Fasting & Hormones: Keys to Women’s Heart Health

Felice Gersh, MD

That would be my pleasure. It’s a very big deal. I’m so happy we have this opportunity.

Joel Kahn, MD, FACC

Thank you for taking the time. When you see a 45, 50, or 55-year-old woman over the years, do they come in asking about heart disease or something else you bring up because they should be thinking a bit about heart disease?

Felice Gersh, MD

I would say it is, in the vast majority of cases, something that I bring up because women are quite unaware of their risk for cardiovascular events, and they feel very protected because they’re aware that, as younger reproductive-aged women, they have a lower incidence of heart attacks than men. They don’t understand that as they transition into the perimenopause and menopausal years, their risk grows dramatically. These risks are occurring because changes in the vascular system are occurring silently. I call them the covert symptoms of transition into menopause, and they are not aware of them, so they do not take any proactive steps. So that is my job as a preventive medicine doctor because my role is very best at preventing bad events rather than reversing end-stage disease.

Joel Kahn, MD, FACC

So your opinion and mine wouldn’t match. Of course. I have a cardiology practice. Women come and see me. I would say at least half of my patients are women. They’ve made a decision, maybe because they don’t feel good. Palpitation, fatigue, shortness of breath, or maybe their family history or their lab values. But you’re seeing women who aren’t coming to a cardiologist or an integrative gynecologist, maybe for their PCOS. You’re the one bringing up the heart disease topic. They’re not necessarily focused on it, huh?

Felice Gersh, MD

I do a very thorough history intake on all of my patients because many of them are not aware that events that have been occurring throughout their reproductive lifespan have a big impact on their cardiovascular risk as they age. For example, when they were younger, did they have regular cycles that are now known to be a risk factor, irregular cycles? Did they have PCOS? Did they have pregnancy complications, which are now recognized as a risk factor for cardiometabolic disease as women transition into the menopausal years and thereafter? aking a history, understanding their risk, and then getting tested. I love data. then I get testing on my female patients and educate them as to why this is happening and the fundamental differences between male physiology and female physiology, the role of hormones, what happens within the cardiovascular system, and all of their metabolic regulation as they lose their ovarian functionality, what we call ovarian senescence or aging. The dramatic impact that this has throughout their body and the tremendous increase in risk factors that are created in their bodies.

Joel Kahn, MD, FACC

There are some women before menopause who, well, number one, have a variety of heart diseases. You can have racing heartbeats at age 14. You can have blackout spells when you’re nine, and you’re going to be born with congenital heart disease. But we’re talking more about acquired atherosclerosis. There are some women before menopause; maybe they’ve been smoking a pack or two a day. Maybe they develop type one diabetes as children. Maybe they have had familial hyperlipidemia, a cholesterol level of 450 since birth. We have to be aware of that and do our work. But you see, a woman who’s 48 years old is having irregular periods, and she’s starting to have a few hot flashes. What’s going on in the body? Give us a little bit of that. that over the next ten years is going to bring her heart disease risk as close to many men who, unfortunately, get a premature advantage in heart disease. But you women catch up. What’s happening in the average woman entering menopause? That makes her a heart disease risk by age 60 or 65, for sure.

