ZOE Science & Nutrition - Tired, anxious, gaining weight? It could be your hormones | Dr Helen O’Neill

Starting point is 00:00:00 Welcome to Zoe Science and Nutrition, where world-leading scientists explain how their research can improve your health. Every second of your life, there's an invisible orchestra in your body, whose music is coordinating every aspect of your health. That orchestra consists of over 50 hormones. Each one is an unseen but constantly changing chemical signal. Together, they make beautiful music that helps us wake up ready to go, tells us we're hungry or psychics. us up for an argument. They shape your energy, your metabolism, and over the course of a lifetime, your health itself. However, if just one instrument in the orchestra drifts out of balance, everything can feel wrong. In the modern world, many of us are living in ways that quietly but persistently disturbed that music. Stress, disrupted sleep, highly processed food, everyday chemical exposures.

Starting point is 00:01:04 Over time, they can all interfere with how our hormones work. And often, we don't realize this is happening. We just live with the symptoms and assume it's normal. The good news? It doesn't have to be this way. Misbehaving hormones can be identified, and lifestyle changes can have a profound impact on hormones, even returning the whole orchestra into tune.

Starting point is 00:01:30 In this episode, I'm joined by Dr. Helen O'Neill, a lecturer in reproductive and molecular genetics at University College, who has measured reproductive hormones in over 100,000 people. And I'm also joined by Dr. Federica Amati, Zoe's head nutritionist. Together, we explore the incredible power of hormones, how modern life leads them to misbehave, and what the science says about restoring balance, from fertility and PCOS to gut hormones and testosterone injections.

Starting point is 00:01:58 By the end of this episode, you'll have a clearer understanding of what may be influencing your hormones, and what matters most if something feels wrong, So you're empowered to take charge of your hormonal health. Helen, thank you for joining me today. Pleasure to be here. And Federica, wonderful to see you again. Excited to be here, Jonathan.

Starting point is 00:02:17 So Helen, we have a tradition here at Zoe where we always start with a quick, fire round of questions from our listeners. We have these very strict rules for scientists. You can only say yes or no, or one sentence if you absolutely have to. Willing to give it a go? Challenge accepted. All right. Are there any parts of the body that aren't influenced by hormones?

Starting point is 00:02:36 No. Do women have testosterone? Yes. Do men have estrogen? Yes. Federica, does what you eat change your hormones? Yes. Can body fat influence a man's testosterone levels? Yep.

Starting point is 00:02:52 And Helen, what's your favourite fact about hormones that still blows your mind? I would say that the gut itself is like a hormone factory. That's amazing. I'm still coming to terms with the fact that men have estrogen, which tells you how little that I understand hormones. So I think we should start at the beginning because we've already been established that I have no idea what hormones are. What are they, Helen? Our hormones are essentially like chemical messengers that are responsible for pretty much every aspect of our lives. Our inflammation, our immune systems, our metabolism, our reproduction, our cognitive function.

Starting point is 00:03:33 they are these fundamental and powerful messengers that are produced all over the body, whether it's individual organs or glands or the traditional endocrine organs like our ovaries or testis, but also in non-traditional places like our gut and our fat. We are constantly producing hormones to essentially travel throughout our bloodstream to do various functions, but almost every function relies on hormones or a collection of them. And why do we need hormones? Because we also have like these nerves, my brain controls things. So why do I have hormones wandering around my blood?

Starting point is 00:04:10 I guess when we think about hormones, they're there to protect us to a certain extent. So the best example I always give of a hormone to give you an impact of just how one hormone produced by a single organ can have a multi-organ and systemic effect on you. So when we talk about our adrenal glands or adrenaline junkies, that is our adrenalinal gland producing adrenaline. How do we get an adrenaline shot or how do we get that kind of shock? It's if you see someone, so either a visual cue, you could see your ex, you get this jolt. You could hear something. It's a big bang. You get a jolt.

Starting point is 00:04:49 And what happens when you get that production of adrenaline, your heart starts racing, your cheeks go red, your blood is literally pumping faster. around your body. And that's a protective thing. It's to get you out of danger. But equally, sometimes if you get a big enough shock, you might feel like you need to defecate. Pretty much almost every aspect of your body is responding to this threat. And it may not be a threat. It may be something exciting. But regardless, what it's doing is it's telling you that actually one small hormone can go to the entirety of your body and affect your bowel, affect your heart, your breathing, your skin, all of these things are happening in that instant with the production of one hormone. So that is always the example I give you, gives you an idea of the power of one hormone

Starting point is 00:05:36 and you imagine the collection of hormones constantly working. They really do keep us going in both survival and just maintenance. And I guess it's good to add here that hormones are tiny, tiny proteins so they can reach every single cell. Your nervous system reaches parts of your organs or the outside of things, but it's the hormones that reach every single cell. at cellular level. So that's why we do need them because we need like control of absolutely everything that's going on. And how many hormones are there? Around 50 to 70. They're probably, we're probably underclassified in women. But then there are hundreds of actual peptides and thousands of peptide signaling molecules. So these individual molecules that enable them to travel. Because when we think about

Starting point is 00:06:19 something being produced, we also have to think about the place that it was produced and the surrounding architecture of what is needed to allow that molecule to travel around the body. And I've already picked up from your example with adrenaline that my hormones are not all being made in the same place. That's right. We have the traditional ones that we like to think of like your pituitary or your thyroid gland or your adrenal glands or your testis or your ovaries, but also there's the non-traditional ones that we don't tend to think about like our whole fat system is producing and receptive to hormones and our body. gut is extremely receptive to hormones and what is in there enables us to produce either additional

