[Jen Scheinman] (0:00 - 0:03)
Men go down a gentle hill, whereas women get pushed off a cliff.

[Angela Foster] (0:03 - 0:09)
We question why we can't keep up with everything that we were doing before, but really it's our biology changing.

[Jen Scheinman] (0:09 - 0:20)
We start to lose mitochondrial function, they start to become dysfunctional. There's also this tie-in between oestrogen and our mitochondria, which exacerbates the feelings as we start to go through midlife.

[Angela Foster] (0:20 - 0:23)
I think for some women, it just feels like, oh my god, where did my energy go?

[Jen Scheinman] (0:23 - 0:44)
Mitochondria are like little energy factories that take the food that we eat, which is the raw materials, and turn it into energy. So if you have poor raw materials, you're going to have poor energy output. Mitochondrial decline has been linked to neurodegenerative diseases like Alzheimer's, muscle loss.

So there are some real manifestations about not minding your mitochondria.

[Angela Foster] (0:44 - 0:51)
In terms of the best ways that we can support our mitochondria as women, what are the top three ways that we can do that?

[Speaker 3] (0:51 - 0:55)
The number one thing that's going to help benefit your mitochondria is... Hi, Jen.

[Angela Foster] (0:56 - 1:19)
I have so many women tell me that they don't know why their energy's lower, but they're just experiencing sometimes these dips that come. But then other women saying to me, my energy's on the floor. I just want to feel like myself again.

I can't tell you the number of times that I hear that statement. What is happening to our energy levels and our mitochondria in midlife?

[Jen Scheinman] (1:19 - 2:32)
Oh gosh. Well, I hear that all the time and have felt it myself too. So sympathise with people who are feeling that.

But there's a lot that's happening as we start to go through midlife. The conversation has been amazing as we start really bringing this awareness around what's happening to our bodies and this loss of our reproductive hormones. So oestrogen, progesterone, and that is certainly impacting how we feel.

But there's a piece of the conversation that I think we haven't been chatting that much about. And it's sort of floating around there, but tying it into midlife. And this is this conversation of our mitochondria.

So our mitochondria, the powerhouse of the cell, that's sort of almost like a reflex reaction of what are these little organelles that live inside our cells. But their primary purpose is to help drive energy production. So whether it's a brain cell, a skin cell, or a muscle cell, it's relying on the energy from our mitochondria.

But just as part of the ageing process, we start to lose mitochondrial function. They start to become dysfunctional. But there's also this tie-in between oestrogen and our mitochondria.

So as women, we have the same ageing process that men are having. But we then tie in that oestrogen loss, which exacerbates the feelings as we start to go through midlife.

[Angela Foster] (2:32 - 3:00)
I've noticed that. I've noticed that myself. And I think that it comes on initially, right?

I think for some women, gradually. For other women, it just feels like, oh my god, where did my energy go? And it's so hard.

And I think that then we start to, we don't feel like working out as much. We start to move less, right? It affects our overall energy expenditure.

In terms of the best ways that we can support our mitochondria as women, what are the top three ways that we can do that?

[Jen Scheinman] (3:01 - 4:06)
So the first two ways should be no surprise, because this is really the way that we support our health in general. But that's exercise and how we eat, right? So the number one thing that's going to help benefit your mitochondria is making sure that you're moving.

And whether it's cardiovascular or strength training, both of them will help mitochondria in different ways. But they're both going to be beneficial. And then, of course, diet.

There's some really interesting research on calorie restriction and intermittent fasting to help support your mitochondria. But also, if you just think about in terms of food, I like to think of in really simple terms, your mitochondria are like little energy factories that take the food that we eat, which is the raw materials and turn it into energy. So if you have poor raw materials, you're going to have poor energy output.

And all the workers on that energy factory also come from your diet. So your vitamins and your cofactor. So a healthy diet is going to be super protective and super healthy for your mitochondria.

But there's a third way, and that is with dietary supplement. There's a lot of really interesting supplements that are coming on the market that can help to support your mitochondrial health in addition to what we're doing with that lifestyle foundation piece.

[Angela Foster] (4:06 - 4:40)
Yeah, which is really exciting. And I want to dive into more with you. When we look at mitochondria, so we hear like a lot of people have heard of things like autophagy, for example, and we associate that with fasting and cellulite renewal.

What are the processes that our mitochondria go through? Because my understanding is that they also have a recycling and renewal process and also this creation of new mitochondria. I think like a really short lesson in the biology of what happens and how our mitochondria support us, because as you say, they are our energy, would be great just so people really understand this.

[Jen Scheinman] (4:40 - 6:23)
Yeah, so our bodies are so cool in the way that they work and all of these like quality control mechanisms that are inside our body. And because the mitochondria are so foundational, so every cell, just a little trivia, other than your red blood cells, every cell in your body has mitochondria. And the mitochondria are sadly, they're very susceptible to damage, right?

So they even in the production of energy, they're creating free radicals. And then of course, through our environment, they're very susceptible to damage. So our bodies, because our mitochondria are so critical, have developed this recycling process.

So you mentioned autophagy, that's a full cellular recycling process. Mitochondria is very specific to just the mitochondria. So I think of autophagy as like the house demolition, whereas like mitophagy might be just redoing the kitchen, right?

It's a little bit more specific. And when I think of mitochondrial health, I think of it in three simple buckets, right? If you want more energy, you could build more mitochondria, more energy factories, and that's called biogenesis.

