Measured high endogenous acetaldehyde blood levels, discovered something.


Well-Known Member
In the case the combination ischemia and the body producing it's own acetaldehyde would be a major source of symptoms then this allopurinol drug might be helpful.

So I looked into that.

"Allopurinol reduces the production of uric acid in your body. Uric acid buildup can lead to gout or kidney stones."

=> Dang. Uric acid is a major anti-oxidant in the body and in this hypothesis we need plenty of anti-oxidant in order to fight the oxidative stress. On the other hand it could reduce one source of oxidative stress. So I looked into this further.

"Most of the protein in the liver exists in a form with xanthine dehydrogenase activity, but it can be converted to xanthine oxidase by reversible sulfhydryl oxidation or by irreversible proteolytic modification."

=> Maybe that means that some people make more XO then others, genetically determined?

The following chemical reactions are catalyzed by xanthine oxidase:
  • hypoxanthine + H2O + O2
    xanthine + H2O2
  • xanthine + H2O + O2
    uric acid + H2O2
=> So indeed XO can generate copious amounts of oxidative stress and xanthine can be converted to uric acid and oxidative stress. So this *might* indicate that this allopurinol medicine not only blocks uric acid production but also peroxide production in a 1-to-1 ratio. *IF* that is the ONLY mechanism of action then somewhat lower values of uric acid would be not that bad as they wouldn't have to catch the hydrogen peroxide created at the same moment as the uric acid. That is a big if however.

Now let's look at the rest of the reactions it catalyzes:

  • Xanthine oxidase can also act on certain other purines, pterins, and aldehydes. For example, it efficiently converts 1-methylxanthine (a metabolite of caffeine) to 1-methyluric acid, but has little activity on 3-methylxanthine.[8]
  • Under some circumstances it can produce superoxide ion RH + H2O + 2 O2
    ROH + 2 O2− + 2 H+.

=> Superoxide is really nasty and a lot worse then hydrogen peroxide, so this XO thing seems to be nasty in too high quantities.

I looked into the role of 1-methylxanthine and 1-methyluric acid:
"1-methylxanthine is the major metabolites of caffeine in the human. The oxidation of 1-methylxanthine to 1-methyluric acid occurred so rapidly that the parent compound could not be detected in plasma, and only low concentrations could be detected in brain. "

=> So this component of caffeine converts *really* well and fast into another component called 1-methyluric acid.

That chemical has many names to make it confusing. See

There it appears that the page on my search function delivered has the name 1-Methyl-3-(2-methylpropyl)-7H-purine-2,6-dione and that is the same as 1-Methyl-3,7-dihydro-purine-2,6-dione as the (2-methylpropyl) part is optional IMO. So that IBMX stuff is very likely 1-methyluric acid, the stuff part of caffeine is converted in very rapidly.

1-methyluric acid or very likely IBMX has properties:
IBMX (3-isobutyl-1-methylxanthine), like other methylated xanthine derivatives, is both a:
  1. non-competitive selective phosphodiesterase inhibitor[1] which raises intracellular cAMP, activates PKA, inhibits TNFα[2][3] and leukotriene[4] synthesis, and reduces inflammation and innate immunity,[4] and
"1-Methyluric acid (1-U) is a major metabolite of caffeine and theophylline with antioxidant activity that protects molecules such as low density lipoproteins (LDL) from oxidative modifications."

=> Now that would indicate why I do well on caffeine and even use it daily in moderate quantities at night in order to sleep better. It contains a component that reduces inflammation and innate immunity (as in unspecific, against nothing in specific, immune reaction as seen in ME) and is an anti-oxidant. As a side, it uses / keeps busy part of noxious catalyst XO from producing copious amounts of oxidative stress. What's not to like? I do however understand caffeine has its downsides and I am lucky to tolerate the side effects of many stimulants very well. So that may be the breaking point where some patients fare well with stimulants and others get even more "hyper".

While I'm into it, it gets better. I described like some other ME patients before that "chocolate is a medicine and should be refunded by insurance". I did however add: half of the time it clears up my head, the other half it makes things a lot worse. The latter seems to be digestion induced.

