Treating the American Lifestyle

For the majority of us, the American lifestyle causes physical problems that need medical treatment. Dr. Josh Stout explains how statins and Metformin are used and how to minimize side effects.

Treating the American Lifestyle
Why things tend to go wrong around 50, and some things we can do about it: understanding Statins and Metformin

Eric 0:09

Today is Wednesday, May 29th. We're doing this on a Wednesday. It's been the beginning of summer and things are changing. 

Dr. Josh Stout 0:15

Yeah, Yeah. Well, this works better for both of our schedules right now. Also I get a little bit more time to think about details, take a little more research rather than just stuff off the top of my head. 

Eric 0:28

Because it's summer. You see I lose time when it becomes summer, my kids are young.

Dr. Josh Stout 0:28

Because it's summer, I lose. 

Eric 0:30

Time when it becomes my time. My kids are. 

Dr. Josh Stout 0:32

I get a bit more focus, you know, out of school. I'm not teaching right now. [Right]. So I wanted to talk a little bit about our evolutionary background. And when we don't live the way we were evolved to do, how we then treat that medically. So we evolved out in the Serengeti getting tons of exercise, not eating any simple sugars, only complex sugars. We would binge on protein periodically and not eat any sugars for a while, and then we would eat just roots and raw roots or difficult to digest. So we had very little in the way of insulin spike responding to, you know, glucose rises. At the same time, we were getting tons of exercise. We're walking over six miles a day, we're digging, we're running two things. All of these things were what we evolved to, how we were evolved to live. And as modern Americans, we don't do that. We're lazy. We like to sit around. We love the tasty food we eat. We like our cheeseburgers, we like high cholesterol foods, we like fatty foods with lots of triglycerides, and we like sugary foods that boost the blood sugar. And we're sick because of this. And so various. 

Eric 1:38

Because of the delicious things. 

Dr. Josh Stout 1:39

And our lack of exercise that that that combination. And so, you know, you hit about 50 years old and suddenly your cholesterol through the roof and your blood sugar starts going up and you see the doctor and they start recommending things that you do. And so what are these things? These are things that will get you back on track medically to do what you should be doing in your life. But many of us can't do the lifestyle changes necessary. If you want to lower your cholesterol, you can radically increase your exercise, decrease your particularly red meat contents. But anything with cholesterol in it, we can make our own cholesterol. But if you actually stop eating meat, your your cholesterol will go down. 

Eric 2:23

Is this something that is if you do this earlier in life, will that affect you later in life or this is just a thing you have to do continuously throughout life? 

Dr. Josh Stout 2:31

I would say continuously throughout life. But it seems to be more important as you get older in many cases, particularly exercise, not just as a habit to start earlier in life, but we talked about it in osteoporosis as something that you build up ability early in life so that you can do it later in life. You know, generally stamina, strength, all these things you need to build early in life. Yeah, Later in life is when you really need to have done those things and if you don't do didn't do them now is when you have to start. But it makes it much more difficult so that if you don't have the energy, it's more difficult to exercise. You know, starting off with smaller things and working up definitely does work well. All the studies out there show that even small amounts of exercise can have tremendous benefits. But to try and get up to hunter gatherer levels of exercise is going to be really, really difficult. You know, you literally should be walking at least six miles a day, which almost none of us do. 

Eric 3:27

I don't even see how that's possible. That takes a significant amount of time. 

Dr. Josh Stout 3:31

All of these things are going to be taking a lot of your time. I mean, just the the the the sheer amount of vegetables you eat, you you should be eating essentially raw as much as possible to slow down their absorption. You're just going to be either chewing or walking all of your time, which is what we evolved to do just sitting there, just chewing roots and vegetables and walking all day every day. 

Eric 3:52

I can definitely say I am resistant to the way we have evolved. I do not want to be doing that. 

Dr. Josh Stout 3:56

And that's what we evolved for as well. We evolved to not want to do these things. We evolved to eat the delicious food because that's the stuff that gets the most fat and we really, really want fat. And we evolved to avoid exercise because exercise is costing us calories and we evolve to maximize our calorie storage. So we always have enough fat for our giant brains. So our giant brains are telling us to not do the things that are healthy for us and telling us to sit around and, you know, watch TV and eat potato chips. So, you know, we all can fight this a little bit and any kind of, you know, improve improving of diet, less less simple sugars and more exercise, all of these things are going to help you increment early. But it's still a high bar. It's a really high bar for all of us. And so, you know, letting ourselves off the hook a little bit, what happens? We end up as I mentioned, going to the doctor and the doctor starts prescribing some some medication. 

Eric 4:52

When I hit when I hit 50, the doctor literally said to me, You're 50 now. So there's things we need to talk about. It’s jus that - it’s a trigger. 

Dr. Josh Stout 4:59

Is just a trigger and and it really does seem to happen at that time. So your triglycerides start going up, your your bad cholesterol goes through the roof, your glucose levels start going up, and all of these things are bad for you for obvious reasons. 

Eric 5:13

So this is happening to everyone, is what you're saying. 

Dr. Josh Stout 5:15

This is happening to everyone some more than most, certainly Americans, more than most, because we're sort of at the forefront, the cutting edge of not exercising and eating lots of sugar. [Yeah, that's white flour and lots of refined foods] we're now spreading this to the rest of the world. You know, I don't know if we're a neocolonial power in that sense, but our sort of soft neocolonialism is one of cultural spread. And with our cultural spread comes these other other problems. And so this this is American culture in particular, but it's becoming world culture. And so one of the things that we particularly treat these problems with is statins. So statins actually reduce the formation of cholesterol in in your liver and you can reduce your dietary cholesterol. But we make about 70% of our own cholesterol. 

