The Physiology of Fasting

The simple truth is every body responds to fasting a little differently. Genetics, health, lifestyle…all these things play a part. But for a healthy person embarking on a fasting journey, there’s a general timeline of events—a predictable set of metabolic responses as your fast stretches from hours into days. We’re breaking down that timeline here.

Between 0 and 3 hours, your body is still going through the process of ingesting and storing the last thing you ate. After your body breaks down carbs, protein, and fat into glucose, amino acids, and fatty acids, your body metabolizes them for energy or stores them for later use. Depending on the last thing you ate before starting your fast, a few different hormones could be at play in your bloodstream.

If you’ve eaten a meal heavy in carbohydrates, you’ll have a lot of glucose in your bloodstream. That means a rise in insulin. Your pancreas secretes insulin to help shuttle glucose into cells where it can immediately be used for energy production, protein synthesis in muscles, or stored for later use, either as glycogen (the short-term storage of glucose) or as adipose tissue (long-term storage). Three hours after your last meal, glucose and insulin have most likely returned to “normal” pre-meal levels.

You’ll also experience a fluctuation in ghrelin and leptin. Ghrelin, the “hunger hormone” is what turns on your appetite. Leptin does the opposite. After a meal, your ghrelin levels fall and your leptin levels rise, effectively turning your appetite off, signaling to your brain that you’re full.

The 0–3 hour time frame is what we call an anabolic, or growth period since nutrients are available and the body can burn them, build muscle with them, or store them.

During the 4–24 hour phase, your body switches to the catabolic, or breakdown, state where stored nutrients are put to use. Once blood glucose and insulin levels drop, you’ll experience an uptick in glucagon—a catabolic hormone that stimulates the breakdown of glycogen (stored glucose) for energy. Since glucose is still your body’s main fuel source in this phase, your metabolism will attempt to break down enough glycogen to keep your blood glucose in the “normal” range (about 70–120 mg/dL).

Toward the end of this phase, you’ll likely start depleting your glycogen stores, which means you need access to another fuel source. Your body will begin the switch from glucose to ketones. Glucose is still your primary, preferred fuel source, but when your glucose reserves are nearing empty, you’ll start using fat stores and ketone bodies to make up the difference. Between 12 to 24 hours, blood glucose levels will be reduced by about 20%.

The exact time that your body starts shifting from using glucose to ketones for energy depends on how much glycogen you’ve got stored away and how much energy you’re burning throughout the day. This switch happens faster if you’re exercising since you’ll burn through your glycogen stores more quickly.

Your body is switching into fat-burning mode now—glycogen is significantly depleted, so you’ll produce and use ketone bodies for energy. Through the breakdown of fat (a process called lipolysis), fat cells in the body release free fatty acids. PPAR-alpha (a regulator of fat metabolism in the liver), which is necessary for ketogenesis, is activated and ensures those fatty acids are used.

Fatty acids travel to the liver where they are transformed into ketone bodies through the process of beta-oxidation. When we say “ketone bodies,” we’re referring to three distinct types of molecules: acetone, acetoacetate, and beta-hydroxybutyrate, or BHB for short. Your body can use both acetoacetate and BHB for energy production. Blood ketone meters, which you may have seen people use while fasting or on a ketogenic diet, measure BHB levels in the blood. BHB levels can vary based on the individual, but within 24–72 hours of fasting, you’re likely to see BHB levels rise to somewhere between 0.5–2 mM; the range for nutritional ketosis.

At this point, ketones become your primary fuel, but your brain still needs a bit of glucose to function. With none to be found in your blood, and your glycogen stores completely tapped, your body makes glucose from non-carbohydrate sources like fat, ketones, and amino acids through a process called gluconeogenesis. Yes, your body can actually make sugar out of protein and fat. During this phase of fasting, you produce about 80 grams of glucose per day using this process, most of which is used by the brain. The rest of the body can rely almost exclusively on ketone bodies.

So what’s going on with ghrelin, the hunger hormone? This deep into a fast, It actually starts to decline again. One study showed that even though ghrelin rises and falls in a cyclic pattern related to circadian rhythm, total ghrelin output decreased every 24 hours of fasting. So, by day 3, overall ghrelin output was lower than day 2 and day 1. These results may explain why overall hunger levels seem to decrease around the third day of a fast and beyond.