So I did find:

"Caffeine and theobromine are the most abundant methylxanthines in cacao and their physiological effects are notable. Their health-promoting benefits are so remarkable that chocolate is explored as a functional food."
"Recent interest on these compounds derives from their antioxidant properties."
"In fact, flavonols inhibit lipid peroxidation and affect production of lipid or lipid-derived molecules regulating the immune response and, recently, dietary cacao has been shown to ameliorate obesity-related inflammation in high fat-fed mice"
"These molecules also seem to be key players in the increase of beneficial gut microbes (e.g., Lactobacilli) and the decrease of less beneficial ones (e.g., Clostridia) that follow cacao intake [3,4]. Hayek [5] has recently revisited data showing that cacao and/or chocolate modifies intestinal flora in the same way that prebiotics and probiotics do."

=> Now that may explain my dual chocloate experience:
  • a really good and powerful "clearing the head up effect" from the methylxanthines
  • a potentially nasty digestion based backlash if you do very poorly on prebiotics and probiotics as they act very similar to those. Maybe in some patients they kick of acetaldehyde production by nasty gut microbes?
To finish it off, again in
Other reactions

Because XO is a superoxide-producing enzyme, with general low specificity,[9] it can be combined with other compounds and enzymes and create reactive oxidants, as well as oxidize other substrates...
...XO has also been found to produce the strong one-electron oxidant carbonate radical anion from oxidation with acetaldehyde in the presence of catalase and bicarbonate."

=> Holy crap: this XO combined with acetaldehyde creates a strong one-electron carbonate radical anion in the presence of catalase and !!!BICARBONATE!!!

=> That's wright, it can indirectly produce a seemingly really powerful oxidative stress molecule from CO2, the thing we ME patients breath out as if our life depends on it (and creating poor oxygen uptake due to the Bohr effect because of it)!!!!!!!

That's wright, add CO2 to water (blood) and you get Bicarbonate (component of sprankling water). Add acetaldehyde from alcohol consumption (many ME patients do tolerate alcohol very poorly) or from gut microbiome production and add ischemia (lack of oxygen, believed to be very common in ME) and you potentially get a storm of oxidative stress raging through our veins. If so, no wonder we "hyperventilate" or "breath like a horse" like our lives depend on it.

At night, blood flow gets worse so ischemia may increase. Now breathing at night can get *very* intense in my case.
During exercise, CO2 levels rise a lot. And all ME patients are intolerant to exercise.

It's bold, but it sounds like this may summarize a *potential* "clear, straight" biological line in my disease:
  • On mothers side of the family, there is a clear pattern of several members having severe gut issues with the potential of it being in part the gut microbiome producing acetaldehyde. This chemical aggresses the gut and poisons body and brain. If so the body may well initiate a near permanent "unspecific = hard to have a clear diagnostic marker" "carpet bombing" immune reaction to gut bacteria. Both this strong immune response blocking good digestion and the damage both acetaldehyde and the gut immune response do to the gut should make nutrient absorption pretty poor.
  • On fathers side there is a chain of several generations of easy increase in uric acid even when drinking only limited amounts of alcohol and I am in at least three generations of males who developed sudden very strong leg weakness. These uric acid levels *may* be the consequence of easy/increased XO production. Note that my uric acid levels are not too high. But having ME I likely have very high levels of oxidative stress so uric acid levels should be low rather then normal if uric acid metabolism were average.
Combine both in one person and if this hypothesis holds sufficiently true disaster is waiting to happen.


Well-Known Member
There is a hereditary component to consider. Some people are genetically deficient in acetyldehyde dehydrogenase. This is common in east Asiua


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There is a hereditary component to consider. Some people are genetically deficient in acetyldehyde dehydrogenase. This is common in east Asiua

Indeed. Acetyldehyde dehyrogenase is chief responsible for decreasing the amount of it in the blood. My mother tolerates alcohol very poorly so she may have that gene and have past in on to me.

Still, If it were the only component then it would affect over a third of Asian people and it clearly does not. Probably many people with own acetaldehyde production and good acetyldehyde dehyrogenase are far less affected then those with own acetaldehyde production and poor acetyldehyde dehyrogenase.

