High Cortisol Wakes You Up at 3AM (Do This to Fall Back Asleep)

DeLauer builds the case for glycine through multiple studies: a sleep and biological rhythms study showing 3g improved REM and memory; a nocturia study showing reduced nighttime voids; a rodent study proving the NMDA/SCN mechanism; and a creatine study explaining ATP stabilization. He emphasizes that 3g is the research-backed sweet spot, and many people underdose. He personally struggles with 2 a.m. awakenings to pee and sees glycine as a way to push that to 4 a.m., yielding 7 solid hours. He also notes the emotional blunting benefit, comparing it to a mild, legal form of dissociation that helps detach from pre-sleep stress. The timing advice—1 hour before bed—is based on absorption kinetics to ensure the cooling and calming effects align with sleep onset.

DeLauer describes a study published in the Journal of Complementary and Alternative Therapy that aimed to validate earlier rat findings in humans. Participants took 3g glycine or placebo for 4 weeks. The glycine group had significantly fewer nocturia episodes, reduced urgency, and a longer delay before the first nighttime void. DeLauer relates this to his own struggle: he wakes at 2 a.m. to pee and then has trouble returning to sleep. He notes that even if he still had to urinate, pushing that time to 4 a.m. would give him 7 solid hours. The study also found glycine improved bladder pain, suggesting a broader neurological effect on bladder sensation. He emphasizes that glycine suppresses the micturition reflex, meaning it dampens the sharp signals that wake you up, so you only wake when the bladder is truly full.

DeLauer cites a rodent study where glycine increased blood flow to the paws, improved REM sleep quality (more spindles), and reduced total sleep need. To test the mechanism, researchers blocked NMDA receptors and destroyed the suprachiasmatic nucleus (SCN). When they did, glycine no longer redirected blood flow or improved sleep. This demonstrates that glycine's effects depend on these brain regions. DeLauer interprets this as glycine acting on anxiety centers in the brain, not just as a passive vasodilator. The SCN is the master circadian clock, and NMDA receptors are involved in excitatory signaling; glycine's modulation there leads to a calming, cooling effect that facilitates sleep onset and REM.

DeLauer references a 2024 study in Sleep Medicine Reviews that strongly linked negative emotions to poor sleep quality and showed that emotion regulation ability can improve sleep. He then describes a fish study where glycine feeding decreased circulating cortisol, and notes human anecdotes of lower cortisol. He proposes that glycine blunts the emotional response itself, not just the aftermath. He draws a direct comparison to ketamine therapy for PTSD: ketamine floods NMDA receptors with glutamate, causing dissociation that allows patients to process trauma without the physiological stress response. Glycine, as an NMDA receptor co-agonist, may produce a similar but much milder dissociation, enabling a person to step back from a stressful event (like an argument or nasty email) and avoid the adrenaline surge that ruins sleep. He calls it 'almost a level of ego dissolvement,' which is a bold claim for an over-the-counter amino acid.

DeLauer explains a study in Journal Sleep Research showing that creatine reduces the amount of sleep required by increasing phosphocreatine in the brain, which decreases ATP depletion. He interprets this as the brain using creatine properly during sleep, preventing the energy dips that cause micro-arousals. However, he notes that creatine stores can be depleted. Glycine, as a precursor for creatine synthesis (via glycine aminotransferase), can continually fuel creatine production, preventing those valleys. So while taking creatine is beneficial, adding glycine ensures a steady supply, making sleep more resilient to ATP drops. He suggests that the combination could be more effective than either alone for people who wake up feeling alert but then crash.