Intermittent Fasting: Hungry for Facts?
Chapter 1: Fasting: the fad and the fears
Hi I’m Wendy Zukerman and you’re listening to Science Vs. This is the show that pits facts against forgoing food. Today we are tackling intermittent fasting. Can it make you shed pounds, and live a healthier, longer life?
Intermittent fasting diets are basically where you don't eat for a certain period of time… whether you have this really long gap between dinner and breakfast…or perhaps you're just eating one meal a day … also called OMAD diet.. get it? .. One Meal A Day…
And these fasting diets are going bonkers right now – follow the gossip mags and you'll see that … celebs are all over this …From Chris Pratt
CP I did something called intermittent fasting
To Vanessa Hudgens ... Kourtney Kardashian, … and even Hugh Jackman
HJ Everyday what I do is… I eat for 8 hours and I fast for 16… I actually got the diet from Dwayne “the Rock” Johnson who is a mate of mine.
We first ate up the science on fasting a few years ago .. but since then, the hype around fasting hasn't been slowing… down. In fact, it feels like these diets have kind of taken on a life of their own. Headlines are screaming "I Did Intermittent Fasting and it Changed My Life"[1]... it's all over Tiktok and instagram and podcasts… Tech bros[2], and health-influencers[3] can't get enough!
The data behind fasting is so strong
Like who's idea was it - 3 meals a day anyway?
It's absolutely one meal a day - ifs, ands or buts
We've been hearing that not only does fasting rev up your metabolism … making you shed pounds... but that the benefits of fasting go way beyond weight loss…
Going hungry could the key to a healthier and even longer life
Fasting reduces the risk of cancer, Alzheimer’s …
So there's all these claims about how amazing fasting is for you… but then some research came out last week that spoiled the fun… just like someone cooking fish in the office microwave… Because it suggested that intermittent fasting might actually be dangerous… [4]…
[NEWS CLIPS]
An alarming new study on intermittent fasting…
Suggests that intermittent fasting could lead to a 91% increase of cardiovascular DEATH
91% ohh!
So what's going on here?? Today on the show, we are dropping our spoon back into the science soup – to find out:
When it comes to fasting there's lots of …
The data behind fasting is so strong
… but then there’s science.
Ahhhhh
Science Vs Fasting is coming up. After the break.
PRE ROLL
Does fasting help you burn fat?
Welcome back. On today’s show, we’re tackling fasting. And we'll start by looking into weight loss. Online people say that fasting puts your body into this special state – ramping up your metabolism and helping you to lose a bunch of weight. To find out what's going on here we sent Kaitlyn Sawrey to the University of Alabama in Birmingham.
It’s our pleasure to welcome you to Birmingham…
Kaitlyn used to be our senior producer. And she’s in Alabama to meet researcher Courtney Peterson[5] ...
Hey hi!
Who’s going to hook Kaity up to a state of the art machine to measure how her body responds to fasting… And because people argue that fasting ramps up your fat burning[6]
CP So this machine is going to measure how much fat you’re burning
Courtney is going to find out if it’s true … that fasting really does change how Kaity, or any one else, burns fat…
CP So we’ll have you try 18 hours fasting…
So first up, she took baseline measurements - and Kaity left the lab … had her final meal
KS Crammed a sandwich in my face…
and stopped eating at 5PM that day… the next morning… she headed back to the lab at about 11AM. And heads up: Kaity does not sound as chill as Hugh Jackman after she’s been fasting
KS [SIGH] I’m running late because the bloody printer wouldn’t work. And then I couldn’t get a sandwich to have for after the test. So now like I’m frustrated and just like, moody and emotional. And I just need some goddamn sugar in my face. Honestly. [SIGH]
Now that Kaity is good and hangry… Courtney will measure how much fat her body is burning ... To do that .. Courtney puts a weird-looking hood contraption over Kaity’s head. Just picture this giant plastic device that kinda looks like a space helmet.
CP And it’s connected to plastic covering. Which as you’ll see we’ll put the hood over you... Tuck the plastic around your body to create an airtight seal so all the air you breathe in comes from our tube and and the air you breathe out we can measure.
KS So nothing getting in or out without you guys measuring it — that’s the game?
CP That’s correct.
KS All right, so we’re inside the hood… just stay very calm, breathe normally…
To understand why Kaity’s breathing is important here you need to know… that mainly your body burns sugars[7] and fats for energy.[8] [9] and when it does that… some of that fuel gets converted into carbon dioxide, which you breathe out[10].… And that is actually what Courtney is measuring in that snazzy helmet. She’s looking for changes in the amount of carbon dioxide Kaity is exhaling[11] …
CP The less carbon dioxide you breathe out relative to oxygen… the more fat you’re burning.
KS Weird. Ok.
Before Kaity was fasting … Courtney could see that about half of her energy was coming from burning fat[12]. How did fasting change that?
CP So on day 2… After you were fasting for nearly I think it was 18 hours.
KS Yeah it was 18. It was hard.
CP We found about 70%[13] of what you’re burning now is fat.
KS Wow,
CP So you had a big increase in your fat burning. So you can see …
Yeah, at the start, before she was fasting, about 50% of the energy she was burning was coming from fat – and that went up to around 70%. Kaity has ramped up the amount of fat she’s burning because her body started looking for more sugar to burn… but because she wasn’t eating more sugar … So her body had to look elsewhere for energy. And turned to fat so started burning more of it[14]… Other studies have found this kind of thing too.[15] [16] [17] [18] [19] [20] [21]
CP if you’ve been fasting you really are in this fat burning mode. And your body kind of revs up its ability to burn fat.
Now… that fat burning mode… doesn’t last forever. As soon as Kaity rips off the hood…
KS it’s time to eat!!
And stuffs her face … with a pumpkin muffin
KS So I’m so starving OMG
her body gets back its sugar fix[22]. And all returns to normal[23] [24].
But the fact that we burn more fat at least when we’re fasting… is giving the internet some food for thought[25] … because it sounds like this is going to mean you lose a tonne of weight. Is that true?
How much weight do people lose with fasting?
We talked to Krista Varady from the University of Illinois, Chicago,[26] about this. She’s run trials on weight loss and fasting in hundreds of people - probably more than any other researcher out there[27]… And Krista told us that yeah. People do lose weight on these fasting diets.[28] [29] [30] [31] [32] [33]
KV: That's definitely the main thing that we see., So there's always like a, a range. Like some people don't lose any weight, but the majority of people tend to lose on average like 10, 15 pounds.[34]
So for your standard intermittent fasting diet - where you say you skip breakfast - and have your first meal at lunch time? A few trials have found that after several months, on average, people tend to lose between 5-15 pounds, so that's around 2 to 7 kilos.[35] [36] But every now and then she’ll see these dramatic results. So for example, she told us about someone who after several months of this diet, someone who really wanted to lose a bunch of weight - and lost about 60 pounds….
