00:00:24
Speaker 1: This show is not a substitute for professional medical advice, diagnosis, or treatment. It is for informational purposes. Please consult your healthcare professional with any medical questions. Also, in this show, we use women as shorthand for people with XX chromosomes. We understand sex and gender are more complex. and acknowledge the experiences we describe reach beyond that word.
00:00:54
Speaker 2: When I was doing my immunology fellowship at Stanford, when I was really getting into fasting, I was able to do experiments on my cells. I was able to do experiments on my blood to see how intermittent fasting actually affected me. And so I looked at my blood at like a 12-hour fast, a 16-hour fast, a 24-hour fast, a 36-hour fast, all the way up to a 72-hour fast. just got to see all the changes that were happening at the cellular level there.
00:01:19
Speaker 3: That's Dr. Chris Rhodes. He's a researcher who has spent much of his career steeped in the science of intermittent fasting. He earned his PhD in nutritional biochemistry at UC Davis, and I invited him on the show today to unpack the way fasting works and what the research says about the impact fasting can have on everything from longevity to weight loss and even brain health. Now, I should say up front, intermittent fasting is not for everybody. There's plenty of anecdotal evidence that women in particular don't necessarily tolerate fasting well. Personally, I haven't found it to be successful. But my husband, a recent convert to intermittent fasting, really loves it. He's lost a ton of weight and advocates to just about anybody who will listen to him about the benefits of intermittent fasting. And as you'll hear, Dr. Rhodes has applied much of what he has learned through his research to his daily eating habits also.
00:02:22
Speaker 2: Dr.
00:02:23
Speaker 3: Rhodes is the co-founder of Mimeo, a biotech company that has been developing supplements to help our bodies unlock the same health benefits that research has shown intermittent fasting can provide. And I want to say, even if you're thinking right now, no way, fasting is not for me, there's still lots in this conversation. about how to personalize your approach to nutrition, and about how to potentially access the same health benefits of fasting without actually needing to fast that we can all apply to our lives. So let's just get right into it. Let's talk about intermittent fasting. And let's just start with a straight, forward, short explanation about what is intermittent fasting. And I think it's also referred to as IF, right?
00:03:11
Speaker 2: Yep, it is. And that is actually like, seems like a simple question, but is a little bit more complicated than most people think. There's many different kinds of intermittent fasting, but by and large, just as an overarching general definition, intermittent fasting is just going for long periods of time without taking in calories. So that's just, you know, like no food, but like water, coffee, tea, non-caloric beverages, all of those would be allowed. And then after you're done fasting, you go back to eating for a while and typically eating normally. So there's different types that go into that. There's the most common type, which is 16-8, which is fasting for 16 hours and eating in an eight-hour window. This is more what we consider to be like time-restricted eating. Then there's also one meal a day. Oh, man, that's pretty self-explanatory. You're just eating the one meal a day and fasting for the rest of the time. Then there's more complicated protocols like alternate day fasting, where you're eating normally one day, fasting the next day, rinse and repeat basically forever. And then there's multi-day fasting, which is usually three to five days, sometimes up to a week, sometimes up to two weeks, depending on what the person is trying to achieve or if there's some kind of medical intervention that's happening to get that fasting going. So that's kind of the broad strokes category buckets that we kind of put intermittent fasting into.
00:04:37
Speaker 3: How did you become interested in this space? And what led you to get your degree in advanced nutritional biology?
00:04:46
Speaker 2: I got my BS in biochemistry from Loyola Marymount University down in L.A., I took an immunology fellowship at Stanford, just kind of trying my hand at lab science, going through all of the papers that I could get my hands on, going to all the research seminars, and eventually came across healthy aging and longevity research, which I thought was so fascinating because it used to be a myth and legend, Ponce de Leon and the Fountain of Youth and all of that stuff that has now become a very, very rigorous and very, very active section of scientific discovery. And when you're in that space for long enough, eventually you come across fasting. Because fasting is one of the ways to reliably extend the lifespan in animal models. So it's not this superfood or this wonder drug, but somehow fasting is activating what I call this inherent dormant longevity bio program that we all have inside of us, but just isn't ordinarily turned on. So that's what really propelled me into I have to figure out what is going on in the body during a fast and whether or not there's a way that we can recreate it, turn that longevity bio program on without having to do alternate day fasting for the rest of our lives.
00:06:03
Speaker 3: So you gave us a list of benefits of intermittent fasting. Is that based on mainly animal data or clinical data or where does that come from?
00:06:12
Speaker 2: It's definitely a mix of both. So definitely the lifespan extension data, that's all going to be coming from animals. On the disease prevention components, that's a lot of animal data, but lots of human data on that as well.
00:06:26
Speaker 3: How long has intermittent fasting been around? Sometimes we think of this as being a little trendy and out there. How long has it been around?
00:06:34
Speaker 2: I would say, from an evolutionary point of view, as long as humans have existed, there has been intermittent fasting. This is more or less the way that we evolved to engage with our environment, survive and eat, right? And you go through naturally these cycles of, you know, feast and famine, intermittent fasting.
00:06:54
Speaker 3: So you also gave us a long list of different ways to achieve intermittent fasting. What does research say about which ways are most beneficial for disease prevention or longevity preservation?
00:07:05
Speaker 2: Yeah, that's a great question. So generally what we see with intermittent fasting research is that the most beneficial interventions for longevity are going to be alternate day fasting. So that's a period of eating normally and then fasting, eating normally and then fasting and then rinse and repeat throughout an entire organism's lifespan. And a lot of the times that's actually without reducing calories. There are some really cool studies out there. showing that the benefits of intermittent fasting are not like totally tied to caloric restriction. It's definitely a portion, but fasting has its own special benefits that it provides as well. So from a lifespan extension, longevity perspective, alternate day fasting is kind of the best information that we have right now. But from a more holistic, how can this help with disease management? Usually what we find is fasting under medically supervised conditions can be really beneficial, especially for things like enhancing autophagy.
00:08:05
Speaker 3: So let's talk about the molecular mechanisms a little bit and focus maybe on autophagy, because that's a word we hear an awful lot in the longevity space.
00:08:13
Speaker 2: Definitely.
00:08:14
Speaker 3: So can you unpack a little bit, what is autophagy? Why is it important? Why should we care about it? How is intermittent fasting impacting autophagy?
00:08:24
Speaker 2: So autophagy, a complicated word, but it also says exactly what it is. So It's autophagy, which is basically self-eating, and that's what's happening during autophagy. Your cells will enter this state where they realize that they don't have a lot of nutrients around, and so they will turn on, essentially, these cellular recycling processes where they'll go out, they'll find dysfunctional, broken, old proteins, organelles, they'll break them down into their parts, and then use those parts to create new proteins that are functional or new organelles that are functional. And so that whole process is essentially how our cells conserve resources and conserve energy when there's not a lot of nutrients or energy around in general. You can think of this as a process of essentially cellular rejuvenation, right? We're taking these old out-of-shape parts and and we're turning them into shiny new parts, which really helps with cellular health. And then it also helps with cellular functionality as well. When you have a bunch of new parts that are working correctly, you don't have any of the old ones that are maybe spitting out cellular junk or pro-oxidants or any kind of just not functioning at full capacity, then you're going to have greater cellular function overall because you're just going to have the new stuff and none of the old stuff. The healthier our cells are, the healthier we are, and having better functionality over time, the more healthy and functional we're going to be as well.
00:10:00
Speaker 3: So are there any other ways to stimulate autophagy without fasting?
00:10:05
Speaker 2: Yes, there definitely are. One that we know of right now is this molecule called spermidine. And spermidine is an autophagy enhancer, essentially. And that will just promote autophagy. It's naturally produced by the body, number one, but it's also something that you can get in your diet. It's present a lot in things like wheat germ, and whole grains and seeds because that's also part of their growth cycle. But also, outside of fasting, you can also promote autophagy through protein restriction. One of the main things that inhibits autophagy is mTOR, which is both associated with aging and also associated with growth. So when you take in protein, it's a big stimulator of mTOR, which then will ultimately help inhibit autophagy because it's very much a recycling process. And if you have plenty of proteins and nutrients around, autophagy typically is not going to be turned on. Okay.
00:11:07
Speaker 3: So then how do you reconcile that with the midlife woman that I actually recommend eat a significant amount of protein to maintain muscle mass and build muscle?
00:11:16
Speaker 2: Yeah, there's always going to be a trade-off for sure. So I would say intermittent fasting is going to be probably the best bet there. That's how I like to use intermittent fasting because I'm also definitely into building muscle and taking in protein because it is so important and essential. And it's one of the most metabolically beneficial macronutrients that you can have, but also we don't want those pro-aging effects. So That's how intermittent fasting can really come in is that you can have these cycles of both anabolism and growth that are going to help maintain your muscle mass, your strength, and your mobility while also having these periods of catabolism and fasting.
00:12:01
Speaker 3: We blew by ketosis. What is ketosis and how does that play in intermittent fasting? Mm-hmm.