Felice Gersh, MD

It is all about the reduction in the production predominantly of estradiol, the estrogen produced by the ovaries. As women are approaching menopause, we need to recognize that the word menopause is an arbitrary definition of an event that occurs over time. So the official definition of menopause is 12 consecutive months without any spontaneous bleeding. It could be 18 months. It could be 11 months. It could be six months. These are arbitrary, made-up definitions. Women need to understand that it’s a scope. It’s a progression of ovarian changes and decline. Throughout this time frame, which can easily go over ten years and kind of accompany fertility decline, we know that women in their late thirties are less fertile than women in their early twenties, and so on, and it’s because of changes within the ovaries, the egg quality, the number of eggs, and the production of hormones. Although there can be fluctuations, there can be steep jumps in the production of estrogen along this path. But the general trajectory is down and estradiol is the master of metabolic homeostasis. It regulates metabolism, and that is essential for optimal fertility and pregnancy. We need to have the proper creation of energy to match the energy intake. That’s all about the production, distribution, and storage of energy, the utilization of energy, and the maintenance of every organ system to be optimally functional. When you no longer need to have reproduction, of course, nature just says you’re done, and it’s kind of on the decline, and then it’s over. You lose your vital life hormone, estradiol, which is produced from the ovary. Unbeknownst to women, as this process is occurring, they may have some of what I call the overt symptoms, like night sweats and hot flashes, which are sort of the most commonly recognized symptoms. That’s because the thermoregulatory centers in the brain in the hypothalamus are regulated in great measure by estradiol. So they become dysregulated. But that’s like the tip of the iceberg because the vascular system has estrogen receptors. The myocardium, the neurological system that is the autonomic nervous system that helps maintain a proper heartbeat so that you maintain your stress under proper control on the dilation, produces many enzyme systems that are modulators and are regulated by estradiol, which is not well recognized. The whole system called the RAAS system, the rhenium, and the renin-angiotensin-aldosterone system, which regulates blood pressure and fluid and electrolyte imbalances, is modulated by estradiol. all systems in the body as you transition and the estradiol level production is going down, these are all becoming less optimal in terms of how things are working. without any recognition of a woman may notice her well. If she has her blood pressure checked, her blood pressure starts to rise. If it were checked, it would be found that the energy production in her heart could go down. This is an interesting finding that many cardiologists may notice when they do echocardiograms on women as they’re going into menopause that they have mild diastolic dysfunction like an energy deficiency because mitochondria are the essential energy-producing model little organelles in each cell that produce energy. The mitochondria cannot work properly. When you don’t have enough estradiol for a whole host of reasons, you can’t produce enough energy, and you can’t maintain the health of the mitochondria because you produce a toxic byproduct when you create energy that needs to be eliminated, it is called superoxide, and that requires the proper function of the enzyme superoxide dismutase, which requires estradiol. There are so many systems in the body that require estradiol for proper function, and that includes every aspect of the cardiovascular system. Things are changing, but they’re not recognized because, except for a few obvious symptoms like night sweats and hot flashes and sometimes vaginal dryness, the systems that are changing are not overt, like changes in blood pressure, vascular health, and myocardial energy production. Those are not obvious. These are happening to women before that last period even happens during the years preceding.

Joel Kahn, MD, FACC

You see a woman again, 50 years old. She’s gone 14 months without bleeding. She’s probably having a few menopausal symptoms. I’m sure you asked her. She is an internist, a family doctor, and all the rest, she says. But it’s the same routine blood work. Are you going to dive in as an integrative gynecologist? Recognizing there aren’t a lot of integrative gynecologists, are you going to dive in and get a more-than-average blood panel? What else might you do? Let’s say she has a family history. Her mother had a stroke at age 54, and her father had bypass surgery at age 48. That sounds dramatic, but there’s a lot of people out there like that. Are you going to dive in and order some stuff?

Felice Gersh, MD

I sure am. I do want to work as a team. Everything that I do, I tell them to bring to their other physicians because I’m not trying to work behind anybody’s back whatsoever, but I do want to help them recognize their risk and then also share that knowledge with every other physician. I like to get inflammation markers. I know we’ve talked about this many times in the past few years because now we do understand that inflammation is underlying many of the problems that occur. Then, of course, you have to go into why this inflammation is happening. It can be a host of things, including hormonal dysregulation, endocrine disruptors, chemicals, pollution, nutrient deficiencies, sleep deprivation, and chronic stress. There’s a whole host of things, and usually, it’s what I call the perfect storm. It’s not just one thing; it’s a host of things. But I love to get inflammation markers by looking at high-sensitivity C-reactive protein. I like to look at some of the enzymes, like Lp-PLA2, and sometimes Myeloperoxidase. I like to look at homocysteine, and I like to look at nutrients—some of the basic nutrients, at least like B12. I always want to check for ferritin, like iron. I want to check vitamin D too, and I may look at some of the others, like CoQ10, and Omega 3. I want to look at some of the nutrients. I look at the thyroid because thyroid disorders are extremely prevalent in women. Autoimmune thyroid disease is very common. I like to look at all of these markers, and I like to look at a more advanced lipid profile, not just the standard one from like 60 years ago. I also like to look at more particles, the Apolipoprotein, LP(a), which I know are getting a lot of attention and a lot of people don’t know that talking about lipoprotein LP(a), estradiol is one of the modulators of it, so it tends to go up after menopause, as well as other genetic factors. But that’s terms of cholesterol, all cholesterol almost always goes up in women when their estradiol level goes down because the LDL receptors in the liver, which are so key to modulating lipid levels, really don’t function as well. As well, the whole immune system is modulated by estradiol. You tend to have more inflammation occurring, which creates oxidation or increases the acidity of your cholesterol, which can then lead to plaque formation and more inflammation. I like to get as many of these tests as possible, and in my office, I have an amazing ultrasound tech who does ultrasounds of the carotid arteries, the aorta, and the leg arteries, and I also order coronary calcium scores, which I know we’re both big fans of. I want to get all this data. Unfortunately, sometimes very busy practitioners are missing the boat, in my opinion, and they’re not getting these tests on women. At least they’re not even thinking of them until they’re over 65.

