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Metabolic Inflexibility and the Mitochondria with Emma Sutherland and Dr. Felice Gersh

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Metabolic Inflexibility and the Mitochondria with Emma Sutherland and Dr. Felice Gersh

Dr. Felice Gersh discusses the role metabolism plays in maintaining optimal mitochondrial function in our latest podcast with our ambassador, Emma Sutherland.  

As an experienced Obstetrician and Gynaecologist, Felice illustrates the connection between metabolic health and reproductive health outcomes and the impact metabolic dysfunction can have on hormonal regulation.  

We hear about changes to metabolic function across the lifespan and about metabolic ‘inflexibility’, the connection between blood glucose regulation and hormone control and the circadian rhythm. 

Covered in this episode

[00:42] Welcoming Dr. Felice Gersh
[01:41] Connections between metabolism and reproductive health
[04:34] Defining metabolic dysfunction and its causes
[08:25] Clinical signs of metabolic dysfunction
[11:25] Pathology testing for metabolic dysfunction
[14:45] Metabolic flexibility and mitochondrial function
[20:53] The Ma-Pi diet
[25:07] How the microbiome impacts glucose metabolism
[29:00] Time restricted eating 
[34:25] Permimenopause and insulin resistance
[43:15] Thanking Felice and final remarks

Key takeaways 

  • Imbalances in metabolism carry through to conception, pregnancy, birth, and postnatal health outcomes, with pregnancy being like a ‘metabolic stress test for women’. 
  • Metabolic function changes over the lifespan. 
  • Metabolism is the creation, storage, and distribution of cellular energy throughout the body and is essential to life. Regulation of metabolism is controlled by energy intake in the form of food and energy output, with imbalances leading to poor weight management and mitochondrial dysfunction. 
  • Clinical signs of metabolic dysfunction include abnormal body composition and weight distribution. 
  • Sarcopaenia is a sign of metabolic dysfunction as muscle is one of the biggest utilisers of glucose and bones are key to metabolic health through the production of hormones for glucose utilisation. 
  • Brain fog, poor cognition, cardiovascular disease, menstrual irregularities, and poor gut health are associated with poor metabolic function. 
  • Inflammatory markers including CRP, lipoprotein lipase (Lp-PLA2), myeloperoxidase (MPO) and homocysteine are indicators of metabolic dysfunction. 
  • Metabolic flexibility allows the body to switch from glucose or fats as a source of energy. If the mitochondria are not functioning well, the body will not be able to utilise the energy from fats properly. People with metabolic dysfunction will experience a sensation of extreme hunger and hypoglycaemia when fasting for extended periods.  
  • The Ma-Pi diet has been shown to support a reduction in HbA1c and body weight levels. The Ma-Pi diet is high in complex carbohydrates, resistant starch and support the health of the gut microbiome.  
  • Eating with the circadian rhythm can influence blood glucose levels, with greater insulin sensitivity in the morning. 
  • Reduction in oestrogen levels associated with menopause has a direct impact on blood glucose management, mitochondrial function, microbiome composition and gut barrier integrity. Phytoestrogens can bind to oestrogen receptors and mimic the role of oestrogen. 

Research discussed in this episode

Research: 'A 6-month follow-up study of the randomized controlled Ma-Pi macrobiotic dietary intervention (MADIAB trial) in type 2 diabetes’ Nutrition and Diabetes, 2016
Research: 'Probiotic With or Without Fiber Controls Body Fat Mass, Associated With Serum Zonulin, in Overweight and Obese Adults-Randomized Controlled Trial,' EBioMedicine, 2016
Research: 'Randomized controlled trial for time-restricted eating in healthy volunteers without obesity' Nat Commun, 2022
Research: ‘Metabolic inflexibility in women with PCOS is similar to women with type 2 diabetes’, Nutrition and Metabolism, 2018

Additional resources and reading

Dr. Felice Gersh 

Dr. Felice Gersh
Research: ‘Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment’ Environmental Research and Public Health, 2022
Research: ‘Postmenopausal hormone therapy for cardiovascular health: the evolving data‘ BMJ Journals, 2021
Research: ‘Controversies Regarding Post-Menopausal Hormone Replacement Therapy for Primary Cardiovascular Disease Prevention in Women’ Cardiology in Review, 2020
Presentation: ‘Fast-Mimicking Diets: Therapy to combat the relentless effects of ageing’

Insulin Resistance 

Research: ‘Insulin resistance is a cellular antioxidant defense mechanism’ Proc Natl Acad Sci USA. 2009