00:12:09
Speaker 2: So ketosis is essentially once your body runs through all of its stored carbohydrates, its glycogen stores, like we were talking about before. It no longer has carbohydrates to utilize for fuel, which it prefers to do because it likes to take the carbohydrates and create blood glucose, which we need just to survive. The brain is a obligate glucose consumer, which means that it needs energy from glucose. So your body will always be making glucose in some way or another. And the easiest way that it has to do that is just through the breakdown of glycogen. Once the glycogen is gone, then you'll switch over to ketosis, which is essentially breaking down fat in order to create the ketone bodies, which then serve as an alternative fuel source to mainly the rest of the body, but also to the brain. So ketones can fuel every organ in your body, including muscle, liver, kidneys, what have you, and they will also fuel your brain. So you'll be creating a lot of ketones from fats when you're fasting. So very big metabolic switch from carbohydrate metabolism to fat and ketone metabolism that happens during fasting. And then the other major component of that is that your brain will still need the glucose. So instead of being able to get it from glycogen, it will start breaking down proteins in your body in order to make glucose from that. So it'll start breaking down proteins to create the glucose that the brain needs to survive. But that is in general how ketosis works and how it fits into fasting.
00:13:44
Speaker 3: Any data with IF and brain health?
00:13:47
Speaker 2: Yeah, definitely. And the evolutionary mechanism behind that is really cool because it makes total sense to what we were talking about before, how humans did not evolve to be in this nutrient-rich environment that we find ourselves in now. We evolved to go through these periods of fasting and feeding. And during the periods of fasting, when there is not a lot of food or nutrients available, our brains... are going to become a lot more focused on being able to find that food, right? It doesn't do your body any good to be doubled over in hunger pangs or not able to think clearly when there's no food around. That's when your brain really needs to kick into high gear and be able to recognize patterns better. It needs to be able to remember where things are. Like, where was that, you know, that field of berries that I remember? Or you know, okay, how am I going to trap this rabbit or this gazelle or whatever it is, right? So during periods of fasting, that's a mechanism by which in nutrient deprivation, our brains are better at solving problems so they can get food.
00:14:58
Speaker 3: We need to take a quick break. When we return, we dive into weight loss. Does intermittent fasting or calorie restriction lead to better results? The answer may surprise you. We've talked about longevity. We've talked about brain health. Let's talk a little bit about weight loss and ability to maintain weight with IF. But let's talk about weight loss first. My husband recently did IF and really lost like 30 pounds still eating his bang bang chicken sandwich. Still eating like kind of what I consider junk food. But let's talk about IF and weight loss. Would somebody want to do IF for weight loss?
00:15:42
Speaker 2: This is always a really fascinating question because You can definitely do intermittent fasting for weight loss. A lot of people find that intermittent fasting for weight loss is kind of the easier way to do it because it really separates when you're supposed to be eating and when you're not supposed to be eating. And so it helps people kind of naturally reduce calories without all that much effort versus chronic caloric restriction where You kind of always feel like you're in a hungry state to a certain degree or kind of always feel like you're in a deprived state to a certain degree. Intermittent fasting avoids that problem of you are only ever going to feel like you're in a hungry or deprived state during the fasting window. And then you kind of get to release that and you get to then kind of... get all of your calories in a shorter window, which feels more like a treat. It feels much better for people, I think, in general, because it's almost like mini vacations rather than just like a slog of endless weeks and months of constantly cutting back. A lot of people do find that intermittent fasting for weight loss ends up being easier than chronic caloric restriction. However, in the scientific literature, what we have seen is that there is not that much of a difference between chronic caloric restriction and intermittent fasting in terms of the type of weight loss that it's going to achieve, mainly because all weight loss is part of an energetics equation. So it's always going to be based around the amount of calories that you're putting into the body versus the amount of calories that are being expended by the body. So all other things being equal, if you are, say, cutting out 300 calories a day with chronic caloric restriction, or you're cutting out 300 calories a day via intermittent fasting, you're going to achieve incredibly similar, if not identical, weight loss results.
00:17:36
Speaker 3: So what do we do about the person who doesn't need to lose weight, but wants to maybe change their body comp, lift weights, typical midlife woman, right? Needs to change body comp, get rid of the visceral fat. And how does IF segue into that in terms of being able to build muscle, change your body comp, not just lose weight?
00:17:54
Speaker 2: Yeah, you can really optimize the catabolism that you're doing and the anabolism that you're doing to make sure that you're retaining your muscle mass properly. When I'm in my eating phase, that's when I can focus more on anabolism, building things up so I can do strength training then, things that are going to need more protein and things that are going to need more energetics that then can be incorporated into muscle mass. So this is actually a lot of how I live my life right now. I'm doing one meal a day, generally speaking. And so I really like to work out in the morning doing cardio to just really promote the catabolic effect and the fat breakdown effect of all of that. And then I'll usually work out again at the end of the day, still in the fastest state. That'll all be strength training and resistance training. And then almost immediately after I do the strength training and resistance training, that's when I'll have my one meal in the day. So I'm immediately... giving my system a lot of protein, a lot of, um, a lot of nutrients that then give it the growth signal that it need to say, okay, great preserve muscle mass.
00:19:05
Speaker 3: What do you think about the advice that women should not strength train or workout in a fasted state?
00:19:12
Speaker 2: I would say that you should just be doing it anyway. You know, like there, there's not a lot of research to show us one way or another, unfortunately, Because for a very long time, there just has not been enough research that's been done on women and especially not in the fasting space. I would say that, you know, if you want to strength train, just go and do it. That's the most important thing for longevity is just preserving that muscle mass, preserving that balance, preserving your flexibility, making sure your bone density is high. And strength training helps you do all of those things. So fasted state or non-fasted state, just go out and do it.
00:19:49
Speaker 3: Let's talk about GLP-1s. How have the use and proliferation of GLP-1s really impacted intermittent fasting? I mean, can you do a GLP-1 and do IF, or how does that work?
00:19:59
Speaker 2: I would say that you definitely can do intermittent fasting on a GLP-1. Most people on a GLP-1 find that intermittent fasting is actually much easier because GLP-1s really take away that desire, craving, even interest in food for a lot of people. And So anything that you're doing, like chronic caloric restriction or intermittent fasting, that can definitely be aided by a GLP-1 because you're just not going to have the same level of cravings, food noise, distraction that you ordinarily would have. The one problem that can come up during intermittent fasting and a GLP-1, especially like, you know, let's say it's me. We're doing one meal a day. I'm on a GLP-1. I'm sure I'm going to feel fine throughout most of the day because it's like I don't have these hunger responses anymore. So the fasting part is really easy. But then I'm going to get to my one meal a day and suddenly I have to eat, you know, 2000 calories in order to sustain, you know, like a healthy body weight.
00:20:59
Speaker 3: Right.
00:21:00
Speaker 2: And I might not be able to eat all of that in one setting because the GLP-1 is like really going to shut it down. So I would say that that is one of the primary concerns with GLP-1s and intermittent fasting is just making sure that you are getting the proper level of nutrients and especially micronutrients that you need to sustain a healthy lifestyle. in a very condensed eating window. Because if you can't, if you get halfway through what you're really supposed to be eating for the day, and all of a sudden GLP-1 is put on the brakes, then that's going to cause problems in the long term.
00:21:36
Speaker 3: So let's talk about women specifically in intermittent fasting. Is it urban myth, or is there science to back this up, that women don't tolerate intermittent fasting as well as men, and it can be more stressful for them or more stressful on their body?
00:21:52
Speaker 2: There is and there isn't. So there's a lot of anecdotal evidence to say that, you know, mainly feedback from women on like, I tried intermittent fasting and this was my problem with it. There are not a ton of studies that have ever really looked at, okay, let's take a cohort of men and let's take a cohort of women and put them on the exact same intermittent fasting schedule and see how the two respond differently and how they, um, yeah, the underlying biochemistry, as well as just the, the effort that goes into fasting and like kind of the mental strain that goes into it. In my personal experience of, uh, seeing both men and women go through a 36 hour long fasting protocol, I would say that I have definitely seen women struggle a bit more, especially with the hunger and energy components of it than men do. And I think that there is definitely like an underlying biochemical reason behind that. That has a lot to do with the hormonal cycle and the menstrual cycle that women go through. Because when we were looking at it, we were looking specifically at premenopausal women. So that can often have some effects depending on where you are in your cycle. And there's just more of the, I guess, like, you know, noise that happens that's going to be like, no, you should be eating right now. Your biology is kind of like fighting you against that to a certain degree. But unfortunately, yeah, there's not a ton of great scientific evidence to really back that up from a biochemical perspective. It just seems like This is what women report all the time when they try to actually fast.
00:23:39
Speaker 3: So for a woman who's still cycling, so premenopausal or perimenopausal, would you say that she's probably more apt to maybe cycle her intermittent fasting and do IF during the first half of the cycle and then in the second half of the cycle, the luteal phase, when she might not be feeling so great, maybe taper off of it and maybe cycle off and on of IF? Do you ever recommend that to women?
00:24:01
Speaker 2: Yeah, that could be a great approach. I think that just moving with the natural phases of your biology for anyone is always a good decision because nutrition especially is so much a different strokes for different folks kind of science. Everybody is going to have a different body. Everybody's going to have a different response to different things. So I would say that that's probably a great thing to do. Just listen to your body when you feel like fasting, when you can, when fasting is easy for you and you want to do it. go ahead and do it. And when it's not, listen to what your body is telling you.
