How To Hack a 7-Day Fast in 24 Hours
What happens when researchers take 12 people and place them on a 7-day fast? The results may change how you think about fasting. And I will give you some practical tools hack a 7-day fast in 24 hours.
Surviving long periods without food has shaped human evolution.
In both ancient and modern societies, fasting has been practiced by billions of people and been used to treat diseases ranging from autoimmune and inflammatory disorders to neurological disorders, such as epilepsy.
But we still have a limited understanding of the adaptations humans undergo during a prolonged fast, and how these relate to chronic disease.
So, what happens when you fast for one day, two days, three days, or even a full week?
What changes occur across your metabolism, and different organ systems?
And are there ways to capture some of these benefits without having to starve yourself for seven days?
In fact, is there a way to achieve some of the benefits of a 7-day fast in just 24 hours?
Today, we’re going to answer those questions.
(Hint: the answer to the last question is, “yes.”)
Let’s begin with a rather famous 2024 study published in the journal Nature Metabolism.
And to give credit where it’s due, the opening hook of this letter was actually modeled on the paper itself, which I thought the authors framed perfectly.
The study design was straightforward — and that’s part of what makes it so valuable.
The researchers recruited 12 healthy volunteers and put them through a 7-day water-only fast.
No food. No caloric beverages. Just water for an entire week.
These were healthy individuals whose average starting BMI was 25.4 kg/m2.
As a little nuance, the study excluded anyone with body fat below 15% for women and 12% for men, which is quite lean, and was almost done for safety reasons.
And to the credit of the 12 participants, every single one completed the study, which is impressive. I think we need to give them some props.
Throughout the 7-day fast (days 0 – 7, below), and during a subsequent refeeding period (days 8 – 10, below), the researchers drew blood samples. But they didn’t just measure the usual suspects like glucose, insulin, and ketones…
They deployed a high-throughput proteomics platform capable of measuring 2,923 circulating proteins simultaneously.
Think of it this way: it’s a bit like fishing.
Often in science, we cast out a line looking for a specific protein, molecule, ketone body, or perhaps a hormone like insulin or ghrelin, and then reel it back in.
This technology is more like dragging a massive fishing net behind a trawling boat.
Instead of catching one or two targets, you pull up an enormous amount of biological signal that can then be studied.
As a result, the picture that emerged was far more complex, and far more fascinating, than anything that had been published before.
The way I want to approach this is by walking through the timeline: what happens on:
Days 1–2
Days 3–5
Days 5–7
The refeeding period.
Weight Loss: Lean Mass Loss Reversed vs Fat Loss Sustained
But before we get there, I know the question on a lot of people’s minds is: How much weight did they lose, and how much of that was body fat versus lean mass?
Over the seven-day fast, participants lost 5.7 kg (12.5 lbs; in panel b, above), equivalent to ~2 kg/m2 BMI units.
Looking at the raw numbers, a large proportion of that loss appeared to be lean mass (3.6 kg) which sounds concerning at first.
But there’s an important caveat.
The technologies we use to measure lean mass aren’t necessarily measuring just muscle. They also capture tissues such as the liver, as well as factors like water content and glycogen stored within muscle, rather than just the functional contractile proteins that make up muscle tissue. (More HERE.)
As a result, it’s possible to see a substantial decline in measured “lean mass” during a fast, without that reflecting a meaningful loss of muscle.
Importantly, as the authors noted, the apparent loss of lean mass was “almost completely reversed” during the three-day refeeding period, “while the loss in fat mass (1.85 kg) was sustained.”
So, in short, even though measured lean mass decreased during the week-long fast, much of that either wasn’t muscle to begin with, or it rebounded very quickly. That’s reassuring. The fat that was lost, on the other hand, stayed lost.
Now, let me walk you through the timeline.
And it gets better as we go…
Days 1–2: The Fuel Switch
During the first couple days, your body burns through its liver glycogen stores, driving a switch to fat burning, which requires an increase in the machinery responsible for fat metabolism.
The broad sweep of changes in the proteome the researchers observed aligned perfectly with this pattern.
Proteins involved in fat transport, fatty acid metabolism, and ketone production all surged during the first 48 hours.
There’s no surprise there; that’s fasting 101.
Nuance Note on PCSK9 and LDL-cholesterol
If you’d like to save a couple of minutes and aren’t particularly interested in cholesterol or lipids: feel free to skip ahead to the Day 3–5 section.