Eric 6:11

Yeah, I know that in my body personally that ingesting cholesterol did not necessarily translate to serum cholesterol if it had it had a dip and then it came back even when I was maintaining the same diet. 

Dr. Josh Stout 6:24

Your body can make cholesterol just fine, even if you have a zero cholesterol diet. So if you're entirely plant based diet, there'll be no cholesterol and you'll make tons of cholesterol, particularly so from something like potato chips. Say potato chips have zero cholesterol. They're all plant matter at the, you know, plant based oils in it. But the sugars in the in the potato chips, the starches that are made out of pure glucose and the fats themselves are going to work together to provide all the things you need to make lots and lots of cholesterol. And so it doesn't matter if you completely avoid cholesterol, you can still make it and your diet can still be bad, you know, and. 

Eric 7:02

Your diet can still be bad in a way that will cause your body to make too much cholesterol. 

Dr. Josh Stout 7:08


Eric 7:09

I no one ever explained no one ever explained that to me. 

Dr. Josh Stout 7:13

Oh, I'm so sorry. Yeah. So it's glucose again, is directly related to triglycerides, which is related to the whole insulin problems. And you're going to be directly making more cholesterol in response to a high fat, high sugar diet, even if none if there's zero cholesterol in your diet. So again, you make about 70% of your own cholesterol. 

Eric 7:37

And it doesn’t even need to be high sugar. It can be high carbohydrates, right?  That could still get you there. 

Dr. Josh Stout 7:40

The simpler the carbohydrate, the the more circulating insulin you're going to have and the more circulating insulin you're going to have, the more cholesterol you're going to end up with. Right. So so, yeah, if you're eating raw fruits, you're going to have very low circulating insulin and you're not going to end up with high cholesterol. But since we don't eat raw fruits, we eat cooked potatoes. That's going to go directly into high glucose and it's going to lead to high triglycerides and high cholesterol. So, yes, you can change these things through diet even better. You can change it through exercise. Exercise reduces cholesterol. But again, it's going to be really, really difficult. You should be striving for these things on your own regardless. I'm not saying you should just let yourself off the hook and eat potato chips and watch TV. But let's say you've hit 50 because life has been good and you made it that far. Yeah. Now you have to do something about the lifestyle you have, which is not evolutionarily perfect. But let's say you're doing your best and it's still just not quite good enough. 

Eric 8:43

Still not good enough. 

Dr. Josh Stout 8:45

Exactly. So the doctor is going to recommend you take statins to control your overall cholesterol. Now…

Eric 8:52


Dr. Josh Stout 8:53

Exactly. So your liver makes statins mostly overnight. Sorry, not statins, that that makes cholesterol mostly overnight. And statins inhibit the coenzyme that basically starts that process. So cholesterol is made out of fats. And those fats are modified to become the different kinds of cholesterol, the high cholesterol, so high density lipoprotein and the low density lipoproteins. And so if you slowed down the production of all cholesterol by this rate, limiting reaction, so you've you've actually blocked that enzyme, then that's going to have a whole bunch of sort of knock on health benefits. So by slowing down the production of cholesterol, the statins actually bind it. Something like 10,000 times the rate of the natural enzyme. So they really interfere with that enzyme's binding. Now you have less cholesterol in your liver, so when your liver doesn't get enough cholesterol, it needs cholesterol. So it actually is going to make or allow to be made or pref prefer that some of that some of the biochemistry is not completely clear on this, but it's going to encourage the production of the good cholesterol, the high density lipoproteins. So the good cholesterol is the kind of cholesterol that goes to your body and brings fats and triglycerides back to the liver. And so now your liver is hungry for cholesterol because it can't make its own. And so it's actually scavenging it from the rest of your body. So you're getting this sort of extra added benefit of not having overall levels of cholesterol. And now your body is switched into a metabolism that is going to decrease the bad cholesterol, taking fats from your liver and increasing the good cholesterol, taking fats back to the level. 

Eric 10:48

Levels, basically sending little cannonballs around, knocking out the the the puffy stuff. 

Dr. Josh Stout 10:54

Well, it’s gotten hungry. It's saying bring food to me. So normally your liver provides you with food. It provides you with your glucose, it provides you with your fat, it's your it's your general storage unit. You know, it does some cleaning of the blood as well. But this this very large organ takes up a significant amount of of, of your, you know, region in, you know, below your lungs sort of internal. 

Eric 11:16

Real estate. 

Dr. Josh Stout 11:17

Your internal real estate. And it's significant amount of your overall metabolic costs. It's something like, you know, ten, 20% of your total metabolic [wow] issue. A lot of your blood is in your liver as. 

Eric 11:28

It’s as big as your brain. 

Dr. Josh Stout 11:29

It's as big as your brain. Yeah. So, like, there's like your muscles, your brain, your heart and liver and your your gut. These are the things you do with your body. And so this is one of the main the main uses of blood and energy is your liver. So when your liver gets hungry, it starts scavenging fats and cholesterol from the rest of your body. And so that's really good. The statins also do some really interesting things in terms of overall heart benefits. It gives secondary effects that benefit your heart because it stabilizes plaques. So if you have high cholesterol, you will have started to form plaques. Plaques are what cause hardening of the arteries. It's cholesterol sticking to the side of the artery, which then gets a sort of fibrous mat over them that holds them in place. And then you actually get white blood cells sticking on that. So the whole thing starts to form permanently. Sclerotized to arteries, and this is what causes, you know, long term heart issues, right? 

