Does anyone try ITP longevity drugs (rapamycin, metformin, canagliflozin, empagliflozin, acarbose) to help reduce glucose and supplement keto?

(Alex K Chen) #1

or at very least, decrease blood glucose levels to the point that it makes it easier to not “get out” of keto on margin?

http://rapamycin.news has lots of them

(Alex K Chen) #2

Eg

Sodium glucose cotransporter 2 (SGLT2) inhibitors, an effective therapeutic option for diabetes, increase the urinary excretion of glucose, which subsequently improves hyperglycemia and promotes weight loss [103]. Although the elevation of ketone bodies caused by SGLT2 inhibitors has raised concerns about ketoacidosis as a side effect, the organ-protective effects of adequate levels of ketone bodies on the kidney [104,105] and heart [106] have recently been suggested. SGLT2 inhibitor-induced β-OHB inhibits the progression of renal injury by suppressing mTOR complex1 (mTORC1) signaling involved in the pathogenesis of diabetic kidney disease and by restoring energy metabolism through fatty acid oxidation

(You've tried everything else; why not try bacon?) #3

It’s called “euglycaemic ketoacidosis” because it’s a condition of elevated serum ketones without the elevated serum glucose seen in diabetic ketoacidosis. If your doctor puts you on an SGLT-2 inhibitor your should be warned about the risk of euglycaemic ketoacidosis. It can be just as deadly as diabetic ketoacidosis, and it can occur without warning in people whose pancreases are secreting insulin. Otherwise, in someone with a functioning pancreas, ketoacidosis is not a concern.

I didn’t know that an SGLT-2 inhibitor could stimulate the production of serum β-hydroxybutyrate. That is interesting. Normally it is the insulin/glucagon ratio that determines whether ketogenesis occurs in the liver, and glucagon is primarily activated by a lack of dietary carbohydrate (part of its job is to stimulate gluconeogenesis as well as ketogenesis in the liver).

In any case, it sounds as though you are looking for a way to continue consuming carbohydrate but promote health by taking a pill. Good luck on that. A low-carbohydrate/ketogenic diet renders the medications you mention unnecessary, and a high-carbohydrate diet is going to have effects that will interfere with the drugs. The human body is an intricately balanced system adapted to handling a wide range of conditions. We tinker with it at our peril, as our current world-wide experiment with a low-fat, high-carbohydrate diet is showing us.

In any case, all the speculation that some of these drugs might help encourage longevity is just that, speculation. The only way to determine their actual effect would be to take two matched populations, put one of them on one of the drugs for 90 years and prohibit the others from taking the drug for 90 years (all the while keeping the subjects from knowing which group they are in), and see how many of each population is left at the end of the experiment. And it would be even more interesting if they added a third group to the experiment, one that took no drug, but which ate a low-carbohydrate, high-fat, ketogenic diet, leaving the control group not only to refrain from the drug being studied, but also to eat a standard American diet. That might actually tell us something!

(Allie) #4

@PaulL that’s a lot of effort to put in to a response to a spammer…

(You've tried everything else; why not try bacon?) #5

Oh, I don’t know, it was fun. Gave me something to do while knocking back my first coffee of the day.

(Allie) #6

Well at least you got something out of it… :rofl:

(Bob M) #7

The data for Sglt2 inhibitors for heart diseases is…less than impressive. And I’d bet that a long term study looking at overall death rates would find higher overall death rate with the people taking them.

If anyone is actually interested in this area, Dr. Peter Attia has written a book:

Personally, I gave up a long time ago on Dr. Attia. The cognitive dissonance is strong with that one. But he does have a book.

(Alex K Chen) #8

I most definitely am not spamming - this is a serious question. I agree that keto reduces the need of these drugs but it’s possible they may reduce the damage from cheat days. Also I’m longevity centered

I think interactions between keto and these drugs are totally worth investigating

(You've tried everything else; why not try bacon?) #9

It may be possible, but eliminating cheat days is a very simple way to eliminate the damage they cause. Furthermore, not partaking of an addictive substance removes the control it has over us. This is why alcoholics in recovery abstain from alcohol.

