Timestamps/Annotations: 00:00:00 RP Longevity Part 2 Teaser Trailer 00:01:35 Personalized strategy benefits and intro to Dr. Miriam 00:05:40 These are some things almost everyone can do to promote longevity 00:07:17 Why is the thymus important for longevity? 00:10:43 Simple strategies to help with longevity (Vitamin D3, K2 Nattokinase, Zinc and it’s interaction with other minerals) 00:18:25 Metformin, Akkermansia 00:30:00 Why Dr. Miriam prefers Berberine over metformin 00:32:14 DHEA 00:38:44 Why would I mess with my hormones? 00:42:13 Growth Hormone, Rapamyacin 00:50:05 Melatonin 00:57:20 Calorie restriction 01:07:46 Chronic stress is the worst thing for longevity 01:15:01 Rapamyacin  01:27:33 Rapamyacin and balancing it with growth hormone 01:29:50 GLP1s 01:40:07 Part 3 to come/ Where to find Dr. Miriam

00:00

Hey, it's Owen Orngson here, your host for today of the Rejuvenate podcast, founder of Genetic Insights and author of the Rejuvenate Blueprint. And I'm delighted today to be joined again by Dr. Miriam Mikitsky, normally shorn to Dr. Miriam, who is our resident MD and functional medicine doctor and expert and lots of other stuff.

00:19

We had Dr. Miriam on recently to talk about longevity. And in the first episode, we talked about the kind of the causes or like the root issues when it comes to what would cause premature aging or reduce longevity. And we talked about testing and we emphasized how, you know,

00:41

It's much better to come up with a personalized strategy based on testing rather than only doing a very general strategy. However…

00:50

As Dr. Miriam and I both know very well, even though you do need to customize your strategy for every person because every person is different and what's good for one person is not good for another person. However, it is also true to say that a lot of the time as a practitioner, you are just repeating yourself over and over again because there is a lot of adaptability.

01:10

advice for longevity which is if not universally applicable then at least applicable to most people and so in this episode we thought we would go through and talk about uh you know dr miriam's favorite longevity strategies and i will be asking her about uh in the second half of the episode i'll be asking her about any of the things that we haven't already covered in terms of the advanced strategies which you may have you know heard other people talk about um

01:37

to hear from Dr. Miriam from her expertise both as a medical doctor and as someone who works with a lot of people in practice like does this actually work? Is this worth doing? Is this worth the money? Does it cause too many side effects? So we'll get her take on a dozen or so of the

01:54

most commonly recommended advanced longevity anti-aging strategy as well. We're not going to be talking so much about appearance. We already did an episode recently about skin health and stuff like that recently. So this is more longevity as in, you know, feeling younger and lasting longer as opposed to looking younger. So with that long introduction over, welcome Dr. Miriam. Yes, thank you so much for having me. And yes, we're going to be focusing more on

02:22

what we can do to expand your health span and, you know, generally feeling not just living longer biologically with your chronological age, but just, you know,

02:32

preventing the aging of your organs essentially and feeling more energetic and cognitively with it really yes and in the last episode we already talked about why this is a passion of yours um you talked about how people uh you spent time with people especially in asia right where you saw that people even as they were getting quite old they seem to still have a long health span is that right and made you kind of question how we could have more of that

02:56

Um, and in the Western countries, if I remember that correctly. Yes, exactly. And I think, you know, made a good point when you said, oh, we're not talking about appearance. Cause I think that's sort of what people kind of zoom in on when it's longevity. But for me, it's more about like, what can we do to maintain balance, uh, like actual balance. So you're not falling over strength. Um, and, you know, and actually just like brain function. So you're, you know, without the older age and you could just see that.

03:22

the scene they were ahead just even through their lifestyle practices so you know I would say that generally my my hacks are a little bit of a combination of yeah lifestyle strategies that can be applied and to most people in addition to in addition to you know herbs and supplements that I think some of them

03:42

are quite underrated. And then also some of your more newer age therapies like exosomes, PRP, rapamycin, those things. Excellent. All right. So it's an exciting episode. We did a brief kind of rundown before we started recording, but you know, there's a couple of things there. I was like, Oh, I'm not familiar with that. So I'm looking forward to this. And I'm looking forward to hearing, you know, your take as well, you know, about everything. So yeah, let's get into it, Dr. Miriam. So let's start with, as we said, like, what's the endocrine,

04:10

And again, I don't know if you agree with me that there's almost nothing that's universally applicable. Like there's always exceptions, but still what's the advice, the longevity advice that's the closest to universal as possible, right? Like the things that you tell most of your clients, if not all of them, which is, you know, going to help them. It's a tough one. It's such a broad question, but I would say that, yeah,

04:33

You know, basics, there was a study done called the TRIM study where they were looking at what you could do to help with thymus regeneration, immune restoration, and also lowering insulin and lowering blood sugar. And that was one of kind of the first studies where they used, you know, like an epigenetic clock to verify that there's actually going to be a decrease in biological age.

05:01

And they use quite basic things. So there's zinc and vitamin D, DHEA, metformin and growth hormone, and sort of that combination. So I would say…

05:14

More or less, everyone could, you know, can have a strategy where they have some basic nutrients to help with immune function, some hormones that can help with aging and with stress mitigation, and then things that can help with blood sugar. So that would probably be my kind of nutshell.

05:33

what you want to start with. So nothing that actually seems too advanced, but I think, you know, you need a groundwork to work on. Definitely. You know, yeah, excellent. Let's start with that. So let's do one of those at a time then. So if that's okay. In fact, just rewind a second. You talked about the thymus. So can you tell us what the thymus is, why it's important? I don't think we covered that in the previous episode. So tell us what it is, why it's important for longevity and anti-aging. I guess in a nutshell, the thymus is, you know,

06:02

you know, essentially where a lot of your, you know, a lot of your immune system development and maintenance happens. And that's where you, you know, you're producing your immunity cells and where they mature. And so that is very important for your adaptive immunity so that which, you know,

06:21

Again, it's important for your body's ability to recognize and then respond to pathogens in the environment, to abnormal cells. So you really want to make sure that the thymus is healthy to protect against infection, cancer, inflammation, all of which really influence aging and lifespan. And we think that as you age, your thymus actually starts to shrink and disappear and that's

06:51

That's sort of what we call involution of the thymus is one of the reasons why you're then more susceptible to infections, why you might have a higher risk of aging-related conditions like neurodegeneration, cancer, but also autoimmune conditions. And then as that thymus also grows,

07:10

deteriorates, goes away, that is when your body starts to accumulate those senescent immune cells which themselves produce a lot of inflammatory cytokines. And senescent cells we talked about last time, so those are kind of zombie cells or cells which become rigid and basically they are not contributing anything and they're kind of getting in the way. That would be the simplified way of looking at it, I think. So, okay, in the thymus…

07:39

I think I heard this theory before, possibly from a different source than what you were talking about. They talked about the thymus. I think this is actually Russian research. So the thymus and the pineal, as you said, they atrophy very early, right? What age is it that the thymus starts to atrophy, roughly? Is it like 15 or 20 or something? Like by the time you're an adult, it's already… It is quite early. I want to say that…

08:05

It definitely is at its largest in early childhood and puberty. I believe it's kind of in the early 20s that the thymus starts to atrophy. And we think it's sort of almost non-functional by 40 to 50 years of age. So, yeah, so really…

08:25

Kind of something to start thinking about particularly if you're interested in longevity and you happen to be of that younger age group You know that you're already kind of aging just through that process And I heard about it shriveling away a long time ago But I recently read something as well that said that it starts to become more fatty almost like a fatty liver Yeah, you're nodding. So that's correct as well, right? Yes, exactly. Hmm interesting. Okay And so that is reversible. That's your take. I

08:50

to some degree or is it fully reversible what's possible i wouldn't say it's it's um it's fully reversible but uh we certainly can slow that process from happening and and this i mean this trial did show that there was partial regeneration of the thyrus of the thymus with with just these quite simple interventions excellent all right well that's a great starting point let's talk about those simple interventions because that's quite an achievement as you said and it does explain why um

09:17

You know, I mean, it's, God, things are different now. Even when I first started teaching this stuff in 2010, I used to say, you know, when you're a child, you're healthy and you get less healthy as you get older. But of course, there's so many children these days who are born unhealthy because of,

09:30

various factors. But anyway, if you're an older person watching this, you kind of remember back when children used to be healthy and, you know, as you said, the famous not being atrophied plays a significant role in that. So, yeah, what were the strategies, Dr. Miriam? So, I mean, in this study, it was particularly just those actual supplements. Well, let's break them down. Let's go through them one at a time and tell us, you know, which ones you use and what dose and all that kind of stuff. Again, obviously, as

09:59

Personalize is always better, right? But just as a general strategy. So, yeah, I would say vitamin D is something that I think most people need to take, especially even if they live in a sunnier climate. I find most people just really seem to struggle to just absorb the vitamin D from the sun on its own. So I would say…

10:25

Really, you need to have your levels checked. But wintertime, I'm usually telling people to take at least 5,000 units per day. But that can even go up to 10,000 in those where we just see really low levels. And we think they might have a vitamin D receptor problem.

10:43

a snip that maybe just prevents their absorption. I guess also taking a step back from that, we know vitamin D is fat soluble. So if somebody has poor gut function and may struggle with fat absorption, they're also then going to struggle with absorbing vitamin D so that you might have to work your way back there and improve fat absorption. Okay. Um,

11:04

And are you ever concerned that that's too much or like in terms of in reality and testing, do you see, you know, that never becomes excessive at that level? I've only seen it once.

11:14

a couple, like I would say one or two times, and I'm still not convinced it was the vitamin D. Also, I like to pair it with vitamin K2 in the form of MK7. And actually, I would say on that front, the MK7, natokinase, I also sort of use as a longevity supplement. We can probably add that. I don't leave it to the end of the list. Yeah.

11:37

But I think those two in combination, I haven't seen any adverse effects. All right, awesome. What's next? Zinc. So zinc we know is a co-factor for many reactions in the body. So it's important for immune health, hormone health. And then I would say from a longevity point of view, I think we…

12:04

We know just that it's important for so many of these biochemical processes. So even in

12:08

in the clearance of senescent cells, um, probably requires zinc. And, um, and because immune function is so important for longevity, um, you know, we, zinc really helps us keep that immune balance. So, um, that's also something I usually recommend in, um, for most people, I would say for adults, usually around 30 milligrams, which is also quite a high dose. Um, and I like to use zinc picolinate, um, but, uh,

12:38

Again, that's just what I've seen research on. Is there a reason you prefer that to like an amino acid salator type like magnesium glycinate or some of these other…

12:49

I use zinc at quite high doses for people with mood disorders. And that was through the work of William Walsh and the Walsh Institute, where we know that zinc has a profound effect on lowering oxidative stress and pyrols.

