There are two main camps when it comes to methylation issues it seems. The first group has had their pathway poisoned by (principally) mercury and the second camp has significant SNPs in the pathway. There are a few of us with one foot in each camp.

These two groups share symptoms and presentation. Both tend to worsen after the age of 40 when the body's production and availability of things like glutathione and Co Q10 start to decrease as part of the normal aging process. Fatigue, fog, malaise, ME/CFS, weakness and endocrine problems is only the beginning of the list of symptoms shared by these people.

We have extra capacity to provide and recycle glutathione. Inherent redundancies and back-ups start to get tired and when this happens people start to look for help. By the time the afflicted find the on-line communities or help from a Naturopath, they are usually already on supplements.

One of the supplements that seems like a no-brainer is NAC = n-acetyl-l-cysteine. This is an amino acid that along with glycine and glutamate form glutathione.

Our lives would be a matter of seconds without glutathione as free-radicals would tear things up. It is crucial for energy production and the sequestration and processing of mercury.

The problem is that many people do not react well to NAC…or at least not until they reach a certain level in their recovery. The symptoms and complaints are the same and are essentially worsening of the person’s given symptom-set. Fatigue, fog, malaise can be part of this.

The “mercury people” say that the single sulphur group on the NAC molecule is dragging mercury around. We don’t want this because in theory mercury could be moved from our little toe into circulation and find its way into the brain.

Rat studies show that NAC can increase Hg movement into the brain where it will be trapped behind the blood-brain-barrier. While humans have a more sophisticated BBB than rats it should still serve as a warning.

If you read this blog you know that I had a fantastic response to NAC and then became worse…. much worse actually. Was this due to mercury finding its way into the brain? The answer would be purely speculative and we will leave it at a resounding “maybe”.

The ME/CFS community say that the symptoms are do to an increased excretion of B12 which for people with certain SNPs could prove problematic and symptomatic.

In the end, it doesn’t matter. The take away is that people with impaired methylation can reasonably anticipate that their Hg levels will be higher than the general population because the methylation pathway is integral with the detox pathways.

NAC may not be safe to take if someone is high in mercury and so being tested might be supportable.

For one reason or another, NAC may be hard for some people to tolerate until they reach a certain level of recovery and have to some extent recovered or supported methylation.

I am taking NAC again but was not able to return it to the line-up until chelation was almost over.


Or avoid NAC and get L-cysteine which can be used to make glutathione but does not have the negative effects like NAC. NAC has effects against biofilms which I believe is really why many people react badly to it. It degrades biofilms which is why it is used in some antibiotics and doing that increases digestive permeability with resulting consequences.

I only use it against biofilms that I am attempting to destroy. At other times I prefer l-cysteine for it's much gentler effect. l-cysteine is cheaper than NAC too.

BTW chelation also has an effect against biofilms which is why so many people try it but without specific targetting it is not effective at resolving the biofilm problem because the bacteria inside are not destroyed.

I have both l-cysteine and NAC but I now only use l-cysteine for supplementing for glutathione production. Many foods are quite low in cysteine/cystine and supplementing can be helpful. It is meant to be the limiting factor in glutathione production.
Thanks Carl. That makes a lot of sense. It is used to break up thick secretions in the lungs...and well, mucous is mucous. I may try to change at some point in the future because leaky gut is a big problem for me. Anything gut related, actually.

I will try a NAC holiday and see if I notice any difference before deciding where to go after.
If I was you I would get a little l-cysteine and substitute it for NAC and see how that goes. Your glutathione production needs to be maintained after all so I don't think stopping NAC would be ideal without a usable substitute such as l-cysteine. Then keep what NAC you have left as well as possible for attacking the biofilms when you need to. It sounds like your digestive system is as bad as mine was. I did manage to destroy most of the largest biofilm in my stomach which reduced the permeability by quite a bit. The other biofilms are far more resistant and not so easily defeated. Each biofilm increases the digestive permeability, it's not the tight junctions which cause Increased Intestinal Permeability Syndrome aka leaky gut, it's the bacterial biofilms which use it to provoke histamine release and saliva production. Destroying the infection causes the stomach and transverse colon to heal instantly but without destroying the bacteria the stomach and colon cannot heal. No amount of supplementation with all the so called leaky gut fixes will fix leaky gut until the bacteria are defeated.

