Glucose Supplementation for Sustained Stimulant Cognition
Published on December 27, 2025 7:58 PM GMTThe Observation
I take 60mg methylphenidate daily. Despite this, I often become exhausted and need to nap.
Taking small amounts of pure glucose (150-300mg every 20-60 minutes) eliminates this fatigue. This works even when I already eat carbohydrates. E.g. 120g of oats in the morning don't prevent the exhaustion.
The Mechanism
Facts:
https://www.cell.com/current-biology/fulltext/S0960-9822(22)01111-3
found that cognitive fatigue correlates with glutamate accumulation in the prefrontal cortex.
Glutamate is the brain's main excitatory neurotransmitter.
Excess glutamate is neurotoxic.
Hypothesis-1: The brain throttles cognitive effort when too much glutamate has accumulated.
Facts:
Glutamate is cleared by astrocytes.
This process costs 2 ATP per glutamate molecule (https://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2006.04083.x
).
The ATP comes from astrocyte glycogen stores.
https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1471-4159.2009.05915.x
found that blocking astrocyte glycogenolysis impaired glutamate uptake even when glucose was available.
Hypothesis-2: High-dose MPH increases brain glucose consumption. More neural firing means more glutamate released, faster glycogen depletion.
Hypothesis-3: Slow-release carbs like oats provide adequate total glucose but limited delivery rate. Pure glucose absorbs quickly, keeping blood glucose elevated so astrocytes can replenish glycogen as fast as they deplete it.
If these hypotheses hold, supplementing small amounts of pure glucose while working on stims, should reduce fatigue by supporting astrocyte glycogen replenishment. Possibly this has an effect even when not on stims.
The Protocol
150-300mg glucose every 20-60 minutes, taken as a capsule.