Glucose Supplementation for Sustained Stimulant Cognition
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.
Proposed 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.
Hypothesis-2: Sustained stimulant use depletes astrocyte glycogen faster than it can be replenished.
Hypothesis-3: Elevated blood glucose helps glycogen synthesis, thereby maintaining clearance capacity.
If these hypotheses hold, supplementing small amounts of pure glucose while working on stims, should reduce fatigue by supporting astrocyte glycogen replenishment, which in turn increased how much glutamate can be cleared. Possibly this has an effect even when not on stims.
Protocol
150-300mg glucose every 20-60 minutes, taken as a capsule.
Isn’t this a really small amount, like a single raisin has this much free glucose in it right? Why not just microdose raisins? How does this create a signal against normal blood glucose variation? Your gut should be releasing a lot more glucose from just the oats. Do you have a metabolic disorder? I guess I’m trying to reason out about why your body isn’t already supplying the glucose to your brain in the first place from current digestion, and why would glucose microdosing get around this.
It’s possible I have a metabolic disorder that wouldn’t be detected by regular blood tests. And yes the amount of glucose is absolutely tiny. I also bought a blood glucose meter. It doesn’t show elevated values at all from supplementing glucose. When eating it does increase measurably in line with what is normal. I do have sleep apnea which might do weird stuff, like give you diabetes. I do have a CPAP though maybe there is still some effect from that.
I don’t quite understand why it works. But it seems really strong of an effect. Once I increased the amount of MPH I took, then I took 0.6g of glucose, and it suddenly made me feel a pressure in my heart. The effect of the MPH was now too much. Something was throttling the effect of MPH before taking the glucose. And somehow taking the glucose stopped the throttling. This happened in less that 10 minutes. Probably less than 5.
Have you tried double-blinding yourself, Gwern-style? (I. e., prepare a box with glucose capsules and a box with some placebo (empty capsules + close your eyes when taking them out of the box?); at the start of the day, pick the box to take capsules from at random; at the end of the day, try to guess whether it was the placebo box; then check; repeat for several days.)
No, but great idea! I’ll likely run one. I already ordered some microcristaline cellulose and designed an experimental protocol.
Agreed that this would clarify a lot. On the other hand, if you’re very confident that taking the capsule helps, then at worst you’ve stumbled on the cheapest and least harmful placebo known to humankind (a sugar pill!!). Maybe you should just run with it (acknowledging that it helps while releasing or holding lightly to the proposed mechanism).
+1 this. Wouldn’t it work pretty much just as well if not better to just, like… eat a spoonful of honey under those circumstances?
Blood sugar spikes are heavily blunted by short duration light exercise 10-20 minutes following sugar consumption. Additionally, exercise improves brain blood flow, which seems to be one of the bottlenecks.
Can confirm with a somewhat spectacular N=1.
My mother is a diabetic, and on medication for it. Her fasting sugar in the mornings used to be ~150, and she naturally wakes up at ~7 AM.
After doing a few minutes of moderately strenuous exercise ~25-20 min after a meal and before sleeping (blood sugar spikes slightly later after a meal than after straight glucose ingestion), on my suggestion, she now occasionally finds herself waking up due to hunger pangs at ~5-6 AM; her blood sugar at this point is often ~80-100. Even when she sleeps through the night, her fasting sugar in the morning is now almost always in the 80-120, usually 80-100 range after waking up, whenever she has followed the protocol.
(We’re probably going to reduce her medication dosage after this after consulting and confirming with her doctor, since it appears the reduction is significant enough that her current dose is now slightly too high.)
This seems to be an absolutely busted intervention for hyperglycemia, to the extent that I think a case can be made to upgrade this to the level of population-level general advice (“exercise semi-strenuously for a few minutes ~15-30 min after a meal as just a default thing you do and everyone else does”).
Some evidence from research in support of the claim made in sentence 1:
(from https://www.nature.com/articles/s41598-025-07312-y; emphasis added)
You specify glucose. Have you tried small doses of sucrose/fructose/fruit and found it to not work in the same way?
Have you tried larger doses?
This is very interesting. I’m very curious to hear how the self-blinded experiment goes.
In what form you buy glucose?
Glucose monohydrate powder, and then put it in capsules. (Dextrose/D-glucose monohydrate to be extra precise.)