As a person gets ME or likewise, the basic building blocks for the enzyme production (amino acids) come into short supply too. Increasing protein intake however does increase uric acid production. And that may be problematic in combination with acetaldehyde too. I now am shifting some protein intake towards more vegetarian proteins as those tend to produce less purines that are the base to form uric acid. But then again vegetarian proteins can interfere with food intolerances... :-(.
There is a hereditary component to consider. Some people are genetically deficient in acetyldehyde dehydrogenase. This is common in east Asiua
Yes I have given that some thought too but it is not what is the problem with me. I never had any problem with alcohol could withstand it quite well but towards getting ill and when I was very ill I completely developed (partial) alcohol-intolerance. It is LINEAR in amount with the severity of my illness.

When I knew what the cause of my problems were I have tried all sort of things to see how I react to them ( carbs, coca-cola or sugar water, alcohol-free beer all make me more acetaldehyde drunk) but I also experimented how I reacted to alcohol once in a while. At the peak of my illness I could only tolerate about one-third of the amount of alcohol than normal. It becomes more “overwhelming”, you start to feel unwell much earlier, flushing etcetera. However more “euphoria / good ideas” the acetaldehyde part is responsible for that. Overall alcohol reactions are just more severe. Acetaldehyde is an active part of what it means to be drunk. And afterwards feeling bad for a longer time. Also : I think more acetaldehyde seems to be produced from the alcohol itself. But it is not because of a genetic ADH or ALDH problem.

There was also a very interesting comment on one of Cort’s articles and I just can’t find it anymore, if some one remembers this or where it was or the person who wrote it reads this please let me know. Also : that person probably has the same problem as me ! So I hope he reads it. But that person said that if he drank alcohol then quickly after that he felt all kinds of pain sensations in his muscles / body everywhere.

I have had exactly the same effects. Very soon after drinking alcohol all kind of pain sensations in my muscles all over, as if the alcohol “pulls” through my bodily tissues and just strange body effects overall. I never had that before.

To me it makes complete sense that if I already have too much acetaldehyde circulating everywhere you get all these reactions. It makes every living tissue hypersensitive.

I have practically all of the general ME / CFS complaints ( I still have to write some more about that) and we know that the alcohol intolerance is a major component with ME / CFS. Was it not Charles Shepherd who said that he would not even diagnose someone with ME / CFS if there was no alcohol intolerance ? And I already know that my higher acetaldehyde levels are responsible for my ME / CFS and all my complaints.

People wake up. I tell you that I have found something incredibly important concerning ME / CFS.


Well-Known Member
I see this as a potential problem with me too. I don't have the gene for this, at least not the one that is checked on 23&me. (But there is another one that could be checked.) But the first part if this thread described me perfectly. I do not tolerate alchohol and a very tiny amount makes me ill very fast and consequences last a long time. I think there is something worth exploring here.


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The Pivotal Role of Aldehyde Toxicity in Autism Spectrum Disorder: The Therapeutic Potential of Micronutrient Supplementation.

Hi, you may more then appreciate following link between histamine and acetaldehyde.

We have been working around MCAS and Issie kept coming back to the histamine question. It appears that histamine reacts relatively strong with acetaldehyde, making histamine release in case of excessive acetaldehyde build up potentially an additional detox pathway.

"AA was found to have much higher reactivity towards histamine than towards indoleamines. For example, when a reaction mixture of AA (1 mM) and histamine or tryptamine (5 mM) in 0.1 M phosphate buffer (pH 7.4) was incubated at 37 degrees C for 24 h, AA decreased by 11% in the case of tryptamine, while in the case of histamine, it decreased 88%."

See Figure 1! and also figure 2.
=> Info points to this route to be potential significant under physiological conditions.

Since we've also looked into the connection histamine-acetaldehyde-methylation
As histamine *might* offer a good additional acetaldehyde detox route, the body *could* try and block the typical histamine removal route in case of dangerous acetaldehyde build up, namely methylation, by trying to block methylation. If so, that would interfere with major other detox pathways and potentially with gene expression of countless genes themselves.

Still early ideas, so still plenty of checking and referencing needed. No solid science yet.


Well-Known Member
Since alchohol can cause such a strong mast cell response, it makes sense that there is a connection with histamine. That sent us to exploring WHY. Dejurgen remembered this thread and the connections with acetaldehyde and alcohol. Leading us into research with histamine.

