Incomplete digestion of food (and possible malnutrition) due to dysautonomia?

[Pyrrhus]

Incomplete digestion of food (and possible malnutrition) due to dysautonomia?​

For years, I have wondered why nutrients in a purified supplement form seem to have much stronger effects on me than the exact same nutrients in food form:

I tried a 150mg dose of malic acid once.

It gave me a brief energy boost, followed by a 2-week crash. But that's just me.

The weird thing is that there is 500-2000mg malic acid in a single apple, but I can eat apples without any problem. This is just an example of a larger observation I have made: purified nutrients in supplement form often have much stronger effects on me than the exact same nutrients in food form. Differential digestion or absorption?

There are a couple of possible explanations that could clarify this observation. But I keep coming back to one possible explanation: dysautonomia.

1) In order for food to be properly digested, the pancreas and gall bladder must release digestive enzymes into the intestines to break down the food. The release of these digestive enzymes from the pancreatic duct and the bile duct is controlled by the vagus nerve:

2) The vagus nerve also controls the "Sphincter of Oddi", which connects the pancreatic duct and the bile duct to the intestines. The Sphincter of Oddi opens or closes to allow the release of digestive enzymes into the intestines:

3) Therefore, if there is dysfunction of the vagus nerve, there could be insufficient release of digestive enzymes into the intestines. This would result in incomplete digestion of food, and over a long period of time, could possibly lead to malnutrition.

4) Since the vagus nerve is a part of the autonomic nervous system, such a dysfunction of the vagus nerve is a form of dysautonomia.

 

[Wishful]

That makes sense to me. I liken ME to a defect in a CPU, in some commonly-used function. It's not enough to totally crash the computer (death), but it's effects show up in seemingly random malfunctions in software. Think of Intel's Pentium CPU which had a bug in its arithmetic unit, which gave errors in certain division calculations. The computer might run most of its functions normally, but if it was controlling a chemical factory, for example, you'd get some processes with too much or too little flow, or the wrong ration of chemicals.

ME seems to cause functional errors in areas depending on the individual. Digestion is really quite complex, and small errors can cause noticeable symptoms. The secretory responses to chunks of apple will certainly be different from powdered chemicals. The sensory feedback to the brain would be different too, which would then send different signals apart from the vagus nerve.

 

[Booble]

Love the comparison to the Pentium CPU!

Interesting stuff, Pyrrhus.
That vagus nerve does seem to be a prime contributor to various health challenges.
I get that weird that thing where I can be feeling perfectly fine (my level of fine) in the morning and then I go to the bathroom to make a poop and suddenly feel awful for 1 - 3 hours afterwards. Word on the street is that has something to do with the vagus nerve.

 

[Wishful]

and then I go to the bathroom to make a poop and suddenly feel awful for 1 - 3 hours afterwards.

Do people downwind feel awful too?

 

[Pyrrhus]

I go to the bathroom to make a poop and suddenly feel awful for 1 - 3 hours afterwards.

Just in case you haven't already seen it, there's a discussion on that weird symptom:

Feeling exhausted after bowel movement
https://forums.phoenixrising.me/threads/feeling-exhausted-after-bowel-movement.42146/

 

[Booble]

Thanks, Pyr. That was interesting reading.

I lean toward a few different theories:
- low blood sugar tied into some unknown mental processing. I have a sense that my body thinks that a full colon means I have the nutrients I need and an empty one means trouble. Alert. Alert.
- vagus nerve stimulation some how alerting the brain to that same mental process.
- some connection to MCAS histamine release.

I guess I really am "anal retentive." My body likes keeping my poop inside!

 

[bob800]

For years, I have wondered why nutrients in a purified supplement form seem to have much stronger effects on me than the exact same nutrients in food form

My attempt to rationalize this is that supplements can achieve supraphysiological concentrations locally in the stomach when the capsule initially dissolves. If something in the stomach is truly the cause of some ME/CFS (like re: Chia's enterovirus hypothesis), then this can help explain why even supplements that are not very bioavailabile still have an effect: because they're being dumped directly onto the target tissue.

I'm skeptical that significant nutritional deficiencies are a very common feature of ME/CFS, since studies usually contract this (at least for the most part). But I think it's very possible there might be localized deficiencies, for example in stomach tissue, caused by some sort of localized inflammation.

 

[Pyrrhus]

supplements can achieve supraphysiological concentrations locally in the stomach when the capsule initially dissolves

Good point about the potential for nutrients to act directly on the intestinal cells themselves.