00:24:36
Speaker 3: Let's talk about the risk of IF. You talked about medically supervised IF and such. What are the risks to IF? And what if I've had an eating disorder in the past? Yeah.
00:24:45
Speaker 2: Generally speaking, I would say if you have had a pattern of disorder eating, intermittent fasting might not be right for you because it can be very triggering for some people. Again, it's one of those things where if you have made really good steps in being able to have a healthier relationship with food and you want to give it a shot and it works out for you. That's great. But definitely do understand like the risks, especially if it's, you know, if it's bulimia and there's like a binge purge mentality, intermittent fasting can exacerbate that because you're basically building that into your daily life of like, I'm not doing anything here and I'm going to have like a really big meal. So it's definitely always going to be, again, like a different strokes for different folks situation. But yes, do be aware of the risks that it can be a triggering behavior and that some folks might find it helpful and some folks might find it really harmful. So talk to your doctor, talk to your clinician, talk to your counselor, your therapist, whoever it might be that's helping you with the disordered eating and see what might be right for you.
00:25:48
Speaker 3: We talked a little bit about food noise, which is huge. And GLP-1s help to get rid of food noise. Do you think IF helps to get rid of food noise also for individuals?
00:25:58
Speaker 2: Yeah, I think it does. Your hunger responses really change around with IF. And I'm saying this from personal experience, but also scientific experience as well. So from the personal side of things, when I was doing my immunology fellowship at Stanford, when I was really getting into fasting, I was able to do experiments on my cells. I was able to do experiments on my blood to see how intermittent fasting actually affected me. And so I looked at my blood at like a 12 hour fast, a 16 hour fast, a 24 hour fast, a 36 hour fast, all the way up to a 72 hour fast. Just got to see all the changes that were happening at the cellular level there and was able to see, oh, my cells are really functionally enhanced. They are more antioxidant, they're more anti-inflammatory, they're more cardioprotective, they're more metabolically flexible, they have better survivability, they produce less oxidative stress, they have better repair mechanisms, they have better protection mechanisms. It's all kind of like you know, really overwhelming. And when you see that, it's kind of like the ultimate quantified self thing. You're like, oh, I'm addicted to this thing now because I can see how much it's actually helping me. So I started doing alternate day fasting for basically those two years while I was there. And your hunger levels just completely change. At this point, I am almost like immune to hunger to a certain degree because when your body goes for long periods of time, over and over and over again of just, I'm not going to eat today. It kind of ends up shutting down that biological hunger response to a certain degree because it comes to know when to expect food. A lot of hunger is based around circadian rhythms. People will often find if you have breakfast, lunch, and dinner at 8, noon, and 5, let's say, that's when your hunger responses are going to start coming in. You're going to be like, my body expects a meal at 8 a.m. And if I don't eat at 8 a.m., it gets hungry because it's like I'm anticipating food and it's not here. There's a problem and I'm going to let you know. So once you break that circadian cycle by doing something like a 24 hour fast or alternate day fasting where your body doesn't know when to expect food anymore, it oftentimes isn't going to even bother telling you that it's hungry. And part of that also has to do with an evolutionary response and like the biochemical response that happens during a fast. And this is part of the research that I was doing looking into the underlying biochemistry of fasting. What we found was that there's this specific molecule that's produced during a fast that actually has an appetite suppression effect. And this makes sense because when you're out there in the wilds, And you just don't have access to food, right? You're not making a conscious choice to intermittent fast. It's just naturally happening. It doesn't do your body any good, like we said before, to be doubled over in hunger pain, right? Like you got to go out there. You got to find those berries. You got to get that gazelle.
00:28:58
Speaker 3: So we talked a little bit about circadian rhythms. If you're going to do one meal a day fasting, should that meal be in the morning, afternoon? When should it be?
00:29:07
Speaker 2: That's like going to really depend on who you are as a person, what you like to do, what your lifestyle is like. but also the meal that you're eating at the end, beginning, or middle of the day. If it's the end of the day and you're like, great, I haven't eaten all day, I'm going to house this whole pizza, that's probably going to be not great for your sleep patterns and your circadian rhythms there. However, if I want to do one big meal at the end of the day and it's going to be a bunch of slow digesting protein and fiber and vegetables and all my micronutrients and things like that, That can actually help people fall asleep faster because then they have that big feeling of fullness and satiety that allows you to go to sleep a lot better. than you know going to bed in a fasted state which can you know be very excitatory for your nervous system because it's going to sleep essentially in a you know in an unfed state so it's going to be more like willing to get up and move around and want to go find food what we call food seeking behavior And that can happen at the end of the night too. So again, I've seen it both ways and I've seen it work for morning eaters and night eaters. Usually people don't eat midday. That's like usually not where the one meal is, but I could see that working too.
00:30:23
Speaker 3: So individualization and personalization like anything sounds like.
00:30:29
Speaker 2: Yeah, exactly. That's really what it is. And when I was at UC Davis getting my PhD, the lab that I was working in specialized in personalized nutrition. So that's where a lot of my answers are going to come from.
00:30:40
Speaker 3: I love that. So let's talk about medical contraindications to intermittent fasting. I'm pre-diabetic. I'm a type 2 diabetic. I have thyroid disease. Any of these contraindications to intermittent fasting?
00:30:55
Speaker 2: Yes, there definitely can be thyroid conditions, especially because when we're messing with fasting, we're almost naturally going to be messing with hormonal balance. So you can run into some problems there. Type 1 diabetes, certainly you have to be very careful about fasting. You have to really be on top of your insulin and glucose levels there. And I generally would not recommend intermittent fasting for type 1 diabetics. Type 2 diabetics, however, see benefit from intermittent fasting because it really helps to improve insulin sensitivity, which is the major problem with type 2 diabetes. Some other folks that might not want to do it, obviously like pregnant or nursing, not a great time to be intermittent fasting. And also just older cohorts in general, probably anybody who's at more of a risk for sarcopenia or bone loss, frailty, lack of motion, even though there are great longevity benefits to intermittent fasting, what we generally see is that intermittent fasting is really beneficial for younger cohorts. And then after age 65, is more when you want to encourage people to actually eat more because that's when you're really fighting against muscle and bone loss and you want to promote those growth pathways versus in the younger stages of life where you kind of want to control them more and lean more towards the anti-aging catabolic pathways like AMPK and NRF2 and things like that. And not promote quite so much of the out-of-control mTOR signaling or IGF-1 signaling that can lead to pro-aging effects.
00:32:40
Speaker 3: What about an active strength training individual who's really paying attention to their health and longevity, who has a lot of muscle, not aging passively, but aging actively? Would you say for somebody who's 65, 70, good muscle mass.
00:32:55
Speaker 3: Good activity, good cardiovascular health that actually IF could be beneficial for them, or is it just not beneficial at all?
00:33:03
Speaker 2: I would say that it can definitely still be beneficial, for sure. The longevity effects of the caloric restriction or the lack of nutrient intake, the fasting itself, are going to be conserved. Then as long as you're actively maintaining good muscle mass, good bone density, you're doing the strength training, if you're monitoring yourself to make sure that you know, you're not in a, in some kind of, you know, free fall in any of those things, then I think that intermittent fasting can definitely still be a good option. It's typically for folks who are not as actively managing that, you know, if you're going to be what we, what we like to call in my business, a active health optimizer, you know, a lot, a lot of things are going to be, you know, more beneficial for you because you just, you know, more about your body. You've been doing it for forever. And you're making sure that everything you're doing is actually healthy a lot more than an ordinary person, especially an ordinary sedentary person is going to.
00:34:00
Speaker 3: Yeah, I think that sometimes as we age, we think of older people such as myself as just backsliding and becoming a little bit more passive and everything. So I think there's some of us who are like super active about our aging and think that maybe IF could be helpful to us too, even though we're past a chronologic age.
00:34:17
Speaker 2: Yeah, no, for sure. That's part of the tension. There's always going to be a balance that has to be struck between anabolism and catabolism, between fasting and feeding, between the anti-aging pathways and the pro-aging, but still pro-growth and pro-muscle retention pathways. So you're just constantly moving in and out of those cycles. And the cycling between the two extremes is really the thing that creates good health balance.
00:34:46
Speaker 3: Still to come, how can you get the benefits of fasting without having to fast? Plus, we discuss the most important nutrition advice that everyone needs to know. Let's talk about fasting mimicking. What is it and what is a fasting mimicking diet and why would you do that and not do intermittent fasting?
