Episode 281: Myth Busting, Fasting Research, Fat Burning, Inflammatory Markers, Media Spin On Studies, Early Vs. Late Night Eating, And More!

Intermittent Fasting


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Sep 04

Welcome to Episode 281 of The Intermittent Fasting Podcast, hosted by Melanie Avalon, author of What When Wine Diet: Lose Weight And Feel Great With Paleo-Style Meals, Intermittent Fasting, And Wine and Cynthia Thurlow, author of Intermittent Fasting Transformation: The 45-Day Program for Women to Lose Stubborn Weight, Improve Hormonal Health, and Slow Aging.

Today's episode of The Intermittent Fasting Podcast is brought to you by:

LMNT: For Fasting Or Low-Carb Diets Electrolytes Are Key For Relieving Hunger, Cramps, Headaches, Tiredness, And Dizziness. With No Sugar, Artificial Ingredients, Coloring, And Only 2 Grams Of Carbs Per Packet, Try LMNT For Complete And Total Hydration. For A Limited Time Go To drinklmnt.com/ifpodcast To Get A FREE Sample Pack With Any Purchase!

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LMNT: For A Limited Time Go To drinklmnt.com/ifpodcast To Get A FREE Sample Pack With Any Purchase! Learn All About Electrolytes In Episode 237 - Our Interview With Robb Wolf!

BEAUTYCOUNTER: Keep Your Fast Clean Inside And Out With Safe Skincare! Shop With Us At melanieavalon.com/beautycounter or beautycounter.com/cynthiathurlow And Use The Code CLEANFORALL20 For 20% Off PLUS Something Magical Might Happen After Your First Order! Find Your Perfect Beautycounter Products With Melanie's Quiz: Melanieavalon.Com/Beautycounterquiz
Join Melanie's Facebook Group Clean Beauty And Safe Skincare With Melanie Avalon To Discuss And Learn About All The Things Clean Beauty, Beautycounter And Safe Skincare!

Get On The Email List To Stay Up To Date With All The Special Offers And News About Melanie's New Supplements At avalonx.us/emaillist, And Use The Code Melanieavalon For 10% On Any Order At Avalonx.Us And MDlogichealth.Com!

Oura Referral Link!

Get $30 Off A CGM At Nutrisense.Io/Ifpodcast With The Code IFPODCAST!

Listener Q&A: Knowles - Myth Busting3

Paleo Mom Podcast Episode 386: Intermittent Fasting

Paleo Mom Podcast Episode 381: Is Breakfast the Most Important Meal of the Day?

Intermittent Fasting: Secret to Weight Loss or Dangerous Fad? 

Is Breakfast The Most Important Meal of the Day? New Science Has Answers!

Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans  

Short-term modified alternate-day fasting: a novel dietary strategy for weight loss and cardioprotection in obese adults

Alternate day fasting for weight loss in normal weight and overweight subjects: a randomized controlled trial

FEALS: Go To feals.com/ifpodcast To Become A Member And Get 50% Off Your First Order, With Free Shipping!

Impact of breakfast skipping compared with dinner skipping on regulation of energy balance and metabolic risk

Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans

Is advice for breakfast consumption justified? Results from a short-term dietary and metabolic experiment in young healthy men

The effectiveness of breakfast recommendations on weight loss: a randomized controlled trial 

Effect of skipping breakfast on subsequent energy intake

The causal role of breakfast in energy balance and health: a randomized controlled trial in lean adults  

Early Vs Late-Night Eating: Contradictions, Confusions, And Clarity

Our content does not constitute an attempt to practice medicine, and does not establish a doctor-patient relationship. Please consult a qualified health care provider for medical advice and answers to personal health questions.


Melanie Avalon: Welcome to Episode 281 of the Intermittent Fasting Podcast. If you want to burn fat, gain energy, and enhance your health by changing when you eat, not what you eat, with no calorie counting, then this show is for you. I'm Melanie Avalon, biohacker and author of What When Wine: Lose Weight and Feel Great with Paleo-Style Meals, Intermittent Fasting, and Wine. And I'm here with my cohost, Cynthia Thurlow, Nurse Practitioner and author of Intermittent Fasting Transformation: The 45-Day Program for Women to Lose Stubborn Weight, Improve Hormonal Health, and Slow Aging. For more on us, check out ifpodcast.com, melanieavalon.com, and cynthiathurlow.com. Please remember, the thoughts and opinions on this show do not constitute medical advice or treatment and no doctor-patient relationship is formed. So, pour yourself a mug of black coffee, a cup of tea, or even a glass of wine, if it's that time and get ready for The Intermittent Fasting Podcast.

[intro ends]

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They have counter time for anti-aging, counter match for normal skin, counter control for acne and oily prone, and counter start for sensitive. I use their Overnight Resurfacing Peel and vitamin C serum every single night of my life. And their makeup is amazing. Check on my Instagram to see what it looks like. Tina Fey, even wore all Beautycounter makeup when she hosted the Golden Globes. So, yes, it is high-definition camera ready. They have so many other products, deodorant, shampoo and conditioner that I love, products for babies, and so much more. You can shop with us at beautycounter.com/melanieavalon or beautycounter.com/cynthiathurlow and use the coupon code, CLEANFORALL20 to get 20% off your first order. 

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Hi, everybody, and welcome. This is episode number 281 of the Intermittent Fasting Podcast. I'm Melanie Avalon and I'm here with Cynthia Thurlow.

Cynthia Thurlow: Hello, there, my friend.

Melanie Avalon: How are you today, Cynthia? It's been a while?

Cynthia Thurlow: Yeah, I'm doing well, because it's like hard for me to say this, but my kids are all going to be in high school as of next week.

Melanie Avalon: Oh, wow.

