¶ Glycine
¶ The "Semi-Essential" Architect of Youth
Glycine is the simplest amino acid in the human body, yet it plays a disproportionately massive role in structural integrity, sleep regulation, and longevity. Often overlooked because the body can synthesize it, recent research suggests we cannot make enough of it to meet the demands of optimal health—specifically for collagen turnover and detoxification.
It is best known today as a powerful, non-sedative sleep aid and for its demonstrated ability to extend lifespan in rigorous mouse trials.
¶ At a Glance
- What is it?: The smallest amino acid. It tastes sweet (the name comes from the Greek glykys, meaning sweet) and is often used as a sugar substitute.
- Primary Benefits: Deepens sleep, fuels collagen production, and mimics the longevity benefits of methionine restriction.
- The "Deficit": Researchers estimate humans run a daily deficit of ~10 grams of glycine, as our endogenous synthesis cannot keep up with the needs of our connective tissues.[1]
- Longevity Status: ITP Confirmed. The NIA Interventions Testing Program found it extended median lifespan in both male and female mice.[2]
¶ The "Why": Key Benefits
¶ 1. Superior Sleep Quality
Unlike sedatives that force unconsciousness, glycine works by working with the body's natural sleep rhythms. It acts on NMDA receptors in the suprachiasmatic nucleus (the body's master clock) to induce peripheral vasodilation. This lowers core body temperature—a critical physiological signal for deep sleep onset.[3][4]
- Outcomes: Studies using 3 grams of glycine before bed show reduced sleep latency (time to fall asleep), improved subjective sleep quality, and reduced daytime sleepiness.[5]
¶ 2. The Collagen Bottleneck
Collagen is the most abundant protein in the body, and every third amino acid in the collagen helix must be glycine. Without it, the structure cannot form.
- Rate-Limiting Factor: Theoretical analysis suggests that while we need ~12g of glycine daily for collagen turnover, our metabolism only produces ~3g. Diet provides another 1.5–3g, leaving a massive deficit.[1:1]
- Clinical Implication: Supplementing glycine may be more effective for collagen synthesis than consuming collagen itself, as it directly addresses the metabolic bottleneck.[6]
¶ 3. Lifespan Extension (ITP Results)
Glycine is one of the few molecules to pass the rigorous Interventions Testing Program (ITP) by the National Institute on Aging.
- The Result: In the 2019 cohort, glycine supplementation extended median lifespan by approximately 4–6% in both male and female genetically heterogeneous mice.[2:1]
- Mechanism: It is believed to mimic Methionine Restriction. High methionine intake (common in muscle-meat heavy Western diets) accelerates aging; glycine counteracts methionine toxicity and helps clear excess methionine via the glycine N-methyltransferase (GNMT) pathway.[7]
¶ Reality Check: The Methionine/Glycine Ratio
Ancestral human diets included the whole animal—skin, cartilage, and bone broth—which are rich in glycine. Modern diets focus on muscle meat (steaks, chicken breast), which is high in methionine and low in glycine. This imbalance mimics a pro-aging signaling state. Supplementing glycine helps restore the ancestral balance.
- Bioavailability: Glycine is highly bioavailable and easily absorbed.
- Taste: It is a white powder that tastes like sugar. It mixes easily into water, tea, or coffee.
- Non-Essential?: It is technically "conditional" or "semi-essential." You won't die without it, but you will likely age faster and heal slower.
¶ Evidence Watch
¶ The Sleep Trials
A pivotal study by Bannai et al. (2012) demonstrated that 3g of glycine taken before bedtime significantly improved sleep quality in healthy adults with sleep complaints. Polysomnography (sleep tracking) revealed that glycine promoted a rapid drop in core body temperature without altering sleep architecture (i.e., it didn't disrupt REM sleep).[3:1]
¶ The Collagen Calculation
Meléndez-Hevia et al. (2009) performed a metabolic control analysis of collagen synthesis. They concluded that the enzymes responsible for synthesizing glycine are constrained and cannot meet the high demand of the collagen system. This suggests that osteoarthritis and other connective tissue disorders might be, in part, symptoms of a chronic systemic glycine deficiency.[1:2]
¶ The ITP Longevity Data
The ITP is the "gold standard" for longevity research because it uses genetically diverse mice (simulating human genetic variation) and runs experiments across three independent laboratories. The finding that glycine worked in both sexes is significant, as many interventions (like Acarbose or 17-alpha-estradiol) often show strong sex-specific bias.[2:2]
¶ Dosage and Protocols
¶ For Sleep
- Dose: 3 grams (approx. 1 heaping teaspoon).
