[Angela Foster]
So many women's heads, they feel like their metabolism suddenly breaks in their 40s or 50s, even though they're doing everything right.

[Siobhan Mitchell]
We have a lot of fluctuations of oestrogen as we get towards perimenopause. That can change a lot on how you're using lipids, on how you're losing glucose and how you're storing fat. You're doing your best, but it's just getting harder on every level.

It's not so much that anything has changed in their diet or exercise or anything else like that. It's literally just your hormones changing.

[Angela Foster]
What is happening to women as oestrogen declines in relation to the mitochondria? Because also this impacts on their energy.

[Siobhan Mitchell]
Their mitochondria start to look more like a man's mitochondria. So it starts to have more oxidative stress. It starts to have problems with making as much energy.

It's a master hormone. It's not just reproduction.

[Angela Foster]
It's a master of everything. Siobhan, welcome back to the podcast. It's so great to have you here.

I just was fascinated last time we recorded together about the health of our mitochondria and how they get affected in that peri to postmenopause transition. Welcome back. Yeah, it's great to be here.

I'm excited for this talk. Yeah, me too. Let's start with something that I know is in so many women's heads.

They feel like their metabolism suddenly breaks in their 40s or 50s. So many women kind of hit that point, even though they're doing everything right. They're doing their best to prioritise sleep.

They're eating healthily. They're exercising. What is happening to their body during this stage of life?

[Siobhan Mitchell]
Yeah, this is something that I think could be one of the first signs of perimenopause, because even though everyone emphasises vasomotor symptoms, hot flashes, night sweats, that kind of thing, usually what women notice maybe in their late 30s, like early 40s, that they just feel like their body shape is changing. And that can be very upsetting, but it also is just one of those insidious things that some of you just wake up and you notice like, oh, I have a gut where I never had a gut before. That kind of thing.

And so what I just want to emphasise here is that, woman, you're not having anything happen to you that is your fault. It's not like, I know everyone's trying to be really good with their diet and exercise and all the rest. But what's happening is that we have a lot of fluctuations of oestrogen as we get towards perimenopause.

And that can change a lot on how you're using lipids, on how you're losing glucose, and how you're storing fat. And so, as I just mentioned, belly fat, that's one of the first things that people usually tend to notice that's different about them, is that women normally store most of their fat on their hips and their thighs, you know, sort of part of like the womanly shape. But as you start to lose oestrogen, you tend to then start to look more like a guy.

So men store more of their fat around their middle. And this is going to happen to women too, as they lose oestrogen, because oestrogen is helping them store that kind of fat. So when you take in a meal or whatever, it's basically oestrogen is telling your body, all right, put it on your subcutaneous fat around your thighs.

That's where it's good. But then as you get older, and that oestrogen declines, now you're not having that same signal. So a lot of that fat now gets stored around your belly.

And when it's stored on your belly, especially when it's next to your organs, like your belly and your liver and all the rest, this is called visceral fat. And this fat is inflammatory. It has a whole bunch of, I would say, negative kind of risks to it in terms of your overall health.

So I don't know if women have heard much about belly fat besides just slightly, but it can also make it so you have higher risk of cardiovascular disease. There's a recent study, this is an interesting study, showing that middle-aged women who have more belly fat, so a higher hip to waist ratio, they are going to have more likelihood of cognitive issues. So literally just brain fog at the time.

And they're going to have more issues with white matter changes in their brain. To give a sense of what that means when I say white matter, white matter is these kind of fatty kind of sheaths around our neurones that help our neurones send signals faster. And as soon as you lose that kind of insulation, this fatty insulation around your neurones, you're now going to be slower in the way your brain works.

So that's even probably one of the reasons why when people start to have more belly fat, their brain fog starts to get worse. And that's because they're having less white matter. And so I think this is a whole kind of just a different arena of symptoms that are all sort of tangled together.

But as I said, the first thing that women notice is that they're not getting their pants on as easily, that sort of thing. And this is one of the reasons why. So just to kind of reiterate, it's not so much that anything has changed in their diet or exercise or anything else like that.

It's literally just your hormones changing.

[Angela Foster]
And I think this is so difficult for so many women because it strikes at the core of who they feel they are, right? Because when you have that belly fat show up, it affects their confidence. They're not used to seeing it there.

They also are doing the right things. And then what you mentioned there around brain fog, I speak to so many women who find that really difficult. By the time they're in their 40s and their 50s, they're leading teams, right?

People are reliant upon them. And so it becomes even more difficult. And it's very interesting what you said around the link there between increased belly fat and then increased brain fog.

What is happening to women as oestrogen declines in relation to the mitochondria? Because there's also this impact on their energy.

[Siobhan Mitchell]
Yeah, and this is really important. So one of the reasons why women are so protected from so many diseases that men get at a younger age, like cardiovascular disease, is because their oestrogen helps keep their mitochondria, I would say, healthier than men's. And so there is data showing that, for instance, women's mitochondria have less oxidative stress overall.

So they have more protection against oxidative stress. And they also seem to be having more ability to have biogenesis. So mitochondrial biogenesis, increasing your mitochondrial levels.

And this is all oestrogen mediated. So oestrogen is kind of basically signalling to our mitochondria to be very good at adapting to all sorts of different situations. And this makes sense because if you think about the whole purpose of oestrogen is that it's there to help us produce a new human being.

And so in order to do that, to make a really good, healthy human being, you wanna be able to control your nutrient sources really well. What is the main thing that's controlling your nutrient sources? It's your mitochondria.

Because your mitochondria are using the glucose, the fat, the proteins that you're eating. So what has been seen is when women then start to have declines in oestrogen, their mitochondria, yeah, start to look more like a man's mitochondria. So it starts to have more oxidative stress.

It starts to have problems with making as much energy. And especially seems to affect the way that glucose is being used. So a lot of women notice when, yeah, they get to a certain age around perimenopause, that they're not really feeling like, they're having the same kind of blood sugar control as they used to.

And that's because oestrogen is really important for helping us use glucose through the insulin sort of signalling that bring all the glucose into our muscles. So overall, there's a lot of different effects. I would say that oestrogen is having on mitochondria, but the main thing that is really changing is that we're not gonna be using energy as efficiently.

So we're not gonna be using glucose efficiently. And we're also going to be more prone to not using fats as well. We're going to be sort of sticking fats into places that we didn't want it before, like the belly.