I proved this to myself at the end of last year when I destroyed most of one of the biofilms and my stomach and colon healed. Unfortunately the other 4 biofilms are far more resistant. I have had some effect against the most important one but so far have not defeated it. I have never had any feeling in that part of my stomach with anything I have ever taken before so the effect was encouraging as it was very similar to the effect I had when I destroyed the biofilm on the right hand side of my stomach. Not enough though unfortunately.

The one I defeated I have had some feeling in the past when taking essential oils but they were never enough to destroy it. The more intense the feeling the greater the effect. I still have some way to go to defeat it but I am getting there.

Take a look at Radii Solaris. ;)
You seem to have spent considerable time on this subject. I had no idea that biofilms even populated the stomach. I thought that the low ph would be protective.

I have a myriad of food sensitivities and eat only meat, most veggies, fruit and oils. Gluten, milk, eggs, garlic, corn, soy tomatoes and many more are off the menu and I have to be careful at restaurants, You'll know about this.

My colon was removed for over 100 polyps. I do not have an ileocecal valve and have slow peristalsis. This is the recipe for SIBO.

Because of this, I have kind of given up any idea of my gut actually recovering and while I am going to follow up with your ideas on cysteine. I remain guarded. I have had lots of help along the way with chelation and methylation from other people, both directly and indirectly, but so far, I have not been able to incorporate anyone else's ideas on the gut. Thank-you for the suggestion about cysteine, it makes sense.
Nothing should live in the stomach. The ph should be protective and the stomach is intelligent and does try and destroy anything pathogenic. However bacteria have ways to overcome this. Just consider H. Pylori which is only one known bacteria to live in the stomach. It creates a biofilm in the stomach and requires triple therapy to defeat. Some CFS sufferers have been treated for pylori and yet that did not defeat these bacteria. That is how resistant they are. There are others which have been identified but some are difficult to classify. There is research on these bacteria. I have tried to find the full research papers rather than just the extracts without having to pay but so far have not succeeded. It might help narrow down possible bacteria names. However it probably won't be the one I am looking for.

Many of these bacteria are urease positive. Urease converts urea in saliva into ammonia. That is why many CFS sufferers have high ammonia levels and why they take supplements to attempt to reduce ammonia.

A biofilm is protective of bacteria it is what enables them to survive in the stomach. However protein digesting enzymes and stomach acid can degrade a biofilm if the acid is not neutralized. That is why CFS sufferers have hypochlorhydria.
I have had allergy tests done at a hospital and I was found to have allergic antibodies to every food I had been eating plus dust mites and pollens.

I spent 20 years eating the same foods at the same time each day because that was the only thing which provided relief and prevented total exhaustion. While doing that I could walk miles each day but if I varied the food or times I was left exhausted which took days to get back into my previous eating pattern. Food transit and antibody production seemed to work together. Since then I noticed an article on wikipedia about B12 which has since been edited and removed, high dose B12 up regulates T-Suppressor cells which suppresses IgE antibody production and calms the immune system. I have used that, high dose B12, since I found it and it has helped a lot. Since then I have been able to adjust the times of food much more, I no longer eat to a strict timetable and I do not get the exhaustion provided I do not change the foods. If I do then I am exhausted.

Eating your protein as liquid, maybe liquidized to speed up digestion should help. I eat protein powders because they are quick to digest. Pea and hemp protein mixed with sulphur amino such as extra Methionine and l-cysteine and glycine and maybe a little l-glutamine but food contains quite a bit of that anyway. Pea and Hemp are quite low in Methionine and Cysteine which is why I supplement with it. Pea and Hemp, 80% protein and 50% protein are quite low reactive proteins and don't seem to cause me problems. Whey did cause problems where my bowel became very loose. I do tend to be fairly constipated but can manage that with lecithin which helps my liver and provides the choline for acetylcholine production because the choline tends to be used up by the liver and leads to constipation.
Eating vegetables separately should be okay as they require no stomach acid. It's acid which is usually the problem. I eat giant plates of carrots, red onions and beetroot which can be chewed freely because saliva cannot be used against me. I do not chew protein so make up for it by chewing fruits and veg. Chewing protein is probably a mistake for CFS. TCM state that fruits and above ground vegetables are more yin in nature and below ground veg are more yang. CFS is a yin illness so eating yang foods can be helpful. Salt is yang in energy.