I would point out that, in addition to the "incomplete digestion" hypothesis, there are also plausible hypotheses related to absorption, rather than to digestion:

• The "supraphysiological absorption" hypothesis would state that purified supplements are over-absorbed because the body's intestines have evolved to optimally absorb nutrients only in food form, not nutrients in purified supplement form.
• The "sub-clinical gastroenteritis" hypothesis would state that sub-clinical inflammation of the intestines prevents absorption of nutrients from food more than it prevents absorption of purified nutrients.

I'm skeptical that significant nutritional deficiencies are a very common feature of ME/CFS, since studies usually contradict this

I'm not sure which studies you're referring to. Some small studies have looked at vitamins, minerals, and amino acids, with varying results. Some of those studies have found deficiencies, but not all. To date, no large definitive studies have been performed on a well-characterized cohort of patients.

And remember that vitamins, minerals, and amino acids are only one part of nutrition. For example, digestive enzymes are needed to absorb certain lipid nutrients such as phospholipids. And a deficiency in phospholipids has indeed been observed by independent research teams.

More rigorous metabolomic research may uncover clearer deficiencies, but then the question becomes: is the deficiency due to poor nutrition, or is it due to the disease process itself?

I think it's very possible there might be localized deficiencies, for example in stomach tissue, caused by some sort of localized inflammation.

Yes, the occurrence of localized nutrient deficiencies due to localized inflammation is indeed a well-established phenomenon.

 

[bob800]

I'm not sure which studies you're referring to.

Here's one for instance: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0176631

And remember that vitamins, minerals, and amino acids are only one part of nutrition. For example, digestive enzymes are needed to absorb certain lipid nutrients such as phospholipids. And a deficiency in phospholipids has indeed been observed by independent research teams.

Good point, the Ron Davis metabolic research for example shows this clearly: https://www.pnas.org/doi/pdf/10.1073/pnas.1607571113
(Interestingly, I had a standard serum amino acid panel done by Quest, and the pattern matched that reported by Davis. Arginine and phenylalanine were out-of-range high, and the only one that was below-range was ethanolamine, a phospholipid)

More rigorous metabolomic research may uncover clearer deficiencies, but then the question becomes: is the deficiency due to poor nutrition, or to the disease process itself?

Yeah exactly - to clarify my initial skepticism, my speculation is that significant malabsorption isn't a common feature of ME/CFS (except for those with severe autonomic dysfunction / gastroparesis). But I think it's reasonable that the disease process might abnormally drain some specific types of nutrients, e.g. phospholipids like you mention. Studies of intracellular nutrients would probably find more widespread deficiencies, but I would argue this is definitely a result of the disease process and not an issue with normal intake/absorption.

 

[bob800]

• The "supraphysiological absorption" hypothesis would state that purified supplements are over-absorbed because the body's intestines have evolved to optimally absorb nutrients only in food form, not nutrients in purified supplement form.
• The "sub-clinical gastroenteritis" hypothesis would state that sub-clinical inflammation of the intestines prevents absorption of nutrients from food more than it prevents absorption of purified nutrients.

Relevant article you may find interesting (or maybe have already read):
How peptic ulcer disease could potentially lead to the lifelong, debilitating effects of chronic fatigue syndrome: an insight
https://www.nature.com/articles/s41598-021-87018-z

I've actually had mild chronic gastritis, despite a very clean diet, for years before developing ME/CFS. It got a bit worse after ME/CFS onset. Endoscopy shows things aren't bad on a macro-scale, but histology always shows inflammation / reactive gastropathy on the microscopic level. And, my B12/folate and amino acid levels are normal, so malabsorption of these things isn't an issue.

I have very similar reactions as you do to malic acid, NAC, etc, that have very fast onset. Hence my temptation to speculate these agents are acting immediately on the stomach tissue when the capsules dissolve, which then (maybe?) triggers some neural signaling cascade. On the other hand, it's certainly possible that the "chronic gastritis" phenomenon is just another downstream effect of autonomic dysfunction, like you mention. And even if serum nutrient levels are normal, maybe the brief peak in their concentration during "supplement over-absorption" is enough to perturb the CFS state.

But I have trouble rectifying this nutrient-centered view of the disease with the fact that non-nutrient substances, such as cimetidine and valacyclovir, have a strong effect that feels roughly like the same "type" of response as I get from malic acid or NAC. Maybe they facilitate cellular uptake of nutrients from the serum, but in that case, it's not the serum level (reflecting digestive absorption) that was the issue.

 

[Violeta]

There are a couple of possible explanations that could clarify this observation. But I keep coming back to one possible explanation: dysautonomia.

That's a very cool conclusion Pyrrhus.

I have been taking Butcher's Broom and tyrosine for orthostatic hypotension for quite some time, (I have to figure out when I started it), and that may explain my improvement in digestion. I hardly ever have undigested food passing through me anymore. Although I don't know if they help via the vagus nerve, I think I'll see what I can find.

