The biology of fasting
What is actually happening in there
Autophagy, mitophagy, mTOR, AMPK, ketogenesis, the growth hormone response. Each of these is real biology with named machinery, and each is routinely described online with a confidence the measurements do not support. Every page here splits what has been observed in a living person from what has been observed in a mouse or a dish, and tells you how it was measured, because in this field the measurement method is usually the whole story.
12 mechanisms, 12 with human measurement cited.
Autophagy
Macroautophagy · Self-eating
The cell's recycling system: damaged proteins and worn-out structures get wrapped in a membrane, delivered to the lysosome, and broken back down into parts the cell reuses.
6 human studies of 6 cited
Mitophagy
Mitochondrial autophagy · PINK1/Parkin pathway
Autophagy aimed at one target: mitochondria that have stopped working properly are tagged, wrapped and digested, so a cell keeps the ones that still make energy cleanly.
7 human studies of 7 cited
Ketogenesis and beta-hydroxybutyrate
Ketosis · BHB · Ketone bodies
The liver breaks fat down faster than it can burn the pieces, condenses the surplus into small water-soluble molecules called ketone bodies, and exports them as a fuel the brain can use when glucose is scarce.
7 human studies of 13 cited
mTOR
mTORC1 · Mechanistic target of rapamycin
The kinase that decides whether a cell should be building or conserving, and the reason protein specifically, rather than calories generally, is what ends the fasted state.
6 human studies of 15 cited
AMPK
AMP-activated protein kinase
The cell's fuel gauge: a kinase that reads the ratio of spent to unspent energy currency and, when the reading drops, switches on the pathways that make ATP and switches off the ones that spend it.
2 human studies of 8 cited
The growth hormone response
GH · Somatotropin · Counter-regulatory response
Growth hormone secretion rises several-fold within two days of a fast, and the growth factor it normally works through does not follow it, which is the part that changes what the rise means.
7 human studies of 7 cited
Insulin and insulin sensitivity during a fast
Selective insulin resistance
Insulin falls fast and early, and the tissues become measurably less responsive to it, but only for glucose, which is the distinction that separates a normal fasting adaptation from the insulin resistance of metabolic disease.
6 human studies of 7 cited
Glycogen depletion and gluconeogenesis
Glycogenolysis · Making new glucose
The body does not burn through its stored sugar and then switch to making new glucose. It is already making most of its glucose from scratch within the first day, which means the metabolic switch everyone describes does not exist as a switch.
7 human studies of 9 cited
FGF21
Fibroblast growth factor 21
A liver hormone that in mice is the signal of fasting, and in humans turns out to respond mainly to how little protein you have eaten rather than how few calories, and not to a two-day fast at all.
6 human studies of 8 cited
BDNF and the brain
Brain derived neurotrophic factor
The brain's fuel switch during a fast is directly measured and solid in humans; the claim that fasting raises BDNF was tested directly in people and did not happen.
7 human studies of 10 cited
Sirtuins and NAD+
SIRT1 · SIRT3 · NAD+
A family of enzymes that can only work when the cell has NAD+ to spend, which ties them to nutrient state, and a field whose two most cited supporting results did not replicate.
4 human studies of 11 cited
Refeeding, the leucine threshold and refeeding syndrome
Breaking a fast · Hypophosphataemia
Coming out of a fast is its own physiological event with its own rules and, in a genuinely malnourished person, its own danger, and the danger is not that phosphate is lost but that insulin drives it inside cells all at once.
12 human studies of 18 cited