Dietary Influence on metabolism 

Research: ‘A 6-month follow-up study of the randomized controlled Ma-Pi macrobiotic dietary intervention (MADIAB trial) in type 2 diabetes’ Nutrition and Diabetes, 2016
Research: ‘A paleolithic diet is more satiating per calorie than a Mediterranean-like diet in individuals with ischemic heart disease’ Nutr. Metab., 2010
Research: ‘Probiotic With or Without Fiber Controls Body Fat Mass, Associated With Serum Zonulin, in Overweight and Obese Adults-Randomized Controlled Trial’ EBioMedicine, 2016
Research: ‘Randomized controlled trial for time-restricted eating in healthy volunteers without obesity’, Nat Commun., 2022

Metabolic Dysfunction 

Research: ‘Metabolic (dysfunction)-associated fatty liver disease in individuals of normal weight’, Nature, 2022
Research: ‘Adipose tissue inflammation and metabolic dysfunction in obesity’, American Journal of Physiology: Cell Physiology, 2021
Research: ‘Metabolic inflexibility in women with PCOS is similar to women with type 2 diabetes’, Nutrition and Metabolism, 2018
Research: ‘Sedentary behaviour is a key determinant of metabolic inflexibility’ The Journal of Physiology, 2017


Emma: Hi and welcome to FX Medicine where we bring you the latest in evidence-based, integrative, functional and complementary medicine. FX Medicine acknowledges the traditional owners of country throughout Australia. We pay our respects to elders, past and present. 

With us today, I'm very excited to say, is Dr. Felice Gersh, an obstetrician and gynaecologist who is also board certified in integrative medicine. Felice has written several books on topics including menopause and PCOS. With over 30 years in clinical practice, Felice specialises in all aspects of female health with a focus on managing female hormonal dysfunctions. She has a particular interest in metabolism and weight which is what we're going to be discussing today.

Welcome to FX Medicine, Felice. Thank you so much for being with us today.

Felice: Oh, it's my pleasure. I'm so glad I could join you.

Emma: Me too, let me tell you. Now in 2018, the average waist measurement for an Australian adult man was 98 centimetres and for women, it was 88 centimetres. And unbelievably, three out of five Australian men and two-thirds of Australian women had a measured waist circumference that put them at an increased risk of disease. And insulin resistance affects 1 in 2 people over the age of 40. The impact of metabolic health is profound, and as clinicians we need to be proficient in this topic. Felice, can you start off by sharing with us how you became so interested in the topic of metabolism?

Felice: Well, it turns out that I spent much of my career as a practising obstetrician, and I'm also a gynaecologist so I delivered thousands of babies. I took care of so many women who were pregnant and it became very apparent to me that you cannot have a healthy woman, a healthy pregnancy, fertility if you don't have healthy metabolism. So, the link between reproductive health and metabolic health became very clear. But now it's finally being recognised that pregnancy is essentially like a metabolic stress test for women, that women who fail pregnancy by having preeclampsia, gestational diabetes, hypertension and so forth, preterm delivery, that they have underlying metabolic issues. And so the link between metabolism and all of the metabolic-related factors that go into a healthy or an unhealthy individual have such a big connection to reproductive health. So, the link between all of this. And then how it all manifests and how hormones are underlying all of these issues. 

So, you can't be, in my opinion, you can't be a functionally efficient OBGYN if you don't understand the critical importance of metabolic health. And then, of course, what happens as women age and they lose their fertility — because that's what menopause is all about, it’s loss of capability to reproduce — that it's not just that you lose your ability to reproduce but you lose that metabolic spark. Your metabolism changes. Your metabolic health status changes and evolves once you lose normal ovarian function. So, it's just a part and parcel of everything that I do as a women's healthcare expert at every decade of life that women will go through.

Emma: Yeah. And metabolic disfunction, can you explain this for us? What is it exactly and what causes it?

Felice: Sure. So, you need to know what the heck is metabolism? So, metabolism is the creation, utilisation, storage, distribution of energy. So, it turns out that it's critically important for every living creature to have a very carefully and very precisely regulated metabolism which would include that energy intake which is food, eating, that it matches the metabolic needs and output like energy utilisation of the entire body of that living creature, whatever it is. And that is essential for overall health. 

So, like you started off when we talked in the very beginning when you introduced this whole program about the large waistline and how that is indicative of metabolic dysfunction. Well, someone who has a large waistline and they have excessive visceral fat that accumulates around the midline part of the body and belly fat, that those individuals have clearly a mismatch in terms of energy intake and energy utilisation.
Now it can be because they're overeating. It can also be because their metabolic functioning is being damaged by things like endocrine disruptors and so on or chronically high stress, hormonal deficiencies. So, it's a multi-pronged thing. It's what you take in but it's also about what you expend and how you utilise the energy that you take in. 

