Substantial improvement with (strange) dietary adjustments

Wishful

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I don't think the sublingual route, if it exists, plays a significant role.
I was suggesting it as a test for solubility. Holding water-soluble chemicals in your mouth will get then into your bloodstream, even if you then spit out the food and rinse well. So, this might reveal whether it's a chemical in the food that affects you through the bloodstream, or if the food affects gut biochemistry. If it's fat-soluble, it should show no effect.
 

Wonkmonk

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Happy New Year, everyone!

I made a significant observation:

1. Homemade pita bread made with cold overnight ferment in the fridge and homemade peanutbutter (made right before use)

vs.

2. Homemade pita bread made with only a very short (1-2 hours) yeast-only ferment and homemade peanutbutter (made right before use)

(1) Cause very strong symptoms about 1 hour after consumption, (2) didn't cause any noticable worsening at all.

This is a very interesting result, because it is theory-consistent:

Certain ubiquitous bacteria (one or more) produce metabolic products (one or more) that cause, trigger or strongly contribute to the symptoms during longer fermentation times. That's why these compounds are abundant in the bread fermented overnight but hardly present in the short fermented bread using only yeast.

Now here is what's new: These compounds are very likely fat soluble or fat contributes strongly to their absorption. They are probably not produced from the fat, but it's a solubility/absorption issue. This is because the long-fermented bread with peanut butter or cheese causes strong early-onsetting symptoms whereas the same bread eaten plain causes much less symptoms. It can't be that the compounds are produced from the peanut butter because the short-fermented bread with peanut butter caused much less symptoms or no symptoms at all.

--> From now on, I will make all my bread myself, home-pasteurize the flour beforehand (30 minutes in the oven at 60 C), take measures to shorten the bacterial fermentation time (activate the yeast thoroughly in a separate bowl) and bake it quickly.

Reminder: Yeast fermentation does not appear to cause any symptoms, so these compounds are probably not produced by yeast. This also tells us it's likely a very special metabolic product produced by only certain strains of bacteria, it's not a ubiquitous fermentation product produced by most bacteria present in food like alcohol or lactic acid. It's probably something special.
 

Wonkmonk

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One thing I can't really explain so far with this theory: Cheese, yoghurt, kefir etc.

All of these are long-fermented by lactic acid bacteria and have lots of protein, but they seem to cause very little symptoms when consumed plain even in larger quantities (I took one for the team and checked that).

The only explanation I could think of would be that the bacteria that produce the problematic compounds cannot use lactose as a carb substrate. The same foods made vegan froma soy basis (e.g., soy yoghurt) do cause strong symptoms, presumably because the fiber and starches in the soy beans are a useful substrate for the bacteria.

It's possible, but I am not 100% satisfied with this explanation because lactose is converted into galactose and glucose and all ubiquitous lactic acid bacteria should be able to use glucose.
 

Wonkmonk

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I was suggesting it as a test for solubility. Holding water-soluble chemicals in your mouth will get then into your bloodstream, even if you then spit out the food and rinse well. So, this might reveal whether it's a chemical in the food that affects you through the bloodstream, or if the food affects gut biochemistry. If it's fat-soluble, it should show no effect.
This is a great idea. But can everything that's water soluble be well and quickly absorbed sublingually? I remember for instance that thyroxine can NOT be taken sublingually and that the tablet has to be swallowed so it all goes into the stomach and is available for absorption.
 

Wishful

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But can everything that's water soluble be well and quickly absorbed sublingually?
No, but a limited test is better than no test at all. We have to make do with what experimental methods are available to us. If a simple, easy test does show interesting results, better tests can be done at more cost and inconvenience.

When my ME first started, and I went to a doctor, I assumed he'd order some standard tests, and if those didn't reveal the problem, another level of less often ordered tests would be done, and that might continue for several levels, leaving the most expensive tests for last. I was very disappointed when after the first tests showed nothing, he simply said "Sorry, can't help you."
 

