Glycine Does Not Lower Cortisol
There is no evidence that glycine supplementation lowers cortisol concentrations in humans. The available evidence actually suggests the opposite effect may occur under specific circumstances.
Evidence Analysis
Direct Evidence on Glycine and Cortisol
The only human study directly examining this relationship found that intravenous glycine infusion increased serum cortisol only in one patient who developed signs of glycine toxicity 1. In the remaining healthy volunteers receiving 1 liter of 2.2% glycine solution over 20 minutes, cortisol levels did not change significantly. This study concluded that glycine does not typically stimulate cortisol secretion under normal conditions 1.
Clinical Context from Guidelines
The clinical guidelines provided address cortisol measurement and management extensively but make no mention of glycine as a cortisol-lowering intervention 2, 3. When discussing factors that can interfere with cortisol testing, glycine is only mentioned as a potential confounding factor - specifically, glycyrrhizic acid (found in licorice and chewing tobacco) can falsely elevate salivary cortisol by inhibiting 11β-hydroxysteroid dehydrogenase type 2 2. This is the opposite of lowering cortisol.
Medical Management of Hypercortisolism
When cortisol reduction is clinically indicated, established medical therapies include 4:
- Steroidogenesis inhibitors: ketoconazole (400-1200 mg/day), mitotane, osilodrostat
- Glucocorticoid receptor antagonists: mifepristone
- Surgical intervention: adrenalectomy for appropriate cases
Glycine is conspicuously absent from any treatment algorithm for hypercortisolism across multiple authoritative guidelines 5, 6, 4.
Important Caveats
Glycine Toxicity Risk
The FDA drug label for glycine irrigation warns of systemic absorption risks including cardiovascular, pulmonary, and neurological complications 7. When glycine toxicity does occur, cortisol elevation - not suppression - may be observed 1.
Animal Studies Not Applicable
While one animal study showed glycine reduced feather corticosterone in heat-stressed laying hens 8, this finding cannot be extrapolated to human cortisol regulation given the different physiological contexts and species-specific stress responses.
Clinical Bottom Line
If cortisol reduction is your therapeutic goal, do not use glycine. Instead, consult endocrinology for evidence-based interventions including steroidogenesis inhibitors or surgical options when appropriate 4, 9. The absence of glycine from any major endocrine society guideline on cortisol management reflects the lack of supporting evidence for this indication.