Cynthia Thurlow: They're going back to school. Two different schools, but, yeah, we're in that mode of back-to-school shopping and supply purchases and new computers. And it's just hard to believe the summer is effectively over for them.

Melanie Avalon: So, this is actually a mind-blowing moment for me. So, when I was in high school, I was like the only person-- I brought a laptop to class, like nobody had laptops. Do all the kids use laptops now?

Cynthia Thurlow: Oh, it's interesting. My youngest is going to a magnet high school and they require laptops, so we had to purchase one for him. And my other son who goes to the local public high school, they are supplied with Chromebooks, which is like a laptop. And that's what they utilize. But I'm actually giving my oldest son my Apple because I'm going to get a new laptop. And he'll have that he can use for school.

But, yeah, it depends on where you are in school, like the STEM focus magnet schools and the school where my younger son is going, they require them, because they want them to be able to work from anywhere, not from the perspective of 24/7, like a lot of adults do. But they allow them to have a lot of freedom during the course of their day. And they like them tethered, not tethered to an outlet that they can just get up and use their laptop anywhere. Outside, inside, in the lounges, etc.

Melanie Avalon: It's just so funny to think about how things have changed, because literally I was the only person and I brought a laptop to-- I had to get permission to do it. And they were fine. But it was because I was like it's so much more efficient for me to type my notes during a lecture than write them because I ended up retyping them anyways.

Cynthia Thurlow: I'll really date myself here. When I went to college, there were three of us in college at the same time. Back then computers were super expensive, like prohibitively expensive. I had a word processor. I'm sure there are probably some listeners who remember what that was. But I had a word processor, not even a computer. I didn't have a computer until I went to graduate school. I think it was even like a hand me down like iMac that my mom had. So, yeah, past facts.

Melanie Avalon: Things have been changing.

Cynthia Thurlow: Absolutely.

Melanie Avalon: I have an interesting experience to share with listeners. How long have you had an Oura ring, Cynthia?

Cynthia Thurlow: A little more than a year, might be about a year and a half.

Melanie Avalon: Okay, I've had mine about two years. I can verify on it that I got sick for the first-time last week, with the exception of COVID. I don't really count COVID. I haven't gotten sick in at least two years. I don't remember getting sick, like before my Oura ring. I think it's probably been about three years of getting sick non-COVID. I had a fever and chills. And it's so funny, I was so excited-- not excited, but that night that it hit me, I was like, I can't wait to wake up and look at my Oura ring and see if it knows that I'm sick. I did. And my score was awful, and it knew, that's when I was able to look back through the data and see if I'd had a fever at all in the past two years. But what's interesting is, the very next day, I was completely back to normal HRV wise, readiness score wise, and I've actually been better since before getting sick. But I have been so tired. It's like I'm experiencing the COVID fatigue that people talk about. But I didn't have COVID because I tested, I didn't have COVID this time around. Some things I've noticed during this experience, to share with listeners is one, for people who take my Serrapeptase, I'm blown away because my memories of being sick are congestion and runny nose and not being able to breathe. Interestingly, I haven't had barely any of that. I know it's all there, but the Serrapeptase just keeps me so clear. So, I've been so, so grateful for that.

And then secondly, I mean, it's a little bit disconcerting that I'm still really tired. Normally I've been canceling everything, calls, going out with friends. Normally I do business calls when I'm running errands, and I haven't been doing any of those because I've been like I can't run an errand and talk on the phone at the same time. I've been scratching my head about what to do. I was talking with my friend James Clement, who wrote a book called The Switch. And actually, Morgan Levine talks about him in her book as well, who I interviewed and who you are interviewing in an upcoming episode. She's amazing. I've been talking to him about what to do. And he keeps saying that I said high dose NMN. Cynthia, do you take NR or NMN?

Cynthia Thurlow: I don't. Admittedly, it'll be fully transparent. I don't feel like I know enough about the better brands for those products. I think that's really what it comes down to, because I know there's a lot of smoke and mirrors in the supplement industry. For full disclosure, I usually just lean on Melanie's recommendations, if it's something I don't know a lot about. I'm like, "What would Melanie do?

Melanie Avalon: Oh, it's so funny. Well, especially with NR and NMN. For listeners who are not familiar, there's something called NAD in our body. And Peter Attia, did you listen to this episode, he recently did an episode with a guest expert in NAD?

Cynthia Thurlow: It's on my list. But it's like I really have to set aside the time like I've been listening to the Huberman and Attia podcasts. And since it's like more than two hours, it's been two gym workouts, and I'm still not done with it.

Melanie Avalon: We talked about this. So, you listen to podcasts while working out?

Cynthia Thurlow: I do, or books. It depends on my mood. But lately, I've been getting back to podcasting.

Melanie Avalon: I have to do music if I'm at the gym. I listen at night, usually to podcasts. But he did do a recent dive into NAD. In any case, NAD is how I keep talking about magnesium being the master mineral in the body. NAD is basically the master coenzyme in the body, literally involved in everything. It's an all of the cells. And there are some theories out there and talking to James, this is his theory that especially with COVID, that post COVID fatigue and long COVID, might be due to depleted NAD in the body. And we see with age that NAD actually goes down as well. A lot of scientists also think a lot of aging effects are due to depleted NAD. So, keeping your NAD topped up is super important.

But you can't take NAD as a supplement. But you can take the precursors, which are NMN and NR and there's been so much debate about which version is better. And like you just said, Cynthia, especially with NAD and NR, a lot of just sketchiness in that industry. I've been historically taking both and experimenting. And I think I can announce this, I announced before that we were going to make NMN at AvalonX. And then we couldn't because it's in the gray zone with the FDA. But things are changing. I probably will be releasing an NMN upcoming sort of soon, which I am so thrilled about. So, needless to say, I was talking with James, and his direct quote to me was, "Do not underestimate the effect of high dosing NMN."