So yeah, these are all problematic. The other area that is also, I think really interesting for women to be aware of that oestrogen is helping with in terms of mitochondria is muscle strength in our overall amount of lean body mass. So once again, when people go through perimenopause and oestrogen goes down, there has been a lot of data showing that your lean mass starts to also just slowly also go down.

And this is because mitochondria in your muscles are no longer as efficient as well too. So yeah, these are all the different things that oestrogen is affecting. The oestrogen is affecting so many things, I can't even tell you.

It's a kind of master hormone. It's not just reproduction, it's master everything.

[Angela Foster]
And a master hormone for longevity. I think the thing there as well, right, is as it's affecting your energy levels and your mitochondria, then you're less inclined to move more or as much as you would have done. Your activity goes down.

I think that's the other thing I was having an interesting conversation with Dr. Bill Campbell around this because he's doing a lot of research into why are women putting on weight even though they're doing everything right is by definition just that stage of your life. You're actually like, I've definitely become more of a taxi driver as a mom. Do you know what I mean?

I'm taking my kids everywhere. They're just more sedentary stuff than when they were toddlers. And so it feels like everything's kind of coming against you.

Do you know what I mean? You're doing your best, but it's just getting harder on every level.

[Siobhan Mitchell]
Yeah, and I get that sense too of just there's so much stress that's going around with women as they try to juggle all these things. And that's the killers, that stress, especially the cortisol that comes with stress is also affecting your mitochondria. And it's also affecting, once again, your glucose control and bringing on more insulin resistance.

So that's, I think, even like a worse situation of just especially at this stage of life. If you're having stress and your oestrogen is declining, you're going to have even more problems using fuel. And what's, I think, ironic is that a lot of women notice their appetite is increasing during this time as well too.

So yeah, during perimenopause, there's actually data showing that the risk of binge eating increases by 65%. And so this is something where, yeah, everyone gets that urge of like, when you're stressed out, let's grab sugary food or whatever. And I think the thing about once you reach the age of like your 40s, you're pretty good at self-control, but it's so frustrating that this is suddenly coming on.

Right when you have it together, when you feel like, all right, I'm juggling all these things, I've figured out my routines, and then this happens. So it is really hard, but I want to also make sure that we're talking doom and gloom, but there's some light at the end of the tunnel. There's some things we can do.

So we'd love to also talk about that.

[Angela Foster]
Yeah, definitely. We're going to dive into that. So just so women listening to this understand, so multiple things going on here, your mitochondria are affected, which is affecting your energy levels.

We see a difference in the way we metabolise both glucose and lipids, so fats. We see our fat deposition changing. So from the hip and thigh area to more of the abdominal area, we see inflammation rising.

And then if we have visceral fat, that's also driving more insulin resistance and inflammation. We see cortisol going out, so we have more stress. This is impacting our sleep, which also affects metabolism.

And cortisol itself, I think signals more of that belly fat. So there's all this going on. But as you say, Siobhan, it isn't about doom and gloom.

There are some things that we're going to dive into now that can help women. One thing I think before we do that, just so women understand, because when we think about oestrogen, many of us have been conditioned to think that oestrogen could be bad, to think about it in terms of oestrogen dominance. It's feeding things like fibroids.

It's feeding endometriosis and to have concerns around that. You and I were talking offline about the differences in oestrogen and the way it's recycled and used in the body. And I think it would be really helpful to explain a bit around that first of all.

[Siobhan Mitchell]
Yeah, yeah. So I think there's been a lot of fear about oestrogen for the last few years, because of a certain study, the Women's Health Initiative that made it seem like, oh, you know, any kind of HRT, any kind of oestrogen therapy is going to really hugely increase your risk of cancer. So I just want to make clear that that's been looked at again.

And now it's understood that that was a misinterpretation of the results. There's like basically almost no increase of cancer risk with HRT. So that is an overblown thing.

So oestrogen is still your friend. It's so much your friend. And that's I think what's really frustrating is that before that one big study, a lot of women were using HRT and having a lot of success with it and kind of feeling good about it and having much better kind of overall health effects.

And I can just start listing some of the health effects you can see with HRT. So there's less risk of cognitive decline. There's like improvement in overall sort of metabolic function, blood glucose, all the rest.

So oestrogen is a good thing. We want to kind of preserve it as naturally as we can. But you know, HRT is also helpful.

But I also just want to talk a little bit about the kind of unknown system in our body that probably women don't really know about. And this is your estrobolome. Your estrobolome is basically your system of your gut having microbes help use oestrogen more effectively.

And I think this is kind of like a very sort of novel idea for some listeners because it sounds like, well, you know, I thought oestrogen is made by my ovaries and a little bit my fat and then it just gets used. It's not that simple. So what's going on is when you have oestrogen being made in your body, it's going around, it's going around and then it gets to your liver.

And your liver is basically your organ that's getting rid of things for you, right? So it's getting rid of toxins. And the way it does that is it basically conjugates things.

So it basically puts sugar molecules onto molecules like toxins and stuff like that. But it also takes sugar molecules and puts them onto oestrogen. And this is kind of a signal to the body that you want to get rid of this.

So once oestrogen has a sugar molecule put onto it, it's the sign of like, OK, this is going to get flushed out. And indeed, it will now get flushed out into your intestines. But the beauty of the estrobilone is when this happens, if you have a certain kind of strain of microbiota, so B.

brevi, amphetamine strains, for instance, or lactobacillus strains, these often have a activity. They have this activity called beta-glucuronidase capability. And what that means is they have the capability of taking that sugar off the oestrogen.

And once they take the sugar off the oestrogen, lo and behold, the oestrogen is now ready to work again. It can do all the same things. And so once that happens, your body's like, oh, there's some oestrogen.

Like, let's shunt this back into the body and use it over again. And this is a really important thing to know because it's so, I think, kind of important that, especially when we get to that perimenopause, that we preserve the oestrogen that we have, right? So it's not like, oh, you know, we're really going to have to go to HRT at the very first sign of anything going wrong.

There's a lot of sort of natural things you can do first that might be kind of, you know, helping out sort of that first, very first sort of stages. So taking care of your microbiome might be one of those. And I think this is something that women just have never heard about.

They've never even thought about taking care of your microbiome to have a better perimenopause. So I would love to talk about that more.