And it's a creation of more mitochondria. You could also make that energy factory work better, right? You could make sure that it has all of the nutrients that it needs.

Like that's where something like CoQ10 comes in. It helps to move energy around in the creation of the electron transport chain, increasing, creating mitochondrial energy. But then at the end of the day, that factory is still going to become dysfunctional.

That's just the way that it is, no matter how well you take care of your car, right? At the end of the day, you can do all the oil changes. You can do all the things.

Your car doesn't last forever. That's the same thing with your mitochondria. And that's that recycling process.

That's mitophagy. So I think of it in three different buckets. And then when I think about how I'm targeting my mitochondrial health, I also think of it in those three different buckets.

[Angela Foster] (6:24 - 6:59)
So the three buckets are basically the creation of new ones, which is biogenesis. Then we have our existing ones and we want them to perform as well as they can. And then when things go a bit array, we need to be able to renew them or repair them just like we would with our car or service them and look after them.

So when we're looking at the middle bucket, right? Making sure that what we have is functioning really well. You mentioned that there's lots of nutrient cofactors that we need for our mitochondria.

There's also things like inflammatory, processed foods, sugar, I think that would damage. Inflammation is also linked to damage to mitochondria. Is that correct?

[Jen Scheinman] (7:00 - 7:29)
Absolutely, yes. And so poor quality diet absolutely is going to help to further that damage to the mitochondria. So and that link of inflammation is because, as I mentioned, the mitochondria are producing these reactive oxygen species as just like a byproduct of your metabolic state.

Yes, like you want to be doing things that are going to like a healthy anti-inflammatory diet or supplements or things that are going to help to quell the inflammation that's happening in your body. And that's going to help be protective of those mitochondria.

[Angela Foster] (7:29 - 7:51)
And we know that when we look at perimenopause, inflammation is rising and also oxidative stress is increasing. So independently of the link between oestrogen and the mitochondria, these two things are also having an effect. Before we go a little bit deeper on the oestrogen link there, what about stress is, I know that so many midlife women are under so much stress.

How is that impacting on mitochondria?

[Jen Scheinman] (7:52 - 8:27)
I would imagine that it is impacting them greatly. I mean, they're very, they're delicate, right? And they also, not only are they delicate, they sort of work in a little bit of a community with each other.

So there's really interesting when we look at images of the mitochondria, they are healthy ones at least are sort of almost like holding hands, right? They're sort of next to each other so that they're working together in tandem. And when our bodies go through stress, and I would imagine that psychological stress, just the same way that a physical stress is going to damage that network of mitochondria and going to contribute to having mitochondrial decline.

So, yeah.

[Angela Foster] (8:28 - 8:31)
Yeah. So there's a lot of things going on for midlife women that are affecting them.

[Jen Scheinman] (8:32 - 8:59)
Yeah, we're in this sort of perfect storm where there's this natural ageing decline that's happening, but then we also have our oestrogen levels, our progesterone levels starting to decline as well. And so we, I like to say that men sort of go down a gentle hill, whereas women get pushed off a cliff. And so we feel it much more acutely.

We see it in our muscle, in our body shape, in our skin. We notice it in just our mood and our fatigue. And we just feel it everywhere from our joints to our hair, right?

[Angela Foster] (9:00 - 9:36)
Yeah. And it shows up in different ways, right? For different women.

Some women will find that they've got really achy joints. Other women, as you said, like this massive nosedive in terms of energy. And I think as women, we're so, I think we just, we take so much self-responsibility that we feel it's our fault.

We pressurise ourselves. We question why we can't keep up with everything that we were doing before. But really it's our biology changing that's going on here.

You mentioned that we have oestrogen receptors on all of our mitochondria. So this is affecting apart from, as you say, red blood cells, right? This is affecting every organ system across the body.

[Jen Scheinman] (9:36 - 10:54)
Yeah, absolutely. So it's interesting because the mitochondria are also the first seat of where sex steroid hormones are produced. So testosterone, oestrogen, progesterone, the very first step is taking cholesterol and turning that into pregnenolone.

And that happens inside the mitochondria. And then of course, oestrogen can help regulate how well the mitochondria are performing. So it's a little like chicken or the egg.

And we have this conversation a lot, like is ageing causing mitochondrial decline or is mitochondrial decline causing ageing? I don't have the answer, but we know that there is this sort of, this feedback loop that's happening where as we start to have lower levels of oestrogen, that's impacting how our mitochondria function. But then also as we have mitochondrial dysfunction, that's also impacting how we feel.

So lots of conversations around using things like oestrogen therapy and hormone replacement or menopause hormone therapy, there's different terms now, but that does seem to help our mitochondria to function better because we are replacing that lost energy. And I think that's a really interesting area of study right now. But there's also lots of women who either can't use hormone therapy or just are not interested in using that.

And so that's where things like supplements or lifestyle factors can come in and to help to support our mitochondria as we start to age and as we start to go through perimenopause.

[Angela Foster] (10:55 - 11:34)
Super interesting. So when we look at that middle category that we were on first in terms of getting them to function better, eating a healthy diet is really, really important, getting the right nutrients, exercising is important, right? So I think doing stuff like sort of zone one, two exercise can help our mitochondria function and other forms of aerobic exercise.

And then also if we start doing high intensity training, we can help with the creation of new mitochondria. But what you found, the other two buckets in terms of the servicing of our mitochondria and the renewal, but also the creation of new mitochondria, there's a powerful compound, urolithin A that helps in these two other buckets.

