The 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:

Wiehler et al. (2022) 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 (Escartin et al. 2006).
The ATP comes from astrocyte glycogen stores.
Sickmann et al. (2009) 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 [...]

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Outline:

(00:11) The Observation

(00:39) The Mechanism

(02:13) The Protocol

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First published:
December 27th, 2025

Source:
https://www.lesswrong.com/posts/rA7wMkH3JdMRgdgLo/glucose-supplementation-for-sustained-stimulant-cognition

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Narrated by TYPE III AUDIO.

“Glucose Supplementation for Sustained Stimulant Cognition” by Johannes C. Mayer

LessWrong (30+ Karma)