Joel Kahn, MD, FACC

You are doing what we’ve talked about in other interviews at this summit, which is don’t accept the average. We talk a lot about being moderate and everything. I was thinking about that this morning, but we’re moderate in our lab values and moderate in our testing. We’re moderate in our conversations with patients about lifestyle and diet. When Dr. Esselstyn certainly is talking about extreme,  be extreme in diet. But you and I, are a bit extreme compared to the mainstream in testing because we do know that this disease called coronary artery disease is a big risk to men and women. We have the technology right now to know everything about anybody’s heart. It isn’t necessarily expensive if you don’t have health insurance; you can get these amazing panels of blood work now that you self-pay for by a company like lifeforce.com, lifeextension.com, and functionhealth.com. We never had that before. The calcium score is inexpensive. It’s probably a bit more expensive in Orange County than it is in Detroit, where it’s about $75, but it’s still worth it, whatever it is. How about women? Women tell you that figures before I go, they always say this is because they’re about to walk out of the exam room. I’ve been having fatigue from my workouts are not as good. My heart’s racing. I’m getting a bit winded up on the stairs. What kind of symptoms have you seen in your career that have caused you to be a bit concerned about actual heart disease? Not the potential, but actual heart disease in women?

Felice Gersh, MD

Women may have much more subtle findings and symptoms compared to men when they’re developing coronary artery disease. What you just described is just feeling fatigue or just sort of a sense of low energy or poor sleep. This can be a sign of vascular disease. One of the other big ones that’s so ignored is anxiety. Women sometimes will just feel this sense of unease, like something is wrong and they’re just like written off, like, oh, another woman who needs Prozac or something, and it’s a sign of coronary artery disease. You think differently. They don’t necessarily come in with that, like television, heart attacks, or the crushing pain type of thing. They can also have GI dysfunction; they may just have nausea or just sort of feel like they’re having some GI disturbance or something going on that’s wrong in their intestinal tract. It can cardiovascular disease. Women don’t have everything the same as men. and you have to think that once again, I always go back, and this became so evident to me as a woman obstetrician delivering thousands of babies. That pregnancy—even now, it’s talked about. But it wasn’t until years ago—decades ago—that pregnancy was the ultimate stress test for women. A woman’s heart during pregnancy has to pump at least 50% of the amount of blood volume that you would ever pump at any other time in her life. The heart and vascular system of a woman have to be able to accommodate a pregnancy. that makes it different than a man’s. That’s why she can react differently. We know the immune system in a woman is much more robust than in a man. When it goes wrong, like with autoimmune disease, it goes wrong in spades. A lot of doctors don’t realize that autoimmune diseases, which are so prevalent now, 80% in women, are cardiovascular risk factors, just like rheumatoid arthritis is a risk factor. Even issues like endometriosis and unique female diseases—even women who’ve had a history of uterine fibroids—have a higher risk of hypertension. Being aware of these subtle things like fatigue, nausea, anxiety, prior history of autoimmune diseases, current history, pregnancy, or female-related specific issues are all red flags that this woman may have an active disease, not just the potential for disease.

