Speaker 1: Hey, everyone, Welcome to another edition of Wisdom Wednesdays. And
Speaker 1: just before we start, another shameless plug for my book,
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Speaker 2: They had eight weeks on the app.
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Speaker 1: standby for an announcement. There will be a one day
Speaker 1: workshop in Melbourne, probably at the end of October start
Speaker 1: of November, but what's this space?
Speaker 2: So now on with the podcast.
Speaker 1: So today we're going to go deep into one of
Speaker 1: the oldest practices knowing to humankind, and that is fasting.
Speaker 1: As you probably were, it's been used across cultures for religious, spiritual,
Speaker 1: and therapeutic purposes for thousands of years, and in recent years,
Speaker 1: intermittent fasting and time restricted eating have taken the health
Speaker 1: world by storm.
Speaker 2: But today we're not going to talk about.
Speaker 1: Skipping breakfast or doing sixteen eight or any of those things.
Speaker 1: We're talking about a prolonged water fast only and specifically
Speaker 1: going to look at the effects of a seven day
Speaker 1: fast and what it does to the human body right
Speaker 1: down to the level of thousands of proteins circulating in
Speaker 1: your blood. And we're going to explore a groundbreak and
Speaker 1: study that was just published in Nature Metabolism, and also
Speaker 1: some other commentary that was published again in the journal Nature,
Speaker 1: really looking at the comparison of shorter fast the three
Speaker 1: or four day waterfast that many of you have tried,
Speaker 1: with some longer fasting. And by the end of this episode,
Speaker 1: I hope you'll have a pretty nuanced understanding of the benefits,
Speaker 1: the risk, and the biological effects of extended fasting, and
Speaker 1: a bit of clarity about were, if any were it
Speaker 1: might fit in your own health journey.
Speaker 2: So let's start with the research.
Speaker 1: A team of scientists from Berlin, Cambridge, Copenhagen and Oslo
Speaker 1: recruited twelve healthy young volunteers. Five of them were women
Speaker 1: and seven were men, and this is important because it
Speaker 1: was both sexes.
Speaker 2: And they asked them.
Speaker 1: To do something simple but definitely challenging for anybody who's
Speaker 1: ever done it. Drink only water for seven days straight,
Speaker 1: no calories whatsoever. And throughout the week, the researchers collected
Speaker 1: blood samples every morning and use the cutting edge proteumic
Speaker 1: platform to measure nearly three thousand proteins circulating in their plasma. Now,
Speaker 1: anybody who's heard me talk about the twelve major hallmarks
Speaker 1: of aging, one of those major hallmarks is loss of proteostasis.
Speaker 1: So basically, changes in how these proteins that circulate in
Speaker 1: our blood changes in them and how those changes actually
Speaker 1: accelerate to aging. And proteins are really the building blocks
Speaker 1: of all life. So in this study, they also tracked
Speaker 1: their body weight, their fat mass, their lean mass, their
Speaker 1: hormones and then metabolites like ketone bodies and fatty acids.
Speaker 1: So let's talk about what happened. So, as I said,
Speaker 1: twelve participants, five women and seven men, and they measured
Speaker 1: them before, during, and after a prolonged seven day fast
Speaker 1: with absolute calorie restriction, and they can just drink as
Speaker 1: much water as they wanted. So they took fasting blood
Speaker 1: early in the morning between six and nine am from
Speaker 1: all participants two days prior to the intervention. Then they
Speaker 1: took it daily during the intervention and then again three
Speaker 1: days after stopping the intervention, and in their plasma they
Speaker 1: looked at a total of twenty nine and twenty three
Speaker 1: protein targets. So this is a brilliant study. Hence I
Speaker 1: got into the journal Nature, which is one of the
Speaker 1: top journals around. Now what they find headlines is that
Speaker 1: on average, participants lost about five point seven kilos, which
Speaker 1: is roughly twelve pounds for those who use that currency. Now,
Speaker 1: most of the stuff that they lost was subcutaneous fat,
Speaker 1: the fat just under the skin, and they lost some
Speaker 1: lean muscle tissue. But interestingly, their muscle mass rebranded quickly
Speaker 1: once the food was reintroduced, whereas the fat loss was
Speaker 1: sustained and somewhat surprisingly, they didn't lose a lot of
Speaker 1: visceral fat. Most of the fat that they lost, as
Speaker 1: I said, was subcutaneous in nature. Now, one other thing
Speaker 1: is that is these guys weren't weren't huge. Their average
Speaker 1: WEE was seventy seven point five kilos. Now it was
Speaker 1: a mixture of men and women, but their average BMI
Speaker 1: was twenty five point four, which is just above the
Speaker 1: sort of cutoff of twenty five for overweight. So they
Speaker 1: were certainly by no means obese. But they lost five
Speaker 1: point seven kilos. So that is probably equivalent of, just
Speaker 1: off the top of my head, about eight percent of
Speaker 1: their weight loss, which is.
