Glycine Supplementation and Neurological Benefits
Supplemental glycine has demonstrated specific neurological benefits, primarily in improving sleep quality through direct inhibition of orexin neurons, but there is no evidence supporting its use for cognitive enhancement or dementia prevention.
Sleep Quality Improvement
Glycine's most well-established neurological benefit is enhancement of sleep quality through specific mechanisms:
Oral glycine administration (3g before bedtime) significantly improves subjective sleep quality in individuals with insomniac tendencies by inducing a decrease in core body temperature associated with increased cutaneous blood flow 1
Glycine directly hyperpolarizes and inhibits orexin neurons (wake-promoting neurons), leading to increased non-REM sleep time and decreased wakefulness, particularly when administered during the dark period 2
The amino acid acts through glycine receptors (GlyR) on orexin neurons, with immunoelectron microscopy confirming glycine receptor alpha subunits localized at inhibitory synapses on these neurons 2
Peripheral administration increases both plasma and cerebrospinal fluid glycine concentrations, allowing central nervous system effects 1
Neurotransmitter Functions
Glycine serves dual roles in neurotransmission, though supplementation effects are primarily related to inhibitory pathways:
Functions as both an inhibitory neurotransmitter via glycine receptors and as a co-agonist at NMDA-type glutamate receptors 1, 3
Participates in synthesis of glutathione, providing potential cytoprotective and anti-inflammatory effects in neural tissue 4, 3
Lack of Evidence for Cognitive Enhancement
Despite glycine's role in neurotransmission, there is no clinical evidence supporting its use for cognitive improvement or dementia prevention:
Clinical guidelines explicitly recommend against amino acid supplementation (including glycine) for cognitive decline prevention in the absence of documented deficiency 5
Historical stroke trials testing glycine antagonists (gavestinel) for neuroprotection were negative, suggesting glycine modulation does not provide acute neuroprotective benefits 5
The ESPEN guidelines strongly recommend against single nutrient supplementation for dementia prevention or treatment when no deficiency exists 6, 7, 8
Safety Profile
Glycine supplementation appears safe within studied dosage ranges:
Normal serum glycine levels are approximately 300 μM, and supplementation can increase levels to >900 μM without harmful side effects in most contexts 3
One important caveat: remifentanil (an opioid) can cause glycine toxicity specifically in patients with renal dysfunction, but this relates to the drug's metabolite rather than dietary glycine supplementation 5
High-dose glycine may cause toxic effects, though the safe range requires further investigation 3
Clinical Recommendations
For patients seeking neurological benefits from glycine:
Consider glycine supplementation (3g before bedtime) specifically for sleep quality improvement in individuals with insomnia or poor sleep quality 1, 9
Do not recommend glycine for cognitive enhancement, dementia prevention, or neuroprotection, as no evidence supports these uses 5, 6
Avoid glycine supplementation in patients with significant renal dysfunction due to potential accumulation concerns 5
Recognize that while glycine has broad anti-inflammatory and cytoprotective properties in vitro and in animal models, these have not translated to proven neurological benefits beyond sleep improvement in humans 4, 3