Joel Kahn, MD, FACC

So that’s a wake-up call to everybody that even subtle findings like fatigue, shortness of breath, palpitations, and exercise intolerance that previously were not a problem whether they occurred before menopause, particularly from menopause or when atherosclerotic risk goes up, should never be ignored. Women have an advantage when their lifespans are dropping. I read today that the gap isn’t exactly relevant to the conversation, but we all know that women on average live longer than men, not necessarily in the best quality of life. There’s a life span, and then there’s a health span. That healthy period of your life. Hopefully, your health span is as long as your life span, but we don’t all get that. But the gap between men and women has expanded, mainly because men’s life spans are going down and women are stable. They’re not going up anymore. Coronary disease remains. that, number one, because they’re, so we need to be aware of all these topics. How do you relate to the cardiology just in town? Some of them have never seen the lab work that you do. I don’t know. Do you use LabCorp Quest to use Vibrant Health, one of the other lab providers?

Felice Gersh, MD

I most of the time use Quest and Cleveland Hall Lab, which is part of Quest. But I’ve had patients come in with all of the above that you mentioned. I do try to, like I said, work cooperatively with everyone’s doctors. I will sometimes just write little notes. I’ll say I’m happy to make a phone call or to talk about it. like what you were talking about is so important for everyone to recognize that, for example, by the time a woman reaches 65, her potential for a stroke or a ruptured aneurysm becomes greater than for a man. These are like big-deal issues, cardiovascular disease for women, and many cardiologists, such as you, recognize it. But not all the family doctors and most of my patients don’t have cardiologists unless they’ve already had some major event or somebody told them they should go to a preventive cardiologist. But it’s not common in my area for people to just go to a cardiologist. It happens. But without having a prior issue, like at least one being found to have mitral valve prolapse or A-fib, which is now, I’m sure you see tons of it. A-fib is common in women, and that’s probably the leading cause of my patients ending up in a cardiology office. That’s a whole different world than just trying to be proactive and preventative. But I would say that most of the family doctors that are in the area are not as knowledgeable as I wish they would be about women and cardiovascular health. If everyone had a cardiologist, it’d probably be a little different. I don’t think there’s enough to go around.

Joel Kahn, MD, FACC

You explain things so clearly. Now I understand why, for at least 13 years, you won the Physician of the Year award from the Orange County Medical Association and have many times been on the Super Doctor Award list, too, because you just make it clear. Before we go, and I don’t want you to go anywhere, Dr. Gersh. I want you to just share an interest in fasting. We both used Dr. Valter Longo’s role in a program of five-day fasting-mimicking the diet of L-Nutra. I did have a chance to interview Dr. William Hsu, their medical director for this summit. We talked mainly about diabetes. Just give us a couple of minutes on your experience with role-playing in women and what you hope they benefit from doing a periodic five-day fasting-mimicking diet.

Felice Gersh, MD

I am pushing them as much as I can to do more studies involving a lot of women and women at unique times in their lives. But based on my observations, what I find is that women do have more challenges with the fasting-mimicking diet than men. They don’t lose as much weight. They have higher rates of dropout. I prepare all of my women patients before they get into fasting of any sort, particularly fasting-mimicking diets, by doing a month or even a little longer of what we call the anti-inflammatory gut reset, which is taking them off proactively of all processed foods and sugar-added foods, trying to get them on a high vegetable plant-based diet, increasing their fiber intake, trying to nurture their gut microbiome, helping them to get on a more timed eating regimen, and preparing them for doing the fasting-mimicking diet for doing ProLon. I’m also finding that women who are not on any if they’re in menopause if they’re not on an estrogen supplement or hormone replacement therapy, don’t do as well. I’ve done a bit of a deep dive, and all of the mechanisms that are involved in you may have talked about these things: the production of ATP, talking about the sirtuins and the histone deacetylase, which are the sirtuins, and all of the different mechanisms that come into play: autophagy, programming, cell suicide. All of these mechanisms require estradiol for optimal function. I’m finding that I don’t do as well with women going through this process if they don’t have adequate estrogen on board. We do need to do more research on that. In terms of women on birth control pills, I don’t think so because those are not natural hormones either. I don’t think we’re getting an optimal outcome. We need to do more research involving women and the relationship between their hormones. Even in terms of when a woman is having natural menstrual cycles, say she’s not perimenopausal yet, in menopause, or she’s still having cycles, when is the best time? My research suggests that it should be done in the proliferative phase. That’s rather, I’m sorry, the opposite. Let me make that very clear. I want it done in the luteal phase because if you do fasting of any kind in the proliferative phase that is before ovulation, you may prevent ovulation. After all, the brain will sense that there are not enough nutrients coming in. Let’s not make a baby the cycle, and we’ll just prevent ovulation. We don’t want to do any sort of multiday fasting during the time preceding ovulation. But actually, some published data goes back to the 1990s that if you do fasting, multi-day fasting, or fasting-mimicking, they didn’t do the study on that, but it should be similar during the luteal phase or after ovulation. It increases vagal tone or parasympathetic output. It lowers heartbeat and blood pressure; it’s calming; and it improves premenstrual syndrome symptoms. Is it any multi-day fasting or fasting-mimicking the luteal phase?