[Jen Scheinman] (11:35 - 12:57)
Exactly. And when I think of that sort of mitochondrial like life cycle, as I talked about, I think that foundational piece is removing the damaged mitochondria that has to come first, because otherwise what happens is there's only so much space in a cell, right? Again, if we think about factories, right?

There's only so much real estate that you can build factories. And those damaged cells, or sorry, those damaged mitochondria, as I talked about that like community of mitochondria, damaged mitochondria are going to impact, they're almost like senescent or zombie mitochondria. We talk about senescent cells a lot in the ageing community, but there's also this, basically a senescent mitochondria that can damage other mitochondria.

So I think of removing the damaged mitochondria through that process of mitophagy first, then you have room to build mitochondria, and then you can do all the things to protect those healthy mitochondria. So that's how I think of it. There's probably room to layer different things, whether they're supplements or just types of exercise or diet, but the foundation is you've got to get rid of the junk drawer.

Otherwise, it's just kind of cellular mess in there. And urolithin A is very unique in the fact that it is the only molecule that has been proven in humans to stimulate mitophagy. So there's some other great, wonderful mitochondrial support, things like NAD boosters and CoQ10, but they're not working on that mitophagy.

They're not working on that foundational recycling process.

[Angela Foster] (12:58 - 13:38)
It's interesting, isn't it? Because as you were describing that, I was kind of almost thinking like, you could sort of use an analogy. It sounds a bit silly, I suppose, but analogy almost of our hair, right?

If you were thinking about your hair and you were like, I'm just going to really, really look after the hair I've got and really just protect it, but you never really had any new hair grow and you never ever trimmed off the ends, they would split, right? And then it would affect all the other hair. You could only go on for so long before you had to trim your hair and actually make the ends healthy again and also have new hair start to grow before eventually the whole thing would just break down, right?

And it sounds like what you're saying there is we need to think about this renewal as much as we do taking care of what we have.

[Jen Scheinman] (13:38 - 14:07)
Yeah, and what's really interesting about that analogy, I love that, is that as we go through certain times in our life, right? Especially women, like midlife, pregnancy as well, it impacts our hair, right? So you do have to also think about your hair in a different way for not everybody, but for a lot of women.

I mean, I've definitely noticed that I'm shedding a lot more and I've been noticing also that I'm having some thinning hair where I've always had this beautiful thick hair. So that's a perfect analogy because at certain times in your life, you might have to give even a little bit extra notice to the care that you're doing.

[Angela Foster] (14:08 - 14:27)
And if we're not taking care of mitophagy properly, what will happen? Will we over time just start to feel more and more inflamed, that real like kind of sluggish feeling, the brain fog we can experience? So those kind of sort of heavy symptoms, almost like you're lugging yourself around.

Is that how it would manifest?

[Jen Scheinman] (14:27 - 15:28)
Yeah, so I mean, mitochondrial decline has been linked to several different, from just sort of the everyday, how we feel, that sort of energy slump or the not recovering at the gym or just feeling like you're even sort of losing some of your power and ability at the gym. But it's also linked to some really significant chronic diseases. So things like neurodegenerative diseases, like Alzheimer's, it's linked to muscle loss.

So there are some real manifestations about not minding your mitochondria. Now that doesn't mean that every single person has to be like doing all the things, but mitochondrial decline is slowly happening in the back end. So again, that foundation, like if you're not eating well and you're not exercising, that builds up of dysfunctional mitochondria is going to be more prevalent in that type of person than somebody who is actively like eating really well and who's exercising, right?

So it's sort of slow, it's happening in the background for everybody, but it's almost like if you're doing all the self-care things, you're putting the dimmer switch on that background process.

[Angela Foster] (15:29 - 15:33)
And when did it start to happen? What sort of age does this take place?

[Jen Scheinman] (15:33 - 16:39)
It's kind of when we peak and then everything just starts to decline after that. But there's been some really interesting research lately that's showing that we aren't necessarily ageing in this slow decline, that there seems to be like in the 40s and there are 60s, there seems to be like a stronger dip in, we sort of age faster in those two buckets. And then of course, with women, when we throw in, because perimenopause doesn't necessarily happen in your 40s for some women, it happens sadly even earlier, but for most women, they don't actually go through menopause until their early 50s.

So that transition could be plenty of years there, but I think that's really a very noticeable time for women as well. So, and if we're in midlife and we didn't exercise or take the best care of ourselves when we were younger, that doesn't mean it's not too late to start. You certainly can start now, you can start even in your 70s, it's never too late to start.

But I think this is also a really good conversation for anyone who's younger, or who has younger children that you have to start thinking about your health earlier because you do peak it kind of in your 30s. And so if you're starting at a higher place, you don't have quite as far to fall.

[Angela Foster] (16:40 - 17:19)
If you're getting value from this show, the single best thing you can do to help us keep bringing you the highest calibre guests is to subscribe or follow wherever you listen or watch. It takes 10 seconds, but it genuinely makes a difference to the quality of the guests we bring you week after week. And ovarian ageing, right?

I mean, our ovaries are very, very rich in mitochondria. And so there's just, I think it's kind of the thing now, isn't it for 2026? It's not even just looking at longevity, but how can we extend ovarian ageing?