So, it turns out that understanding that when people have obesity or if they have anorexia, though that's obviously less common, that what you have is a mismatch between intake and utilisation of energy. And that is very finely tuned through nutrient sensors that are in the hypothalamus area of the brain that puts out these little triggering factors that then trigger the pituitary gland to put out its stimulating hormones to the ovaries called gonadotropins, LH, luteinising hormone, and FSH, follicle-stimulating hormone. So, reproduction is completely interlinked with nutrient status. That's why if you're over-nutrionalised and you're obese, you're going to have fertility problems and as well if you're very emaciated, if you're anorexic, you also have fertility problems. 

So, we need to recognise metabolism is then affecting every organ system of the body in terms of how it's creating energy through the mitochondria, the energy-producing organelles of every single cell and then how that impacts on the function of that particular organ. So, if you don't have proper creation of energy because you have some problem with your mitochondria, then that organ that carries that energy-producing mitochondria is going to have issues with basic functions of that organ. In the brain, it can manifest with emotional problems, cognitive problems. In the heart, it can lead to conduction problems, arrhythmias, heart failure. And in, of course, the kidney, then you can have kidney failure. So, every single organ needs to have proper regulated energy production for its functionality and proper function. So, this is all what goes into this global term of metabolism.

Emma: Yeah, it's so big, isn't it? It's like throwing a stone into a pond and the ripple effect affects every system in the body. But for all the clinicians out there listening to this, what are the clinical signs of metabolic dysfunction. What should we be looking at for when we have a patient sitting in front of us?

Felice: The first thing is what you started out with, when you have an abnormal body composition. So, in my office, we have the luxury of having a body composition machine. But if you don't have that, you can do old-fashioned things like getting callipers. You can get out your tape measure, all of those things. Look at waist to hip measurements and so on. Because it's not just being on the scale. It's like, "Well, where is the weight distributed?" And then if you can get a body composition, then you look and see how much lean body mass do you have. Do you have adequate muscle? Because muscle is probably one of the least recognised and appreciated organ system that's very heavily linked to metabolic health or lack thereof. If you don't have enough muscle which we call sarcopenia which happens with ageing, also with very sedentary lifestyle, muscle is the biggest utiliser of glucose in the body. 

Emma: Okay.

Felice: It’s burning glucose for energy so you've got to have proper amounts of muscle. So, if you have someone that is getting older and then you see just by looking at them that they are frail, they have very small amounts of muscle, if you do a bone density, they do not have adequate amounts of bone, they’re not going to have proper metabolic health because many organs like muscle I already mentioned but also bone. Bone is heavily linked to metabolism. Bone makes hormones. People don't even realise it's an endocrine organ that actually has a lot to do with regulation of glucose utilisation which of course is a very key part of metabolic health.

So, you want to look at cognition and mood. People who have brain fog, that’s a sign of metabolic dysfunction. If they're chronically fatigued and they just are dragging, that's a sign of metabolic dysfunction. If they're having a lot of gut problems, they're probably not digesting and getting the nutrients that they need. So that's going to be a very high suspicion for having metabolic problems. So, there are so many of the signs and symptoms of just not being well are really related to metabolism because once you recognise metabolism is about making energy, so then you're not going to have proper organ function if any organ is not having proper energy production. Same thing with the heart. If somebody is having cardiovascular disease, that's a sign of metabolic dysfunction. And of course, if they have lab testing that shows that they're prediabetic, that's pretty darn obvious.

Emma: Yeah. So, let's dive into the lab testing because this does fascinate me. There are always so many tests that we can order or run but which are your top three for assessing metabolic dysfunction? What would be your cherrypicked ones?

Felice: So, I would look at inflammation markers. I would look at comprehensive lipid markers, and thyroid, a comprehensive thyroid panel, if I were going to just choose three general types of panel. And this is such a key thing, in women, it must be recognised, for reproductive-aged women, that the menstrual cycle is a vital sign of health for a woman. So a woman who has an abnormal menstrual cycle, it's very irregular, it's too heavy, she has a lot of pain, she has PMS, pretty much any menstrual cycle dysfunction, that's a sign of metabolic dysfunction. 

Emma: Okay. Yeah.

Felice: So, we definitely want to think about those things. But the thyroid, the lipids and the inflammation markers would be my top three array of lab testing.

Emma: Okay. And for inflammation, do you mean a high sensitive CRP or is there another one that you would pick?