Wishful

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Update on my protein intolerance requiring supplemental arginine: I no longer need the supplementation. Yay! No progress on the grain or legume germ intolerance. I hope that's a microbiome issue, rather than an immune response, because changing immune response is so much harder.
 

Wishful

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One thing I can't really explain so far with this theory: Cheese, yoghurt, kefir etc.
Maybe there's a microbial product resulting from alcohol produced by yeast? You could test that by adding some alcohol to your ingredients and letting it sit for a while before adding the yeast.
 

Wonkmonk

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Maybe there's a microbial product resulting from alcohol produced by yeast? You could test that by adding some alcohol to your ingredients and letting it sit for a while before adding the yeast.
But even extensive yeast fermentation doesn't seem to cause any problems at all. I tried this by drinking a yeast-oat ferment (similar to homemade beer) which I fermented for more than 1 hour at >30 C. It tasted very much like alcohol and didn't noticably worsen my symptoms.

If some other bug used the alcohol produced by the yeast, I would expect that to have happened in that experiment.
 

Wonkmonk

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I think I am not doing well with large meals, especially carbs. I can eat a pound of frozen french fries with few problems, but not two pounds in one meal. Two times one pound a few hours apart seems to work though. I will try to split up big meals into two smaller ones 2-3 hours apart.
 

Dysfunkion

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Ok I have found a trigger but one that doesn't immediately cause chaos upon eating it in a food once. Citric acid as an additive. Lately I've been adding it to my food as it was in that jarred garlic and I know what my reaction to garlic itself is like, the first time I did I didn't notice much out of the norm. Maybe a bit off but it could have been anything. The next day after putting in I felt more blank and out of it followed by extreme neurological sensitivity the next day. Again I just wasn't sure so I tried it again but this time the fish I used was salmon in my rice and veggies which tends to make me feel a bit better the next day so I didn't notice the "tired and wired" as much. The next time I used it which was last night in some Peas and corn I knew it was that stuff because the same feeling came back but much more intensely and today the brain fog and sensitivity is ridiculous. My eyes also burn a bit and my stomach is much more acidic and bloated. For some reason I'm pretty sexually tanked too because of it today and can't really respond to as much. Nothing else has changed but using the citric acid included garlic.

So lesson learned, stay away from all citric acid as it seems to be one of those building reaction ones that can sneak up on me. Does anyone else have a weird reaction to citric acid. Ill make it today but the brain fog coupled with the allodynia flare isn't fun. Maybe my body can't clear it fast enough? There's none of that brain burning feeling though, just caused my CNS and something else to get out of whack.
 

Wonkmonk

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So lesson learned, stay away from all citric acid
Is this just as an additive or also in a natural form. Because naturally, it would rule out almost all fruit and many vegetables like tomatos. Even bananas have a relatively high amount (which surprised me when I learned it).

What about other organic acids (malic acid, tartaric acid, acetic acid. succinic acid)? Is it just citric acid? And is it just the acid in its free form or also e.g., as a citrate salt (like in magnesium citrate supplements)?
 

Wonkmonk

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I think I have to look at choline again as a potential precursor for harmful fermentation products. The day before yesterday, I ate 5 eggs with pasta for breakfast. Then bread and cheese for lunch. The result was strong symptoms and heavy headaches for two days.

Interestingly, on other occasions I felt that I could tolerate eggs with white bread or pasta pretty well. I think the problem was that I at the cheese for lunch with a good amount of fat.

I think the bacteria make something (like TMAO) from the choline and protein in the eggs and the carbs in the pasta/bread, but when I eat that only once, a lot of the fat is absorbed so once the compound is made, it has not much fat for solubility. But when a second high-fat meal comes after it, even if relatively low in choline (like white bread and cheese), the pre-formed fat soluble compounds from the last meal can be absorbed and cause stronger symptoms.

Fat solubility might be a key part of why "meal mixing" causes problems. It may not necessarily be that fat is required to make the harmful compounds.
 