What he actually does, he has a lab; he made his name by doing work on the blood work of super centenarians. And now he does a lot of anti-aging lab work. And he's literally testing NMN and NED and stuff like that in his lab all the time. He's been helping me figure out a dosing schedule. I started high dosing the NMN that I'm taking right now two nights ago. And I actually did start feeling a little bit better. And today's the first day I feel, like this is not wearing me out right now to talk. And I took so much NMN last night. And I think it's so important that I actually over the next four days, I said, you can't take NED as a supplement, but you can as an IV, or as an intramuscular injection. So right after this, I'm going to go get an NAD injection. And then I have two IVs scheduled and then another injection. I mean, I can't keep being sick this long. I'm like not down with this. That was a lot. But basically, listeners, I think NAD is so, so important.

Stay tuned, because, hopefully, I'll be releasing my own NMN soon. For updates on that, definitely go on the email list. That's at avalonx.us/emaillist, avalonx.us is also where the Serrapeptase is and the magnesium and the coupon code MELANIEAVALON gets you 10% off. But I just share all of that because I mean, I love these supplements, but getting sick has made me realize, it's when you're sick that you realize what's important to you. So that was a long spiel, but you got sick sort of recently, right, with laryngitis?

Cynthia Thurlow: When I came back from Europe, I was convinced I must have had COVID because I spent two days in bed. And then I was like, "If I didn't have COVID, I must have flu." And I kept coming up negative for both. But I started a whole regimen of high dose vitamin A, vitamin D, a slew of other things that thankfully, my physician friends called in for me and I felt better, usually within a day and a half. But my Oura ring, the day before I started feeling poorly was already telling me something was brewing and it stayed abnormal for like four or five days. And then it went back to normal. I don't know what I had. But I do think for all of us we lean into the narrative that, "Oh, it has to be COVID." And I just think you can get an apparent virus.

Melanie Avalon: There are other things. Sorry, I'm so glad you said that, didn't mean to interrupt, because so many people I've talked to they're like, "Oh, it's probably COVID. I'm like, "Well, I had COVID. I tested this time around, it was negative. And they're like, "Oh, but it's probably still COVID. I'm like, "Guys, there are other viruses besides COVID."

Cynthia Thurlow: And, unfortunately, that's the mentality is, "Oh, if you get sick now, you can't just have like a common cold virus."

Melanie Avalon: What happens all the other coronaviruses, like it's COVID19 because there are a lot of other coronaviruses.

Cynthia Thurlow: Right. We flew from Budapest to Amsterdam, ran through an airport, I'm not kidding, ran, sprinted to our flight to Boston, Boston to our home. And I was like, "Who knows what I got exposed to?" Even though you know, travel to me is generally pretty enjoyable. But your immune function can be impacted by a lot of things. And certainly six hours ahead, the net impact of time differences and things you get exposed to while you're traveling and the stress of traveling. Let's be honest, it's not stress free. I'm mentally gearing up for three trips I have back-to-back in September and early October. And I was telling my husband, in between the LA and Scottsdale trip, I think I'm home for two days. And I'm like, "Oh, I'm going to be like really hunkered down as an introvert in between those big trips. So, yeah, there's a lot that goes into it. And not every viral illness is the pandemic bug, it could very well be just a latent, benign summer virus that people used to never think twice about.

Melanie Avalon: I'm so glad you said that, because it's like everything's COVID now.

Cynthia Thurlow: Right. And it doesn't have to be. In between my trip and then I had a week at home and then I went to a business trip in Austin and I felt like I did tell every single person I saw that I tested four times for COVID only because I wanted to be able to demonstrate I really didn't have it. Not because I thought I had it but it's now become an expectation that people are hypersensitive, hyperaware to what is now an endemic virus. And the joke is amongst my ER medicine friends, the only people that don't have COVID are the ones who have been tested. Meaning, you probably have had it; you may just have had a really mild case, you may not have tested. Anyway, I don't want to dive down that rabbit hole. But the point is not every viral illness is COVID, or flu for that matter.

Melanie Avalon: Yeah, exactly. So definitely been an experience. And I'm really excited to see again, so the high dose NMN is helping, but I'm really excited to see over these next four days with the NED, if that just gets rid of the fatigue, although I've heard that the IV can be a very unpleasant experience. We'll see if I make it through that. Oh, and last thing, I had a call with Oura ring yesterday. Listeners, I might have a code soon, finally. So stay tuned for that. People ask me for a code like every day in my life.

Cynthia Thurlow: I actually have an Oura ring code.

Melanie Avalon: With your name?

Cynthia Thurlow: Why did they sign--? It's people get money off and they get six months of free service?

Melanie Avalon: What? Like a CYNTHIATHURLOW code?

Cynthia Thurlow: I don't even know. I mean, we'll include it in the show notes. But they made it just for me.

Melanie Avalon: Whoa, I have been trying so hard. I had the call yesterday. And they were like, "Well, we'll fix that for you." Treasure that, they do not give those out easily. My listeners know I've been trying.

Cynthia Thurlow: Well, because I tagged them constantly. I'm always like showing my data and then I talk about Oura ring probably as much as you do. And I tell everyone, it's like my favorite form of technology that really has been helpful for me determining what I need to do to-- for me, it's really been-- my REM sleep was always good. My deep sleep was the one that needed work. And so, I'm constantly working on that, constantly.

Melanie Avalon: Yeah, wow. The show notes will be at ifpodcast.com/episode281.

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Melanie Avalon: All right. Shall we jump into everything for today?