13:09

Uh, so he preferred percolonate and he was the one that sort of did that a lot of research onto it. So I just stuck with that one. And I found that, uh, when we would check plasma zinc levels, it seemed to absorb best. Um, I'm not, I find sometimes you can't get percolonate. So I found that zinc, um, zinc bisglycinate, um, is, um, even zinc citrate isn't too balanced, but, uh, I've just

13:35

Yeah, I just always had a preference for the Bacillin A type. Fair enough. Yeah. And so you said 30 milligrams. Are you ever concerned that it's going to deplete copper or…

13:44

I think a lot of our viewers are kind of anti-copper these days, to be honest, but I don't know what your take on copper is. Is that a concern, that it might reduce it too much? Yeah, it's a tough one because I would say Walsh, when I did that training, was also anti-copper. But we know copper can also, with that depletion in copper, we often see depletion in iron levels.

14:04

And so I was seeing that and I mean, usually, you know, biochemically recommending a dose of 15 milligrams of zinc to two milligrams of copper. So if I see that copper fall very low, I will add one or two milligrams. But generally, if we look at the foods people are eating, they're eating foods that are richer in copper than in zinc. So often…

14:25

often I think it balances itself out. 100% yeah. I've been on the fence on this one as well but I'm leaning more and more to like higher and higher zinc to copper ratios and even iron getting low isn't necessarily always bad right? The

14:40

there's a whole anti-aging contingent I've noticed these days who are blaming iron for like aging, uh, especially free iron. And they're saying that, cause obviously it acts as a free radical of his excessive amounts and like it rusts the cells and damage them and stuff like that. Um, I mean, obviously I know there's a medical condition, hemochromatosis, where it's definitely the case, but what's your take on, um,

15:03

you know, reducing iron as a longevity strategy. Do you think there's any validity to that? - I think it's, yes, I definitely think there's validity to that, particularly when the iron is high

15:15

Well, particularly when you have someone where they're not losing iron. So I see, for example, women with hormonal imbalance and let's say they're having heavy periods, they might be losing a lot of blood and therefore have chronically low iron levels. So in that sort of a cohort, you wouldn't necessarily want to deplete their iron stores. But I'd say once you get, once people are sort of in a stable state, especially if they tend to accumulate iron, then I would say that that is one of our strategies.

15:43

I would even go so far as to say that I've used kind of active chelators to try and get that iron down when it hasn't really come down in other strategies, kind of like you do with other heavy metals. So yes, I do believe in that. I would just say there's still a percentage of people that aren't getting that much iron through their diet at all. And also with the work with…

16:07

with the Walsh Institute where we're looking at zinc, copper and mood. I've actually used that work for a lot of children and so you didn't really want young children with low iron levels and like very low ferritin so that was where I had to, I often would add a little bit of copper back in to balance it out and that did seem to correlate with an increase in iron. This goes to show yeah that again you kind of have to personalize a lot of this stuff.

16:34

Yeah, it's funny enough, I just saw someone today, like number one longevity strategy, if you're a man is to, you know, give blood regularly to reduce those iron levels. But crucial caveat, if you're a man, right, as you just said, you know, not a child and not a woman of menstruating age. Anyway, sorry, I went on a tangent there. So back to this kind of standard protocol that you talked about. So we did

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with K2 and nettoquinase. We talked about zinc and its interaction with other minerals. What's next? So we also have metformin. Okay. Yeah, tell us about that. You know, so metformin is a medicine that is to

17:12

traditionally used to lower blood glucose and lower insulin. And of course, it's usually actually the first line for that. So it's probably a medicine you've all heard of. But we now know that actually metformin is… We know that high insulin is aging, promotes inflammation, and

17:41

And therefore, yeah, it can be a very effective strategy for longevity. It's not my favorite one, but it just happened to be in the study. But it was part of that study, right? Okay, yeah. And why is it not your favorite? Well, so just to go back, so we know that it's improving your body's response to insulin and lowering glucose levels. But in that process, the way that it's working is it's kind of suppressing urination.

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your body's, your liver's ability to produce glucose from non-carbohydrate sources. And we, I just find that as some of these medicines at the doses that you're supposed to take them

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in a way, can then deplete other nutrients in the body. So we know that some of the side effects of metformin include GI issues, and that could, of course, affect your microbiome and your ability to absorb nutrients. We also know that it can… Sorry, before we go to the next one, I have had people react to that criticism by saying, well…

18:50

It's because, you know, it's similar-ish to berberine, right? It's because it's killing bad organisms. That's what they say. So would you… And then it increases some of the good ones like akkermansia, which I know we're going to talk about later. So would you agree with that? Or would you say, actually, no, it's not the case. It is killing some good organisms as well and potentially creating a problem? Yeah, I mean, I'd say when I've done the gut microbiome tests on people on metformin, they do tend to be low in…

19:17

of the good bacteria too um and i mean i would say that it does work just in a similar way to um to berberine and neither one is going to be as specific to killing off only the bad bacteria as as they're made out to be i i find that in general um yeah metformin and berberine that are

19:40

They're better at killing off the bad bacteria because you typically have more of them, but you will also just affect the good strains too. And actually, I haven't seen, maybe I just haven't read this study, but I haven't particularly seen anything about metformin particularly increasing acromantia. But

20:02

I don't know if that's something you have read? Yes, that was one of the claims as to why it worked or how it worked is by increasing acomancia. The acomancia actually improved the insulin sensitivity. So that was the theory behind it. Yeah.

20:19

As I said, I don't know if it actually works in practice because I haven't seen as many as you, but I have seen plenty of people who've taken berberine and none of them had high acromantia. So I kind of would go along with you, but that was what the study said. Because I thought in a way it was if you had acromantia, then you were a better candidate for using either berberine or metformin. But then acromantia,

20:47

then if you didn't have it, taking it wouldn't sort of magically cause it to grow back. No, no, not grow back, but like increase levels. I think that was the claim. Because most people have at least a tiny bit, right? Well, I don't know. I would say that's a big problem I see in my practice is no acromantia. And I guess I know we're going to speak about the acromantia probiotics later on.

21:12

Might as well, actually, because that is a big problem I had. And before the acromantia-based probiotics were produced, you know, I was trying to use certain prebiotics that were supposed to help with acromantia, like aronia, modified citrus pectin, some of your antioxidants, and

21:35

Those sorts of strategies. And sometimes we would then actually see some acromantia growth, but not always. And then, you know, kind of the consensus in the field was actually, if you don't have acromantia at all and there's no growth, it's very difficult to suddenly have growth. I'm just looking at the GIFX and the coins of M, 30% of the tests they do have zero acromantia. So…

22:00

But yeah, I guess you're probably seeing the sicker. I was going to say that's probably like my entire K-Ship pool. Yeah, fair enough. I know that mine was almost zero. So I'm one of those people. Okay.

22:12

So, all right. So we talked about, so acromantia, oh, let's, yeah, let's talk about that for a second then. So yes, you can get that as a, as a probiotic now, right? You can buy it, which was not the case until fairly recently. Is that right? Exactly. So there is, because acromantia to actually produce it as a probiotic, it has to be produced under like zero oxygen conditions. So you can imagine that's hard to do in a, you know, in a lab. And so, you know, really it,

22:41

I'm familiar with Acro Manse, at least potentially from the last four years, but I think it hasn't been around for that long of a period of time. It's not common, right? I think if you look for it on Amazon, there might be zero brands selling it. It's not like Bifido or Lacto where there's millions of versions of it. And in fact, a lot of them…

23:05

Because it's so hard to produce, you would be suspicious of a lot of brands, I think you said when we talked about it, right? So we don't normally do brand shout outs and I don't sell it, but is there any particular… I know I said I got some from Laird Origin. You said that's probably one you would trust.

23:21

I mean, I heard about it through the company Pendulum. They reached out to quite a lot of practitioners. So they're from the US and they've actually, I think apart from just the acromantia and mesenophylla, they've also isolated other practices.

23:40

like beetroot producing bacteria and certain strains that work in conjunction with um with the acromantia but i believe their first product was actually acromantia um and um so that that is the brand that i use uh it's just it can be quite difficult to get a hold of in the uk um where i practice but um that's the one that i i like to use

24:03

Great, okay. And you do practice throughout Europe as well, I know, right? You're allowed to prescribe throughout Europe and you have clients from throughout the world. Actually, I realized about Comancio.

24:13

We didn't tell people why they should care. Let's tell people what Acomancia does. We've talked about how you can buy it and how a lot of people do not have a lot of it. I don't think we talked about it last episode. So we talked about Acomancia. I think I just mentioned that it increased insulin sensitivity, which obviously is a big deal. I think most of our viewers and listeners have heard of insulin resistance and why it's bad. But why else would I want to increase my Acomancia and what's good about them? Yeah.

24:39

you know acromantia um so we know that it's a um a specific bacteria in the gut microbiome that um is actually um quite instrumental for breaking down um and mucus which is a kind of a vital part of the the guts barrier and um and it's essentially able to use kind of as mucus as a food source and it can take um like prebiotics from what you're eating and kind of

25:08

Basically convert that into the short chain fatty acids that make an important part of your gut barrier. And we know that having that healthy gut barrier is essential, not only from a absorption digestion point of view, but also just from an immune balance point of view and reducing inflammation in patients.

25:29

that part of the body. But we know particularly that the acromantia, we think because of its role in helping with nutrient breakdown, also regulates blood glucose levels and reduces fat accumulation. So we've actually, there's been, before even they made the acromantia probiotic, we knew that acromantia, having a low level of acromantia actually predispose you to

25:56

type 2 diabetes and other metabolic conditions. Yeah, very interesting. All right, so there's an important one just as much as bifidobacteria, which I think more people are familiar with, and for anti-aging as well. Okay, right, so that's a big tangent again, but let's go back to your list. So we talked about metformin, and there are a bunch of people in the longevity anti-aging community that do recommend metformin.

26:22

So do we cover all the pros and cons to metformin already? Is there anything you want to add about that? I'm not anti-metformin. I have used it in practice. And also for some patients, it has helped to lower their blood sugar. And we can always…

26:41

give a methyl B12, you know, or something to mitigate the effects on absorption. You know, so, and we do know that there is evidence to suggest that it's a, it activates

26:57

basically the pathway AMPK that is activated during caloric restriction. And also that activation helps to promote glucose uptake. So it still is a good medicine. I just think that it's quite strong and can then, for people who may not be, may

27:17

may not be well and still have some issues and with their gut microbiome, it may not be the best choice. In an ideal world, you'd meet all of your nutritional needs in the form of vitamins, minerals, phytonutrients, and more from the foods you eat. However, unless you prepare all of your food at home from scratch using the highest quality ingredients possible, the reality is that most of us need some nutritional support.

27:37

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28:38

Why do you prefer berberine? Let's put it that way. Or do you? No, I do prefer berberine. I would say that generally I think that often when we look at plants and herbs, sometimes those compounds in the herbs haven't completely been isolated and I think a lot of them do work in synergy. So we think that berberine might be the…

29:07

the component that has the biggest effect, but there might be other synergistic polyphenols that work in combination. So when you're getting berberine, let's say from golden seal or from coptis chinensis, you're going to get some other factors in there. So I think that, yeah.

29:22

There might be some sort of compounded effect there. But yeah, berberine, just like metformin, also activates AMPK and can help to reduce glucose levels. It also just has some studies showing that it can help with fatty liver and diabetes.

