By Kerry Bone, BSc (hons), Dip. Phyto.

A team of British and Australian scientists recently undertook a series of investigations on plants that may improve memory and might therefore be relevant to the treatment of Alzheimer's disease (AD).^3,4,7 One of the herbs they chose for investigation was sage (Salvia officinalis) because of its traditional reputation as a tonic for the nervous system and memory.

For example, the 16th-century English herbalist Gerard wrote about sage: "It is singularly good for the head and brain and quickeneth the nerves and memory." Culpeper stated: "It also heals the memory, warming and quickening the senses." From the writings of Hill, we find a possible reference to AD: "Sage will retard that rapid progress of decay that treads upon our heels so fast in latter years of life, will preserve faculty and memory more valuable to the rational mind than life itself."¹

Despite these references, sage is not currently regarded as a supplement for improving memory. It is utilized primarily for the treatment of hot flashes, excessive sweating and infections of the mouth and throat.²

Initial findings from the researchers' investigations were that sage extracts possessed significant antioxidant, anti-inflammatory and cholinesterase-inhibiting activities. Current conventional drugs for the treatment of AD are cholinesterase inhibitors. Much of this activity appeared to be in the essential oil. Anticholinesterase treatments increase the concentration of acetylcholine at the cholinergic nerve ending by inhibiting its breakdown by the enzyme acetylcholinesterase. AD is characterized by the loss of activities relating to acetylcholine in the cerebral cortex of the brain.

The next step in the scientists' research was a clinical trial in healthy young volunteers.³ Two experiments utilized a placebo-controlled, double-blind, crossover methodology. In the first trial, 20 participants received 50, 100 and 150 uL of a standardized essential oil extract of a type of sage (Salvia lavandulaefolia) and placebo. In the second trial, 24 participants received 25 and 50 uL of a standardized essential oil extract of S. lavandulaefolia and placebo. Doses were separated by a seven-day washout period.

Assessment was undertaken using the Cognitive Drug Research computerized test battery prior to treatment and 1, 2.5, 4 and 6 hours thereafter. The primary outcome measures used were immediate and delayed word recall. The 50 uL dose of sage essential oil significantly improved immediate word recall in both studies. These results provide the first systematic evidence that sage may be capable of improving memory in healthy young adults.

This was followed up by a pilot, open-label study in patients with AD.⁴ The trial included 11 patients ages 76 to 95 with mild to moderate AD. They received 50 uL S. lavandulaefolia  essential oil (building from one to three capsules per day during the six-week trial). No patient experienced any adverse physical or neurological effects during the study, except possibly an unrelated increase in blood pressure in two patients with a history of hypertension. There were some promising indications of a therapeutic effect, specifically statistically significant differences for neuropsychiatric symptoms (reduced) and attention (improved).

While the above clinical trials used sage essential oil, it is conceivable that other components in sage might have therapeutic value in the context of AD. For example, sage contains diterpenes, which can interact with the gamma-aminobutyric acid (GABA)-benzodiazepine receptor.⁵ Two diterpenes from dan shen (Salvia miltiorhiza) have recently been shown to inhibit acetylcholinesterase.⁶ Dan shen is used in China to treat age-related cognitive degeneration.

The same team of scientists also found that whole extract of sage (S. officinalis) improved memory and attention in healthy older volunteers.⁷ The researchers used a randomized, placebo-controlled, double-blind crossover design to investigate the effects of a single dose of sage over a six-hour period (with assessments at 1, 2.5, 4 and 6 hours). Twenty volunteers with an average age of 73 years received one of four active doses of extract or a placebo at each visit, with a seven-day washout period between visits. The doses were 167, 333, 666 and 1,332 mg, corresponding to around 1.25, 2.5, 5 and 10 g of starting leaf material, respectively. The selection of the dosage range enabled the assessment of any dose-response effects.

Compared with the placebo phase (which generally exhibited the characteristic decline in performance over the six-hour test period), the 333 mg dose caused a highly significant enhancement of secondary memory at all testing times. Secondary memory is longer-term memory, in which recently supplied information is processed. To some degree, the same benefit was also seen at the other doses. Perhaps surprisingly, the higher doses did not work nearly as well as the 333 mg dose. There were also significant improvements in accuracy of attention following this dose, but not for the other doses. The extract used also inhibited cholinesterase in test-tube experiments.

The authors concluded that the overall pattern of results was consistent with a benefit to pathways involved in efficient processing of information and/or consolidation of memory, rather than enhanced efficiencies in retrieval or working memory. In their discussion, they note that this is the first time sage has been shown to improve cognitive function in healthy older individuals. The optimum sage dosage of 333 mg (2.5 g) improved secondary memory by about 30 units. The decline with age for the healthy group tested (compared to healthy 18- to 25-year-olds) was around 40 units. Hence, the benefits seen in the present study reflect a substantial temporary reversal of the deterioration in secondary memory that typically occurs with about 50 years of normal aging.

Another interesting finding of the study was that the dose response curve was an inverse U-shape. While the 333 mg dose gave better effects than the 167 mg dose, the higher doses did not work as well as the 333 mg dose. The active components in sage responsible for these effects and their exact mechanism of action are not yet understood, but the diterpenes and essential oil components could be relevant.

So, there is now a very promising body of clinical research that seems to confirm what the old herbalists already knew. At the very least, even if sage cannot help AD, it appears to be able to reverse some aspects of normal aging as it impacts our memories. What is still not understood is how it works, and what specifically in sage makes it work. That makes the aforementioned insights of the herbalists of old even more impressive.

Kerry Bone is a practicing herbalist; co-founder and head of research and development at MediHerb; and principal of the Australian College of Phytotherapy. He also is the author of several books on herbs and herbal therapy, including Principles and Practice of Phytotherapy and The Essential Guide to Herbal Safety.