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GlyciRest Glycine

Luna

3,000 mg (3g)

Effect

Sleep-Promoting

Core Temp

↓ 0.5°C

Sweet Taste

Naturally Sweet
The body’s thermostat for sleep. Glycine is the simplest amino acid — just two carbons — yet it orchestrates one of the most powerful natural sleep mechanisms: core body temperature reduction. When you take 3 grams before bed, glycine activates NMDA receptors in the suprachiasmatic nucleus (your master circadian clock), triggering peripheral vasodilation that radiates heat from your core to your extremities. Your core temperature drops ~0.5°C — the same physiological signal that naturally initiates sleep. Clinical trials demonstrate faster sleep onset, improved sleep quality, enhanced slow-wave sleep, and remarkably, better next-day cognitive performance despite no sedation. Beyond sleep, glycine serves as a collagen precursor (33% of collagen is glycine), a glutathione building block, an inhibitory neurotransmitter, and an NMDA receptor co-agonist. This is the most versatile amino acid in the human body, and at 3 grams nightly, it becomes a cornerstone of restorative sleep.
Glycine produces its sleep effects through a unique thermoregulatory mechanism distinct from sedative compounds:

The Thermoregulation Mechanism

This is glycine’s unique and most powerful sleep mechanism:

Why Temperature Drop Induces Sleep

Multiple Mechanisms Summary

MechanismReceptor/TargetEffectSleep Relevance
ThermoregulationNMDA in SCN↓ Core temp 0.5°C★★★★★ Primary
Inhibitory neurotransmissionGlyR (glycine receptor)↓ Neural excitability★★★★☆
NMDA co-agonismNMDA glycine siteModulates glutamate signaling★★★☆☆
GABA potentiationIndirectEnhanced inhibition★★★☆☆
Cortisol modulationHPA axis↓ Stress response★★☆☆☆

Glycine Receptor (GlyR) Pharmacology

NMDA Receptor Co-Agonism

Glycine is an obligate co-agonist at NMDA receptors — glutamate alone cannot activate them:

Why Glycine Doesn’t Cause Sedation

Key Distinction: Glycine promotes sleep by mimicking the body’s natural thermoregulatory sleep signal, not by forcing CNS depression. This preserves normal sleep architecture and explains why glycine users wake feeling more alert, not less.

The Science of Sleep Temperature

Core body temperature and sleep are intimately linked:

Distal-Proximal Temperature Gradient

The key to sleep initiation is the distal-proximal skin temperature gradient (DPG):
TermDefinitionSleep Implication
DistalExtremities (hands, feet)Heat dissipation surfaces
ProximalCore/trunkHeat source
DPGDistal temp − Proximal tempHigher DPG = faster sleep onset

Clinical Temperature Data

StudyDoseTemperature Finding
Bannai 20123g↓ Core temp; ↑ peripheral temp
Kawai 20153g↓ Core temp during early sleep
Inagawa 20063g↑ Cutaneous blood flow (vasodilation)

The SCN-Thermoregulation Connection

Practical Implications

FactorEffect on Sleep TemperatureRecommendation
Glycine 3g↓ Core temp ~0.5°CTake 30-60 min before bed
Hot bath before bedParadoxical: initial ↑ then rapid ↓1-2 hours before bed
Cool bedroomFacilitates core cooling65-68°F (18-20°C)
Warm socks↑ Foot vasodilationCan help if cold feet
Heavy blanketsMay trap heatLight, breathable preferred
Exercise (late)↑ Core temp (delays sleep)Avoid within 2-3 hours
The Temperature Connection: Many effective sleep interventions work through temperature:
  • Glycine: Pharmacological vasodilation → core cooling
  • Hot bath: Post-bath vasodilation → rapid cooling
  • Cool room: Environmental heat sink → easier cooling
  • Melatonin: Also promotes peripheral vasodilation
Glycine is unique in providing a pharmacological trigger for the body’s natural temperature-based sleep initiation.