29:43

And generally seems to work broadly as an anti-inflammatory agent. There are some side effects associated with it, but I find that those side effects tend to be milder with berberine compared to metformin. So the kind of bloating or loose stool people get, you know,

30:02

tends to be milder. I personally like to use berberine in combination with things like licorice or more warming herbs, ginger, because that, at least in a traditional Chinese medicine sense, that helps to kind of offset those side effects.

30:21

So generally, berberine is also used as an antimicrobial. So if someone is only taking it for a short period of time as an antimicrobial, then I'm happy with them using berberine on its own. But if they're going to be using it longer term for longevity, for lowering insulin, then I want them to have a more balanced formula. All right, so let's go back to the list, your original protocol again. So we've done that form, and what's next? So we have DHEA.

30:51

which is, I'd probably say, one of my favorite longevity interventions. So DHEA is just a hormone that's produced by the adrenal glands, and it is…

31:03

it's helping you sort of counteract cortisol and is a, um, it's kind of known as the longevity hormone. Hmm. Uh, yeah. Okay. Awesome. I know, you know, uh, repeat who, uh, a lot of our viewers are familiar with and a lot of them are a fan of, was a big fan of the HCA. Um, a lot of people and other people I've interviewed as well. A lot of people who recommend the HCA, like, uh,

31:31

Oh yeah, Dr. Platt, for instance, that's another one we had on here, the author of Adrenaline Dominance. A lot of them say you've got to kind of be careful with the dosage because if you have too much, it can convert into estrogen. And I had been reluctant to try it for ages or, sorry, not try it, but to have a high dose for that reason. But I've been doing 50 milligrams for quite a while now because I…

31:53

in my test results i always had high cortisol and low dhea so i was like finally okay i'm just gonna you know that ratio as we talked about the last episode of high cortisol to low dhea is not good it's a you know predictor of early mortality so um and i have a genetic tendency to high cortisol so to a certain degree that's always going to be at least a bit higher than average so it's like all right i'm going to try upping my dhea and actually um i didn't show you this

32:18

Dr. Miriam, but my estrogen actually went down since I started taking the DHA. So it went in the opposite direction. So what do you think about those concerns that you often hear about? Oh, I mustn't take any DHA or I mustn't take anything other than a very small amount. Was it converse to estrogen? I mean, I'm sure it's true sometimes, but when is it true? When should people be concerned about that?

32:42

I would say in clinical practice, so it is a precursor hormone to both estrogen and testosterone. So, I mean, I would say because I generally see more women than men. My concern with DHEA is, for example, women who have PCOS. Conversion to testosterone is the opposite. Yeah, okay. Right. But it's interesting because I find that I'll often see women with PCOS where their DHEA sort of

33:12

a bit borderline. And I'm like, I wonder if prior, you know, like 10 years ago, your DHA was actually much higher and it's now depleting. And so, you know, would we say no to DHA? Particularly not. I think you'd want to improve DHA

33:27

the um you know hormone metabolism and still consider dhea because it's it's a bit of a conundrum that you will sometimes see high dhea in what you will see high dhea women with pcos but they may actually have had a much higher level and their energy levels being better way back might have actually um like yeah so once you once you let's say how do i i'll rephrase this actually um

33:53

If we know that the high testosterone is sort of then kind of retroconverting into DHEA, once you sort out the PCOS, drop the insulin, actually the DHEA can dramatically drop. And we know that that's actually their sort of true DHEA in terms of, you know, that would reflect why they might have low energy, for example. Yeah.

34:14

uh but but sorry just to kind of answer your question from before i don't use particularly high doses of dha um i would say 50 is actually kind of the maximum dose i generally use um and i do find that some people just mop up the dha very quickly so i always like to retest about ideally three months later but sort of three to six months later because i've had

34:38

patients with non-existent DHEA on their first test and then we would start something like 25 and then they would be in the they would be in the kind of hundreds range way over their their um the range they were supposed to be okay so in many cases there's actually no need to do a high dose that's good to know and uh

34:59

I think the level of body fat makes a difference, right? I'm thinking for our male viewers. So if you have, the more body fat you have, the more your body's going to convert that DHEA to estrogen. Is that right? Exactly. And I would also say that, yeah, we have to take into account your body fat percentage, bone density. Also, I think just

35:20

If you're somebody who, like, you have a high level of testosterone, let's say in the PCOS crowd, or estrogen because your, you know, your adipose tissue percentage is too high, then you don't want to just give DHA without addressing those other concerns. So what's a moderate amount? Like you said in that study, you know, it was obviously effective. What kind of amount is a reasonable starting amount?

35:46

For women, I usually give higher doses for men. But I would say for men, I normally start at 20 to 25, whereas with women, I sort of start at 10. But yeah, but they did use 50 milligrams in this trim trial that I discussed. Okay.

36:05

And what about, I think you and I talked before about the seven keto DHEA. You said sometimes you prefer that, right? Yeah. Under what circumstances would you recommend that one instead? So exactly. For those people who have high testosterone levels or who they started to take DHEA and then they noticed that they had

36:30

facial hair, acne, um, you know, implying that there was too much conversion into testosterone. I will sometimes use the seven keto DHEA. Um, and then also if I'm in the seven keto DHEA won't raise your DHEA as quickly. So, um, so actually in those, in those

36:50

patients where I wasn't quite sure their DHEA levels looked okay, but they had the classic sort of symptoms of low DHEA, fatigue, brain fog, low immunity, frequent infections. I would sometimes start the 7-keto DHEA to see if those would improve and then wasn't too worried about the levels rising too high. What about to all the people watching this right now who are of the mentality like, you know, okay, fair enough, taking a supplement, taking zinc or whatever, but

37:19

especially if it's low in my diet, but why would I want to be messing with my hormones, Dr. Miriam? That sounds like a bad idea. I know a lot of people feel that way. Can we just address that in the context of longevity specifically? Of course. I mean, I completely understand where people are coming from and I would never blindly recommend hormones without testing the levels and then making sure we get the levels back to a certain point. But the way that…

37:49

In the longevity community, we are replacing hormones that

37:52

decline as you get older and we see that hormone decline as a sign of aging essentially you're doing the same with DHEA and I would say with DHEA because it's depleted with stress and if you're somebody who is putting a lot of stress on yourself because you're not sleeping well not eating well mentally quite stressed then you may have a low DHEA at you know in your 20s and

38:20

And then, you know, you would almost, you could have that DHEA level of somebody who's in their 80s. At age 20, you'd want to do something about that. Yeah, but it's hard one to answer because I'm generally quite pro-replacing the hormones that are lost. I mean, you know, because we, a lot of the longevity studies have been done on males. And whereas, you know, we know that females actually have what have,

38:48

Better longevity until menopause and then that protection that women have against cardiovascular disease and the lower rates of cardiovascular disease that disappears after menopause, then women actually have higher rates. And we think that hormone decline is one of the factors that precipitates that. Yeah, that's good. I'll give my take on this as well, which is, as you said, with some things, maybe I don't know if we're going to get to thyroid, but

39:16

You could say you could make an argument You know, you should really only take it if you need it But you have to understand that with some things like you said the HCA or like with progesterone and estrogen beyond a certain age for a woman pretty much inevitably It's gonna go lower and it's gonna make you feel worse that it is lower and it is gonna you know reduce your quality of life quite possibly a lifespan and That's natural

39:45

In the sense that that's not a sign of, that's not because you haven't eaten well, because you haven't exercised enough or whatever. It's just what happens to you as a human. And so it's just a choice about, am I going to accept that I am going to decline as I age? Or am I going to actually attempt to cheat a bit and augment myself? And if you're watching an episode of Longevity, I hope you understand that

40:09

you know, what you're trying to do is you're trying to cheat nature to some degree, right? This is not an episode about just having a healthy lifestyle and doing your best while staying within the cycles of nature. This is like, well, actually we're trying to, you know, a little bit reverse the inevitable decline that happens with nature. And so if you're interested in doing that, if you're interested in longevity, if you're interested in anti-aging, then I would encourage you to be open, obviously not indiscriminately and stupidly as Dr. Miriam said, but yeah, I would be open to these things. So now,

40:38

we'll go back to growth hormone which is a little bit more controversial than dhea um i think a while ago in the anti-aging community it was there was a lot of enthusiasm around it but i think i don't know if i've got this exactly right up to moment you can tell me but the last five years or so especially i've seen a lot of like anti-growth hormone sentiment people concerned that it's growing the wrong thing um you know the c word that we don't talk about on youtube but that it can you know

41:06

contribute to that so first of all yeah tell us what the study said and then tell us your take on it yeah so the study was using about one milligram of growth hormone per day and it was this is over the course of one year and I

41:23

It's interesting because in a sense, when we think about longevity, it's like on the one hand, we want to maintain muscle mass and have good muscle repair and good cellular repair and growth hormone plays a big part of that. But I agree that then where you have…

41:46

and you have like insulin like growth factor, it almost then kind of flies in the face of, you know, when you're wanting to prevent aging, you almost want to slow the body down so that you don't have this kind of

42:03

these processes that are generating inflammatory cytokines. So I would say actually what, you know, the longevity community, I think now there are proponents of actually alternating growth hormone with rapamycin to sort of, you know, kind of in a way mitigate that because, and yeah, so that's,

42:24

But I think it is an important, I wouldn't say it's something that I use kind of as a mainstay in my practice, but it just, again, happened to be in the study. But I think in terms of, you know, something that can help with, yeah, cell regeneration, muscle preservation, fat reduction, bone density, I mean, it does have benefits.

42:49

good effects from that point of view. And of course, fat loss and muscle gain, which is why a lot of people use it like in the, you know, celebrities, models, actors, all those kind of people, sports people, right? They like it because of, for those reasons. And although that's aesthetic, it's not only aesthetic, right? Obviously,

43:09

High levels of fat has correlated with all kinds of bad health outcomes. High levels of muscles, as long as it's not excessive, correlates with all kinds of good health outcomes. So there is that to be said for growth hormone as well, right? Yeah. And I would say the cancer risk, I mean, it's…

43:25

I think what the studies have shown is that it can promote the growth of cancer cells in those who are predisposed to certain cancers or potentially already have the cancer cells. You would never want to give birth hormone to somebody who has cancer.

43:40

who has cancer, I would say even someone who has a strong family history of cancers, of certain hormonal cancers like breast cancer, prostate cancer, you know, you'd have to really look at how they're detoxing their hormones before starting that. So, you know, so I would say that it's,

43:59

you know, you just have to, you can't just blink it, give it to everybody. Okay. And I think we should talk to rapid mice and next, then we can talk about that. As you said, the advanced strategy, but just before we get to that, um, so other problems with growth hormone is it has to be prescribed, which is not an issue for you, but for a lot of our viewers. Um, and then of course it's very expensive, right? Compared to most things. Um,

44:21

And so cheaper alternatives would be growth hormone-promoting peptides like ipamoralin and CJC-1295. I think that in the peptide world, that's often what's recommended. One of them is a growth hormone-releasing peptide and one of them is a growth hormone-releasing hormone. So that combo is the most popular, the most common. There's others as well, tesamoralin and stuff like that.