By the way, eating protein activates mTOR and therefore shortens longevity. But not eating protein leads to muscle wasting, which also shortens longevity. Hmm . . . how to choose . . . how to choose?

However, as Bikman points out, the hyperinsulinaemia from eating carbohydrate activates mTOR far more than eating protein does, so his advice is “Control carbohydrates, prioritise protein, and fill in with fat.”

We are a long way from understanding what promotes human longevity, but it stands to reason that diet has a large part to play. After all, the Plains Indians of the U.S. were renowned for the high percentage of centenarians in their population—until they abandoned their diet of largely meat and adopted the white man’s diet of refined sugar and refined grains.

(Alex K Chen) #10

Rapamycin is precisely what may reduce the harm from high-protein (esp from keto). https://twitter.com/Blagosklonny advocates rapamycin + keto. This is why rapamycin may synergize with it.

" After all, the Plains Indians of the U.S. were renowned for the high percentage of centenarians in their population"

They don’t have birth records - this needs a strong source.

(Robin) #11

Sorry, won’t follow a link to a Twitter page or read stuff copied straight from the internet. If you want a conversation, use your words, as my. Mom used to say.

(Alex K Chen) #12

I saw a recent study about how dapagliflozin can increase ketones

https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.060402 (this isn’t the study but it shows smg)

(You've tried everything else; why not try bacon?) #13

As Dr. Phinney, the researcher who coined the term “nutritional ketosis,” always points out, a well-formulated ketogenic diet is not a high-protein diet, it is a moderate-protein diet, in the range of 1.0-1.5 g protein/kg lean body mass/day. It is others in the ketosphere, most notably Ted Naiman, who claim that protein should be unlimited on a ketogenic diet.

The researchers Raubenheimer and Simpson, authors of the protein-leverage hypothesis, claim that human beings, like all other mammals, have an instinct for getting the needed amount of protein, which is typically about 15% of calories consumed, on a decent-quality diet. I haven’t looked closely at their data, but they could well be right. One of their points is that people on a diet poor in protein (such as the one recommended by the U.S. government), typically overeat calories, in an attempt to take in enough protein.

(Allie) #14

Which is a demand driven and very necessary process, why would you want to stop your body doing what it needs to do?

Gluconeogenesis doesn’t just happen when you eat excess protein as many used to believe.

(Alex K Chen) #15

I also saw a recent study showing dapagliflozin increasing BHB levels

“SGLT2 inhibitors already mildly increase serum BHB and BHB esters have a horrible taste. Intermittent fasting for ~12-14 hrs already gets you additional mild ketosis with a peak at ~20-30 hrs”

In terms of epigenetic signaling, initial studies of the effects of BOHB on class-1 histone deacetylase activity against oxidative stress (Schimazu 2013), NLRP3 inflammasome suppression (Youm 2015), mouse longevity (Roberts 2017), and other epigenetic regulatory effects suggest that levels as low as 1 mM have potent effects. Furthermore, the association between very mild ketonemia and reduced coronary mortality with SGLT2 inhibitor use in patients with type 2 diabetes (Ferranini 2016) suggests that there might be clinical benefits with chronic BOHB levels as low as 0.3 mM (Gormsen 2017. Vetter 2017).

(Bob M) #16

The problem I have with these is that a lot of them can make me feel bad. Berberine, which supposedly has actions similar to metformin, was bad for me. Alpha lipoic acid: terrible. Felt as if I had no energy.

Rapamycin is the thing everyone seems to be effusive about. But are there any human studies with this for anti-aging? I see a lot of mouse studies, but the entire theory that saturated fat causes fat cells to be insulin resistant and PUFA causes fat cells to be insulin sensitive appears to be based on mouse studies. My testing of this is poor. Saturated fat + starch = weight gain for me, not satiety.