individual input.
 

Lotus97

Senior Member
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United States
L-Cystine, L-Cysteine, and NAC can cause problems for mercury toxicity. Another option for increasing glutathione is non/undenatured whey protein (which would also carry the same mercury risks). It must be specifically this type of whey protein (other types of whey protein also would pose the same risk for mercury toxicity). It also has lactoferrin, albumin, and immunoglobulins which might be a good thing or bad thing depending on a person's immune system. I'm finding there's a downside to certain immune system supplements, but I'm not sure about the one's in whey.
 

xjhuez

Senior Member
Messages
175
I took NAC for about a year and it did help my OCD a bit. I have no way of knowing whether it raised by brain GSH. I stopped taking it after learning here about the possibility of it depleting B12, and also because I feared improper chelation of mercury and unwanted chelation of minerals.
 

Lotus97

Senior Member
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I took NAC for about a year and it did help my OCD a bit. I have no way of knowing whether it raised by brain GSH. I stopped taking it after learning here about the possibility of it depleting B12, and also because I feared improper chelation of mercury and unwanted chelation of minerals.
That's interesting because according to Rich, glutathione protects B12.
http://phoenixrising.me/research-2/...etion-theory-of-mecfs-by-rich-von-konynenburg
One of the jobs that glutathione normally does is to protect your supply of vitamin B12 from reacting with toxins. If left unprotected, vitamin B12 is very reactive chemically. If it reacts with toxins, it can’t be used for its important jobs in your body. A routine blood test for vitamin B12 will not reveal this problem. In fact, many people with CFS appear to have elevated levels of B12 in their blood, while their bodies are not able to use it properly. The best test to reveal this is a urine organic acids test that includes methylmalonic acid. It will be high if the B12 is being sidetracked, and this is commonly seen in people with CFS.

When your glutathione level goes too low, your B12 becomes naked and vulnerable, and is hijacked by toxins. Also, the levels of toxins rise in the body when there isn’t enough glutathione to take them out, so there are two unfortunate things that work together to sabotage your B12 when glutathione goes too low.

The most important job that B12 has in the body is to form methylcobalamin, which is one of the two active forms of B12. This form is needed by the enzyme methionine synthase, to do its job. An enzyme is a substance that catalyzes, or encourages, a certain biochemical reaction.

When there isn’t enough methylcobalamin, methionine synthase has to slow down its reaction. Its reaction lies at the junction of the methylation cycle and the folate cycle, so when this reaction slows down, it affects both these cycles.
 

xjhuez

Senior Member
Messages
175
I understand you disagree with Freddd about NAC and B12.

I'm taking mB12 to increase methylation which should increase GSH, so if the possibility exists that NAC flushes it out then I'm not going to take it. Yes, it may in fact raise it or be otherwise beneficial, but as I said I took it for a year and I have nothing positive to show for it.
 

Lotus97

Senior Member
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I understand you disagree with Freddd about NAC and B12.

I'm taking mB12 to increase methylation which should increase GSH, so if the possibility exists that NAC flushes it out then I'm not going to take it. Yes, it may in fact raise it or be otherwise beneficial, but as I said I took it for a year and I have nothing positive to show for it.
I'm not necessarily recommending NAC (and neither was Rich btw). I'm just pointing out that there are other viewpoints (backed up by science) and I'm not convinced a handful of anecdotes and conjecture. If someone has mercury issues then it would be a bad idea to take NAC, cysteine, cystine, or non/undenatured whey.
 

Hip

Senior Member
Messages
17,824
Glutathione-
-Pro: This is exactly what you are looking to increase. Supplementing with this means you don't have to deal with issues involved with precursors.
- Ineffectively absorbed by the body. This is a rather large molecule and is broken down in the gut, so you don't get the amount that you supplement. (However could this just be overcome by supplementing with a lot of Glutathione, ignoring the expense that would incur).

Glutathione powder can be applied to the skin, where it is absorbed. You can rub on say ¼ teaspoon of glutathione powder into the top of your thighs (or any convenient area of skin on your body), and then add just a few drops of water to help the glutathione sink into the skin.

Rectal administration of glutathione powder is even better (higher absorption), but you need to buffer with sodium bicarbonate to neutralize the acidity of glutathione (else it irritates the rectal mucosa).

You can buy glutathione powder cheaply here and here.