00:35:17
Speaker 2: So yeah, there's two different types of fasting mimicking, the fasting mimicking diet, and then there's the other category, which is more what I do, which is fasting mimetics. So a fasting mimicking diet is essentially a specialized diet that is designed to give you a just enough calories, but not so many that it kicks your body out of a fasting state. And then also it is designed with macronutrient and micronutrient profiles to also not kick you out of a fasting state. And to a certain degree, that is marketing, and to another degree, that is biologically accurate. And what the distinction comes down to is typically caloric intake. So With a fasting mimicking diet that exists right now, it's about like a five-day meal program that essentially gives you around 700 calories a day on average. The reason why this works, biologically speaking, is because you know, if you're doing 700 calories a day, that's very, very severe caloric restriction. And that is going to have like very dramatic impacts on your body, your metabolism, how your body operates. That's usually what a fasting mimicking diet ends up being. And around that like five day protocol as well. So you can definitely get benefits from that. But one of the problems with those is, of course, that you have to eat 700 calories a day, which Some people don't have a problem with and other people find, you know, like incredibly challenging, even more challenging than intermittent fasting itself. On the other side of the coin, you have fasting memetics like Mimeo, which is what my company makes. And that was based on my seven years of clinical research that I was doing as part of my Ph.D., we looked at what happens in the body during a 36-hour fast. And what we found was that there was a unique set of molecules produced by the body that were elevated during these prolonged periods of fasting. And when we screened through those molecules, we were able to find this synergistic combination of four of them that when we put them together, we could recreate these same cellular health effects, we could recreate these same metabolic effects, these anti-inflammatory, antioxidant effects. We were able even to extend lifespan in animal models by 96% just by using these, you know, fasting memetic molecules. So essentially what a fasting memetic is, is it's taking what your body would naturally produce during a fast and then just giving it back to you as a supplement so that you can recreate fasting at the molecular level, get those same benefits without actually having to fast. So it's kind of like a big biohack. And of course, the reason why you would want to do that is because you can get a lot of those same longevity, metabolic, cellular health benefits just through taking a pill and eating normally. And we've done three clinical studies to show that at this point. And then it can also be used as a fasting enhancer. So if you're doing something shorter, like a 16-8 fast or a 24-hour fast, then this can actually help you to accelerate the benefits of your fasts, give you benefits that you might not otherwise experience, like the autophagy that we were talking about before, and also just help make fasting easier because that molecule that we were talking about before, oleoethanolamide, is also in this formulation. So it can give you hunger and appetite suppression effects that can make fasting easier.
00:38:51
Speaker 3: How do you measure success in your clinical trials and your data, and how does this apply to women?
00:38:57
Speaker 2: Yeah, great question. So We measure success through clinical blood markers, through epigenetic tests for biological age, as well as clinically validated surveys on cognition, hunger levels, quality of life, things like that, stress levels as well. So we're doing everything from a clinical perspective, looking at the blood work and using clinically validated tools in everything that we do. We've been able to show improved glucose levels. We've been able to show better cholesterol levels as well, lower cellular stress levels, lower oxidative stress levels in the body. And then, of course, we also saw like these clinically validated reductions in appetite, cravings, food noise, distractions from food, mealtime appetite, daily appetite, like a lot of different metrics. So that's really like our goalposts there are trying to recreate at the cellular level and then at the whole body level these benefits of fasting.
00:39:58
Speaker 3: And female-specific?
00:40:01
Speaker 2: In our studies, because I was brought up in the nutrition department of UC Davis, which is female-dominated and awesome, we got a lot of education around how underserved women have been in science and scientific research. And so we're making sure that everything we do is applicable to the entire population and not just one subset or the other.
00:40:25
Speaker 3: And when you speak about intermittent fasting or fasting mimicking molecules, should you change your macros? Like if I'm 30% protein, 30% carbs, and the remainder fat, right, do I change that with IF or mimicking types of strategies?
00:40:45
Speaker 2: No, you really shouldn't have to. With Intermittent fasting itself, I would generally lean more towards the protein side of things than anything else, just to make sure that you are preventing any potential muscle loss that could be happening. Especially if you're doing deeper stages of fasting, that's really going to be when it becomes most important. Probably if you're doing a three-day fast or anything beyond that, you really want to make sure that when you're eating, you're prioritizing protein. And before you go into that fast, you go in with a good degree of glycogen stores as well. So kind of more on the protein and carbohydrate heavy side rather than the fat heavy side going into it. But if you're doing, you know, just general intermittent fasting, one meal a day, even alternate day fasting, you don't generally have to modify your macros all that much except for, again, like an emphasis on protein. But I don't have to tell people to eat more protein at this point in time. And then with the fasting mimicking, you really don't have to change anything at all. When we did the clinical studies, we just had people come in and eat normally, didn't change exercise, didn't start fasting more, didn't have any kind of dietary change whatsoever. And we still saw these fasting-like benefits.
00:42:01
Speaker 3: So I just want to talk about general nutrition in women. For women in midlife, where do you see mistakes made? And what is the one thing that you would advise midlife women for their nutrition?
00:42:13
Speaker 2: Yeah, generally in midlife, I would say that the biggest mistake that I see is like some kind of yo-yo dieting in some way or another, where I think that a lot of times people don't have a good understanding of how long-term nutrition works because they kind of assume like, okay, I'm going to go on this big crash diet. I'm going to be very, very restrictive for this very short amount of time, and then I'm going to get to my goal weight, and then I'm going to release that pressure on myself. And then they get surprised when the weight comes back on, right? So the best thing that you can do, and the thing that I see people really struggle with, especially in middle age, because of changes in metabolism, because of changes in hormones, because of changes in hunger levels, is that constantly getting stuck in this cycle of, trying this diet, it works for a while, and I like go off of it, and I like regain more weight, and then I come back down again, but then I regain more weight, and you kind of get into this upward trend of really deregulating your appetite responses, deregulating your circadian rhythms around food, deregulating your relationship with food to a certain degree that then kind of cascades as we get older. So that's kind of one of the main issues that I see is that people are not adopting sustainable lifestyle changes and nutrition changes that they can actually sustain long term so my biggest advice for people anytime you're ever gonna try to do any kind of nutrition intervention exercise intervention whatever it is just ask yourself could i do this for the rest of my life and if the answer is no don't do that thing don't start yeah don't start.
00:43:55
Speaker 3: Any supplements that you would recommend for midlife women across the board.
00:44:00
Speaker 2: Yeah, across the board, based on what we have available to us in the scientific data, calcium, of course, is going to be a good one. Calcium, vitamin D, omega-3s, those are going to be the main things that you really want to make sure that you're getting enough of. Magnesium is another big one, especially for sleep quality. Magnesium is also a very easy one to recommend because we find a lot of people to be deficient in magnesium, which has a whole host of problems. So that's one that I always very easily recommend to everyone. In terms of longevity, we know specific natural supplements right now that have been tested in the NIA's intervention testing program for lifespan extension. And so the validated ones that we have at the moment are astaxanthin, And then glycine itself. So glycine is a big component of like collagen peptides. And then astaxanthin is a very, very potent antioxidant that seems to help with immune regulation as people get older.
00:45:07
Speaker 3: What about creatine?
00:45:09
Speaker 2: Yeah, creatine is another great one. Anything that you can do to maintain strength is going to be great. And then the new data on creatine is that it also helps to improve cognition. And it's also one of the most well-studied supplements in history. I think it is the one with the most clinical studies backing it up, showing its safety. and efficacy. It's not just for bodybuilders anymore.
00:45:35
Speaker 3: So I want to learn more about intermittent fasting. I want to maybe try it. Where do I go to get that information?
00:45:42
Speaker 2: Yeah, if you want to learn more about intermittent fasting, there are some great scientific review papers about that. But generally speaking, if you're not, you know, as nerdy as I am, PhD in nutrition, You can go to sources like Healthline. I love what Healthline does. They back everything that I re-articled with a lot of scientific evidence and a lot of scientific data. So if you just want an easy access point to learn more about intermittent fasting, I would definitely check out Healthline.
00:46:13
Speaker 3: I was so fascinated by the growing body of research around intermittent fasting, fasting-mimicking diets, and fasting-mimicking supplements. This is a space I'll continue to follow as it develops, but it's clear at this point it's more than just a fad. As Dr. Rhodes and others' research has shown, IF may help with weight loss, and people are studying it for longevity, and medically supervised fast may be helpful to people living with autoimmune diseases. As with anything, intermittent fasting can be a tool, but it might not be the right one for you. Consult your doctor or registered dietitian to see if intermittent fasting is something you may be interested in trying. For me, the main questions for women who are considering intermittent fasting are 1. Can you get enough protein? When you have limited eating windows, it's super important to make sure you're still getting the protein and other nutrients necessary to support your overall health. And 2. Strength training. Personally, I don't want to train in a fasted state and I want to eat after I train. Your muscles need that energy to support you. So I'd stress it's worth thinking about your life and your schedule and how you fit this all in. I encourage women of all ages to be active participants in their health. As I often say, it's never too late to start strength training. There are so many benefits like preventing muscle loss, strengthening your bones and and even protecting your brain health. And even if you're not considering fasting, you may want to explore whether supplementing your diet with calcium, magnesium, vitamin D, omega-3s, and creatine could help improve your bone health, your sleep quality, and your overall health. And of course, as always, the key to unlocking better health outcomes will always be a personalized approach. Decoding Women's Health is a production of Pushkin Industries and the Atria Health and Research Institute. This episode was produced by Amy Gaines McQuaid. It was edited by our executive producer, Alexander Gerriton. Fact-checking by Abigail Abrams. Mastering by Sarah Berger. Our theme song was composed by Hannes Braun. Concept and Creative Development by Siobhan O'Connor. Special thanks to Vicki Merrick, Alan Tisch, David Saltzman, Dr. David Dodik, Sarah Nix, Jacob Goldstein, Leah Rose, Jordan McMillan, Owen Miller, Eric Sandler, Morgan Ratner, and Greta Cohn.
00:48:54
Speaker 2: I'm Dr.
00:48:55
Speaker 3: Elizabeth Pointer. Thanks for listening, and until next time.