Eric 12:32

Right. It seems so therefore, the volume is reduced. 

Dr. Josh Stout 12:35

Is reduced, Yeah. So these are not going to grow as fast. And you have statins because you have less cholesterol. But the other problem with these, with the plaque formation and these sort of blood clots, which is what's actually forming, is that they can break off right? They can break off and travel through the body, they can try to cause strokes. But the most common problem is that they're stuck somewhere in your heart, often on another plaque that's already in your heart. So one will break off, stick to the other plaque, and then this whole big lump starts forming inside the arteries of your heart. This is what we use. You know, you put in a stent to open up the blood vessel so your heart can keep working. So the statins actually stabilize these plaques. They stabilize that sort of fibrous network over it. 

Eric 13:19

Oh, you mean throughout the body? 

Dr. Josh Stout 13:20

Throughout the body. 

Eric 13:22

They these things don't go rogue and get caught in heart. 

Dr. Josh Stout 13:26

Exactly. They also lower overall inflammation. Lowering inflammation reduces the potential for plaques to form. Plaques tend to form when there's, you know, a narrower artery, you get more turbulence, see that turbulent flow basically slams molecules against the wall of the artery and they stick. And so with lower inflammation, it's actually working on the the nitric oxide things that are related to vasodilation in general. So you're going to have better flow through the heart. It actually improves the endothelium, which is very speculative. Okay. Statins, statins actually improve your endothelium, which is really weird. Okay, I just want to. 

Eric 14:13

But not. 

Dr. Josh Stout 14:14

Yeah. Anyway, I just wanted to point out that very much not a medical doctor. I very much am a biological doctor, so I feel quite able to talk about these things. This is, you know, totally things. I can read the papers very easily and understand them, but any information I give you terms of recommendations for a particular person, I am not doing that. I am not a medical doctor recommending a particular medication. 

Eric 14:39

You're saying there is literature that says there is scientific proof that it does this? 

Dr. Josh Stout 14:44

There is evidence indicating, well, support for this. And so I just wanted to speculate briefly that thinking about COVID, which really attacks the endothelium, this might be one of the reasons that Long-covid is a problem, is if you're endothelium has been damaged or has swelling or something like that, this is going to have all sorts of issues throughout your body, including in your heart. 

Eric 15:08

The endothelium is the the it's the wrapper basically. 

Dr. Josh Stout 15:13

Yeah. Yeah. And so so this this this is going to be improving all of these functions. You could actually end up with slightly more energy because of this and or possibly countering what Long-covid did. Very speculative, not seeing anything in literature. I'm just thinking about it because I happen to know two things that affect the air. This helium, right? We've got COVID is bad for it and statins are good for it. So it's interesting to think about it as being good for it in that in that sense. 

In addition, it actually reduces formation of blood clots in general. So it's antithrombotic. So thrombosis is blood clots and swelling. And this is actually going to reduce the formation of platelets and clots. 

Eric 15:58

I hate I hate how I sound like a like a salesperson. But it sounds like from what you're saying, the earlier in life that you get on this particular drug, the better it would be for you. 

Dr. Josh Stout 16:08

I don't know about that. I don't know about that. 

Eric 16:10

But if you're saying that the that these plaques develop as you get older then and these these keep things in place and prevent new plaques from forming. 

Dr. Josh Stout 16:21

That could be. 

Eric 16:22

Then getting on it sooner means you have less plaques overall? 

Dr. Josh Stout 16:27

Usually the symptom of increasing plaque would be increased blood pressure. I don't think treating things that haven't been a problem yet or is a good idea. So you know yeah if you you're young and you started seeing your blood pressure going up and you noticed your cholesterol going up, yeah, you should treat it early. But if your cholesterol is fine, your blood pressure's fine. I don't think you should treat a problem. 

Eric 16:49

No, no, but. But I'm just saying, like, when you the moment you see a problem, you can start. 

Dr. Josh Stout 16:54

Yeah. You might not want to to, to muck around too much. If this is something where… 

Eric 17:00

I don’t like being on drugs, I'm just saying it sounds like… 

Dr. Josh Stout 17:03

Yeah. No, once. Once your cholesterol starts going up, you should really start thinking about statins for a whole number of reasons. And there's been some very, very large gold standard double blind placebo studies showing improvements not just in cholesterol, but also in just total longevity. So this will help you live longer, mostly because of the heart improvement, because you're not forming blood clots, you're not forming arteriosclerosis, you're not getting high blood pressure. All of these things are improved by the statins. Now, I want to talk about. 

Eric 17:36

Isn't this like this is one of the most prescribed drugs in the United States. 

Dr. Josh Stout 17:41

Yeah, there's a reason for it.

Eric 17:43

And it's been prescribed since, what, the early fifties? 

Dr. Josh Stout 17:46

It's well understood and there's there's, there's a whole number of different kinds of statins. They all pretty much work in the same way inhibiting this particular enzyme that starts. 

Eric 17:56

Do you have any knowledge of what the some of the side effects… 

Dr. Josh Stout 18:01

Well that’s just what I just wanted to get into is, what are the negative side? Why don't why don't we just take this from birth? 