We’re now in the prolonged fasting phase. After day 3, glucose and insulin levels remain low, hunger stays suppressed, and you’re in a steady state of nutritional ketosis. You’ll also see a decrease in something called IGF-1 (insulin like growth factor). IGF-1 is a hormone involved in growth and development. When nutrients are restricted, your liver decreases its IGF-1 production, plus there’s a decrease in IGF binding proteins. Short-term decreases of IGF-1 activity in adults have been associated with less oxidative stress and may be an important part of anti-cancer and anti-aging dietary interventions.

Prolonged fasting has also been shown to activate cellular resistance to toxins and stress in both mice and human studies. A minimum of 72 hours of fasting seems to be required to experience these benefits. Fasting for 3+ days has been shown to decrease circulating insulin and glucose by 30% or more, which can contribute to decreased risk of metabolic disease. The decreased levels of growth hormone and insulin in the bloodstream also seem to have benefits for immunity, inflammation, neurogenesis, and overall metabolic health.

BHB (one of the three ketone bodies) levels continue to rise throughout your fast. At this point, they’ll likely settle out around 1.5–3 mM. BHB levels above 2.0 mM may correlate with lower hunger levels as well, since the body is now producing sufficient amount of ketones to fuel the body.

After fasting for 5 or more days, glucose, insulin, and IG-F are all significantly reduced, and you’re in a steady state of ketosis. Five days of fasting in humans has been shown to cause over a 60% decrease in IGF-1 and a significant increase in IGF-1 inhibiting proteins. After 10 days of fasting, IGF-1 levels may be as low as those seen in people with growth hormone deficiency—a population associated with reduced risk of cancer, diabetes, and overall mortality.

Conversely, BHB levels will continue to rise. It’s important to note here the difference between ketosis (burning ketones for fuel) and ketoacidosis (dangerously acidic blood from overly high ketone levels, usually only seen in alcoholics, diabetics, and cases of extreme starvation). Normally, the presence of insulin tells the body to stop increasing its production of ketones and plateau them at a safe level, but since your insulin levels remain low throughout a prolonged fast, this feedback loop doesn’t occur. One study showed that BHB levels will eventually plateau between 5–6 mM by day 20–25 of fasting. So if you’re contemplating an extremely long fast, it’s worth consulting with a medical professional to make sure you’re doing so safely.

Summary

As you can see, there is plenty of promising research on the metabolic benefits of fasting. Precisely which benefits you’ll experience depends on the duration of your fast. As always, we suggest working with a medical professional to find the plan and approach that’s best for your health and goals.

8 comments on “The Physiology of Fasting

  • Can I make 16:8 a continuous way of life to both loose/maintain weight whilst benefiting from the positive medical outcomes as researched?
    I look after an elderly parent with dementia so the stress levels can be heightened regularly for which I am prescribed Fluoxetin.
    I have found first 6 days of this TRF quite easy to follow and recorded my efforts which are positive I believe I have lost at least 3-4lbs since starting, just returned from holiday where junk food and alcohol were consumed over 9 days( I do eat healthily most of the time and try to make better food choices regularly)
    My goal is to stay within my prefered weight of 9-9st 7lbs as any lower makes me look too skinny and OLD!
    I do look much younger than my years coming up to 65 December.
    Any advice appreciated
    La-Verne Lee

  • It’s discouraged to omit the author’s name in such articles — and detracts from it’s reputation.
    Kindly honor the reader, and yourself, by attributing these fine articles to the individual/s who wrote them.

  • I have started a Keto based diet ( less than 20g carbs/ day) with a ratio of 5%C, 70%F and 25%P on 2000 calories/day. Couple with IF of 18 hours. What if any would be the equivalent fasting duration using this regimen?

  • A very wide eyed open read for the better. I’m certainally doing this. With being overweight for over 25 years I’ve tried every diet. Nothing has worked. I’m a big believer in visual learning expecially when its backed up with evidence like you have shown. Thrown in with exercise I’d like to in the future get back in touch with my results?

    Why don’t drs tell you about things like this instead of saying go to slimming group?

Leave a Reply

Your email address will not be published. Required fields are marked *