Speaker 1: This show is not a substitute for professional medical advice, diagnosis, or treatment. It is for informational purposes. Please consult your healthcare professional with any medical questions. Also, in this show, we use women as shorthand for people with XX chromosomes. We understand sex and gender are more complex. and acknowledge the experiences we describe reach beyond that word.
00:00:54
Speaker 2: When I was doing my immunology fellowship at Stanford, when I was really getting into fasting, I was able to do experiments on my cells. I was able to do experiments on my blood to see how intermittent fasting actually affected me. And so I looked at my blood at like a 12-hour fast, a 16-hour fast, a 24-hour fast, a 36-hour fast, all the way up to a 72-hour fast. just got to see all the changes that were happening at the cellular level there.
00:01:19
Speaker 3: That's Dr. Chris Rhodes. He's a researcher who has spent much of his career steeped in the science of intermittent fasting. He earned his PhD in nutritional biochemistry at UC Davis, and I invited him on the show today to unpack the way fasting works and what the research says about the impact fasting can have on everything from longevity to weight loss and even brain health. Now, I should say up front, intermittent fasting is not for everybody. There's plenty of anecdotal evidence that women in particular don't necessarily tolerate fasting well. Personally, I haven't found it to be successful. But my husband, a recent convert to intermittent fasting, really loves it. He's lost a ton of weight and advocates to just about anybody who will listen to him about the benefits of intermittent fasting. And as you'll hear, Dr. Rhodes has applied much of what he has learned through his research to his daily eating habits also.
00:02:22
Speaker 2: Dr.
00:02:23
Speaker 3: Rhodes is the co-founder of Mimeo, a biotech company that has been developing supplements to help our bodies unlock the same health benefits that research has shown intermittent fasting can provide. And I want to say, even if you're thinking right now, no way, fasting is not for me, there's still lots in this conversation. about how to personalize your approach to nutrition, and about how to potentially access the same health benefits of fasting without actually needing to fast that we can all apply to our lives. So let's just get right into it. Let's talk about intermittent fasting. And let's just start with a straight, forward, short explanation about what is intermittent fasting. And I think it's also referred to as IF, right?
00:03:11
Speaker 2: Yep, it is. And that is actually like, seems like a simple question, but is a little bit more complicated than most people think. There's many different kinds of intermittent fasting, but by and large, just as an overarching general definition, intermittent fasting is just going for long periods of time without taking in calories. So that's just, you know, like no food, but like water, coffee, tea, non-caloric beverages, all of those would be allowed. And then after you're done fasting, you go back to eating for a while and typically eating normally. So there's different types that go into that. There's the most common type, which is 16-8, which is fasting for 16 hours and eating in an eight-hour window. This is more what we consider to be like time-restricted eating. Then there's also one meal a day. Oh, man, that's pretty self-explanatory. You're just eating the one meal a day and fasting for the rest of the time. Then there's more complicated protocols like alternate day fasting, where you're eating normally one day, fasting the next day, rinse and repeat basically forever. And then there's multi-day fasting, which is usually three to five days, sometimes up to a week, sometimes up to two weeks, depending on what the person is trying to achieve or if there's some kind of medical intervention that's happening to get that fasting going. So that's kind of the broad strokes category buckets that we kind of put intermittent fasting into.
00:04:37
Speaker 3: How did you become interested in this space? And what led you to get your degree in advanced nutritional biology?
00:04:46
Speaker 2: I got my BS in biochemistry from Loyola Marymount University down in L.A., I took an immunology fellowship at Stanford, just kind of trying my hand at lab science, going through all of the papers that I could get my hands on, going to all the research seminars, and eventually came across healthy aging and longevity research, which I thought was so fascinating because it used to be a myth and legend, Ponce de Leon and the Fountain of Youth and all of that stuff that has now become a very, very rigorous and very, very active section of scientific discovery. And when you're in that space for long enough, eventually you come across fasting. Because fasting is one of the ways to reliably extend the lifespan in animal models. So it's not this superfood or this wonder drug, but somehow fasting is activating what I call this inherent dormant longevity bio program that we all have inside of us, but just isn't ordinarily turned on. So that's what really propelled me into I have to figure out what is going on in the body during a fast and whether or not there's a way that we can recreate it, turn that longevity bio program on without having to do alternate day fasting for the rest of our lives.
00:06:03
Speaker 3: So you gave us a list of benefits of intermittent fasting. Is that based on mainly animal data or clinical data or where does that come from?
00:06:12
Speaker 2: It's definitely a mix of both. So definitely the lifespan extension data, that's all going to be coming from animals. On the disease prevention components, that's a lot of animal data, but lots of human data on that as well.
00:06:26
Speaker 3: How long has intermittent fasting been around? Sometimes we think of this as being a little trendy and out there. How long has it been around?
00:06:34
Speaker 2: I would say, from an evolutionary point of view, as long as humans have existed, there has been intermittent fasting. This is more or less the way that we evolved to engage with our environment, survive and eat, right? And you go through naturally these cycles of, you know, feast and famine, intermittent fasting.
00:06:54
Speaker 3: So you also gave us a long list of different ways to achieve intermittent fasting. What does research say about which ways are most beneficial for disease prevention or longevity preservation?
00:07:05
Speaker 2: Yeah, that's a great question. So generally what we see with intermittent fasting research is that the most beneficial interventions for longevity are going to be alternate day fasting. So that's a period of eating normally and then fasting, eating normally and then fasting and then rinse and repeat throughout an entire organism's lifespan. And a lot of the times that's actually without reducing calories. There are some really cool studies out there. showing that the benefits of intermittent fasting are not like totally tied to caloric restriction. It's definitely a portion, but fasting has its own special benefits that it provides as well. So from a lifespan extension, longevity perspective, alternate day fasting is kind of the best information that we have right now. But from a more holistic, how can this help with disease management? Usually what we find is fasting under medically supervised conditions can be really beneficial, especially for things like enhancing autophagy.
00:08:05
Speaker 3: So let's talk about the molecular mechanisms a little bit and focus maybe on autophagy, because that's a word we hear an awful lot in the longevity space.
00:08:13
Speaker 2: Definitely.
00:08:14
Speaker 3: So can you unpack a little bit, what is autophagy? Why is it important? Why should we care about it? How is intermittent fasting impacting autophagy?
00:08:24
Speaker 2: So autophagy, a complicated word, but it also says exactly what it is. So It's autophagy, which is basically self-eating, and that's what's happening during autophagy. Your cells will enter this state where they realize that they don't have a lot of nutrients around, and so they will turn on, essentially, these cellular recycling processes where they'll go out, they'll find dysfunctional, broken, old proteins, organelles, they'll break them down into their parts, and then use those parts to create new proteins that are functional or new organelles that are functional. And so that whole process is essentially how our cells conserve resources and conserve energy when there's not a lot of nutrients or energy around in general. You can think of this as a process of essentially cellular rejuvenation, right? We're taking these old out-of-shape parts and and we're turning them into shiny new parts, which really helps with cellular health. And then it also helps with cellular functionality as well. When you have a bunch of new parts that are working correctly, you don't have any of the old ones that are maybe spitting out cellular junk or pro-oxidants or any kind of just not functioning at full capacity, then you're going to have greater cellular function overall because you're just going to have the new stuff and none of the old stuff. The healthier our cells are, the healthier we are, and having better functionality over time, the more healthy and functional we're going to be as well.
00:10:00
Speaker 3: So are there any other ways to stimulate autophagy without fasting?
00:10:05
Speaker 2: Yes, there definitely are. One that we know of right now is this molecule called spermidine. And spermidine is an autophagy enhancer, essentially. And that will just promote autophagy. It's naturally produced by the body, number one, but it's also something that you can get in your diet. It's present a lot in things like wheat germ, and whole grains and seeds because that's also part of their growth cycle. But also, outside of fasting, you can also promote autophagy through protein restriction. One of the main things that inhibits autophagy is mTOR, which is both associated with aging and also associated with growth. So when you take in protein, it's a big stimulator of mTOR, which then will ultimately help inhibit autophagy because it's very much a recycling process. And if you have plenty of proteins and nutrients around, autophagy typically is not going to be turned on. Okay.
00:11:07
Speaker 3: So then how do you reconcile that with the midlife woman that I actually recommend eat a significant amount of protein to maintain muscle mass and build muscle?
00:11:16
Speaker 2: Yeah, there's always going to be a trade-off for sure. So I would say intermittent fasting is going to be probably the best bet there. That's how I like to use intermittent fasting because I'm also definitely into building muscle and taking in protein because it is so important and essential. And it's one of the most metabolically beneficial macronutrients that you can have, but also we don't want those pro-aging effects. So That's how intermittent fasting can really come in is that you can have these cycles of both anabolism and growth that are going to help maintain your muscle mass, your strength, and your mobility while also having these periods of catabolism and fasting.
00:12:01
Speaker 3: We blew by ketosis. What is ketosis and how does that play in intermittent fasting? Mm-hmm.