Eric 18:05


Dr. Josh Stout 18:06

Yeah, yeah. Okay. 

Eric 18:08

Like a vitamin. 

Dr. Josh Stout 18:10

One of the problems is what's called the nocebo effect. So a placebo is where you get better from taking a sugar pill. A nocebo effect is when you get worse from taking something that shouldn't do that to you. And so doctors will not tell you about the side effects of statins very often because people experience the side effects of statins at much higher rates if they know about them. So it's a nocebo effect. So if you don't know about the side effects, your rate of side effects is about 5%. If you do know about the side effects, your rate of side effects is about 20%. So it's much, much worse for you if you know. So spoiler alert if you are listening, try not to take it to heart too strongly, but I am about to describe what goes wrong. So the common side effects that one sees from statins are muscle weakness, muscle cramping and just general muscle pain. And it's not completely understood how these things happen. But the general hypothesis is that this is due to calcium release. We talked about calcium ions when we were looking into osteoporosis, very tightly controlled in the body. Calcium ions are how nerves are involved in nerve signaling ion pumping across the membranes, all these kind of things. And they're also involved in muscle contractions. And so your muscles have calcium stores that are part of the signal that tells a muscle to contract. The statins, interfere with this and cause calcium stores to be released. So big bag of calcium sitting in a muscle cell is suddenly exploded, releasing calcium everywhere, which causes the neighboring muscle cells to contract. When the neighboring muscle cells contract, it makes them more likely to also release calcium. So it's a lot like the way, let's say, lactic acid works in a fatigued muscle. Lactic acid is is the buildup from anaerobic metabolism. Lactic acid then interferes with the way muscles work and causes further muscle contraction, which is a muscle cramp. That's basically what's happening here. So it's going to interfere with overall muscle function. It's going to cause muscle cramps, it's going to cause muscle weaknesses, It can damage the muscles long term, but that's extremely rare. That would be with someone who had, you know, very, very bad sort of, you know, metabolism within their muscles and probably extremely weak muscles to start with. People with healthy muscles contract these muscles a lot. When you contract the muscle, it pumps the muscle, it moves all those things like lactic acid out. And so it's going to be the number one way to fight this sort of side effect is, again, increasing exercise. So even though you're on statins, you still need to exercise when when you're exercising, you're moving the blood through your muscles. It's going to move this calcium out. You're much less likely to suffer muscle cramps or the muscle weakness. However, if you were sitting there lying in bed all day and you're taking statins and you start to feel weak, what's the last thing you're going to want to do is exercise. So there is a little bit of a catch 22 problem there. 

Eric 21:20

I do. I do have a the anecdotal thing is that when when I was given statins, my doctor told me to take CoQ10, I did take CoQ10. He said take it with it. But by changing the amount that I take and the timing of taking it, I don't experience the side effects that I think I was experiencing. I may be treating a nocebo with a placebo. 

Dr. Josh Stout 21:41

It's really hard to say. Yeah, yeah. So. 

Eric 21:44

So I also am exercising more. So yeah. 

Dr. Josh Stout 21:47

So CoQ10 and ubiquinol are enzymes involved with oxidative metabolism and oxidative metabolism is when it functions correctly, doesn't produce the side effects of muscle fatigue, etc. So by including increasing your ability to properly process and oxidize sugars and turn that into ATP energy for your muscles, you're going to have less fatigue, probably less muscle cramping. All of these things will actually treat the problem, but it doesn't treat it directly. It doesn't interfere with this. These calcium releases the calcium ions in the muscles. It's just improving your muscle ability overall. So to the extent if CoQ10 works and a lot of people say it does, I don't know as much about this. It's not as easy to understand. In the double blind, massive studies haven't been done in the same way. 

Eric 22:42

Have not been done there, yes. 

Dr. Josh Stout 22:43

It should basically give everyone a little bit of energy and so it might well function to to fight the lack of energy that statins could create because you need CoQ10 to metabolize any sugar, you know, to metabolize glucose. So any cell that uses energy, which is all of them have these enzymes in them all the time so they can't be something you actually have a deficiency of. You're not treating a deficiency by taking CoQ10. 

Eric 23:13

Again, it could be a placebo. 

Dr. Josh Stout 23:15

On the other hand, it might be that you're limiting the rate because you have only a limited amount of CoQ10, by giving a little bit more, you speed up that rate just a tiny bit. Again, this is speculative. If you're talking about metabolism across a wide range of things. If there were any place in the body that would need a little bit of extra, you'd expect to find that in your in your muscles and your brain. The two things that are going to be using a lot of energy, all the time. CoQ10 is supposed to help with both of those things, so it improves oxidative metabolism in your brain and your muscles. You get fewer oxygen radicals, you have fewer of the things that cause damage. So basically the whole the whole process is improved. So I'm not saying CoQ10 is bad. I'm just saying it's a it might do nothing. It probably does something and it probably does something that will help you. 

Eric 24:03

And we have no proof of any of this except that my doctor said, take CoQ10 with a statin. 

Dr. Josh Stout 24:09

People have been recommending CoQ10 for a number of different reasons. For over 30 years I've heard it, particularly for brain health. But this muscle health basically is going to be working the same way. It's reducing it's reducing the the toxic byproducts of oxidative metabolism and increasing the rate of oxidative metabolism so that you're getting more energy from the system. So it's energy for your brain, it's energy for your muscles. You're going to feel better. 

