Human Metabolism during Fasting – Phases I to V

Human Metabolism during Fasting – Phases I to V

The human body is capable of extraordinary feats, if challenged. Modern life allows little room for challenge (physiologic or psychologic) and most people remain inside the boundaries of their comfort zone. Let’s take nutrition for example.

We are used to eating multiple times a day everyday and we assume this was the ‘norm’ for all human history. But, common sense should have us think that this might not have always been the case.

Historic Perspective

Going only as little as 100 – 200 years in the past, humans did not ‘benefit’ from 24/7 food availability. It is reasonable to assume that often times they may have gone for days between meals, especially if we consider pre-modern societies where people lived in tribes.

During food shortage it might not be advantageous to die if perpetuation of the species is a priority. We wouldn’t be here if our ancestors died when times were tough. So, one may think, what are the mechanisms by which humans are able to survive, and sometimes even thrive, when no food is available?

The science literature of the 1960s is rich in prolonged fasting experiments, especially in the context of obesity. Some subjects have lived on nothing but water for months at end (yes, months). The longest medically recorded fast comes from the 1970s: a grossly obese subject fasted his way to stable normal weight (from 207 kgs to 82 kgs). Angus Barbieri fasted for 382 days.

Of course, not all fasting experiments ended successfully. Many of them were failures and some of them were even fatal. The ill health of the subject gave rise to complications leading to the failure of some experiments, while others were resulted in fatality.

Modern Day Practices

Nowadays, those who undergo prolonged fasting usually purpose for 7 – 21 days of water fasting – supervised or unsupervised. Some do it for alleviating or curing different medical conditions, while others for rejuvenation, thus allowing their bodies to shift focus from food digestion toward cellular repair and maintenance processes.

Can you imagine going for 7 days without eating? Most people cannot. But most people have the built-in mechanism to go through a fasting experience.

The research field shows an active interest on the topic, but regulations are stricter than they were back in the 1960s. Fasting is often coated with religious ideologies, and this may render it less ‘scientific’. But those who read the science literature know that is not the case.

Moreover, fasting, as a practice, does not grow in popularity as there are no entities to gain financially from it. Telling someone not to eat implies not selling them anything (this magic pill, that amazing product, etc). You may see my point.

If you are somewhat familiar with medical terminology and scientific research, you can read the papers of George Cahill from the 1960s. You can find them in many medical and non-medical libraries and databases online or offline. For online search, Pubmed and Google Scholar can be a starting point.

George Cahill was one of the leading researchers on fasting, diabetes, and obesity. So, in the next paragraphs, I’m going to derive from his wisdom and discuss the major metabolic adaptations that take place when someone undergoes prolonged fasting.

Metabolic Adaptations during Fasting

Assuming that the person undergoing prolonged fasting is on a normal diet, here are the phases, as described by George Cahill (and other researchers):

[Image Source: Cristi Vlad]

[Image Source: Cristi Vlad]

1. Phase I – the first few hours after you stopped eating

The body’s primary source of fuel is glucose, derived from the substrates you provided in your last meal (exogenous).
Glucose oxidation rate: 40 grams per hour.

2. Phase II – from 4 to 16 hours after the last meal

The body’s primary fuel is still glucose, but at this point the reserves provided from the last meal may have been completely used.
There is an increased production of glucose in the liver, a process known as gluconeogenesis.
Glucose oxidation rate: 7-8 grams per hour.

In this initial phase of the fasted state, gluconeogenic substrates (from which glucose is made in the liver) come from muscle catabolism, recycled lactate, recycled pyruvate, glycerol (not so efficiently at this point) and to a certain degree from the conversion of:

BOHB (beta-hydroxybutyrate) -> AcAc (Aceto Acetate) -> Acetone -> Propanediol -> Pyruvate -> Glucose. [66]

3. Phase III – between 16 – 32 hours after the last meal

Gluconeogenesis (GNG) gradually increases until the end of this third phase.
Glycogen stores (bundles of glucose molecules in the liver and muscles) are depleted.

4. Phases IV and V

Gluconeogenesis decreases significantly.
Glucose oxidation rate: 3.5 – 4 grams per hour.
The body starts burning fatty acids and ketones (substrates derived from fat) efficiently.
Ketones become the major fuel for the brain.
Muscle catabolism decreases significantly.

[Image Source: Cahill]

[Image Source: Cahill]


The biggest trouble encountered by practitioners (fasters) is during the first three phases. As blood glucose levels drop and as glycogen is depleted, symptoms like hunger, sugar cravings, low energy levels occur. I assume the purpose of these symptoms is to urge the subject to consume food, thus providing glucose substrates. But, glucose is not the only source of fuel we can use predominantly.

As more time passes from the last meal, oxidation of fat gradually increases. As the body switches to predominantly using fat for fuel (fatty acids and ketones, glycerol for GNG) the brain gradually reduces the ‘panic’ mode as it learns it can safely rely on these substrates.

Here we assume the subject is healthy and does not have any genetic mutations or medical condition to prevent him to adapt to the fasted state.

Late Phases, Ending the Fast

24 to 30 hours into the fast hunger symptoms fade away – hunger is the least of problems among fasters – it’s mostly non-existent.

Glycogen is depleted.
Gluconeogenesis occurs, but at a lower rate.
Insulin secretion is low (since there’s no need to handle circulating glucose levels)
Fats and ketones are oxidized at an increased rate.

The signal to end the fast in healthy people is when bodyfat is critically low and the body cannot rely on it anymore (for energy production and usage).

At this point, hunger (real hunger) comes back strikingly, signaling the subject: eat or die! This is a point of no return because when the metabolism cannot rely on fat stores anymore, it will start catabolizing muscle and organ tissue. This is life threatening.

However, it’s difficult to reach such low bodyfat levels nowadays. Let’s take myself for example. I amfairly lean. I could possibly undergo at least a couple of weeks of fasting (water only) without reaching the point of no return.

If lean people can fast for so long, what would you think about overweight and obese subjects? I think that’s why we see ‘unbelievable’ 382-day fasts.

Thoughts and Personal Experience

The possible negative symptoms that I mentioned (hunger, fatigue, headaches, lightheadedness, etc) are usually gone after the first 2-3 days in most people. Drinking plenty of water and unsweetened tea may alleviate these symptoms. Unsweetened black coffee may help with adherence.

For more safety some folks take 1 multivitamin/multimineral pill everyday of the fast. In my first prolonged fasting experiment, I did not experience these negative symptoms – possibly because of my adaptation to the fat burning mode (due to ketosis). During my fast I did not stop from doing my heavy lifting routine. I wrote about this in detail in Periodic Fasting.

Please do not take this post as medical advice. I am not a doctor and I don’t play one on the Internet either. Any strategy you may want to pursue, do it on your own and do it under supervision.

To educate yourself about fasting, search the medical databases that I mentioned at the beginning of the post. Whatever you read, try interpreting it as critically/skeptically as possible.

If you have thoughts, comments or concerns you want to discuss, let’s do it below!

Cristi Vlad holds a Master of Science (M.Sc.) in Civil Engineering. He did not profess in the field yet. He got absorbed into self-experimentation and writing books about the details of his experiments. More, on his personal blog:



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