Starting point is 00:07:00 or less hormones depending on what is in our gut. So I definitely shouldn't think about this as being like there's one place in my body that's churning out all of these different hormones. There's no individual hormone factory now. All these different places are producing hormones because they have different purposes, these hormones? Yes, they all have different roles. But I always think about our hormones like an orchestra. I often think that the thyroid is like the condoes. I often think that the conductor of an orchestra. And when you think about each of the organs as being a musical instrument and each of the hormones as being the sound that they make, those hormones or organs can produce individual sounds, but collectively and together it can make for a beautiful symphony. But one,

Starting point is 00:07:41 playing a bomb note, ruins the entire song. That's a beautiful image, Helen. So you're painting this picture where hormones are central to how my body works and they're very complicated and many of them they're doing very different things. I feel like when I was brought up, hormones were something that only women had and that somehow women have, at least have more hormones or are more hormonal is something people, you know, as a phrase that people say, what does that come from? We like to weaponize hormones, and I think it just stems from a complete misunderstanding of what they are. We like to use the word hormonal as being almost an insult when actually. actually, of course, we're all hormonal. Our hormones allow us to know whether we're hungry,

Starting point is 00:08:28 whether we're full, whether we should wake up, whether we should go to sleep. Those are all very hormonal aspect of our lives that keep us going. But because there is a system-wide misunderstanding of what the role of hormones in our bodies play, we like to think of hormones as only being to do with reproduction. And we like to think of reproduction as only having a role with women. And when we talk about the changes that we see in our hormones, we often associate it with the menstrual cycle. And so therefore it lends to this narrative that is hormones equals reproduction or your menstrual cycle. And if your mood changes or alters, therefore you are hormonal. You are a victim of this hormonal cascade that happens to you every single

Starting point is 00:09:13 month. And really it just comes down to ignorance. So I think this episode is going to focus mainly on research conducted on women, I would like to ask one question about testosterone because there's been a 50% increase in men injecting testosterone in the US within the last five years. What is that about and is it a good idea? I think men are way more aware now and everyone is aware of hypogonodism. So this idea that men have lower testosterone levels, if somebody has been identified as having this low testosterone hypogonidism, which is something you have to do like repeated, fasted, like tests for to make sure that you have it, then testosterone therapy is really helpful. The problem is people are now seeking testosterone therapy when they don't have this low testosterone level, and actually

Starting point is 00:10:01 that does carry some risks. It also has major risks for your reproductive function as a man, because if you think that testosterone is largely produced in the testis, and you are then injecting anabolic steroids and you're taking exogenous or external testosterone, your testicles think, I don't need to do this anymore. And they will literally stop producing testosterone. If you are, especially a young man, injecting testosterone, it leads to infertility. So it's really important to think of what your own testes are doing to produce and support your own basal level of testosterone. And when you say why? Because people are more educated now. We're able to disseminate information, whether right or wrong, and information can land.

Starting point is 00:10:47 And information around our health tends to be very polarized. Yeah, and that's why measuring, testing your hormones is actually important. So you can understand what your baseline is and where it sits compared to what would be appropriate for your age, because then you can make an informed decision on whether it's worth intervening or not. I'm thinking now back to this discussion that we had a moment ago talking about hormones and hormonal.

Starting point is 00:11:11 And the other thing that we had a bunch of questions about is this phrase, a woman's biological clock. What does that mean and what is it? If we say hormones, what's the first thing that comes to mind? Probably your reproductive system, or maybe your thyroid? We're going to guess you're not thinking about your gut. Well, you should be. It's a hormone factory. It produces some of the most important hormones for our overall health, like ones that regulate our metabolism, appetite and energy levels. All your hormones together function like an orchestra, each playing their own part to contribute to a symphony.

Starting point is 00:11:54 When your gut health suffers and your microbiome is disrupted, it can throw the whole orchestra off. The good news is that tuning things up is helped by your diet. Feed your gut the right variety of plants, fiber and other key nutrients, and it will be able to do its job, producing and processing hormones much more effectively. At Zoe, we want to help you to listen to and understand your internal hormonal orchestra. Find out more about hormonal health with our free guide. You can download it now at zoe.com forward slash fertility or click the link in the show notes. Back to the podcast.

Starting point is 00:12:36 It essentially refers to the fact that speaking of testicles, testicles produce sperm over a life cycle, of about three months. So every three months, you're producing more sperm. On the other hand, for women, we're actually born with all the eggs we'll ever have. So the eggs that are laid down for us in our ovaries, they're called the primordial follicles, are laid down when we're actually in utero. So when our mum is pregnant with us, that is when our egg cells form. That's amazing. So actually, what your mom eats during pregnancy and what your mom has been exposed to, your mom's nutritional deficiencies impact your eggs. They impact your overall fertility. So when you're born, you're born with this one to two million egg cells and you lose them over time. And that is the

Starting point is 00:13:21 idea that you have this biological clock that every single year you're losing them. And I think people often put the emphasis of the discussion on this clock and time running out. But actually, what's never mentioned enough is the idea of egg quality as well. And the fact that if you think about bringing your eggs everywhere with you, then everything you are eating, are exposed to, are drinking also is impacting your egg quality. Now, it might seem a little bit bleak to think, oh no, everything I've done in my life is going to affect my eggs. But equally, when you think about all those cells, those egg cells aren't just ready to go and be released. They are primordial. They're in their infancy. And they still need you to grow and mature within the ovary. And so what we do

Starting point is 00:14:05 over the course of three to six months prior to getting pregnant is really important to the health of an individual egg as we ovulate every month. Ovulation being the production of an egg that's being released for potential pregnancy. The biological clock idea is this sort of shrinking number and you're also describing shrinking quality of these eggs over time as you slowly move towards menopause? Yes, exactly, where you have no eggs left at all. So I think the two of you have painted a brilliant picture of just how important hormones are. And I sort of want to go back, Helen, to your example of this orchestra where, like, if it's all working together, it's playing this beautiful harmony.