Eric 24:31


Dr. Josh Stout 24:32

Probably. Or maybe it's all a placebo, but I suspect it actually helps. And that's why your doctor was recommending it. Yeah, so these are things you can do, but again, it's not going to directly affect this calcium buildup problem. Right. The other. 

Eric 24:47

Exercise, though, will. 

Dr. Josh Stout 24:49

Exercise. Well, right. These are calcium ions that are naturally occurring in your muscles and you just want to pump them out. 

Eric 24:54

Combining these things. Yes. Always. 

Dr. Josh Stout 24:56

Yes, absolutely. And so, you know, even if you're on statins, if you are eating nothing but fat and sugar, you're still going to end up with high cholesterol. So, again, you still need to have better diet and improve your exercise. You just don't need to live like a hunter gatherer. 

Eric 25:12

I have to admit that when my doctor increased my statins, I was like, I can eat a little more meat now. 

Dr. Josh Stout 25:19

May have been true, but yeah, I I'm on a very low dose of statins and it's only barely touched my, my, my cholesterol. 

Eric 25:27

I see everyone's body is different. The lower dose of statins really sent my cholesterol down. 

Dr. Josh Stout 25:32

If I'm going from taking it every other day to taking it every day, which is what my doctor recommended in the first place. So yeah. 

So yeah. Anyway, doctors have different opinions than I do where I was being a little careful. 

Eric 25:45

It's a thing of art. 

Dr. Josh Stout 25:47

It's a thing of art. Exactly. Yeah. Being a doctor is a lot like being a cook. There's a lot of science involved, but each time is a single occurrence, right? Every meal just happened once. Next time you try and do it better. Exactly. Right. So anyway, this the calcium isn't just happening in your in your muscles. It also happens in the Isle of Langerhans, in your pancreas. So the isles of Langerhans in your pancreas are what produce insulin. And so you actually have a problem producing insulin correctly when you're taking statins. And it can lead to type two diabetes as a possible side effect as your glucose levels go up. So I think in your case, your doctor also recommended metformin. 

Eric 26:34

Yes, as my A1 C is slowly creeping up in. Is it because of the statins? 

Dr. Josh Stout 26:39

It's your entire life. Everything is going to be creeping up as you get older, but the statins aren't going to help. Yeah, so. So your glucose levels are going going up your statins are just going to make this worse. And so you run into more problems. And so one of the things that doctors then recommend is, is metformin. And so metformin again, has been around for a really long time. It has relatively few side effects and is generally recommended. It's been around since it's since the twenties. 

Eric 27:09

My doctor actually said that ‘some of us in the community use this as a supplement’. 

Dr. Josh Stout 27:13

Yeah, I'm going to talk about that because this is this is something that is relatively new and is only just being talked about like in this last year. I read a paper from April 2024 saying that this is a brand new idea. 

Eric 27:27

He said this to me about about four years ago. 

Dr. Josh Stout 27:31

Right. And so the 2024 paper was summarizing the literature where people have been on this idea. So your doctor was actually ahead of the curve and it's seeming like he was right, which is good. Nice to hear your doctor’s right. 

Eric 27:41

Yeah, he's good. 

Dr. Josh Stout 27:43

So the metformin is designed to control blood glucose and it actually also increases insulin sensitivity. So it's the main treatment for type two diabetes, lowers blood glucose, blood glucose, while also increasing insulin sensitivity and inhibiting overall insulin levels. Because if you have higher insulin sensitivity, you don't need as much insulin. So it's it's tremendously good for you. It was first found in the twenties. There were a couple of different versions of it. I'm not positive about this, but I think that where everything went wrong was fen, fen. I think it was related to a kind of metformin relative combined with some amphetamines and it started causing bad effects. I can't remember what they were exactly from the seventies and eighties, but a lot of people had really bad effects and so they banned it. And so then it was out of favor for a while and starting, I think in the nineties it started coming back into favor as a limited treatment for Type two diabetes and then it became well accepted for that. And so the current formulation, not combining it with a stimulant seems to work really, really well for that particular thing, the Type two diabetes. But because so many people in this country, because of our American lifestyle, have type two diabetes or are pre-diabetic, this means hundreds of thousands of people have been taking metformin and they started discovering that in this formulation it has a whole bunch of other beneficial effects. So much like statins have a range of things they do for you. Metformin has a range of things that it does for you. It seems mostly related to lowering glucose. So glucose is a poison and glucose causes oxidation around your body. So glucose ages you and by reducing the amount of glucose you take in, you're actually going to possibly lower your aging process. So it actually slows down the amount of glucose being taken out of your stomach so you're not eating as many calories from your food. And so this is going to also help you lose weight. So even if you are not type two diabetic, this will lower your glucose circulating through your body, will lower the damage from the glucose and start helping you lose weight because you're not absorbing that glucose. 

This is going to cause sort of benefits throughout the body as you are now no longer storing as much fat because one, you don't have as much glucose in your body, in your in your circulation. So you can you can lower the amount of insulin. Insulin tells your body to turn glucose into fat. So with less glucose and less insulin, you're going to be making less fat in your body. You're going to be able to handle the small amount of glucose that you are getting.

It can cause some problems because it will end up with less glucose in your blood. Less glucose is going to your liver to be stored for energy. That means you have less energy stores in your liver. It doesn't just start on the top end. It also interferes with the release side of things. So your your liver stores glucose as glycogen, this giant molecule with lots of glucose is on it. And when you're hungry, you're exercising insulin. Sorry, the insulin stops and you get the the glycogen hormone telling you to release the glucose into your blood. And so this gives you the energy when you need it. 