Felice: Yes. Well, included under inflammation markers would be also if you have accessible to you some of the enzymes like Lp-PLA2 which is the symbol for lipoprotein lipase. So, when you have inflammation in your artery walls which is a very high sign of metabolic dysfunction, you will have an elevation of certain enzymes that are released by white blood cells because you have unstable or inflamed plaque in the wall of the arteries. So, there are these enzyme markers. Another one is MPO or myeloperoxidase. Also, homocysteine is actually an inflammation marker. So can ferritin be, high ferritin is another inflammation marker. 

Emma: Great.

Felice: But also of course we need to get a basic thing like a blood count. And we should look for what the white count is looking like. And a chemistry panel because if you have elevated liver enzymes, which is not an early sign of non-alcoholic fatty liver disease, but once you have elevated liver enzymes, assuming that you don't have something else going on like acute hepatitis or something, you know, like from viral hepatitis or something else. 
But assuming you don't have that kind of thing going on, non-alcoholic fatty liver disease which is not easily diagnosed...an ultrasound of the liver will show it. But by the time you have liver enzymes and you really have significant liver disease, that is a very huge problem for metabolism. And it's very common in women who have fertility problems like polycystic ovary syndrome and women after menopause, obese people. Non-alcoholic fatty liver disease is at epidemic levels and it's the number one cause of chronic liver failure and liver transplants in the United States now. 

Emma: No, that is a fascinating point there. So, we're looking at inflammation markers, our lipids and our thyroid panel. And for cycling women, always check in on their menstrual cycle and see what's going on there. 

But I wanted to delve into metabolic flexibility, which is the ability to switch between burning glucose or burning fat which happens in the mitochondria, which you mentioned before. So how does mitochondrial dysfunction affect metabolic flexibility?

Felice: Well, it should just happen without even missing a beat that this is how the body is supposed to work. That the number one preferred energy source for the body is glucose. But we do not have glucose coming in. We're not supposed to be eating all the time. And if you go back into the ancient societies and so on, ancient humans, they would go through cycles of feast and famine. They could go days even without food coming in or very marginal amounts of food. 

So, you need to have a backup system and that's what fat is. So fat was designed to be stored in our bodies and women, by the way, are way more efficient than men at creating and storing fat. That's why, ladies, it's harder to lose weight. Nature made it that way because we're the ones that should be getting pregnant and having babies and nursing. So, it's more critical for women to have more storage fat. So, it's not our fault that it's hard to lose weight. 

But definitely, we should be able to easily switch when we're not eating food because most foods can be turned into glucose except fat. So, proteins can turn into glucose. Of course, carbs can turn into glucose and that's what people tend to eat. And then we have storage forms of glucose, that's called glycogen and it's stored in the liver, it's stored in muscle tissue. But it only lasts us for just so long. And if you're doing a lot of heavy exercise, you're going to go through your glycogen stores even faster. 

But once you're not eating — because humans did not have food all the time in ancient civilisations and ancient times — and you've used up all your storage form of glucose in the form of glycogen, what are you going to do to survive? You're going to start burning fat. And that should be seamless to convert from using glucose to the backup system which is burning fat. So, you shouldn't even feel the difference. You shouldn't go through starvation. I'm going to die. I'm so hungry. But that's what's happening to people now because they have just poor functioning of their mitochondria. And it's not even all that well understood whether it's the carnitine transport system that gets the long-chain fatty acids into the mitochondria, or it's the fact that the electron transport chain isn't working well.

Endocrine disruptors that interfere with normal oestrogen because oestrogen has functions all throughout the mitochondria and we live in a world of ubiquitous endocrine disruptors, these chemicals that interfere with our normal hormone signalling system. 

Nutrient deficiencies. You need manganese for the function of manganese superoxide dismutase which helps to detoxify one of the metabolic by-products of creating energy in mitochondria which are called superoxides. If you don't have manganese on board, then you're going to end up poisoning your mitochondria and they'll die. So, you need to have the proper nutrients to run the machinery of the mitochondria as well.

But for a host of these different reasons, people don't transition seamlessly and readily and appropriately from burning glucose which is simple. That's easy except if you can't transport the glucose in. That's another problem. That's what insulin resistance is about. And then you really can't seem to utilise your fat. Then what happens is you have truly energy-deficient cells. They're starving. Without energy, they die. And that happens in the brain, okay? So, the brain can seamlessly go back and forth between glucose and fat. That's critical for brain health and when you can't do that properly, then your brain is energy deficient and it puts out signals like, "Eat, eat, eat, eat. Go do anything you have to do. Just get food into you."