Cynthia Thurlow: Absolutely. So, this is from Knowles. "Hi, Melanie and Cynthia. I'm a 65-year-old woman 110 pounds, and I've been fasting since August of 2021. I'm doing it for the health benefits. When I read something like the issues raised by Dr. Sarah Ballantyne below. I don't know what to think. She sounds legit, and so do the studies. I'm doing fasting for health reasons, so need to know the scoop. Please address this soon. Thanks, and I love your show. I hope you can shed more lighter on this and other recent studies. Thanks for all the information." And here's what she says, "Myth busting intermittent fasting." "Most studies in humans have shown that intermittent fasting doesn't provide any additional benefit compared to other diets, with metabolic and cardiovascular benefits attributable solely to the weight loss during the study. In addition, the most common way of IF'ing by skipping breakfast results in higher inflammatory responses, and increases in measured insulin resistance after lunch. Studies also show that routinely skipping breakfast increases the risk of type two diabetes by a shocking 55%. Increases the risk of cardiovascular disease by 21%. And increases all-cause mortality by 32%. All in all, there's far more science pointing to the benefits of breakfast, and eating dinner on the early side to support better sleep."

Melanie Avalon: And then she lists out two different blog posts. One is called Intermittent Fasting Secret to Weight Loss or Dangerous Fad. One is called, Is breakfast most important meal of the day. New Science has answers." And then there are links to two of her podcast episodes. Episode 386, Intermittent Fasting and episode 381, "Is breakfast the most important meal of the day?" And that is on her, what podcast is that?

Cynthia Thurlow: The Paleo Mom.

Melanie Avalon: I have so many thoughts here. Okay, well, to start things off, when her podcast episode 381 published, I breakfast most important meal of the day came out, or it might have been one of those that she links, people were asking about it in my Facebook group. And she actually co-host The Paleo View. Or at least she used to with my good friends, Stacy Toth. This came up in the group, I listened to the podcast episode, and I did a deep dive into what she talked about. And so, I'm going to talk about all that here. And all of this is not to argue her, try to discredit or disprove what Dr. Ballantyne is saying, I just think she brings up a lot of good topics. And I learned a lot listening and diving into what she was referring to. And then I also did a deep, deep dive into one of the specific studies that she talks about because her blog post Is breakfast the most important meal of the day, new science has answers, that is an analysis of a 2017 study called Impact of breakfast skipping compared to a dinner skipping on regulation of energy balance and metabolic risk.

I was reading that study, and it was actually a really fascinating study. I'd love to talk about it anyways. So, I'm just going to talk about all that and then people going to-- we can see where we go from there. So maybe I'll start with that blog post about the 2017 study. So basically, in one of her emails, I'm going to read what she says about the study, and then I'll read what the study actually said. She says that a 2017 study used a randomized crossover design to evaluate skipping breakfast versus skipping dinner, compared to the standard three meals per day. Time restricted feeding, either skipping breakfast or skipping dinner resulted in slightly higher energy expenditure for the day. And while skipping breakfast, but not skipping dinner increased fat oxidation. It came at the expense of higher inflammatory responses, a whopping 54% increase in the postprandial HOMA index, meaning increased insulin resistance, and higher blood sugar and insulin levels after lunch. 

And then she says, "A recent study of how intermittent fasting affects insulin sensitivity showed that the feeding window didn't really matter. What did matter was having the first meal before 8:30 AM." That's Dr. Ballantyne's words. The actual study, what they did was they looked at-- well, first of all, a problem I have with the study, it was very short. So, people basically did like a day of skipping dinner and a control day, and a day of skipping breakfast with a washout period. And it was only a day of each of these. And I think that right there is a problem because it doesn't give people time to acclimate to whatever IF pattern they're doing, because we know it can take the hormones a little bit of time just sorts of regulate to a new rhythm. So that's just a little bit problematic, starting thing off. But that said, there were a lot of good findings in the study.

The participants ate the same similar macronutrients throughout the days. One of the biggest things, the biggest takeaway, at least for me, and Dr. Sarah Ballantyne mentioned this, was those that skipped breakfast, so when they ate dinner, they actually burned more fat. So, it's a huge takeaway from the study is that the participants who skipped breakfast, so basically, they were having a leader eating window, they not only did they burn more fat than those that skipped dinner, they burned fat when the other group was burning carbs. So basically, the people who ate all throughout the day, were burning carbs more. And it was the exact same for the people who skipped dinner. So, the people who were eating earlier burn the same amount of carbs, essentially, as those that were eating throughout the day, compared to those that skipped breakfast and only ate dinner. It's like flipped. They basically burn fat all day, not all day, but they burned a lot of fat. So, they were fat burning for the majority of the day compared to the other group that wasn't. And I just think that that is huge. 

What's interesting is, she mentioned how the HOMA-IR at lunch was worse for those that skipped breakfast. And what HOMA-IR can tell us is, it's like she mentioned a measure of insulin and glucose that can give us a picture of insulin resistance. So, it was worse for those who skipped breakfast after lunch.

One of the problems about the setup is they didn't test HOMA-IR all throughout the day, they only tested one data point, which will-- it was a few different times, but it was basically amount of time surrounding the lunch meal. And what's important to note about that is that's testing the HOMA-IR at a different timeline for the two setups. So, like if you really wanted to make it controlled, I think you would have needed to have tested HOMA-IR, so that it would match the amount of time into the eating window for both of the two arms, the breakfast skippers and the dinner skippers. I don't know if that's quite making sense. But basically, just like looking at one snapshot, I don't think gives a full picture of the entirety of everything, especially when fasting insulin sensitivity 24-hour glycemia, and glucose variability, and 24-hour insulin secretion were all similar for all of them. So basically, all of that was really similar. But when they looked at this one time point, they found a difference. I don't know that that's actually a full picture of what's going on.

