Glycine
Glycine is a non-essential amino acid found in protein-rich foods and synthesized by the body, playing a key role in collagen formation, neurotransmitter function, and muscle repair. As a dietary supplement, it is often used to improve sleep quality, reduce inflammation, and support joint and skin health. Preliminary studies suggest glycine may enhance sleep, protect against muscle loss, and aid in metabolic health, but more research is needed to fully validate its benefits.
Benefits
Improved Sleep Quality
Glycine may enhance sleep by reducing core body temperature and calming the nervous system. Studies suggest 3 grams taken before bed can improve sleep onset and quality, reducing daytime fatigue.
Cognitive and Mood Support
Glycine acts as a neurotransmitter and may improve memory, attention, and mood. It’s involved in NMDA receptor function, which supports learning and memory. Some evidence links glycine to reduced symptoms of depression and anxiety.
Collagen and Joint Health
Glycine is a key component of collagen, supporting skin, joint, and connective tissue health. Supplementation may aid tissue repair and reduce joint pain, particularly in conditions like osteoarthritis.
Metabolic Health
Glycine may improve insulin sensitivity and reduce inflammation, potentially lowering the risk of metabolic disorders. It’s been studied for its role in managing blood sugar and protecting against oxidative stress.
Liver Protection
Glycine may support liver function by aiding detoxification and reducing damage from alcohol or toxins. It’s shown promise in animal studies for protecting against liver injury.
Muscle Preservation
Glycine may help prevent muscle wasting, especially in conditions like sarcopenia or during caloric restriction, by supporting protein synthesis.
Mechanism of Action
Sleep Quality
Neurotransmitter Role: Glycine is an inhibitory neurotransmitter in the central nervous system, acting on glycine receptors to hyperpolarize neurons, reducing neuronal excitability and promoting calmness.
Thermoregulation: Glycine lowers core body temperature by increasing cutaneous blood flow, facilitating sleep onset. It interacts with NMDA receptors in the suprachiasmatic nucleus (regulating circadian rhythms).
Cognitive and Mood Support
NMDA Receptor Modulation: Glycine is a co-agonist at NMDA receptors, enhancing glutamatergic signaling critical for synaptic plasticity, learning, and memory.
GABAergic Effects: Its inhibitory action on glycine receptors reduces overexcitation, potentially alleviating anxiety and depression symptoms.
Collagen and Joint Health
Collagen Synthesis: Glycine is a primary amino acid in collagen (about 33% of collagen’s structure), providing structural support for connective tissues, skin, and joints.
Anti-inflammatory Effects: Glycine inhibits pro-inflammatory cytokines (e.g., TNF-α, IL-6), reducing joint inflammation and supporting tissue repair.
Metabolic Health
Insulin Sensitivity: Glycine enhances insulin signaling, possibly by improving glutathione synthesis, which reduces oxidative stress and supports glucose uptake.
Anti-inflammatory: It inhibits NF-κB activation, reducing systemic inflammation linked to metabolic disorders.
Liver Protection
Detoxification: Glycine is a precursor to glutathione, a key antioxidant that neutralizes reactive oxygen species and supports liver detoxification.
Cytoprotection: It reduces oxidative damage and inflammation in hepatocytes, protecting against alcohol- or toxin-induced liver injury.
Muscle Preservation
Protein Synthesis: Glycine supports mTOR signaling and provides building blocks for muscle protein synthesis, counteracting muscle breakdown.
Anti-catabolic: It reduces muscle degradation by inhibiting inflammatory pathways and oxidative stress.
Clinical Trials
Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks
Study: A 2023 randomized, placebo-controlled trial with 24 older adults (age mean = 65 years) and 12 young adults. Older adults received GlyNAC (glycine 100 mg/kg/day and N-acetylcysteine 100 mg/kg/day) or alanine placebo for 16 weeks; young adults received GlyNAC for 2 weeks. Outcomes included glutathione (GSH) levels, oxidative stress, mitochondrial function, inflammation, insulin resistance, physical function, and aging biomarkers.
Findings: GlyNAC improved GSH deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, muscle strength, and cognition in older adults. Benefits declined after stopping supplementation. No significant side effects were reported, indicating safety and tolerability.