It's worth looking at radii solaris because this indicates leaky gut and if you have such high reactions to foods as you say then you will probably have a number of these.
Take a look at this chart. Notice the location of hypothalamus and pituitary, it's near 12 o clock. Look for a radii solaris going into this zone. I have a very large one which has destroyed part of my pituitary and hypothalamus on the right hand side. I have to use Tu Si Zi (dodder seed) to counter my lack of pituitary function. Also notice the adrenal glands and any under functioning. Mine were badly affected until I partially restored their function. This also did improve my mood. I did that back in the late 90's using a very strong Aloe vera juice with turmeric.
I am also type 1 diabetic and the pancreas tail shows a black diamond shape which indicates tissue destruction. Recent research indicates that not all the beta cells in the pancreas tail are destroyed in type 1 diabetics. My pancreas tails shows some blue iris fibres inside the pancreas tail which backs up that research. It also shows why my beta cells did not repair. It was leaky gut which caused the initial attack against those cells, an infection which has existed for 40 years. No antibiotics has ever harmed them.
SIBO is usually a result of poor stomach function and low stomach acid. If you can raise your stomach acid it should destroy any bacteria in your small intestine. That is where not swallowing saliva helps. I spit all saliva into a bucket while I digest protein and it allows me to digest protein quite quickly. It allows my stomach acid level to rise providing I deny them the saliva that they would use to neutralise my stomach acid. It keeps ammonia levels low too.

I do not eat wheat, corn, soy or tomatoes. I do eat garlic and have eaten eggs and milk but do not ATM. I eat bananas and tangerine/mandarines etc but the acid can cause a reaction and burping/wind. Lots of methyl B12 (30-40mg/day) to suppress my immune system .

Notice any wind and burping when you digest protein. It's worth watching out for as it is indicative of urease activity.
Thanks for all of this Carl, must have taken you ages. My Dr has offered to treat SIBO but I don't see anything positive, or I should say, permanent coming from that. Without an ileocecal valve it would only be a matter of time until I would need to be treated again. I do not have radii solaris.

I use coconut kefir to try to lower the ph in the ileum. I have no clue whether it works in this way but the hives and worst of the histamine issues are gone. It could also be the anti-inflammatory properties or perhaps the high fat content is modifying the gut biome. I have been having a problem with something I am eating and have been laid-up with gastro symptoms the past week. It could be cinnamon and I have some elimination to trial before I go to my useless GP.

I can have all the animal protein that I want. It is plant proteins that will eventually cause me trouble. I have not tried hemp but I suspect that it would be no different. I would get along great with it for a couple of months and then it would be off the menu. This is what happened with rice and soy proteins.

What you wrote about B12 is interesting and perhaps is part of the reason I seem to need as much as I do. I take 2 mg by needle daily plus a couple of mg of adenosyl.

My gluten reaction is unique in that it gives me arthritic pain on top of the GI stuff. The other foods exacerbate my skin problems mostly. Turmeric, sulfites and corn make me itchy and everything else eczema, psoriasis and folliculitis. It can get pretty miserable. I tested (+) for antibodies to food as well but the immunologist said that these tests are useless. Dairy, egg whites, egg yolks and garlic were the worst and I react the most to them. I am not as quick to dismiss the testing.
Recently, I added canned tomatoes to a couple of meals with white rice pasta and got away with it. Now I need to protect these and take them sparingly. They are the first foods that I have been able to add back in the last 4 years.

Thanks again, I hope that you continue to progress and find solutions to your health issues. Sounds like someone is in your corner, many of us can not get the testing we need.
I find NAC very stimulating, even at tiny tiny doses (like 1/64 tsp). I'm curious about why this may be. I have some ideas. Maybe underlying Mercury toxicity (I had amalgam fillings for years), or perhaps due to my really impaired liver metabolism (especially sulfur metabolism).
That is interesting @Star-Anise. I have heard of this before but I don't know if it is a common reaction. If you have had your amalgams out for a while, you can trial alpha-lipoic acid every 3 hours around the clock for at least 3 days and 2 nights continuous and any response (+) or (-) indicates that mercury is moving.

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