And then something fascinating from the study. And I find it interesting that Dr. Ballantyne didn't mention this at all when she talks about the study, even though later in her email, because what we read was from her email, later, in her email, she talks about other studies looking at the role of cortisol and how fasting might have a negative effect on people's cortisol levels and people's stress levels. This study actually found that those who skipped breakfast had a better stress response. While the cortisol and the 24-hour cortisol profile was similar between all the groups. Those that skipped breakfast, I will quote, "It says overall HRV," so we were talking earlier about Oura ring. HRV is your heart rate variability, and it can be used as a marker of your body's stress levels, and higher HRV is basically a better stress response. The study says that overall HRV, heart rate variability, was higher on the breakfast skipping day than on the dinner skipping day. It says that the findings of the study argue against a higher sympathetic tone and suggest improved autonomic regulation with breakfast skipping. 

The sympathetic part of the nervous system is basically like our fight or flight version of our nervous system. The parasympathetic is the more relaxing, calming part of our nervous system. This study found that for those who skipped breakfast, they had a better stress response. They're less of the sympathetic, more the parasympathetic, and improved autonomic regulation. They found that skipping breakfast was better for their stress levels, which is the-- Well, Dr. Ballantyne didn't even mention that from the study, and then it contradicts what she says a little bit later about another study on cortisol. The study makes this case and Dr. Ballantyne makes this case that maybe breakfast skipping is leading to metabolic inflexibility because of that HOMA-IR score. But what's confusing to me, and I'll be curious to hear your thoughts on this, Cynthia, it's like why would we assume metabolic inflexibility based on this one HOMA-IR score taken at one point, when overall, when we look at the entire day, those that skipped breakfast were burning more fat? 

It just doesn't make sense to me. If they're burning more fat for a substantial amount of time, clearly it's a different message than metabolic inflexibility. I find it interesting that that's a conclusion that's drawn. Interestingly, what the study concluded their final, final conclusion was that-- and this is also interesting, because you can make a lot of conclusions from this study. And this is what I want listeners to understand the way these studies are handled, because we'll talk about how there'll be a study, and then it gets interpreted in the media or interpreted by bloggers, or doctors or scientists or influencers, and you can put whatever spin on it you want. But even the study itself, they often put whatever spin on it they want. They focus on what they want to focus on. So, everything I just told you, you could have concluded so many things. You could have concluded skipping breakfast is better for your stress levels, you could have concluded, skipping dinner decreases fat burning. There's a lot of things you could have concluded. But what did they concluded a causal role of breakfast skipping for the development of obesity is not supported by the present data. They basically concluded a negative. Rather than saying, skipping breakfast leads to more fat burning, they concluded that skipping breakfast does not encourage obesity. And it's a small thing, but it just really shows, I think, what the aim can be with certain studies.

So, that was my analysis of that study, honestly reading it, I was like, this makes me want to skip breakfast. Like you'll burn more fat--Oh, I left out the inflammatory response potential. I am so sorry. There was another aspect of this study, where they looked at the immune response. And Dr. Ballantyne talks about this. And it's interesting about here what they did is they looked at the-- again, look, they looked around lunch, and they looked at the blood of the participants, and they didn't look at the inflammatory response of the blood, right then. It wasn't like they looked at them eating the meal and then they looked for levels of inflammatory markers like IL-6. So, they put into the blood either LPS, which is lipopolysaccharide, which is basically a byproduct of gut bacteria that our body registers as a toxin, or they put in hemagglutinin, which is a glycoprotein that causes an immune response in red blood cells. It's kind of like the whole lectin type thing. And they saw how the blood reacted.

So, they didn't look at the inflammatory response of the blood right then. They took the blood, they put in something that the immune system that would react to, and then they tested to see how the blood reacted. And they did find that those who skipped breakfast, had a more exaggerated inflammatory response when they put in basically, a toxin or something that aggravates the blood into the blood. And I don't know enough about immunology to really speak more length on that. Other than to say that I'm not really sure what's going on there and I'm not really sure what the implications are. They concluded that it was maybe because the participants who skipped breakfast were burning more fat when they ate, so they had higher levels of fat in their blood, and that that could exacerbate the immune response to LPS and hemagglutinin. I don't know. Again, it's a thing where I would set it up differently where I would have that response tested so that it's being tested on the early eaters and the late eaters equivalently based on how long they've been fasted, or how long they've been eating, that was in there as well. That was so much, and I also have thoughts about her other blog posts. But I'm going to stop talking for a little bit. Cynthia, do have thoughts?

Cynthia Thurlow: I think this really speaks to what happens in the media and many other well intended, I have to believe, this is a well-intended email and blog posts that were written. It's under the presumption that most people don't know how to read research. And it's under the presumption that we aren't going to question what she believes was the key takeaways from this research that was done. And this is why Melanie and I are very committed to really taking the time to thoughtfully look through the research and to be able to say, "This actually isn't the case. If you really look at the research, you really look at the variables, there are so many things that impact, the HPA, the hypothalamus pituitary axis, the stress response in the body, a lot of that could have absolutely nothing to do with meal timing. I feel fervently and strongly that this is one of many reasons why there's so much fear mongering about fasting. And really, we would not be here as a species if it wasn't something that was very aligned with ancestral health perspectives. But when you start layering in the stresses of a modern-day lifestyle, like many of us experience, stress going to work, and stress with kids, and stress with getting sick and all these other things adding in additional layers of stress on top of fasting may make it a less than ideal circumstantial choice. But I don't think that the key tenets from that email and from that study were extrapolated in a way that's particularly helpful. In fact, I think it contributes to the fear mongering mantra and message that we see all over social media, from health influencers, etc. 

And Melanie did a really, really nice job kind of diving into the research, and looking at what it did actually really show. Even when I do little IG lives or I do really short videos, I always say, "Look at the research, was it statistically significant? What was the endpoint they were looking for?" So really getting at least somewhat knowledgeable about what to be looking for and to question. And really, that's what science is doing is, is forcing us to question and to consider, do we need to look at this differently? But it has always been my experience that fasting-- and when we look at the bulk of the population here in the United States is one example. It's anywhere from 8% to 9% of the population is metabolically healthy. So hello, that's most everyone is not metabolically healthy, eating less often is not going to hurt you. I think that's the big thing to stress, like, the big takeaway is, who benefits from us eating all day long? What industry benefits? 