Eric 31:30

The glycogen is converted into glucose in the liver before it is released?

Dr. Josh Stout 31:36

So so so so insulin tells glycogen to store sugar and holds it because if it was just stored as glucose, it would be toxic. So it holds it in a molecule that detoxifies it essentially. And then when you have low blood sugar, you're exercising glucagon tells the glycogen, sorry, I think I misspoke there. Glucagon tells the glycogen to release the sugar. That that's why you ask me because I missed that word. Yeah. Yeah. Thank you. So. So now you're releasing more sugar back into your system when you need it. The metformin is going to interfere with this. It's actually going to lower the amount of glucose that is released. So you're going to have less being stored, less being absorbed and less being released. 

Eric 32:19

Could cause a cycle of depression, of energy. No? 

Dr. Josh Stout 32:23

Right. So so while all of this is good for you because glucose in your blood is bad for you. Yeah, you need sugar for energy, you need blood sugar for energy. So if you're taking metformin, you could easily start feeling tired all the time. You're going to start having muscle weaknesses and things that really start to make you feel tired all the time. And so this could then actually be accompanying the statins where you have muscle weakness and muscle fatigue making you really not want to exercise. So this is this is the downside is is the overall fatigue that both of these drugs are likely to to cause. Now, you mentioned CoQ10 as a way of increasing oxidative metabolism. This will increase energy across the board. It's not going to change the the symptoms of calcium release caused by the statins. It's not going to change the amount of sugar being released, but the sugar you have will burn more efficiently if you have all the enzymes you need. And CoQ10 is one of them. So you'll you'll be burning that sugar more efficiently, which is, which is good presumably. 

But there are other things that metformin will do. It actually interferes with B vitamin uptake and formation. And so if you start lowering, particularly B12, this also is going to make you tired. B12 is necessary SRY for again I well, it's all about your energy system, but B12 is involved with hemoglobin, so B12 is involving where you get the oxygen to burn the sugar to make the energy. And so if you don't have enough B12, you're going to start you're going to start having less oxygen in your system with which to burn that sugar if you end up with very low B12. And this does this can happen for metformin, you can end up with anemia. You actually don't have enough red blood cells in your body. So the weakness can be really pervasive and progressive. So you'll start off fine. But over the years as you're, you know, getting older and everything is not working as well, your B12 is going to be going down and down and down and down and down. So one thing you might consider again, talk to your doctor is a B12 supplement. When people have low B12 from from metformin, they recommend something like 2000. I can't remember what the dosage thing. It's not milligrams, definitely not milk four grams. Yeah I think it's micrograms is MCG but they are… 

Eric 34:57

MCG is not microgram? 

Dr. Josh Stout 34:59

It probably is. I'm just used to like scientific notation for a micrograms which is the Greek letter Mu, followed by a G. 

Eric 35:05

You can't put that on a vitamin bottle. 

Dr. Josh Stout 35:07

Exactly. So anyway, so it's MCG’s, so I think it's micrograms, but I didn't actually look that one thing up. I said that's probably micrograms. 

Eric 35:14

Does say MCG that I know. 

Dr. Josh Stout 35:15

Know. Yeah. Anyway so if you have low, if you have low B12 they recommend between one and 2000 to bring it back up and then 1000 micrograms as a steady dose to keep your energy there. So it sort of gives you a rough idea of these things. These are, these are dietary supplements. So they're not prescription B12 will help anyone get a little bit more energy. It's something that they put in energy drinks. It's something they recommend for energy. Why is it doing that? Because it's going to increase your red blood cell count and it's going to increase your ability to take in oxygen. 

Eric 35:50

Is an increase in red blood cell count always a positive thing? 

Dr. Josh Stout 35:55

There's I don't think of any way it can be bad. I mean, there's obviously there's going to be some sort of limit, but I don't know what that upper limit is. 

Eric 36:02

It will make you feel like less short of breath. 

Dr. Josh Stout 36:04

You're going to you're going to feel like someone who's had more training, you're going to feel because what does exercise do? It increases your red blood cell count. So it's going to it's going to give you more energy. It's going to it's going to increase how much oxygen goes into your body. You're going to just have more stamina, etc.. And B12 can help with all of that. You know, up to a point, once you saturated the system, you're not going to keep making more and more red blood cells as you increase the dose. 

Eric 36:27

I've also read that the B12 is water soluble like like vitamin C and therefore what what's not necessary in the body just washes away. 

Dr. Josh Stout 36:36

I'm not sure about its water solubility. I didn't look into that in particular, but that's true of a lot of these supplements is that it will just wash away you. Same thing. Yeah. Even if it's not water soluble, your body can't use the access you're taking. It's not, it's not like, you know, vitamin A in a polar bear liver that's going to murder you. 

But these are, you know, vitamins that within the range you're taking them are probably not dangerous. Yeah, but also like vitamin C, you probably already have enough. Most of the time, if you're living a normal life, you don't need extras. I'm saying things that because you're on these medications and you start feeling a little tiredness, this might be a way you can approach the issue. There was one last thing I wanted to mention about the the metformin. So I want to stay focused. 

Eric 37:26

I just want to ask I also read that metformin also improves the health of the. 

Dr. Josh Stout 37:34

Yeah, we were just getting to. Okay, okay. That was my last thing. 

Eric 37:36

Forgive me, I we're on the same thing. 

