Alex K. Chen metabolic / CGM progress (my "everything in longevity" thread)

Are you getting woken up/annoyed by your low glucose alarm going off?

I put my phone into airplane mode at night. No problems.

What is the benefit from luteolin that you’ve heard of? I’m not that familiar with the compound. Here is what I found interesting after searching:

Luteolin is a fructokinase inhibitor, but I’m unaware what this means for blood glucose levels.

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the higher the fat content, the lower the spike
try the berries in sour cream or full fat yogurt

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Interesting - from the podcast you referenced - here is more information. Can you share some of the research on luteolin and fructokinase that you found compelling? Any idea of the dose? At the bottom I link to a sample product that has luteolin as a supplement - is that the type of product you think might work to help inhibit fructokinase?

  • But when fructose is metabolized… the enzyme that metabolizes fructose is called fructokinase
    • And when that metabolizes fructose, it consumes ATP in an unregulated way
    • So if the cell sees a lot of fructose, the ATP levels can plummet by 40 or 50% in the cell
    • And that produces a “May Day” signal, “we’re under attack, we’re running out of energy!
    • So it switches the animal into a condition in which they’re trying to preserve their energy
      • They reduce their metabolism
      • They reduce their resting energy expenditure
      • They push the calories eaten into fat and glycogen as opposed to making more ATP as a way to protect the body by putting you into a system where you try to store fuel
      • Additionally, it triggers hunger and thirst that makes you want to eat more so you eat more to restore the energy but at the expense that you’re shunting much of it into fat and into fuel storage

and further on…

-If you block fructokinase, many cancers don’t do as well

  • If you take intestinal colon cancer, for example, and you put high fructose corn syrup on it, they love it, they grow, they metastasize…
  • …But if you block fructokinase and block fructose metabolism, you can block a lot of the growth of those cancers by 50+%
  • Furthermore, we know it’s the fructose and NOT the glucose because the glucose metabolism pathway was not blocked at all in that experiment
  • They were able to show that this was driven by that shift from a mitochondrial based metabolism to a glycolytic metabolism.

and at the end:

Fructokinase inhibitors—a potential blockbuster? [1:07:15]

Are there any people with naturally occurring mutations in fructokinase that render it less capable?

  • There’s a condition called the essential fructosuria where they are born without active fructokinase and they live normally
  • These people don’t get type 2 diabetes or obesity
  • It’s a rare condition but that are basically immune to the harmful effects of sugar

Is there any benefit to having fructokinase if you’re not hibernating or in a world where famine is potentially come in your way?

  • Fructokinase was an evolutionary thing that allowed us to survive long periods without food
  • So in the Western world where we have an abundance of food it’s really not necessary
  • In fact, Rick thinks “living without fructokinase would probably solve a lot of the world’s health problems

Fructokinase inhibitors

  • There are fructokinase inhibitors that are being developed by Pfizer
  • It was quite successful at treating fatty liver and so now they’re taking that drug to phase three
  • Peter says “wow, that’s a potential blockbuster

Luteolin product examples:

More info:

Fructokinase inhibitors that are being developed : Pfizer Study Finds Progress in Combating Fatty Liver | Riley Griffin (bloomberg.com)

Findings show that at least 10 to 20% of fructose can escape into the circulation which can cause kidney problems : Ketohexokinase-Dependent Metabolism of Fructose Induces Proinflammatory Mediators in Proximal Tubular Cells (Cirillo et al., 2009)

Putting high fructose corn syrup intestinal colon cancer will cause the cancer to grow and metastasize and if you block fructokinase and block fructose metabolism, you can reduce the growth : High-fructose corn syrup boosts intestinal tumor growth in mice

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It’s also interesting because it’s apparently very similar to quercetin in structure, and apparently helps against inflammation and prevents senescence to some extent.

I think a lot more research is needed but it seems relatively harmless at usual doses (50-200mg). It’s already a part of my stack where I use it for its fructokinase inhibition before consuming sweet fruit, and also along with my “Dasatinib(low mg) +Fisetin+Quercetin+Raw Cocoa+Blueberry powder” senolytic dose.

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Yeah, it was a fascinating episode. Researching this led me only to luteolin, but of course I’d be interested in any pharmaceutical and cleaner fructokinase inhibitors.

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Every now and then I hear about how sugar and fat in combination is more dangerous than either alone! But then there’s also the effect of lower spikes when there’s fat with sugar.

This makes me think that the former is just an urban myth, unless it is somehow referring to how they go well with each other when it comes to how tasty it can be.

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carbs on its own is less damaging then carbs with fat
hence people can lose weight on the potato diet, eating only plain potatoes
if you think of unhealthy foods, they almost always combine both together.

seems that when you eat pure carbs, its very difficult for your body to turn it to fat, but fat eaten alongside carbs are very easy to get stored as fat.

so from a high glucose perspective, eating fat with the carb may be helpful.
however, from a weight gain perspective, it may be worse

see attached show notes from attia

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Oh thanks, this is really useful! But, what is the mechanism by which additional weight gain happens? Do carbs and fat in combination produce more insulin for the same number of calories than either alone?

Or is it just an effect of people consuming more calories when it comes to sweet potato + butter, because it tastes better?

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  • Preliminary studies suggest that your body uses less insulin and has better metabolic response to having all of your carbs at once without any fat present (rather than spacing it out in mixed meal)
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The strawberry spike last night came after eating 750 calories of almonds…

Meanwhile… below is the barely a spike after 750 calories beans

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One can of black beans and one Cole slaw package WITHOUT ACARBOSE, damn this increase is weird I need to try again to reconfirm

i ate some cloves after to blunt appetite and it seems to work for

WTF COLE SLAW

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One can black beans this morning, then 2 cans later this afternoon. Also finally took SGLT2 inhibitors will see if that does anything

Omfg

And after 400 more calories of frozen vegetables too. This might literally be the best - peeing out all your excess calories

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How many mg of which SGLT-2 are you taking?

Are some of the SGLT2 inhibitors more effective than the others?

Also at what dose is the effect highest? Like, I’m taking 100mg canagliflozin - don’t some people take 300mg and is the effect higher at 300mg?

Cole slaw and salsa late at night (I really resisted my nut cravings) then cole slaw when I woke up

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I’ve heard people take between 100- 300 mg canagliflozin and 10 - 25 mg empagliflozin. I never had the luxury of titrating the dose based on CGM readings, and I was erring towards around 200-250mg canagliflozin. I’m impressed by how well 100mg worked out for you (based on your previous message) – this makes me feel that I can be more conservative with my SGLT2 use and save some more for the future.

It’s still unclear how much my SGLT2 use helps, it didn’t prevent the spike to 125 after I ate cole slaw+salsa (and those are STILL much lower-calorie than bread or fruit). It’s still unclear if I can eat most carbs ever again.