Starting point is 00:14:46 But you said if, like, even one hormone is going wrong, then it's almost like this terrible noise that breaks everything out. Helen, what are the main factors that cause, like, the orchestra to go wrong and these hormones to go sort of outside of the range they should be in? There are so many different things that can impact our hormones, whether it is our external environment and stresses. When we are unhappy, whether it's in our work environment, in our daily commute, in our relationships, the stress of that actually does impact our hormones and it does so in quite a significant way. The next thing that can impact our actual health conditions, so our reproductive health conditions, for example, impact our hormones, but also our life stage, so we know categorically that our hormones are going to change as we go through life.

Starting point is 00:15:37 The easiest example that we can all relate to in terms of being hormonal are teenagers. We tend to describe teenagers as being moody, spotty, hormonal. They are, I guess, victims of that hormonal transition, and we allow for that. But we don't make the same allowances through other life stages. In fact, only now are we starting to make allowances for the other end of the spectrum where we're witnessing this huge or hormonal transition through perimenopause and menopause. And it's due to a lack of understanding. And then the third thing I would say is what we put in our bodies from a food perspective. Some of our hormones quite literally cannot be produced without certain nutrients. So when I said that the thyroid was the conductor of this endocrine

Starting point is 00:16:22 orchestra, we cannot make our thyroid hormones without iodine. And so having an iodine deficiency, which is one of the most prevalent deficiencies we have, means that that conductor is sitting down. He's not sending anyone where they should be, what an instrument they should be playing. And how can someone tell if their hormones are unbalanced that, you know, this orchestra isn't quite playing right? What are the symptoms that I might experience?

Starting point is 00:16:49 The top reported symptoms we see are, I like to think, we are failing. Fatigue, anxiety, irritability, low mood. It's not necessarily the physical aspects that we report. Because we like to think of our mental health as being above and our reproductive health as being below and everything else in between. But actually, they're inextricably linked our mental health and our physical health. Our mental health is controlled and governed by our hormones. And if any aspect of our hormones is really subject to stresses, high cortisol,

Starting point is 00:17:23 then we're going to see that throughout the rest of our bodies. It's really interesting that you talk about this combination of both how I'm feeling in terms of my mood, but then also sort of these more physical effects, like I'm tired, and that they'd all just linked together from this same hormonal thing, because I was definitely brought up to say, like, you know, your mind, your body's separate. If you're feeling depressed, it's got nothing to do with, you know, being physically exhausted so that you can't walk around. Yeah. And that's the problem. I think many of those symptoms are very insidious, how tired. as anybody else, it's all relative to how tired the next person is. Or even feeling cold, it's, you know, we all have different sensitivities to hot and cold. Men and women have very

Starting point is 00:18:06 different sensitivities to hot and cold. And so when you have somewhat of a subjective and insidious nature to a symptom or how someone feels, then it's very hard to pinpoint it. And moreover, we self-eliminate from getting help. So even though you know you're tired, even though you know you don't feel great, we're the first person to blame. So we'll say, well, I didn't go to bed on time. Or I haven't been eating well. You'll look to a reason to blame yourself instead of saying actually maybe something internally and physiologically isn't right with me and therefore. And it actually makes me quite sad thinking of people who live their lives potentially with just a small deficiency or something as simple as being able to fix their thyroid with iodine. It makes me sad that they could

Starting point is 00:18:49 go almost their whole lives being substandard in what they actually are in themselves. just because of a lack of understanding of the link between feeling tired or feeling low mood and the role that our hormones are playing in that. You mentioned the thyroid a few times. I've literally no idea what it is. But you also said I think it was like the most common problem. So how common is that? And how do you figure out that there's something going wrong?

Starting point is 00:19:17 Again, it's to do with your symptoms. Feeling tired, feeling cold, hair loss, weight gain or weight loss. one of the most prescribed drugs in the world is labourthoroxine for thyroid. As Helen mentioned, micronutrients are really important. So iodine is the most important. And knowing whether you're getting enough iodine in your diet, now, the UK is one of the only countries that doesn't have fortification of salt as a public health intervention. So many other countries, table salt, will have iodine added to it exactly to prevent this. But we don't have that here in the UK. And not everywhere in the US, the different countries have different interventions.

Starting point is 00:19:53 For example, if you eat no seafood whatsoever, you don't eat fish, you don't eat shellfish, those are the main sources of iodine in our diet. So it's worth finding out, okay, what are my levels like? Is my thyroid struggling? So is it trying to stimulate TSA as a hormone? Is that like really high because it can't quite produce enough of the hormones I need? And then you can look to either supplement or intervene before it becomes a problem where medication is then needed for the rest of your life normally.

Starting point is 00:20:18 Actually, iodine deficiency tends to get higher the further inland you go. further away from the sea, you see fewer cases and then the further inland you go, the higher the prevalence. And in fact, actually spending time by the sea, Jonathan, because there's so much iodine in the sea, when you spend time by the beach, you actually inhale iodine from the sea spray. That's brilliant. So just stand by the beach with my mouth open. Oh, you can just breathe. I just breathe. All right. You don't have to.

Starting point is 00:20:41 Then everything is solved. So it sounds to me also as though you're saying, Helen, that there are a fairly straightforward tests to understand the. level of these hormones because you were, you know, someone saying, I think this is unbalanced. What's your next step? The next step is to check your hormones. One of the most routine medical exams will do is to look at your hormones. I do want to caveat hormones being unbalanced versus hormones being clinically out of range. There's a lot of online move towards balancing your hormones. And what balancing your hormones means in that context is say, I'm going to use a male example rather than a female one. You have lower testosterone in the evenings, eat something

Starting point is 00:21:24 that would make your testosterone naturally rise. And so from a menstrual perspective, if we know that in the latter half of your menstrual cycle, you are lower in estrogen, people are saying, let's balance your hormones by eating foods or seeds that might mitigate that loss of hormones. So there's the difference between balancing your hormones and the idea that your hormones are unbalanced versus clinically out of range, which is still unbalanced when you think about the overall physiological. But I just wanted to take a moment for the distinction between the two. And do I want to balance my hormones or the way you're describing it sounds as though, you know, these changes during my day or I guess, you know, as a woman during a month, a sort of natural?

