GABA vs. Glycine: Two Calming Neurotransmitters, Very Different Stories

Introduction

If you’ve ever browsed supplements to manage stress, improve sleep quality, or reduce anxiety, you’ve likely seen GABA and glycine mentioned in the same breath. Both are classified as inhibitory neurotransmitters. Both are marketed for relaxation. And both are often assumed to do essentially the same thing.

But here’s the dilemma: they don’t behave the same way in the human body at all.

Despite sharing a calming reputation, GABA and glycine differ profoundly in how they’re absorbed, how (and whether) they affect the brain, and which real-world problems they’re best suited for. Choosing between them isn’t about which one is “stronger,” but which one aligns with your physiology, goals, and tolerance.

This article unpacks the science behind GABA vs. glycine—mechanisms, benefits, risks, and use cases—so you can make a grounded, evidence-informed choice rather than relying on marketing shorthand.

At A Glance

What Are They?

GABA: The Brain’s Primary Brake Pedal

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the adult human brain. Its job is to reduce neuronal excitability, preventing overstimulation and maintaining balance between excitation and inhibition.

Pharmaceuticals like benzodiazepines and barbiturates work by enhancing GABA signaling, which explains their powerful anxiolytic and sedative effects. Supplemental GABA, however, is a very different story—because it does not behave like drug-enhanced GABA.

GABA is naturally synthesized from glutamate via the enzyme glutamate decarboxylase and is also found in small amounts in fermented foods like kimchi and miso.

Glycine: A Neurotransmitter and Structural Amino Acid

Glycine is the simplest amino acid, involved in protein synthesis, collagen formation, detoxification pathways, and neurotransmission. In the nervous system, glycine functions as an inhibitory neurotransmitter primarily in the spinal cord, brainstem, and retina.

Unlike GABA, glycine also plays a modulatory role at NMDA receptors, where it can enhance or stabilize glutamatergic signaling depending on context. This dual role—both calming and regulatory—gives glycine a broader physiological footprint than GABA.

Glycine is obtained from protein-rich foods and synthesized endogenously, though intake often falls short of estimated physiological needs, especially in modern diets [Meléndez-Hevia et al., 2009].

Mechanism of Action

How GABA Works

GABA exerts its effects by binding to two main receptor types:

• GABA-A receptors, which are ligand-gated chloride channels producing rapid inhibitory effects
• GABA-B receptors, which are G-protein-coupled receptors with slower, longer-lasting actions

When GABA binds to these receptors, it hyperpolarizes neurons, making them less likely to fire. In theory, this creates calm, reduces anxiety, and promotes sleep.

The complication is bioavailability. Multiple studies suggest that oral GABA crosses the blood–brain barrier (BBB) poorly, if at all, under normal conditions [Kuriyama & Sze, 1971]. Some effects may occur through peripheral nervous system pathways, the enteric nervous system, or indirect signaling via the vagus nerve [Abdou et al., 2006].

This means GABA supplements may calm the body without strongly sedating the mind.

How Glycine Works

Glycine binds to glycine receptors, which are also chloride channels, producing inhibitory effects similar in principle to GABA. These receptors are especially concentrated in the spinal cord and brainstem, influencing motor control and sensory processing.

More uniquely, glycine acts as a co-agonist at NMDA receptors, which are critical for learning, supporting memory formation, and synaptic plasticity. Rather than overstimulating NMDA activity, glycine appears to stabilize it, preventing excitotoxicity while preserving cognitive function [Johnson & Ascher, 1987].

Unlike GABA, glycine does cross the BBB, allowing supplemental glycine to directly influence central nervous system activity [Yamashita et al., 2012].

Shared Benefits

Despite their differences, GABA and glycine overlap in several important ways.

Both promote a state of physiological calm, supporting nervous system calm and reducing markers of stress and sympathetic nervous system activation. Human studies suggest both can lower subjective stress and improve relaxation, particularly in acute settings [Abdou et al., 2006; Inagawa et al., 2006].

Sleep support is another shared domain. GABA and glycine can both reduce sleep latency and improve perceived sleep quality, though through different mechanisms. Rather than acting as sedatives, they appear to optimize sleep architecture, encouraging deeper, more restorative stages of sleep.

Finally, both compounds demonstrate excellent safety profiles when used at typical supplemental doses, especially compared to pharmaceutical anxiolytics or hypnotics.