I'm attempting a different way of treating my MCAS and it's NOT with blocking histamine. It's actually by adding it. And I am close to getting it regulated and figured out. (Bayard actually is who turned me on to this approach of using histamine as a support and to regulate receptors. He has a thread on this forum about it.) There is still tweaking to do, but getting closer.

Will be interesting to get more research and science on histamine and acetaldehyde and see the connections.
I see this as a potential problem with me too. I don't have the gene for this, at least not the one that is checked on 23&me. (But there is another one that could be checked.) But the first part if this thread described me perfectly. I do not tolerate alchohol and a very tiny amount makes me ill very fast and consequences last a long time. I think there is something worth exploring here.

Yes Issie it all makes perfect sense to me that these things happen if a person has already got an acetaldehyde problem. There has been some talk about whether the alcohol intolerance or at least strange reacting to it gives a clue to the cause of ME/CFS. For me personally there is no doubt about that because all my symptoms are directly related to the amount of acetaldehyde that is produced in me. But for the most part this whole phenomena stays quite stable so once you have it you stay ill at some sort of level and you walk around with it without knowing that cause. Also without surprisingly little outward visual aspects or digestive tract issues ! It is a very " hidden" illness and in some way you could say I got lucky that it got so much out of hand with me that I found out what caused it, other people just walk around with it without knowing.

Did you develop this strange reacting to alcohol when you got ill compared to the past ? (don' t know your illness history)

The Pivotal Role of Aldehyde Toxicity in Autism Spectrum Disorder: The Therapeutic Potential of Micronutrient Supplementation.

" Autism is consistent with aldehyde toxicity"......

Yes I had seen that one and it is also about the only thing you will find online about acetaldehyde + autism. Nothing has ever been done with it. Pubmed.... nothing. They have seriously overlooked something I tell you !

I have not been feeling that well for quite some time for all kind of reasons not only illness. I have not written much I have complete writers-block a lot of the time, just can' t get anything done can' t write a single letter I just want rest. It seems quite common though in ME/CFS where people suddenly stop blogging and such, they just can' t bring themselves to do it anymore, so I am certainly not alone in this. Just so you know that I cannot give long responses but it is nice to see some renewed interest in the acetaldehyde stuff, please chat away.
I have some plans we will see how it works out.


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@AcH influenced , I've never been a big drinker and when I tried, it didn't take much and I was affected. Then the after affects were not worth a very brief mellow. The after affects lasting a long time......of not good. Not a hangover, but just a general very unwell feeling. Always tried to blame it on the substance it was made from. And then mast cell issues from alcohol triggering that.

And you are not alone with having writers block or just feelings things are not coming to you as they should. Many of us have this "brain fog" and over stressing our brains cause the fatigue to be worse. So, chime in when you can.

Would like to hear your ideas!


Well-Known Member
@AcH influenced , do you know why your levels are so high? Have you gotten them down since you wrote this? Obviously you aren't feeling much better, with your last comment.


Active Member
For me personally there is no doubt about that because all my symptoms are directly related to the amount of acetaldehyde that is produced in me.

Just curious, how can you possibly be sure about this? We know almost nothing about ME/CFS, so to attribute any symptom by virtual certainty to one particular issue seems to me unwise. Apologizes in advance if brain fog caused me to miss the part where you link your issue to acetaldehyde, but symptoms like generally feeling worse after eating carbs and sugar are the rule rather than the exception in ME/CFS. I and several other people suffer from this and I never saw any theory or even hypothesis linking these ME/CFS symptoms to acetaldehyde.

As a side note, in Scandinavia there is a slow-release L-cysteine supplement that is marketed for alcohol users and those with increased risk of stomach cancer. Apparently cysteine binds to acetaldehyde in the stomach, which should in theory reduce symptoms and this supplement also has some science behind it. So if you consume carbs or alcohol, it could be an interesting experiment to take L-cysteine with it and see if it mitigates the side effects.
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Dejurgen and I research together and we are looking more closely into this idea. There is a lot of information out there that too high levels of acetaldehyde can be attributed to. Someone having lab results showing high and "symptoms " connected to that is worth exploring in my book.

