#1025

My biggest concern about SGLT2Is is that they take a lot out of your blood and send it to your urine. For instance, it helps excrete glucose (good), sodium (good), and lithium (bad). I wonder if it also affects other blood trace minerals such as magnesium, iron, copper, boron, etc… If so, you may lose many of the benefits from supplementing these other minerals. Would it also act on amino acids, proteins, or other food/supplements?

I’ve already upped my dose of lithium orotate to compensate (5 mg to 10 mg) due to the 70% increased excretion of lithium by empagliflozin. And, I’m still only getting 3 mg with the new higher dose.

It does appear to increase potassium levels due to the increased excretion of sodium.

In a pooled analysis of heart failure patients with reduced or preserved ejection fraction, empagliflozin reduced the composite of investigator-reported hyperkalemia or initiation of K±binding drugs without increasing the incidence of hypokalemia.7

5 Likes
#1026

I hear you DeStrider, very valid concerns.

But here is an odd thought - what exactly is the primary function of SGLT2i drugs? It gets rid of glucose. What is the most frequent cause of excess glucose? It could be insulin insensitivity or insulin insufficiency, but often both have a common cause - a long period of excess calorie consumption which results in insulin resistance, then insulin underproduction, and all from a consistence overabundance of glucose. In other words overfeeding.

What SGLT2i are countering, is the first consequence of overfeeding - excessive glucose levels. In other words, SGLT2i acts as if you are not overfeeding. As if you are eating less, because food enters your mouth but before the resulting glucose can wreak havoc, it is removed, effectively as if a portion of your food was removed from your mouth.

Curtailing food intake is another name for Calorie Restriction. Perhaps SGLT2i can be called crypto CR agents. From anecdotal reports you hear people say they can eat alot, yet not gain weight.

Yet, what is the effect of CR? Very healthy, seemingly. Undernutrition is healthy, while overnutrition is unhealthy. Now, if you are on CR, you expect all aspects of the food you take in to be at lower levels. It’s not as if when you consume lithium in your food and water intake, the CR only cuts out glucose, and leaves the lithium behind. No. CR cuts out ALL of the food, including ALL of the constituents, salt, lithium and everything else. So if SGLT2i cuts down on lithium, perhaps we can take our complaint not just against SGLT2i, but also CR. Yet, CR is healthy. Now, we can speculate that SGLT2i gets rid of nutrients unevenly, unlike CR that simply gets rid of it all, so perhaps some kind of unhealthy imbalance results… but…

In fact, doesn’t the same “losing micronutrients” rule that happens with SGLT2i in humans also apply to rodents? Yet, the mice on cana as tested in the ITP seemed to live longer. How hurt were those mice by all that micronutrient loss and imbalance - not much, and not more than CR, both of which extended lifespan. Let us remember, why SGLT2i were developed in the first place - to get rid of excess glucose. But if you are on CR, you never have excess glucose in the first place! So, CR is superior to SGLT2i and as Matt Kaeberlein says, CR is superior to rapa, because it takes care of many other pathways of aging compared to rapa. And CR gets rid of ALL extra nutrients - one can quibble but that’s the gist of it.

Bottom line, I’m not sure what to make of this, but perhaps - PERHAPS - loss of nutrients or molecules from using SGLT2i is not quite as worrisome as may seem at first glance. But hey, it’s just some crazy speculation - either way, for or against SGLT2i. YMMV.

8 Likes
#1027

@CronosTempi I agree with you. I’m not going to stop empagliflozin because the benefits are amazing. As you said, I can eat more AND lose weight and not have it affect my insulin resistance. That’s a win-win. However, if it is causing a nutrient deficiency, I want to be aware of it and address it.

I want my cake and eat it too… And not gain the weight from eating it.

That’s why I’ll continue with empagliflozin no matter what. But, I’ll be upping my lithium dose to compensate. Now I just need to be aware of what else I may have to adjust.

7 Likes
#1028

Did you ever learn anything more on this?

#1029

Here are some posts that might be helpful when thinking about Cana vs Empa or Dapa for longevity:

CLICK ON THE LINK OF EACH FOR CORRECT FORMATTING (all formatting is just deleted in the summary views below)

2 Likes
#1030

Yes, it’s very interesting

Could as you say be a sign that SGLT2i alone (Empa) can drive longevity

Could also be a sign that SGLT1i is needed (Cana) for any large longevity effect

2 Likes
#1031

I have to assume that SGLT2I will lead to longevity as it is a form of caloric restriction. Given that the mice eating the same amounts of food, the ones on an SGLT2I will be urinating more glucose thereby having the same effect as eating less food.

3 Likes
#1032

Do you mean using the class of drug? Or do you mean Empa specifically and think Empa is better for longevity than Cana?

#1033

That effect should be pro longevity

But other things are happening in the body too, so you cannot with logic alone determine if the net effect is pro longevity and we need more actual data

(For instance, two very simple logic examples sleep and hydration are both important for health and longevity and could be interrupted enough by more frequent peeing to have a negative longevity effect over a long term use).

1 Like
#1034

Actually, I am much thirstier after taking empagliflozin. I drink at least another 4-6 cups of water daily now due to the thirst. Personally I think that’s a good thing.