[Angela Foster]
Yeah, I definitely want to talk about that because I think that many women, actually, when they start to see their brain fog, they might look at their blood work and they see that their insulin sensitivity isn't as good, right? So they're developing a little bit of insulin resistance. They've got those symptoms of brain fog they're putting on weight.

They often start to restrict carbohydrate sources and whole food carbohydrate sources that have fibre, have these beautiful polyphenols, these dark pigmented coloured foods that support our microbiome. Often we can cut these out because we feel like it's going to actually stabilise some of these problems that we're seeing on our blood biomarkers. Whereas what I'm hearing from you here is the diversity of the gut microbiome is absolutely paramount during this transition.

And that one of the ways we can support that is through eating lots and lots of plants, right? Fruits and vegetables, nuts, seeds, things like that. And also phytoestrogens as well.

[Siobhan Mitchell]
Yeah, and this is part of the oestrogen that I want to talk about as well because this is another key thing that your microbiome can do. So once again, your microbiome is really this nutrient enhancing thing in your body. So like, for instance, we all know that a lot of the nutrients like fibre, we can't actually digest fibre very well.

We need our microbiome to break it down for us so we can use it better. And when we kind of feed our microbiome with that fibre, it's then doing us a lot of other favours by helping break down polyphenols. So polyphenols, these plant substances that then have a range of very, very useful activity in the body.

And so now I just want to talk about one particular kind of plant source. And these are the phytoestrogens. So just to get a sense of what phytoestrogens are, they're basically oestrogen-like.

So we're basically looking like oestrogen molecules from plants. So they have the similar structure of oestrogen, but they might not be as potent. In fact, they're never as potent, but they can have very specific activities on certain oestrogen receptors.

And this is going to be really important for instance, some of the effects that they can have on your mitochondria, on brain fog, on overall metabolism that I'll talk about later. But the main thing to know about a lot of these phytoestrogens is they also have sugar molecules attached to them. So they look like oestrogen, but they have that sugar molecule on them.

So then they're probably not going to get used by your body unless you have a certain kind of microbiome that can break that sugar off and then bring that kind of oestrogen-like phytoestrogen into your body to get used. And so, yeah, bifidus, it's a great strain. I think this is one of the ones that people look at, for instance, for longevity, just overall, like centenarians usually have a lot of bifidus in their microbiomes because it's so useful.

And bifidus is also, I think, one of the dominant kinds of bacteria that you see in younger children. So people sometimes say that centenarians look younger in terms of their guts because they have so much bifidus. And that bifidus is allowing us to use a lot of these plant molecules like phytoestrogens better.

So just one more thing I want to say about phytoestrogens is there's all different types, but I would say one of the best sources is isoflavones from soy. And the reason why I really want to emphasise soy, even though I think sometimes it gets a bad rap, is that it is probably the biggest source of phytoestrogens you're going to get from your diet. There are other phytoestrogens you can get from clover, from black cohosh, but like, let's be honest, no one's eating that in their diet, right?

So soy is really the best way to get a decent amount of phytoestrogens.

[Angela Foster]
So before we dive into soy, so just so everyone kind of, because there's a lot of information here, right, it is a tonne to take in. So for women listening to this, so as you go through perimenopause, right, it's not like your oestrogen is just coming down very slowly. Unfortunately, it's going up and down and up and down.

And that's why you see these changes in like one day you feel great, and then the next day you don't feel good. And one day you're feeling pretty sharp and then you have brain fog and you're just so up and down, right? It can affect your mood as well.

And so the estrobolone is helping to stabilise that because it can release these, take off these sugar molecules and release some of that oestrogen back into the body. So bring you back to a nicer baseline. So you need a good gut microbiome for that.

But then these phytoestrogens can also have that effect. So now we're getting more stability. So menopause hormone therapy, it's not the same as your own oestrogen insofar as it's not going to bring you up to those top levels.

But again, it's trying to raise the baseline, right, so that you're not so symptomatic. But looking after your estrobolone and having phytoestrogens are natural ways that if you're someone who isn't taking menopause hormone therapy can support you. And if you are somebody who is, can also support alongside that menopause hormone therapy.

Would that be a good summary of where we've got to so far?

[Siobhan Mitchell]
That's a great summary. It's really just softening the edges. This is really what it's about.

So, and I think that's appealing because I know HRT should be more available to women. And I think that's a whole other story to talk about. But if you're just starting to notice those first signs like, the accumulating belly fat or the brain fog, or maybe trouble sleeping, this is where, yeah, focus on your microbiome, focus on maybe increasing a little bit of soy in your diet and kind of also just taking the stress off.

But yeah, I would say those are the first things maybe to see. And you can tweak that and see how that's working.

[Angela Foster]
Yeah, or if you're taking some oestrogen alongside, you're still having a cycle. So you don't want to go up yet to higher dosages. This is going to really help support you.

When we think of, and many of my listeners will have listened to this episode with Dr. Sarah Berry, when we were talking about soy isoflavones and how to utilise these properly, we need to be an S-equal producer, which again comes back down to our microbiome. Can you clarify that? How is that working and what do we need to do to optimise that?

[Siobhan Mitchell]
Yeah, so this is a whole interesting one. And I want to just give a little story about how I first heard about S-equal. So like maybe about 20 years ago, I was looking for things that just would help overall metabolism.

So I was really interested in understanding, you know, what are the things in plants that can help us best in terms of heart health, metabolic health. And I kept hearing about S-equal because especially in Asian populations who have high amounts of soy intake, their microbiomes are more likely to have the ability to make this S-equal. And if they have that S-equal production, they seem to just be in better health in so many different ways.

So there was just a flood of studies coming out from places like Japan showing that if you have S-equal production, you have lower risk of dementia. You have overall less belly fat, you know, lower body weight, better cardiovascular health, better arteries. It just went on and on.

So I was so intrigued. Like, how do I get this S-equal? You know, where is it?

And the more I understood about the microbiome, the more I was kind of like, oh, you could eat soy like crazy and you might never get it. You're never going to get this effect. You're never going to get this S-equal production.

So that was really interesting to me. And I spent a lot of time trying to understand, like, can we get just plain old S-equal? And at that time, no, you could not.

You know, either you're a lucky person and you could make S-equal in your microbiome or you couldn't. But today there actually are now sources of S-equal, which I'll talk about later. But just to get back to your sort of question about, yeah, how do you become an S-equal producer?

It's not clear. And I will say 20 years of research went into trying to understand this. There's a bunch of different things that seem to correlate.