KV They were extremely happy. They looked like an entirely different person. It’s really interesting to see someone be like transformed
Is this just calorie restriction?
How much weight you lose can depend on a bunch of things[37][38] [39] … like how heavy you are to start with[40]… what you're eating when you're not fasting[41] … and what your eating window is – Courtney told us that there's growing good evidence that if you squish all your food into an 8 hour period – like from 11am to 7pm – there's a good chance you'll lose weight. But it did make us think... wait a sec.. are you really losing weight because fasting puts you in a special fat burning mode... or could it be because of something much simpler: you're not eating as much… because if you’re not eating for a big chunk of the day… then over the course of a week you’re probably putting less pies down your piehole than you used to.[42] [43] … So you're just losing weight because you're eating less…??
And to find out which idea was right - special metabolism theory or you’re just eating less - Courtney from the lab in Alabama did this one small study to see what happened if you got people to fast ... but didn’t change how many calories they were eating.[44] So, people ate their normal amount of calories for five weeks … but they had to down it in a small window of time. Like you'd do with some fasting diets. And Courtney made sure she knew what they were eating.
CP We had all our participants either eat the meals in our kitchen, or they had to eat their meals on skype, so we could make sure they were eating all the food we were providing them.
KS OMG
And you’d think if there was something special about fasting… people would lose weight even though they were eating the same number of calories. But…
CP They did not lose weight[45] . So we now think that this intermittent fasting does not help you burn more calories.
So bottomline why does Courtney think people drop pounds with fasting?
CP Because they're eating less. That’s what our data suggests. It’s simply because they’re eating less
And several studies have backed this idea up.[46] [47] [48] [49]
OK, so what all this means is that when you’re on a fasting diet you’ll probably find yourself eating less…that is - unless you have scientists force feeding you via Skype…. And if we're not putting so much crap down our trap. … ? Less mullet down our gullet? Not so much jelly in our belly? That’s probably the main reason we’re losing weight. But still - if you're interested in losing weight - this all sounds pretty promising except… one little thing. Jelly is great. Not eating? Sucks[50]… remember how hard it was for Kaity…
KS And I just need some goddamn sugar in my face. Honestly. whhhyyy do people want to do this to themselves!
So does it get any better? Or if you go on one of these diets will you just be miserable and hungry? Well… the few studies that we have tracking people’s hunger levels during fasting diets… actually show a really mixed picture… so sometimes people feel fuller as the fasting diet goes on and they get to used to it, and sometimes they just stay hungry… [51] [52] [53] [54] [55] [56] [57] [58] [59]
Kaity kept fasting for about 16 hours each day… and she did it for 3 weeks .
KS: 3 weeks!
WZ: 3 weeks… Brought her into the studio… how are you finding it?
KS: : less hangry
WZ: Really?
KS Yeah in the beginning I was going to bed pretty hungry, I was like I’m going to chew the side of the bed…I’m going to chew on this pillow, so now I’m just not as hungry….
So that’s weight loss.. But while you're digesting that Wellness bros and healthfluencers say that fasting can do much more than help you slim down… some people say the power of fasting can help you live longer and even fight cancer. … Could fasting really do all that?
Or is this diet more dangerous than we thought? Coming up… after the break.. fast … breakfast?
BREAK
Welcome back!
Can fasting help you live longer?
Today we’re chewing up the research into fasting diets… We've just found out that fasting can help you lose weight... Now we're going to tackle some of the bigger claims about this diet... Starting with whether fasting can make us live a longer and healthier life? …
Because the internet bros[60] and[61] goop-fluencers out there say one of the benefits of fasting is that it can slow down the aging process…[62] [63]
People who fast a lot end up looking younger than they actually are
To enhance regeneration, decrease inflammation…
This is great for dementia, improving your memory, focus, concentration
And they say this is possible… thanks to this very science-y sounding word ….
Something known as autophagy.
Autophagy, Autophagy, Autophagy,
We’re going to talk about Autophagy.
What is autophagy?
Ok so not to be that guy at the party, it's actually pronounced autophagy… that's according to the five Ancient Greek speakers that we asked… so I'm gonna go with them. But the question isn't how to pronounce it … it’s what is it?
Autophagy is a process[64] that works INSIDE your cells...and it helps your cells ... replace damaged parts.[65][66] And by the way it does this is really cool ... The cell literally eats chunks of itself. In fact, that’s what autophagy means in Ancient Greek - self eating[67]. It’s the little cannibal inside us all. And the key is that the cells can recycle those old, dud pieces to make new shiny parts. [68]
Here’s researcher Krista Varady again.
KV It’s like of a weird term… the body starts cleaning itself up … kind of like gobbles, gobbles itself up
The story you’ll hear online[69] [70] is that fasting ramps up autophagy[71][72]… which means you’ll be getting rid of more bung cell parts… and creating new, shinier parts… and keeping us healthy, whether that means fighting off Alzheimer’s[73]… or making us live longer[74].
And a lot of the claims that you’ll hear come from studies in animals… So like when fruit flies, mice and rats are put on fasting diets they tend to live longer[75] [76][77] [78] [79] [80] [81][82] [83] ... and a recent study in fruit flies found that fasting ramps up their autophagy[84] – and this was a really important reason as to why they lived longer[85] ...
So there's this big question about whether fasting makes you and me live longer - humans - or even if it boosts autophagy in YOU and ME… Which takes us back to Courtney, our researcher from Alabama?
Wendy?!
Who also studies autophagy —
Uh huh yeah absolutely
And she told me that knowing if intermittent fasting is ramping up autophagy in humans - is tricky
So it's actually really, really hard to measure in people
When scientists do these studies in flies … or rats …sometimes they'll mess with their DNA, remove bits of tissue … kill them… which can be a tough sell for a human study … so when scientists like Courtney are trying to sort out this autophagy question - they have to get creative. Several years ago Courtney got almost a dozen people to fast for 18 hours – that meant they could only eat between 8am and 2pm. Harsh right?[86]
CP Right - cos then if there's a benefit, we'll see it!
They did this for four days; and as a control the same people did a much nicer fast – where they would eat from 8am to 8pm.