But I can’t resist mentioning one specific early change for the lipid nerds among us: PCSK9.
You may have heard of PCSK9 in the context of PCSK9 inhibitors, a class of cholesterol-lowering drugs that includes Repatha.
PCSK9 is a protein that promotes the breakdown of LDL receptors in the liver.
Since LDL receptors are responsible for clearing LDL particles from the bloodstream, more PCSK9 generally means fewer LDL receptors and higher circulating LDL cholesterol and ApoB levels.
PCSK9 inhibitors work by blocking this process.
In effect, they inhibit the inhibitor, leading to more LDL receptors, greater LDL clearance, and substantially lower LDL cholesterol levels.
Interestingly, fasting reduced circulating PCSK9 levels, starting within the first 48 hours, as you can see below.
Why?
One possibility relates to the massive increase in fat trafficking that occurs during fasting.
As the body transitions from burning glucose to burning stored fat, fuel must be continuously mobilized from fat cells, processed by the liver, and distributed to tissues throughout the body.
Efficient fuel movement requires both the export of fat via triglyceride-rich lipoproteins, such as VLDL, and the uptake of lipid components from circulating lipoproteins, including LDL particles.
From that perspective, lowering PCSK9—and thereby increasing LDL receptor activity—may help facilitate the movement and recycling of lipid fuel during fasting.
In other words, the body may temporarily increase its capacity to handle lipid traffic during a period when fat becomes the dominant energy source.
*As a nuance note on the nuance note (I know: “Oh boy...here Nick goes again…”), what actually happens to LDL and ApoB levels during fasting depends on several competing factors. You can have increased production of VLDL and LDL particles at the same time that you have increased clearance through inhibition of PCSK9 and higher LDL receptor activity. In other words, both sides of the equation are changing simultaneously. So don’t get too hung up on the cholesterol numbers themselves. The bigger picture is that fasting appears to dramatically increase fat fuel flux throughout the body, and many of these lipoprotein changes are probably part of that adaptation. Hopefully that makes sense. Don’t stress if it doesn’t.
The point is a broader theme of this study:
The changes observed during fasting appear to be coordinated adaptations working together to support a fundamentally different metabolic state.
Or, if I had to distill the last 500 words on the first two days of fasting into three words, they’d be: “burn fat now.”
Days 3–5: The Deep Remodeling Begins
But here’s where the story really gets interesting.
After the initial fuel switch, the researchers observed a massive second wave of protein changes that went far beyond energy metabolism—far larger than anything that happened in the first two days.
It’s like first two days are mostly about changing what the body burns. Day three is when the renovation crew shows up. Instead of merely swapping fuel tanks, the body begins rewiring systems throughout the building.
Proteins related to the immune system, inflammation, the brain, blood clotting, cellular stress responses, cardiovascular disease, all began shifting.
A total of 1,034 proteins changed significantly over the 7-day fast, and the majority didn’t really begin to shift until day 3.
We’re going to return to this “day-3 threshold” in a moment because it’s one of the most important findings of the paper.
But let’s complete our timeline…
Days 5–7: A New Metabolic Steady State
By the end of the week, many of the protein changes were approaching a new equilibrium.
The body wasn’t panicking.
It had settled into a reconfigured metabolic state that looked, at the protein expression level, fundamentally different from the original baseline state.
And, notably, some of these late-stage changes mapped onto proteins and pathways that have been independently linked to longevity, neuroprotection, and reduced risk of cardiovascular disease and autoimmune diseases.
Seriously. Think about this: more than one-third of all ~3,000 measure proteins changed significantly. And those specific changes provide remarkable insight into how fasting physiology actually works, and why it may matter in common diseases.
So, like an ATP synthase rotor spinning furiously in the inner mitochondrial membrane, that’s where we’re going to excitedly turn next!
The rest of this letter is for StayCurious Metabolism Premium members. We’ll dive into:
The Day 3 Threshold: Why it matters, what changed, and what it tells us about the fasting literature.
The Refeeding Surprise: What snapped back, what didn’t, and why that distinction matters.
Practical Takeaways: Including how to hack a 7-day fast in just 24 hours, with a little metabolic demonstration conducted by yours truly.
If you’re someone who loves diving into the deepest corners of human metabolism and questioning nutritional dogma along the way, come join the fastest-growing community of metabolic health nerds on the platform and find out why so many members say becoming a premium subscriber was the best investment they’ve ever made in their health.