Unique Benefits of GABA

What makes GABA distinct is its rapid, body-centered calming effect.

Even if it doesn’t robustly cross the BBB, studies show that oral GABA can reduce markers of stress such as heart rate variability and cortisol responses during acute stress tasks [Abdou et al., 2006]. Many users report a sensation of physical relaxation—looser muscles, slower breathing, reduced somatic tension.

This makes GABA particularly useful for:

• Situational anxiety (public speaking, acute stress)
• Physical restlessness rather than racing thoughts
• Stress-related muscle tension

Interestingly, some individuals experience a noticeable calming effect within 30–60 minutes, suggesting peripheral nervous system involvement. However, others feel little to nothing, likely due to individual differences in receptor sensitivity and gut–brain signaling.

GABA is best understood as a short-acting, situational tool, not a foundational nervous system modulator.

Unique Benefits of Glycine

Glycine’s strengths lie in its system-wide and long-term effects.

One of its most compelling benefits is sleep quality. Multiple controlled studies show that 3 grams of glycine before bed enhances sleep quality, reduces daytime sleepiness, and improves cognitive performance the following day—without sedation [Inagawa et al., 2006; Yamadera et al., 2007].

Beyond sleep, glycine supports metabolic health. It plays a role in insulin sensitivity, glutathione synthesis, and inflammation regulation. Low plasma glycine levels are associated with metabolic syndrome and type 2 diabetes [Adeva-Andany et al., 2018].

Neurologically, glycine’s modulation of NMDA receptors gives it neuroprotective benefits and cognitive-stabilizing properties, making it appealing for individuals prone to overstimulation, burnout, or glutamate-driven anxiety.

Unlike GABA, glycine tends to feel subtle but cumulative—less like a switch, more like a recalibration.

Side Effects & Safety

Both compounds are generally well tolerated, but they are not entirely risk-free.

GABA Safety Considerations

GABA supplements can occasionally cause:

• Tingling or flushing sensations
• Shortness of breath
• Lightheadedness

These effects are typically transient and dose-dependent. People with asthma or blood pressure issues should exercise caution, as GABA may influence respiratory and vascular tone.

Long-term data on high-dose GABA supplementation are limited, which reinforces its role as an occasional aid rather than a daily cornerstone.

Glycine Safety Considerations

Glycine has an impressive safety record, even at doses exceeding typical supplementation levels. Clinical trials have used up to 9 grams per day without serious adverse effects [Adeva-Andany et al., 2018].

Possible side effects include:

• Mild gastrointestinal upset
• Nausea at high doses

Because glycine can enhance NMDA receptor function, individuals with certain neurological conditions should consult a clinician before high-dose use.

The Verdict

So—GABA or glycine?

Choose GABA if you’re looking for fast, situational calming, especially when stress manifests physically rather than mentally. It’s best suited for occasional use during acute stressors rather than daily nervous system support.

Choose glycine if your goals include better sleep quality, long-term stress resilience, metabolic support, or cognitive stability. Glycine is more versatile, better absorbed into the brain, and supported by a broader base of human research.

In short, GABA is a momentary brake, while glycine is a system tuner. Neither is inherently better—but one is almost certainly better for you.

References

• Abdou, A. M., et al. (2006). Relaxation and immunity enhancement effects of γ-aminobutyric acid (GABA) administration in humans. BioFactors.
• Adeva-Andany, M. M., et al. (2018). Glycine metabolism and its alterations in obesity and metabolic syndrome. Nutrients.
• Inagawa, K., et al. (2006). Effect of glycine ingestion on subjective sleep quality. Sleep and Biological Rhythms.
• Johnson, J. W., & Ascher, P. (1987). Glycine potentiates the NMDA response. Nature.
• Kuriyama, K., & Sze, P. Y. (1971). Blood–brain barrier to H3-GABA in normal and amino-oxyacetic acid-treated animals. Neuropharmacology.
• Meléndez-Hevia, E., et al. (2009). A weak link in metabolism: the metabolic capacity for glycine biosynthesis. Molecular Biology Reports.
• Yamadera, W., et al. (2007). Glycine ingestion improves subjective sleep quality in human volunteers. Sleep and Biological Rhythms.
• Yamashita, S., et al. (2012). Glycine transport across the blood–brain barrier. Journal of Neurochemistry.

Related Comparisons