CP And what we did is we collected blood cells and isolated their DNA
What Courtney wanted to know – was whether the activity of these genes that have been linked to autophagy ramped up after people were on the hectic fast. And so if you picture how autophagy works – you've got some proteins toddling about picking up all that trash, the damaged parts in your body… and then you've got
CP like the incinerator. Ok bring in the trash, we're gonna incinerate it and make new things, new proteins out of it
Well, Courtney zoomed in on one gene that creates the outside casing of that incinerator, and what she found is that after people did their 18 hour fast – that gene did get more active… [87]
WZ Amazing and so you found that after fasting we have more incinerator casing …
CP Exactly, exactly, it’s just super cool, I wasn't expecting to see such striking results
So, Courtney research is exciting… but it's not all cupcakes and cookies.. we have a handful of other studies looking at this autophagy question in people, that are a bit conflicting. Some, like Courtney, seem to suggest that fasting boosts autophagy… others don’t.[88] [89] [90] [91] …
And then we have some research… that has tried to tackle this question of does fasting boost longevity in a completely different way… Scientists will follow people for years – to see if those who fast live longer than those who don't. Some are done in people with heart failure, or diabetes… and it’s just important to know that the research we have that does this is far from perfect – so many of them… survey people for just a couple of days about their eating habits and then years later see… ahh are you dead yet?? And so we don't know if they were practicing fasting for that whole time… But still, what these studies tend to find is that people who said they were fasting for 16 hours.. don't live longer[92][93][94][95]…
And just away from these studies… Krista reckons the hype around fasting as a longevity booster - is overblown..
KV first and foremost, there’s never been anything showing like in humans that either calorie restriction or fasting helps people live longer. Those are all studies done in worms, and yeast and mice and that we are just kinda extrapolating from.
So for the evidence that fasting will make you live longer? The proof is in the pudding. Which for now I’m eating…
Can fasting fight cancer?
But there is an area of fasting research that is racing ahead…and it’s in cancer…
Fasting may actually weaken tumors
Researchers are looking into the benefits of starving cancer
And when we first heard this, we were like - wait, what?? … but there’s actually some science as to why this might work. You see… many types of cancer LOVE sugar[96]…. They just, like, eat it up[97] [98] [99] [100], and this has been known for ages[101]… But more recently… scientists wondered ... well if cancer loves sugar so much… and. when you fast… your body kinda runs out of sugar… couldn't this cut off the cancer’s food supply… ?
Valter Longo… a professor in aging at the University of Southern California[102] he told us what it might be like for the cancer cell when someone is fasting.
VL the cancer cell now for the first time finds itself in a strange environment that it has never seen before
The idea is… that once the cancer is confused and weakened by fasting .. if you then add conventional medicine ...… like chemotherapy… it’s like a one-two punch. So - combined with fasting - they’re hoping the chemo …
VL Is able to search and destroy every cancer cell. I call it death by confusion and the reason that I call it that, is because it's really about the cancer cells being able to adapt to this confusing environment where everything is changed.
So to test this Valter [103] gave a bunch of mice… cancer… in a kinda creepy way…
VL the cancer cells are injected into the mouse[104]. the mass starts growing. eventually if you don’t do anything, that will kill the mouse
WZ wow
To save the little mousies.. Valter put them on a fast as well as giving them chemo… And it worked. Way more of the mice survived - compared to the mice who just got chemo but didn’t do the fasting[105]… Other scientists doing similar work found this too.[106] [107] using that one - two punch some mice were living cancer free![108] [109] .
VL We cure lots of mice when we combined the two, so it’s really interesting how the combination can be so much more powerful than the intervention alone.
Valter and other scientists are NOW researching whether fasting can help fight cancer in people[110] [111].[112] [113] [114] [115].. which can be a little more complicated than working with mice. Valter told us that just convincing some experts to get patients to try this can be tough – because, many doctors and dietitians have been taught that if you have a patient going through chemo - you need to get them to eat, not fast[116]... years ago he'd go to conferences and doctors would say…
VL You know, this is ridiculous. It's like, Oh, you know, will I tell my patients to fast during chemotherapy? Absolutely not!
But little by little things have been changing…. thanks to some exciting crumbs of research.[117] Like, just recently, this one trial came out - which had[118] more than 100 people with breast cancer. Some went on a fasting diet for three days before chemo as well as on chemo day - while others stuck to their regular diet. The research team, which included Valter, took images of the patients' tumors … and found that for those on the fasting diet - it was more likely that their tumors had shrunk[119]
VL The more the cycles of the fasting diet, the more shrinking of the tumor and the more killing of the cancer cells within the tumor.
Another study from a few years back of over 2000 women[120] who had breast cancer, found that for those who fasted more than 13 hours each day - they were less likely to get breast cancer a second time.
And then just quickly, in Italy researchers did this study where they just wanted to see if fasting diets were safe for people with advanced cancer - and they found that it was[121] - but then they followed 75 people in that trial for years to see: if it actually helped with their survival?[122] And it looked like it did. It definitely wasn't a cure for everyone, and in fact around half the people in the trial died from cancer within a few years – but the authors said that was still better than expected for these patients who, remember, had this advanced cancer[123].
And in that trial there was something that got Valter really excited – a handful of patients who were, what the researchers called "extraordinary responders"...[124]
VL They were all stage four colorectal, breast, lung, and pancreatic cancer. I mean, the type of patient that all oncology will say, this patient is going to die very soon. And all of them went into remission, right? So, I mean, all five, all five went into remission. So I think that certainly brings everything to a different level
So clearly, fasting isn't a silver bullet for cancer – but this research suggests that for some people, with some cancers – when combined with chemo - fasting could be a game changer.
VL I hope it gives a lot of hope. I hope it gives hope, obviously you still have some, some doubts because you never know. But I mean, I say overall that the results have been very positive,
WZ: Do you think that all patients right now who have cancer and are going through chemo should start a fasting diet?
VL No, I don't. So it looks very, very promising, right? We would all be very surprised if it didn't work. But what if, right? What if, uh, it makes it worse for some patients and, or, you know, it doesn't work.[125] So yeah, I would say that all patients with advanced stage cancer, or cancer for which there is nothing working should talk to their oncologist
One of the uncertainties with cancer patients is that some fasting diets could cause other problems, like people might lose too much weight and then become malnourished[126][127][128]
And away from cancer, this got us thinking, are there other downsides to these fasting diets? Like, other than losing the joy of eating..
Well this takes us to the new research that came out last week… which seemed to suggest that fasting could actually be dangerous… this made big news… all around the world..
Well now to a recent health alert that causing quite a stir, we're talking intermittent fasting
This was really shocking!
Intermittent fasting — is it dangerous?
The study – which by the way hasn't been peer reviewed yet (I know, I know!) – found that people who said they were eating in an 8 hour window… so let's say fasting for 16 hours – had a higher risk of dying from heart disease, years later[129] [130] … And actually this isn't the first study to find this kind of thing[131][132][133][134][135]... which might sound a little scary - but some scientists are quite critical of these kinds of studies – because they're not randomized control trials - so we really have no idea whether these deaths had anything to do with fasting or perhaps this is just kind of a coincidence … and I know this is frustrating… we just don't have a lot of long term data on people going on these diets.