- Timing: 30–60 minutes before bed.
- Protocol: Dissolve in a small amount of water or chamomile tea. Its sweet taste makes it palatable.
¶ For Longevity & Collagen
- Dose: 5–15 grams daily.
- Timing: Can be taken in divided doses with meals or added to coffee/tea as a sweetener.
- Strategy: To mimic the methionine restriction effect, some users take glycine specifically with high-protein (muscle meat) meals.
While generally very safe, high doses (10g+) taken immediately on an empty stomach can cause mild nausea or digestive gurgling in some people.
¶ Safety and Side Effects
- Safety Profile: Glycine is an amino acid found in food and is considered extremely safe. Studies in schizophrenia have used massive doses (up to 0.8g/kg body weight, or ~60g/day) with no serious adverse events.[8]
- Side Effects: Mild gastrointestinal distress (soft stools, nausea) at very high doses.
- Contraindications:
- Clozapine: Glycine may decrease the effectiveness of clozapine (an antipsychotic).
- Stroke: Some conflicting data exists regarding glycine and acute stroke recovery; consult a neurologist if you have a history of stroke.
¶ Compare With
- Collagen Peptides: Collagen provides glycine, but usually in peptide chains. Pure glycine is cheaper and allows for precise high-dosing to balance methionine.
- NAC (N-Acetylcysteine): Glycine is one of the three precursors to Glutathione (along with Cysteine and Glutamate). If you take NAC for glutathione support, ensuring adequate Glycine is critical to complete the synthesis.[9]
- Magnesium: Often stacked with Glycine (or bound to it as Magnesium Bisglycinate) for synergistic sleep benefits.
¶ References
Meléndez-Hevia, E., De Paz-Lugo, P., Cornish-Bowden, A., & Cárdenas, M. L. (2009). A weak link in metabolism: the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis. Journal of Biosciences, 34(6), 853–872. https://pubmed.ncbi.nlm.nih.gov/20093739/ ↩︎ ↩︎ ↩︎
Miller, R. A., et al. (2019). Glycine supplementation extends lifespan of male and female mice. Aging Cell, 18(3), e12953. https://pmc.ncbi.nlm.nih.gov/articles/PMC6516426/ ↩︎ ↩︎ ↩︎
Bannai, M., et al. (2012). The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers. Frontiers in Neurology, 3, 61. https://pmc.ncbi.nlm.nih.gov/articles/PMC3328957/ ↩︎ ↩︎
Kawai, N., et al. (2015). The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. Neuropsychopharmacology, 40(6), 1405–1416. https://pmc.ncbi.nlm.nih.gov/articles/PMC4397399/ ↩︎
Yamadera, W., et al. (2007). Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes. Sleep and Biological Rhythms, 5(2), 126-131. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1479-8425.2007.00262.x ↩︎
de Paz-Lugo, P., Lupiáñez, J. A., & Meléndez-Hevia, E. (2018). High glycine concentration increases collagen synthesis by articular chondrocytes in vitro: acute glycine deficiency could be an important cause of osteoarthritis. Amino Acids, 50(10), 1357–1365. https://pmc.ncbi.nlm.nih.gov/articles/PMC6153947/ ↩︎
Brind, J., et al. (2011). Dietary glycine supplementation mimics life-span extension by dietary methionine restriction in Fisher 344 rats. The FASEB Journal, 25(1_supplement), 528.2. https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.25.1_supplement.528.2 ↩︎
Heresco-Levy, U., et al. (1999). High-dose glycine added to olanzapine and risperidone in schizophrenia. Biological Psychiatry, 45, 11S. https://pubmed.ncbi.nlm.nih.gov/10086452/ ↩︎
McCarty, M. F., & DiNicolantonio, J. J. (2019). An increased need for dietary cysteine in support of glutathione synthesis may underlie the increased risk for mortality associated with low protein intake in the elderly. Age, 37(5), 96. https://pubmed.ncbi.nlm.nih.gov/26362762/ ↩︎