00:12:09
Speaker 2: So ketosis is essentially once your body runs through all of its stored carbohydrates, its glycogen stores, like we were talking about before. It no longer has carbohydrates to utilize for fuel, which it prefers to do because it likes to take the carbohydrates and create blood glucose, which we need just to survive. The brain is a obligate glucose consumer, which means that it needs energy from glucose. So your body will always be making glucose in some way or another. And the easiest way that it has to do that is just through the breakdown of glycogen. Once the glycogen is gone, then you'll switch over to ketosis, which is essentially breaking down fat in order to create the ketone bodies, which then serve as an alternative fuel source to mainly the rest of the body, but also to the brain. So ketones can fuel every organ in your body, including muscle, liver, kidneys, what have you, and they will also fuel your brain. So you'll be creating a lot of ketones from fats when you're fasting. So very big metabolic switch from carbohydrate metabolism to fat and ketone metabolism that happens during fasting. And then the other major component of that is that your brain will still need the glucose. So instead of being able to get it from glycogen, it will start breaking down proteins in your body in order to make glucose from that. So it'll start breaking down proteins to create the glucose that the brain needs to survive. But that is in general how ketosis works and how it fits into fasting.
00:13:44
Speaker 3: Any data with IF and brain health?
00:13:47
Speaker 2: Yeah, definitely. And the evolutionary mechanism behind that is really cool because it makes total sense to what we were talking about before, how humans did not evolve to be in this nutrient-rich environment that we find ourselves in now. We evolved to go through these periods of fasting and feeding. And during the periods of fasting, when there is not a lot of food or nutrients available, our brains... are going to become a lot more focused on being able to find that food, right? It doesn't do your body any good to be doubled over in hunger pangs or not able to think clearly when there's no food around. That's when your brain really needs to kick into high gear and be able to recognize patterns better. It needs to be able to remember where things are. Like, where was that, you know, that field of berries that I remember? Or you know, okay, how am I going to trap this rabbit or this gazelle or whatever it is, right? So during periods of fasting, that's a mechanism by which in nutrient deprivation, our brains are better at solving problems so they can get food.
00:14:58
Speaker 3: We need to take a quick break. When we return, we dive into weight loss. Does intermittent fasting or calorie restriction lead to better results? The answer may surprise you. We've talked about longevity. We've talked about brain health. Let's talk a little bit about weight loss and ability to maintain weight with IF. But let's talk about weight loss first. My husband recently did IF and really lost like 30 pounds still eating his bang bang chicken sandwich. Still eating like kind of what I consider junk food. But let's talk about IF and weight loss. Would somebody want to do IF for weight loss?
00:15:42
Speaker 2: This is always a really fascinating question because You can definitely do intermittent fasting for weight loss. A lot of people find that intermittent fasting for weight loss is kind of the easier way to do it because it really separates when you're supposed to be eating and when you're not supposed to be eating. And so it helps people kind of naturally reduce calories without all that much effort versus chronic caloric restriction where You kind of always feel like you're in a hungry state to a certain degree or kind of always feel like you're in a deprived state to a certain degree. Intermittent fasting avoids that problem of you are only ever going to feel like you're in a hungry or deprived state during the fasting window. And then you kind of get to release that and you get to then kind of... get all of your calories in a shorter window, which feels more like a treat. It feels much better for people, I think, in general, because it's almost like mini vacations rather than just like a slog of endless weeks and months of constantly cutting back. A lot of people do find that intermittent fasting for weight loss ends up being easier than chronic caloric restriction. However, in the scientific literature, what we have seen is that there is not that much of a difference between chronic caloric restriction and intermittent fasting in terms of the type of weight loss that it's going to achieve, mainly because all weight loss is part of an energetics equation. So it's always going to be based around the amount of calories that you're putting into the body versus the amount of calories that are being expended by the body. So all other things being equal, if you are, say, cutting out 300 calories a day with chronic caloric restriction, or you're cutting out 300 calories a day via intermittent fasting, you're going to achieve incredibly similar, if not identical, weight loss results.
00:17:36
Speaker 3: So what do we do about the person who doesn't need to lose weight, but wants to maybe change their body comp, lift weights, typical midlife woman, right? Needs to change body comp, get rid of the visceral fat. And how does IF segue into that in terms of being able to build muscle, change your body comp, not just lose weight?
00:17:54
Speaker 2: Yeah, you can really optimize the catabolism that you're doing and the anabolism that you're doing to make sure that you're retaining your muscle mass properly. When I'm in my eating phase, that's when I can focus more on anabolism, building things up so I can do strength training then, things that are going to need more protein and things that are going to need more energetics that then can be incorporated into muscle mass. So this is actually a lot of how I live my life right now. I'm doing one meal a day, generally speaking. And so I really like to work out in the morning doing cardio to just really promote the catabolic effect and the fat breakdown effect of all of that. And then I'll usually work out again at the end of the day, still in the fastest state. That'll all be strength training and resistance training. And then almost immediately after I do the strength training and resistance training, that's when I'll have my one meal in the day. So I'm immediately... giving my system a lot of protein, a lot of, um, a lot of nutrients that then give it the growth signal that it need to say, okay, great preserve muscle mass.
00:19:05
Speaker 3: What do you think about the advice that women should not strength train or workout in a fasted state?
00:19:12
Speaker 2: I would say that you should just be doing it anyway. You know, like there, there's not a lot of research to show us one way or another, unfortunately, Because for a very long time, there just has not been enough research that's been done on women and especially not in the fasting space. I would say that, you know, if you want to strength train, just go and do it. That's the most important thing for longevity is just preserving that muscle mass, preserving that balance, preserving your flexibility, making sure your bone density is high. And strength training helps you do all of those things. So fasted state or non-fasted state, just go out and do it.
00:19:49
Speaker 3: Let's talk about GLP-1s. How have the use and proliferation of GLP-1s really impacted intermittent fasting? I mean, can you do a GLP-1 and do IF, or how does that work?
00:19:59
Speaker 2: I would say that you definitely can do intermittent fasting on a GLP-1. Most people on a GLP-1 find that intermittent fasting is actually much easier because GLP-1s really take away that desire, craving, even interest in food for a lot of people. And So anything that you're doing, like chronic caloric restriction or intermittent fasting, that can definitely be aided by a GLP-1 because you're just not going to have the same level of cravings, food noise, distraction that you ordinarily would have. The one problem that can come up during intermittent fasting and a GLP-1, especially like, you know, let's say it's me. We're doing one meal a day. I'm on a GLP-1. I'm sure I'm going to feel fine throughout most of the day because it's like I don't have these hunger responses anymore. So the fasting part is really easy. But then I'm going to get to my one meal a day and suddenly I have to eat, you know, 2000 calories in order to sustain, you know, like a healthy body weight.
00:20:59
Speaker 3: Right.
00:21:00
Speaker 2: And I might not be able to eat all of that in one setting because the GLP-1 is like really going to shut it down. So I would say that that is one of the primary concerns with GLP-1s and intermittent fasting is just making sure that you are getting the proper level of nutrients and especially micronutrients that you need to sustain a healthy lifestyle. in a very condensed eating window. Because if you can't, if you get halfway through what you're really supposed to be eating for the day, and all of a sudden GLP-1 is put on the brakes, then that's going to cause problems in the long term.
00:21:36
Speaker 3: So let's talk about women specifically in intermittent fasting. Is it urban myth, or is there science to back this up, that women don't tolerate intermittent fasting as well as men, and it can be more stressful for them or more stressful on their body?
00:21:52
Speaker 2: There is and there isn't. So there's a lot of anecdotal evidence to say that, you know, mainly feedback from women on like, I tried intermittent fasting and this was my problem with it. There are not a ton of studies that have ever really looked at, okay, let's take a cohort of men and let's take a cohort of women and put them on the exact same intermittent fasting schedule and see how the two respond differently and how they, um, yeah, the underlying biochemistry, as well as just the, the effort that goes into fasting and like kind of the mental strain that goes into it. In my personal experience of, uh, seeing both men and women go through a 36 hour long fasting protocol, I would say that I have definitely seen women struggle a bit more, especially with the hunger and energy components of it than men do. And I think that there is definitely like an underlying biochemical reason behind that. That has a lot to do with the hormonal cycle and the menstrual cycle that women go through. Because when we were looking at it, we were looking specifically at premenopausal women. So that can often have some effects depending on where you are in your cycle. And there's just more of the, I guess, like, you know, noise that happens that's going to be like, no, you should be eating right now. Your biology is kind of like fighting you against that to a certain degree. But unfortunately, yeah, there's not a ton of great scientific evidence to really back that up from a biochemical perspective. It just seems like This is what women report all the time when they try to actually fast.
00:23:39
Speaker 3: So for a woman who's still cycling, so premenopausal or perimenopausal, would you say that she's probably more apt to maybe cycle her intermittent fasting and do IF during the first half of the cycle and then in the second half of the cycle, the luteal phase, when she might not be feeling so great, maybe taper off of it and maybe cycle off and on of IF? Do you ever recommend that to women?
00:24:01
Speaker 2: Yeah, that could be a great approach. I think that just moving with the natural phases of your biology for anyone is always a good decision because nutrition especially is so much a different strokes for different folks kind of science. Everybody is going to have a different body. Everybody's going to have a different response to different things. So I would say that that's probably a great thing to do. Just listen to your body when you feel like fasting, when you can, when fasting is easy for you and you want to do it. go ahead and do it. And when it's not, listen to what your body is telling you.