And then there's some other risks… like diets like this can sometimes mask other things going on, like eating disorders. And some people do report [136] feeling constipated, dizzy or weak. And then there's this thing you might not expect. [137] [138] [139] [140]
VL Gallstone formation[141] or need of gall bladder removal [142]goes up[143] [144].[145]
WZ Oh wow.
Gallstones are lumps in the gallbladder … which can be really painful…[146] …
VL So that’s just an example of how you cannot think everything is always going to go the way you want it to go.
And it’s these kind of surprising… side effects … that are why people should be a bit cautious before they’re diving into these fasting diets, particularly the more extreme versions. [147]...
So when it comes to fasting … does it stack up like pancakes with maple syrup?
Here's our conclusion:
So to cap us off ... is this a wonder diet or a .. wonder why your friends are on it diet? I think we’ve gotta say it’s a bit of both. There is some interesting work happening here… but the bro-hards… and healthfluencers… are getting a bit carried away. WHAT A SURPRISE!!?
That’s Science Vs Intermittent Fasting.
Citations: There are 147 citations!
CREDITS
This episode was produced by Kaitlyn Sawrey, Nick DelRose, and me, Wendy Zukerman with help from Michelle Dang, Rose Rimler, Joel Werner and Meryl Horn. We’re edited by Blythe Terrell, with extra editing help from Caitlin Kenney and Annie-Rose Strasser. Fact checking by Eva Dasher and Michelle Dang. Mix and sound design by Peter Leonard and Bobby Lord. Music by Peter Leonard, Emma Munger, Bumi Hidaka and Bobby Lord. A huge thanks to all the researchers we got in touch with for this episode including Dr Peter Chisnell, Dr Mikkel Holm Vendelbo, Dr Jiahong Lu, Dr Dorothy Sears, Prof. Mark Mattson, Dr James D Dvorak, Dr Calloway Scott, Professor Richard Billows, Professor Nancy Worman, Dr Barbara Kowalzig and the University of Alabama, Birmingham. Also thanks to Kimmie Regler, Helen Zaltman, Frank Lopez, the Zukerman Family, and Joseph Lavelle Wilson.
I’m Wendy Zukerman… fact you next time.
[2] Jack Dorsey https://www.podcastone.com/episode/The-Jack-Dorsey-Podcast-Advanced-Stress-Mitigation-Tactics-Extreme-Time-Saving-Workouts-DIY-Cold-Tubs-Hormesis-One-Meal-A-Day--More
(2019)
00:44:29–00:44:37 (and up to 00:44:50) “He said- I only eat one meal a day. And I’m like wow– that’s extreme but also like, really simple…and I just decided OK I’m going all in on this.” “For the past 2 years I only have dinner” (Jack Dorsey)
00:47:58 During the day I feel so much more focused…
[3] https://www.youtube.com/watch?v=LiF8M52wyy4
(2021)
4:37–4:43: “Basically for the last 10 years I’ve fasted anywhere from 12-16 hours for ever 24-hour-cycle” (Huberman)
[4] https://newsroom.heart.org/news/8-hour-time-restricted-eating-linked-to-a-91-higher-risk-of-cardiovascular-death?preview=6245&preview_mode=True From the researchers’ poster: Eight-hour TRE was significantly associated with higher risk of cardiovascular mortality in the general population as well as in people with CVD or cancer./ https://www.newscientist.com/article/2422585-intermittent-fasting-linked-to-a-higher-risk-of-heart-disease-death/?utm_campaign=RSS%7CNSNS&utm_source=NSNS&utm_medium=RSS&utm_content=currents
[5]https://www.uab.edu/shp/nutrition/people/faculty/courtney-peterson
[6] https://www.youtube.com/watch?v=lwCRjwDs1Ek / https://www.youtube.com/watch?v=YW_oGL3Ui1A&t=83s / https://www.youtube.com/watch?v=8RcQ-nmqJlo&t=222s / https://www.youtube.com/watch?v=Ojt9PmqAfhA
[7] When people eat a food containing carbohydrates, the digestive system breaks down the digestible ones into sugar, which enters the blood.
[8] These macronutrients are obtained from the diet, with about 50% of the energy derived from carbohydrates, 35% from fat, and 15% from protein. p6
[9] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897177/ Carbohydrate is usually the main source of dietary energy, yet the body stores of glycogen are very limited: 500–1000 g. …Protein intake is usually about 15% of dietary energy
[10] Fig 2: When somebody loses 10 kg of fat (triglyceride), 8.4 kg is exhaled as CO2. The remainder of the 28 kg total of CO2 produced is contributed by inhaled oxygen. Lungs are therefore the primary excretory organ for weight loss.
[11] https://www.coursera.org/lecture/science-exercise/3-calorimetry-oxygen-consumption-llaYq 5m
“For example, if you are burning pure fat your respiratory exchange ratio (VCO2/VO2) will be 0.70. If you are burning pure carbohydrate your respiratory exchange ratio will be 1.0.”
[12] Carb calories 641, fat calories 787 after 12 hours of fasting (baseline reading) (45% carb / 55% fat) *updated with assumed protein values: Fat: 45% Carb: 40% Protein: 15%
[13] Carb calories 326, fat calories 1166 after 18 hours of fasting (21% carb / 79% fat) *updated with assumed protein values: Fat: 69% Carb: 16% Protein: 15%
[14] Therefore, the EODF treatment appears to favor fat burning. [Study in mice]
[15] it was shown that FA and glycerol turnovers increase robustly between 18 and 24 h of starvation and approximately two- to threefold after 3 days of starvation compared with an overnight fast (Table 1) (60, 116). P2 Also, look at Fig1. P2.
[16] Study of 16 women during Ramadan using a metabolic chamber: Fat oxidation was increased and carbohydrate oxidation was decreased during the light span of the nycthemeron
[17] During fasting, adipose tissue, muscle, liver, and kidneys work in concert to supply, to convert, and to conserve fuels for the body.
[18] Lipolysis and primary (intraadipocyte) free fatty acid (FFA) reesterification increased 2.5-fold (1.7 ± 0.2 to 4.2 ± 0.2 µmol·kg−1·min−1 and 1.5 ± 0.4 to 4.2 ± 0.8 µ mol·kg−1·min−1, respectively, both P < 0.05). This provided substrate for the increase in fat oxidation (from 2.7 ± 0.3 to 4.3 ± 0.1 µ mol·kg−1·min−1, P < 0.01), which contributed ≈75% of resting energy requirements after the 60-h fast and increased the supply of glycerol for gluconeogenesis.