That's when people get hypoglycaemic. There's no glucose coming in. They can't burn the fat and they feel like they're literally going to die. They feel like they're starving to death because their brains are so energy-deficient at that moment. And they will go crazy. When I've tried to do fasting regiments with people that don't have that metabolic flexibility, they go through this point when they run out of all their glycogen stores and they should be seamlessly burning fat but they're not doing it well because their mitochondria are not doing their job. They will go crazy. And what I find is that they will immediately break the fast. So, they ruin all the benefits that we were going to get out of doing a little fasting and they start eating the fallback which — I don't know why this is but I've seen it over and over again — they start eating peanut butter and jelly sandwiches. Maybe because they just have some in their pantry. I don't know. 

So now before I would ever do any kind of fasting regimen with people when they have to burn fat because they're not getting any other glucose food source, I make sure that we work on their metabolic flexibility. The way that you do that is just work on fitness and get nutrients into them and work on lifestyle for several weeks before you start trying to do fasting regimens with people. That's the shortcut to failure, discouraging everybody so that they never feel like they want to do anything with you again.

Emma: Yeah, it can be brutal.

Felice: I learned that the hard way. Yeah. When you see it, when you see that metabolic inflexibility and they can't convert to burning fat, it is very dramatic. So, everybody should keep that in mind. No fasting until you've conquered this metabolic problem and get metabolic flexibility on board.

Emma: Yeah. And looking at that food as medicine approach which I always love to bring into my conversations, I know that you have experience using the Ma-Pi diet which was designed by Mario Pianesi and it consists mainly of whole grains, vegetables, legumes and some fish and seasonal fruits and nuts and seeds and some fermented products. And I read a study on this, on the Ma-Pi diet and diabetes and it showed that after six months the subjects had an improved HbA1c and had reduced their body weight. Can you share with us your clinical experience of using this diet?

Felice: Oh, I've had great luck. When it first came out, I don't think anyone had a good, clear idea of why does it even work. But now we understand that fibre foods...and these are high complex...in the old-fashioned sense of complex carbohydrates which means they're not in any way processed. So, we're talking beans and lentils and things like the ancient grains like buckwheat and amaranth and quinoa, millet. Things that have not been in any way processed. Root vegetables and so on. So, it's very, very high starchy type of carbohydrate diet. 

But these are foods that include resistant starch so they don't actually break down into sugar. They are pure food for the gut microbiome as well as creating some degree of energy source but they're really hard to break down. They do not turn rapidly into blood sugar. So we're not talking about pulverised grains of any sort. These are in the whole form of root vegetables and grains and so on. And this is nutrients for our microbial population because we didn't even know about the gut microbiome until relatively recently in terms of its critical importance as a symbiosis kind of relationship that we nurture them, they nurture us back. Without them, we're actually dead in the water. We cannot survive and we cannot be healthy if we don't have a healthy complex of microbials in our gut.

It's the most complex ecosystem ever, ever, ever discovered. And there are trillions and trillions of bacteria of different types. And these are living creatures. They need nutrients to survive. They need to get the right diet. So, we're eating for them. That's what this type of microbe nourishing diet is really all about. Now what I've definitely pushed more and more as I've learned and the research has come out of Stanford is that you need to include is fermented foods, the probiotics foods and the prebiotic foods. So that's really what the fibre products are is the prebiotics, and then the probiotics foods which are fermented foods. 

So, it's all about nurturing not just our own nutrient needs but our microbial nutrient needs. That's the beauty of this diet which you will not get, for example, on a ketogenic diet. A high-fat diet will help people lose weight in the short run and the reason people often feel good on it is because they're basically starving out their bad bacteria. Remember, bacteria don't live on fat. That's not their food source. They need fibre. 

So basically, by starving the bad guys out, but you're also starving the good guys out. You're not going to create a healthy microbial population that way. You're just killing bad guys. That's why fasting does that too. Sometimes the best people feel is if they stop eating altogether. But that's not a long-term solution. That's the problem. You can't just stop eating and starve all your bad bacteria out. You've got to also nourish and support the good bacteria.

Emma: Yeah, that's right. And for those people listening, if you want to look further into the Ma-Pi diet, it's a high fibre diet. It's around 27 grams of fibre per 1,000 calories. So, it is nice and high in those forms of fibre and the different forms of fibre as well. 

Talking about the microbiome and the impact on weight, a paper that I read was super interesting. They gave a bifidobacteria strain of bacteria along with a fibre for six months and the overall result was a drop in abdominal fat and waist circumference plus a decrease in their calorie intake, their zonulin and their CRP levels. So how does the microbiome impact glucose metabolism? What's the mechanism there?