Speaker 2: Very very significant.
Speaker 1: So let's that I go and talk about the other
Speaker 1: things that they measured. Their blood glucose dropped, their fatty
Speaker 1: acids rose, and their ketones climbed steadily throughout the week,
Speaker 1: and that confirmed the metabolic switch from glucose to fat
Speaker 1: and ketone metabolism. And that's pretty standard for fasting, and
Speaker 1: it is one of the major benefits of people doing fasting,
Speaker 1: particularly time restricted feeding on the sixteen to eight is
Speaker 1: they develop what we call metabolic flexibility, where your body
Speaker 1: can switch from burning glucose to burning fat, and this
Speaker 1: is hugely important in this metabolic flexibility, and it's one
Speaker 1: of the biggest detrimental effects of our modern lifestyle about
Speaker 1: having food always available is that we tend to stay
Speaker 1: in glucose metabolism and it's not that good for us
Speaker 1: from a long term perspective. So that ability to switch
Speaker 1: over into ketones is pretty key. And they measured ketones
Speaker 1: such as beta hydroxy butyrate and beta hydroxy buryate is
Speaker 1: known to trigger a lot of different health benefits. But
Speaker 1: here's the big thing was the proteomic response, the deep
Speaker 1: systemic shifts in proteins across multiple organs, and that shift
Speaker 1: didn't really start until day three. In fact, over a
Speaker 1: third of all proteins measured, which was more in a
Speaker 1: thousand and changed significantly during the week. And these included
Speaker 1: proteins involved in immune signaling, tissue scaffolding, lip metabolism, hormones,
Speaker 1: and even brain related proteins like tenaskin art which is
Speaker 1: critical for maintaining synaptic plasticity. And so this wasn't just
Speaker 1: about weight loss this study. It was about multi organ recalibration.
Speaker 1: And the timeline is really important. Day one and day
Speaker 1: two seemed to be just a metabolic adjustment, and from
Speaker 1: day three onwards the body then appears to begin a
Speaker 1: deeper systemic reset. Now, the companion commentary in another paper
Speaker 1: published in Nature Metabolism. So this is a bunch of
Speaker 1: other researchers doing a commentary on it. It took it
Speaker 1: a step further, and the title of that was the
Speaker 1: weight loss independent Benefits of fasting, and that free as
Speaker 1: weight loss independent.
Speaker 2: That's pretty key.
Speaker 1: We often assume that fasting is just good for us
Speaker 1: because it reduces calories and weight loss, and whilst that's true,
Speaker 1: this commentary that appeared in Nature Metabolism highlighted that many
Speaker 1: of the benefits observed in the proteomic data are not
Speaker 1: tightly correlated with how much weight someone lost. In other words,
Speaker 1: fasting isn't just dadding with zero calories. It's doing something
Speaker 1: unique to our biology. These other researchers pointed out that
Speaker 1: some of the earliest protein changes oc curved before much
Speaker 1: of the weight had actually been lost, and many of
Speaker 1: the shifts, particularly in immune regulation, in mitochondrial function and
Speaker 1: stress response proteins, don't map neatly into the fat loss story.
Speaker 1: And this means that fasting may offer therapeutic potential beyond
Speaker 1: obesity for conditions that are linked to inflammation, autoimmune conditions,
Speaker 1: or neurological health as well. So when you hear people
Speaker 1: say that fastings just another way to cut calories, this
Speaker 1: paper and the associated commentary strongly suggest otherwise. They are
Speaker 1: unique biological processes triggered only when you completely abstain from
Speaker 1: food for a few days or more. Now, one of
Speaker 1: the most fascinating things is how feased these adaptations actually are.