Starting point is 00:22:04 They are, but for some, they can impact you a lot more than others. And so I think it does stand to reason that in the latter half of your cycle, your luteal, or we call it your low teal because you feel quite low during your luteal phase, that you might want to do anything to mitigate feeling so. Low. Hormones very tightly regulated and there's feedback loops for basically every hormone. So the way that works is like if one hormone gets sent out and it arrives at the destination, there's like another hormone that will come back and say, hey, we've received this message. So we don't want people to think that they should be going out of their way to interfere with that messaging. So we see online going back to more like dietary hormones. People talk about being scared of insulin, right? Oh, well, we don't want insulin to spike. It's like, well, you do actually. Insulin's super important hormone and we're not trying to prevent insulin from ever being secreted, right? So there is, I think sometimes this narrative of balancing hormones makes it sound like you can just go in there and hack it and change it. But it's very tightly regulated. There's a lot of homeostasis. So keeping things balanced naturally. And then to

Starting point is 00:23:06 Helen's point, when your own body is struggling to keep that balance, it can become problematic, even before it goes out of range. And I guess we'll talk about some of the conditions where that happens. Just before we move on to that, we had a lot of questions about weight gain associated with hormonal changes? Are people wrong to associate these hormonal imbalances with weight gain? No, definitely not. Because as part of the signaling, we now are starting to understand what's called adipogenesis, which is our production of fat cells. And the idea that actually our fat in itself sends signals to the brain, which can send signals to our other organs to enable us to actually want to eat more or eat less. And so the most...

Starting point is 00:23:50 common of metabolic conditions, this is the first part of that feedback loop that becomes interrupted. And what I mean by that is if you have a chemical imbalance within your hormones and a metabolic, therefore, dysfunction, your ability to either burn fat or continue to produce it is at fault. So one of the most prevalent metabolic conditions in the world is polycystic ovarian syndrome, which affects women, around one in ten women. And that's That's one of the predominant things that actually happens, that signaling process, both that goes to the brain and goes to the ovaries, has been affected through multiple different reasons. We call it a three body problem. When there's two things you can predict where they're going to hit, when there's three things you almost can't predict where something's going to hit.

Starting point is 00:24:37 And when there's three systems at play, your ovaries, your fat cells and your brain, it's actually quite difficult to predict what is going wrong and how to actually prevent it when it comes to polycystic ovarian syndrome or PC. But often one of the biggest complaints that women make is that actually from our data, we see that it's low mood and depression, but from a clinical standpoint, it's weight gain and difficulty losing weight. So you're saying PCOS, firstly, one in ten women are affected by this. So it's very common. And it's the most common endocrine disorder in women of reproductive age. So more than type 2 diabetes, which is shocking, I think, actually. And I don't understand however what's causing it. But what I heard you say is that it really doesn't. affect this sort of weight gain along with the set of other. It could just help me again to understand a little bit what's going on here. So what we know is that PCOS lends to hyperandrogenism, which means you have high levels of what are typically described as male hormones, which we now know

Starting point is 00:25:35 are not. Your antigens are like your testosterone, and you have higher levels of those. And so what that lends to is from a reproductive standpoint, you have lots of these follicles. We said we're born with all of them. You have lots of these follicles, which are in. immature eggs, but they don't necessarily reach, they don't get enough signal to mature fully. And so you don't actually necessarily every month release a mature egg, which means you don't ovulate. And so there's the hyperandrogenic aspect of PCOS, meaning you have higher levels of testosterone, which can lead to excess facial hair, it can lead to loss of hair on your head. But also then you have the ovulatory part of it, which means you don't release an egg,

Starting point is 00:26:16 and so you become an ovulatory. And so that means it's affecting your physical health, your appearance, but also your reproductive health. But because of the high receptivity of all of our hormones in our brain and the hormone receptors in our brain, it also significantly affects our mental health. So it really does impact so much of our lives and is so prevalent. And so it really is unfair how misunderstood it is when you think about how much research and funding goes into type 2 diabetes. And yet no funding goes into PCOS. It's a real hormonal syndrome, and it affects risks later in life. So a woman who has PCS, for example, she's three times more likely to then develop type 2 diabetes later in life. So it's a risk factor as well as being a syndrome in itself. And as Helen said, it often affects weight. So women put on a lot of weight and then that changes their metabolic health. So there are hormones that are involved in signaling from fat to brain, for example, leptin, they're disrupted. And the gut hormones that are involved in signaling for satiety and for, for fullness are also disrupted. So we'll get to the solutions data, but some very interesting

Starting point is 00:27:24 research, Jonathan, looking at how you can actually really improve PCOS symptoms and outcomes with dietary intervention. So it sounds like pretty severe from the way you're describing in it and also really common. Do we understand why your hormones are being disrupted in the first place and you're ending up with PCOS? There are a number of theories. Some say that it is due to antigen exposure in utero. So it stands to reason when I mentioned about all our eggs forming when our mother is pregnant with us. They say that higher levels of testosterone exposure while you are forming could be one of them. They also say that it is passed on the paternal side, that there is actually a male phenotype for PCOS. But no, we don't fully understand what causes it.