44:49

And then really that still requires injection. So really bargain basement is just like MK 677, right? Which is just a powder or a capsule that you can take, which is really not very expensive. Um, so what's your take on those alternatives and maybe others I haven't heard of versus, you know, actual growth hormone. Yeah. I mean, I'm my, um, yeah, I would say that, um, from a

45:15

cost perspective and also I would say even from a side effect perspective I'm a big fan of those particularly Ipamorelin CJSA 1295 and you know I think that

45:32

I was going to say rapamycin in my book I think is better. And I wouldn't say that everybody that takes rapamycin has to cycle it with growth hormone. But I would say that, you know, I think, for example, on those who might be at higher risk of poor hormone detox, I prefer for them to use the peptides rather than the growth hormone itself.

45:54

I've seen that there's less risk of those negative side effects, right? Even at an effective dose. Yes, exactly. And we know that, for example, in some people, growth hormone can increase cortisol levels. We don't really tend to see that with the peptides. What about MK-677? Do you have experience with that? It's not something I use so much in my practice. I've heard about it, but…

46:23

Yeah, but not something I'm actually that familiar with. I can tell you my experience. One of the doctors we had on there, I think he said that that's what he likes to use. I took, I think it was a tenth of a dose. I think the normal dose is 50 milligrams, and I took five. And then suddenly, like a few hours later, I had this immense kind of stress. It felt like my blood sugar had crashed more than anything, and I felt ravenously hungry. And I ate loads, and I overate, like it caused a digestive problem. This is about when my digestion was worse.

46:51

And then I read more into it and they said, like, the problem is it spikes the growth hormone and the ghrelin, which is the hunger hormone, which correlates with it at almost random intervals. And obviously I was sensitive to it. I mean, I know

47:09

As I said, a lot of people are taking 50 milligrams or even more, 100 milligrams, 150 milligrams. But that thing about the sudden, unpredictable, random attack almost of low blood sugar and hunger, I found very… And high stress, the high cortisol, I found this in something. So I've tried it once and once only. For people who are a little bit less sensitive maybe and who are eating all day anyway, it might work better for them. And so it is the cheapest option. It doesn't require injecting anything. So…

47:38

It's certainly, I think, defective. It's just that a lot of people don't like the random nature of its effects. Yeah, I would say that I, again, see a lot of patients who are very sensitive to supplements, medications, and have blood sugar issues. And so I almost feel like that would put a lot of people off. Yeah. And I don't have blood sugar issues usually, but yeah, I did with that. So…

48:08

Yeah, that was not great. Okay, so…

48:12

But yeah, so now I guess, have we done enough on growth hormone? Should we go into the rapamycin? Yeah, I mean, I was going to also say, I mean, maybe it's a bit too basic, but obviously you can stimulate your growth hormone release to things like high intensity, the neural training, strength training, getting enough sleep. I would add to that list, I think maybe before we get to rapamycin, we know that you are…

48:39

doing a lot of your detox so like your glymphatic system at night when you sleep so you really want as a part of the longevity to optimize sleep and that's where i'd say from a hormonal perspective i also like to use a melatonin oh yeah tell us about that then because obviously some people are not a fan they're very popular andrew hooverman you know talks uh

49:00

has been saying that he doesn't like it because he feels that it suppresses other hormones. Well, not just he feels, he says this research thing, it suppresses other hormones. But then again, I've seen some people who claim that they're

49:11

you know, healing people of all kinds of things by having really high doses of melatonin, like 100 milligrams or 200 milligrams. So I've seen the whole gamut. I think possibly both things are true. And then there's the whole thing about how there's pernil melatonin, but then there's also intercellular melatonin, right? Which is stimulated more by red light. So there's a whole gamut of stuff about melatonin out there. What's your take on it?

49:34

Yeah, I mean, I would say my views on melatonin are largely positive. I mean, I think now that we have seen studies where people are using super high doses of melatonin, like 200 milligrams in, for example, immunosuppressed people who have been undergoing chemotherapy, and

49:51

I vouch for its safety. I just haven't really seen any kind of adverse effects. What about the next morning drowsiness? I've had a lot of people report that, talk about that. Well, there's, I mean, it's a bit controversial, but some people actually say that that's a sign that your body actually needs more. And I have tried that. And I have had a few people who actually are taking sort of upwards of 20 milligrams and

50:17

have said that it has actually, that drowsiness has gone away. I would say there's actually, there's not much of a harm. There really is no harm in trying to do that. Apart from, of course, you know, if you are drowsy, then you've got to just be sensible about, you know, not getting into a car or like, you know, managing your day. That's sort of more the risk. But in terms of just a health risk, I think you could safely go up to at least

50:43

24 milligrams and see if then you feel less drowsy the next day. It has worked for myself because I used to say the same thing, but I saw that once I took upwards of 10 milligrams, I found that I was not drowsy the next day. Interesting. And what about the criticism that it is messing with other hormones? Do you give any credence to that? I have a few patients actually who started to take melatonin about

51:12

you know, 40, even 50 years ago. So, I mean, older patients of mine who are interested in the research that was done in melatonin back then, I've never seen, I mean, it's not a huge number, of course, but I haven't seen any, there didn't seem to be any issues with melatonin

51:31

you know, like early menopause or things like where their hormones were suppressed in those women. Interesting. Well, Andrew Huberman is talking more about men, I guess. Maybe that's a distinction. He was worrying about lowering testosterone. But then again, a lot of people into longevity are on TRT once they get older anyway. So I guess it was, I don't know, it matters. So yeah, it's interesting to hear that take. As I said, I had seen the research that you're talking about as well, very, very high doses being, you know, curing all kinds of very interesting diseases

51:59

things that were very effective that nothing else is working for. So I actually don't have a strong opinion on this either way. I'm definitely interested in hearing your take and your experience. Okay, so there you go. For someone who likes to experiment, if it makes you feel drowsy and spawning, double the dose and see what happens. But make sure you do it on a weekend or a day when you're not working, right, in case it doesn't work. Interesting. So you said this is a sign that you need more

52:27

Uh, is it like, could it be something else? Could it be like, you're not methylated well or something like that? Like if you, if you feel drowsy the next day, um, cause I, I never feel drowsy next day. If anything for me, it's like when I used to take it, I would have to make sure to go to bed quickly, um,

52:43

Or, you know, just go to bed. Go turn the lights off, everything quickly, because otherwise it would run out. Like, it barely did anything. You know what I mean? Like, that was more my… Or I'd wake up maybe an hour later and I wasn't sleepy anymore. So, like, if anything, maybe I should try diaboling the dose, I guess, because it wasn't very effective. Yeah, the other thing is some people say that…

53:03

people are taking it too soon before they go to bed. Like ideally it should be, you know, 30 minutes to an hour before. And that if you take it right when you're hoping to get to sleep, that can still kind of disrupt the natural circadian rhythm in the sense that you would have wanted that melatonin to increase before you actually do feel sleepy. I don't really think that, um,

53:29

There's a different form you can take. I'm sure if you improve your methylation problems and detox. Not a different form, but is there something else? Is it methylation? Is it something where your body is not breaking it down? So therefore you're still drowsy the next morning is what I was thinking.

53:45

Not that I'm aware of, to be honest. I'm wondering if it's like one of the MAO enzymes or something like that that processes serotonin. I wondered if it might be something to do with them. It certainly could be. I mean, I would say that, you know, you…

53:59

How you absorb melatonin, I mean, I like to use the liposomal forms and the liquids. So certainly you could try a different form. I find that those sometimes work better than the capsules. But I would say if you're not somebody who has optimal detox pathways, then yes, it probably wouldn't be as effective. So you'd want to optimize detoxification pathways, DNA methylation pathways, and, you

54:25

in any way. Okay. I'm also thinking of an experience I had once when I was in a complete mess back in 2020 and, you know, anxious and all these issues, right? That pain issue that I've talked about before and I tried to take a melatonin to calm myself down and

54:41

And it kind of worked, but the next day I was like so woozy and like, whoa, like almost, you know, and I felt full. It's because my body is in such a state, you just wasn't able to process it and detoxify it. And so, whereas I normally, my experience is what I said, like it clears very quickly and I barely does anything. In this case, when my detox bath was completely overloaded,

55:03

Like it was the opposite. Like it was, I was still very strongly affected by it like a long time afterwards. That's what made me think that it could be, um,

55:12

you know, the body's ability to process and detoxify it. That's significant. I mean, I would say with, you know, detoxification where you have the phase one and phase two, the phase one detox actually tends to make a more toxic metabolite. And then often people really struggle with that phase two detox. And so potentially that could have been the issue that, you know, that first breakdown product was, you know, more stimulating, more toxic, right?

55:40

Maybe, yeah. Maybe turn it into DNT. I remember it was pretty tricky at the time. Anyway, sorry. We'll carry on. Okay, so sleep, very, very important. Is there any other kind of more general advice you want to go before we go to the advanced stuff? I mean, calorie restriction. Do we want to talk about that? Yeah, let's talk about that. Anything you want. Yeah. I mean, I would say that that is a strategy that is – I think everyone could employ some element of calorie restriction, but I would say –

56:07

The type of calorie restriction needs to be personalized, you know, and those who, you know, do suffer from hormonal imbalance, high or low cortisol levels might struggle with, you know, your kind of extended calorie restriction or fasting. Okay.

56:26

Okay, so I think everyone's heard of calorie restriction. I know it is pretty much the only longevity intervention that has a lot of evidence behind it. I know a lot of people who are a fan of this show, though, are fans of people like Ray Peet, fans of maybe people like Dr. Jack Cruz. And they talk about, well, certainly Ray Peet talks about how…

56:51

The issue is not that… Well, okay, so a couple of things. First of all, I know he talks about studies where just restricting specific things were just as effective as calorie restriction, specifically if you reduce certain amino acids. I think methionine, tryptophan, and maybe isoleucine, it was just as effective as calorie restriction. And I remember another study he talked about where…

57:13

because a lot of these are my studies, right? Where they just restricted, like they removed all the heavy metals from the food and then they found that

57:22

that giving food completely absent of any heavy metals was just as effective, if not more effective, at restricting the calories. And so the theory behind it is that it's not the food or the calories, it's the stuff that comes with the calories that's the problem. And so obviously, if you're having more calories, then you're having more heavy metals, you're having more tryptophan, you're more methionine, because all of that stuff generally comes with the food. But it's not the calories that are the problem itself, but the things that

57:50

usually will always come with the calories. Yeah, it's a tough one because I mean, I would say that if you think about who lives the longest, it's essentially trying to get your body into a state where it's almost…

58:02

using less energy and is in this kind of low metabolic state which to me would equate lower calories and lower okay well that's a more primary debate then because yes the vp people would say that's not the case that's the that's like that's a mechanistic idea that um that you know the body is like a machine that it only has a certain amount of uh capacity to do things whereas

58:23

If you're increasing in metabolism, you increase the amount of energy available to all the systems in the body. So you don't buy into that. You prefer the idea of reducing the metabolism and reducing the level of energy expenditure and creation. I mean, I just think it's a tough one. I see your point and I do agree.

58:46

I would say that if we look at the blue zones, many of them do eat a naturally low methionine diet. And I wouldn't say that they, I mean, maybe apart from the Seventh Day Adventists in California, I think they don't actively practice a fasting diet.