Temperature Timeline with Glycine

Impact on Sleep Stages

Glycine doesn’t just help you fall asleep — it improves sleep quality:

Sleep Stage Data from Trials

StudyMeasureFinding
Yamadera 2007Sleep onset latency↓ Significant reduction
Yamadera 2007Time to SWS↓ Reached faster
Bannai 2012Sleep efficiency↑ Improved
Inagawa 2006Subjective sleep quality↑ “Slept well”
Kawai 2015PSG architecture↑ SWS proportion

Slow-Wave Sleep Enhancement

The Next-Day Paradox

Remarkably, glycine improves next-day cognitive performance:
StudyNDoseNext-Day Finding
Bannai 2012113g↓ Fatigue; ↑ “clear-headedness”
Yamadera 2007193g↓ Daytime sleepiness
Inagawa 2006153g↑ Psychomotor vigilance

Sleep Quality Metrics

MetricWithout GlycineWith Glycine 3gChange
Sleep onset latencyBaseline↓ ReducedFaster
Sleep efficiencyBaseline↑ ImprovedBetter
Time in SWSBaseline↑ IncreasedMore deep
Night awakeningsBaseline↓ FewerLess disrupted
Morning fatigueBaseline↓ ReducedMore refreshed
Daytime alertnessBaseline↑ ImprovedMore alert

ADME Parameters

ParameterValueClinical Implication
BioavailabilityHigh (amino acid transporters)Excellent oral absorption
Tmax30-60 minRelatively rapid
Half-life~3-4 hours (plasma)CNS effects longer
Volume of Distribution~0.5 L/kgDistributes to tissues
Protein BindingMinimalMostly free
MetabolismMultiple pathwaysSee below
ExcretionRenal + metabolicNo accumulation

Plasma Glycine Kinetics

Metabolic Pathways

Glycine is metabolized through several important pathways:

Dose-Plasma Relationship

DosePeak Plasma IncreaseThermoregulatory EffectSleep Benefit
1gModestMinimalMinimal
2gModerateMildMild
3gHighSignificantOptimal
5gVery HighStrongSimilar to 3g
9gMaximumStrongNo additional benefit

Why 3 Grams?

Why Such a High Dose? Unlike many supplements effective at milligrams, glycine requires grams because:
  1. Amino acid transport competition: Must compete with other amino acids for transport
  2. High endogenous production: Body makes ~3g/day; supplemental 3g doubles this
  3. Rapid metabolism: Multiple pathways consume glycine quickly
  4. Receptor saturation: Need sufficient CNS levels for NMDA/GlyR effects
  5. Clinical validation: All positive sleep trials used 3g
The 3g dose is remarkably consistent across all successful glycine sleep research.

Glycine Form Comparison

FormPurityTasteApplicationNotes
GlyciRest (NTRPX)≥99%SweetSleep, RecoveryPharmaceutical-grade
USP Glycine≥98.5%SweetGeneralStandard pharmaceutical
Food-grade Glycine≥99%SweetSupplementsCommon, quality varies
Glycine from gelatinN/ANeutralDietary~33% of collagen
Magnesium Glycinate~14% glycineNeutralMg delivery + glycineDual benefit

Glycine’s Unique Taste Profile

Glycine is the only amino acid that tastes distinctly sweet:
Amino AcidTasteNotes
GlycineSweet60-70% as sweet as sucrose
AlanineMildly sweetWeaker
SerineSlightly sweetWeak
Most othersBitter/NeutralUnpleasant

Quality Specification (GlyciRest)

AttributeSpecificationMethod
IdentityGlycineHPLC, IR
Assay≥99.0%HPLC
pH (5% solution)5.5-7.0pH meter
Loss on drying<0.5%Gravimetric
Residue on ignition<0.1%Gravimetric
Heavy metals (total)<10 ppmICP-MS
Lead<1 ppmICP-MS
Arsenic<1 ppmICP-MS
Chloride<0.007%Titration
Sulfate<0.02%Turbidimetric
Microbial (TPC)<1000 CFU/gUSP <61>

Delivery Form Options

FormatDose FlexibilityTaste ExperiencePracticality
Powder (loose)★★★★★ ExcellentSweet, pleasantRequires measuring
Powder (sachets)★★★★☆ Pre-measuredSweet, pleasantConvenient
Capsules★★☆☆☆ LimitedNoneRequires 3-6 capsules for 3g
In Luna formula★★★☆☆ FixedMixed (formula)NTRPX choice

Manufacturing Methods

MethodPurityCostNotes
FermentationHighestHigherPreferred for supplements
Chemical synthesisHighLowerStrecker synthesis
Hydrolysis (gelatin)VariableLowBy-product; less pure
GlyciRest Specification: NTRPX sources pharmaceutical-grade glycine (USP/EP compliant) produced via fermentation. Each batch is tested for identity, purity (≥99%), heavy metals, and microbial contamination. The naturally sweet taste allows for pleasant powder administration or formula inclusion.