Oh, sorry, extend ovarian function, should I say. When we look at urolithin A, first of all, where do we find it? And how is that helping with mitophagy?

[Jen Scheinman] (17:19 - 19:50)
So urolithin A, let's talk a little bit about just, yeah, where it is and where you would find it in nature. And then we can kind of dive into the, what it does. So it is a natural molecule.

It does exist in nature. It's not something that was like lab grown, but unfortunately most of us aren't being exposed to it. So it's not directly available in food.

It's what's called a postbiotic. So that means that theoretically your gut microbiome would make this molecule for us. So again, in like really simple terms, it's increasingly well-known like how important our gut health is for us and that we have all these microbes who live inside our gut.

And one of their primary functions is they create these molecules that benefit us. I like to say, we give them room and board where our microbes get to kind of live inside us and metabolise the things we can't digest. So things like fibre.

And in the case of urolithin A, there are these polyphenolic compounds, these plant compounds that are often found in foods like pomegranates and berries and nuts. So our gut microbiome will convert those into urolithin A for us. And it's a by-product for them, but it's something that's really helpful for us.

And we probably co-evolved based on like how our diets were in years ago when we ate a lot of these polyphenolic foods and our gut microbiome would basically pay us with these wonderful nutrients. But unfortunately, we sort of evolved out of having a healthy and robust gut microbiome. And also most of us are not eating the right dietary precursors.

So most of us are not getting nearly enough or any at all urolithin A. And in fact, there's been a really well-done study that looked at populations. This one was actually specifically a population in Chicago, but we have also looked at, it's not published data, but we do have some studies that have looked at populations around the globe.

And really only like 30 to 40% of people even have the right gut microbiome to make urolithin A. So no matter how great your diet is, if you don't have the right gut microbiome, you aren't making it. And I know for myself, like I was a C-section baby.

I was not breastfed, I was bottle fed. So I just didn't even like start off with a great microbiome, no matter how well I take care of it now as an adult. I just never in my early stages got all the microbiome that I needed.

So there's probably a really good chance I don't make it. And I also, while I do love pomegranates, I do love berries. You would actually have to drink six cups of pomegranate juice a day to get the equivalent of taking a 500 milligrammes of urolithin A.

And that is something, I think pomegranates are great. Love for people to include them in their diet. Would never recommend somebody drink six cups of pomegranate juice a day.

[Angela Foster] (19:51 - 20:22)
Yeah, that's a lot. So by taking 500 milligrammes, you're effectively, well, I mean, it's doing two things, right? You're drinking the equivalent of the six cups of pomegranate, but you also are giving it to your body and your gut bacteria, even if you drank six cups of pomegranate, may not produce the urolithin A unless you're within that 30 to 40% criteria.

It's interesting because that might explain why we see variations in the way people age and energy levels widely.

[Jen Scheinman] (20:23 - 20:54)
Absolutely. That's something I have sort of chatted with our chief medical officer about like doing a study of like centenarians and are they like higher natural producers? Do they have more urolithin A in their system?

I think that would be really interesting to find out. I think there's so much to learn from people who are living into their late 90s and early 100s and what's different. Certainly there's differences in their immune health and in their neurones and their brains.

There's definitely a lot of differences there, but is some of that stemming from also a difference in their gut microbiome? It would be really interesting to find out.

[Angela Foster] (20:55 - 21:12)
Mm, really interesting. So that urolithin A is then helping us with mitophagy, right? So we're clearing out anything that's old and defunct, recycling new parts.

How is it also helping with the first bucket of mitochondrial biogenesis? So this creation of new mitochondria.

[Jen Scheinman] (21:13 - 21:33)
Yeah, so it is also triggering that same, that process. So it seems to work both ways where it works in a similar way to the way that exercise is triggering these. So many of those similar biomedical pathways are being triggered to first recycle the mitochondria and then to help support creation of new mitochondria as well.

[Angela Foster] (21:34 - 21:42)
Which is amazing. It's transformational. I mean, for me, it's been like really, really amazing in terms of my energy levels.

That's what I can notice. Just such a big difference.

[Jen Scheinman] (21:42 - 23:09)
We hear that so often. And I, you know, for anyone who's listening and interested in trying it, I think it's also important to know that it's a subtle and slow energy. So it's not energy like I just had a cup of coffee or even like I had low B12 and got a B12 shot and you feel that instant energy.

It's happening at a slower rate. So it seems to take about two weeks to clear out the dysfunctional mitochondria and then another two weeks to start to build newer mitochondria. And what we see by doing muscle studies is at around that one month mark.

That's where we see this really nice, robust, significant improvement in mitochondrial function. And we see that because we actually do muscle biopsies where we take a little bit of tissue and we can look at several genes that are regulating how well our mitochondria work and genes that are regulating mitophagy. So it takes a little bit of time to feel it.

This is not like an overnight success. And the other thing is, I call it like feeling like myself again. So, you know, again, it's like women go through midlife.

Some of us, the energy decline feels a little bit slower. Some of us, it feels a lot more quick and impactful. But I kind of like when I reflect on like, how did I feel before I started taking it?

And then like, how do I feel now? And I'm like, oh my God, I feel like myself again. Like before I started going through perimenopause, I just kind of can get through my day.

I'm not crashing and burning at 3 p.m. or like afraid to drive home after work because I'm closing my eyes as I drive home. It's just like, I feel like myself again. And it's noticeable, but yet subtle.

It's not like a jittery type of energy like caffeine.