Essential reading:
Augmenting Glutathione in Chronic Fatigue Syndrome (ME/CFS) by Rich Van Konynenburg
 

Lotus97

Senior Member
Messages
2,041
Location
United States
That's interesting because according to Rich, glutathione protects B12.
http://phoenixrising.me/research-2/...etion-theory-of-mecfs-by-rich-von-konynenburg
One of the jobs that glutathione normally does is to protect your supply of vitamin B12 from reacting with toxins. If left unprotected, vitamin B12 is very reactive chemically. If it reacts with toxins, it can’t be used for its important jobs in your body. A routine blood test for vitamin B12 will not reveal this problem. In fact, many people with CFS appear to have elevated levels of B12 in their blood, while their bodies are not able to use it properly. The best test to reveal this is a urine organic acids test that includes methylmalonic acid. It will be high if the B12 is being sidetracked, and this is commonly seen in people with CFS.

When your glutathione level goes too low, your B12 becomes naked and vulnerable, and is hijacked by toxins. Also, the levels of toxins rise in the body when there isn’t enough glutathione to take them out, so there are two unfortunate things that work together to sabotage your B12 when glutathione goes too low.

The most important job that B12 has in the body is to form methylcobalamin, which is one of the two active forms of B12. This form is needed by the enzyme methionine synthase, to do its job. An enzyme is a substance that catalyzes, or encourages, a certain biochemical reaction.

When there isn’t enough methylcobalamin, methionine synthase has to slow down its reaction. Its reaction lies at the junction of the methylation cycle and the folate cycle, so when this reaction slows down, it affects both these cycles.
One quick clarification about what I posted earlier from Rich. He wasn't talking about supplemental glutathione. Rich did say that there were certain SNPs that could have a problem with glutathione and B12 (but most people wouldn't):
Hi, Freddd.

I think that what needs to be done is to figure out how people can be separated into groups on the basis of their genetic polymorphisms, so it can be known what treatment is most suited to them. I'm hopeful that the 23andme genotyping will be useful for this. As I've posted before, the folic acid intolerance likely depends on polymorphisms in the DHFR gene. The folinic acid intolerance likely depends on polymorphisms in the MTHFS gene. The inability to use B12 forms other than methyl B12 and adenosyl B12 and the glutathione intolerance are likely due to polymorphisms in the MMACHC gene.

Concerning the difficulty in getting enough B12 into the brain, here's a thought: As you know, in your case, I have suggested that there is a genetic issue with the MMACHC gene, so that your cells are not able to convert other forms of B12 to the two active coenzyme forms, and you have gotten around this problem by raising the concentration of these coenzyme forms in the blood high enough that sufficient amounts of them will get into the cells by diffusion across the cell membranes, without use of the transcobalamin transport mechanism. O.K., now consider the brain. The cells in the brain will likewise have this genetic problem with the MMACHC gene, so they will need to receive methyl B12 and adenosyl B12 directly, also. However, there is an additional hurdle to be overcome for them, because they are behind the blood-brain barrier. So it will be necessary to push the coenzyme B12 forms through the blood-brain barrier first, before they can diffuse into cells in the brain. Perhaps this is the reason that you have found that much larger dosages are needed to help the brain in your case. The B12 forms have to surmount two diffusion barriers to get into the brain cells, and that will require higher concentrations in the blood. What do you think about this?

Rich
NOTE: Freddd disagrees with this
 
Messages
66
Glutathione powder can be applied to the skin, where it is absorbed. You can rub on say ¼ teaspoon of glutathione powder into the top of your thighs (or any convenient area of skin on your body), and then add just a few drops of water to help the glutathione sink into the skin.

Rectal administration of glutathione powder is even better (higher absorption), but you need to buffer with sodium bicarbonate to neutralize the acidity of glutathione (else it irritates the rectal mucosa).

You can buy glutathione powder cheaply here and here.

Essential reading:
Augmenting Glutathione in Chronic Fatigue Syndrome (ME/CFS) by Rich Van Konynenburg

Hip, do you know if the transdermal application of GSH is more effective than taking an oral dose?

L-Cystine, L-Cysteine, and NAC can cause problems for mercury toxicity. Another option for increasing glutathione is non/undenatured whey protein (which would also carry the same mercury risks). It must be specifically this type of whey protein (other types of whey protein also would pose the same risk for mercury toxicity). It also has lactoferrin, albumin, and immunoglobulins which might be a good thing or bad thing depending on a person's immune system. I'm finding there's a downside to certain immune system supplements, but I'm not sure about the one's in whey.

Lotus, the whole idea of mobilizing a bunch of mercury doesn't sound too good. I am somewhat familiar with Andy Cutlers ideas about chelating properly with ALA and that you're supposed to keep taking it so the mercury doesn't land in the brain, primarily. Is this a problem that even straight glutathione supplements could cause?