Wonkmonk

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I am always coming back to the same theory:

*Ubiquitous bacteria - probably lactic acid bacteria - produce compounds that are for some reason harmful to me (but good or neutral to healthy people) from protein, carbohydrates and possibly choline.
*These compounds may trigger reactivation of a virus or microbe (e.g., like EBV and butyric acid) or might help the microbe multiply.
*Absorption of the compounds is facilitated or enhanced by fat.
*Other foods may increase absorption, too (e.g., chili, spices or black pepper, which does this with many other compounds like curcumin)
*Some foods for some reason may enhance the harmful effects, e.g., blueberries (possibly due to enhanced tissue blood flow, which would distribute the harmful compounds more widely) or oxalate containing foods (possibly due to crystal formation and micro thrombosis in very small blood vessels - I'm merely guessing)
*Large meals, especially carbs, also cause symptoms irrespective of other factors, possibly because of an oversupply of nutrients in the cells that can then be used by a virus or microbe for reproduction.

It is extremely difficult to find a diet that takes all of this into account. It has to be low oil, low carb, low protein, low choline, low oxalate, small meals and that has to be at least 12 hours before and after each meal, otherwise the precursors can mix.
 

Dysfunkion

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Is this just as an additive or also in a natural form. Because naturally, it would rule out almost all fruit and many vegetables like tomatos. Even bananas have a relatively high amount (which surprised me when I learned it).

What about other organic acids (malic acid, tartaric acid, acetic acid. succinic acid)? Is it just citric acid? And is it just the acid in its free form or also e.g., as a citrate salt (like in magnesium citrate supplements)?
The label on the garlic just says citric acid, I'd bet its just unnatural as cheap as possible origin. I'm not sure on the others besides malate anything makes me extremely fatigued. I haven't had anything with tomato in a while but I suppose I could throw a pizza down the hatch for tasty science and see what happens.

For some reason salmon specifically also helps me a lot but 9nly cooked salmon. I've eaten tons of raw fish in a meal before enjoying sushi sometimes but it specifically cooked salmon that for some reason drastically cuts my brain fatigue levels down but on the rebound I get more of a jittery anxious energy thats less focused but less foggy. Not sure what that implies but it happens every time it in any circumstance from multiple sources. Other cooked fish doesn't do it.
 

Wonkmonk

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Germany
I am always coming back to the same theory:

...
I wanted to add to this: Oil/fat can definitely not be the decisive factor. I once went on a potato-rice diet to check for food allergies, which is basically the most low fat diet on can go on and with that diet, I had some of the most severe symptoms ever.
 

Wonkmonk

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Germany
I have made important observations, which I think pertain to choline as a culprit or contributor for my malaise.

I compared the following meal series, each 3-6 hours apart and once overnight each:

(1) 5 Eggs & white bread --> chesse & white bread --> white spaghetti with 1 tomato --> pinto beans, plain --> blueberries

(2) Pinto beans, plain --> blueberries --> spaghetti with some nutritional yeast --> blueberries --> pizza --> pizza (both times homemeade with white flour, tomato sauce and cheese) --> blueberries

Meal series (1) caused very strong symptoms over about 3-4 days. Meal series (2) caused hardly any symptoms at all.

From a nutrient perspective, both are very similar, with one important difference: Eggs, i.e., choline.

One large egg contains about 170mg of choline, so 5 large eggs (~300g) contain 750 mg of choline.

100g of low-moisture mozzerella contains 14mg of choline. I also used some parm, which is not on the list, so lets assume it's maybe 30-40mg of choline on my pizza. That's a HUGE difference.

https://www.ars.usda.gov/ARSUserFiles/80400525/data/choline/choln02.pdf

Now, here, I am reading that choline absorption is dose-dependent:

"At high concentrations part of it is left unabsorbed. Absorbed choline leaves the enterocytes via the portal vein, passes the liver and enters systemic circulation. Gut microbes degrade the unabsorbed choline to trimethylamine, which is oxidized in the liver to trimethylamine N-oxide." (emphasis added)

https://en.wikipedia.org/wiki/Choline

So my theory is that the unabsorbed choline after larger doses like eggs, whole grains, beans or hummus causes a problem when the choline is then degraded by gut microbes. That would also explain why it seems to help to split my meals into smaller parts with some time in between. Lower choline dose per meal means less is left unabsorbed and available for bacterial degredation.