Dose-Response for Sleep

DoseSleep OnsetSleep QualityNext-Day CognitionGI Tolerance
1gMinimalMinimalNo changeExcellent
2gMildMildSlight improvementExcellent
3gSignificantSignificantImprovedExcellent
5gSignificantSignificantImprovedGood
9g+SignificantSignificantSimilarVariable

NTRPX Protocol (Luna)

ParameterRecommendationRationale
Dose3,000 mg (3g)Clinical trial standard
Timing30-60 min before bedAllow thermoregulation
FormIn Luna formulaSynergistic stack
FrequencyNightlyNo tolerance; safe chronic

Optimal Timing Window

Population-Specific Dosing

PopulationDoseTimingNotes
Standard adults3g30-60 min pre-bedClinical standard
Elderly (65+)3g60 min pre-bedMay benefit more
Sleep onset insomnia3g45-60 min pre-bedAllow full onset
Sleep maintenance insomnia3g30 min pre-bedAlso effective
Children1-2g30 min pre-bedLimited data; safe amino acid
Athletes (recovery)3-5gPost-training + bedtimeCollagen support bonus

Administration Notes

  • With or without food: Absorption good either way; empty stomach slightly faster
  • Water: Mix in water (pleasant sweet taste) or any beverage
  • Consistency: Nightly use optimal; no tolerance development
  • Combination: Synergistic with L-theanine, magnesium, apigenin
  • No dependency: Can stop anytime without rebound insomnia

Dose Adjustment Scenarios

ScenarioAdjustmentRationale
First-time useFull 3gWell-tolerated; established dose
No effect perceivedEnsure 60 min pre-bed; add cool roomOptimize conditions
GI sensitivity (rare)Split: 1.5g + 1.5g over 30 minReduce bolus
Taking with proteinSeparate by 30 minReduce amino acid competition
Shift work3g before target sleep timeSame protocol, shifted
Jet lag3g at destination bedtimeHelps reset

Split Dosing Option

For collagen synthesis AND sleep (athletes, connective tissue focus):
TimingDosePurpose
Post-workout5gCollagen synthesis peak
Bedtime3gSleep optimization
Total8gCombined benefits

Glycine as Collagen Precursor

Glycine comprises 33% of collagen — every third amino acid in the collagen triple helix is glycine:

Collagen Type Distribution

Collagen TypePrimary LocationGlycine Need
Type ISkin, tendons, bone, ligamentsHigh (most abundant)
Type IICartilageHigh
Type IIISkin, blood vesselsHigh
Type IVBasement membranesModerate

Glycine for Glutathione Synthesis

Glycine is one of three amino acids required for glutathione (GSH):Emerging research suggests glycine may become limiting with age:
FindingImplication
GSH levels decline with ageGlycine supplementation can restore
Collagen synthesis slowsGlycine + Vitamin C may help
Endogenous glycine synthesis may be insufficientSupplementation beneficial

GlyNAC: Glycine + N-Acetyl Cysteine

Combining glycine with NAC may optimize glutathione synthesis:
ComponentRoleTypical Dose
GlycineGSH substrate; often limiting in elderly3-5g
NACCysteine donor (rate-limiting)1-2g
CombinedFull GSH precursor supportSynergistic
Dual Application: GlyciRest glycine serves both sleep (via thermoregulation) and structural/antioxidant functions (via collagen and glutathione). The 3g nightly dose for sleep also provides meaningful substrate for these anabolic and protective pathways — particularly valuable in aging populations.

Luna Stack Composition

Synergy Matrix

PairingMechanismSynergy Type
Glycine + L-TheanineThermoregulation + Alpha wavesComplementary
Glycine + MagnesiumBoth modulate NMDA; Mg aids relaxationAmplifying
Glycine + ApigeninThermoregulation + GABA-AComplementary
Glycine + MelatoninBoth promote vasodilationReinforcing
L-Theanine + MagnesiumGlutamate modulationOverlapping

Why Magnesium Glycinate in Luna

Timing Protocol: Luna Stack

What NOT to Combine

CombinationIssueRecommendation
+ Sedative sleep aidsExcessive sedationAvoid (Luna sufficient)
+ AlcoholDisrupts sleep architectureAvoid
+ Large protein mealAmino acid competitionSeparate by 2 hours
+ Stimulants (late)Opposes sleep promotionNo caffeine after 2 PM