[Angela Foster] (23:10 - 23:57)
Yeah, exactly. It's like that sort of clean energy, right? That just all day you've got, you can maintain it.

That's what I found. Yeah, it's definitely like a biohack to running a business and having a family and kids to run around. It's been super helpful for me.

For someone listening to this, when they're taking it, the dose that you've studied is the dose that is in the soft gels and the gummies. The gummies, by the way, are very addictively good. So that's 500 milligrammes, right?

Does it matter? I mean, I take it on a daily basis. I look forward to it.

But if, for example, you were travelling or something like that, does it matter? Like a little bit like calories, it's important the dose across a week. If we're trying to be consistent, could you double up on one day?

Like how does a urolithin A work? How should we approach it?

[Jen Scheinman] (23:57 - 25:20)
Yeah, so it is safe to go up to a thousand milligrammes. The benefits seem to plateau at a thousand milligrammes. So our studies have actually looked at both 500 and a thousand milligrammes.

So, but we do see mitophagy. We do see strength improvements happening at 500 milligrammes. So that's definitely a great place to be.

But if someone's not feeling it at 500, they could up to a thousand milligrammes. Now it has about, it seems to peak in the bloodstream about six to eight hours after you take it. You can take it with or without food.

And then it has about a 24 hour half-life. So you do want to take it regularly on a daily basis. But, you know, if you're travelling and you forget to bring it with you, is it the end of the world that you don't have it with you?

No, it's still, you know, it's not a light switch. It's probably more of a dimmer of what's happening when you skip a day or two. But if you skip it for an extended period of time, what we do here is that people do start to notice that that fatigue does creep back in.

So that's something. And a lot of times, because the energy is, they said it's sort of noticeable, but subtle. Sometimes people will say, I don't think this is working.

And then they stop taking it. And then after a couple of weeks, after a month, they're like, oh gosh, yeah, that was actually working. I didn't realise that like I was feeling like myself.

It's so easy to remember how poorly you feel. But sometimes when you're feeling good, you don't notice it in a weird way, right? So yeah, so perfectly fine to skip it if you're travelling, but not ideal.

[Angela Foster] (25:21 - 25:47)
But there wouldn't be a benefit then. So if, for example, like if you're travelling for a couple of days, you could then take a thousand milligrammes on one day. But if you try to, like you're travelling for four days, so now you take four times the amount, actually it sounds like there wouldn't be a benefit once you go above a thousand, you're better off.

Like many things, right? They always sound really boring, but the consistency and the frequency is important. So it's that constant signal, is it to the mitochondria for this renewal?

[Jen Scheinman] (25:48 - 26:46)
Yeah, and that's how, I mean, it's never been studied that way in any sort of like cyclical approach. So I truthfully, like I'm just speaking from how my understanding of how it works. I don't have like a true answer that, yes, it will work the same if we cycle it that way.

But because we know it does peak in the bloodstream at about six to eight hours, that's kind of where you're getting that big bang for your buck. And then it hangs around. And then at about 24 hours, you have half of that concentration in you.

So if you've gone, and so the way the half-life works is like every 24 hours, you have less, half left, less, half left. I can't speak, but you get it, half, half, half. So after about four days, there's not that much that's in your system anymore.

And it's not like it's a, we store fat as energy for when we go long periods of time without food. It's not like we're storing this. And so if we go a long time without it, then it's still doing its job.

But it's not like you stop taking it. And that day, all of a sudden, mitophagy. Yeah, suddenly just stops.

Yeah, exactly.

[Angela Foster] (26:48 - 27:07)
But if it peaks around six to eight hours, then would there be a benefit to taking it in the, say, mid to late afternoon so that you're timing it when, for example, most of that activity is then happening in deep sleep, for example, like between midnight, 2 a.m.? Would there be a benefit to doing that rather than taking it in the morning?

[Jen Scheinman] (27:07 - 28:22)
Yeah, and that's a great question that has been asked plenty of times. We have not studied it that way. There was one study.

We didn't actually do this study. It was in young, I think they were about 24-year-old strength-trained men who they did actually do a split dose. So they did 1,000 milligrammes.

And they didn't measure, to my understanding, I don't think they were measuring like serum levels of your olefin A. They were actually looking at performance outcomes. But they did split the dose between 500 in the morning and 500 at night, to your point.

Would that give a higher threshold? And so I think there's an argument to be made that taking it twice a day, 500 or 250 in the morning, if you're doing the gummies or the soft gels, doing one in the morning and one in the evening could potentially have a higher level. I think there's certainly an argument that could be made.

Or timing it for when you're working out or when you sort of need it the most. I personally find that overcomplicates things. I just need to take my supplements at the same time every day.

As many of them as possible. As soon as I introduce something, like even a digestive aid that I'm supposed to take an hour before I eat, I forget it. I just do.

I can set all the reminders, and then I'm like, oh, I'll take it. So when we've got enough on our plate, I don't think we need to overcomplicate this by timing this. But if that works for you, more power to you.

[Angela Foster] (28:22 - 28:29)
Just take it every day. And the difference between the gummies and the soft gels is just personal preference.

[Jen Scheinman] (28:29 - 28:39)
Absolutely, yeah. So we have studied that we have the same bioavailability. It's just really, to your point, I think the gummies are delicious.

I look forward to them.