Link: https://bit.ly/3C8sD5Z[](https://pubmed.ncbi.nlm.nih.gov/35975308/)
Glycine by Enteral Route Does Not Improve Major Clinical Outcomes in Severe COVID-19: A Randomized Clinical Pilot Trial
Study: A 2024 open-label, controlled trial with 56 patients with severe COVID-19 requiring mechanical ventilation. Patients received usual care or usual care plus glycine (0.5 g/kg/day) enterally. Outcomes included mortality, time to weaning from mechanical ventilation, and serum cytokines.
Findings: No differences in mortality (63.6% glycine vs. 52.2% control, p = 0.60) or other major outcomes. Glycine reduced serum fibrinogen levels (p = 0.001), but no other laboratory or cytokine changes were observed. The study suggests glycine’s anti-inflammatory effects may require longer administration.
Link: https://bit.ly/3C9tE6A[](https://www.nature.com/articles/s41598-024-62321-7)
A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation
Study: A 2022 trial with 114 healthy older adults (age mean = 65 years) receiving GlyNAC at low (2.4 g/day), medium (4.8 g/day), or high (7.2 g/day) doses for 2 weeks. Outcomes included plasma glycine, N-acetylcysteine, and oxidized cystine levels to assess bioavailability and oxidative stress.
Findings: GlyNAC dose-dependently increased plasma glycine and reduced oxidative stress markers. No significant side effects were noted. The study supports GlyNAC ’s potential to improve glutathione status and metabolic health in older adults.
Link: https://tinyurl.com/4n6p8xjd
Effect of Oral Glycine on the Clinical, Spirometric and Inflammatory Status in Subjects with Cystic Fibrosis: A Pilot Randomized Trial
Study: A 2017 pilot RCT with children with cystic fibrosis, receiving oral glycine (dose not specified) for 8 weeks. Outcomes included clinical symptoms, spirometry, and inflammatory markers in serum and sputum.
Findings: Glycine improved clinical symptoms and reduced pro-inflammatory cytokines in serum and sputum by the end of 8 weeks, with a carry-over effect suggesting slow-onset anti-inflammatory action. No significant side effects were reported.
Link: https://tinyurl.com/2p9v4m8k
Double-Blind, Placebo-Controlled, Crossover Trial of Glycine Adjuvant Therapy for Treatment-Resistant Schizophrenia
Study: A 1996 RCT with 22 patients with treatment-resistant schizophrenia, receiving high-dose glycine (0.4–0.8 g/kg/day) or placebo added to antipsychotics for 6 weeks. Outcomes included negative symptom severity and side effects.
Findings: Glycine significantly reduced negative symptoms (e.g., apathy, withdrawal) and improved some side effects of antipsychotics. No effect on positive symptoms (e.g., hallucinations). No significant adverse effects were noted, but larger trials are needed due to the small sample size.
Link: https://tinyurl.com/yc8p5n4v
Glycine Intake as Nutritional Supplement Against Virus Infections
Study: A 3-year study (published 2020) with 127 volunteers prone to frequent viral infections. 85 received glycine (10 g/day), and 42 received no glycine. Outcomes included frequency, severity, and duration of viral infections.
Findings: Glycine reduced the incidence of flu (16/85 in the first year, none in subsequent years) and decreased severity/duration in those affected, likely by strengthening the extracellular matrix (collagen). No side effects were reported at this dose.
Link: https://tinyurl.com/3r7k9m2t
Dietary Glycine Decreases Both Tumor Volume and Vascularization in a Combined Colorectal Liver Metastasis and Chemotherapy Model
Study: A 2020 study in rats with colorectal liver metastasis, evaluating glycine alone or with FOLFOX chemotherapy. Outcomes included tumor volume, microvascular density (MVD), and proliferation (Ki67).
Findings: Glycine (dose not specified) reduced tumor volume by 35–42% (p < 0.05) and MVD by 60% (p = 0.004) without affecting proliferation. It did not reduce FOLFOX efficacy, suggesting synergy via anti-angiogenic effects. No toxicity was noted, supporting clinical trial potential.
Link: https://tinyurl.com/2s4w6n9p
Potential Side Effects
Gastrointestinal Issues:
Mild nausea, upset stomach, diarrhea, or soft stools. These are the most frequently reported side effects, typically occurring at doses above 10 g/day. Studies using 3–5 g/day (e.g., for sleep or metabolic benefits) report minimal gastrointestinal effects, comparable to placebo.
Drowsiness or Sedation:
Mild drowsiness or lethargy, particularly when taken in the evening for sleep benefits. Glycine’s calming effect on the nervous system (via glycine receptor activation) can cause drowsiness, which is often intentional for sleep improvement but may be undesirable during the day.