Starting point is 00:28:11 So why isn't it better investigated? Ah, it's just that 50% of the plant. planet that we didn't bother creating any medical solutions for including any clinical trials or, you know, just innovate generally towards women. So you know, Jonathan, until 1993, women didn't have to be included in clinical trials. So before 2000, about 80% of all drugs that had to be removed from the market had to be removed because of the side effects of women that weren't accounted for that to be completely removed. Now, since 93, you have to include women in trials, but we still have some blockers where the researchers then don't necessarily actually look at the data and separate men and women in their analyses to understand the differences. So we're still sort of playing

Starting point is 00:28:57 catch-up to medical science actually involving women and including them all. A lot of the research also, we didn't include women because we were worried about the effects of the menstrual cycle and the changes in hormones. So PCOS, which directly affects your menstrual cycle and hormones, is one of the reasons really why women were excluded from medical research in the first place. and now there isn't so much investment in it because, as you said, lots of reasons, but it's one of these syndromes that are so complicated for atiology and treatment that I think it's made it difficult to make it a really strong proposition for furthering research, unlike, for example, cancer, which obviously gets a lot of research.

Starting point is 00:29:36 I think things are changing slowly, but it's taking quite a while for endometriosis and PCS, which endometriosis is another condition, which is massively impacted by hormonal health. When you think about conducting a clinical trial and wanting to ensure that everyone is at the same stage, we tend to, even when taking blood, you say, come in the morning when fasted. And that's so you're not interrupting all of the daytime hormones that start to kick in or your blood result isn't impacted by what you have eaten. When you think about the huge change in hormones, I call it like a very complex calculus of hormones that change every single month in women, in order for us to, understand and not be subject to the changes, you would want to take a blood sample from a woman, from every woman in your trial at the same day. And that is on the earliest part of their menstrual cycle before all of your hormones start to really cycle in order to create, release an egg. And so capturing enough women at that one menstrual time point is actually technically very difficult to do. And it's meant that even in pre-clinical animal studies, we exclude female mice or models from the experiments that are done.

Starting point is 00:30:50 So can you imagine trying to capture women at scale and they all have to be on the third day of their menstrual cycle? It almost seems impossible. And with PCOS, where you have often very irregular periods, it would be even hard to guess when that would be. That sounds like a really interesting way to ask you about your research into reproductive hormones at this company, Helen, that you've built. because I know you've now tested the hormones over over 100,000 women. Yes. I think when we started, it actually started as a clinical trial so that we could better understand the role of our hormones

Starting point is 00:31:23 and our symptoms in different reproductive health conditions. So when I said it's almost impossible to capture women at scale on the third day of their menstrual cycle, that's exactly what we've done. So we've done that by enabling at-home testing as opposed to physically needing to go to a clinic. So if you think that actually if you only only, can test on the third day of your menstrual cycle, you only have 12 of those every year. Fewer if you have PCOS. And so by removing that barrier to entry and enabling somebody to do a

Starting point is 00:31:51 blood test from home on the third day of their menstrual cycle, irrespective of where they are, really means that something that seems so simple from a data, a global data standpoint, has been transformative in unlocking one of the most underserved areas of medicine there is and has enabled us to create the richest and largest data set of its kind. What insights has this data given you about the reality of women's health in 2026? So many insights. And actually what we see is that women of today are not the same as women of yesterday and decades before. And when the books were written about women from decades ago, those women weren't exposed to the flippancy of alcohol that women of today have. the change in smoking habits, vaping habits, the change in our daily exposures to chemicals

Starting point is 00:32:45 that literally disrupt this whole orchestra, chemicals that are in our environment, in our clothes, in our skin care products that are quite literally blocking or disrupting or interrupting the ability for our bodies to produce these hormones. So these are called endocrine disrupting chemicals and 10, 20, 30, 40 years ago, we didn't see the same level of exposures to these chemicals in our day-to-day lives. Having a data set that accounts for a modern woman, today's woman, and all of her exposures and her lifestyle factors is the most relevant data set there is. We can't rely on old inference data. I think one of the things you've also been looking at is endometriosis, which I heard mentioned earlier, but I'd love for you to explain what it is as well as what you've

Starting point is 00:33:34 discovered? So endometriosis is a devastating condition that actually acts almost in a similar way to cancer. So it acts in a way whereby it can travel to other places in the body, starting typically in the uterus and parts of our highly receptive lining of our womb. If you think about it, it's almost like the most receptive and susceptible to change environment there is because it can literally accommodate huge growth to expand and accommodate the growth of a fetus. But those cells, can also undergo massive changes and are hugely receptive to our hormonal changes. And when they migrate elsewhere, they tend to form almost lesions that can be inflamed and cause extreme both cyclical and systemic pain, meaning cyclical being that it can be

Starting point is 00:34:23 worse at a certain part of your menstrual cycle, and then systemic being it's all over your body. And this pain is as a result of these endometrial cells that migrate elsewhere in the body, or remain within the uterus, and they build up. And what we don't understand yet about endometriosis is really how do we treat it. But moreover, what are the things that are causing that to happen? There are a number of theories out there, but nothing that really actually lands true for everybody.

Starting point is 00:34:51 There's really interesting research looking at the role of the gut microbiome with endometriosis and dietary factors. So some of the research looking at like early life exposures, for example, is identified that children and young women who are exposed to a very high red meat diet have a much increased risk of endometriosis in adulthood. And we do know that the gut microbiome plays a role in downregulating the inflammatory pathways that are very, very, very involved. And endometriosis really is an inflammatory disease.

Starting point is 00:35:19 And gut health can help to downregulate this and bring it down. But it's a devastating condition. And I think now we know more about it a little bit. There's more in the public sphere. but around one in ten women suffer with endometriosis as well. So it's quite a high number of women. I think one of the most devastating things about it is that women know there's something wrong with them. They seek help endlessly and don't receive help. And because of the role that it plays in terms of, think about what's between our hips. There's a lot. There's our bowels, large, small intestine. There's our uterus, our ovaries, our bladder. It's all crammed within this one space.