Felice: Well, first of all, that study is so wonderful. It sort of correlates with the findings of the group out of Stanford where they said instead of giving a supplement of a probiotic, they gave them fermented foods along with the fibre foods. So, more and more data is supporting that approach. And it is very fascinating because you could take the same food, we’ll just say an identical apple and give the same apple to three different people at the same time of day and everything else has been stable and identical for everybody, they'll all have different blood sugar levels. So, it's how the bacteria in the gut digest or break down that apple to create a utilisation ability of the food that's in the apple in terms of then creating blood sugar that crosses out into the bloodstream.

So it turns out that microbes, they're doing so many complex things because when you have the right microbial population, you actually produce the right metabolic by-products which are called short-chain fatty acids. One of them is called butyrate and butyrate actually binds to the vagus nerve and it alters how the autonomic nervous system works which means it alters as well not just feeling happy or calm, but also how the peristalsis of the gut works. So, it's the enteric nervous system. 

In addition, the microbes themselves make neurotransmitters. So, it's like dopamine and serotonin which affects also peristalsis, mood and also how food is digested, and so how the food is broken down to actually release the simple breakdown products from the different foods that are eaten. And so when you have certain types of bacteria and they've looked at firmicutes and different things that you'll actually end up having higher caloric intake from the same foods and higher blood sugar level if you have the wrong microbial population. So, there is something protective about the right bacteria that you don't have an overwhelming release of blood sugar into your system that will spike then your insulin levels, which is very harmful. And having high blood sugar spikes is very harmful. You don't want to have these ups and downs, big ups and downs. You want to have more of a stable release. 

So, the microbes actually have a big role in how food is broken down and the speed at which sugar is released into the system. So yeah, it's so critical that we get that microbial population as healthy as possible So you can see the obstacles that people face when they're trying to lose weight and get metabolically healthy. It's a big challenge. For some people, it's unfortunate, but some foods need to be avoided for a while. That's the beauty of getting continuous glucose monitors because you can then individualise, well, how does eating this food actually affect your blood sugar, not somebody else's but yours. And then you work on improving your gut microbial population and maybe for three months you just avoid eating that food altogether until you get your microbes in a better state of affairs.

Emma: Yeah. I don't think we can underestimate the importance of the microbiome. But I want to talk about another area that you do have extensive experience which is time restrictive eating and weight management and as clinicians, it can be so overwhelming to know what style of fasting is best. I was reading a paper that was published in February this year and it compared early time-restricted eating to middle-of-the-day time-restricted eating and the outcomes were clear. This is one study that I looked at, that eating your calories in the earlier part of the day produced better insulin sensitivity and fasting glucose and reduced inflammation and improved gut microbial diversity. But everybody's different. But can you just talk us through, as clinicians, we've got someone sitting in front of us. How do we work out what the best style of fasting is for that person?

Felice: Well, there has been some very interesting studies and they all really come back to the fact that we are circadian creatures. So, the Earth has these really interesting movements. There are seasonal movements and other things but the big one that has the most research is the circadian 24-hour rotation of Earth on its axis. And so every living creature which includes humans have evolved for optimal survival and that means for optimal food accessibility and safety. 

So, humans, like many creatures on the planet, are diurnal. That means we're metabolically most active and we're awake and we're doing things physically in the daytime. And this is not a choice. It's not like you can wake up one day and say, "I just would like to be like an owl and become nocturnal." No. This is actually programmed into our genes. And one third of all the genes in the human body are called clock genes. And 90% of all genes in the body whether they're clock genes or not, they're associated with clock genes.

So basically, everything in our body is on a timer. And you can actually get a clock face. You can find them online where it shows this time of day, your immune system is doing this. Your natural killer cells peak in the morning. Male testosterone peaks at 10:00 a.m. and you have your temperature and your blood pressure and everything is on a timer. And these are not changeable. And it turns out that we are most insulin sensitive in the first part of the day so that when we eat food in the morning time, we get more function out of our insulin. So, for the same amount of insulin, we will lower blood sugar much more effectively. So, blood sugar incursions will be lower. Insulin levels will be lower which is very good because we don't want those big, giant spikes.

So, eating in the morning is all about eating with our circadian rhythm. There was a fabulous study out of Israel with women with polycystic ovary syndrome who have major metabolic dysfunction and 80% are obese. And what they found was in just one month where they had them eat two-thirds of all their food intake in the morning and then they had one third for either late lunch or early dinner. In just one month, their insulin levels dropped by just over 50% and their testosterone level — they have high testosterone — dropped 50%. And they started ovulating. It's amazing. So, it's so critical to know that we are time creatures. Also, our GI tracts work better in the morning. We're going to have better peristalsis. We're going to have better digestion when we eat in the morning.