[Angela Foster] (28:39 - 28:50)
I was going to say, if you want my personal feedback, because they don't have any nasties in them, it's like a little sweet treat all the same, right? They taste really good. So yeah, for me, I like the gummies.

[Jen Scheinman] (28:50 - 29:13)
I will say it took us a long time to formulate those because we wanted none of those nasties. We wanted it to be clean. It had to taste good.

It also had to look good. And when you're using natural dyes and you're not using artificial preservatives, to get something that also looks good for a while and doesn't start to oxidise and change colours, that's not an easy feat. So it took us a long time to perfect it.

And I also agree. I think they're delicious.

[Angela Foster] (29:14 - 29:42)
Yeah, they are. They taste really good. The other thing that I've noticed, right?

So energy, yes. And I know this is how you almost accidentally came upon this, right? Is that I felt like my skin has improved now.

It's definitely improved even more now because I'm using the skincare. But tell us about this because I think you found this by accident, right? That people not just had improvements in energy, but they were getting compliments on the fact that they looked younger when they were taking urolithin A.

[Jen Scheinman] (29:42 - 30:51)
Yeah, so that's absolutely right. And that's no surprise. Like when you're just healthier, I mean, your skin is a biomarker of your health.

Like we talk about skin so much as like aesthetics, but it's the first place we see ageing, right? We start to see wrinkle development that's happening. And again, as women go through midlife, like we get pushed off the cliff.

But yes, people were starting to notice that their skin was improving. And it was kind of this like, aha, like, well, your skin have mitochondria. What's happening there?

And so when you apply urolithin A topically and we've developed a whole skin line, what's happening is that that mitophagy is happening in the skin cells. And the benefits are staying very potent and localised to the skin, which is really nice. So what we start to see is basically the skin cells are acting in a more youthful way.

So just how your muscle cells have more energy from mitochondria when you take the supplement, when you apply it topically, your skin cells have healthier mitochondria. And so what that means is that they're better at kind of being more resilient to the damaging effects of the sun. We see reduction in fine lines and wrinkles.

People notice that their skin is glowier and healthier. So there's a great benefit that's happening there too.

[Angela Foster] (30:55 - 33:29)
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So if we can look after our skin cells, the other thing that's been super interesting to me is the research now, which I think you just touched on there around the fact that we think of, you know, we automatically think of skin ageing as being an aesthetic thing, but it isn't, right? Because our skin ageing is actually releasing inflammatory chemicals and things that is ageing our body. So we think, oh, I must be ageing inside because my skin's getting wrinkles, but actually the wrinkles themselves are also ageing the body, right?

This was really interesting to me.

[Jen Scheinman] (33:29 - 34:17)
That was so fascinating to me too. We forget that like our skin has a function, right? Besides just like how we present to the world.

I mean, it's part of our immune system. It's our first barrier to pathogens, to the UV light. It's basically like what keeps our inside, temperature regulation, detox, we sweat.

I mean, it's got a huge, huge important role in our health. And there is this sort of cross-functional relationship. Like obviously we can look at smokers who have maybe not lived the healthiest life and that shows up in their skin, but vice versa.

Your skin, as you pointed out, as it's starting to age, is sending inflammatory markers through the body as well. So taking care of your skin should be, at least when we talk about like a longevity and health span and lifespan conversation, I think that has to be part of the conversation as well is what you're doing on the inside, but what you're doing on the outside as well.

[Angela Foster] (34:17 - 34:56)
Yeah, so important. When we look at the skin range, I think it's gonna be a lot of questions. So let me make sure that I have this right in the way I use it.

So there's a serum that I use, which goes on first, right? So that will penetrate deeper. There's also the eye cream, which I love because you can go very kind of close to the eye.

And I've definitely, that's an area that I have noticed has really improved. And then a beautiful, I don't want to call it a night cream, but it's a richer pot, right? That just is so moisturising without being greasy.

I feel like that's what's responsible in part for a lot of the growth. So am I using it correctly? This is how I've been using it.

I know we'll have a lot of questions about the skincare.

[Jen Scheinman] (34:56 - 37:04)
Yeah, so we do have now a full range of products, everything from a face wash to that sort of thicker cream and that eye cream. So every single one of our products has 1% urolithin A. And that's truly where the magic is because it's triggering that mitopogy in the skin cells.

What we see is that all the genes that are regulating collagen assembly and organisation, they're all turned on. That's translating into reductions and fine lines and wrinkles. But then we've also paired that 1% urolithin A with other targeted actives that seem to have a synergistic approach or synergistic benefit.

So niacinamide and trehalose also are working on the mitochondria kind of again in those different pathways that I talked about, like whether they're protecting them or helping create new mitochondria. So that sort of triple trehalose, niacinamide and urolithin A, they really seem to pair well together. And what we also start to see is improvements in barrier function and moisture that's happening in the skin.

And so you get this much more resilient, dewy skin. And I love, like you had pointed out, so like the serum is probably our most popular because it's just like easy to incorporate in any regimen, right? Like if you already have a skincare line that you're really happy with and are not ready to like shift, we can be very loyal to our skin, skin products, right?

So if you're not ready to kind of jump ship, the serum is really nice because you can layer it with like a tretinoin or you can layer it with a vitamin C if there's other things that you want to use or you have a moisturiser you love. And then there is the eye cream. I agree that's like one of my favourite products as well because it's really hydrating and it locks in the moisture.