[19] Metabolic balances and glucose turnover studies were performed and demonstrate again the predominance of lipid as fuel and emphasize the diminution of glucose metabolism, which, in turn, spares nitrogen stores as gluconeogenesis decreases. p16
[20] During short-term fasting, substrate utilization in skeletal muscle shifts from predominantly carbohydrate to fat as a means of conserving glucose. p1
[21] The metabolic switch typically occurs in the third phase of fasting when glycogen stores in hepatocytes are depleted and accelerated adipose tissue lipolysis produces increased fatty acids and glycerol 21. The metabolic switch usually occurs between 12 and 36 hours after cessation of food consumption, depending on the liver glycogen content at the beginning of the fast, and on the amount of the individual's energy expenditure/exercise during the fast.
[22] The intake of dietary carbohydrates mainly has the effect of inhibiting fat oxidation while glucose oxidation is increased.
[23] With the reintroduction of carbohydrate via oral feeding, EN, or PN, there is a sudden shift back to glucose as the predominant fuel source. p3
[24] In summary, there is a major switch from glucose to FAO during starvation that needs some time to become apparent. A similar duration of time is required for reversal of these fasting-induced changes upon refeeding. p7
[25] “While skipping just the occasional meal can be beneficial, cycling periods of fasting (usually in the morning) and feasting (usually at night) can aid detoxification, encourage fat burning, and improve immune function.” - Fat burning man
[27] Confirmed over email: Yes, I've run the most studies of fasting in humans for sure. This statement is accurate.
[29]E.g. Body weight decreased (P < 0.05) in the combination group (6 ± 4 kg), ADF (3 ± 1 kg), exercise group (1 ± 0 kg), with no change in the control group (0 ± 0 kg).
[31] Recent studies show that obese adults lose 4 to 8% of body weight after 8 to 12 weeks and that adherence to ADF remains high (90 to 95%) throughout the duration of the trial
[32] Shortterm studies of ADF demonstrate 3–8% weight loss after 2–3 months of treatment (Bhutani et al., 2013b; Eshghinia and Mohammadzadeh, 2013; Johnson et al., 2007; Varady et al., 2009). Our lab recently conducted a 12-month ADF trial in obese adults (Trepanowski et al., 2017) and we observed a mean weight loss of 6%. p1
[33] Human trials of alternate day fasting and 5:2 generally demonstrate reductions in body weight of 3 to 8% after 8 to 52 weeks of treatment, accompanied by decreases in blood pressure, LDL cholesterol, triglycerides, and insulin resistance [4–10]. The effects of time restricted feeding on the other hand, have only been tested in three human trials to date [11–13].
[34] Participants who adhered to eTRE ≥5 d/wk every week had greater improvements in body weight (−3.7 ± 1.2 kg; p = 0.003), body fat (−2.8 ± 1.3 kg; p = 0.04), heart rate (−7 ± 3 beats/min; p = 0.02), insulin resistance (−2.80 ± 1.36; p = 0.047), and glucose (−9 ± 5 mg/dL; p = 0.047) relative to adherers in the control group.
[35] KV email: “In our recent trials, we see that those who are adherent to the TRE protocol lose 5-15 lbs (on average) after 3-6 months.” https://www.sciencedirect.com/science/article/abs/pii/S1550413123004540?dgcid=author
[37] https://www.sciencedirect.com/science/article/abs/pii/S1550413123004540?dgcid=author
"After 1–3 months of TRE ignoring calories, body weight decreased by 3% to 5% versus controls,6,7,14,15 but not always.16,17 Only one study evaluated the longer-term ef- fects of TRE.8 After 12 months of 8-h TRE (12–8 p.m.), Lin et al.8 demonstrated 5% reductions in body weight in a racially diverse group of men and women with obesity. Since this longer-term study (12 months)8 did not produce greater body weight reduc- tions than short-term trials (1–3 months),6,7,14,15 it is possible that the weight loss efficacy of TRE may peak around 3 months. How- ever, more long-term studies will be required to confirm this."
[38] 3. It appears that almost any intermittent fasting regimen can result in some weight loss. Among the 16 intervention trials included in this review, 11 reported statistically significant weight loss. 4. Alternate-day fasting appeared to result in weight loss, as well as reductions in glucose and insulin concentrations, in the three studies evaluating this regimen. However, this fasting regimen may not be practical because it leads to intense hunger on fasting days. Modified alternate-day fasting regimens result in reduced weight, with reductions ranging from 3.2%, in comparison with a control group (10) during a 12-week period, to 8.0%, in a one-arm trial during an 8-week period (57). There was limited and mixed evidence for reductions in insulin concentrations, improvements in lipids, or reductions in inflammatory factors. 5. Research has not demonstrated that alternate-day fasting regimens produce superior weight loss in comparison to standard, continuous calorie restriction weight-loss plans. p16
[39] Our lab recently conducted a 12-month ADF trial in obese adults (Trepanowski et al., 2017) and we observed a mean weight loss of 6%. While this level of weight loss is not remarkable, it should be noted that weight change varied widely across participants, with some participants gaining þ3.7% and others losing –17.5% of baseline body weight. p1
[40] From Email with Krista: Yes, people that weigh more will lose more weight with intermittent fasting. For instance, obese people tend to lose 2-3 pounds per week, while normal weight/slightly overweight people tend to lose 1-2 pounds per week.
[41] It is possible that a higher level of protein intake by the ADF high-weight-loss group contributed to
their improved feelings of fullness (Astrup et al., 2015; Paddon-Jones et al., 2008). It can also be speculated that the increase in fullness and decrease in hunger helped these ADF participants better adhere to their fast-day calorie goals. p3
[42] Research has not demonstrated that alternate-day fasting regimens produce superior weight loss in comparison to standard, continuous calorie restriction weight-loss plans.
[43] This study compared intermittent energy restriction with continuous dieting found same amount of weight loss
[44] We conducted the first supervised controlled feeding trial to test whether IF has benefits independent of weight loss by feeding participants enough food to maintain their weight. Caloric intake was tailored to each participant’s unique energy requirements, and each meal provided about 33% of daily caloric needs.
[46] This strategy is called alternate-day fasting and involves a fast day where individuals consume 25% of their usual intake (approximately 500 kcal), alternated with a “feast day” where individuals are permitted to consume food ad libitum. Weight loss after 1 year in the alternate-day fasting group (6.0%) was not significantly different from that of the daily calorie restriction group (5.3%), relative to the no-intervention control group. Extra material: everyone eating basically same calories in Krista’s study
[47] Food intake was matched on a meal-by-meal basis across the two arms to eliminate any confounding effects from differences in food intake or meal frequency. p3
[48] 2022 Review (Krista Varady) “Findings to date suggest that ADF, the 5:2 diet and TRE produce mild to moderate weight loss (3–8% loss from baseline) over 8–12 weeks. This degree of weight loss is on a par with that achieved with traditional dieting approaches (daily calorie restriction).”