Starting point is 00:35:55 And so when you have pain, for example, if that tissue is deeply infiltrating into your bowel, will you present with bowel-like symptoms? And so you're sent down a very different route to traditional gynecology. And so what we've seen is that symptoms can be highly predictive of this pathology and that the time it takes to get somebody to a diagnosis is on average nine years. Nine years. Nine years it takes a woman on average because, again, sometimes symptoms are quite insidious. We've also normalized pain in women. We say that you should tolerate it, expect it, and that that's just part of being a woman is getting monthly pain, but it should never be debilitating and crippling pain. And so we oftentimes tend to minimize menstrual pain. And so we either have to justify it or validate

Starting point is 00:36:48 why we are feeling this and really scream for medical attention. So that time to diagnosis, is actually one of the worst impacts about endometriosis. And so what we've seen from our data is that when you look at nearly a million health assessments and you look at the women who have a diagnosis of endometriosis, then we can blind everything else and we can say what were the things that could have predicted endometriosis in this person.

Starting point is 00:37:14 And one of the most powerful predictors is whether you have a painful poo. So painful bowel movements is one of the most powerful predictors of endometriosis. And very often that is a question that is not asked of you if you are undergoing a gynecology examination. That actually can be transformative in reducing a diagnosis time from what could be nine years for some to fewer than nine days. Wow. So you are now able to diagnose endometriosis? You can never diagnose it in the absence of an investigation. You need to see the tissue.

Starting point is 00:37:46 But what we can do is say with 98 to 99% confidence, both precision and recall, that we suspect you will have it. And therefore, the first person you should go see is a gynecologist or an expert in endometriosis. So you've reduced the wait time from 10 years to like eight days? Yeah. That's amazing. Yeah. And that really is the power of data and being able to collect data at this critical time point so that you have blood results, you have health assessment results. But moreover, then we have scan results.

Starting point is 00:38:14 So it enables us to really create this multimodal data set that enables us to interrogate different pathologies. Do you have a friend who has questions about fertility, cycles, PCOS, or maybe unexplained symptoms? If so, why not send them this episode? You could save them hours of confusion and provide information that actually helps. I'm sure they'll thank you. I'd love to now talk about actionable advice so that anyone listening to this says, well, what could I actually do to get back on track? Does diet really matter if you want to manage this? or should we go and saying like really drugs is the only way to have an impact?

Starting point is 00:38:55 No, it really matters. And it goes hand in hand with medicine, right? Both can be useful. But if we start by looking at the hormones that influence metabolic health and appetite, Jonathan. So inside our gut, about 1 to 2% of the cells in our gut are there just to make hormones, their little hormone factories. And we have a dozen of different hormones, including GLP1, which is now made famous thanks to GLP1 medications, that's actually a hormone we produce in our gut ourselves.

Starting point is 00:39:21 from these amazing cells, my favorite are called the L cells. So if we feed these L cells properly, they will produce GLP 1 for us. They will produce another peptide called PYY for us. And these hormones have a multitude of effects, not just on how hungry you feel, but how slowly your gut empties, or whether your pancreas starts to secrete some pancreatic enzymes to digest fats. PYY, especially, travels to the brain and literally tells our brain to stop eating or to seek more food, they work together in harmony. Now, when we think about these enter endocrine cells, they're little hormone cells in your gut, they're so important for conditions like PCOS, because if these L cells are happy, they can produce these hormones and they can help to regulate satiety and signaling

Starting point is 00:40:08 for hormones like insulin, insulin resistance, which is created in the pancreas. Now, insulin resistance is one of the hallmarks of PCOS, for example. So when we think about our diet, by nourishing our gut microbes, They produce short-chain fatty acids. They produce the food that these cells, specialised cells in our gut, thrive off. So if we can feed these cells well, they'll actually work for us. Now, I was talking about PCOS earlier. Some amazing data shows that giving women with PCOS a high-fiber diet, especially high and fermentable fibers, such as inulin or beta-glucan,

Starting point is 00:40:43 which is found in oats, for example, can actually improve insulin resistance as match as taking a pharmaceutical drug that does the same at formin. So it can be incredibly powerful, as powerful as the drugs. But formin doesn't really help with the weight management, whereas the high-fiber diet does. Even better than the drug. It's exciting to see that actually diet can play a fundamental role, but we have to feed our guts, the food it needs, to maintain a very healthy system that can actually help these cells make the hormones for us.

Starting point is 00:41:13 I think what you're saying is, like, in my gut, I have these L cells. and that they're being fed basically by the output of these microbes inside my gut. And so I need to make sure that I'm feeding the microbes, the food they need, because they are then giving these outputs for these cells, and these are then helping to manage a number of the hormonal imbalances that we've been talking about today with both of you and that you're actually saying this is linked to, for example, being able to reduce symptoms of PCOS?

Starting point is 00:41:45 Yes. And the same with endometriosis, when we think about inflammation, again, if you feed your gut well, the gut microbes make the chemicals that are necessary to make sure that you have a really good gut barrier, which reduces the leakage of what's supposed to stay inside your gut to the outside, so endotoxin leak. If you reduce that, then you're reducing inflammation. And we've seen in our research on menopause, very similar patterns where the gut microbiome, the astralome, so the microbes that are involved in estrogen, regular, they suffer if we don't feed them well. Let's say I'm really wanting to make sure that I'm trying to maximize, you know, the output of these L cells because I'm worried about these hormones. You know, what's the key things? What's the gourmet meal for an L cell? So it is a lot of the principles that we know for gut health generally, a variety of plants. So gut microbes each thrive on slightly different, fibers and prebiotics from phytonutrients,

Starting point is 00:42:41 for example, polyphenols. So we need to give our guts a wide range. range of foods, right? We have to give them several plants, 30 plants a week is a good starter, is a good aim. We want to make sure that we're including plants that are also high in healthy fats. So omega-3 fatty acids, you know, the best sort of source is fish and seaweed, but we also find a source of omega-3 fatty acids in nuts and seeds as well. And actually, those types of fats are really good for our gut microbes, making sure that we introduce things like fermented foods, which can bring even more benefit from live microbes themselves, but also,

Starting point is 00:43:15 from the fermentation products of those microbes. So focus on adding those in more. And as I said, fermentable fibers are the ones that have been shown in clinical trials to really move the needle with PCOS, but they're all found in plants. So if you're having this really nice variety of plants, you'll be doing that. And to Helen's point earlier, micronutrients are really important for things like thyroid health. I mean, we haven't talked about zinc, for example, but zinc is essential for testosterone production, for example. If you're having nuts and seeds in your diet, you'll get zinc. you don't need to worry about taking a supplement for it. And Federica, I just heard the word zinc.