So if you're a vegetarian, you might have more likelihood of S-equal production. If you drink a lot of green tea, that seems to help. If you eat soy just in general, this seems to help.

Though there was one intervention trial where they had women have a whole bunch of soy milk and, you know, kind of drinking that every day for a certain amount of time. And they saw a few women convert, but not everyone. So it's not as simple as, like, go out and have some soy and then you're going to have S-equal.

It's a bit more complicated than that. But they did do a lot of understanding of some of these microbiome bacteria that you need. And they definitely knew that B-Bravae, Lactobacillus, these types of things are absolutely essential to start the process of making S-equal from Dadecene, which is a soy isoflavone.

So that was one thing. But yeah, once they figured out a way to make S-equal, I feel like this was a really interesting moment because then they're able to start doing all these interventions with S-equal and seeing all these amazing effects. So for instance, with S-equal, they saw that this could improve overall metabolic health.

So it helps with body composition. So less of that belly fat that we just complained about. Like, if you make S-equal yourself or if you take S-equal, you can help relieve some of that belly fat.

Obviously, exercise and diet helps, but we all want something else to help as well. The other areas it seems to help with is bone health. So it helps with bone mineral density.

It's helping with blood glucose control. So when people took S-equal, they had kind of more normal blood glucose biomarkers like A1c. And then they also saw that they had overall better arteries.

So their arteries or flexibility was improved. So that is really indicative to a better blood flow. And interestingly enough, they also saw with S-equal that you could improve skin health So women who took S-equal had better hydration of their skin, less wrinkles.

So it just goes on and on. The one other thing I think that is interesting to point out, because I know this is not talked about as a perimenopause symptom, but it is something people notice really early on, is joint pain. So a lot of people don't even realise that could be a menopause symptom.

For instance, I had frozen shoulder when I was 41 and I had no idea where this came from. I'm like, suddenly my arm isn't really working that well. And I started getting worried that I was getting multiple sclerosis.

And I went to a doctor, no one could figure out what was wrong. And that was literally a perimenopause symptom that is now, I think, much more well-defined that you can get frozen shoulder. Just your arm feels a little bit numb and it's not working as well.

And then the other thing that I noticed was I started to have more joint pain when I did my runs, all that kind of thing. And that is once again, because of loss of oestrogen. But interestingly enough, when sEqual was given to women who are showing signs of joint pain, it actually really helped them.

And not only that, it helped improve their mood at the same time. So I thought that was really cool that they weren't really particularly looking for a mood effect from sEqual, but they saw that, with any kind of relief of pain, believe it or not, ladies, this will also improve your mood. And so I was really kind of thrilled to see that one as well too.

That just recently came out.

[Angela Foster]
That's really fascinating because everything you've mentioned there are the things that women are either struggling with or worrying about when they're going through this transition, right? Mood stability is a big one. Anxiety, feelings of depression, also brain fog, as you mentioned, the belly fat, the joint pain, the inflammation, and then concerns around how is my glucose looking at my blood lipids?

What about my cardiovascular health? And these are all the areas that are affected by oestrogen, which is dropping, are also affected by sEqual. One of the things that you mentioned when we were talking a little bit offline, and I think we could do this on a kind of, I guess, a kind of grade school level so we don't get too detailed, is just the difference on the oestrogen receptors that it's acting on.

Because you were mentioning how the oestrogen beta receptors, people still have those concerns that you highlighted earlier around oestrogen, and does it cause proliferation or things like cancer? And those are actually different receptors. I think if you could explain that distinction, that would be really helpful, sure.

[Siobhan Mitchell]
Oh, yeah, yeah. And this is, I think, really interesting. So this is a whole new world about oestrogen signalling that, once again, should be better understood.

And that's basically that we have different kinds of oestrogen receptors on different parts of our body for different functions. And so the main ones are oestrogen alpha and oestrogen beta receptors. And they have, yeah, I would say, very, very specific purposes.

Oestrogen alpha is more on your reproductive organs. So it's on your breast tissue, it's on your ovaries, it's on your uterus. And it's kind of there helping, I would say, mediate nutrients for more reproductive purposes.

So for instance, it's proliferative, helps with proliferation of cells, for instance, which is very important in pregnancy. But then you also have oestrogen beta receptors. And oestrogen beta receptors are kind of located in many more places.

So there's a lot in your brain, they're on your muscles, they're on your fat tissue. And these oestrogen beta receptors seem to be really important for your metabolism, especially important for your mitochondria. And these ones are the ones that S-Equal hits.

So S-Equal isn't really doing much on your oestrogen alpha receptors, but it is really hitting those oestrogen beta receptors and helping with all those things we just talked about. So helping with blood glucose, helping with fat metabolism, helping keep your arteries clean by increasing nitric oxide release on these daylights, your arteries. And so this is, I think, what's really nice about phytoestrogens is you're not getting those overall side effects that people don't like with hormonal replacement therapy.

You're really just hitting those oestrogen beta receptors that are managing the symptoms that are problematic, like the brain fog. So all those oestrogen beta receptors in your brain, S-Equal, interestingly enough, is probably the most brain bioavailable of all the phytoestrogens. So it can go straight to your brain and really help out with that oestrogen signalling that can increase neurotransmitters, things like serotonin, things like GABA that can help with anxiety, that can help with overall mood, and it can also help with the sort of cognition that we notice, especially when we start having mitochondria dysfunction and energy's not being used as well.

This is where S-Equal can take the place of some of that and then bring your mitochondria back to a bit more of a functioning level and protect them at the same time.

[Angela Foster]
It's so interesting because when we look at these statistics, you know, women are most likely to take their own life between the ages of 45 and 54, which is right during this period of transition. So to think of S-Equal being able to target the belly fat, improve your lipid and glucose control, help to clear brain fog, and improve neurotransmitter function so that you're having an improved mood is pretty amazing. Because, you know, one of the things you've noticed, but I've noticed on my own kind of journey through perimenopause, I'm happy to share this, is, you know, as someone who also had a history of depression, I really have relied on exercise.

And then what I've noticed as I'm going through this process, even despite menopause hormone therapy, is that the workouts that used to give me... Everyone says, oh, what used to work doesn't work anymore. We often default to the muscle gain, the fat loss.

But actually what used to work wasn't working in relation to my mood, right? So I would get a huge kick from, you know, working out in the morning and I feel amazing. It would order my brain because I'm kind of very ADD prone, but it would also give me that mental boost.