Joel Kahn, MD, FACC

Everybody, we have had a wonderful discussion with Dr. Gersh, Professor Gersh, and she is beaming in from Southern California. We thank you for taking your time. For our general audience, we thank you. I know you learned a lot. That is an expert. I do want to give it a shout-out. She has written a book about PCOS, but she has a new book out. We discuss Menopause: 50 Things You Need to Know About What to Expect During the Three Stages of Menopause. You can go to her website, or you can, I’m sure, go to the book and the usual book sites. But she’s at the Integrative Medical Group of Irvine, and the website is integrativemgi.com, where you can read all about her and order her book. Half of the world should buy her book, so there will be about 4 billion sales, and that would do well for her. Anyway, thank you. Don’t go away. Dr. Gersh. 

We are back here for a few more minutes with our expert on everything female and heart disease, Dr. Felice Gersh, the author of Menopause: 50 Things You Need to Know. I just want to shift gears for a couple of minutes. Your other book is on PCOS, or Polycystic Ovarian Syndrome. Nobody has mentioned that during this summit. We’re talking about women and their risk for heart disease. Tell us about whether PCOS, first of all, is Polycystic Ovarian Syndrome. We tried to find it. Tell us how you would recognize it. In under a minute, I meet you in an elevator and say, What’s PCOS? then what’s the relationship to the development of heart disease, young or old?

Felice Gersh, MD

It’s a hormonal dysfunction that is the most common endocrine disorder in reproductive-age women. It’s associated with elevated androgens. That would be like high testosterone. They have acne, facial hair, thinning hair, and irregular cycles. On ultrasound, the typical tiny little cysts are around the rim or cortex of the ovary. That’s how you define the condition.

Joel Kahn, MD, FACC

Since we’re talking about heart disease, predominately atherosclerotic heart disease blockages, that was about any concern between that syndrome and developing heart disease.

Felice Gersh, MD

There is a very high correlation. Unfortunately, women with PCOS tend to be quite metabolically unhealthy. About 80% are overweight and often have very severe obesity. By age 40, they have seven times the risk of being diabetic. They have a significantly increased risk of having nonalcoholic fatty liver disease. They have a high risk for hypertension, heart attacks, and strokes at earlier ages. It is a very serious disease. I consider it a condition of premature aging, and some clever person out there came up with the term meta-flammaging, inflammation due to metabolic dysfunction. Then there’s the older; the more typical they call inflammaging, inflammation associated with aging. They are the meta-flammaging group. They have metabolic dysfunction, creating systemic levels of inflammation that lead to a host of metabolic disorders, including diabetes, hypertension, heart attack risk, and a whole host of pregnancy-related problems and complications.

Joel Kahn, MD, FACC

I read your book. I learned a lot from it. Again, PCOS S.O.S., I got that right.

Felice Gersh, MD

That’s it.

Joel Kahn, MD, FACC

I wasn’t sure if I had it backward. You do talk a lot about supplements. Most of us have not heard much about Inositol being of some use in this syndrome. There are other ways to treat it. But tell us a little bit about Inositol. 