The other thing that I like to look at, Melanie, I'm not sure if you actually looked at this. But I'm always like, "Who funded this study? Who funded the research that we're looking at?" To see if there's any biases, because I think that can also be very, very impactful. But this is trying to throw the baby out with the bathwater, one of those old sayings that my grandmother used to say that, you really have to dig a bit deeper and understand that even people with research backgrounds can actually cherry pick data. It happens super commonly. This is one of many reasons why I think it's important to get savvy or at least familiarized with basic research tenets, and to also, is it something that is outside the norm of how you would normally think about, something like be humble enough to say, "No, maybe there's something here I haven't looked at." But I looked at this as well, and I have to agree with Melanie that, there's nothing to support, the key takeaways that Dr. Ballantyne has in that article or in those emails. I think it's unfortunate, because many years ago, I think I did actually follow her, but I got to a point where I had to unsubscribe. But I think in a lot of levels, I appreciate when our listeners bring these things to our attention, so that we can address them proactively and say, sometimes there's going to be a time when we might say, "Hey, we may need to rethink our thought process on a particular area," versus saying, "I still felt pretty confident that eating less frequently, and not eating large boluses of food throughout the day is ultimately going to improve metabolic flexibility, is going to keep our insulin levels lower, is going to improve those HOMA-IR scores that you were referring to." It just goes to show that even well-meaning people can put out cherry pick data, which is when I first read this that was my visceral response.

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It's really interesting, because I understand that that HOMA-IR when they measured it around lunch seemed worse on the breakfast skippers. But I don't know how you draw the conclusion that they're becoming metabolically inflexible when they started burning fat, and the control group didn't and the dinner skippers didn’t. And then interestingly so, I mentioned that it concluded that skipping breakfast was better for your stress. So later on, Dr. Ballantyne talks about how IF might negatively affect cortisol levels, two references to 2019 study where she says, early time restricted feeding altered the diet neural patterns and cortisol, morning cortisol was elevated and evening cortisol was lowered. And she says this implies that this is not an appropriate dietary strategy for anyone with unmanaged chronic stress. So, this really confuses me, because last time I checked, the cortisol pattern that we wanted was higher cortisol-- like the natural cortisol rhythm is higher cortisol in the morning, lower at night. The study found that, that fasting led to higher cortisol in the morning and lower at night. I don't know. Do you have thoughts on that? That's what I think we would want to see.

Cynthia Thurlow: Yeah. The circadian biology, if you look, you actually get a spike in cortisol about 30 minutes after awakening, and you want to see it ebb and flow throughout the day. But it follows a very commonly, and a healthy person follows a common distribution and higher in the morning, it ebbs and flows throughout the afternoon, and then it's lower in the evening. And you wouldn’t want your cortisol to be the opposite. If it was low in the morning, you would be dragging, you can barely get out of bed. And if it's high at night, then you're wide awake and you can't fall asleep and you can't relax. Circadian biology is something that I have really gotten to know very well. And so that doesn't seem at all aligned with the way things should ideally be. Meaning, we want to see a vibrant cortisol response in the morning. It's what gets us up out of bed, it suppresses melatonin, gets us moving. And then we want cortisol to be lower in the evening when we're getting ready to go to bed, some of us earlier than later. And we want to see a nice vibrant response with melatonin. So that doesn't make any sense to me. And maybe there's something I'm missing.

Melanie Avalon: I've read it so many times. I remember when I heard it in the podcast, and she said that and I was so confused, because I was like, "Well, what do you want to see then?" I just don't understand.

Cynthia Thurlow: Well, sometimes I think some of these individuals, and maybe it's not even Dr. Ballantyne, who wrote that maybe it was an assistant or someone on her team. But the assumption is made is that most people don't know basic science. And if you understand, like very basic science, you would say, "Hmm, that doesn't make sense to me because the normal distribution of cortisol and I look at these labs almost every day," that's what you want to see. When it's dysregulated, when you've got hypothalamus pituitary dysregulation, meaning your brain and your pituitary gland and your cortisol, or the adrenal axis, so it's HPA axis. When that axis is disrupted, that's when you'll see an abnormal distribution of cortisol throughout the day into the evening. And so, I have to agree with you.

Although it's interesting when you think about stress, like if someone is going through a divorce, they're having like they've lost their job, or they're going through a contentious move, that might be the time not to add more stress to the body, even if it's a beneficial hermetic stress. But in most instances people can take their foot off the accelerator, and maybe they're doing 12 hours of digestive rest, but I still don't understand how you could say that it's not beneficial, honestly. We're looking at the degree of metabolic ill health we have here in the United States, it's almost-- I actually am getting more bolder on social media, I was saying on Twitter, something along the lines, like, if you're a health care provider, and you're not advising your patients to check their blood sugar's or to recommend a glucometer or CGM, and I'm getting a little off on a tangent, we're really doing them a disservice. And so, I think the same thing, if you're not telling every single patient to go 12 hours without eating, that's criminal, absolutely criminal.

Melanie Avalon: That ties in a little bit to one of the podcast episodes that was referenced. She did bring up a lot of topics, which I think are good topics for discussion. There are things we will be talking about anyways. The one that that made me think of was, she believes the benefits of intermittent fasting are often basically all due to calorie restriction. And that the fasting is harder than calorie restriction. And I have a lot of thoughts surrounding that. Even if the benefits because I know this is an age-old debate, or as long as it can be an age-old debate, which is as long as IF has been a colloquial idea. But even if the benefits of IF are just due to calorie restriction, which I do not believe they are, I believe they activate similar pathways as calorie restriction. But that you can get the benefits without calorie restriction. Even if the benefits are just due to calorie restriction, and people are just accidentally eating less by doing IF, I think it's very hard to get people to do calorie restriction normally, so if people can easily, "unintentionally" do calorie restriction because they're fasting, I see that as a win. I don't have any issue with that.