And I've just found that it's harder to get that kick, you know? And I think this is another frustrating thing because of the way it affects neurotransmitters. So this is super interesting if SQL is affecting your mood in addition to the brain fog and the belly fat.

That's just kind of like a golden trio.

[Siobhan Mitchell]
I know. It's one of those areas where every woman knows that oestrogen is affecting their mood and it's just that fear of, you know, the PMS. And then as you say, like perimenopause, like you could just have crazy dips in your mood for no reason at all and you don't know what's going on. But then it just feels a little bit like, what do I do about it?

Like I'll go exercise or whatever. But maybe that's not always the thing. It's really about how can you address the root cause?

And the root cause is you just need a little boost of your oestrogen signalling. And there's just things you can do with your diet that can really, really help. And why not take advantage of those?

So yeah, I have the same experience where I exercise all the time too to improve my mood and I try to eat right and all the rest. And when I was going through perimenopause, still am, I just started getting massive night sweats all the time. And I'm like, what am I doing wrong?

I'm trying so hard. And that's actually, you know, just to sort of talk about menopause symptoms, the vasomotor symptoms. S-Equal was really able to take away those night sweats for me.

So that's another thing. There's been several clinical trials showing S-Equal is effective for the hot flashes and night sweats. So once I got those night sweats taken care of, I was now sleeping better and I just felt like, oh, I'm kind of back.

I'm back to how I should feel rather than kind of being all frustrated all the time.

[Angela Foster]
Yeah, absolutely. Because then, I mean, then you can tackle the things. I mean, it should be an expansive period of your life.

You've achieved, you know, so much in it. We've achieved so much in our careers by this stage. Many of us are kind of raising children.

It should be like a real opening up. And that's very much how I want us to embrace it. But I think the rocky road in the meantime can just feel so challenging.

When we think about S-Equal, so just so we can clarify this. So if you're eating phytoestrogens, you may be benefiting, but you might not be because I think only 20% of women in the West have the right microbiome to actually convert those phytoestrogens into S-Equal. The other thing that Dr. Sarah Berry was speaking about is I think many will then go to their health food shop and start taking soy isoflavones. But that doesn't mean that because you still got to go through the conversion process as well. So just going and buying soy isoflavones isn't necessarily going to cut it. What we need is the S-Equal unless we are a natural producer, which is only a fifth of the Western population.

Is that correct?

[Siobhan Mitchell]
Yeah, exactly. So that is the problem. And I felt like that was so unfair for years and years.

So what was cool was that MinoQ, so where I work, we saw that there was a gap in the way women were being helped through this perimenopause. Because I agree, it should be this amazing time where you just realise I have acquired so much wisdom, so much understanding of the world, all these accomplishments. And instead, you're just kind of feeling like, God, you know, I just got hit by a truck by all these things I didn't expect.

And so what we found out was now that S-Equal can be made by a fermentation process. So we basically made this product that has S-Equal in it, as well as B-Bravais, which is, as I said, one of these molecules that helps with your oestrogen. And basically kind of feel like this is the sort of two kind of hero ingredients that can really bring women to a better kind of overall metabolic state as they're going through perimenopause.

But then also address, you know, that the whole kind of slew of other things like, as we talked about, the brain fog, the feeling of like appetite out of control, the bloating, the rest of that sort of joint pain and whatnot that seem to just affect us. And just, it seems like there's so many diverse things that can go wrong. We were like, what is the sort of main kind of molecules that can really fix all these diverse things?

And it really seemed like S-Equal and B-Bravais were the way to go.

[Angela Foster]
It's interesting, isn't it? You sort of wonder why it hasn't been done before. Is that because it has been a difficult thing to produce?

Like you mentioned there that it needs to be fermented because we've had supplements of soy isoflavones for a long time, right? And like Sarah said, it's kind of a lottery because people would take them and some women would get benefit and some wouldn't because they weren't necessarily these producers. Is it quite a difficult thing to produce on its own?

[Siobhan Mitchell]
It is somewhat difficult, but just because I mentioned Japan as one of these places where they saw that S-Equal was so beneficial, there was a lot of work there to try to understand like, how do we make this? Like we need to make this so we can really solve all these sort of issues that people notice when they go through perimenopause. So they've perfected a sort of way of doing it.

So now it's somewhat simple, but it's just not well-known. I think that's sort of ironic is that in Japan, it's a very popular supplement. So everyone knows about it, but just in the Western world, we have not talked about it.

I think there's just been that, once again, that feeling of like soy, I'm not sure. I'm not sure if it's good. And I totally agree with Sarah Berry.

A lot of the studies that came out with soy were quite variable in their effects. So sometimes it worked, sometimes it didn't. So I can see where people were like, what is soy doing?

I'm not sure if it's like the thing I need, but what I can tell you is that it seems like whenever they try to see who's really benefiting from soy intake, it's those S-equal producers. So then why not find a way of giving S-equal to people who can't do that? And I don't know if I can make S-equal myself, but I think just from my experience of starting to take S-equal, I'm like, oh, I probably wasn't because now I was eating a lot of soy because I am sort of vegetarian, but now I'm like, okay, now I'm really being helped.

So yeah.

[Angela Foster]
Because you can see the material difference.

[Siobhan Mitchell]
I can see the material difference. So, and that's, I think what's nice about it is, you know, after a few weeks you're like, oh, this is way different. And just to be clear, like I am taking HRT at the same time, but I think HRT for all its benefits, sometimes it's just not hitting enough in one spot.

And so for me, I think it was really like those brain oestrogen beta receptors that need a little help. So once I got that helped, you know, a lot of those, for instance, vasomotor symptoms, which we know originate in the brain. So it's not going to be something where take anything and those night sets will go away.

You have to take something that's brain bioavailable. And that's the good thing about this molecule as it gets into the brain. I've studied a lot of stuff.

I am a neuroscientist. I've studied so many different plant molecules, whatnot. And I tell you, getting into the brain is really tough.

So if you can find something that gets into the brain, that's really going to change everything.

[Angela Foster]
So this is because it's basic, it's crossing the blood brain barrier and actually getting into the brain. It's really interesting. I mean, yeah, when, when you came out with this, this product, hormonal metabolic control, I knew that I wanted to have you back on because it's just so fascinating.