59:05

you know, like have a fasting practice. But I would say, because I really like mixing kind of the medical science with the more anthropological, like cultural and, you know, seeing how people who actually have long, what do they have lived long, what have they done as a community? And I've just found it quite interesting. I think a lot of that culturally, you know, for example, I think Okinawans have, you know,

59:31

I've always tried to eat until they're 80% full. And a lot of those, I would say, groups, I would say they naturally calorie restrict because they're more active, not really snacking. Well, okay, so we're getting to some points of agreement now because I'm dead against snacking, first of all. I've always told people not to do that. Meals, not snacks, I always say. And second…

59:59

second of all i also agree that overeating or eating until you're full is a bad idea um it overloads the digestive system it's more likely to feed you know bad organisms can create endotoxins and all that kind of stuff so i think even you know red people also agree with all of that so so i think yeah not overdoing it with calories agreed not snacking agreed but actually like

01:00:22

You know, fasting, I think, you know, raises cortisol, it raises a lot of stress chemicals, it kind of puts a stress on various systems in the body. You know, Ray Peet talks about how when you fast, it like raises estrogen, it raises adrenaline, all this kind of stuff, which, you know, potentially is not good. So I think, yeah, I think it's especially the fasting part of calorie restriction that probably…

01:00:43

the percentage of our viewers are against it or against as opposed to, I think no one thinks that you should stuff yourself every meal or a snack between meals. I think everyone into longevity does agree on that point. So, yeah. I mean, I would say that, you know, when I say calorie restriction, I mean, fasting, I generally support more of like an overnight fast and, you know, kind of even sort of like, you know, 12 to 16,

01:01:11

14 hours, maybe going up to 16. But I'm not a fan of day-long fasts or these fasting retreats unless I don't…

01:01:24

unless someone is in an environment where they don't really have to do very much and you think that they could actually be maybe sleeping and then detoxing, that's the kind of environment where maybe I think fasting could have some benefit. But in today's society, if you're trying to fast and also function, I just think with already high cortisol levels, you're going to make that problem worse with fasting. I think that's a great distinction. And I 100% agree that fasting

01:01:53

Because there are some people who heal themselves with fasting, right? We also can't dismiss that evidence. They make themselves healthier by fasting. And I think what you just said is a key determinant, right? How are you fasting? And if you're doing it in a very supportive way,

01:02:08

non-stress-inducing atmosphere and environment, maybe with a bunch of other people who are fasting, that's much more likely to be effective than if you just try and do your normal job or whatever. Because if you're trying to do your normal job and fulfill your normal responsibilities, you may feel great. A lot of people say they feel great, but they feel great because they're flying high on stress chemicals, right? That's the problem. And then eventually they crash. But there is a right way of doing it. So I 100% agree with that. But I will say, you know, it's interesting because I have, yeah,

01:02:35

a few members of my family who are very much into the repeat mindset. And I agree with most of the things he says, I'll say. But I would say calorie restriction is difficult. And I think a lot of people emotionally, when you start talking about calorie restriction, you just get a lot of anger because they themselves struggle with it. And my kind of response to that is always, well,

01:03:00

you know, it is, it's a difficult thing to do. And, you know, for example, if you look at, you know, like how people eat in Japan, for example, you know, they're able to have much less calories because they plan their meals differently, or it looks like it's a bigger portion of food. And I think like there are hacks that can help you with calorie restriction that

01:03:19

that doesn't involve you know sitting and feeling like you're starving which is what i think people associate when they give calorie restriction um but yeah i mean that's i know i'm the opposite boat because for a decade and a half i would only ever have two meals a day so i had intermittent fast all the time just because i had digestive issues so i couldn't eat more than two meals a day and i feel way better eating three meals a day than i do on two meals a day um like it's it's

01:03:46

much, much, much, much better. Um, but I don't need to lose weight. And I will say if I, I always say people, if they want to lose weight and they want to restrict calories for that reason, which a lot of people do. And as you just said, a lot of people should, then it's an,

01:03:58

and I agree with Dr. Jack Cruz on this one, skip that last meal, not the first meal. That's the crucial distinction. Eat within an hour of waking up, but then don't eat for like five or six hours. And I think that's, in my opinion, that's where everyone gets it wrong with this intermittent fasting. They just drink coffee until midday or whatever. And it's like, that's the wrong way of doing it. So I think that's the compromise between, as you say, the two opposite systems is like eat, you know,

01:04:26

not long after waking up to keep your blood sugar balanced and make sure you're not running on stress and all that stuff then don't eat at night and what i just said that's really hard to do because people who are running on stress all day then when they finally calm down at night then suddenly they're hungry and not eating then is really difficult so um but that is the right way of doing intermittent fasting in my opinion if you want to what do you think of that no i agree i think um as you know

01:04:52

the earlier you can eat, the better. I think where it gets tricky is, you know, another thing that we talk about with longevity and hacks for longevity is just the kind of social connection, finding meaning. And often if that revolves around food, then it's very difficult to kind of cut your eating time. And most people then, you know,

01:05:14

really value let's say their dinner because that's the one time they can sort of sit down with their family or eat on a relaxed you know in a relaxed environment so i i generally say like you know ideally if you can eat four hours before bedtime or even earlier i think that's still okay so early dinners are still fine because then you get a little bit of the social connection too um

01:05:36

100%. Yeah. And, you know, if any of you want to eat a large meal, you know, just before you go to sleep, that's totally, you know, that's up to you, of course, but don't think that you are intermittent fasting to be healthy if you are starving yourself all morning and then binging at night. That's not, that's because you want to do it, but it's not helping like health-wise.

01:05:57

Okay, so awesome. Sorry, I went on a bit of a tangent on that, but that's calorie restriction, right? That's what we were talking about. So there's a right way and a wrong way to do it.

01:06:08

And I think we've come to an agreement about all the way. Awesome. Okay. What's next? I guess we could talk about rapamycin. Sorry, that was supposed to be the tangent after the growth. No, no, it's okay. We want to talk about your general advice first. So any other general longevity advice? Let's cover that first. So we talked about sleep. We talked about calorie restriction. Do you want to talk about stress at all? Yeah. I mean, I would say stress is probably, you know, even though they're

01:06:33

even though stress is essential for life, I would say chronic stress is probably the worst thing for longevity. And unfortunately, that is what I think is the most challenging to decrease in your life. But I do find that

01:06:54

actively measuring to see like how stressed are your adrenals is is one of the best strategies to then actually kind of prove that yes stress is actually um having a bad impact on your life because i i would say i'm always surprised like i and i would say it's

01:07:10

When I think about in the male versus the female patients I see, males often will say, well, I don't feel like I'm stressed and I don't think that's a problem. But then we'll look at it on an adrenal test and it'll be like, no, like clearly your cortisol is through the roof, your DHA is very low. You may not feel stressed, but that doesn't mean your body isn't stressed.

01:07:31

Um, so, uh, you know, and that's where I think you kind of have to do a bit of a 360, you know, degree approach with, um, looking at, you know, what you're eating, your sleep, um,

01:07:43

your relationships, your work, if you're actively trying to lower that, you need to balance that out. I agree. And I think among challenges, people are addicted to stress. They enjoy stress because I think, unfortunately, it's a vicious circle. The more depleted you get and the more toxic you get, which a lot of us are, then the more you feel like your two choices in terms of what state you're in is you're either kind of exhausted, depressed, or you're like stressed, right?

01:08:12

And stressed feels like the upgrade. So it's like I either feel bad, which is exhausted, depressed, tired, depleted, or I feel good, which is stimulated, energized, but also, as you just said, stressed, right? High cortisol and all the rest of it. And so it's kind of teaching people more how to go into that third state, which I call ventral vagal, based on the polyvagal theory, where you are both

01:08:38

relaxed but also uh present and engaged and um so not relaxed as in sedated in any way but relaxed uh but also present and mentally sharp and and motivated and all the rest of it and for a lot of people i think that state of being simultaneously relaxed and confident and stuff and at the same time mentally sharp and energized and focused and and motivated is

01:09:06

something they can distantly remember from a long time ago and you know as I said I was in that time when I never felt that way for quite a while and so I know exactly what it's like and so I think helping people get to that is one of the best things you can do for them but it's not easy right a lot of people are very far away from that unfortunately. Agreed I mean I think you know there's so much research to support practices like meditation for longevity and I think I mean

01:09:35

I tell everyone must have some sort of, it doesn't have to be necessarily called meditation, but meditation, prayer, reflective time, like you should be able to sit for five minutes, breathe and will not fall asleep and not go crazy that you have to be doing something. Like I think if you do that experiment and you can't cope, that is a problem that you need to work on.

01:10:00

I think people just have a tendency to walk away from it and just say, well, no, it's not for me. But it's like, no, that's a problem that it's not for you. Like you need to be able to, because that is a sign that you are one of these people with high adrenaline and have to go. And that's just not healthy in the long run. 100%. It's so funny you say that. I'm sure you haven't seen it, but I talked about that before in the episode. That's the best test for whether you're able to be in that third state. So I 100% agree. Yeah, yeah.

01:10:25

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01:12:37

movement, but not too intense. Like, you know, for some people running and, but, you know, to the point where they're just able to clear their head, that can sometimes help with releasing that adrenaline. And then they actually, after that can come and sit calmly for five minutes without, you know, without, you know, not being able to sit still. And so that can be a form of how you get to that point. And, and I say that, I mean, I've certainly can be one of those people too. And, and I've just,

01:13:05

always struggling with meditation, but you know, it's a work in practice, not something you're going to be able to do overnight. But, you know, I think that that's an underestimated tool. Yeah, fantastic. All right. 100% agree.

01:13:19

Anything else you want to talk about in the general advice category? I think I've pretty much covered it. So let's go back to some of these more controversial, maybe considered advanced strategies. So we talked earlier about Growform as part of that basic package that you would sometimes do. And then we talked about how you said that in the longevity community, they'll often balance it with rapamycin. So

01:13:47

So I've come across this, but I'm sure I don't know much about it compared to you. So first of all, if you could tell us all about rifamicin and then we'll go into, you know,

01:13:57

the strategy of balancing it with growth hormone. I've known about rapamycin for a long time because it's actually a medicine that's used to suppress the immune system after organ transplants. So it's been around for a long time, but it's just that we're talking about low-dose rapamycin for longevity purposes. And could we just talk about where it comes from? Because I think that's quite an interesting story. Yeah, so it comes from…

01:14:26

So my understanding is it comes from a particular bacteria, Streptomyces, something from, but they isolated on Easter Island. And they actually, let me just kind of get these details straight. But basically when I know that they, researchers found that people who lived on Easter Island, the natives there had AIDS.

01:14:47

a higher amount of these bacteria on their skin and that actually it seemed to be protective against for wound healing so that these people were actually able to like walk on the beach and they would step on a coral and they seem to have just kind of thicker skin and then when they would get a cut it would they would heal much faster.

01:15:07

And then, of course, then it was researched and found to basically inhibit a pathway that's quite essential for cancer.