Felice Gersh, MD

I would be so excited to do so. One of the big problems that underlies the development of PCOS is that in the ovary there is a conversion from testosterone into estradiol. That’s all. Estradiol, which is the estrogen produced in the ovary, is derived from testosterone, made in the ovary in a different part of the ovary. The conversion requires the action of an enzyme called aromatase. For this enzyme to work properly, you need to have the action of Myoinositol. So in the normal, healthy ovary of a reproductive woman, there is a ratio of inositol, called Myoinositol, to a different form called D-chiro of 100 to one. But in women with PCOS, the ratio is only 12 to one on average, and D-chiro, which has other benefits in the liver but in the ovary, can block the effect of Myoinositol. The inositol cells are sugar alcohols, and they’re all stereoisomers. What that means is that they’re all the same molecular composition, but they’re arranged differently in space, like my hand in different configurations; it’s still my hand. Those are stereoisomers. The form called Myoinositol is critically important in the ovary for the conversion of testosterone to estradiol. When that doesn’t happen, you end up with too much testosterone, which is what they have, and not enough estradiol. That’s why, as you can see, I’m so glad you brought this up. The similarities in the cardiometabolic dysfunctions of women with PCOS and women going into menopause are that they have a similar problem spectrum of cardiometabolic diseases, but women with PCOS are having them because of an estradiol insufficiency. Then they go into all of these problems. But that is treatable. We can help the ovary be healthier and make estradiol better in PCOS women. Whereas in menopause, when it’s done, it’s done. You either give the hormone or they don’t have it with PCOS, that’s why I talk about so many lifestyle issues, giving Myoinositol to women with PCOS has been shown to improve their capability of making estradiol and improve the quality of the eggs and the health of the ovaries. This, to me, is an essential part of the therapeutic approach for women with PCOS.

Joel Kahn, MD, FACC

You can just do it if a person wants to work with somebody, but this is not an exotic supplement. You can go to our favorite online seller, which everybody uses, good or bad, and you can find many, many brands of Inositol. What’s a typical dose, and what is your preferred provider?

Felice Gersh, MD

Myoinositor, the dosing is typically two grams twice a day, and I typically use pure encapsulation, but there are many other very good companies, I just want to mention that with D-chiro, there is sort of an undercurrent of use of a small amount of D-chiro in the ratios.

Joel Kahn, MD, FACC

A version of Inositol, D-CHIRO.

Felice Gersh, MD

That’s just a different arrangement of the same formula in molecular formulation. In the liver, D-chiro-inositol is very important for glucose regulation. So it’s very important. But in the ovary, it can block the action of Myoinositol; orally, it can block their absorption. You have to be careful. But there is more and more research coming out to suggest that there may be some proper ratio of giving. There is no harm in giving it in as a small amount of D-chiro, but we don’t want to give too much, so we have to be careful about that.

Joel Kahn, MD, FACC

I’ve read like 40 to one. I don’t know; it’s at 40 Myoinositol and one D-chiro.

Felice Gersh, MD

That ratio was found in the blood. But the problem is, if you had that in the blood, first of all, if you swallowed it even in that ratio, how’s it going to be in the blood in that ratio and the ovary? You want it to be a 100-to-one ratio, not 40-to-one. But it’s not harmful. Anyone who wants to take it in the 40 to one, that’s not going to be a problem.

Joel Kahn, MD, FACC

Last question, then. We’re done. Does a man ever use inositol as a supplement?

Felice Gersh, MD

Yes, actually, in rather high doses, it’s a combative agent. It can treat anxiety. Yes, it can be used, and predominantly for anxiety. D-chiro should also be of benefit for men and postmenopausal women, where you’re not even worried about the ovary at all because it’s just not online anymore in terms of producing estrogen, but D-chiro does have benefits in terms of glucose regulation. I know much more about it for women, but I can’t imagine why it wouldn’t be beneficial for men as well.

Joel Kahn, MD, FACC

Excellent. Dr. Gersh, thank you for taking your time. Thank you for sharing with us. Reversing Heart Disease Naturally Summit. You’ve added so much value and so much education. Thank you. Have a healthy, happy 2024.

Felice Gersh, MD

Same to you.