And a lot of people figured this out at some point in life. When they eat late at night, they have more indigestion, more heartburn. That's not a chance happening. It's because we are programmed that way. There's a whole system in the body called the endocannabinoid system which is a lipid signalling system and that is incredibly circadian. And that will affect mood and weight control and so many things that are so critical with our immune system. And so, we need to accept we are who we are. We are day creatures, we're diurnal. We will do much better as a group if we eat early in the day. Now we're all going to go to parties, we're going to go to weddings and sometimes things are late at night. But as much as humanly possible, try to do the old-fashioned big breakfast, medium lunch and early, small dinner. 

Or if you can't do the big breakfast, then try to do the big lunch. I mean, there are cultures all over the world that make lunch their biggest meal but the worst thing that we can do is have a giant, late dinner. And trying to have a 13-hour or more from dinner to breakfast.

Emma: Yes, okay. So, the eating window is pushed earlier in the day and we want at least a 13-hour where we are not eating overnight. So, I think that's a great baseline.

Felice: Correct.

Emma: Yes, a fantastic baseline for clinicians to start with and just getting patients to tune in to how they feel when they're eating in that natural rhythm that suits their body as a human being. 

So, I wanted to move to perimenopause. And I know it does affect glucose management. Why do you think that is and what, as clinicians, what can we do to help women in this phase with their glucose resistance and insulin resistance?

Felice: Well, reproduction and metabolic health are all completely intertwined. And oestrogen in the form of oestradiol — that’s the form that the ovaries make during reproductive years — is like the glue that links reproductive health and metabolic health. And a critical part of metabolic health is transporting sugar into cells and that does not work well in an absence of inadequate oestrogen production which, of course, is inevitable during the perimenopause as oestrogen levels start to decline, become very inconsistent and then, of course, menopause when the ovaries cease to make ultimately any oestrogen at all.

So, the glucose transporters called the GLUTs, do not work properly without oestrogen. As well, the mitochondria don't work properly without oestrogen. So, you have these problems in terms of transporting glucose into cells and then utilising it properly. And also what happens after menopause, this has been shown, is that you have an alteration of the gut microbiome which we've just been talking about how critically important it is. So, after the onset of menopause, the composition of the gut microbiome becomes what we call dysbiotic or abnormal. And women then develop what's called impaired gut barrier function or leaky gut because the proper microbes create this mucus protective coating which goes away and then you have the wrong microbes. They make what are called endotoxins also known as LPS, lipopolysaccharides which can cross into the body creating activation of immune cells which creates a systemic level of low-level inflammation. 

So, after menopause, women become sort of low-level chronically inflamed. They have leaky gut. And the immune cells which are also oestrogen controlled in large measure, have a lower threshold to creating inflammation. So, you just have more and more triggers to inflammation. Inflammation promotes more insulin resistance. So now you have insult to injury, right? So, you have trouble transporting. You have more insulin. You have more inflammation. So that's the ticket to developing obesity too because insulin which is essential for life, if you don't have enough insulin like type 1 diabetics, in the old days before they had insulin, people died.

But insulin among its many critical functions, but it's the promoter for the production and storage of fat. Well, uh-oh. That's what women do very well. It's a totally different skill set to burn fat and to create fat and store fat. So, women lose really the best ability to burn fat to create energy, but still totally great at storing and making fat. And that's what they do. And when you don't have enough oestrogen and you have that state of inflammation, the body goes into the default state which is producing visceral and belly fat.

Emma: Goodness me. It's such a vicious cycle, isn't it, for women? I mean, it's just one thing leads to the next leads to the next leads to the next. I know clinically we see women all the time that are so frustrated about this situation. So, I think we can get some strategies on board for helping these women such as...

Felice: Yes, definitely.

Emma: Yeah, try...

Felice: I was going to say it otherwise comes across as all doom and gloom. I don’t want it to sound like that, like we’re all doomed because there are amazing things that we can do. One is actually eating phytoestrogen foods after menopause and perimenopause. And there are many phytoestrogen foods that people don't even realise. So, phytoestrogen foods are foods that contain these polyphenols. People are familiar with soy, but not just soy, other legumes and beans and grains, they can have what are called isoflavones. So that's a specific type of nutrients that actually bind to oestrogen receptors.