And why have we not, you know, had this before? And I just don't think people, people are aware of it. As you say, I also think that a lot of women have been kind of conditioned to worry about soy because, you know, in the West it's spoken about how it's, you know, monocrop farming, there's GMO, there's these things.

But what you're talking about here is S-Equal that's been fermented from soy from Japan. It's, it's a different process.

[Siobhan Mitchell]
Yeah, it's kind of funny when we're making this product, we actually got to put a soy-free label on it because it's not technically from soy. So it's kind of like, okay, if you have a fear of soy, this is, this is not actually soy derived. So I know some people feel like, oh, I have a soy allergy or something like that.

S-Equal, it's just one molecule. So it's totally fine if you do have a fear of soy. Not that you should, because I think soy can be very beneficial in a lot of ways, but maybe not for like that oestrogen beta receptor stuff that we always talk about.

Like I love soy protein, I give you soy protein all the time. But just if you want to get, I would say the most phytoestrogen benefits from soy, you need to have S-Equal.

[Angela Foster]
And then you've got the E-Brevet that you've put alongside it. So that will also then be enhancing the estrogloam and also our ability potentially to make the most out of phytoestrogens that we're hopefully eating on top.

[Siobhan Mitchell]
Yeah, exactly. So this is where, you know, we know that you shouldn't always just say like, okay, one molecule does it all. Like B-Brevet really made sense in terms of the way that it does help bolster your overall gut health.

So, you know, the bloating, bringing your gut barrier back to normal, because that's another thing that goes away with loss of oestrogen is you get leaky gut, right? So a lot of women start to have like stomach issues as well too. So B-Brevet, we knew that that was really something it can help with.

So it just seemed like a really good complimentary kind of effect in terms of helping recycle the oestrogen, but also having its own kind of power in terms of helping your gut, helping with, you know, overall sort of, once again, lipid metabolism and yeah, the way you're using fuel, because that is really, I think what makes the difference in the end is the way we're using fuel.

[Angela Foster]
And I think also for the small number of women who can't take menopause hormone therapy, this is pretty amazing. Or for women who simply, you know, choose not to do that. It has some chromium in the formulation that you have.

It also has some chromium, which can help with, you mentioned earlier, it made me smile because I was thinking about my propensity for chocolate cravings since hitting perimenopause and how chromium, I might be the only one. I'm sure there's other listeners like and viewers thinking, yes, that's also me sometimes. Chromium can help with food cravings.

It also helps with blood glucose control as well. Can you explain a bit more about chromium?

[Siobhan Mitchell]
Yeah, chromium is just one of these really solid nutrients for helping with blood glucose control, as you say. So we knew it just was something that could bring on some extra effects. So we thought that was really important.

But at the same time, we also thought that the way that people experience whether something's working is, yeah, if they are feeling like their appetite is kind of more covered, that kind of thing. So yeah, we thought addition of chromium would help at least give that recognition of like, yeah, you feel like your appetite is a little bit not what it should be. So, you know, maybe this can help as well too.

So yeah, chromium, I think it's once again, these really nice kind of nutrients that, for instance, can really help with postprandial glucose, which is the big problem that women experience. I don't know if you've ever worn a CGM. I'm more of a continuous glucose monitor.

And I'm mostly OK with my glucose, except that it really does spike a lot during meals. And it was very surprising. So then it just made me realise like, OK, I have to have something that helps smooth over the way that glucose is flooding my system.

So chromium is a great molecule for that.

[Angela Foster]
And helping to quieten some of that food noise? Yeah. Yeah, yeah, alongside.

When we look at, because I think it would be really helpful to just kind of pause a little bit on the mitochondria and how we can influence them, because I get asked a lot of questions around this. I think for many women and men, I think it can get really confusing over what should I be taking? Or what should I be thinking about, right?

And how can they affect my, how can these different compounds affect my body? So when we're looking at S-equal, this is hitting multiple of the symptoms, right? That are being expressed by our body in terms of perimenopause.

We've mentioned already, like the belly fat, the blood glucose control, the brain fog, the fact that it crosses the blood brain barrier, inflammation in your joints, energy. But to come back to it, primarily it's also affecting, in a big way, the mitochondria. And you have, as a company, MitoQ, have three different supplements that affect our mitochondria in different ways.

I think it'd be really helpful for people to understand what exactly each one is doing to the mitochondria.

[Siobhan Mitchell]
Yeah, I would love to. So just to preface, mitochondria is my main passion in life. I think mitochondria are one of the main reasons why we age.

And so we need to take care of our mitochondria in as many ways we can. And it starts early. Mitochondria dysfunction can start in your 30s.

So even when you feel great, you think everything's going well, think about your mitochondria. And of course, the reason why mitochondria are so problematic and I would say even causing some of the diseases of ageing that will ultimately actually kill us is that mitochondria, while regulating energy and making energy for us, are causing a lot of oxidative stress. And so that oxidative stress can be controlled while we're young, but gradually the systems that control oxidative stress break down, they break down.

And then at some point, that oxidative stress can damage your DNA, damage your proteins, damage your cells, and basically cause ageing. So at MitoQ, we have this molecule called mitoquinol. So the kind of full name is MitoQ Mitoquinol that was developed as a special antioxidant to get inside the mitochondria because I've studied mitochondria for decades and it's really hard to get stuff in the mitochondria, hard to get stuff in the brain, but even harder to get stuff into the mitochondria.

It's very well protected. But this mitoquinol was designed to penetrate mitochondria by being very positively charged because the mitochondria is negatively charged so it could get sucked into the mitochondria. And once inside the mitochondria, mitoquinol has a very strong antioxidant activity.

So as you age and you lose your own antioxidant systems inside your mitochondria and you're starting to get that damage, that wear and tear, increasing, mitoquinol has been shown in at this point, like almost 30 clinical trials to protect your mitochondria and thus protect your heart, your vasculature, all sorts of organs like your liver and your kidneys and your immune system. So mitoquinol, I would say, because it's so good at protecting the mitochondria, it has many other benefits because of the fact of oxidative stress being so important for how our organs are ageing. And I would say all of our organs.

So that's one thing.

[Angela Foster]
And for younger women then as well, right? When we look at the ovaries, they're really rich in mitochondria when you're thinking about fertility as well.

[Siobhan Mitchell]
Totally, yeah. And mitoquinol has been used so far in preclinical models of infertility and shown to be very good for helping with fertility in terms of helping with egg quality, helping ensure that, you know, you can get healthy embryos. For instance, we actually have a trial going on funded by the Gates Foundation that's looking at mitoquinol for preeclampsia.