Speaker 2: In the first couple of days, they.
Speaker 1: Found that the changes were relatively modest. A few hormones
Speaker 1: like grellin or thorroid hormones shift a bit, but nothing
Speaker 1: really dramatic. But by day three the proteonomic landscape transformed.
Speaker 1: Hundreds of proteins suddenly begin to increase or decrease, initiating
Speaker 1: cascades of tissue remodeling, immune modulation, and metabolic rewiring. And
Speaker 1: I want you to think of it like this. Fasting
Speaker 1: has a switch point, and it seems to be about
Speaker 1: seventy two hours in And that is why the study
Speaker 1: authors and commentary emphasize the calming fasting routines like intermittent fasting,
Speaker 1: time restricted feeding or twenty four are fast may not
Speaker 1: trigger and probably don't trigger these deeper metabolic adaptations. You
Speaker 1: might need at least three to four days to start
Speaker 1: unlocking them.
Speaker 2: So what does this mean. Here's how I would frame it.
Speaker 1: By day three, you're entering the doorway of metabolic shift.
Speaker 1: You've switched from glucose to ketones. You've suppressed leptin, down
Speaker 1: regulated thyroid signaling a bit, and begun to trigger some
Speaker 1: of the weight loss independent protein shifts across metabolism. By
Speaker 1: day four, you seem to be consolidating these early adaptations.
Speaker 1: Your ketones are picking fatty acids plateau, and some immune
Speaker 1: and brain related changes begin. But and this is crucial,
Speaker 1: many of the later adaptations, especially around tissue remodeling, the
Speaker 1: extracellular matrix and deep brain signaling proteins, really start to
Speaker 1: accelerate from day five to day seven.
Speaker 2: Now here's where I just want to add my lanes
Speaker 2: to it. And it's only my thoughts, but.
Speaker 1: I think you would be able to accelerate the positive
Speaker 1: effects of the fast by taking k tone esther supplements.
Speaker 1: So these are supplements that are now commercially available that
Speaker 1: will very quickly in the absence of food and switch
Speaker 1: you over from glucose metabolism to ketone metabolism to metabolism
Speaker 1: from fat, and in that driving you into ketosis triggers
Speaker 1: the release of being hydroxy buriod and other ketones, which
Speaker 1: I think seem to signal a lot of these changes.
Speaker 1: But this is just my theory and it's something that
Speaker 1: should tested. And actually I'm going to talk to Grant
Speaker 1: Schofield and my partner in the Hormesis Lab about doing
Speaker 1: just this and seeing if we can tweak or accelerate
Speaker 1: the timeline of those really really important metabolic shifts.
Speaker 2: And the other.
Speaker 1: Comment that I had, I initially when I read the paper,
Speaker 1: I thought, I'm guessing that these guys are older adults,
Speaker 1: because it didn't actually say in the paper. But then
Speaker 1: when I rechecked it, it said twelve and young healthy adults,
Speaker 1: So they weren't older adults, which is actually surprising for
Speaker 1: me because I believe that a lot of the benefits
Speaker 1: of fasting would really be in your forties and your
Speaker 1: fifties and your sixties. It is very frustrating that they
Speaker 1: did not give the ads. And I checked the supplementary
Speaker 1: materials online looking for the AEDs of the participants, but
Speaker 1: it didn't give it, which I don't know why they
Speaker 1: did not do that, but anyway, it is what it is.
Speaker 1: But what that would appear is that these benefits are
Speaker 1: not just for old bastards like me when everything starts
Speaker 1: to fall apart.
Speaker 2: Now we know, and I have talked about it before, and.
Speaker 1: That there are waves of aging that happen with us,
Speaker 1: and the first wave seems to be in the early forties,
Speaker 1: and then there's another way around sixty. There's potentially another
Speaker 1: way around the age of eighty. But the fact that
Speaker 1: they said they were young, healthy adults, that suggests to
Speaker 1: me that they were in their twenties or their thirties
Speaker 1: and still had significant benefits in metabolism, proteins involved in inflammation,
Speaker 1: involved in immunity, and all of these things.
Speaker 2: So this is.