There are several reasons why a person can have high levels and they can be addressed. But not easily addressed. It would take diet change and microbiome changes and would be a bit of a challenge. But is probably something that could be done with great effort.

There are actually several supplements that could be of benefit. But we want to experiment with them before suggesting them. Will post more later.
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Active Member
Forgot to link, here is the study I mentioned about L-cysteine. 200 mg slow-release L-cysteine, which seems like a fairly low dose, reduces gastric acetaldehyde concentration by 68% after alcohol intake, which should be pretty significant.


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Forgot to link, here is the study I mentioned about L-cysteine. 200 mg slow-release L-cysteine, which seems like a fairly low dose, reduces gastric acetaldehyde concentration by 68% after alcohol intake, which should be pretty significant.

Thanks for the link. Interesting when reading is the following:
"Objective: To assess gastric production of acetaldehyde and its inert condensation product, non-toxic 2-methyl-1,3-thiazolidine-4-carboxylic acid (MTCA), after alcohol intake under treatment with slow-release L-cysteine or placebo."

That mechanism is not that unsimilar to the reaction of histamine with acetaldehyde, making histamine a possible candidate for a tool to remove acetaldehyde from where it is released. Or, like said before, excess histamine response could be an attempt of the body to remove excesses of toxic acetaldehyde.

Excess histamine release goes hand in hand with MCAS, strongly associated with not only POTS but likely also with ME. I learned to recognize the symptoms better thanks to Issie's guide. The difference with POTS is that in ME there seems to be lower but more frequent bursts of it. I sort of sense they might be related to PEM and there is some preliminary science pointing to this. Still a lot of IF's.

So I agree, AcH influenced may not be 100% certain, but he may have found a crucial piece of the puzzle. Issie and I came from a different angle to it being a very real possibility.

Note: dietary acetaldehyde may not be the main problem if you don't consume much alcohol. Very high ROS within cells can destroy the lipids in the walls of cells and mitochondria and create plenty of acetaldehyde in this way. The reaction of ROS with lipids (PUFA) is a well known source of acetaldehyde. And excessive ROS has more then once been linked with ME.

Edit: Note: Having H. Pylori may complicate things. What protects our stomach may also protect these buggers. Sometimes fighting this disease seems like a rigged game with us on the losing end.
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Alright I am giving it a try again and type something I am feeling slightly better we'll see how it goes I really hope I have the energy to do it. I had strong urges to respond to some of the discussions following some interesting news articles / topics covered by Cort lately wanting to say "look I know why that is !" but I just could not bring myself to do it at that moment. Especially the topic about sleep.

So everyone who wants to know more about the relationship between acetaldehyde and sleep please take a look at what I have written about it on my blog

My brain symptoms post might also be interesting to read about. Why do people with ME / CFS have such weird brain symptoms ? Why do they become so dysfunctional ? And we all know that it is not psychological right ? But the acetaldehyde influence can explain that. It amplifies emotions, makes you hyper-sensitive to everything, is an anxiety producing substance, gives you brain fog and so much more. It is a true "drug" and although a very interesting one it can make you truly dysfunctional in so many ways. The thing is that the acetaldehyde is a good complete explanation for both the physical and brain problems together, it does both.

I read so many interesting responses describing people's experiences following Cort's articles that match my own exactly but I already KNOW that it is the acetaldehyde problem that is causing all that. There can only be two possibilities :

- I have something else that mimics ME / CFS
- I have the same thing that at the least a whole lot of you have. Maybe not all, but many.

So it is worth taking it seriously. I am absolutely sick and tired of seeing all the suffering of everybody and seeing it all continue with no results of research getting anywhere so I think it is about time now to start figuring out how we can find a laboratory that can measure blood acetaldehyde levels accurately. It's a chance that we should take, only then we will know. Do what I did but then a bit better, and maybe we will actually get somewhere for a change.

More later about this.
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> Issie and dejurgen I am curious to what you come up with concerning supplements that may help in general. As I have said I have tried several supplements to address the excess acetaldehyde but never had any results. In fact I went quite a step further and even tried D-peniccilamine that they have tried on lab rats in the alcohol research to try to find out about the nature of acetaldehyde. Here is just one example : (With a lot of difficulty I got hold of that stuff through a vet believe it or not. The things you have to do....)