So you will see not only that like instant plumping of the fine lines and wrinkles, but then that long term benefit of the urolithin A. And then we have two creams. We have that thicker cream, the barrier cream, which especially for women as we start to go through midlife, like our skin gets a lot drier, we start to lose barrier function.

That can be really helpful and really healing. And then the dewy cream, which is actually my personal favourite. It's more of like a lighter, milkier cream.

And it gives my skin, I just think this like amazing glow. Like I use that and then I just use like a tinted moisturiser, like sunblock over. I don't even use like a foundation and I feel like it gives my skin this really beautiful glow.

[Angela Foster] (37:05 - 37:08)
It does. For anyone who's listening here on audio, Jen has a beautiful glow.

[Jen Scheinman] (37:08 - 38:02)
You do too. So I'm glad to see the products are working for you too. But yeah, and then we do have a couple other just interesting things in our mix like our face wash is this really nice, again, for women who have dry skin as they're going through the menopause transition, it's this really nice cream base.

Like you wash your face with it. And when you add water, it kind of gets this very gentle foam. So it's really gentle, but hydrating and it preps the skin really nicely to absorb the urolithin A.

And then we have this really nice exfoliator too. It's a chemical based exfoliator that has some gentle plant based acids. So you're starting to kind of take that top layer of dry skin off.

But then you have the really hydrating, beautiful properties of the urolithin A, the soothing properties of it. So it's a really gentle exfoliator. So unlike I said, lots of different ways that people can kind of play around with how they want to integrate a topical urolithin A into their already great skincare routine.

[Angela Foster] (38:03 - 38:27)
Yes, and that exfoliation helps with the penetration, right, I guess, because you're taking off that top layer. The niacinamide is interesting as well, because so many women that you've combined it with, right, I find that just helps with keeping your skin clear, because that's the other thing that happens in perimenopause is we get these changes, right, in the amount of oil we're producing. Some women go dry, some women go actually a lot oilier at first, and niacinamide can just really help with that kind of balance in the skin.

[Speaker 3] (38:27 - 38:29)
Exactly, exactly.

[Jen Scheinman] (38:29 - 39:06)
And the other thing that's really nice about our skin products as well is we've tested them for allergy and sensitivity. So they're really gentle, especially a lot of the traditional things that women are using in their sort of ageing skin products, like they're using tretinoin, they're using alpha hydroxy acids that can be really irritating and really drying, especially when we're kind of rediscovering. It's almost like we're going through like reverse puberty.

It's like, what is happening? I don't know anymore. So they're really gentle products.

And we've also tested them on different age groups, different ethnicities, so different types of skin. So it's really safe for people to use.

[Angela Foster] (39:06 - 39:46)
I think what's interesting as well with the barrier cream, when you were talking there around, you know, some people are reluctant, they don't want to like jump from the whole of their current skincare routine, is I like to use a very strong retinol a few times a week. And that does cause a little bit of irritation, right? That's part of it.

You can almost kind of, if you've got a strong one, you almost never get used to it. But I find the barrier cream is such a godsend because it was interesting what you're saying around the sun and protecting against inflammation, because I find that any kind of dryness that I get from using retinol, then using the barrier cream the next day, everything just totally calms down immediately and the glow like comes back. So it just, yeah, I find it's just very enhancing.

[Jen Scheinman] (39:46 - 40:10)
I have the same experience. I use a prescription, tretinoin about three times a week. I'm too sensitive to use it every night and I sometimes even use it a little bit less in the summer because I just am worried about being in the sun with it.

But agreed, like when I use the barrier cream on the next days, it just really helps to soften my skin and to just give it that like healthy glow again. And any little dry flakes, it's like flake eraser.

[Angela Foster] (40:11 - 40:34)
Yeah, yeah, exactly. It is. It's amazing.

There might not be an answer to this, Jen, because it might not have been studied. But when we're talking about mitochondria and the skin, the question that then comes to my mind is are there any benefits to utilising this skin care in conjunction with a red light therapy? I know like there'll be so many women listening to this going, what about my red light therapy whilst can I use these together and will it enhance it?

Do we know?

[Jen Scheinman] (40:34 - 41:10)
Yeah, so there is no studies, but I personally use a red light therapy. I definitely think, you know, our mitochondria are declining like we need to pull out the big guns at this point in our life, right? So if you have a red light therapy that you're already using, I think it's a great thing to use in conjunction with a urolithin A topical because you're just helping to support your mitochondria in any way.

Plus, I just think there's something for me that's like very relaxing and soothing about using my red light mask. It's just kind of like my like 10 minutes that like I just kind of have to myself. So I think I wouldn't say give that up.

[Angela Foster] (41:11 - 41:27)
Yeah, it's nice when you, it's funny, isn't it? With the red light therapy mask because half the time I'm like, I'll walk around with it because I can do other things with it. But if you give yourself that time and you just sort of lie there, I almost feel like the effects are kind of even better, right?

Because you're just giving your nervous system a reset.

[Jen Scheinman] (41:28 - 41:41)
Yeah, that's exactly because I feel like when I wear it, like I try to like fold the laundry, but it's like, I don't know, it like shifts then and I don't see as well. So I just I'm like, you know what? That's my 10 minute, like whether I'm going to meditate or just like breathe deeply or close my eyes and that's it.

[Angela Foster] (41:41 - 42:00)
So yeah, it's pretty amazing. I'm going to put a link in the description to the products that I'm using, the skincare products. And because I think it's, we've got some separate links that our audience can use in terms of getting a discount on the skincare and also on the gummies.