[49] 2022 Review: "Based on the evidence reviewed here, the majority of studies evalu- ating ADF, the 5:2 diet and TRE found a similar ratio of fat mass to lean mass loss (75% to 25%) as calorie restriction. Thus, it is probable that intermittent fasting does not help individuals with obesity to lose more fat mass or retain more lean mass during weight loss than traditional dieting."
[50] Difficulty in managing sensations of hunger is one of the main reasons given for aborted or unsuccessful attempts to diet
[51] Study that tried to repeat Krista’s didn’t find an increase in PYY *There were no significant changes in basal CCK or total PYY plasma concentrations over time within groups or differences between groups.*
[52] Alternate-day fasting appeared to result in weight loss, as well as reductions in glucose
and insulin concentrations, in the three studies evaluating this regimen. However, this
fasting regimen may not be practical because it leads to intense hunger on fasting days.
[53] Study in 10 people: Hunger levels were unchanged - > see (Fig. 1c). There was a significantly higher level of hunger on CR days compared to the ad libitum days throughout the study.
[54] In this study no significant changes in subjective feelings of appetite were seen with WL and no differences between groups were found, which it surprising given the magnitude of WL (12.5% WL).
[55] In this study in 16 non obese people - hunger didn't go down after 22 days of on and off fasting These results suggest that a prolonged schedule of fasting and feasting would be marred by aversive subjective states (eg, hunger and irritability), which would likely limit the ability of most individuals to sustain this eating pattern.
[56] Hunger on the fast day decreased (P < 0.05) by week 2, and remained low. [ONLY 16 people in this study]
[57] There was no increase in subjective hunger by the end of the study. Furthermore, fullness and PYY increased (P < 0.05).
[58]2019 Courtney Peterson’s study: Despite the longer daily fast (intermittent fasting), eTRF decreased mean ghrelin levels by 32 ± 10 pg/mL (P = 0.006), made hun-ger more even-keeled (P = 0.006), and tended to increase fullness (P = 0.06-0.10) and decrease the desire to eat (P = 0.08)”
[59] Intermittent fasting studies generally find that hunger levels remain stable22,31 or decrease during IF.38,45 A study of 30 participants over 12 weeks by Varady et al found reports of hunger during IF were no higher than with unrestricted consumption (level I evidence).49 Kroeger et al found that among those with the highest weight losses over 12 weeks of IF, hunger decreased and fullness increased.45 In the study by Harvie et al, 15% of participants reported hunger.27 Sundfør et al saw higher reported hunger in the IF group compared with those in the calorie restriction group.
[62] “Autophagy, a naturally occurring process in our bodies where cells remove toxins, recycle parts and repair their own damage is receiving new focus in the last few years for it’s promising longevity benefit…. Remember, autophagy is turned on when your body is in stress response mode. Stressing your cells is the natural way to turn on autophagy. You can do this through intermittent fasting and protein cycling to create nutrient deprivation in your cells”
[63] the best way to induce is through practicing fasting…. it’s now being called a “key in preventing diseases such as cancer, neurodegeneration, cardiomyopathy, diabetes, liver disease, autoimmune diseases and infections.” Autophagy has many anti-aging benefits because it helps destroy and reuse damaged components occurring in vacuoles
[65] We conclude that both fasting and CR have a role in the upregulation of autophagy, the evidence overwhelmingly suggesting that autophagy is induced in a wide variety of tissues and organs in response to food deprivation. “. Results demonstrated that autophagy was induced by starvation and nutrient deprivation. “ - in mice “For example, tumorigenesis may occur due to disturbances in cell growth and genome instability as a consequence of autophagy inhibition.” deregulated autophagy is known to be associated with several disorders, including metabolic diseases, neurodegenerative disorders, infectious diseases and cancer (6). “Autophagy is a lysosomal degradation process and protective housekeeping mechanism to eliminate damaged organelles, long-lived misfolded proteins and invading pathogens. Autophagy functions to recycle building blocks and energy for cellular renovation and homeostasis, allowing cells to adapt to stress.”
[66] It provides a routine “garbage disposal” service to cells, eliminating damaged components that could otherwise become toxic. . p2
[67] This process was aptly termed autophagy from the Greek “auto” or oneself and “phagy” or to eat. p2
[68] Autophagy is a process of self-cannibalization. Cells capture their own cytoplasm and organelles and consume them in lysosomes. The resulting breakdown products are inputs to cellular metabolism, through which they are used to generate energy and to build new proteins and membranes. Autophagy preserves the health of cells and tissues by replacing outdated and damaged cellular components with fresh ones. In starvation, it provides an internal source of nutrients for energy generation and, thus, survival.
[69]https://www.youtube.com/watch?v=16raAYQVOLA
https://www.youtube.com/watch?v=88COMmlA8uo (1:45-2:45)
[71] The most typical trigger of autophagy is nutrient starvation; in this sense, lack of any type of essential nutrient can induce autophagy. ...
[75] Starving mice or mammalian cells triggers autophagy in various tissues, which is regulated by several genes that also regulate aging and stress resistance, such as AMPK, mTOR, and sirtuins (Kroemer et al. 2010; Marino et al. 2010; Morselli et al. 2009)... Whether or not CR has the potential to reduce cancer incidence in humans remains largely unclear. [Also mentions evidence in yeast and c elegans (worm)]
[76] https://www.karger.com/Article/Abstract/212538 rats live longer
[77] Fig 1. Experiments on dietary restriction (DR) and genetic or chemical alteration of nutrient-sensing pathways have been performed on a range of model organisms. The results differ widely, and little is known about the long-term effects in humans.