The sleep issue is more serious IMHO. I do wake up an extra time each night to urinate. I probably need to drink less before bedtime!

3 Likes
#1035

All your reasonings appear to be correct, but for the fact that practitioners of CR are aware of this and supplement potentially (or actually) lowered micronutrients, in what is called CR-ON, Calorie Restriction with Optimal Nutrition. Probably they don’t supplement lithium, but almost everything is accounted for religiously tracking their intake with cronometer.

1 Like
#1036

Canagliflozin alone amongst all known SGLT2 inhibitors has a significant anti-cancer effect (in human clinical studies of cancer patients). Mice lifespan is primarily limited by cancer.

In humans cancer is not nearly as dominant as in mice, so I will stick with Empa for its superior kidney protection. But, if I am ever diagnosed with cancer I am switching to Cana.

2 Likes
#1037

It does lower ferritin but I think it’s because it improves the iron metabolism. It INCREASES magnesium by improving magnesium homeostasis. Papers report SGLT2i being used to cure magnesium deficiency. (check papers posted in this thread). So… It’s more complex than just “it excretes things”.

Also: it’s not a diuretic. People don’t urinate more in trials, check these two papers: Rilmenidine vs Telmisartan or other BP meds for Longevity - #95 by adssx

3 Likes
#1038

Yes, which is why I say you can quibble. But while CRONies indeed do that, the literature on classic CR studies is not uniform. A ton, especially of earlier studies, simply cut food rations with no macro or micronutrient adjustment, and the animal appeared to experience dose dependent life extension. And while CRONies did indeed stress the “ON” part, there has never been agreement as to what constitutes the “O”. Furthermore I am not aware of any studies showing the validity, necessity, or superiority of such adjustments. It appears that straight CR works. Whether adding ON gives better results needs proof.

Classic calorie reduction posited undernutrition without malnutrition, meaning you weren’t f.ex. feed the animals only sugar and in small quantities, because that would be malnutrition. Instead, what CR studies routinely did, was put the mice on standard chow, but smaller portions.

Until we have more sensitive studies we won’t know definitively if adding micronutrients to CR is beneficial. We do know that there is danger in such adding, because for example adding molecules (such as methionine) which trigger nutrient sensing pathways often can abolish the CR life extension benefits, despite the cut in calories. So it could be dangerous to add you don’t know what… f.ex. zinc might give the body a strong signal “plenty of calories”, because zinc rarely is consumed by animals without calories, so evolution primed the body to respond as if a huge dose of zinc means there is a surplus of food, and the body signals accordingly and your CR is wasted.

Bottom line, it is a cleaner intervention, when the body gets a pure signal “not much food, and not much anything that comes with food, methionine, cysteine, zinc, lithium(?), X”. But if it also gets a false signal because of supplements, the message becomes blurred, and your benefits might suffer or disappear. Little food means little food, period, and not "wait, little food but blood full of vitamins, minerals, aminoacids etc… feels like a lot of food!

As you can see, unless we have specific studies, you can never be sure how one intervention interracts with another - it might be additive, or subtractive, or neutral. Be careful assuming. Which is one of Matt Kaeberlein’s mantras: as you stack more and more molecules on top of each other, the odds of unanticipated interactions rises geometrically - fewer is simpler, safer, more knowable and better. YMMV.

2 Likes
#1039

Cronies definitely supplement zinc, in moderate amounts.
I’m speaking about the Cronies I know, the members of the now inactive CR forum, many of’em took part in the Calaries study by Luigi Fontana.

I agree that the issue is more complex than it seems, for example the RDAs of micronutrients, do they refer to mere maintenance or more, they also are probabilistic and usually represent a 97.5th percentile so a lower dose would be enough for 50% of the population, and so on and so forth…

1 Like
#1040

I know that empagliflozin is not a diuretic, but for me, I am a lot thirstier so my water intake has increased by 1-3 cups daily. This is not a bad thing IMHO as water is readily available.

Great to know about the increase in magnesium on empagliflozin.

As for stacking molecules, when I look at my mother’s stack of 14-16 medications that she needs to take after her heart attack, I think that the 8 prescription meds I take to prevent health problems are worth it. I am on the lookout for negative interactions, but so far everything seems to be working well together.

Also, aren’t our diets quite varied with a huge number of different molecules? I’m not worried about my diet unless I’m eating very unhealthily!

1 Like
#1041

I had to take electrolytes due to muscle cramps. Might have come from excessive urination

2 Likes
#1042

14-16!? What is your mother even taking?

#1043

Do we have any data or can we speculate on whether the positive effects described in this thread would still apply to people who have normal glucose metabolism?

I know that some studies have shown benefits in non-diabetic people, but non-diabetic people can still have spikes up to 180mg/dl and HbA1C up to 6.5. What about people with healthy metabolism and diet whose glucose never spikes above 120mg/dl? Would they still see the benefit (e.g., CVD, CKD, and dementia prevention; life extension)?

2 Likes
#1044

I know it’s a long thread, but it has a LOT of great info, most of it thanks to @adssx . IMO, signs point to “yes” and that’s why I’m taking empagliflozin daily.

2 Likes