You could do the soft gels, but I have to say the gummies are just too good, I think.

[Jen Scheinman] (42:01 - 43:15)
And one interesting thing I wanted to mention, this is actually what I thought you were going to ask is benefit to taking both, like doing the topical and the supplement. And that's one thing we're really looking to unlock. And we believe that what's happening is, so we know that when you put it topically, it's getting to the first two layers of the skin.

It's getting to the epidermis and the dermis, but it's not really getting deep enough to be, it's deep enough to do a benefit, but not deep enough to be systemic, which like a lot of topicals, like you don't want them to kind of become systemic when you put them on your skin. And then, so what we think is happening is that when you take the oral supplement, it's sort of like working on that, like deeper layer of the skin. And so you're kind of getting this like sandwich inside out approach, right?

And then also, if you are sort of looking for the muscle benefits, the whole body benefits, you're not going to get that with just like the topical alone. So I think there's a place to really use both. And especially when you're using the supplement, it's like that controls, you know, you're getting 500 milligrammes, you know that that's going to impact muscle health.

And we're starting to kind of study it in other areas as well, like brain health. We had a really interesting study on immune ageing that was just published back in October. So anywhere that you have a mitochondria, there is a potential for a benefit here.

So I think it can really work well together.

[Angela Foster] (43:15 - 43:23)
Yeah, using inside out. That's the approach I'm going with, with both of those. Immune health.

That's interesting. What did that study show?

[Jen Scheinman] (43:24 - 45:18)
So, you know, to just set the stage, right? I think the conversation around ageing and we think about brain health and we think about heart health and we think about muscle health, we aren't really talking about immune ageing, but that is probably one of the key pillars of determining how well we are going to age. As we get older, our immune cells decline, just like so many of our other cells.

And they're also really metabolically active. So they require a lot of energy from our mitochondria. So when you start to have mitochondrial decline, it's going to impact our immune cells.

Obviously, there's several other hallmarks of what's happening to the immune system as it ages. But that's part of why older adults like either don't respond to vaccines as well, or they get sick or even like things like cancer, because you don't have immune surveillance as strong, right? Kind of like noticing these different cells.

So what we studied, we looked at about, I think it was like 50 middle-aged healthy adults and they were randomised to either having, this was a thousand milligrammes, but either a thousand milligrammes of urolithin A or a placebo. And what we saw in just one month was this really robust improvement in immune fitness. So the types and concentrations of immune cells that you had moved into a more favourable pathway.

We also looked at those mitochondria in the immune cells, and they were all shifting to kind of, you want your mitochondria to be, it's like a little bit of a cleaner fuel source when they're using free fatty acids and amino acids, as opposed to when they're using glucose for their fuel source. So they shifted from glycolysis into more free fatty acid oxidation. So that's a really good sign that they're working better.

And then again, we saw mitophagy and biogenesis was happening in those immune cells. Another cool thing, when we took those immune cells out of the body and we exposed them to, in this case, it was E. coli, but a pathogen, they seem to clear up that pathogen more quickly.

So this is now, that was sort of like a small pilot study that showed a great promise. And so now we're going to be studying some different ways that, and different potential outcomes for immune health as well.

[Angela Foster] (45:19 - 45:35)
That's super interesting. So this is looking at kind of, I suppose, immediate immunity, right? When you're exposed to something like you were saying there, E.

coli like a bacteria, but also longer term immune health in terms of protecting you against sort of chronic disease and things like that.

[Jen Scheinman] (45:35 - 46:00)
Exactly. And so you want both. That's your innate and adaptive immune system.

So you, and what happens is like, as we get older, there starts to be like a shift where you have all these like memory immune cells around, but you don't have as many of those like strong early responders. And so what we saw here was that we started to have more, specifically, it was these cytotoxic CD8 T cells. We had more of those after taking the urolithin A and those are those like potent early responders.

[Angela Foster] (46:01 - 47:22)
I hope today's episode inspired you on your journey to vibrant health and high performance. Make sure you check out the show notes for a summary of all the important links to everything we talked about. And if you enjoyed this episode, hit the follow button and share it with a friend on social media or leave a review over on Apple Podcasts.

Remember, achieving high performance health is about getting 1% better each day. So think about one thing you learned from today's episode and start implementing it today. Share with me what you've learned on social media over at Angela S.

Foster. I love hearing from you and connecting with you. Have a beautiful day and always remember, you are worthy of your dreams.

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Most women in perimenopause assume their energy crash is a sleep or a stress problem. Jen Scheinman, Head of Nutrition Affairs at Timeline, explains what the real reason is, and why estrogen loss makes it dramatically worse for women than men.

If you have been doing everything right and still feel like you are running on empty, this episode explains what is actually happening at the cellular level, and what women in midlife can do about it.

WHAT YOU’LL LEARN

• Why women's energy levels drop faster in perimenopause?

• When does mitochondrial decline start and how fast does it progress?

• What is Urolithin A and why can't you get enough from food?

• What is mitophagy and why does it matter for energy after 40?

• Does Urolithin A build new mitochondria or just clear out damaged ones?

• What is the right dose of Urolithin A and does timing matter?

• Can Urolithin A reduce fine lines and improve skin in perimenopause?

• What does the research say about Urolithin A and immune aging?

• Should you take Urolithin A as a supplement and use it topically?

• Can Urolithin A help with brain fog after 40?