01:15:20

growth proliferation. And yeah, so that's kind of, I thought it was quite an interesting story of where it came from because I didn't know that until actually fairly recently. Yeah, I like that. I'm often telling people the line between food supplements and drugs is pretty arbitrary. And I think rapamycin is a good example because there are loads of supplements where

01:15:40

It's just a byproduct created by a bacteria. But then this is a byproduct created by a bacteria, but it's classified as a drug. And of course, it's classified as a drug because, as you say, if you have a very, very high dose of it, which is what they use as a medication, then it suppresses the immune system enough that if you have an organ transplant, your own immune system doesn't fight the organ transplant, right? So that's the drug-like dose. But this is typical of mainstream science and medicine to me that

01:16:07

like they always do like the most ridiculously high dose of something that, you know, can possibly kill you if you take it in the wrong context. But, you know, there's a, you can have a much lower amount of it. And I think we're going to talk about low dose naltrexone as well, right? That's a similar story. So a much lower amount is much less dangerous. And in fact, you know, it could be very beneficial. Okay. So now we've gone into that. Yeah. Tell us what, so the low dose, what were we doing with that? Yeah. I mean, I'll just add to that, that obviously,

01:16:37

you know, someone having an organ transplant, that's something that only like modern medicine could accomplish. And so then the rapamycin serves a great purpose. But obviously, you know, we don't want to suppress your immune system to that degree if you don't have that kind of a scenario. And just explain, why would we want to suppress the immune system at all? I guess maybe we should explain that as a concept.

01:17:00

I mean, where you've had an organ transplant, then… No, sorry, just a normal person. Why would you want to suppress it at all? At all, ever, to any degree. Well, for those who are suffering from autoimmune conditions, or we think that inflammation can just be stimulated by your own immune system,

01:17:20

like revving up the production of a lot of inflammatory molecules. So it's not really, I guess, suppressing it. I like to use the term more modulating so that you have a balance of those cells that are, you know,

01:17:34

who are that are like fighting off toxins and pathogens and those that are kind of regulating the whole picture to make sure that the immune system is not overactive. And that balance is difficult to achieve. And we're certainly seeing that it's getting kind of worse with just the prevalence of autoimmune conditions. Yeah.

01:17:50

Yeah, so the fear is understanding that with our modern lifestyle, with the amount of toxins that we have to cope with, which are novel, maybe it's not as much, maybe it's not much more than our ancestors, that's debatable, but there's certainly thousands of new ones that our body is not used to, right? Or maybe more than that. So with that, the immune system…

01:18:09

like the as you just said the fighting elements of the immune system are like overstimulated and the regulating elements are understimulated but my understanding of reprimand my sense is it did it does suppress both of those like isn't it the case that people who take it even with a low dose they've that like they're more likely to take antibiotics and stuff like that or is that old news is is you know is there a better way of doing it well that's not the case well i

01:18:32

Well, I think, I mean, the low dose that I normally recommend is around sort of like four to six milligrams once per week. So quite low dose. And I've seen with that, I haven't really seen many side effects at all. I think the one thing that's kind of come up has been more like canker sores. And, you know, some people and, you know,

01:19:00

like an increase to glucose and cholesterol, which I can talk about that in a moment, but I haven't really seen that it's had that kind of effect. And I think when people think that they're susceptible to infections, often what they're thinking about, for example, like when they have a cold, when they then have that prolonged runny nose, that's actually more the

01:19:24

the inflammatory post-viral part, not the kind of active infection. And so they sort of mistake that, oh, I'm getting, it's taken me so long to get over this. It's like, you've probably actually fought off the pathogen. You haven't gone into a sort of a septic picture. That means in effect that you're dealing with more of that inflammatory response after the infection. Okay. And so which, which reference,

01:19:49

mycin would then help with, right? Because it reduces that inflammatory response. Okay, interesting. And we know, I mean, I was, we recently kind of attended a talk about rapamycin and just kind of was reminded of a lot of that research that it has essentially expanded the lifespan in every organism it's been tested on. Even most recently, dogs, there was a study on dogs. And now there's actually, sorry, I'm,

01:20:17

I have three dogs, so that kind of always peaks by interest. But actually, they're trying to do a two-year canine longevity study using rapamycin. They're actually looking for people who are willing to have their dogs in parts of that. Interesting.

01:20:37

Yeah. Interesting. I just saw funny enough, a news article the other day about how, uh, dogs are, I think it was golden retrievers. Like their lifespan is reduced by 40% in the last 20, 30, maybe 30 years, something like that. Like, and I think it is the amount of toxins again, um,

01:20:53

is, you know, a primary cause. In the case of dogs, right? Because it's not probably so much, you know, stress and lack of sleep and stuff. It's probably more toxins than anything in the case of cats and dogs. Yeah. And I would say that's actually a good point because you don't think about like how, you know, animals are much lower to the ground. They have, you know,

01:21:14

for paws. And for example, like if they're walking around a lot of glyphosates from, you know, from, uh, you know, from the lawns and from plants, they're much easier. They're able to mop it up much quicker than humans. Well, that's a good point. I was actually thinking more about what's in their food, but, uh, yeah, but that's, that's absolutely true as well. And in the air and the water, I guess it's everywhere. Um, and I know some of the people watching, especially, um, like our anti-

01:21:41

the vitamin a fans who are watching that they're probably listening to this going oh all this is unnecessary all you got to do is uh reduce your toxic input and everything would be great um i just want to remind them that first of all um yeah both dr miriam and i are a big fan of reducing toxicity a lot of when we work people that's exactly what we do focus on so we're we're big on that one as well but this is just like extra stuff you know that

01:22:05

there is a lot of evidence to show. So sure, if you want to increase a dog's lifespan, the first thing to do might be to clean up their diet and their air and their water and all the rest of it, as Dr. Miriam just said, their contact with poisons. But another thing you can do

01:22:20

On top of that is also something like rapamycin potentially, right? It doesn't have to be mutually exclusive. No, exactly. And I think what I like about, what I like about rapamycin is it's just something you take once a week and then you take it three months on, three months off. So it's, you know, it's not that difficult to add into your routine, but we know that essentially that it turns on autophagy and that really helps with getting rid of those degraded

01:22:49

organelles, proteins that are essentially toxic, and it helps you sort of get rid of those senescent cells that we don't want hanging around. But actually, the more that it's studied, the more that we've even seen it helping things like long COVID, mood, as well as your kind of inflammatory neurodegenerative conditions too.

01:23:13

Excellent. And so just the bottom line of this is that inflammation is blamed for a lot of, as a root cause for a lot of issues. Rapamycin is possibly the most effective thing

01:23:24

found at reducing inflammation is that a bottom line of it yes i'd say one of the most studied things that um can help and and this is something you take although again for our purists out there certainly massively reducing your toxin intake and extremely more toxins would also make a big difference to your level of information uh we both agree with that one as well

01:23:46

And since we're having it once a week, I remember Hannah, my wife, trialed this a few years ago. And I think we had one milligram capsules and she was just taking it every day. I think that was the kind of recommendation at the time. So can you tell us why once a week is better than just a smaller amount every day or a smaller amount five days a week? Oh, actually, to be honest, that is just how I was taught to dose it. I mean, I presume that…

01:24:13

You want to activate that recycling process and

01:24:20

And perhaps, you know, you kind of then, that maybe uses up some of your antioxidants as well. So potentially you just want your body to have time to rest and then do it again. That would be my theory because I don't know off the top of my head. What's the amount given to someone if they have, you know, an organ transplant? I probably would have to look that up. I want to say it's about, I mean, it's orders of magnitude higher. I think it's something like,

01:24:50

It might be, I think it's a little bit less than that. I think it's something like 10, 12 milligrams, but yeah, every day. So that's what I was wondering. So you're having a kind of half the amount given to an organ transplant person on one day. So doesn't that mean on the one day you take it that your immune system function is significantly reduced? That's kind of what I was wondering. I wouldn't say that it's, I mean, to be honest, at the moment now,

01:25:15

It's not the immunosuppressive drug that's given. I think that there are potentially better ones, but I have for the perspective of transplant rejection to prevent that. But yeah, it's a good point. Personally, though, I just haven't really seen that happen in practice. I think that if you're…

01:25:41

Yeah, I mean, I haven't just seen that people seem to be more susceptible to infections on the rapamycin dose. So, yeah, I've never really had to look into that, to be honest. Yeah, fair enough. Well, you know, that's what we want you here, not only for your theory knowledge, but for your practical, you know, technical experience. So, yeah, great. Okay.

01:26:01

And then you talked about three months on, three months off. So is that the three months off rapamycin? Is that where you might then do three months on with the growth hormone or growth hormone analogs? Exactly. I mean, you wouldn't necessarily have to do it. I wouldn't say some people actually don't even stop the growth hormone when they're on the rapamycin. I would, though. At least that's how I would dose it in my practice. But yeah.

01:26:28

But yeah, I think that would be a good way to do it so that you balance the growth and the kind of proliferation that you see with the growth hormone and the stimulation IGF-1 versus the kind of slowing down of the body with the rapamycin.

01:26:45

And actually, I don't think we talked about growth hormone. So again, you said you have your longevity clinic, right? Are you giving people actual growth hormone or do you prefer giving them peptides? What do you like to do? I mean, I actually use more peptides. I do prescribe growth hormone. But generally, because it is something that is used daily, you then typically have to…

01:27:10

inject it yourself. And I was a little bit wary about people doing it themselves from a medical liability point of view, but I have, I have instructed people to have had to do it and have used it. But, and, and those, I, I don't necessarily cycle, I actually just use the growth hormone promoting peptides and these, they're up in my soap at the same time.

01:27:34

Okay. But you still do cycle the rapamycin, just not the growth hormone? Yes. I always cycle the rapamycin, yeah.

01:27:41

Very interesting. Okay, fantastic. And both of those are prescription only. Actually, I don't know, do you do growth hormone? I don't think they're available at all in the UK, right? But they are available in the US. Yeah, no, you can. Growth hormone is available from compounding pharmacies. Sure, no, no, the growth hormone peptides, I was saying, in the UK. Okay.

01:28:03

Yes, you can still get it in the UK. You just have to be a bit careful about your sourcing. Okay, awesome. So GOP1s, obviously, is a big thing at the moment.

01:28:18

I think this might be another one for you and I for doing perspective, but that's okay. I'm a little bit more wary of them. So GOP ones are things like semaglutide, and there's some other ones I can't remember how to pronounce. Most of you can tell us. Commonly known as things like Ozempic or Wegovy. Obviously, these are originally diabetes drugs. I think most people have heard of them, but…

01:28:41

that they're so effective at weight loss that they've become very popular. So what's your take on these, Dr. Miriam? Yeah, I would say, I mean, initially I was very skeptical of the GLP-1 agonists and I still am a little bit worried about…

01:29:00

people using them longer term and at the high doses that medical community tends to use. But I, I just, the reason why I am, I think we can't discount them is because I, you know, I've seen people who have just been very unhealthy who, you know, I think as a strategy, getting, getting excess weight off of them and lowering their insulin can be then a catalyst for them applying sort of better lifestyle practices. Yeah.