Cynthia Thurlow: Melanie, I think it's also this very reductionistic thinking, when people say, "Oh, the only benefits are that you've reduced your calories." And I'm like "No, that's actually not correct." And it's an opportunity to really help educate people that there's so much more to the benefits of fasting that people are unaware of. I think people come to it because they want to change body composition or lose weight. But if it were simply about the calories, then we wouldn't have all this other vibrant research that suggests that there's a lot of benefits that maybe aren't apparent, reduction in inflammation, autophagy upregulation, all these other things that people sometimes lose sight of.

I think it also speaks to the fact that we have conditioned our patients to believe that they need to be eating all day long, and eating snacks and many meals and the reality situation is. Even people who are thin have plenty of stored food in their bodies, stored fat that they can access if they're fat adapted. And there's a lot to unpack here. And I'm trying to restrain myself, because I could go off on many different tangents about the fear mongering and the cherry picking of data that seems to be really prevalent, much more so now than ever before.

Melanie Avalon: That's why I thought about this part of it because how you're saying that doctors should be telling people to go a certain amount of time without eating. But there's often this response of it requires calorie restriction or it's not sustainable. And it's just better to eat all day. I don't see that. In that podcast, she talks about how-- she speaks specifically about ADF, alternate day fasting, and how it's more difficult than calorie restriction. So, interestingly, ideally for me, it wouldn't be more difficult than calorie restriction, but I do find ADF, it does not appeal to me, I think it'd be too difficult for me, not something that I would like. That said, there are so many studies that have found that not to be the case. So, I'll put links in the show notes. But for example, one called alternate day fasting improves physiological and molecular markers of aging and healthy nonobese humans. That one they saw no dropouts in six months for people doing ADF. They saw two drop outs in two months for people who were not doing ADF compared to one drop out in three months of ADF.

And then there's one called short-term modified alternate-day fasting, a novel dietary strategy for weight loss and cardio protection and obese adults. They found that the compliance on ADF was very high, 86%. And it was even higher, because often in studies, they'll do like an enforced part of it, where they basically give the people the meals, and then there's like the self-done version. And they actually found that people were more compliant when they were doing it themselves, which is pretty cool. And then there's one called alternate day fasting for weight loss and normal weight and overweight subjects, a randomized control trial. And they found that people doing ADF had adherence rates of 98%, and that their hunger did not change. And the longer they did ADF, they felt more satisfied and more-full. ADF is probably hard for a lot of people. Like I said, I don't want to do it. But there's been a lot of studies where people find it very easy to adhere to. I wouldn't make a blanket statement about it being something that's not practical or not implementable.

And then she does have a lot of takeaways about breakfast studies. And this claim that the majority of studies show the benefits of breakfast, and I have dived deep into breakfast studies, especially when I was writing What When Wine. What Cynthia was talking about earlier with funding, this is where it is shocking the amount of studies that are funded by the breakfast cereal industry. It's just shocking. And there's actually a 2013 meta-analysis. Up until that point, their conclusion was "a majority of pro breakfast studies feature bias interpretations, misleading language and proper citations and inappropriate terminology." So, basically, there's a huge bias in the literature.

On top of that, there's the healthy user bias. That's the idea that the people who skip breakfast are often the type of people that are engaging in other healthy habits, because we've been told for so long that breakfast is the most important meal of the day. Sorry, I said people who skip breakfast, people who eat breakfast tend to smoke less, drink less, eat more fiber, eat more micronutrients, be physically active, that can be a misleading thing for all the studies. And then if you actually look at the studies on skipping breakfast, that's just not what it shows. A lot of the studies show that skipping breakfast, people do not overcompensate, they usually end up eating less throughout the day overall, when they skip breakfast, they don't make up for skipping an entire meal, even if they eat like a little bit more at lunch. I'll put a link in the show notes to my blog post that I did on early versus late night eating. And that was more in the context of fasting. But when I actually looked into the literature on everything, and I tried to be as unbiased as possible, and I walked away thinking that the best time to eat, it's not what I do, by the way. It's not like late at night, like I do. But it did seem to be between like 4:00 to 7:00. Basically, later afternoon to early evening, while the sun is still up. I tried my hardest to be as unbiased as possible. And I looked at so many studies.

Cynthia Thurlow: Well, I think you're also a unicorn. I lovingly say that I think that it works for you. You're metabolically flexible, you are insulin sensitive, but the average metabolically inflexible individual would probably struggle with-- like when I think about late night eating, when it's dark outside, it's not aligned with the way our bodies are designed to thrive. For the average person in that subsect, it could be detrimental if it was something they did all the time. But this is when bio-individuality really rules. And this is certainly a degree of experimentation. I know when I used to work crazy shifts in the hospital like 11:00 AM to 11:00 PM. More often than not even would get a dinner break in the evening, and you would just eat because if you didn't eat then you weren't going to be able to eat later. But I think it's really leaning into what works for each one of us.