So the rule would be to avoid high-choline foods like eggs or organ meat and choline-containing supplements altogether and limit meal sizes for any other meals that contain significant amounts of choline (whole grains, beans, meat).

There is a hole in that theory: Why does it seem I also have to avoid fruit (very low in choline) at higher doses? This could be explained if the carb substrate for fruit is very suitable for the bacteria, so choline degradation is faster (before absorption) or more complete/efficient, so less is needed to cause symptoms. According to the list above, bluberries have 6 mg of choline per 100g, so when - as I often do - I eat 3-4 pounds plain as a replacement for one whole meal, that's 90-120mg of choline, which might already be enough that a fair amount of it is unabsorbed.
 

Wonkmonk

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It also remains a mystery why cauliflower rice doesn't cause strong symptoms despite being very high in choline (39mg per 100g). I can eat a huge bowl containing 2 pounds of cauliflower with not much happening, despite almost 400mg of choline. This should be as bad as eggs.

Now, this is interesting from a video from Dr. Greger (I posted this before I think), see 5:24:


People who eat high-choline cabbage-family vegetables make less TMAO from the choline, possibly because a liver enzyme that converts trimethylamine to TMAO is downregulated.

But even with that assumption, there remains a hole in the theory: The same studies say vegans don't make any TMAO at all. I was 100% vegan for weeks and months and it didn't help.

That's why I think if choline is involved, the culprit is not TMAO, but some other degradation product.
 

Wonkmonk

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I have made some observations that largely fit with my theory:

1: Splitting meals into 2 equal portions of not more than 500 calories each 1-2 hours apart (1 hour appears to suffice) reduces symptoms, no matter what the type of food is. Splitting into 3 portions does not seem to help and even be counterproductive (worse than just 2 portions).

Theory-consistent explanation: The substrate (or a part thereof) for bacterial degradation is absorbed rapidly but only up to a point and it takes a while until more can be absorbed. So with smaller meal portions, what is there gets quickly absorbed and is no longer available for bacterial degradation. Then when the second portion comes, absorption capacity is restored and the same amount can be rapidly absorbed again leaving not much for the bacteria again.

I haven't found out what the exact pharmacodynamics is for choline, especially for real-life foods (not supplements), but I could imagine that the most problematic agent is in fact dietary choline.

2: Not drinking any liquid 2-3 hours after meals seems to be helpful. Though not tested yet, I would assume that avoiding foods with watery sauces (which is basically the same as drinking water with a meal) would be a good idea, too.

Theory-consistent explanation: Three possible rationales. First is bacteria thrive in substrates with higher water content (e.g., higher hydration doughs rise more quickly). Second, water dilutes the stomach acid and raises the ph, whereas a lower ph kills bacteria or stymies their growth. Third, the watery part of the meal passes the stomach more quickly and likely contains the nutrients from which the bacteria form the harmful compound(s). It then quickly goes into the small intestine where ph is much higher and the bacterial community is much more numerous and diverse. That's probably bad. We want as much as possible to be absorbed in the stomach.

If this theory is correct, we are in fact looking for a nutrient that can be absorbed to a large part in the stomach and not only once it reaches the small intestine. That box isn't checked for choline, which is absorbed in the small intestine.

https://ods.od.nih.gov/factsheets/Choline-HealthProfessional/

3: Splitting up the meals into two portions doesn't work for multigrain porridge with berries (flakes of multiple grains and water only with freshly prepared fruit jam of various berries pureed with dates for sweetness).

Theory-consistent explanation: The berries and the sugar provide such a good substrate for the bacteria that they work much faster (like dough takes less time to rise with some added sugar) so more harmful compounds are produced even with the smaller meal size.
 
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