As far as my mercury status goes, I have something like 5-7 fillings, but none of them have a metallic appearance, and they are tooth colored. I am pretty sure though that my dentist did an initial filling with some merc/silver based substance and then sealed it with ceramic or porcelain, which is unfortunate. :(
 

ukxmrv

Senior Member
Messages
4,413
Location
London
Pgoody,

I don't know if you have heard of this group? They started selling Glutathiodne precursors to patients years ago. Put together different formulas to try and increase glutathione. My blood test was low so I bought the Defense and the Replenish forumulas.

http://www.cfsn.com/

The result for me was a massive down turn in my health and functioning.

Same thing happened when I tried Whey Protein (also to try and increase my blood glutathione and general health)

I've no idea why this doesn't help. Sensitive to quite a few different supplements.

Also I tried NAC alone and that didn't increase my Glutathione but at least it didn't make me worse.
 
Messages
66
ukxmrv,

Did you ever try a straight Glutathione supplement just for the sake of it? I feel like any sort of whey protein, if it's not specifically one of the L-cystine/ l-cysteine types like ImmunoPro or Immunocol, that it would be impossible to tell what is helping you and what is hurting you. I don't even know if ImmunoPro/col are purely those substances, it just seems like such a broad brush type of way to treat low glutathione
.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
Lotus, the whole idea of mobilizing a bunch of mercury doesn't sound too good. I am somewhat familiar with Andy Cutlers ideas about chelating properly with ALA and that you're supposed to keep taking it so the mercury doesn't land in the brain, primarily. Is this a problem that even straight glutathione supplements could cause?

As far as my mercury status goes, I have something like 5-7 fillings, but none of them have a metallic appearance, and they are tooth colored. I am pretty sure though that my dentist did an initial filling with some merc/silver based substance and then sealed it with ceramic or porcelain, which is unfortunate. :(
Glutathione is made up of cysteine, glycine, and glutamate. Some people have said that it breaks down into those 3 components when ingested and then is reassembled so then it would carry the same risks as taking cysteine. I'm not too familiar with Cutler's ideas, but I'm definitely aware of his position on alpha lipoic acid. A quick Google search revealed that he's against supplementing with glutathione for the same reason he's a against NAC, cysteine, chlorella, and spirulina. Rich has also said not to take cysteine, cystine, or NAC if you have mercury issues. I'm not sure if Rich got his information from Cutler or arrived to that conclusion based on another source. I'm not sure I have an opinion yet on the best way to chelate mercury. I am concerned about Alpha Lipoic Acid being able to cross the blood brain barrier. While it could potentially remove mercury from the brain it could also redeposit mercury into the brain. I want to do more research before I make any decisions, but I'm not sure I'd want to have my amalgams removed like Cutler suggests even if I could afford to do so. I found a post from someone that offers a counterargument to Cutler. I don't know enough to agree or disagree with this person, but it is good to hear other points of view.
His reasoning is that glutathione is not a "true" chelator but only a redistributor of mercury because it doesn't have a double thiol bond. Therefore, glutathione and NAC and pretty much all other sulfur compounds are to be eliminated due to the fact that they'll pick up mercury and leave it somewhere else in the body instead of having a strong "true" bond that will bring it out of the body.

That being said, I don't buy it. People forget that Andy is just another researcher and he speaks the part of a chemist. Chemistry isn't everything in medicine. There are people that do well and actually REQUIRE glutathione. People who lack GSTP1 and have genetic mutations that produce less or less effective glutathione. These people have their natural and most potent antioxidant depleted. Some people are not lacking GSTP1 such as myself, and I seem to have ample amounts of glutathione. For people like myself, maybe i could have an adverse reaction to too much of it but I've had a glutathione IV push and didn't really feel all that much better or worse.

Oral glutathione is apparently largely ineffective in being absorbed into the body's bloodstream, but liposomal and IV will work great. Even sublingual may work well. However, people do feel well and a difference from taking oral glutathione so it's hard to say. It is very good for the GI tract so the benefits maybe from helping the GI tract and the entire immune system from oxidation.
You can also take NAC or ALA as precursors to boost your glutathione levels but be aware that ALA can cause chelation.

The thing I don't get about andy is when he makes statements like "half the people who take it get worse". Where is he getting these numbers?? From his yahoo groups? I'm sorry but he's not a medical practitioner. A researcher may know things very well in terms of specifics but they lack clinical experience and patient evaluations, just like doctors with lots of clinical experience lack the time to do their own specific research most of the time. I have his book and he does have a big list of sources at the back but there are so many claims throughout the book telling doctors what they should or should not do that go uncited. I don't know where this information is coming from. I would take those statistics with a grain of salt. He does make very good points and is right about many things and as far as I'm concerned, he's on the same SIDE as everyone else, including the DAN doctors and their methods which he hates because it's all working to the same goal. But he isn't right about everything.
 

golden

Senior Member
Messages
1,831
Can I ask how much NAC are people taking when they do take it?