Speaker 1: Surprising, but again quite frustrating, because I'd love to know
Speaker 1: the age of the people and whether there were any
Speaker 1: age related differences them. But that notwithstanding, I do think
Speaker 1: that you could potentially shorten that seven day fast down
Speaker 1: by taking a key tone ester right at the start,
Speaker 1: and you could get yourself some keytone strips from the
Speaker 1: chemist and just measure and if you go into ketosis
Speaker 1: on day one. That to me would appear to accelerate
Speaker 1: it by a couple of days. So you might get
Speaker 1: away with a five day fast rather than a seven
Speaker 1: day fast.
Speaker 2: But that's only my thinking, and I do.
Speaker 1: Want to run an experiment and we'll talk to Grant
Speaker 1: about that. So but what is clear is that a
Speaker 1: three or a four day fast is certainly not a
Speaker 1: waste of time, particularly if you take a key tone ester.
Speaker 2: It is a powerful intervention.
Speaker 1: And a three to four day water fast is a
Speaker 1: shit loat easier than a seven day waterfast.
Speaker 2: So I've done I've done a.
Speaker 1: Five day one, but I've also done ten days that
Speaker 1: was rather forced on combat survival and resistance to interrogation training,
Speaker 1: which I don't recommend you can bin all of that.
Speaker 1: But a seven day one, I think would be a
Speaker 1: shitload harder. So if we can shorten this process a
Speaker 1: little bit and get all those protein changes, that would
Speaker 1: be really interesting. But also what happens in a ten
Speaker 1: day fast is that even better than a seven day fast,
Speaker 1: And the fact that these guys were able to recoup
Speaker 1: the link tissue, the muscle that they lost, and they
Speaker 1: had no loss and bone loss, but they were able
Speaker 1: to after three days, I think recoop their muscle. That
Speaker 1: is actually a good thing. So let's talk about pros
Speaker 1: and cons just before we sum up.
Speaker 2: So the benefits here, they is very clear.
Speaker 1: There are weight loss independent benefits of our prolonged fast.
Speaker 1: There's unique shifts in immune stress and neural proteins, and
Speaker 1: there is significant subcutaneous fat loss while spurring bone mass,
Speaker 1: but some loss of muscle. Now, it didn't say that
Speaker 1: these guys did resistance training. That's another thing I would
Speaker 1: throw in there. If you did some resistance training on
Speaker 1: those days, just be aware that your kind of top
Speaker 1: end will be gone, but you could minimize the loss
Speaker 1: in muscle if you did that. And then there's real
Speaker 1: good potential therapeutic angles here for conditions like epilepsy. We
Speaker 1: know that a chidogenic diet is great for epilepsy, but
Speaker 1: also autoimmune diseases. And I've talked to a number of
Speaker 1: people I know who have autoimmune diseases, and I've recommended
Speaker 1: a five day fast or a five day fasting mimicking
Speaker 1: diet in conjunction with regular cold water exposure. But there's
Speaker 1: also benefits here for potential cardiovascular disease and even neurodegenerative diseases.
Speaker 1: But they're a little bit speculative, and there is this
Speaker 1: rebound resilient. As I said, the lean muscle tissue was
Speaker 1: largely recovered after refeeding. So let's talk about the drawbacks
Speaker 1: and the risk because I've heard a number of people
Speaker 1: talking about fasting and how it is risky and dangerous.
Speaker 1: So potential drawbacks and risks. Now, I remember these were younger,
Speaker 1: healthy adults. So one is hormonal suppression. Thyroid and reproductive
Speaker 1: signaling decrease was noticed, and now that's adaptive here, but
Speaker 1: if you already have thorroid or hormonal issues, it could
Speaker 1: be problematic. And there are some potential issues with coagulation
Speaker 1: and bone markers. Now, some of the signals suggested temporary
Speaker 1: risks for clotting or bone turnover, but again we don't
Speaker 1: know from the long term perspective. And then individual variability,
Speaker 1: while there were broad responses were pretty consistent, some protein
Speaker 1: shifted differently between participants. Not everyone will have the same
Speaker 1: benefit profile now and if any, but it's her doctor,
Speaker 1: Stacy Sims. She was on my podcast. She's brilliant. She
Speaker 1: talks about women are not small men. And now she
Speaker 1: has said previously that women shouldn't be fasting. I think
Speaker 1: this study shows that that's not the case. What I
Speaker 1: would add to the stacy sims women are not small men.
Speaker 1: Not all women are equal, and not all men are equal.