Sleep Trials

StudyDesignNDoseDurationKey Finding
Yamadera 2007RCT, crossover193gAcute↓ Sleep latency; ↑ sleep satisfaction
Bannai 2012RCT, crossover113gAcute↓ Fatigue; ↑ alertness next-day
Inagawa 2006RCT, crossover153gAcute↑ Sleep quality; ↑ morning vigilance
Kawai 2015RCT103g4 nights↓ Core temp; ↑ sleep efficiency

Mechanism Studies

StudyFocusFinding
Bannai 2012Thermoregulation↓ Core temp; ↑ peripheral temp
Kawai 2015Temperature + SleepConfirmed SCN-mediated mechanism
Kawai 2014NMDA in SCNGlycine acts via NMDA receptors

Cognition Studies

StudyPopulationNDoseFinding
File 1999Healthy volunteers203g↑ Memory retrieval
Ota 2016SchizophreniaMetaVarious↑ Cognition as adjunct

Metabolic/Glutathione Studies

StudyPopulationDoseFinding
Sekhar 2011Elderly3.6g (+ NAC)↑ GSH; ↑ mitochondrial function
Kumar 2021Elderly3g (+ NAC)Reversal of age-related GSH decline

Schizophrenia Adjunct (Research Context)

StudyDesignNDoseFinding
Heresco-Levy 1999RCT220.8g/kg↓ Negative symptoms
Javitt 2001Open-label110.4g/kg↓ PANSS scores
Ota 2016Meta-analysisMultipleVariousConsistent NMDA-based benefit

Effect Size Summary

OutcomeEffect SizeConfidence
Sleep onset improvementModerate (d=0.4-0.6)Moderate-High
Sleep qualityModerate (d=0.4-0.6)Moderate-High
Next-day fatigueModerate (d=0.5-0.7)Moderate
Core temp reductionSignificant (~0.5°C)High
GSH restoration (elderly)LargeModerate

References

Sleep Studies:
  • Yamadera W et al. Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes. Sleep Biol Rhythms. 2007;5:126-31.
  • Bannai M et al. The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers. Front Neurol. 2012;3:61. PubMed
  • Inagawa K et al. Subjective effects of glycine ingestion before bedtime on sleep quality. Sleep Biol Rhythms. 2006;4:75-7.
  • Kawai N et al. The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. Neuropsychopharmacology. 2015;40(6):1405-16. PubMed
Mechanism:
  • Bannai M, Kawai N. New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep. J Pharmacol Sci. 2012;118(2):145-8. PubMed
Glutathione:
  • Sekhar RV et al. Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine. Diabetes Care. 2011;34(1):162-7. PubMed
  • Kumar P et al. Supplementing glycine and N-acetylcysteine (GlyNAC) in older adults improves glutathione deficiency. J Gerontol A. 2021;76(1):1-13. PubMed
Cognition/Schizophrenia:
  • Heresco-Levy U et al. Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia. Arch Gen Psychiatry. 1999;56(1):29-36. PubMed
  • Ota M et al. NMDA receptor and antipsychotic-resistant schizophrenia. CNS Drugs. 2016;30(3):271-86.

Adverse Event Profile

EventIncidenceSeverityNotes
None significantGlycine is extremely safe
Mild GI discomfortRare (<2%)MildUsually with >5g
Soft stoolsRareMildUsually transient
Morning drowsinessVery rareMildOnly reported occasionally

Safety Data

ParameterFinding
LD50 (rat, oral)7.9 g/kg (very low toxicity)
NOAELHigh; not clearly defined (safe at all studied doses)
Maximum human studied60g/day (schizophrenia research)
Typical sleep dose3g (highly safe)
Endogenous production~3g/day (body makes it)
GenotoxicityNegative
CarcinogenicityNo evidence

Regulatory Status

RegionStatusNotes
United StatesGRASGenerally Recognized as Safe
European UnionFood additive (E640)Approved
JapanApproved food additiveLong history
Codex AlimentariusNo ADI specifiedConsidered very safe
FDANo upper limit setNo safety concerns identified

Contraindications

CategoryConsiderationSeverity
Clozapine usersTheoretical interaction (both NMDA-active)★★★☆☆ Consult prescriber
Pregnancy/NursingLimited specific data; likely safe (endogenous)★★☆☆☆ Consult provider
Kidney disease (severe)High-dose amino acids may stress kidneys★★☆☆☆ Consult provider