I have 100mg in my multi antioxidant tablets and after a bumpy and bit scary start am doing ok on them...
 

Hip

Senior Member
Messages
17,824
Hip, do you know if the transdermal application of GSH is more effective than taking an oral dose?

I guess oral glutathione might be effective to some degree if you took say a ¼ teaspoon of sodium bicarbonate a few minutes before taking oral glutathione, as this would help neutralize your stomach acids, and thus help prevent these acids breaking down the oral glutathione. Though I have not tried this; I just thought of this idea now.

I find transdermal application of glutathione powder fast and easy, so I tend use this approach. The armpit area is another good area to apply the glutathione powder, as the skin there seems thinner, and so I think may better absorb the glutathione.


For me, glutathione gives me a slight antidepressant, mood lifting feeling around 30 minutes after I take it (glutathione increases the sensitivity of the brain to dopamine, and dopamine is one of the brain's happy neurotransmitters), so I use this mood lifting feeling of glutathione to judge roughly how effective each mode of application is.

I find sublingual administration of glutathione powder is effective, but I don't recommend this, because glutathione is acidic, and it seems to rot your teeth if you apply it sublingually too often (ie, you get sensitive teeth after a few weeks).
 

Lotus97

Senior Member
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Can I ask how much NAC are people taking when they do take it?

I have 100mg in my multi antioxidant tablets and after a bumpy and bit scary start am doing ok on them...
Are you saying that your multi antioxidant tablets caused side effects? What other ingredients are in them? And do you think it's the NAC that caused the side effects? I mainly buy all my supplements separately because it's cheaper, but another reason would be so you could tell which ingredient is causing side effects.

I was taking 600 mg twice a day, but after finding out the information about NAC/cysteine and mercury I stopped them until I can figure out my mercury situation. Like 95% of my supplements, I'm not sure if NAC was helping or not. I also have Lyme and Rich said that the Lyme bacteria uses cysteine so I might be depleted of cysteine. I'm not sure what to do since I can't afford to get my mercury tested right now. I'm doing methylation right now and methylation will increase cysteine, but I would also like to supplement with it if it's not going to cause me problems. I've stopped NAC, ALA, chlorella and spirulina until I learn more information about mercury.
 

Lotus97

Senior Member
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2,041
Location
United States
For me, glutathione gives me a slight antidepressant, mood lifting feeling (glutathione increases the sensitivity of the brain to dopamine, and dopamine is on of the brain's happy neurotransmitters) around 30 minutes after I take it, so I use this mood lifting feeling of glutathione to judge roughly how effective each mode of application is.
I've noticed the same effect from glutathione sometimes which makes me wonder if that means that I'm depleted of glutathione.
 

golden

Senior Member
Messages
1,831
Are you saying that your multi antioxidant tablets caused side effects? What other ingredients are in them? And do you think it's the NAC that caused the side effects? I mainly buy all my supplements separately because it's cheaper, but another reason would be so you could tell which ingredient is causing side effects.

I was taking 600 mg twice a day, but after finding out the information about NAC/cysteine and mercury I stopped them until I can figure out my mercury situation. Like 95% of my supplements, I'm not sure if NAC was helping or not. I also have Lyme and Rich said that the Lyme bacteria uses cysteine so I might be depleted of cysteine. I'm not sure what to do since I can't afford to get my mercury tested right now. I'm doing methylation right now and methylation will increase cysteine, but I would also like to supplement with it if it's not going to cause me problems. I've stopped NAC, ALA, chlorella and spirulina until I learn more information about mercury.

i couldnt follow all the supplement/methylation plus I am not good at detailing what causes what due to the fluctuating nature of M.E. plus delayed effects plus possible delayed toxicity plus weighing all this against combination effects good and bad under similar conditions.

So I am just taking in powdered form from capsules:

vit A 10,000
c - 500mg
e - 200iu
b2- 6mg
zinc 15 mg
selenium 200 mcg
manganese 2 mg

blue-green algae 100mg
garlic 100mg
ginger 100mg
green tea 100mg
NAC 100mg
Sweet Cherry fruit 100 mg
Turmeric (90% curcuminoids) 50 mg
grape seed extract 10mg


First time I tookvit before bed and forced awake in night it felt like I had stopped breathing.

Then even though I was exhausted I had to stay awake breathing was exceptionally laboured and slow (like you see before someone dies).


I never take before bed as moving and my lymph system massage stops this extreme from happening.

