Theory of GLP-1 deficiency?

[kib1]

https://youtu.be/hiCxpHDAlbs

This is Nicholas Norwitz, who can get a bit tiring. This is an excerpt:

GLP-1 agonist medications , like Ozempic, mimic a natural hormone (GLP-1) that is crucial for metabolic health. Interestingly, insulin-resistance disorders, including obesity and diabetes, are characterized by GLP-1 deficiency.

So - at a high level - it makes sense to " replace what’s missing " as a form of therapy.

Think about it by way of analogy… if you have hypothyroidism, you treat with thyroid hormone…. if you have adrenal insufficiency… you treat with corticosteroids.

Make sense, right?

But that doesn’t answer the question: What is the CAUSE of GLP-1 deficiency in obesity, diabetes, metabolic syndrome and insulin-resistance disorders?

There have been some hand-wavy explanations in the past, like that “inflammation” harms GLP-1 producing L-cells or that inflammatory T-cells “mop up” GLP-1 in the gut, decreasing bioavailability.

But I like precision… causal pathways… specific mechanisms. Now, FINALLY (!) we have at least one…

These New Data…

These data, published in Nature Metabolism , use a mouse model to demonstrate a causal pathway whereby:

• An obesogenic (Westernized) diet increases levels of the gut bacteria Desulfovibrio .
• Desulfovibrio generates hydrogen sulfide in the gut.
• This hydrogen sulfide overwhelms detoxification mechanisms in the L-cells that make GLP-1, leading to damage to the L-cells’ mitochondria.
• The resulting energy (ATP) deficit in the GLP-1 producing L-cells, leads to a GLP-1 deficit.
• The GLP-1 deficit leads to metabolic dysfunction.

Any thoughts on this?

[Just because I’m being a wordy smart-ass today, hydrogen sulfide certainly overwhelms everything else in the room … ]

And here’s a little kicker, directly from the Nature Metabolism study, which I cannot access beyond the abstract:

Remarkably, blocking Desulfovibrio and H2S with an over-the-counter drug, bismuth subsalicylate, improves GLP-1 production and ameliorates diet-induced metabolic disorder in male mice.

Bismuth subsalicylate = … pepto bismol.

Take pepto bismol. Stop having stinky gas. Cure diabetes …

[CFLBob]

I watched that video today also, and I think you got it but you left out one little thing.

It seems that the Desulfovibrio bacteria that damages the L-cells and that whole chain of causation is also susceptible to a specific fiber and can be reduced by taking a few grams of inulin fiber per day. ISTRC he said 5 grams. I happen to have the Walgreens web page open and did search for inulin fiber. They list inulin “Fiber Good Gummies” as a product. While watching the video my wife said she had seen something, I think a kind of yogurt, that advertised it had inulin in it. Since I Don’t Do Gummies, the yogurt sounds better to me, but I’m sure those aren’t the only options. Can’t be.

[Just_Juju]

Why not just avoid a “westernized diet” altogether and then not have any need to understand the complex science behind what it does and how to fix it?

Sorry just wanted to join in on the smart-ass train. Lol

[kib1]

Lol. It’s true, we seem to have circumvented this with a “non westernized diet”. I just found it interesting, because I do agree with him. I’m not so interested in solutions unless I understand what causes the problem in the first place so I might potentially either avoid it or find a simpler answer (pepto bismol v. Ozempic, you know which one I’m picking!)

If true, it’s useful to know that hydrogen sulfide in the intestines (you know, those eye-watering farts that cause you to sidle away pretending that couldn’t Possibly have been you ) - caused, I would say, by incompatibility between gut biome and diet - could be a causative factor of “western disease”.

[ctviggen]

I happened to be on vacation with a tiny bit of time to kill and saw this.

So, I decided I’d look to see what happened if someone took Inulin as to their GLP-1 levels. Here’s one study, which is one where they look at a ton of other studies:

The Prebiotic Potential of Inulin-Type Fructans: A Systematic Review

As always, it’s complex:

His theory was that you could adjust the bacteria by taking inulin, and that would raise your GLP-1 levels. Not so sure that will work.

On the other hand, I have been testing allulose, which supposedly raises GLP-1. I think this actually does work, though (1) it takes a while (a few hours); (2) it’s not clear how much I have to ingest; and (3) at some ingestion level, I do get some stomach/digestion issues, though I haven’t figured out exactly what level that is. (I have been adding teaspoon(s) of allulose to my normal raw milk/collagen peptides mixture, but I’ll also – sometimes – have some high protein “pudding”, which has allulose in it, but I haven’t figured out how much per serving.)

I’ve been taking allulose at lunch, and have had multiple times where not only was I not hungry at dinner, I ate less. Normally, even if I’m not hungry at dinner, I’ll end up eating the same. Using allulose, I’ve actually eaten less a few times. Not always, but enough times that I think allulose does something.