Drug Interactions

Drug ClassInteractionSeverityNotes
ClozapineBoth affect NMDA system★★★☆☆Consult prescriber
Other antipsychoticsPossible additive benefit★★☆☆☆May be synergistic
SedativesPossible additive relaxation★★☆☆☆Usually not problematic
NMDA antagonistsTheoretical opposition★★☆☆☆Memantine, ketamine

Long-Term Safety

ParameterFinding
Chronic use (weeks-months)Well-tolerated in trials
Daily useNo tolerance, no dependence
StoppingNo withdrawal or rebound insomnia
AccumulationNone (efficiently metabolized)
Organ toxicityNone observed

Special Populations

PopulationSafety StatusNotes
Healthy adultsExcellentExtensive safety data
ElderlyExcellent; may benefit GSHSekhar/Kumar studies
ChildrenLikely safe; limited dataAmino acid; endogenous
PregnancyProbably safe; consult providerEndogenous compound
Schizophrenia (adjunct)Studied at high dosesUnder medical supervision

Tier 1: Foundation

Efficacy

High (Sleep)

Validation

Strong — Multiple RCTs; clear mechanism

Safety

Excellent — GRAS; endogenous compound
Tier Rationale: Tier 1 (Foundation) classification. Glycine demonstrates consistent sleep benefits in randomized controlled trials with a well-elucidated mechanism (thermoregulation via SCN NMDA receptors). Effect sizes are moderate for sleep outcomes with the remarkable bonus of improved next-day cognition. Safety is exceptional — glycine is an endogenous compound the body produces daily. The 3g dose is well-established across multiple trials. Additional benefits for collagen synthesis and glutathione production add value. Foundational component of any evidence-based sleep stack.

Discovery and Naming

YearMilestone
1820Isolated from gelatin by Henri Braconnot
1848Named “glycine” (Greek glykys = sweet)
1858Structure determined
1900sRole in metabolism elucidated
2000sSleep mechanism discovered (Kawai et al.)

Glycine: The Simplest Amino Acid

Endogenous Glycine Metabolism

PathwayDirectionSignificance
De novo synthesisSerine → GlycinePrimary endogenous source
Threonine catabolismThreonine → GlycineMinor source
Dietary intakeCollagen/gelatin → Glycine~2g/day typical diet
Glycine cleavageGlycine → CO₂ + NH₃ + one-carbonPrimary catabolism

Glycine in the Body

FunctionLocationSignificance
Collagen synthesisConnective tissue33% of collagen is glycine
NeurotransmitterCNS (brainstem, spinal cord)Inhibitory
NMDA co-agonistThroughout CNSEnables glutamate signaling
Glutathione synthesisAll cellsAntioxidant defense
Creatine synthesisLiver, kidney, pancreasEnergy metabolism
Heme synthesisBone marrowOxygen transport
Bile acid conjugationLiverFat digestion
One-carbon metabolismLiverMethylation

Daily Glycine Flux

Conditionally Essential? While glycine is classified as “non-essential” (body can synthesize it), emerging evidence suggests endogenous synthesis may not meet all metabolic demands — especially for collagen turnover, glutathione production, and optimal sleep signaling. This makes glycine a candidate for “conditionally essential” status, particularly in aging populations. The 3g supplemental dose meaningfully augments the body’s glycine pool.

Why Glycine Tastes Sweet

Glycine is uniquely sweet among amino acids because its small, simple structure interacts with sweet taste receptors (T1R2/T1R3):
PropertyGlycineMost Amino Acids
SizeSmallestLarger
Side chainJust -HBulky/complex
ChargeZwitterionicVariable
Taste receptor fitGoodPoor
TasteSweetBitter/neutral
This natural sweetness makes glycine pleasant to consume as powder — a practical advantage for the 3g dose required for sleep benefits.

GlyciRest Summary: Glycine (3g) promotes sleep through a unique thermoregulatory mechanism — activating NMDA receptors in the brain’s master clock (SCN) to trigger peripheral vasodilation and core body temperature reduction. This mimics the natural sleep signal rather than forcing sedation, resulting in faster onset, better quality sleep, and remarkably improved next-day cognition. As a foundational amino acid also required for collagen and glutathione synthesis, glycine serves both restorative sleep and structural/antioxidant functions.