I have from this had a bumpy stop start/ pacing with them but feel they are now doing me good.

But I am working on a foundation of The lymphatic System...

I can take them no probs now. If I feel too laboured I skip a day.
 

golden

Senior Member
Messages
1,831
I've noticed the same effect from glutathione sometimes which makes me wonder if that means that I'm depleted of glutathione.

My blood test showed I had low Glutathione. I decided to eat foods rich in Glutathione as I read it was useless to supplement this.
 

Lotus97

Senior Member
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2,041
Location
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i couldnt follow all the supplement/methylation plus I am not good at detailing what causes what due to the fluctuating nature of M.E. plus delayed effects plus possible delayed toxicity plus weighing all this against combination effects good and bad under similar conditions.

So I am just taking in powdered form from capsules:

vit A 10,000
c - 500mg
e - 200iu
b2- 6mg
zinc 15 mg
selenium 200 mcg
manganese 2 mg

blue-green algae 100mg
garlic 100mg
ginger 100mg
green tea 100mg
NAC 100mg
Sweet Cherry fruit 100 mg
Turmeric (90% curcuminoids) 50 mg
grape seed extract 10mg


First time I tookvit before bed and forced awake in night it felt like I had stopped breathing. Then even though I was exhausted I had to stay awake breathing was exceptionally laboured and slow (like you see before someone dies).
I never take before bed as moving and my lymph system massage stops this extreme from happening.
I have from this had a bumpy stop start/ pacing with them but feel they are now doing me good. But I am working on a foundation of The lymphatic System...I can take them no probs now. If I feel too laboured I skip a day.
I'm glad to hear they're working better for you now. Maybe it was just your body detoxing. It's hard to know which ingredient was causing the problems so I'd be careful as far as supplementing with additional NAC until you know more information.
My blood test showed I had low Glutathione. I decided to eat foods rich in Glutathione as I read it was useless to supplement this.
I don't know if taking glutathione is useless. I think the jury is still out on whether it can be beneficial or not. While Rich doesn't necessarily hold a strong opinion against supplemental glutathione like Freddd, both Rich and Freddd agree that the best way to raise glutathione is through methylation. This is what Rich said about glutathione in 2012. It seems that he was unsure whether taking glutathione was a good idea or not:
Historically, from about 1999 to 2004, I encouraged PWMEs to try to boost glutathione in various ways. Doing that alone did give some people symptomatic improvements, but they were temporary. Others could not tolerate it, and we did lots of guessing about why. When I caught on to the methylation cycle problem in late 2004 from the autism researchers, I shifted to encouraging PWMEs to boost their methylation cycles and stopped promoting glutathione boosting, and that has worked out better in terms of results.

However, this treatment has been difficult for some people to take, especially initially, and I think that one of the problems is that it probably lowers glutathione even further initially, because more of the homocysteine gets converted to methionine, and less is available to go into making cysteine and glutathione. So I have started suggesting that people might try adding either some liposomal glutathione or some acetylglutathione, because I think they are most able to get glutathione into the cells. I haven't had much feedback on whether this has worked for people or not, and I don't know how many have tried it.

Now, the question you're asking is what about getting a lot of glutathione into the cells while also putting in B12. I don't know how that would work out. One concern I have is that I think it's important not to ramp up the methylation cycle, the B12 function, the folate metabolism, and glutathione too fast in a person who has been ill for an extended time. These things will make major changes to the metabolism, and I think it's best to take it slow enough so that things can adjust as you go. I do think that for one thing, it could mobilize toxins a lot faster than they could be excreted, and that could make a person pretty miserable.

I also think that there could be a problem in recycling the glutathione fast enough when it becomes oxidized in a body that is under a lot of oxidative stress. This could shift the ratio of glutathione to oxidized glutathione too much, and that could affect the biochemical reactions in a big way.

So I don't have a very good answer for you. Don't have experience to go on, and the system is too complicated for me to figure it out on the basis of theory. Sorry about that.

Rich

 

Hip

Senior Member
Messages
17,824
I am not good at detailing what causes what due to the fluctuating nature of M.E.

The solution to this is to keep a journal of your supplement and drug experiments, and make a note every time you observe an improvement or worsening of any particular symptom. Then when you look back at your notes, if a medication was consistently making an improvement each time you took it, you can be reasonably confident it was the medication (and not just random symptom fluctuations) that was responsible for the improvement.

Making notes is particularly important for ME/CFS patients, because our memories are well below par anyway, so we are unlikely to remember things unless we write them down. I keep my journal in a word processor document on my computer, as I find that I can type in information quicker that I can write it on paper.