[78]When 3xTgAD mice (which express APP, presenilin 1 and Tau mutations) were maintained for 1 year on either 40% CR or ADF diets beginning when they were 5 months old, they did not develop the cognitive impairment exhibited by 3xTgAD mice fed ad libitum: IF induces the expression of antioxidant enzymes and neurotrophic factors including BDNF and FGF2 (Arumugam et al., 2010); BDNF stimulates mitochondrial biogenesis (Cheng et al., 2012); IF up-regulates autophagy (Godar et al., 2015); neurotrophic factors and interventions that bolster mitochondrial bioenergetics (Mark et al., 1997; Caccamo et al., 2010; Liu et al., 2013) and autophagy (Majumder et al., 2011; Lin et al., 2013) can protect neurons in experimental models of AD. p 5-6
[79] we detected elevated levels of autophagic and lysosomal proteins in sciatic nerves from IF mice. The enhanced expression of degradative molecules was paralleled with a reduction in the pathologic accumulation
[80] NB These monkey studies were in calorie restriction, but Krista, and this paper notes “Recently, many studies have shown that intermittent fasting (IF) can have similar effects as CR [62, 64, 80, 81]”
[81] Revealed a statistically significant effect of CR in increasing survival (p=0.03; Fig. 2B) with a hazard ratio (HR) of 3.0 indicating that at any point in time the control animals had 3 times the rate of death from an age-related cause when compared to animals under CR. (This 2003 study found it improved) (This also found it improved 2009)
[82] We report here that a CR regimen implemented in young and older age rhesus monkeys at the National Institute on Aging (NIA) has not improved survival outcomes.
[84] We first examined two signaling markers associated with autophagy induction: increased AMPK phosphorylation and decreased S6K phosphorylation.28 Consistent with iTRF-enhanced circadian-regulated autophagy, iTRF increased night-time phospho-AMPK and decreased night-time phospho-S6K relative to ad lib diets for genetic controls but not per01 mutants
[85] Together, these data suggest that activation of autophagy is necessary for iTRF-mediated longevity.
[86] Eleven overweight adults participated in a 4-day randomized crossover study where they ate between 8 am and 2 pm (early TRF (eTRF)) and between 8 am and 8 pm (control schedule).
[87] Lastly, eTRF increased LC3A expression by 22% in the morning at the end of the 18-hour fast.
[88]https://journals.physiology.org/doi/full/10.1152/japplphysiol.01146.2017 Thus, fasting did elicit a response in several markers of autophagy, but without indications of initiation of autophagy in untrained human skeletal muscle. .. The present observation that fasting decreased LC3II protein content in skeletal muscle from the untrained subjects is opposite of the reported marked increase in skeletal muscle LC3II protein content with fasting in humans with unknown training state (43) and mice (17, 27, 29).
[89] Autophagy initiation is in part regulated by mTOR through ULK1 and fasting increased expression of the autophagic marker LC3B-II by ∼30%. p62 is degraded during autophagy but was increased by ∼10% during fasting making interpretation of autophagic flux problematic. .. Never the less, we are not able to exclude to possibility that the elevated LC3B-II levels in the fasted state reflects autophagosome accumulation and autophagy inhibition rather than autophagy induction
[90] Altogether, these findings reveal that nutrient deprivation does stimulate autophagy flux in circulating leukocytes from mice and in cultured neutrophils from fasted human volunteers"
[91] "Markers of autophagy in liver, but not in muscle, were elevated in response to IF in mice. In humans, autophagy markers in muscle were reduced, likely in response to weight loss."
[93]In adults with HF, an extended eating window is associated with reduced risk for cardiovascular mortality.. When models were adjusted for time of eating variables and all other covariates, extending the eating window beyond 11.02 h was associated with decreased risk of cardiovascular (HR 0.36 [95 % CI 0.16–0.81]), but not all-cause mortality. Time of first and last eating occasions were not associated with mortality.
[94] Higher eating frequency was independently related to lower all-cause and CVD-related mortality in people with diabetes, which can be used as a potential strategy for daily-diet management among populations suffering from diabetes.
[95] This study found that DEF less than 3 times and NFD shorter than 10 h or longer than 14 h were independently associated with greater cardiovascular and all-cause mortality.
[96] Nature review paper on cancer https://www.ncbi.nlm.nih.gov/pubmed/30327499
[97] A markedly increased consumption of glucose by tumors in comparison to the nonproliferating normal tissues was first described more than 90 years ago by the German physiologist Otto Warburg. This observation has been confirmed in a variety of tumor contexts and shown to correlate with poor tumor prognosis.
[98]Glycolysis is a physiological response to hypoxia in normal tissues, but Otto Warburg in the 1920s observed that tumor slices and ascites cancer cells constitutively take up glucose and produce lactate regardless of oxygen availability, an observation that has been seen in many types of cancer cells and tumors. p1
[99] tumour cells metabolize glucose, lactate, pyruvate, hydroxybutyrate, acetate, glutamine, and fatty acids at much higher rates than their nontumour equivalents; however, the metabolic ecology of tumours is complex because they contain multiple metabolic compartments.
[100] Cancer cells preferentially express transporters and enzyme isoforms that drive glucose flux forwards.
[101] It is hard to begin a discussion of cancer cell metabolism without first mentioning Otto Warburg. A pioneer in the study of respiration, Warburg made a striking discovery in the 1920s. He found that, even in the presence of ample oxygen, cancer cells prefer to metabolize glucose by glycolysis, a seeming paradox as glycolysis, when compared to oxidative phosphorylation, is a less efficient pathway for producing ATP(Warburg, 1956). p1
[103] Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy
[104] We selected a particularly aggressive tumor line (NXS2) that models neuroblastoma (NB), the most common extracranial solid tumor and the first cause of lethality in preschool-age children.
[105] The tumor development and survival of the NXS2/STS/Eto group was significantly different from that of the NXS2 group (P < 0.001; Fig. 5 A and Table S1), indicating that STS was highly effective in protecting the mice but only provided partial protection to cancer cells against etoposide. In fact, at least 50% of the NXS2/STS/ETO mice lived 10–20 days longer compared with the NXS2 mice (P < 0.05; Fig. 5 A). Considering that it takes the cells <30 days to go from the injected 200,000 to the metastasis that kill the mouse, this 10- to 20-day-longer survival indicates that many and possibly the majority of the cancer cells have died. In summary, of 28 mice from three genetic backgrounds that were starved for 48–60 h before etoposide treatment, only one mouse died (Fig. 4G). By contrast, of the 37 mice treated with etoposide alone, 20 died of toxicity (Fig. 4G).
[106] short-term food starvation dramatically increased the sensitivity of human tumor xenografts to cisplatin as indicated not only by a significant growth delay, but also by the induction of complete remission in 60% of the animals bearing mesothelioma xenografts, and in 40% of the animals with lung carcinoma xenografts
[108] Overall, mice fasted and treated with DXR had a 40% reduction in metastases compared to controls (Fig. 3B). The combination of fasting and chemotherapy was much more effective than either alone and delayed the progression of a variety of tumors, including breast cancer and glioma, reduced the number of organs affected by melanoma metastases, and promoted long-term cancer-free survival in up to 40% of mice with neuroblastomas. p5
[109]2020 Paper: “In conclusion, periodic fasting or FMD increases the anti-cancer activity of tamoxifen and fulvestrant, delays resistance to these agents and, in combination with fulvestrant and palbociclib, causes tumour regression and reverses acquired resistance to these two drugs.”