Starting point is 00:43:49 And so I'm sure that all the, all our listeners were all the same, it's like, oh, so zinc sounds really important. And when the sperm hits the egg, there's literally a flash of zinc. It's amazing that you can see imaging of when it happens. It's like firework. Yeah, and that's zinc. It's an essential mineral, but you need it in tiny quantities, but it has a very important role.

Starting point is 00:44:07 And zinc you can get from your nuts and seeds from your seafood. So if you're following a Mediterranean-style diet, a diet that we propose in Zoe, all of our app is designed to give you this kind of diet, right? If you follow that advice, you will be getting all these essential micronutrients, all the fibers and the polyphenols that your gut thrives with. I just want to clarify, though, because I think a lot of people will be listened to this and saying, but this is really important for me, for example.

Starting point is 00:44:31 Like my hormones are disrupted or I'm worrying about making sure that, you know, I can have a baby. Surely I need to get like a supplement because that feels like something medical versus just relying on food. I'm always led by food when it comes to supplementing. I think you should supplement first with food. But I think you should never supplement in the absence of actually knowing what's wrong. The only exception here, Jonathan, it's important for public health, is that if you are trying to conceive and you are actively trying to conceive

Starting point is 00:45:00 or just find out you're pregnant, taking a folic acid supplementation is recommended. So you can go to your local pharmacy or even supermarket and pick up a folic acid supplementation. It's recommended for the first 12 weeks. of pregnancy and even before you conceive, if possible. Helen, what about fertility? I know that's a big area of focus for you. And I'd love to understand both what a woman can do to increase her chances of pregnant, but I understand that also there's research that there are things that men can do to increase

Starting point is 00:45:28 chances of fertility. Absolutely. I think we're finally starting to address that at that moment of fertilization, at that flash moment the sperm is delivering, 50% of the DNA that is contributing to, to the fetus. And so it is the 50-50 split in terms of what we are delivering from a DNA perspective. So the sperm plays a really fundamental role. I'll start with that because, as I mentioned at the beginning, sperm have a three-month life cycle. And so in just three months, making changes to your diet as a man can radically improve all of the different parameters of sperm health. So there's an

Starting point is 00:46:04 amazing study saying just a handful of walnuts. Every day, increased every single parameter of sperm health, just from small dietary interventions, lifestyle changes. Is there any other key actual advice you would give if your man listening who wants to improve their sperm count? Yes, you have a very minor role to play and yours is quite enjoyable, in fact, when it comes to making a baby. And so abstaining from smoking, drinking, alcohol, of these things for just three months prior to wanting that perfect swimmer to make it goes a long way. It doesn't go a long way just to contributing to a fertilization event. So we can separate it out and say fertilization has occurred. The sperm has fertilized the egg. But actually, it's more

Starting point is 00:46:48 about what does that DNA contribute to. And we now know that the DNA that the sperm contributes, because the egg is the largest cell in the body, and the sperm is the smallest cell in the body, it means that the role of DNA is playing is quite different. And the role of the sperm plays is actually informing the placenta. And so what we've now, started to learn is that the health of the sperm can be what contributes and dictates whether that pregnancy will last, can be what contributes to miscarriage. And so when we flippantly now talk about miscarriage and it happens to one in four women, and actually we so often end up being victim to the blame or the self-blame or the narrative that we have done something wrong,

Starting point is 00:47:30 actually now we're starting to see that the sperm is playing a huge role in that how And can I just confirm what you're saying is the advice? You're saying that abstaining from smoking and drinking for three months in advance has a real impact on improving the sperm quality and therefore reducing risk of miscarriage. Sperm quality, risk of miscarriage, the overall health of the pregnancy. We're now starting to see studies that say sperm health is linked with whether you have morning sickness. But also like the child's health. So one of the biggest studies that was done, then you see up. looked at, it was called the Healthy Dad Study, but internally the Fat Dad Study. And what we were able to see was that pre-diabetic men who underwent bariatric surgery and then reversed their status, actually conferred that pre-diabetic state in the newborns. And so even though we like to think that our germ cells or our sperm and our eggs are a clean slate in terms of our health,

Starting point is 00:48:34 actually they carry the marks of DNA damage that we have had in our lives. And so that actually has a transgenerational impact on your children's health. So just three months seems nothing, but it could be, it's the rest of... It makes a big difference. Your child's life. And it's interesting because, Jonathan, we think about, like, the egg's health contributes to specific factors in the woman's health, but then paternal health contributes to different factors.

Starting point is 00:48:57 So just as Helen said, like, the placenta is one of them, but the child himself or herself, mental health is often really closely linked to paternal health at conception. So we see that things like autism spectrum disorders are linked to maternal metabolic health at conception. These are all associations, but it's really interesting to see how important it is to think about paternal health just the same way as maternal health. It takes to Titoango. It is 50-50. About 50 to 60 percent of pregnancies aren't planned. So it's not possible for everybody. And it's not about guilt or blame because actually what we also know is that humans are very resilient.