00:24:36
Speaker 3: Let's talk about the risk of IF. You talked about medically supervised IF and such. What are the risks to IF? And what if I've had an eating disorder in the past? Yeah.
00:24:45
Speaker 2: Generally speaking, I would say if you have had a pattern of disorder eating, intermittent fasting might not be right for you because it can be very triggering for some people. Again, it's one of those things where if you have made really good steps in being able to have a healthier relationship with food and you want to give it a shot and it works out for you. That's great. But definitely do understand like the risks, especially if it's, you know, if it's bulimia and there's like a binge purge mentality, intermittent fasting can exacerbate that because you're basically building that into your daily life of like, I'm not doing anything here and I'm going to have like a really big meal. So it's definitely always going to be, again, like a different strokes for different folks situation. But yes, do be aware of the risks that it can be a triggering behavior and that some folks might find it helpful and some folks might find it really harmful. So talk to your doctor, talk to your clinician, talk to your counselor, your therapist, whoever it might be that's helping you with the disordered eating and see what might be right for you.
00:25:48
Speaker 3: We talked a little bit about food noise, which is huge. And GLP-1s help to get rid of food noise. Do you think IF helps to get rid of food noise also for individuals?
00:25:58
Speaker 2: Yeah, I think it does. Your hunger responses really change around with IF. And I'm saying this from personal experience, but also scientific experience as well. So from the personal side of things, when I was doing my immunology fellowship at Stanford, when I was really getting into fasting, I was able to do experiments on my cells. I was able to do experiments on my blood to see how intermittent fasting actually affected me. And so I looked at my blood at like a 12 hour fast, a 16 hour fast, a 24 hour fast, a 36 hour fast, all the way up to a 72 hour fast. Just got to see all the changes that were happening at the cellular level there and was able to see, oh, my cells are really functionally enhanced. They are more antioxidant, they're more anti-inflammatory, they're more cardioprotective, they're more metabolically flexible, they have better survivability, they produce less oxidative stress, they have better repair mechanisms, they have better protection mechanisms. It's all kind of like you know, really overwhelming. And when you see that, it's kind of like the ultimate quantified self thing. You're like, oh, I'm addicted to this thing now because I can see how much it's actually helping me. So I started doing alternate day fasting for basically those two years while I was there. And your hunger levels just completely change. At this point, I am almost like immune to hunger to a certain degree because when your body goes for long periods of time, over and over and over again of just, I'm not going to eat today. It kind of ends up shutting down that biological hunger response to a certain degree because it comes to know when to expect food. A lot of hunger is based around circadian rhythms. People will often find if you have breakfast, lunch, and dinner at 8, noon, and 5, let's say, that's when your hunger responses are going to start coming in. You're going to be like, my body expects a meal at 8 a.m. And if I don't eat at 8 a.m., it gets hungry because it's like I'm anticipating food and it's not here. There's a problem and I'm going to let you know. So once you break that circadian cycle by doing something like a 24 hour fast or alternate day fasting where your body doesn't know when to expect food anymore, it oftentimes isn't going to even bother telling you that it's hungry. And part of that also has to do with an evolutionary response and like the biochemical response that happens during a fast. And this is part of the research that I was doing looking into the underlying biochemistry of fasting. What we found was that there's this specific molecule that's produced during a fast that actually has an appetite suppression effect. And this makes sense because when you're out there in the wilds, And you just don't have access to food, right? You're not making a conscious choice to intermittent fast. It's just naturally happening. It doesn't do your body any good, like we said before, to be doubled over in hunger pain, right? Like you got to go out there. You got to find those berries. You got to get that gazelle.
00:28:58
Speaker 3: So we talked a little bit about circadian rhythms. If you're going to do one meal a day fasting, should that meal be in the morning, afternoon? When should it be?
00:29:07
Speaker 2: That's like going to really depend on who you are as a person, what you like to do, what your lifestyle is like. but also the meal that you're eating at the end, beginning, or middle of the day. If it's the end of the day and you're like, great, I haven't eaten all day, I'm going to house this whole pizza, that's probably going to be not great for your sleep patterns and your circadian rhythms there. However, if I want to do one big meal at the end of the day and it's going to be a bunch of slow digesting protein and fiber and vegetables and all my micronutrients and things like that, That can actually help people fall asleep faster because then they have that big feeling of fullness and satiety that allows you to go to sleep a lot better. than you know going to bed in a fasted state which can you know be very excitatory for your nervous system because it's going to sleep essentially in a you know in an unfed state so it's going to be more like willing to get up and move around and want to go find food what we call food seeking behavior And that can happen at the end of the night too. So again, I've seen it both ways and I've seen it work for morning eaters and night eaters. Usually people don't eat midday. That's like usually not where the one meal is, but I could see that working too.
00:30:23
Speaker 3: So individualization and personalization like anything sounds like.
00:30:29
Speaker 2: Yeah, exactly. That's really what it is. And when I was at UC Davis getting my PhD, the lab that I was working in specialized in personalized nutrition. So that's where a lot of my answers are going to come from.
00:30:40
Speaker 3: I love that. So let's talk about medical contraindications to intermittent fasting. I'm pre-diabetic. I'm a type 2 diabetic. I have thyroid disease. Any of these contraindications to intermittent fasting?
00:30:55
Speaker 2: Yes, there definitely can be thyroid conditions, especially because when we're messing with fasting, we're almost naturally going to be messing with hormonal balance. So you can run into some problems there. Type 1 diabetes, certainly you have to be very careful about fasting. You have to really be on top of your insulin and glucose levels there. And I generally would not recommend intermittent fasting for type 1 diabetics. Type 2 diabetics, however, see benefit from intermittent fasting because it really helps to improve insulin sensitivity, which is the major problem with type 2 diabetes. Some other folks that might not want to do it, obviously like pregnant or nursing, not a great time to be intermittent fasting. And also just older cohorts in general, probably anybody who's at more of a risk for sarcopenia or bone loss, frailty, lack of motion, even though there are great longevity benefits to intermittent fasting, what we generally see is that intermittent fasting is really beneficial for younger cohorts. And then after age 65, is more when you want to encourage people to actually eat more because that's when you're really fighting against muscle and bone loss and you want to promote those growth pathways versus in the younger stages of life where you kind of want to control them more and lean more towards the anti-aging catabolic pathways like AMPK and NRF2 and things like that. And not promote quite so much of the out-of-control mTOR signaling or IGF-1 signaling that can lead to pro-aging effects.
00:32:40
Speaker 3: What about an active strength training individual who's really paying attention to their health and longevity, who has a lot of muscle, not aging passively, but aging actively? Would you say for somebody who's 65, 70, good muscle mass.
00:32:55
Speaker 3: Good activity, good cardiovascular health that actually IF could be beneficial for them, or is it just not beneficial at all?
00:33:03
Speaker 2: I would say that it can definitely still be beneficial, for sure. The longevity effects of the caloric restriction or the lack of nutrient intake, the fasting itself, are going to be conserved. Then as long as you're actively maintaining good muscle mass, good bone density, you're doing the strength training, if you're monitoring yourself to make sure that you know, you're not in a, in some kind of, you know, free fall in any of those things, then I think that intermittent fasting can definitely still be a good option. It's typically for folks who are not as actively managing that, you know, if you're going to be what we, what we like to call in my business, a active health optimizer, you know, a lot, a lot of things are going to be, you know, more beneficial for you because you just, you know, more about your body. You've been doing it for forever. And you're making sure that everything you're doing is actually healthy a lot more than an ordinary person, especially an ordinary sedentary person is going to.
00:34:00
Speaker 3: Yeah, I think that sometimes as we age, we think of older people such as myself as just backsliding and becoming a little bit more passive and everything. So I think there's some of us who are like super active about our aging and think that maybe IF could be helpful to us too, even though we're past a chronologic age.
00:34:17
Speaker 2: Yeah, no, for sure. That's part of the tension. There's always going to be a balance that has to be struck between anabolism and catabolism, between fasting and feeding, between the anti-aging pathways and the pro-aging, but still pro-growth and pro-muscle retention pathways. So you're just constantly moving in and out of those cycles. And the cycling between the two extremes is really the thing that creates good health balance.
00:34:46
Speaker 3: Still to come, how can you get the benefits of fasting without having to fast? Plus, we discuss the most important nutrition advice that everyone needs to know. Let's talk about fasting mimicking. What is it and what is a fasting mimicking diet and why would you do that and not do intermittent fasting?