Dr. Josh Stout 37:37

Yeah, exactly. Yeah Yeah. So, so so microbiome stuff, if you're not absorbing all of that sugar, that sugar is still in your gut. And so you actually end up with more bacteria in your gut. Now, this can be good and or bad, mostly good, but it can be bad. So probiotics in general are good for you. Probiotics in general increase the amount of bacteria in your gut. The makeup of your microflora really matter. Diversity, all of these things matter. So if you are eating lots of sugar and taking metformin, I suspect that's going to lead you towards bad microflora because you're going to have just an excess of sugar in your gut. However, if you have a sort of normal, healthy diet, let's say you're eating a mediterranean diet, sort of the optimal diet that you as an American can eat because you're not eating raw fruits, you're going to have relatively low amounts of of sugar coming in because most of the sugars you eat are going to be complex forms from vegetables or whole grains. This is then going to keep a nice steady supply of food for your gut and you're just going to slightly increase that supply with the metformin because you're not absorbing as much sugar. And so you're not going to send your whole microflora out of whack. However, the microflora that are there are going to end up being the ones that normally eat indigestible sugars. And so these are the ones that often specialize in the soluble fibers. And so these are the ones that you actually want because soluble fiber is something that increases diversity of your medical microflora and tends to increase health across the board, particularly with the chemical butyrate, which I mentioned before. I did a little bit of research on Butyrate. It's a fascinating thing. We get it literally from butter. It's where we get the word from butter to butyrate. It's from the Greek word butyrate butter, and it's it's the smell of butter. It's actually the smell of rancid butter. And it it is a molecule that your stomach actually needs. I'm not saying you should now go on a butter only diet. I'm just saying that it is something that you need in the right amounts and we often don't have the right amounts, partly because it's absorbed before it gets to where it needs to be. 

Eric 40:07

Even if you eat butter, you might not have enough butyrate. 

Dr. Josh Stout 40:09

It might not get to where it needs to be. The butyrate, your lower intestine needs butyrate to live. It's one of the energy molecules that your intestinal cells actually take up. If you starve them of butyrate, you will start damaging your intestine. You'll actually you're at your intestine itself will start to decay and not work as well. These are these are the things related to irritable bowel syndrome and all these other things. 

Eric 40:37

So how do I get butyrate there if eating it doesn't do it? 

Dr. Josh Stout 40:40

The fiber. I mean, you always knew fiber was good for your intestines. This is one of the reasons why. It's not just the pass through rate. It's actually feeding your intestine. 

Eric 40:50

Soluble fiber, not the insoluble fiber, because there's both kinds. They’re different. 

Dr. Josh Stout 40:54

Both kinds are important. But the sugars that get to your lower intestines are the ones you haven't absorbed and that the bacteria that right. 

Eric 41:04

This is non digestible meaning it gets there. 

Dr. Josh Stout 41:06

It gets there. Exactly right. And so sugars, fermentable sugars is what they call them. 

Eric 41:11

Why is something I can't digest important and good for me? 

Dr. Josh Stout 41:14

Particularly for your stomach - your intestine.

Eric 41:17

Things living inside me that need it. 

Dr. Josh Stout 41:20

Well, and that and that and the things they produce, you need. So it produces something in your lower intestine that keeps your lower intestine alive. Without it, your lower intestine is going to suffer. It can actually be starved. 

Eric 41:32

So the insoluble fiber that gets down to your lower intestine feeds the critters that live down there. And then part of what they excrete is the butyrate that your body needs, that your intestines need. [Exactly.] It's a symbiotic relationship. 

Dr. Josh Stout 41:46

Absolutely. It's a symbiotic relationship. 

Eric 41:48

You need to feed them fiber. 

Dr. Josh Stout 41:49

And it's and it's and it's larger than that in that the butyrate, which we talked about in some other talks, also reduces the DNA binding to the histone proteins. And so you're going to increase DNA expression. So butyrate is actually going to allow the DNA to be copied better because it's more accessible to your body. And so it's going to reduce aging. In that sense, a lot of aging is either caused by glucose burning things or by your DNA, no longer expressing all the things it needs to express properly, which is why everything stops working as well. 

Eric 42:30

So that you can’t heal yourself so that you can't remake yourself. 

Dr. Josh Stout 42:32

Everything, everything across the board is why everything starts to going worse when you hit 50. 

Eric 42:38

And fiber is literally at the foundation of what makes this possible. 

Dr. Josh Stout 42:43

Yes. And so one of the reasons that metformin is now being seen as this sort of off label way to extend your life is it has so many side benefits. It may be directly anti-aging in the sense it may be indirectly anti-aging by lowering the glucose. It's going to help you lose weight, which you know is going to be good for you. And so it's going to work really well. 

Eric 43:08

And it also improved the endothelium. Didn't didn't that I think I read that somewhere that it also. 

Dr. Josh Stout 43:12

It may I haven't read that or not read. 

Eric 43:15

You know that both metformin and and I did not know about statins maybe I'm confused I have to go back anyway. Go on. 

Dr. Josh Stout 43:20

Yeah. So anyway, so the metformin is going to increase your, your, your, your intestinal health and it's going to be then causing connections between the vagus nerve which connects to your lower intestine as well as everything else in your body and your brain directly. 

Eric 43:40

So now you're going where I was going to ask about, which is now the the gut brain connection. The gut. 

Dr. Josh Stout 43:46

The gut brain connection. Exactly. 

Eric 43:48

Is directly affected and improved by. Absolutely. Fiber, which feeds that. 