So preeclampsia, just so everyone knows, is this disease where you get severe hypertension while pregnant. And this is supposedly due to mitochondrial dysfunction that can happen to young women during this very stressful time of pregnancy. So we're really excited to see the results of that.

So that's just give you a feeling of how much mitoquinol can help with like all aspects of your health.

[Angela Foster]
So yeah, we're really excited by that. Well, I was just going to ask because like I think when you mentioned about mitoquinol, I just think it's helpful for people to understand because they've heard of coenzyme Q10 being a really powerful antioxidant and that's a cardiovascular protective. And then, you know, some people have kind of dived, is it?

Dive a little deeper than you might in your healthy shot or see ubiquinol, right? Which is this sort of concentrated form. But my understanding from you is that these are still not much of it is making their way, making its way into the mitochondria and to the mitochondria.

And this is where mitoquinol is. Is that the distinction?

[Siobhan Mitchell]
Yeah, that's a very important point. So thanks for also bringing that up that. As I said, mitochondria is really hard to get into.

So CoQ10, along the other antioxidants people think are getting into the mitochondria, like I think people feel like, you know, for instance, urolithin A is getting the mitochondria. It really isn't. It's just a few things.

So mitoQ, mitoquinol was really designed to get into the mitochondria. But CoQ10, I will admit, can help with the rest of your cells. It just is not going to get to the mitochondria.

So it does have some benefits. It's just not, I would say, is important for mitochondrial health, unfortunately.

[Angela Foster]
And then you have, we did a whole episode on this, actually, on the importance of enhancing NAD production within the body. You have your NAD plus dual action, which I just would not be without because the noticeable effects on energy. I also feel like, I mean, this this affects, right, the 12, we've got 12 hallmarks of ageing, kind of when we sort of helicopter out, it's having an impact on all of them.

I notice, you know, just less feelings of inflammation, joint pain and things like that. Even with that, I'm going to link back to the episode because I think anyone that wants to do a deep dive into NAD, we hear so much about it. You should go and listen to the podcast that Siobhan and I did because we really go deep on it.

But if you could summarise it really briefly, how is that helping our mitochondrial health?

[Siobhan Mitchell]
Yeah, I'd love to. So NAD, everyone hears about it and is kind of like, it sounds good. That's all they know.

But just to make sure it's clear what it's doing. So NAD is kind of like a, I would say a cofactor in how our mitochondria can make energy. So NAD is bringing electrons and protons into the mitochondria and helping feed what's called the electron transport chain that helps, yeah, have this kind of energy storage that allows us to make ATP.

That is obviously what the mitochondria mainly do, is make ATP so our cells can run. And so the main thing that people understand about NAD is that you need it to make energy. And if you start to have any kind of decrease in your NAD supplies, you are not going to make as much energy.

So I think that's the real main point for people to recognise. And the other main point is that NAD also has a lot of signalling power. So the way that NAD works in the cell is it's basically telling the cell, oh, the cell is under stress or the cell needs to use nutrients more effectively.

And so for instance, NAD hits these enzymes called sirtuins. And sirtuins are kind of like master metabolic regulators for us. So they help stimulate a lot of repair for instance, when our cells are stressed, it can make more DNA repair enzymes activated.

It can bring all sorts of like mitochondrial biogenesis so you can make more mitochondria to make more energy. So there's a lot of things that these sirtuins can do. And so there's like this whole kind of system that NAD is powering where it's helping make your actual energy, your actual ATP.

But it's also helping keep your cells healthier to make more energy. So the thing that we know about NAD is that it does go down when we get older. Unfortunately, it seems like everything that we want in our body starts to decrease just because of that wear and tear.

So at some point, you are going to need to probably feed your body with more NAD. And in fact, there's a lot of studies showing now that when you are giving the body NAD precursors, so nicotinamide riboside, for instance, or nicotinamide, you can get all sorts of benefits for powering better exercise, for having overall better vascular health. So yeah, and that is due to the fact that you're helping, one, create more energy, but also create more kind of repair systems.

So in a nutshell, NAD is something absolutely essential, but it's not something that mitoquinol is really going to affect, right? Mitoquinol is a great oxidative stress kind of protector of the mitochondria, but I would say, you know, what we're really trying to do is trying to look at all the different ways that mitochondria can dysfunction and how can we make solutions for them. So mitoquinol is really there for your oxidative stress kind of like capacity of like, all right, let's bring that back up to a younger level.

And in fact, we just had a clinical study fix a finish that shows that you can actually bring your mitochondrial capacity up to a kind of younger level in terms of looking at immune cell mitochondria. That's a clinical study we'll talk about later, more to come. But then the NAD is really about ensuring energy supply and ensuring repair if you do have some oxidative stress.

Then at the same time, we're thinking like mitochondria, you know, where else do they go wrong? And especially for women, mitochondria go wrong when you lose that oestrogen for all the reasons we just talked about, that oestrogen are so important for, yeah, making oxidative stress go away, for improving mitochondrial biogenesis, for, yeah, basically using nutrients better. So we knew that we needed to have something that directly went onto that pathway of oestrogen to help with that, especially during midlife.

So, yeah, I think just looking at the sort of three different products we just talked about, I would say, and I often actually do do this myself. I would say all three can help your mitochondria. So in a way, it makes sense to take all three and have that kind of overall kind of insurance against mitochondrial dysfunction, which, as I said, is one of the reasons why we age.

I think the most important, people can disagree with me. There's a lot of back and forth in the healthy ageing field of what it is, but that's the most important. But it's definitely one of the 12 hallmarks.

And it's also, I think, one of the most important ones for our energy using, like our most energy intensive using organs like the brain, like the heart, like the muscle. So if you want to have better brain function, better heart function, better muscle function, you have to think of your mitochondria.

[Angela Foster]
100 percent. And I think if you just, and it's such an opportunity, right, when you go through your 40s and 50s to really like open up, be expansive, live your best life, if you've got the energy to do it. And just the women who really prioritise all the healthy habits, right?

It's not about just taking a supplement. If you prioritise their movement, have, you know, really look after their sleep, eat really well, eat diverse plant-based diet with healthy amounts of protein and fats. And then if you use some of these supplements that can enhance your mitochondrial function on top and things like the S-E-QOL that can reduce the brain fog, help you have a better, have better metabolic health and that cardiovascular health.