This brings to mind Van Elzakker's vagus nerve theory and that an infection is involved.

Have you found anything that seems to specifically help the vagus nerve?

Yikes! "If the vagus nerve is unable to activate the relaxation signal, the sympathetic nervous system keeps active with the stimulation of cortisol and adrenaline (stress hormones). This means we are living in a more-or-less constant state of fight-or-flight. This state wreaks havoc on your mental and physical health."

Does this mean anything to anyone? My brain isn't working too well. "The vagus was selected as a candidate for this role since it is densely embedded with beta-adrenergic receptors"

 

[Pyrrhus]

I've actually had mild chronic gastritis, despite a very clean diet, for years before developing ME/CFS. It got a bit worse after ME/CFS onset. Endoscopy shows things aren't bad on a macro-scale, but histology always shows inflammation / reactive gastropathy on the microscopic level.

Very interesting, I have heard similar stories from other patients.

And some patients report that they get a colonoscopy/endoscopy and their doctor says "it all looks fine, just some hints of inflammation, nothing to worry about..."

On the other hand, it's certainly possible that the "chronic gastritis" phenomenon is just another downstream effect of autonomic dysfunction

Or it's possible that both gastroenteritis and dysautonomia are independent downstream effects of something else...

I have been taking Butcher's Broom and tyrosine for orthostatic hypotension for quite some time, (I have to figure out when I started it), and that may explain my improvement in digestion. I hardly ever have undigested food passing through me anymore.

That's very interesting. Thanks for sharing!

 

[Violeta]

Alpha-1 adrenergic receptors and secretin
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200670/

Cholecystokinin A receptor (CCKAR) encodes a G-protein-coupled receptor that binds cholecystokinin (CCK) family of peptide hormones and is a major physiological mediator of pancreatic growth and enzyme secretion, smooth muscle contraction of the gallbladder and stomach, and secretion from gastric mucosal cells in the ...

α1-adrenergic receptors are G-Protein Coupled Receptors that are involved in neurotransmission and regulate the sympathetic nervous system through binding and activating the neurotransmitter, norepinephrine, and the neurohormone, epinephrine.

Effects of some alpha- and beta-adrenoceptor agonists were investigated on the isolated rabbit sphincter of Oddi and duodenum.
https://pubmed.ncbi.nlm.nih.gov/6141315/

The vagus was selected as a candidate for this role since it is densely embedded with β-adrenergic receptors and the peripheral endings
https://www.sciencedirect.com/science/article/abs/pii/S1074742705000833

This states that the vagus nerve releases norepi into the amygdala, and I will look to see if I can find something about it releasing norepi or epi to the various areas of the digestive tract.
"University of Virginia psychologists have moved the science of memory forward, reporting that stimulating the vagus nerve, which carries sensory messages to and from the brain, releases the neurotransmitter norepinephrine into the amygdala..."

 

[Violeta]

@Pyrrhus, what do you do for dysautonomia?

 

[sometexan84]

@Pyrrhus You do a good job of formatting your posts.

I appreciate this, as it makes it way easier to digest (no pun intended)

 

[Viala]

@Pyrrhus Could taking digestive enzymes and/or betaine HCl solve this problem?

 

[hapl808]

Effects of some alpha- and beta-adrenoceptor agonists were investigated on the isolated rabbit sphincter of Oddi and duodenum.
https://pubmed.ncbi.nlm.nih.gov/6141315/

The vagus was selected as a candidate for this role since it is densely embedded with β-adrenergic receptors and the peripheral endings
https://www.sciencedirect.com/science/article/abs/pii/S1074742705000833

This states that the vagus nerve releases norepi into the amygdala, and I will look to see if I can find something about it releasing norepi or epi to the various areas of the digestive tract.
"University of Virginia psychologists have moved the science of memory forward, reporting that stimulating the vagus nerve, which carries sensory messages to and from the brain, releases the neurotransmitter norepinephrine into the amygdala..."

This vaguely ties into my own symptom patterns. I've noticed that anything which stimulates a bit of adrenaline seems to cause the worst PEM and reflux. For instance, an annoying but low key customer service call won't do it. But a really fun phone conversation will do it. Same with anything that gets me into 'flow state' like feeling, almost guaranteed to cause reflux and a crash.

I've felt that norepinephrine is involved with my GI symptoms, but I haven't really figured out how to affect that.

 

[Nosferatu80]

@bob800 @Pyrrhus I was thinking about taking malic acid to lower my stomach ph and help my gallbladder, since the side effects are similar to NAC could it be that it is chelating some mineral?