Thread by @UntoNuggan

[food]

I've been doing some more research on "why does my body sometimes just start violently rejecting basically every food" and my mystery hypoglycemia

And I wanted to share some of what I'm learning about inflammation (eg from MCAS), the autonomic nervous system, and enzymes

As ever, I will probably need to take intermittent rest breaks while writing this thread

First off, what even are enzymes

Enzymes are handy little chains of amino acids, and life forms like humans, plants, and bacteria all have them

Enzymes are basically used to convert one nutrient into something else our bodies need

So for example, if you eat protein, then a category of enzyme called a "protease" will break the protein down into individual amino acids

And additional enzymes will combine those with other nutrients (eg zinc, iron, etc) to turn them into neurotransmitters or whatever

Amylase enzymes break down carbohydrates (I know this name doesn't make etymological sense, it's a historic nod to the scientist who did a lot of early research on enzymes)

Lipase enzymes break down fats (lipids)

In general, the -ase suffix at the end of a word = enzyme

Also, whatever comes in front of -ase in the enzyme's name indicates the specific compound that the enzyme acts on

And possibly also the mechanism of how it does that

So for example, histidine decarboxylase:

The -ase part tells us this is an enzyme

It breaks down histidine

And it does so via decarboxylation, which involves removing a carbon atom

en.m.wikipedia.org/wiki/Decarboxy…

[medical diet]

The reason I mention histidine decarboxylase is that it's the enzyme that ends up creating histamine in some aged/fermented foods

And so anyone familiar with a low histamine diet for MCAS probably also has some experience with it

https://twitter.com/UntoNuggan/status/1546144262886199297?t=3N1WxFw9Y_8TQ1PfRAi_KA&s=19

Honestly when I was learning about enzymes, I found I actually knew more about them than I realized

I just wasn't thinking about them in terms of "these things are all enzymes"

For example, lactose intolerance typically* happens when people's bodies don't make enough of the lactase enzyme

And so their bodies can't break lactase down, causing Digestive Woes

(*I say typically because apparently some people don't make lactase, but digest dairy ok)

Or here's another thing:

You know how some people need a really high dose of a medication for it to do anything at all?

And other people can only tolerate the most tiny dose, and it's somehow effective even though it's miniscule?

This is probably because of enzymes

The amount of enzymes your body makes + releases dictates how fast it can process something

Lots of enzymes? Fast metabolism of food and meds. They wear off quickly.

Not so many enzymes? Slow metabolism of food and meds. Absorbing a lot at once is not really a thing.

Why do some people have all the enzymes, and other people not so much?

Well, it seems like it's a combination of genetics (nature), and also a lot of environmental factors (nurture)

There are actually some genetic tests now that people can get to see if any genetic mutations that affect the enzymes that process prescription medications

(Unfortunately they're typically not covered by insurance)

mayoclinic.org/tests-procedur…

Many medications also act directly on enzymes themselves

For example, a medication I was taking for my horrible headaches (from idiopathic intracranial hypertension): Diamox

Diamox is in a class of meds called a "carbonic anhydrase inhibitor"

Carbonic anhydrase is an enzyme that helps break down water and carbon dioxide, and turn them into bicarbonate

(Bicarb gets used in the small intestine, and to help regulate our bodies' pH balance)

A carbonic anhydrase inhibitor... inhibits that enzyme, or slows it down

There's also a type of medication called an MAOI, used to treat depression

(And also present in some supplements, like Luteolin)

This stands for "monoamine oxidase inhibitor"

semanticscholar.org/paper/Luteolin…

The names can get kind of overwhelming, but the short version is that monoamine oxidase breaks down tyramine

Slowing down the breakdown of tyramine leads to more tyramine in the brain, which affects your neurotransmitter levels and can help depression

mayoclinic.org/diseases-condi…

Unfortunately, slowing down the breakdown of things like carbon dioxide or tyramine

Affects the whole body, not just whatever system your doctor is trying to treat

So it's possible to get basically a build up of Too Much Tyramine that is Very Bad For You (toxic)

[medical diet]

So if you're taking a medication like an MAOI, that slows down the enzymes that break down tyramine

It's important to avoid consuming Too Much Tyramine, or it can make you very sick

[medical diet]

Popping back over to genetics, it's also possible to have a condition called Tyramine Intolerance

Where basically your body just doesn't make many enzymes that break down Tyramine

So people have to be careful that they don't eat too much

roguescientist.co/tyramine-intol…

Key things to note:

- enzyme levels can be affected by genetics, meds, and other environmental factors

- they help determine your metabolic rate

- lack of enzymes (eg for lactose) typically leads to some flavor of "intolerance" that can make you feel terrible

Gotta take a break for a bit, back later with more on other environmental factors that can affect enzyme levels (and maybe cause intolerances to benign things)

Also: what happens if your body makes Too Many Enzymes?

Spoilers rest break is going to be longer than planned because I just spent twenty minutes trying to figure out where I shoved my phone in a haze of brain fog, and that means it's time for mandatory rest

Ok back for a bit, let's start with "what happens when your body makes Too Many Enzymes?"