It's just, it kind of is like having all the attributes of being that older, right? The wisdom and the experience, but the biological youthfulness. I mean, when you, I got very excited when you told me that it like helps your skin look younger as well.

That's just an added bonus there. But I think you just can, you can really, really enjoy things, enjoy things because this is the time of your life that things open up, right? You have less responsibility if you're a parent over time where you can travel, you can go and, you know, see more of the world and do fun things.

If you have the energy to do it. And I've definitely found that focussing on my mitochondria has been so important during this perimenopause transition. And it makes so much sense because we know that oestrogen directly affects the mitochondria and mitochondria affect oestrogen, right?

There's this bilateral relationship. So I think it's just so, so important and it's been transformational for me. You're always running studies because it sounds like you've got more to come back and share.

What you were saying there is that there's a new trial.

[Siobhan Mitchell]
Yeah.

[Angela Foster]
What's the best way before you come back again? What is the best way people can go and check out MitoQ, the latest product is hormonal metabolic control. I personally take all three.

I feel fantastic. We'll link to that in the description with a special discount. And how can people keep up with everything that you're doing, the clinical trials you're doing and the research?

Because you really are at the forefront of mitochondrial health.

[Siobhan Mitchell]
Yeah, we try to be. We have, I would say, 15 different clinical studies running right now. So we are really busy.

And if you want to hear more about this or just understand more about these products and your own mitochondria, you can go to MitoQ.com. So we have a blog there that can give you a lot of information about some of these studies and other articles to do with mitochondrial health and healthy ageing and perimenopause and everything else when we're going through during this time. Go there, check it out.

We also have Amazon.com that sells our products. And I'm not too sure where we can get in the UK. I think UK Amazon also has it, right?

Probably.

[Angela Foster]
I'm not sure if Amazon. Definitely get them on MitoQ.com. Yeah, that's the place.

Yeah, very easy to do it there. Question that's on my mind and will be for many, many women listening to this. Which of these three can my husband take?

What can their partner take? Yeah, my husband is always taking my stuff, especially he does one work from home day and he's always like, I feel so healthy on my work from home days. And I give him like a bundle of stuff that he'll take into work.

But somehow he just remembers more when he's at home. And I think it's true of many women is that their partners end up taking things because they have it. The NAD plus and the mitoquinol.

But what about the hormonal metabolic control? Is that just for women?

[Siobhan Mitchell]
Yeah, so it's interesting because equal is actually beneficial for men. So there's studies showing that has benefits for men as well. So if you're a man and you can make S equal, you can have, for instance, benefits in your brain.

And oh, this is an interesting effect that S equal has. I thought it was kind of fascinating. It does show a kind of antagonism against DHT, which is a precursor to testosterone that has some of these negative effects that men don't like.

So for instance, DHT is kind of responsible for male pattern balding, that sort of thing. DHT, like very high levels, can sometimes, you know, increase your risk of cancer, like prostate cancer. So S equals seems to antagonise that, which can sometimes even be useful for women too.

Like for sure, women can have too much DHT and that can affect. Yeah, once again, their hair loss, you know, they can have more hair loss if they have too much DHT and affect their skin. They could have more acne, for instance.

So that is something else S equal can do. But yeah, as far as I know, and this is interesting, oestrogen signalling can really help men a lot, especially oestrogen beta signalling. And I'll just quote one study.

So the US Biobank, which you probably know very well, looked at all the kinds of medications that can help people in terms of, you know, prolong their life. And one of the top three for men and women was oestrogen kind of signalling medications. So I thought that was really fascinating.

Things like oestrogen patches, obviously more women are taking those. But I'll also point out that in mouse studies, oestrogen compounds seem to also help benefit male mice in terms of their lifespan. So yeah, I know people get worried about like the feminising effects of things like phytoestrogen on men.

But I will tell you, that's really only going to happen if you have a lot of oestrogen alpha signalling. If it's oestrogen beta signalling, it's really, as I say, just helping your overall metabolism. It's helping with your vascular health, that kind of thing.

So yeah, men shouldn't feel afraid. It's not going to feminise them. It's just going to help their health.

[Angela Foster]
It's going to help them. And men have more, if you're not taking, as a woman who doesn't take menopause hormone therapy post-menopause, men actually have more oestrogen than women.

[Siobhan Mitchell]
Exactly, yeah. Men are also surprised to hear that. They're like, oh, you know, I'm like looking at my husband like, yeah, you probably have more oestrogen than me right now.

So enjoy.

[Angela Foster]
Yeah. Have all those healthy benefits. Very interesting.

Well, thank you. That has been just absolutely fascinating. I think this is one to go back over and listen to again.

There's just so much in here to take away. But really, I just think the studies and things that you're doing around mitochondrial health and just helping us stay energised, right? That is the key to having an enjoyable, fulfilling life is you need the energy to really go after it and enjoy it and spend time with your loved ones and have fun.

So thank you so much for everything you're doing, Siobhan. And also coming back. Sounds like we've got more to come when these new studies are kind of surfacing as well.

And yeah, I'd love to have you back on and dive even deeper. So thank you so much for coming on again.

[Siobhan Mitchell]
Thank you. It's been so much fun.

If you are eating well, exercising, and still gaining belly fat, losing mental sharpness, and waking up exhausted, your mitochondria are likely the missing piece. This is not a willpower problem. It is a cellular energy problem, and it starts earlier than most doctors will tell you.

In this episode, I sit down with Siobhan Mitchell, neuroscientist and mitochondrial health researcher, to explore how oestrogen loss disrupts mitochondrial function and why your gut microbiome plays a bigger role in oestrogen recycling than most women realise. We also cover S-Equol and why it is one of the most powerful compounds for perimenopause belly fat, brain fog, and night sweats. If you are looking for real answers on why your body feels different in your 40s and what you can actually do about it, this episode is for you.

WHAT YOU’LL LEARN

• Why belly fat shifts to your middle during perimenopause

• How the estrobolome recycles estrogen through your gut microbiome

• What S-Equol is and how it reduces brain fog, belly fat, and night sweats

• The difference between estrogen alpha and beta receptors and why it matters

• Why estrogen loss causes joint pain and frozen shoulder in perimenopause

• How NAD+ decline affects your energy and mitochondrial function after 40

• How chromium helps with blood sugar spikes and food cravings in perimenopause