They're not oestrogen, okay? People shouldn't think that they're eating oestrogen. They're not eating oestrogen. They're eating plants that have these polyphenols that can bind to oestrogen receptors. And then there are also things like flaxseed. They're a different type of polyphenol that are phytoestrogens. They're called lignans. But then there are others that come in different fruits and vegetables like the grapes, the red grapes that have resveratrol. That's actually a phytoestrogen. And pomegranate that have ellagic acid that makes urolithin A, that's actually also a phytoestrogen. So eating a very expansive, plant-based diet will have tremendous benefits for the gut because they can bind to the receptors in the gut and actually improve the gut health, the gut microbiome. So don't underestimate the power of food.

But in addition, we can work with our circadian rhythm to get it better because oestrogen helps to regulate the circadian rhythm, which when you don't have the oestrogen with the onset of menopause, you essentially as a female become jetlagged which is not a good healthy state to be in. So, you're always in sort of a jetlag state. Different organs are not perfectly synchronised in the same time zone. So, what happens when your liver and your pancreas are in different time zones? It's not a good state. 

But the way that we can help keep things in proper alignment and having organs work in the same time zone is by getting bright light in the morning. So, we're working with the master clock in the brain that sits atop the optic nerve and can sense light and dark and also nutrient sensors. So, we want to get bright light in the morning, some bright light in the midday and then we want to get to see the sunset. It's amazing. The colours of the sunset will help lower cortisol and start our melatonin to start being produced. And then at night when you're sleeping make the room dark, really dark and make the room really nice and cool because we want our temperature to drop. And so, we want to definitely do all these things that we can. 

And then timed eating that we already touched on. Trying to eat the same times every day. Trying not to snack because that only confuses our gut microbes. And every living creature on this planet also has clock genes and you can help them to get the gut to be healthier and not have leaky gut and all that problem with endotoxins leaking out and everything by getting them to get regimented. Train them. By eating your food at the same time every day, they'll work better because microbes need consistency of time too, like our little pets. You want to feed them at the same time. Think of these as our trillions of little pets inside our gut that need to be fed on regular timed basis. 
And exercise. Exercise has so many health benefits. It's amazing what exercise can do for women. And if you want to lose weight, it's best to exercise in the morning. If you want to build muscle, it's best to exercise in the afternoon. So those are things to keep in mind. And then working on stress, of course. Women after menopause tend to have more cortisol, more stress so doing some kind of mind-body practice. So lifestyle can have these choices of what you eat, when you eat, your mood, your light exposure, your sleep and sleep quality can have tremendous health benefits and just change the dynamic of menopause.

So don't underestimate the value of lifestyle. I'm a big hormone fan but hormones are never going to be the same like you're 25. We don't have the ability to give you back ovaries. So, no matter whether you're on hormones or not on hormones, you still need to do all the lifestyle stuff which you should do at every stage of life because you could be 25 and be metabolically unhealthy. That's for sure and that happens a lot. That's why they have fertility problems and obesity in younger women. So there’s no time of life that you get a free ride that you can just do whatever the heck you want and not worry about lifestyle. But especially once you hit menopause, there's very, very little forgiveness at that stage. You've got to do it right.

Emma: I think menopause just puts everything under a microscope that may have been bubbling away a little bit but then it's just highlighted at that time. But I am so thankful for you taking the time today and sharing with us your expertise. Some key points I've taken from today is definitely the critical importance of a diverse gut microbiome, and that an eating window earlier in the day with at least a 13-hour fasting period and the importance of food as medicine is critical. Never forget that, how powerful that can be. And I love the sound of the study that you just mentioned. 

Thank you so much for listening today, everyone. Don't forget that you can find all the show notes, transcripts and other resources from today's episode on the FX Medicine website, fxmedicine.com.au. I'm Emma Sutherland and thanks for joining us. We'll see you next time.

About Dr. Felice Gersh

Dr. Felice Gersh is a globally-recognized expert on women’s hormones, gut microbiome, and circadian rhythm. She frequently collaborates with numerous research organizations and lectures internationally on women’s health topics.

As Medical Director of the Integrative Medical Group of Irvine, Dr. Gersh focuses on understanding women’s innate physical and emotional make-up. Through her research and practical experience, she has come to understand that women have internal, natural rhythms that are absolutely essential to female health. These rhythms are controlled by hormones, particularly estrogen, and may be kept in balance through both conventional and holistic treatments.

Dr. Felice Gersh also starts with the most natural treatments that produce the fewest undesirable side effects. In most situations, she uses pharmaceuticals as a last resort because, although pharmaceuticals deal with symptoms, they can also disrupt the body’s natural ability to heal and affect women’s reproductive functions.


The information provided on FX Medicine is for educational and informational purposes only. The information provided on this site is not, nor is it intended to be, a substitute for professional advice or care. Please seek the advice of a qualified health care professional in the event something you have read here raises questions or concerns regarding your health.

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