During the first 2 – 3 days after stopping food intake, the body begins to use glycogen reserves stored in the liver. As these reserves are depleted, blood glucose levels gradually decrease, typically reaching around 70 mg/dl.
This drop in blood sugar reduces the secretion of insulin – a hormone produced by the pancreas – and the body begins to rely on an alternative energy source: fat stored in adipose tissue.
How Ketosis Develops During Fasting
Under these conditions, the body releases fatty acids from fat stores. In the liver, these fatty acids are converted into ketone bodies (ketones), which become an alternative source of energy.
The main ketone bodies include:
- beta-hydroxybutyrate
- acetoacetate
- acetone
Among these, beta-hydroxybutyrate is one of the most important energy sources for the brain during fasting.
Ketosis – A Natural Survival Mechanism
Ketosis is considered an important metabolic adaptation in human evolution, as it enabled survival during periods of food scarcity.
As researcher Gary Taubes states:
“We can define this mild ketosis as a normal state of human metabolism during fasting. In this sense, ketosis is not only natural, but also healthy.”
The Role of Growth Hormone and BDNF
During fasting, moderately reduced blood glucose levels stimulate the release of growth hormone from the anterior pituitary gland.
This hormone may support the production of BDNF (Brain-Derived Neurotrophic Factor), which is involved in:
- protecting neurons
- forming new neural connections
- maintaining cognitive function
During fasting, the brain increasingly uses ketones instead of glucose as its primary energy source.
Energy Efficiency of Ketones
Ketones are an efficient source of energy. Research suggests that organs such as:
- the brain
- the heart
- the muscular system
can utilise ketone-derived energy very effectively under certain metabolic conditions.
The Ketogenic Diet
A ketogenic diet is characterised by a high fat intake (approximately 80 – 90% of total energy), with the remaining calories coming from proteins and carbohydrates.
In certain situations, a small portion of the body’s energy may also come from the breakdown of metabolically damaged proteins.
Glycation
An important biochemical process in the body is glycation, which refers to the binding of sugar molecules to proteins. This reaction is also known as the Maillard reaction.
Glycation leads to the formation of Advanced Glycation End Products (AGEs).
These compounds may cause:
- stiffening of protein fibres
- reduced protein function
- cross-linking between damaged proteins
High levels of AGEs have been associated in some studies with:
- cognitive decline
- impaired kidney function
- accelerated ageing processes
For this reason, many researchers are exploring ways to reduce their formation.
The Role of Fasting in Reducing Glycation
By maintaining lower blood glucose levels during fasting, the process of protein glycation may be reduced.
This may also decrease the accumulation of damaged proteins in tissues.
Some hypotheses suggest that these mechanisms could contribute to lowering the risk of certain degenerative diseases.
Effects on the Digestive System
During fasting or a ketogenic state, the digestive system enters a phase of functional rest, characterised by:
- reduced digestive motility
- decreased digestive secretions
- reduced insulin secretion
Under these conditions, blood glucose levels tend to remain stable at relatively low values, around 60 – 65 mg/dl.
Possible Implications for Degenerative Diseases
Maintaining lower blood glucose levels may help reduce glycation and the accumulation of damaged proteins.
Some hypotheses suggest that these mechanisms could influence processes involved in degenerative diseases, including by reducing amyloid accumulation.
Ketosis and Cancer Research
There is ongoing research exploring the role of metabolism in certain types of cancer.
For example, Dr. Giulio Zuccoli from the University of Pittsburgh School of Medicine has studied the potential role of the ketogenic diet in the treatment of glioblastoma.
The working hypothesis is that some tumour cells rely primarily on glucose for energy and may not efficiently use ketones.
These areas remain under active scientific investigation.
Conclusion
Water fasting leads to several metabolic adaptations, including:
- depletion of glycogen reserves
- use of fat as the main energy source
- production of ketone bodies
- stabilisation of blood glucose at lower levels
These processes represent natural mechanisms through which the body adapts to temporary food deprivation and may optimise its metabolic function.