01:29:28

And so, which I think is just kind of an amazing medical achievement. But I think we have to be wary about how something like that that works so potently is likely going to have some side effects. So, you know, want to then mitigate those side effects or try to promote the organ health that

01:29:50

is being kind of damaged by the GLP-1. For example, like pancreatic function, you know, we're seeing a big uptake in pancreatitis rates, people who are on GLP-1 agonists. But then, you know, they're not really taking anything to support pancreatic health. So I wouldn't want to just blindly give that without care.

01:30:11

the support. What would be an example of something that people would take to support pancreatic health if they're already taking one of these? Like, you know, pancreatin, bitters that help just with bile flow, those sorts of things. Yeah, I want to give my updated one actually quickly because I did an episode on this and I was quite negative about it. I think I have a slightly more nuanced approach. I'm still not taking any, by the way, so it's not to justify my own behavior. But, you know, as I've looked into it, I think there was a certain

01:30:39

of the population. And if I go back to the Korean system that I did an episode on a while ago, I think they're the ones who are stomach dominant. They are people who generally have strong stomach function. They produce a lot of stomach acid. They're hungry a lot and they can easily overeat. And also they have quite fast gastric motility. And I think with someone maybe through genetics, like they just have a bit like over-

01:31:07

active stomach function compared to average and it's very easy for them to overeat and they're hungry a lot and so maybe taking a GLP-1 agonist to bring them back into balance as it were would actually make sense my concern is just when people overdo it and you know they get to the point where every week they you know feel sick and vomiting for several days this just doesn't seem like

01:31:30

And the other problem is a lot of people are not eating a very high nutritious diet. I've done quite a few episodes on this recently, trying to demonstrate to people, you know, how to meet even just your 100% RDA of all the nutrients, let alone you should probably gain more, but at least that from food is not particularly easy.

01:31:48

And so even when people are eating, say, a 2,500-calorie diet and they're trying to eat healthily, I observe that a lot of the time they're not really meeting their nutritional needs. So then when they start taking these GLP-1 agonists, they cut down to maybe a 1,500-calorie diet.

01:32:06

like and they're not careful with this stuff then I think it often it creates more and more nutritional deficiencies and as well as all the other you know potential side effects that you just said have slowed you know digestive motility whether it's pancreatitis or you know maybe SIBO or any of these other things that can happen when

01:32:26

things move too slowly so um so yeah i just wanted to share my take on it i'm not universally against it anymore but my thing would probably be that very low doses like so that certainly not enough that you feel sick when you take them so that's my opinion what's your opinion you did say about lower doses um what what kind of doses do you like to and obviously it depends on the person but

01:32:51

you know, what kind of amounts do you find are appropriate, like for people? I mean, even starting as low as 50 to 100 micrograms a week. Wow, that is very, because the minimum usually is like 250 micrograms, right? With a semi-glutide. Okay, yeah, that makes perfect sense to me. Absolutely. And that's what I think has been recommended in the peptide communities before, you know, I think that they can't.

01:33:17

pharmaceutical ozempic really took off in popularity. So I think it's being

01:33:21

massively overdosed and i and i would say i mean in there are also some some natural glp-1 agonists um you know there's a compound called um americate which i believe is derived from like the hops plant that is also supposed to put you know help to increase endogenous glp-1 production uh we know that certain bacteria acromantia um and a couple of other strains can also help so i i usually will um

01:33:49

sometimes bridge somebody to say okay like you know we know that amaricite that that compound can actually um similar side effects so if you're taking that and you already feel nauseous and had a lot of gi issues then you probably need to do a bit of a gut program first before considering it um you know and um so i wouldn't start it blindly i think you you need it would be more of like a

01:34:16

I wouldn't say a last resort, but I would say when I'm really struggling to get someone's insulin down and they're overweight and that sort of food noise that really disrupts people's

01:34:30

eating habits where they're just constantly thinking about food. They never seem satisfied. If that's the sort of presentation I'm getting, then I think that they can be a fantastic tool, but with a lot of added support for that. That's such an awesome nuance to take, Benna. Yeah, I 100% agree. What about GLP-1 antagonists? I heard Dr. Cruz recently talk about how he believed that there was a conspiracy around this, that

01:34:59

because Blue Light is a strong GOP-1 antagonist according to him, and then a lot of the artificial sweeteners like Aspartame are strong GOP-1 antagonists. So his…

01:35:08

uh, theory is that first of all, they flood, you know, for several decades, they flooded people with Gopro one antagonists. And then they, so it's like they created the problem and then they sell you the cure for the problem, uh, you know, a very high price. And then kind of your, you have to keep taking that for the rest of your life. So I thought that was interesting. Um, you know, with conspiracy, you never know there's really that, you know, level of intention behind it, but you had to see a fairly, um, what's, what's the words like, um,

01:35:37

it wasn't just an idea he had, he'd done a lot of research into it and he, uh, you know, he claimed that this was intentional. Um, so I, I think that's possibly part of it as well to, uh, to consider and look into for people is to reduce the level of antagonists. Yeah, no, no, certainly. I mean, I think a lot of those, um, those strategies like kind of fall into just good, good lifestyle habits. Um, and, um, yeah,

01:36:05

And we also know that some medicines that do block GLP-1 include steroids and things that a lot of patients are on. So I would say that you kind of have to, I think a better strategy would be to first make sure that you're not blocking the GLP-1 from a poor lifestyle, poor diet, and

01:36:32

And then use the GLP-1 agonist as a tool when you're really not making the progress that you want. Another big point there is that obviously a lot of people who are on GLP-1 agonists are losing a lot of weight, but they're also losing a lot of muscle mass. And then, you know, they're not, we don't want to talk about appearance, but they are looking quite gaunt and not exactly the picture of health that you would want. So, you know, I think also from a,

01:37:02

From the peptide community, you'd want to combine the similar glutide with muscle-building peptides. Like growth hormone? Yeah, like growth hormone, for example, and then, of course, things like the iprimirelin. I think that's where some people are using the MK-677 as a kind of something that you would take with a similar glutide.

01:37:27

um but then they seem like they're going in completely opposite directions you know one of them is ravenous hunger one of them's sick at the thought of food so maybe they balance each other out yeah i don't know but i was gonna say if you had a big what sounds like then a spike at a crush it might not be the best strategy i mean i i was sensitive to it but i'm not the only one like this is well known i think in the bodybuilding community that

01:37:50

MK-6, 7, 7, if you take the full dose that they normally recommend, you get ravenously hungry. That is definitely part of it because it's a strong ghrelin agonist, right? The hunger hormone. And I would say that with the semi-glutide, apart from just things that help to, with growth hormone increase, I would also say like looking at things that help with muscle recovery. So things like BPC-157,

01:38:15

And then also that help with, as a tissue regeneration, like thymus and beta-4, those are other peptides that I would, you know, I would generally prefer to use kind of the peptides as a kind of a pack of things that you're taking rather than just one. Okay.

01:38:30

Fantastic. Well, I think we're already at time, Dr. Miriam, and we barely got through half our list of advanced strategies. So I don't know if you're open to it, but maybe we could do another episode where we talk about advanced strategies for people, for advanced longevity strategies, and we can continue this conversation then. Yeah, no, certainly. Because I know we really wanted to talk about the low-dose naltrexone. So why don't we just tease that to people? Yeah.

01:38:53

In the next episode, we'll talk about no-gas no-trexotome. We'll talk about Dr. Miriam's take on mRNA gene therapies. We'll talk about platelets-rich plasma. We'll talk about exosomes, different tools for mitochondrial optimization, senolytic cell detox.

01:39:10

autophagy and mitophagy which we already talked about a bit but we'll talk about some specific compounds and then possibly more that we'll come up with by the time we film that so that's all to look forward to in a future episode um in the meantime um

01:39:23

you know if i wasn't already a client of yours i would feel very excited about the possibility of it having heard all you know the different strategies that um you've outlined and wanting to try them so um for people out there can you tell them how they can find you and uh you know have you helped them with this uh yes so you know i think obviously a lot of the strategies we talked about are more like

01:39:45

things you would incorporate into your life, but obviously things like rapamycin or, um, DHEA, uh, in the, in the UK, DHEA is prescription only. So you should just have to come through a compounding pharmacy. Um, that, you know, if you, I think, um, and yeah, that's definitely something I can help you with if appropriate. Um, and, um, you know, let's say you could always find me at, um,

01:40:10

So my longevity kind of base clinic is called Health Miro. And you can find us on Instagram or on our website. And we do have complimentary and a 20 minute discovery calls. So we can get into a little bit about it. Nobody comes to these like consultations 100% healthy. There's always some area like the thyroid or the adrenals. So it'd be about, you know, what we can do to help plus the longevity aspect.

01:40:38

Yes. And so it's health Miro health N I R O.com, um, health Miro M I R O on Instagram. And, uh, you also have your own practices to say no less longevity focus. That's, uh, McKinsey medical.com. We'll put all of those links in the, uh, uh, description of the episode, both on wherever you're watching Spotify, Apple, or YouTube, it will be there.

01:41:05

If you have any questions, if you're on YouTube, please leave them in the comments. Please subscribe and click the notification bell to be notified when part three of this series is coming up. I didn't know there would be a part three, but I'm happy to do it. And I'm actually happy we have more time to talk about some of these advanced strategies in a separate conversation, Dr. Miriam, because I'm sure there's more that I can learn about this, especially if we talk about it in detail.

01:41:32

Um, so thank you so much for your time today. Again, I want to give the recommendation to, um,

01:41:39

you know, there's very, very few practitioners who are like Dr. Miriam, who have both, you know, that excellent understanding of the mainstream medical system and an excellent understanding of not just, you know, the alternative, but it's a functional medicine. Uh, you also, you know, you've mentioned occasionally about energies and stuff and traditional Chinese medicine, which is something that you're also trained in. I know you have a bunch of other specialty certifications. For instance, I found you because you're, you're certified in the, uh, Wilson's temperature, uh,

01:42:08

syndrome treatment protocol which I did an episode about a while ago so you know she just has an excellent range of different skill sets and knowledge bases and all the rest of it and

01:42:24

And unlike most doctors, is not focused on getting you functional and out of the door, but is actually focused on helping you to optimize, which I guess is probably obvious by now, given what we've talked about in this episode. But still, so yeah, not many doctors like that who are actually genuinely focused on helping you optimize. And if I could just add, someone who genuinely cares about you, who doesn't just see you as another number or another body in the door, but who genuinely cares about your

01:42:51

well-being and you know that you are happy and healthy and all the rest of it so definitely check out dr miriam health n-i-r-o dot com thank you so much for your time today dr miriam thank you all window and thank you for that um recommendation as well i appreciate it

D:2025.03.01>

本章探讨了广泛适用的长寿建议，重点关注基本营养素和激素支持。它强调了胸腺健康的重要性，以及锌、维生素D和维生素K2在免疫功能和抗衰老中的作用。

• 基本营养素和激素支持对长寿至关重要。
• 胸腺在免疫系统的发育和维护中起关键作用。
• 锌、维生素D和维生素K2对免疫功能和延缓衰老至关重要。

本节深入探讨了锌的重要性、它与铜和铁的相互作用，以及它在长寿策略中的作用。它还讨论了二甲双胍和黄连素作为血糖调节剂的作用，以及Akkermansia菌的重要性。

• 锌对多种身体功能和免疫健康至关重要。
• 锌、铜和铁的平衡非常重要。
• 二甲双胍和黄连素可以调节血糖，但二甲双胍可能有副作用。
• Akkermansia是一种与胰岛素敏感性相关的肠道细菌。