Speaker 1: And this study showed that there were individual differences, so
Speaker 1: not everybody is going to get the same benefit profile.
Speaker 1: And then finally, adherence and safety. Seven day water fast
Speaker 1: is mentally and physically demanding and for anyone with medical conditions,
Speaker 1: it should absolutely be supervised by your doctor. Now, some
Speaker 1: people might think, and I know health professionals who say
Speaker 1: fasting is dangerous and you shouldn't fast more than twelve
Speaker 1: hours and it can be really dangerous. But here's where
Speaker 1: a history lesson comes in. I am looking at on
Speaker 1: my computer right now. I am looking at a research
Speaker 1: paper in the Postgraduate Medical Journal of March nineteen seventy three,
Speaker 1: and it's a case report and the title of the
Speaker 1: paper features of a successful therapeutic fast of three hundred
Speaker 1: and eighty two days duration. This was back in the
Speaker 1: nineteen seventies. A Scottish dude weighing four hundred and fifty
Speaker 1: six pounds that's over two hundred kilos went to his
Speaker 1: doc and.
Speaker 2: Said, I'm a bit fat.
Speaker 1: I think I need to stop eating for a while,
Speaker 1: and they agreed for him to do a medically supervised fast.
Speaker 2: Wasn't intended to be that long, but he took.
Speaker 1: After a while, he took daily vitamins and minerals and
Speaker 1: had regular check ins, but no calories other than after
Speaker 1: I can't remember how long. It was quite a long
Speaker 1: long time. He started adding a little bit of milk
Speaker 1: in his tea. He lost a whopping two hundred and
Speaker 1: seventy six pounds. What's that one hundred and twenty two
Speaker 1: hundred and thirty kilos. He reached a healthy weight, and remarkably,
Speaker 1: he maintained the vast majority of his weight loss years Now.
Speaker 2: Even when his blood glucose.
Speaker 1: Dropped the levels that would terrify most doctors today, and
Speaker 1: that was around thirty milligrams per DECI leader, he remained alert, functional,
Speaker 1: and symptom three because he completely shifted into ketosis. Now,
Speaker 1: I'm not suggesting that you should go out and fast
Speaker 1: for a year, but this case study shows that the
Speaker 1: human body is remarkably well adapted to prolonged periods without food. Now,
Speaker 1: clearly he had a lot of reserve that he could
Speaker 1: live off. But the short of fast three days, four days,
Speaker 1: seven days, that really appeels in comparison to what's physiologically
Speaker 1: possible for lots of humans, and there are routinely there
Speaker 1: are monks who fast for one hundred days, right, So
Speaker 1: I would not be concerned unless you have current health conditions.
Speaker 2: But again, go and check with your doctor if you're
Speaker 2: keen on doing this.
Speaker 1: So if you're worried you're going to die without food
Speaker 1: for forty eight hours, you'll be all right. And the
Speaker 1: body is built to endure, adapt and even thrive provided
Speaker 1: that fast is done responsibly. So what's the takeout? Fasting
Speaker 1: is not just for weight loss. It triggers system wide
Speaker 1: changes in our proteum, and there are unique weight loss
Speaker 1: independent biological effects that appear to be very beneficial for
Speaker 1: lots of our organs or immune system. All of these things.
Speaker 1: The timing matters. The deepest systemic shifts begin after day three.
Speaker 1: But with my little Asterrex, what happens if you take
Speaker 1: a keto nester, But they continue to build across days
Speaker 1: five to seven, and we just don't know if day
Speaker 1: seven is the peak benefits. It may be that ten
Speaker 1: days is even more beneficial now. The other one is
Speaker 1: as always, fasting isn't for everyone if you have health conditions,
Speaker 1: if you take medications, or you're underweight, So one of
Speaker 1: the exclusion criteria here was females couldn't be below fifteen
Speaker 1: percent body fat and the meals couldn't below twelve percent
Speaker 1: body fat. So please consult the doctor before attempting it
Speaker 1: if you have current health conditions, if you take medications,
Speaker 1: or if you're pretty lean to start with. But for
Speaker 1: those curious, discipline and healthy enough to try fasting, especially
Speaker 1: prolonged fasting, may be one of the most profound, low cost,
Speaker 1: ancient tools that we have for resetting the body. That's
Speaker 1: it for this week, folks, Catch you next time.