Table 5.

Summary of efficacy, pharmacokinetic, safety and tolerability clinical studies with Melissa officinalis (Lemon balm) extracts.

Refs.	Study Design	Endpoints	Dosage & Duration	Results
[115]	RDBPCa	Sleep and anxiety	1500 mg/d (500 mg three times daily) vs. placebo X 7 days	M. officinalis appeared to reduce the levels of anxiety (by 49%) and improve sleep quality (by 54%) in patients undergoing coronary artery bypass surgery.
[116]	RTBPCb, cross-over	Sleep bruxism	Homeopathic tinctures (1 drop per age in 15 mL of water daily M. officinalis, P. decandra, or placebo) X 30 days	Significant reduction in sleep bruxism observed across all treatment groups including placebo, M. officinalis treatment showed better results than P. decandra or placebo.
[118]	Pilot study	Determine bioavailability of rosmarinic acid from lemon balm extract, establish time points for assessing cognition and mood	-	Rosmarinic acid was bioavailable with peak plasma levels achieved within 1 hour of dose, returning to baseline between 4-6 hours post-dose.
[118]	RPCc, balanced cross-over	Cognition, mood	480 mL 0.3 g lemon balm + natural fruit sweetener, 0.6 g lemon balm + natural fruit sweetener, 0.6 g lemon balm + blend of artificial sweeteners, or placebo	0.3 g lemon balm + natural fruit sweetener associated with lower anxiety and better working memory at both 1 and 3 hours post-ingestion
[118]	-	Cognition, mood	250 mg lemon balm in yoghurt	Indications of benefits from 0.3 g dose including improvement in alertness and word recall at 1 hour post-dose and math performance improving at 3 hours. The 0.6 g lemon balm-yoghurt formulation associated with more fatigue even at 1 hour post-dose.
[119]	RPC	Pharmacokinetic, safety, and tolerability	M. officinalis treatments containing 100 mg, 250 mg, 500 mg rosmarinic acid, placebo	No detection in plasma with 100 mg rosmarinic acid in 4 of 6 participants, Tmax of rosmarinic acid at 1 hour post-dose with 250 mg or 500 mg rosmarinic acid. Cmax of 72.22± 12.01 nmol/L and 162.20 ± 40.20 nmol/L after 250 mg and 500 mg rosmarinic acid; respectively. Food intake increased AUC by 1.3 times, and delayed Tmax. M. officinalis containing 500 mg rosmarinic acid did not affect blood chemistries.
[120]	RDBPC	Safety, efficacy (diabetes endpoints)	700 mg M. officinalis extracts daily X 12 weeks	No safety related treatment effects
[121]	RDPBC	Safety, efficacy anxiety (and cardiovascular endpoints)	1000 mg daily (500 mg twice daily) X14 days M. officinalis extract vs. placebo	No indication of side effects, significantly reduced anxiety (and frequency of heart palpitations)

^aRandomized, double-blinded, placebo-controlled. ^bRandomized, triple-blinded, placebo-controlled. ^cRandomized, placebo-controlled.