Now, allulose is also supposed to help with “insulin sensitivity”, so maybe that plays a role. I’m not sure.

But I think hormones like GLP-1 are meaningful, at least to some degree. So, even though I am anti-fiber and prefer to eat a low fiber diet, I ordered some inulin and will be combining that with my allulose to see if there’s an effect.

The problem with the “biome” is – as shown by the study above – the data are all over the map. Some studies have inulin raising GLP-1, but some don’t. And of course, none of these studies were done on people eating low carb/carnivore/keto.

Edit: also note that some of these studies have pretty high levels of inulin/whatever the prebiotic was. I’m starting out at 2.5 grams or so, and might get as high as 10 grams, but I’m not sure. When I started keto, the “in” thing to do was take potato starch and probiotics, to attempt to manipulate your biome. I really had to work up from small (teaspoon) to large (maybe a tablespoon) of potato starch, otherwise horrible gas and other issues arose. I assume that will be the case here too. And the other problem was there was no way to test this. Did you change your biome for the good? No way to know.

Edit2: grammar.

[ctviggen]

Another problem with the biome. Assume that taking Inulin really does change your biome and affect your GLP-1 production, by raising it. Does that take a week? A month? Longer?

If I start today (which I did) taking Inulin, will it be sometime in September before I know there’s a benefit? Or maybe October?

Collagen peptides took a while to work, but I saw an age spot disappearing over time – and it’s pretty much gone now. But “hunger” over the course of 2 weeks to 2 months is really hard to track.

[CFLBob]

The problem with the “biome” is – as shown by the study above – the data are all over the map. Some studies have inulin raising GLP-1, but some don’t. And of course, none of these studies were done on people eating low carb/carnivore/keto.

This is my problem with stuff I read about the biome. In my mind, it’s like a thousand page book and we know a few pages worth of introduction.

I had a routine colonoscopy last week and (of course) that’s about as close to a complete reset of your biome as you’re likely to get. I’ve had a combination of things I’d refer to as “my regular irregularity” for quite a while and I thought this would be a good time to try to introduce some probiotics. For the week, I had some more carbs than usual, mostly in the form of more nuts and some dried apples, so nowhere near the SAD, plus around a cup of unflavored yogurt sweetened with allulose at midday. It has helped that irregularity greatly.

Like you say, the fact that none of the things that we (or at least I) know of are for keto/carnivore.

Edit: the typo error inserter visited after I posted. That’s my story.

[ctviggen]

Yeah, I’ve been trying some inulin (a “large” fiber) along with some allulose at lunch. I can’t tell whether the inulin is good or bad. I have had a few days where I was NOT hungry at all, to the point where I did not eat nearly as much as I normally would. On the other hand, since adding the inulin, I’ve had some times with stomach upset/digestive issues. I may have to take a step back and figure out whether it’s the inulin, the allulose, or both.

I also noticed that I tried the same meals for lunch three days in a row. While every lunch caused some lack of hunger later in the day, it was only the third day of this routine where I think I actually ate a lot less at dinner. The fourth day, I did not eat lunch, so had one day of OMAD.

Do I have to “build up” either insulin sensitivity/GLP-1/biome over the course of days to make a large effect? These three days were coming off a vacation, where I was pretty physically exhausted. Maybe it’s that these have some effect, but that effect is not enough to override what happening?

Not sure. Going to try the same this week to see what happens.

[FrankoBear]

Yes, I heard the term of GLP-1 ‘deficiency’ in a podcast recently. GLP-1 ‘deafness’ might be another way to say it. It had that same reverse engineered logic. Mainstream CICO eaters talking about the amazement of discovering satiety signals from a drug. But keto-eaters discover it from a way-of-eating. The deficiency in the SAD diet being the deficiency of the satiety signal and a pharmaceutical fix, as compared to an improved way of eating and rediscovering a natural signal on a well formulated ketogenic diet.

[PaulL]

So - at a high level - it makes sense to " replace what’s missing " as a form of therapy.

Absolutely–there is no point in changing to a better diet, just eat what you want and supplement with shakes, powders, vitamins, and medications. The body doesn’t know what it’s doing, so it’s our job to figure out what it should be doing and set its goals for it. Our brains can figure out what we need much better than complex systems that evolved over a couple of million years of evolutionary pressure. And epidemiological research showing minuscule effect sizes is ideal for helping us to figure out what our body should be doing and forcing it to do so. Domination of the body by the mind is a core tenet of Western thinking.

(Gee, aren’t you glad I got my Internet back? )

[PaulL]

Why not just avoid a “westernized diet” altogether and then not have any need to understand the complex science behind what it does and how to fix it?

Not to mention having to trace the funding sources of the research in question . . .