Benefits
Memory and cognitive performance
In a maker-funded trial in 94 healthy adults aged 30 to 60, the Cognivia combination (600 mg a day for 29 days) improved working-memory and accuracy scores on several tasks versus placebo, with the clearest differences on day 29; mood, anxiety and a prospective-memory task did not change. In 26 athletes, one dose shortened reaction time and raised a digit-span memory score during cycling.
Memory and attention in older adults
In 20 healthy adults over 65, single doses of a garden sage extract improved delayed (secondary) memory, with 333 mg working best and other doses helping less. In a 16-week trial in 42 people aged 65 to 80 with mild to moderate Alzheimer's disease, a garden sage tincture improved cognitive scale scores versus placebo. Neither trial shows that sage treats or slows memory disease.
Word recall, mood and alertness after a single dose
In small crossover trials in healthy young adults, single capsules of Spanish sage essential oil (25 to 50 microliters) improved word recall and speed of memory, raised self-rated alertness and calmness, and reduced mental fatigue. Single doses of garden sage leaf improved mood ratings at 300 and 600 mg, but the 300 mg dose lowered alertness during a stressful task and lowered task performance at the later session.
Mechanism of action
Acetylcholinesterase inhibition
In lab tests, a Spanish sage essential oil made almost entirely of monoterpenoids was a potent inhibitor of human acetylcholinesterase, and a garden sage leaf extract inhibited acetylcholinesterase and, more strongly, butyrylcholinesterase in a dose-dependent way. Blocking these enzymes leaves more acetylcholine, a messenger involved in memory and attention.
Brain enzyme effects in animals
Given by mouth to rats, Spanish sage essential oil inhibited acetylcholinesterase in the striatum and hippocampus more than in the cortex. Individual monoterpenoids from the oil inhibited the enzyme with varying potency in lab tests.
Antioxidant, anti-inflammatory and sedative activity in lab studies
Spanish sage extracts and constituents have shown antioxidant, anti-inflammatory, estrogen-like and sedative effects in laboratory and animal research. These are lab and animal findings summarized in a review, not results measured in people.
Clinical trials
Randomized, double-blind, placebo-controlled, parallel-group trial at Northumbria University of Cognivia (600 mg a day: 400 mg Salvia officinalis aqueous leaf extract plus 50 microliters Salvia lavandulaefolia essential oil) versus placebo for 29 days. Sponsored by Nexira; one author is a Nexira employee; 69% of participants guessed their treatment correctly, more than chance (P=0.02), partly from a herbal taste on reflux (Wightman et al. 2021, Nutrients)
94 healthy adults aged 30 to 60 (69 women, 25 men), tested 120 and 240 minutes after dosing on day 1 and day 29.
Sage improved working-memory and accuracy scores on the Corsi Blocks, Numeric Working Memory and Name to Face Recall tasks versus placebo, with the clearest differences on day 29 (Corsi span P=0.002). Mood, anxiety, blood pressure and a prospective-memory task showed no significant effect. Of 44 adverse events that could possibly be related to treatment (most often headache), 34 occurred with sage and 10 with placebo; two people taking sage rated headaches as severe, participants judged the events unrelated to the supplement, and all resolved.
Randomized, double-blind, placebo-controlled crossover trial run at INSERM UMR1093-CAPS and the Center d'Expertise de la Performance, University of Bourgogne Franche-Comte (Dijon), of one 600 mg Cognivia dose taken 2 hours before testing. Nexira supplied the product and paid publication costs, one author was a Nexira employee, and the taste could not be masked (Babault et al. 2021, Front Nutr)
26 athletes tested four times while cycling: warm-up, middle and end of a fatiguing task, and after 5 minutes of recovery.
Compared with placebo, simple reaction time was shorter (P=0.023), backward digit-span memory score was higher (P=0.044) and rated perceived exertion was lower (P=0.002). Stroop task performance and heart rate did not differ between sage and placebo.
Randomized, double-blind, placebo-controlled, parallel-group trial at three centers in Tehran of a Salvia officinalis extract (60 drops a day) for 16 weeks; generic garden sage, not Cognivia (Akhondzadeh et al. 2003, J Clin Pharm Ther)
42 patients aged 65 to 80 (18 women) with mild to moderate Alzheimer's disease.
At 4 months the sage group had better ADAS-cog (P=0.03) and CDR sum-of-boxes (P<0.003) outcomes than the placebo group. Side effects did not differ significantly between groups; agitation was somewhat more frequent with placebo (P=0.09). One small trial; it does not show that sage treats or slows the disease.
Two placebo-controlled, double-blind, balanced crossover experiments with 7-day washouts: Experiment 1 gave 50, 100 and 150 microliters and Experiment 2 gave 25 and 50 microliters of a standardized Salvia lavandulaefolia essential oil, with testing up to 6 hours after dosing (Tildesley et al. 2003, Pharmacol Biochem Behav)
Healthy young adults: 20 in Experiment 1 and 24 in Experiment 2.
The 50 microliter dose significantly improved immediate word recall in both experiments. The abstract reports this benefit only for the 50 microliter dose and does not report a benefit for delayed word recall, the other primary outcome.
Double-blind, placebo-controlled crossover study with 7 days between visits; single doses of 300 mg and 600 mg dried Salvia officinalis leaf versus placebo, with mood rated before and after a 20-minute multitasking stressor (Kennedy et al. 2006, Neuropsychopharmacology)
30 healthy young adults.
Both doses improved mood ratings before the stressor: 300 mg reduced anxiety and 600 mg raised alertness, calmness and contentedness. The 600 mg dose improved multitasking performance at 1 and 4 hours, while 300 mg lowered performance at the later session and its anxiety reduction disappeared during the stressor.
Randomized, placebo-controlled, double-blind, balanced five-period crossover study with 7-day washouts; single doses of 167, 333, 666 and 1,332 mg of a standardized Salvia officinalis extract, tested up to 6 hours after dosing (Scholey et al. 2008, Psychopharmacology (Berl))
20 healthy volunteers over 65 (mean age about 73).
The 333 mg dose improved secondary memory at all testing times and accuracy of attention compared with placebo; the other doses improved secondary memory to a lesser extent. The authors judged the effects to be on stimulus processing or memory consolidation, not retrieval or working memory.
Double-blind, placebo-controlled, balanced crossover study with 7 days between visits; capsules of 50 microliters Salvia lavandulaefolia essential oil, which potently inhibited human acetylcholinesterase in lab tests, with testing 1 and 4 hours after dosing (Kennedy et al. 2011, J Psychopharmacol)
36 healthy adults.
Compared with placebo, sage improved secondary memory and attention task performance, most clearly at 1 hour, and reduced mental fatigue and raised alertness, more so at 4 hours.