00:35:17
Speaker 2: So yeah, there's two different types of fasting mimicking, the fasting mimicking diet, and then there's the other category, which is more what I do, which is fasting mimetics. So a fasting mimicking diet is essentially a specialized diet that is designed to give you a just enough calories, but not so many that it kicks your body out of a fasting state. And then also it is designed with macronutrient and micronutrient profiles to also not kick you out of a fasting state. And to a certain degree, that is marketing, and to another degree, that is biologically accurate. And what the distinction comes down to is typically caloric intake. So With a fasting mimicking diet that exists right now, it's about like a five-day meal program that essentially gives you around 700 calories a day on average. The reason why this works, biologically speaking, is because you know, if you're doing 700 calories a day, that's very, very severe caloric restriction. And that is going to have like very dramatic impacts on your body, your metabolism, how your body operates. That's usually what a fasting mimicking diet ends up being. And around that like five day protocol as well. So you can definitely get benefits from that. But one of the problems with those is, of course, that you have to eat 700 calories a day, which Some people don't have a problem with and other people find, you know, like incredibly challenging, even more challenging than intermittent fasting itself. On the other side of the coin, you have fasting memetics like Mimeo, which is what my company makes. And that was based on my seven years of clinical research that I was doing as part of my Ph.D., we looked at what happens in the body during a 36-hour fast. And what we found was that there was a unique set of molecules produced by the body that were elevated during these prolonged periods of fasting. And when we screened through those molecules, we were able to find this synergistic combination of four of them that when we put them together, we could recreate these same cellular health effects, we could recreate these same metabolic effects, these anti-inflammatory, antioxidant effects. We were able even to extend lifespan in animal models by 96% just by using these, you know, fasting memetic molecules. So essentially what a fasting memetic is, is it's taking what your body would naturally produce during a fast and then just giving it back to you as a supplement so that you can recreate fasting at the molecular level, get those same benefits without actually having to fast. So it's kind of like a big biohack. And of course, the reason why you would want to do that is because you can get a lot of those same longevity, metabolic, cellular health benefits just through taking a pill and eating normally. And we've done three clinical studies to show that at this point. And then it can also be used as a fasting enhancer. So if you're doing something shorter, like a 16-8 fast or a 24-hour fast, then this can actually help you to accelerate the benefits of your fasts, give you benefits that you might not otherwise experience, like the autophagy that we were talking about before, and also just help make fasting easier because that molecule that we were talking about before, oleoethanolamide, is also in this formulation. So it can give you hunger and appetite suppression effects that can make fasting easier.
00:38:51
Speaker 3: How do you measure success in your clinical trials and your data, and how does this apply to women?
00:38:57
Speaker 2: Yeah, great question. So We measure success through clinical blood markers, through epigenetic tests for biological age, as well as clinically validated surveys on cognition, hunger levels, quality of life, things like that, stress levels as well. So we're doing everything from a clinical perspective, looking at the blood work and using clinically validated tools in everything that we do. We've been able to show improved glucose levels. We've been able to show better cholesterol levels as well, lower cellular stress levels, lower oxidative stress levels in the body. And then, of course, we also saw like these clinically validated reductions in appetite, cravings, food noise, distractions from food, mealtime appetite, daily appetite, like a lot of different metrics. So that's really like our goalposts there are trying to recreate at the cellular level and then at the whole body level these benefits of fasting.
00:39:58
Speaker 3: And female-specific?
00:40:01
Speaker 2: In our studies, because I was brought up in the nutrition department of UC Davis, which is female-dominated and awesome, we got a lot of education around how underserved women have been in science and scientific research. And so we're making sure that everything we do is applicable to the entire population and not just one subset or the other.
00:40:25
Speaker 3: And when you speak about intermittent fasting or fasting mimicking molecules, should you change your macros? Like if I'm 30% protein, 30% carbs, and the remainder fat, right, do I change that with IF or mimicking types of strategies?
00:40:45
Speaker 2: No, you really shouldn't have to. With Intermittent fasting itself, I would generally lean more towards the protein side of things than anything else, just to make sure that you are preventing any potential muscle loss that could be happening. Especially if you're doing deeper stages of fasting, that's really going to be when it becomes most important. Probably if you're doing a three-day fast or anything beyond that, you really want to make sure that when you're eating, you're prioritizing protein. And before you go into that fast, you go in with a good degree of glycogen stores as well. So kind of more on the protein and carbohydrate heavy side rather than the fat heavy side going into it. But if you're doing, you know, just general intermittent fasting, one meal a day, even alternate day fasting, you don't generally have to modify your macros all that much except for, again, like an emphasis on protein. But I don't have to tell people to eat more protein at this point in time. And then with the fasting mimicking, you really don't have to change anything at all. When we did the clinical studies, we just had people come in and eat normally, didn't change exercise, didn't start fasting more, didn't have any kind of dietary change whatsoever. And we still saw these fasting-like benefits.
00:42:01
Speaker 3: So I just want to talk about general nutrition in women. For women in midlife, where do you see mistakes made? And what is the one thing that you would advise midlife women for their nutrition?
00:42:13
Speaker 2: Yeah, generally in midlife, I would say that the biggest mistake that I see is like some kind of yo-yo dieting in some way or another, where I think that a lot of times people don't have a good understanding of how long-term nutrition works because they kind of assume like, okay, I'm going to go on this big crash diet. I'm going to be very, very restrictive for this very short amount of time, and then I'm going to get to my goal weight, and then I'm going to release that pressure on myself. And then they get surprised when the weight comes back on, right? So the best thing that you can do, and the thing that I see people really struggle with, especially in middle age, because of changes in metabolism, because of changes in hormones, because of changes in hunger levels, is that constantly getting stuck in this cycle of, trying this diet, it works for a while, and I like go off of it, and I like regain more weight, and then I come back down again, but then I regain more weight, and you kind of get into this upward trend of really deregulating your appetite responses, deregulating your circadian rhythms around food, deregulating your relationship with food to a certain degree that then kind of cascades as we get older. So that's kind of one of the main issues that I see is that people are not adopting sustainable lifestyle changes and nutrition changes that they can actually sustain long term so my biggest advice for people anytime you're ever gonna try to do any kind of nutrition intervention exercise intervention whatever it is just ask yourself could i do this for the rest of my life and if the answer is no don't do that thing don't start yeah don't start.
00:43:55
Speaker 3: Any supplements that you would recommend for midlife women across the board.
00:44:00
Speaker 2: Yeah, across the board, based on what we have available to us in the scientific data, calcium, of course, is going to be a good one. Calcium, vitamin D, omega-3s, those are going to be the main things that you really want to make sure that you're getting enough of. Magnesium is another big one, especially for sleep quality. Magnesium is also a very easy one to recommend because we find a lot of people to be deficient in magnesium, which has a whole host of problems. So that's one that I always very easily recommend to everyone. In terms of longevity, we know specific natural supplements right now that have been tested in the NIA's intervention testing program for lifespan extension. And so the validated ones that we have at the moment are astaxanthin, And then glycine itself. So glycine is a big component of like collagen peptides. And then astaxanthin is a very, very potent antioxidant that seems to help with immune regulation as people get older.
00:45:07
Speaker 3: What about creatine?
00:45:09
Speaker 2: Yeah, creatine is another great one. Anything that you can do to maintain strength is going to be great. And then the new data on creatine is that it also helps to improve cognition. And it's also one of the most well-studied supplements in history. I think it is the one with the most clinical studies backing it up, showing its safety. and efficacy. It's not just for bodybuilders anymore.
00:45:35
Speaker 3: So I want to learn more about intermittent fasting. I want to maybe try it. Where do I go to get that information?
00:45:42
Speaker 2: Yeah, if you want to learn more about intermittent fasting, there are some great scientific review papers about that. But generally speaking, if you're not, you know, as nerdy as I am, PhD in nutrition, You can go to sources like Healthline. I love what Healthline does. They back everything that I re-articled with a lot of scientific evidence and a lot of scientific data. So if you just want an easy access point to learn more about intermittent fasting, I would definitely check out Healthline.
00:46:13
Speaker 3: I was so fascinated by the growing body of research around intermittent fasting, fasting-mimicking diets, and fasting-mimicking supplements. This is a space I'll continue to follow as it develops, but it's clear at this point it's more than just a fad. As Dr. Rhodes and others' research has shown, IF may help with weight loss, and people are studying it for longevity, and medically supervised fast may be helpful to people living with autoimmune diseases. As with anything, intermittent fasting can be a tool, but it might not be the right one for you. Consult your doctor or registered dietitian to see if intermittent fasting is something you may be interested in trying. For me, the main questions for women who are considering intermittent fasting are 1. Can you get enough protein? When you have limited eating windows, it's super important to make sure you're still getting the protein and other nutrients necessary to support your overall health. And 2. Strength training. Personally, I don't want to train in a fasted state and I want to eat after I train. Your muscles need that energy to support you. So I'd stress it's worth thinking about your life and your schedule and how you fit this all in. I encourage women of all ages to be active participants in their health. As I often say, it's never too late to start strength training. There are so many benefits like preventing muscle loss, strengthening your bones and and even protecting your brain health. And even if you're not considering fasting, you may want to explore whether supplementing your diet with calcium, magnesium, vitamin D, omega-3s, and creatine could help improve your bone health, your sleep quality, and your overall health. And of course, as always, the key to unlocking better health outcomes will always be a personalized approach. Decoding Women's Health is a production of Pushkin Industries and the Atria Health and Research Institute. This episode was produced by Amy Gaines McQuaid. It was edited by our executive producer, Alexander Gerriton. Fact-checking by Abigail Abrams. Mastering by Sarah Berger. Our theme song was composed by Hannes Braun. Concept and Creative Development by Siobhan O'Connor. Special thanks to Vicki Merrick, Alan Tisch, David Saltzman, Dr. David Dodik, Sarah Nix, Jacob Goldstein, Leah Rose, Jordan McMillan, Owen Miller, Eric Sandler, Morgan Ratner, and Greta Cohn.
00:48:54
Speaker 2: I'm Dr.
00:48:55
Speaker 3: Elizabeth Pointer. Thanks for listening, and until next time.