[110] Trial into prostate cancer and fasting - coming in December 2019 https://clinicaltrials.gov/ct2/show/NCT02710721?term=Fasting%2C+Intermittent+Fasting&cond=Cancer&rank=2
[111]2020 Paper: “the results of this study are the first to suggest that FMD cycles are safe and effective as an adjunct to chemotherapy in women with early breast cancer. These findings together with preclinical data encourage further exploration of the benefits of fasting/FMD in patients receiving a wide range of cancer therapies.”
[112] Here's another one: https://clinicaltrials.gov/ct2/show/NCT02286167?term=Fasting%2C+Intermittent+Fasting&cond=Cancer&rank=3 .. published here-- showed that ketogenic diet + fasting was safe for patients with glioma
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589278/
[113] Prostate Cancer https://clinicaltrials.gov/ct2/show/NCT02710721?term=Fasting&cond=Cancer&rank=5
[114] 2023 protocol for a RCT looking at 16hr fasting + chemo in patients with gynecological cancers
[115] Trials are underway to assess the role of fasting-mimicking diets on advanced lung cancer patients (NCT03709147 and NCT03700437).
[116] When side effects of cancer or cancer treatment affect normal eating, changes can be made to help you get the nutrients you need. Eating foods that are high in calories, protein, vitamins, and minerals is important.
[117] Thus, periodic fasting and FMD cycles lasting less than 5 days applied together with standard
therapies have a high potential to improve cancer treatment while reducing its side effects.
[119] “the radiologically complete or partial response, as measured by MRI or ultrasound before surgery, occurred approximately 3 times more often in the FMD group compared to the control group in univariate (OR 2.886, 95% CI 1.012–8.227, P = 0.047) and multivariate (OR 3.168, 95% CI 1.062–9.446, P = 0.039) analyses.”
[120] Study on the effect of nightly fasting: prolonging the length of the nightly fasting interval may be a simple, nonpharmacologic strategy for reducing the risk of breast cancer recurrence.
[122] Among 75 patients with advanced neoplasms enrolled in the NCT03340935 trial, six patients had haematological diseases, while 69 patients had advanced solid neoplasms, as defined as metastatic or locally advanced, unresectable tumours.. With a median follow-up of 44.2 months (95% CI:
38.4e50.6)
[123] 34 death events occurred in these 69 patients, and median overall survival after the initiation of the study treatment was 29.9 months (95% CI 23.6 – NR) Patients undergoing cyclic FMD in combination with carboplatin-gemcitabine had better OS when compared to patients receiving chemotherapy alone (median OS 30.3 months, 95% CI 18-NR, vs 17.2 months, 95% CI 15.3-25.1, log-rank P value .041).
[125] Whether or not CR has the potential to reduce cancer incidence in humans remains largely unclear, although CR can reduce clinical markers associated with cancer if it also involves protein restriction (Longo and Fontana 2010)
[126] In patients with cancer, there are substantial concerns that it may exacerbate malnutrition and that it will unavoidably cause excessive loss of lean body mass
[127] 2023 Review: “Unwanted weight loss is known to affect clinical outcomes and have negative impacts on the prognosis of the cancer patient.”
[128] “Fasting-related toxicities were limited to ≤ grade 2, most commonly fatigue, headache, and dizziness. …Fasting for 72 h around chemotherapy administration is safe and feasible for cancer patients.”
[129] Participants aged at least 20 years who completed two valid 24-hour dietary recalls and reported usual intake in both recalls were included from the National Health and Nutrition Examination Survey in 2003-2018.
[130] Compared with eating duration of 12-16 hours, eating duration <8 hours was significantly associated with an increased risk of cardiovascular mortality (HR, 1.96 [95% CI, 1.23-3.13]); this association was also observed in adults with cardiovascular disease (HR, 2.06 [95% CI, 1.12-3.81]) and adults with cancer (HR, 2.72 [95% CI, 1.28-5.80]).
[132] The habit of eating breakfast was associated with a lower risk of hypertension among healthy Korean adults.
[133] The results provide evidence that irregularity in breakfast consumption and daily intake timing patterns, particularly early in the day, may be related to weight status and inflammation.
[134]In adults with HF, an extended eating window is associated with reduced risk for cardiovascular mortality.. When models were adjusted for time of eating variables and all other covariates, extending the eating window beyond 11.02 h was associated with decreased risk of cardiovascular (HR 0.36 [95 % CI 0.16–0.81]), but not all-cause mortality. Time of first and last eating occasions were not associated with mortality.
[135] Higher eating frequency was independently related to lower all-cause and CVD-related mortality in people with diabetes, which can be used as a potential strategy for daily-diet management among populations suffering from diabetes.
[136]some subjects reported constipation (17%), water retention (2%), dizziness (<20%), and general weakness (<15%). Bad breath doubled from baseline (14%) to post-treatment (29%), though not significantly.
[137] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1419405/ these findings suggest fasting has a series of effects on gallbladder bile
[138]“Fasting. Fasting decreases gallbladder movement, which causes the bile to become overconcentrated with cholesterol.”
[139] These results agree with several studies showing an increase in the cholesterol saturation of hepatic and gall-bladder human bile after an eight- to 16-hour fast. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1507619/pdf/bmjcred00687-0019a.pdf
[141] Factors associated with gallstone formation after bariatric surgery are a higher rate of weight loss, prolonged overnight fasting, gallbladder hypomotility and reduced intake of calories and fibres
[142] Patients with symptomatic gallbladder stones should be treated, and all evidence thus far points to cholecystectomy as the better option than medical dissolution and extracorporeal shockwave lithotripsy
[143] Risk was greatest for 14 or more hours fasting, intermediate for 8-14 hours, and the least for fasting less than eight hours (Figure 1). p2
[144] figure 1 on p4A Prospective Study of Hospitalization with Gallstone Disease Among Women: Role of Dietary Factors, Fasting Period, and Dieting
[145] “For some, fasting may cause problems. For example, studies have found that people who regularly fast more than 16 or 18 hours a day have a higher risk of gallstones. They’re also more likely to need surgery to remove the gallbladder.”
[146] Overall, up to 20% of adults develop gallstones and >20% of those develop symptoms or complications. P1 Patients with gallbladder stones can present with characteristic symptoms called biliary
colic, which is defined as episodic attacks of severe pain in the right upper abdominal quadrant or epigastrium (P5)
[147] 11% of patients had gallstones... https://https://www.amjmedsci.org/article/S0002-9629(15)34675-9/fulltextwww.amjmedsci.org/article/S0002-9629(15)34675-9/fulltext