Staying Asleep (Wake-Ups)
About this protocol
Where to start
Start with phosphatidylserine in the evening (200-300 mg). The most-evidenced supplement for blunting elevated evening cortisol, the most common cause of 2-4 AM wake-ups.
Add ashwagandha (KSM-66) with breakfast for daily cortisol modulation. Effect builds over 8 weeks.
Add magnesium glycinate before bed for deeper sleep architecture and fewer micro-arousals.
Add glycine for the body-temperature-related fragmentation pattern.
If wake-ups are accompanied by sweating, anxiety, or 3 AM dread — that''s the cortisol signature, prioritize phosphatidylserine + ashwagandha.
4 nutrients
Start here
Strongest evidence — the foundation of the stack.
Phosphatidylserine
200-300 mg, 1-2 hours before bedPhosphatidylserine blunts evening cortisol elevation — the most common driver of 2-4 AM wake-ups. Trial evidence in adults with chronically elevated evening cortisol supports improved sleep continuity and morning energy.[1, 2]
Ashwagandha (KSM-66)
600 mg, with breakfastAshwagandha lowers HPA-axis activation and serum cortisol. Trial evidence supports improved sleep quality and reduced anxiety over 8 weeks. Particularly useful for stress-related sleep fragmentation.[3, 4, 5]
Add if needed
Add these only if the foundation isn't enough.
Magnesium Glycinate
300-400 mg elemental, before bedMagnesium reduces micro-arousals and supports deeper sleep architecture. Foundational for any sleep-maintenance stack.[6, 7]
Experimental
Emerging evidence — try last, only if curious.
Glycine
3 g, 30-60 minutes before bedGlycine improves slow-wave sleep quality and reduces fragmentation. Particularly useful if you wake feeling overheated.[8, 9, 10]
Warnings
Lifestyle improvements
Address evening cortisol behaviorally
Bright screens, doom-scrolling, late workouts, and emotional content in the evening elevate cortisol. A hard cutoff 1-2 hours before bed transforms wake-up patterns within a week.
Eat enough protein at dinner
Blood-sugar dips in the early morning can trigger wake-ups in some people. A protein-containing dinner stabilizes overnight glucose.
Limit alcohol
Alcohol fragments deep sleep in the second half of the night — the exact window when 2-4 AM wake-ups occur.
Address chronic stress
Phosphatidylserine and ashwagandha are downstream of stress. Address the upstream causes directly.
See a sleep specialist if persistent
Persistent maintenance insomnia warrants evaluation for sleep apnea, restless legs, or other primary sleep disorders.
References
- Phosphatidylserine — supplement research overviewExamine.com link
- Hellhammer J, et al. Effects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) on the endocrine and psychological responses to mental stress. Stress. 2004;7(2):119-126.PubMed link
- Ashwagandha — supplement research overviewExamine.com link
- Chandrasekhar K, et al. A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root. Indian J Psychol Med. 2012;34(3):255-262.PubMed link
- Salve J, et al. Adaptogenic and Anxiolytic Effects of Ashwagandha Root Extract. Cureus. 2019;11(12):e6466.PubMed link
- Magnesium — supplement research overviewExamine.com link
- Abbasi B, et al. Magnesium supplementation on primary insomnia in elderly. J Res Med Sci. 2012;17(12):1161-1169.PubMed link
- Glycine — supplement research overviewExamine.com link
- Yamadera W, et al. Glycine ingestion improves subjective sleep quality. Sleep and Biological Rhythms. 2007;5(2):126-131.Sleep Biol Rhythms link
- Bannai M, Kawai N. New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep. J Pharmacol Sci. 2012;118(2):145-148.PubMed link
Related protocols
Other sleep protocols and protocols sharing ingredients with this one.
Better Sleep
sleep
Magnesium, glycine, L-theanine, and apigenin work through complementary mechanisms (GABA modulation, NMDA antagonism, core body temperature regulation) to support faster sleep onset and deeper sleep. Evidence ranges from moderate (magnesium, glycine) to emerging (apigenin). This is a foundational sleep stack — not a substitute for sleep hygiene basics.
Falling Asleep Faster
sleep
Sleep-onset insomnia (difficulty falling asleep) is mechanistically distinct from sleep-maintenance issues (waking up). The drivers are usually nervous system over-activation, melatonin signaling, and core body temperature — not deep sleep architecture. This stack targets sleep onset specifically: magnesium for GABA modulation, L-theanine for alpha-wave relaxation, low-dose melatonin as a circadian signal (NOT a sedative), and glycine for the core body temperature drop that precedes sleep. Use this for "I can''t turn my brain off at night" patterns. If you fall asleep fine but wake up at 3 AM, see Staying Asleep instead.
Shift Worker / Night Owl
sleep
Shift workers and natural night-owls face a fundamental conflict: their work schedule misaligns with their circadian biology. Long-term shift work is associated with elevated cardiovascular, metabolic, and cancer risk. This stack supports circadian phase-shifting and sleep quality when sleeping during atypical hours: timed melatonin to signal "night" to the brain when sleeping in daylight, magnesium glycinate for nervous system relaxation, L-theanine for wind-down regardless of clock time, and ashwagandha for the chronic cortisol stress shift work imposes.
Deep Sleep & Recovery
sleep
Slow-wave (deep) sleep is when growth hormone peaks, memory consolidates, and tissue recovery accelerates. Some people sleep 8 hours but get insufficient deep sleep — often visible in poor next-day recovery, brain fog, and slow gains from training. This stack targets deep sleep architecture specifically: apigenin and magnesium L-threonate (crosses blood-brain barrier better than other forms), glycine for slow-wave enhancement, L-theanine for alpha-wave priming, and zinc for testosterone-mediated sleep architecture support.
Daily Calm
stress· 2 shared ingredients
Chronic everyday stress is a different beast than acute panic — what you want is HPA-axis modulation over weeks, not sedation. Ashwagandha (KSM-66) is the headline ingredient: trial evidence shows lower cortisol and lower perceived stress after 8 weeks of daily use. L-theanine is a fast-acting "calm but alert" add-on for individual stressful moments (presentations, conflicts, mid-afternoon overwhelm). Magnesium glycinate supports nervous system relaxation and downstream sleep quality, which compounds — better sleep → lower next-day stress reactivity.
Anxiety Relief
stress· 2 shared ingredients
Anxiety is different from stress. Stress is a response to external demand; anxiety is the persistent anticipation of threat — often without a clear external trigger. This distinction matters because the supplement levers differ. For acute anxiety (a presentation, a flight, a difficult conversation), fast-acting non-sedating options like L-theanine work. For chronic, lower-grade everyday anxiety, magnesium and ashwagandha modulate the HPA axis over weeks. For panic attacks, severe anxiety disorder, or anxiety that disrupts daily function, please see a mental health professional — supplements are first-line for mild-to-moderate symptoms only.
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Coming to App StoreDisclaimer: These statements have not been evaluated by the FDA. This protocol is educational, not a substitute for personalized medical advice. Talk to your doctor before starting any new supplement regimen — especially if you're pregnant, breastfeeding, on medications, or managing a chronic condition. Last updated 5/20/2026.