Starting point is 00:49:31 So you can have a perfectly healthy baby born, even if you haven't done all the things beforehand, right? So I think another really important thing for pregnancy, it's about having adequacy. So if you have adequate nutrition, adequate, like you're in good health. You don't have to be in perfect health. Then your body will do the rest. Pregnancy is very efficient. It will take what it needs from the mother and for the baby, right? It's not about, oh my gosh, I had that one glass of wine or, oh, my God.

Starting point is 00:49:57 It's about what's the pattern? What's your overall pattern? like what are you consistently doing? Those are the things to think about more. Consistency is king. And then the detail, biology is pretty flexible, and our bodies are good at dealing with some challenges, especially if our consistent piece is strong.

Starting point is 00:50:13 So we've talked a lot about men and what they do that can affect fertility. What would your advice be to a woman who wants to increase her chances of getting pregnant? The diet we've already talked about, Jonathan, so a very high-nutrient density diet with plenty of vegetables and fruits, nuts and seeds and oily fish three times a week. Reducing alcohol intake, stop smoking if you're smoking, reducing behaviours like vaping or illicit drug use. So remember reading one of your reports and saying that about 9% of women

Starting point is 00:50:41 who are actually trying to conceive, we're still taking illicit drugs. Those behaviours are going to impact fertility. Find out where you are on your fertility journey, how healthy are you and how your hormones behaving. And then you can eat and live a lifestyle that can support your fertility further. Amazing. I'm going to try and do a little wrap up. So my starting point is I'm now thinking about hormones like this orchestra inside my body,

Starting point is 00:51:03 all these different hormones, like way more than I realized I had. And if it's all working together, it's brilliant, and it's helping me to deal with these horrible shocks, like suddenly you see my ex across the room. But it is very possible, particularly it sounds like in, you know, our modern Western lifestyle, that some of these hormones are not playing the right tune. And then suddenly it's all going wrong. And that there are some very common situations we talked about. POS, which I think you said affected one in 10 women, which is, I think, related to, like,

Starting point is 00:51:34 high levels of hormones like testosterone. And that has a big impact, not just on your ability to have a baby, but like your weight and your brain, all these sorts of things. But we also talked about endometriosis and just how devastating the pain is for women. And it takes nine years today for this to be identified. So that's really extraordinary. We talked about the thyroid, like the most common problem you said that anyone has. And actually, you can just take iodine and it fixes it. So it seems so simple. And I remember this brilliant thing you said that, Helen, the further you are from the sea, the higher levels of thyroid deficiency. Yeah. We talked a little bit about men and talked about testosterone. And I think my big takeaway was

Starting point is 00:52:20 if I'm injecting myself with testosterone, like my testes are going to stop producing it. I'm going become infertile. So that seems like a pretty important thing to bear in mind before doing it because everyone else in the gym is doing it. And then the biggest thing I took away, I think, was just how important the food is that we eat on this. And I'm struck by it because it's outside really of what we often talk about on this podcast. But we understand it sounds like quite well these mechanisms that there are these specific L cells in our gut that are creating all these hormones, but it only works if they're getting fed sort of the right chemicals from our microbiome. And this issue is that many of us are eating a diet that is just basically

Starting point is 00:53:03 not feeding those microbes what they need. And an example of this hormone you said is GLP1. So if we're eating all the right food, then we probably don't need to inject ourselves with the GLP1, but this is true for lots of other hormones. And what you said is like there's some very clear advice. So eat a variety of plants, 30 or 1. week because what you're trying to do is lots of different fibers and polyphenols to feed all of these different microbes. And you mentioned like whole grains and legumes, but also big focus on healthy fats. So this is like oily fish and nuts and seeds, fermented foods on top. And interestingly, what you're trying to do is you're giving these microbes all of these different sort of fermentable fibers

Starting point is 00:53:44 and micronutrients. But rather than think about that as a massive set of supplements that you're trying to eat, actually these are all found in plants because that's what the microbes are expecting. And if you're eating this diversity, then actually I shouldn't immediately be worrying about, oh my God, I need to take a zinc supplement. Actually, I'm getting this across this set of foods. And then finally, I don't want to leave without talking about fertility. I had this wonderful moment where you just bonded over the flash of zinc. But interestingly, apparently, it takes three months to create sperm. So if I can completely reset the quality of my sperm within three months, but my diet is critical. And today, most men's sperm is like 50% worse than I guess

Starting point is 00:54:26 our grandparents, which is a bit depressing. Literally a handful of walnuts can increase the number of them and how well they swimmer, which gets your sign of sort of how bad it is. And so going to that same sort of diet that we were talking about before really makes a difference, not just for women's fertility, but also for men's fertility. And that alongside that, drinking and smoking have a big negative impact, both for sperm and for women trying to be fertile. So there's an enormous amount you can do within lifestyle that can really profoundly change your ability, not just to get pregnant, but to go on and successfully have a baby. Yeah, one of my best students. I'll end this episode with something I think you'll like, a free Zoe gut health guide. If you're a regular listener,

Starting point is 00:55:13 you know just how important it is to take care of your gut. Your gut microbiome is the gateway to better health, better sleep, energy and mood, the list just goes on. But many of us aren't sure how to best support our gut. I wasn't sure before doing Zoe, which is why we've developed an easy-to-follow gut health guide. It's completely free and offers five simple steps to improve your gut health. You'll get tips from Professor Tim Specter, Zoe's scientific co-founder and one of the world's most cited scientists, plus recipes and shopping lists straight to your inbox. We'll also send you ongoing gut health and nutrition insights, including how Zoe can help. To get your free Zoe gut health guide, head on over to zoey.com slash gut guide. Thanks for tuning in and see you next time.

ZOE Science & Nutrition - Tired, anxious, gaining weight? It could be your hormones | Dr Helen O’Neill

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