I tried to "scavenge" the acetaldehyde away with the D-peniccilamine and see if I would notice improvement, however this stuff is definitely not risk-free, the dosage per weight that they use in these lab rats is a whole lot more than I am willing to take and after 1 pill I chickened out because I didn't notice any difference. In general and also with supplements that are possibly risky if I don' t see any results with something like double the dosage and I still don't notice anything I leave it and move on.

It is also a band-aid of course, you do not really solve the acetaldehyde production in the first place.
But I don' t want to sound too negative so don't let all this discourage you in any way and people with ME / CFS need all the help they can and every improvement is welcome, I hope you find something that seems to help.

There is however one very interesting medicine that I came across that I am actually very interested in myself to maybe still try out in the future if I can get hold of it and that is Metadoxine The very interesting thing about it is that there is anecdotal evidence that it might improve ADHD symptoms you really need to read about it all it is a very interesting medicine. Maybe this would improve ME / CFS symptoms if it would make the acetaldehyde levels less ? I find absolutely nothing when googling ME / CFS and Metadoxine.... I think nobody has ever tried it ! It is a very safe medicine (and very cheap too) so I think even an alternative-medicine doctor would have little objections to prescribe it to try out I think.

Who knows if it would help with ME / CFS symptoms ? Stranger things have happened we might get lucky once in a while. So.... who is going to try this out ?

I would like to point out that the endogenous acetaldehyde production problem might not always follow the same rules exactly when comparing it with things we already know from alcohol research.

Genetic differences in how people handle alcohol also makes no difference I think. It might not even work the same with all the ALDH stuff and such. You would also think that the liver would get rid of the endogenous acetaldehyde but this does NOT happen ! There is also no liver "over-burdening / overwhelming" process happening or so (this is very important to understand).

Something weird and different might actually be happening instead and I have a hunch that there is a special binding process going on with the blood that may not be the same process that would happen if someone drinks alcohol, so that is definitely something to keep in mind with all of this.

The acetaldehyde papers I promised :

Slightly older but interesting for learning some history about acetaldehyde :
"Role of acetaldehyde in mediating the pharmacological and behavioral effects of alcohol."
pdf :

Very recent (2017) and has not changed since :
"Mystic Acetaldehyde: The Never-Ending Story on Alcoholism"
pdf :

You will find lots more of course online but these are sort of reasonably readable. If someone wants to understand what the possible actions of acetaldehyde are on the brain these are definitely the papers to read.

Yes, "mystic acetaldehyde" is correct... because the interesting thing is that after all this time and millions of people getting drunk everyday they still do not really understand acetaldehyde completely on its own and there are still a lot of open questions about it up to this day.

But I can tell you from my own experience that it gives exactly all of those ME / CFS brain symptoms that people have described !


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@AcH influenced , thanks for all the info. I have already found some possible connections with what you posted.

As for the medicine you listed. Have you tried B6 or P5P? As it appears it is a combination of those mixed. Has some sort of properties to GABA too. Which may work on glutamate receptors. And tame those down too. There is a lot of articles saying B6 or forms of it, will take acetaldehyde down. I have tried it and it gave me very vivid dreams with restless sleep. Almost a type "narcolepsy light" experience. I thought for sure it would be a help. But, either it was wrong form for me or, or, or......still working on that one. Just had another possible connection brought to my attention. (Thanks Meirav.) Working to sort that and find connections and if it fits with what we are thinking.

Thanks for the links. I do believe I got another WHY sorted for myself. And I am seeming to have some good response from what I'm doing for this. We are trying to work the science out and then have our experiments of solutions work for both of us and not just one or the other. Having wonky genes is causing me to have to find work arounds. Whereas, dejurgen seems to be going more smoothly along than me.

This isn't our only tweak, we have found other connections.

More to come.......


Active Member
Hi @AcH influenced - you mentioned in one of the comments that your sensitivity to the sun waxes and wanes in relation to acetaldehyde. I can relate to this -
I recently learned this can be a sign of vitamin B6 toxicity deficiency. Have you ever had your blood levels checked for it?
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