本节重点介绍了Akkermansia，这是一种对肠道屏障健康、营养分解和血糖调节至关重要的肠道细菌。讨论还涵盖了Akkermansia补充的挑战及其在预防代谢疾病中的重要性。

• Akkermansia对肠道屏障完整性和营养吸收至关重要。
• Akkermansia水平低与2型糖尿病和代谢紊乱有关。
• 由于生产困难，Akkermansia的补充具有挑战性。

本章探讨了二甲双胍和黄连素在长寿中的优缺点。它强调了黄连素因其副作用较轻而更受青睐，并可能与其他植物化合物产生协同效应。

• 由于副作用较轻，黄连素比二甲双胍更受青睐。
• 两者都能激活AMPK并降低血糖水平。
• 黄连素可能与其他植物化合物产生协同效应。

本节讨论了DHEA（脱氢表雄酮）的作用，它在对抗皮质醇中的作用，以及它作为长寿干预措施的使用。它解决了关于DHEA转化为雌激素和睾酮的担忧，并建议了适当的剂量策略。

• DHEA对抗皮质醇，被认为是一种长寿激素。
• 应谨慎管理剂量，以避免不必要的雌激素或睾酮转化。
• 7-酮DHEA是对DHEA转化为睾酮敏感的人的替代选择。

本章解决了关于激素替代疗法的常见担忧，特别是关于DHEA的担忧。它强调了激素替代疗法在对抗年龄相关衰退、提高生活质量和寿命方面的重要性。

• 激素替代疗法可以对抗年龄相关的衰退。
• 仔细测试和个性化策略对激素替代疗法至关重要。
• 激素替代疗法是一种“欺骗自然”的策略，可以减缓年龄相关的衰退。

本节探讨了生长激素在长寿中的作用，解决了关于癌症风险的担忧，并探讨了生长激素释放肽和MK-677等替代方案。讨论强调了每种方法的优点和缺点。

• 生长激素促进肌肉质量和细胞修复，但具有癌症风险。
• 生长激素释放肽是更安全的替代方案。
• MK-677是一种更便宜的口服选择，但可能导致不可预测的血糖波动。

本章讨论了褪黑激素在长寿、睡眠优化和解毒中的作用。它解决了关于激素抑制和嗜睡的担忧，并提供了优化褪黑激素使用的策略。

• 褪黑激素支持睡眠和解毒。
• 高剂量可能不会导致嗜睡。
• 最佳的解毒途径对于有效的褪黑激素使用至关重要。

本节探讨了长寿的卡路里限制策略，强调了个性化方法的重要性，并避免极端禁食的负面影响。它强调了正念饮食和社交联系的重要性。

• 卡路里限制对长寿有益，但需要个性化方法。
• 避免极端禁食，专注于正念饮食习惯。
• 应考虑社交联系和进餐时间。

本章强调了慢性压力对长寿的有害影响。它讨论了通过冥想和运动等压力管理技术来改善整体健康和降低肾上腺素水平的重要性。

• 慢性压力对长寿有害。
• 冥想和运动等压力管理技术至关重要。
• 能够安静地坐五分钟而不感到不安是压力水平的关键指标。

本节探讨了雷帕霉素的起源及其低剂量用于长寿的用途。它讨论了其作用机制、潜在副作用和最佳剂量策略。

• 雷帕霉素抑制癌症生长并减少炎症。
• 低剂量雷帕霉素（每周4-6毫克）通常耐受性良好。
• 建议使用三个月，停用三个月的周期。

本章探讨了通过平衡雷帕霉素与生长激素或其类似物来实现长寿的策略。它讨论了循环使用雷帕霉素的理由，并建议使用生长激素释放肽作为生长激素的更安全替代方案。

• 应循环使用雷帕霉素和生长激素以平衡生长和细胞修复。
• 生长激素释放肽是生长激素的更安全替代方案。
• 结合两者需要仔细考虑和监测。

本节探讨了使用GLP-1激动剂（如索马鲁肽）进行减肥和长寿的用途。它警告不要使用高剂量，并强调了营养支持和缓解潜在副作用的重要性。

• GLP-1激动剂促进减肥，但可能有副作用。
• 建议使用低剂量（每周50-100微克）。
• 营养支持和缓解潜在副作用至关重要。

衰老的成因及评估方法

@Dr. Miriam McKitsky : 我专注于健康寿命的研究,因为东亚人的衰老方式启发了我。我认为长寿不等于健康,更重要的是拥有更长的健康和青春活力。我将加速衰老的原因归纳为遗传因素、表观遗传因素、慢性压力、病原体、污染物和昼夜节律紊乱等。 慢性压力是加速衰老的主要因素之一,皮质醇等激素虽然在应激反应中发挥作用,但也具有破坏性。长期高水平的皮质醇和肾上腺素会破坏肌肉、肠道屏障,导致血糖升高和炎症。 衰老的标志包括基因组不稳定性(DNA损伤和突变积累)、端粒磨损(端粒随着细胞分裂而缩短)、表观遗传改变(影响基因表达)、蛋白质稳态丧失(蛋白质错误折叠和积累)、巨自噬作用受损(细胞清除受损细胞器和蛋白质的能力下降)、营养物质感知失调(身体调节营养物质感知和代谢的途径出现紊乱)、线粒体功能障碍(线粒体产生能量减少,产生更多活性氧和自由基)、细胞衰老(细胞停止分裂但仍保持代谢活性)、干细胞衰竭(干细胞分化和自我更新能力下降)和慢性炎症(促进斑块积聚、内皮细胞损伤和各种疾病的发生)。肠道菌群失调也会影响消化吸收、免疫功能和毒素产生,从而影响衰老。 除了上述因素外,脱氢表雄酮(DHEA)和三碘甲状腺原氨酸(T3)等激素水平也能反映衰老速度。

@Elwynn Robinson : 我认为间歇性压力可能是有益的,因为它能增强身体的适应能力,但长期高水平的压力则有害。评估衰老速度的关键指标包括炎症标志物(如高敏C反应蛋白、铁蛋白)、空腹胰岛素、糖化血红蛋白、同型半胱氨酸、谷氨酰转肽酶、白蛋白、血沉、平均血小板体积、脂质过氧化物等。甲状腺功能检查有助于评估新陈代谢、免疫功能和排毒能力。此外,胱抑素C可以评估肾脏功能,而瘦素则反映了饱腹感和能量平衡。 生物年龄测试可以更精确地预测寿命,但结果需要结合其他指标综合考虑。线粒体健康指数测试可以评估线粒体的功能,而糖基化年龄测试则可以评估免疫系统的年龄。 我认为个性化医疗是未来的方向,应该根据个人的检测结果制定个性化的长寿方案,而不是依赖于通用的建议。

我一直对健康寿命的研究充满热情，这源于我在东亚的经历。在那里，我观察到老年人的健康状况与西方国家存在显著差异，他们即使到了高龄，依然保持着较高的生活质量和身体机能。这让我意识到，长寿本身并非目标，更重要的是拥有更长的健康寿命——保持青春活力，远离慢性疾病。

我将加速衰老的原因归纳为以下几个关键因素：遗传因素、表观遗传因素、慢性压力、病原体、环境污染以及昼夜节律紊乱。其中，慢性压力尤为重要。皮质醇等应激激素虽然在紧急情况下至关重要，但长期高水平的皮质醇和肾上腺素会对身体造成损害，例如肌肉损伤、肠道通透性增加、血糖升高以及炎症反应加剧。

衰老的九大标志

基于对现有研究的理解，我将衰老的标志总结为以下九个方面：

1. 基因组不稳定性: DNA损伤和突变的积累，损害细胞功能，增加癌症、阿尔茨海默病等疾病的风险。
2. 端粒磨损: 端粒随细胞分裂而缩短，最终触发细胞死亡和衰老。
3. 表观遗传改变: DNA甲基化等表观遗传修饰改变基因表达，扰乱细胞正常功能。
4. 蛋白质稳态丧失: 错误折叠和受损蛋白质的积累，导致阿尔茨海默病、帕金森病等疾病。
5. 巨自噬作用受损: 细胞清除受损细胞器和蛋白质的能力下降，导致细胞内废物堆积。
6. 营养物质感知失调: AMPK、mTOR和胰岛素/IGF-1等通路失调，导致代谢紊乱和抗压能力下降。
7. 线粒体功能障碍: 线粒体能量产生减少，活性氧和自由基增多，损害细胞功能。
8. 细胞衰老: 细胞停止分裂但仍保持代谢活性，分泌促炎因子，加剧炎症反应。
9. 慢性炎症: 持续的低度炎症反应，损害血管内皮细胞，促进斑块形成，增加心血管疾病等风险。

此外，肠道菌群失调也会影响营养吸收、免疫功能和毒素产生，从而加速衰老。 一些激素水平，例如脱氢表雄酮(DHEA)和三碘甲状腺原氨酸(T3)，也能够反映衰老速度。

个性化抗衰老策略：精准检测，精准干预

我并不认为存在放之四海而皆准的抗衰老方案。相反，我认为个性化医疗才是未来方向。 评估衰老速度，需要进行一系列精准的检测，而非仅仅依赖于主观感受或单一指标。我推荐以下关键指标的检测：

• 炎症标志物: 高敏C反应蛋白(hs-CRP)、铁蛋白、血沉(ESR)、平均血小板体积(MPV)等，反映身体的炎症水平。
• 代谢指标: 空腹胰岛素、糖化血红蛋白(HbA1c)、同型半胱氨酸，反映胰岛素抵抗、血糖控制和甲硫氨酸代谢情况。
• 肝脏功能: 谷氨酰转肽酶(GGT)，反映肝脏健康状况。
• 营养状况: 白蛋白(Albumin)，反映营养状态和肌肉质量。
• 肾脏功能: 胱抑素C(Cystatin C)，反映肾脏功能。
• 激素水平: 脱氢表雄酮(DHEA)、甲状腺激素(TSH, Free T3, Free T4)、性激素(雌激素、孕激素、睾酮)，反映内分泌系统功能。
• 氧化应激: 尿液8-OHdG，反映DNA氧化损伤程度。
• 饱腹感和能量平衡: 瘦素(Leptin)，反映脂肪细胞功能和能量代谢。

除了常规血液检测，我还推荐更深入的检测，例如：

• 线粒体健康指数测试: 评估线粒体功能，尤其适用于慢性疲劳等患者。
• 糖基化年龄测试: 评估免疫系统的年龄。
• 生物年龄测试 (例如TrueAge): 基于DNA甲基化模式评估生物年龄，但结果需结合其他指标综合考虑。
• 氘含量测试: 评估体内氘的含量，这与衰老和健康状况相关。

通过这些检测，我们可以更精准地了解个体的衰老速度和潜在风险因素，从而制定个性化的抗衰老方案。 切勿盲目跟风，而应根据自身情况，选择合适的干预措施。 记住，健康长寿并非一蹴而就，而是一个需要长期坚持和精细管理的过程。

D:2025.03.01
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