Spoilers: it is kind of horrifying

Basically if you have too many pancreatic enzymes or for some reason they get trapped in the pancreas (eg bile duct blockage)

Then the enzymes can, um, basically start digesting the pancreas itself

This seems to be a problem in pancreatitis, or inflammation of the pancreas

"The predominant paradigm for pancreatitis is that these enzymes, particularly trypsin, become inappropriately active within the acinar cells themselves or in their immediate microenvironment, leading to autodigestion, necrosis and inflammation."

ncbi.nlm.nih.gov/pmc/articles/P…

The acinar cells are the part of the pancreas that makes digestive enzymes

Our bodies also make digestive enzymes in the small intestine

And the gut microbiome has its own set of enzymes that are very useful for digesting things we don't have enzymes for (like cellulose)

Western medicine has sort of divided the pancreas into two specialties:

The endocrine pancreas, that makes hormones like insulin

And the exocrine pancreas, that makes digestive enzymes etc

But obviously these things are interrelated

Endocrinologists typically are the specialists for the endocrine pancreas

And apparently the exocrine pancreas falls under gastroenterology? Although I have yet to have a gastro actually mention it to me, and the gastro I found who seems familiar with it is in another state

[food]

Back to the old pancreatic enzymes for a second

Due to the whole "too many enzymes can potentially damage the pancreas" thing

It's kind of important for enzyme production to be dynamic, and change in relationship to what we're eating

[food]

I don't know if you've ever been vegetarian, but there's a thing that can happen when you don't eat meat for awhile where your body...stops making the enzymes to digest meat

(And also the microbiome changes, too)

[food]

It's possible to reintroduce meat if you stop being a vegetarian, but it's important to do so slowly

Because your body doesn't have as many enzymes for meat proteins, so you metabolize them slowly

And it's possible to eat too much for your body to process

"Exocrine pancreatic adaptation to dietary changes has been observed in a variety of species (15, 169). The content and secretion of the digestive enzymes...change in proportion to the dietary content....over 5-7 days."

pancreapedia.org/reviews/pancre…

[food insecurity]

Additionally, there's a lot of evidence that malnutrition can cause chronic, long-term changes to pancreatic function

Including both the part that makes insulin, and the part that makes enzymes

[food insecurity, ED]

"Famine survivors studied decades later showed ongoing impaired glucose tolerance.... similar findings from anorexia nervosa, famine survivors and poverty- or infection-associated malnutrition...lend credence to results being due to malnutrition itself."

“Association of Postnatal Severe Acute Malnutrition with Pancreatic Exocrine and Endocrine Function in Children and Adults: a Systematic Review.” British Journal of Nutrition, vol. 129, no. 4, 2023, pp. 576–609., doi:10.1017/S0007114522001404.
cambridge.org/core/journals/…

How do our bodies know how many enzymes to make, and when to release them?

Well, folks with #Dysautonomia are going to love this part

Signals from our friend the vagus nerve are involved in signaling that it's time to release the enzymes

It's kind of hard to study the exocrine pancreas and what makes it function, because Western medicine likes to isolate variables

And there's so many factors involved in pancreatic function that it's hard to isolate variables and not have those changes mess with the outcome

Anyway, a probably incomplete overview of things that affect the exocrine pancreas:

- autonomic nervous system
- inflammation
- acid/base balance, especially including stomach acid
- oral microbiome
- diet/food insecurity
- gut motility
- meds (eg antacids, anticholinergics)

So looping back to my own "why did my body suddenly stop digesting food" experience

It started during a time when literally everything on the list above was happening, due to an unfortunate combo of all the chronic illness problems happening at once

Unfortunately, we don't have a lot of affordable + non-invasive ways of testing what enzymes our pancreas (and also the small intestine) are currently making

It's a lot of info, so I'm just going to link this thread for details about enzyme testing

https://twitter.com/UntoNuggan/status/1631807973344329728?t=9r1tVOuVVHXVSNAC6sTA_A&s=19

There is also a thing called Exocrine Pancreas Insufficiency (EPI), which is basically the more extreme version of "your pancreas isn't making enough enzymes"

They measure it by testing fecal elastase levels, an enzyme that survives the digestive tract

I am still learning more about Exocrine Pancreas Insufficiency, but I think it would be... unfortunately very easy for someone chronically ill to develop

It does seem to overlap with autoimmune conditions, and also microbiome issues like SIBO

medpagetoday.com/gastroenterolo…

The treatment for EPI is typically pancreatic enzyme replacement therapy (PERT)

I have been tempted to DIY this just to see if it would help? But also, I'm a little wary of causing more problems if I just dump a bunch of enzymes into my system if I don't actually need them

What seems to be helping me is sort of a three part technique:

1. Reducing inflammation, autonomic issues, and other factors that negatively affect enzyme production

2. Slowly reintroducing foods to maybe convince my body to make more pancreatic enzymes

3. Using cooking methods that basically rely on plant or bacterial enzymes to start the first phase of breaking down food, so my body doesn't need as many of its own enzymes to actually digest things

That is honestly like...a whole dissertation or book or something

But here are some examples of using enzymes in cooking to make it easier to digest food:

A. Meat tenderizers / marinades

sciencelearn.org.nz/resources/1945…

B. Soaking grains/nuts/beans (basically any seed) can start the germination process, which activates a whole bunch of enzymatic reactions

That decrease a lot of plant defenses we can't digest (eg lecithins, phytic acid, etc)

https://twitter.com/UntoNuggan/status/1505341551458893831?t=4z0l1YFoyCJbYtlTJh1zaQ&s=19

C. Lactase enzymes from the bacteria in yogurt can help people who are lactose intolerant actually digest yogurt made from cow's milk

academic.oup.com/ajcn/article/9…

I have a lot more thoughts but this thread is really long, and also I am tired, so I'm going to go rest for a bit and come back another day

P.S. almost forgot, there's a whole section of the hypoglycemia diagnostic flow chart dedicated to genetic enzyme deficiencies, like hereditary fructose intolerance

Acquired enzyme deficiencies like EPI can also cause blood sugar problems

medicalnewstoday.com/articles/exocr…

Here's some information on testing for genetic enzyme deficiencies that can cause mystery hypoglycemia

https://twitter.com/UntoNuggan/status/1623731559080550403?t=DdDGHmHyAmNTzgAHHVPuXw&s=19