Dr. Josh Stout 43:54

So So so when you have this increased amount of butyrate and other bacteria in your lower intestine, because now these are very happy bacteria, they're telling your vagus nerve that they're happy and that they're getting what they need. And that vagus nerve then goes to your brain and says everything's A-OK. So you get increased dopamine, you get increased serotonin, your mood improves. And so you're going to you're going to you're going to feel happier. All of these things are going to improve. So I just want to want to finish with. So the basic takeaway for both of these things is possible fatigue. The basic takeaway for the fatigue is you can treat deficiencies either with enzymes or vitamin B12. But overall, the combination of statins and metformin are going to increase your your quality of life, your overall life span, and generally work together to improve your oxidative metabolism overall for sort of how you deal with things you're going to need to to to help it along because you're you're, you're actually lowering some of the feedstock for it, right. You're you're getting less glucose into the system and you're possibly lowering the the vitamin B12, which makes the, you know, the oxygen come in with the hemoglobin. So If you if you can stay on top of that side of things, you will really improve your overall quality of life, in my opinion. 

Eric 45:24

Better life through pharmacology. 

Dr. Josh Stout 45:26

Absolutely. And these things, you know, you'd want to start slow and then build it up, keep an eye on on on your your, your blood levels of glucose and cholesterol, etc.. But they really do seem to have the ability to keep your heart working. Well, keep your blood pressure down, keep your weight down. Right. That there's a straight ahead sort of aesthetic value there. And, you know, generally even up to including improving your mood. 

Eric 45:58

With that, it's just crazy. I think. I think, you know, the one thing that that in my mind connects to all of this, but is a whole episode unto itself. If it's something you want to undertake, is this really connects to the whole world of probiotics, which there's no real science. 

Dr. Josh Stout 46:12


Eric 46:13

For I don't know if you want to go there because there's no science. 

Dr. Josh Stout 46:15

No, I don't. I don't really want to, but I did want to mention that both of these work better with a healthy lifestyle. So. So again, to stop the muscle cramps exercise, don't exercise if you have muscles whatsoever, you're just going to make things worse because now you've built up lactic acid, etc., can make the muscle cramps worse. But if if you can start slow work up, you're going to keep pumping out all of those toxins. Same thing with the sugar. Sugar can start building the wrong kind of microflora in your stomach. You're going to get too much of the wrong things and not enough of the good things. So watch your sugar intake. Eat more of the complex carbohydrates, the same things you should have been doing to stop having to take metformin in the first place. But it's going to be slightly more important now because if you eat a lot of sugar, it's going to go directly to those bacteria because you're not able to take it out of your stomach as well. Are your intestines. 

Eric 47:08

So so then, you know, walking down the street with my kid, I'm doing my best to live, you know, the best lifestyle I can. I've actually cut dessert out, don't have sugar in my coffee, all the rest. Most of my refined sugar is gone. But whenever the kids have an ice cream, I want a bite. Like I don't have a whole ice cream. At what point does it become crossing a line? 

Dr. Josh Stout 47:28

So there's no way to know. There's no way to know. 

Eric 47:31

It’s so hard to judge on a day to day lifestyle. You don't want to be puritan about it and cut it out completely because where's the fun in that? But on the other hand, when do you know that you're making a negative difference or not? 

Dr. Josh Stout 47:45

I mean, you should be able to feel it, right, if you eat enough sugar to get the insulin spike and crash and you feel really tired and you get a headache, that was too much. You know, this, this, this. 

Eric 47:56

I’d like, you know, before I hit that. 

Dr. Josh Stout 47:57

Yeah, well, you kind of do. Yeah. You know, the same, same thing for, you know, think about what happens when if you start getting too much bad bacteria in your stomach, some of that you might not notice right away. It could be affecting your mood with insulin spikes, etc.. It could be affecting all sorts of things. But the first thing you going to start noticing is, you know, bloating and gas. Yeah. And you're going to have all those bacteria in your stomach producing gas. That would be an indication that you'd gone too far. So, you know, these are these these are these are ways where you can start thinking about your own lifestyle, you know, taking taking the medications that your doctor recommends, but then trying to understand what they are doing so you can make yourself have sort of, you know, the optimal life where you have energy, you have you have, you know, the ability to eat what you want Up to a point. Yeah. And you and you and you have enough and you have enough energy to keep the exercise going so you can make maintain a healthy lifestyle. 

Eric 48:53

Fascinating and and and very personal. Absolutely. These are drugs that I am actually taking. 

Dr. Josh Stout 49:00

Yeah. Well, we we hit 50 a while ago. So this is this is a line we've crossed. 

Eric 49:04

Yes. All right. Well, thank you so much, Josh, I think I think I hope that we can keep coming back to these. I know that we've had a lot of recurring themes, but this is very real. So. 

Dr. Josh Stout 49:14

Yeah. Thank you. Thank you so much. All right. 

Eric 49:16

Till next time, folks. 

Statin - Wikipedia

Nocebo - Wikipedia

Metformin - Wikipedia

Insulin - Wikipedia

Glycogen - Wikipedia

Blood sugar level - Wikipedia

Coenzyme Q10 - Wikipedia

Ubiquinol - Wikipedia

Vitamin B12 - Wikipedia

Dietary fiber - Wikipedia

Butyric acid - Wikipedia

Vagus nerve - Wikipedia

File:Atorvastatin binding.png - Wikimedia Commons

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