Then the research is helpful. That's one thing I want to respond as clinician. Research is helpful to guide suggestions and recommendations, but ultimately, it's the clinician or the N-of-1 or the patient or the individual really determining what works for them and is in their best interest. I think that's really important. If we get hung up on, and I'm just speaking in very general terms, research is helpful. Research confirms many things that we do clinically. Research can also just leave us with more questions like, "Oh, we need more research done on this area." We know that women there's not enough research done on women as one example, because there have been a lot of fears about subjecting women to research that are of childbearing, ages, for many concerns about the potential teratogenic effects. Meaning, anything that could potentially happened to their fertility or an unborn child. But I think there's now a push and a demand for not just being exclusive and looking just at men or menopausal women, but looking at everyone to get a really good representation of what the research holds for. I mean, that's my feeling. I'm always looking at it objectively and saying, yes, research is helpful, it can confirm what we need, or it can cause us to look at different variables that are impacting fasting or metabolic health. But I always think it's important to determine for each one of us what is working or what is not working,

Melanie Avalon: I cannot agree more. I think bio-individuality is so, so key. I am a late-night person. According to Dr. Breus, I'm a dolphin, and I have cortisol spikes probably late at night. Eating late at night really brings down that cortisol for me. It's just really interesting because I honestly think if we could get rid of all of the biases of society, and we didn't have this narrative about breakfast, and I think if people just objectively sat down and looked at the hormonal profiles of people naturally, like, what would they conclude? I don't think you would conclude that you should eat breakfast, because once you wake up, cortisol spikes, adrenaline spikes, you have hormones that are releasing fuel from your body. It's not a time where your body is asking for fuel. Ghrelin, the hunger hormone raises a little bit later, not right when you wake up. I did a deep dive into the hormonal profile, it was really, really interesting. But then again, there are people that love breakfast, and that's what their body wants. And that's where, like you said, bio-individuality is key.

Cynthia Thurlow: Absolutely.

Melanie Avalon: I feel this was the anti-fearmongering episode. I'm also glad you brought that up about the role of women in studies. One another reason I loved interviewing Morgan Levine, I find that it's the female scientists that are the ones talking about this. She talks about in her book, some of the problems with anti-aging research and how women often historically haven't been as included in the studies. There's definitely a need for more women in studies.

Cynthia Thurlow: Well, it's interesting, even when I was writing my book, and I've got so many references, they're housed on my website, because it would have taken up on a 20 or 30 pages in the book, there just isn't enough. We can't compare ourselves to lab animals. And we can't compare ourselves to primates. We really do need good researchers really looking at all these variables. And to be honest, anecdotally, I'm starting to see emerging trends that are coming up. Actually, I'm doing a webinar for the DUTCH company. So, this is a Precision Analytical DUTCH test, is a test that I use quite frequently in, especially in programs like Holistic Blueprint, which we're enrolling for in September, and they'd asked me to do a very slanted discussion on metabolic health and fasting and nutrition, which, of course, I'm happy to do. And I identified for them, I'm starting to see this triad of women, they are over-fasting, over-restricting, over-exercising, and those are the women I worry about the most in terms of adding in more fasting, it's the extremes that we as women don't weather quite as much.

It's not to suggest women can't work hard and work out hard, and doesn't mean they cannot fast. But if we're over-restricting everything in our diet, and we're anti-carb, we're not eating enough protein, we're eating the wrong types of fats, we're exercising seven days a week during CrossFit. And sorry to pick on CrossFit, I'm just trying to think of a very intense form of exercise without recovery. And then on top of that you're doing two 24 hour fasts a week, guess what? That's not going to balance your hormones, that's not going to put you in an advantageous position. As we are asking and demanding for more research, we're going to see some interesting results that come out of that. And I think Ben Bikman was recently talking about suppression of mTOR and how that can impact, I hope I'm not miss speaking. I think he was talking about ovarian follicle health. You really start to think about the fact of why I always say like, if you're a healthy woman under the age of 35, don't over-restrict your food and don't over fast. That's the kind of research we need to see, what's the net impact of hormetic stress on different stages of life. Not just women's still at peak fertile year, but in perimenopause and menopause, I think that would be really interesting and certainly very telling. I'm glad that there are researchers like Dr. Levine who are advocating for women and certainly doing the research. They're in the thick of things and hopeful that that will yield more helpful information to guide recommendations and clinical decision making, N-of-1 decision making moving forward.

Melanie Avalon: I'm glad there are people like you, like clinicians, working with patients and looking at all of the research and advocating, so strongly for women and all of this. So, thank you.

Cynthia Thurlow: Absolutely.

Melanie Avalon: Well, so that was a deep dive.

Cynthia Thurlow: That was a one question IF Podcast episode, but we will be back next week with lots of questions.

Melanie Avalon: Yes, I knew that was going to happen. When I was reading, it took me a long time to read through the study, I was like, "This is going to be a long episode." For listeners, there will be a full transcript, which I know will be very helpful because that was a deep dive. And links to everything that we talked about, because we talked about a lot of things in the show notes, those are at ifpodcast.com/episode281. You can submit your own questions by directly emailing questions@ifpodcast.com. Or, you can go to ifpodcast.com and you could submit questions there. Lastly, you can follow us on Instagram, we are @ifpodcast. I am @melanieavalon, Cynthia is @cynthia_thurlow_. I think that is all the things.

Cynthia Thurlow: Great deep dive into that question. And thank you, listeners, keep them coming. It's always enjoyable when Melanie and I dive into the research and look at different ways of making observations and certainly helping you, wade through a lot of misinformation that's out there, and there are certainly plenty of it.

Melanie Avalon: Yes. All right. Wow, this was absolutely wonderful, and I will talk to you next week.

Cynthia Thurlow: Sounds good.

Melanie Avalon: Bye.

Thank you so much for listening to the Intermittent Fasting Podcast. Please remember, everything we discussed on this show does not constitute medical advice, and no patient-doctor relationship is formed. If you enjoyed the show, please consider writing your review on iTunes. We couldn't do this without our amazing team. Administration by Sharon Merriman, editing by Podcast Doctors, show notes and artwork by Brianna Joyner, transcripts by SpeechDocs and original theme composed by Leland Cox, and recomposed by Steve Saunders. See you next week.

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