The Acute and Chronic Cognitive Effects of a Sage Extract: A Randomized, Placebo Controlled Study in Healthy Humans.

The short version

This randomized, double-blind, placebo-controlled trial with 94 healthy adults explored whether a sage supplement could improve memory and thinking, both within a day and after a month of daily use. Sage belongs to the mint family (Lamiaceae) and contains terpenes, which inhibit the enzyme acetylcholinesterase and bind brain receptors, and phenolics such as rosmarinic acid, which have antioxidant and anti-inflammatory activity in neurons. Earlier trials had found that single doses of common sage (Salvia officinalis) or Spanish sage (Salvia lavandulaefolia) improved memory and attention within hours. This study tested a commercial combination of both species, called Cognivia, which a rodent study had linked to longer-term memory gains through an enzyme called CaMKII. Participants were aged 30 to 60 (69 women, 25 men) and took either 600 mg of the sage combination or a matching placebo capsule every day for about 29 days. The capsules held a standardized leaf extract of common sage plus Spanish sage essential oil. On the first and last days, volunteers sat computerized memory and attention tests (the COMPASS battery) before dosing and again two and four hours afterward, along with mood questionnaires, blood pressure and heart rate checks. Tests included remembering digit sequences, repeating block-tapping patterns on a screen and recalling names matched to faces. Sage produced consistent benefits on working memory and accuracy. Block-tapping span was higher with sage on day 1 (p = 0.04) and day 29 (p = 0.002), and accuracy on a numeric working memory task was better with sage on day 29 (p = 0.03), meaning participants on sage held information in mind more reliably than those on placebo. Name-to-face recall was also better with sage after four weeks (p = 0.03). A composite working-memory accuracy score fell in the placebo group across the testing day but was maintained with sage. No effects appeared on mood, anxiety, blood pressure or a prospective memory video task. Adverse events were mostly mild or moderate headaches (34 events with sage, 10 with placebo), and all resolved during the study. The authors interpret the results as a benefit that appears within two hours and strengthens over 29 days. Several limitations apply. About 69% of participants correctly guessed they were taking sage, so expectation may have contributed. Placebo participants started with a higher block-tapping score on day 1, diet was not controlled, and the study did not include arms testing each sage species alone, so the contribution of each cannot be separated. Participants were healthy adults tested for one month, so the findings do not extend to people with memory problems or to longer use. The authors call for longer trials and for human confirmation of the proposed CaMKII mechanism.

Key findings

• In this double-blind trial, 94 healthy adults aged 30 to 60 took 600 mg a day of a combined sage supplement (common sage leaf extract plus Spanish sage essential oil) or a placebo for about 29 days.
• Sage improved working memory (the ability to hold and use information briefly): Corsi block span was higher with sage on day 1 (p = 0.04) and day 29 (p = 0.002), and numeric working memory accuracy was better on day 29 (p = 0.03).
• Name-to-face recall was better with sage after four weeks (p = 0.03), while mood, anxiety, blood pressure and a prospective memory task showed no significant effects.
• Headaches were the most frequent possibly related adverse event (14 participants; 34 events with sage versus 10 with placebo), mostly mild or moderate, and all resolved.
• The authors note that 69% of participants guessed they were on sage, diet was not controlled, and the two sage species were not tested separately, so the effects need confirmation in longer trials.

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