Does coffee activate mTOR?

Caffeine does not activate mTOR. The opposite is true: caffeine inhibits mTOR, a protein that drives cell growth, division and metabolism. This effect has been demonstrated in multiple independent cell studies using a variety of cell types, including cancer cells, blood vessel cells and immune cells.

How do researchers know that mTOR is being inhibited? They measure the activity of two proteins that mTOR normally switches on. After treatment with caffeine, both are clearly less active. Reduced activity of these proteins is a reliable indicator that mTOR is being suppressed.

A direct consequence of that mTOR inhibition is an increase in autophagy. Autophagy is the process by which cells clear out and recycle damaged components. This was observed in both cell cultures and animal experiments. How caffeine inhibits mTOR precisely has also been investigated: in gastric cancer cells it occurs via a protein called PTEN, which dampens a signalling chain leading to mTOR. When PTEN was artificially switched off, caffeine lost its inhibitory effect.

A safety note: one cell study showed that caffeine in combination with alcohol amplifies mTOR inhibition and causes additional damage to nerve cells. However, the quantities used were extremely high and are not comparable to normal coffee consumption. This result therefore says nothing about your morning cup of coffee.

An important caveat: all of this research was conducted in cells and animals, not in humans. It is unknown whether, and to what extent, drinking coffee meaningfully affects mTOR activity in the human body. The direction of the effect is consistent across the cell studies, but the translation to everyday practice has not yet been made.