Will Sage Oil Make You Wiser?
Abstracts & Commentary
Sources: Perry NS, et al. Salvia for dementia therapy: Review of pharmacological activity and pilot tolerability clinical trial. Pharmacol Biochem Behav. 2003;75:651-659; Tildesley NT, et al. Salvia lavandulaefolia (Spanish Sage) enhances memory in healthy young volunteers. Pharmacol Biochem Behav. 2003;75:669-674.
In 1597, the herbalist John Gerard reported that an extract of the sage plant, "is singularly good for the head and brain and quickeneth the nerves and memory." More than 400 years later, British investigators have put Gerard’s observation to the test by examining the effects of an essential oil derived from Spanish sage (Salvia lavandulaefolia) on memory in normal volunteers and patients with Alzheimer’s disease (AD). Researchers from the Medicinal Plant Research Centre (MPRC) at the Universities of Newcastle and Northumbria hypothesized that sage oil extract would improve memory acutely in normals and have positive long-term effects on AD patients. Their rationale included past reports in the herbal literature about sage’s cognitive-enhancing effects and recent studies of sage oil’s antioxidant, anti-inflammatory, and acetylcholinesterase inhibitory properties.
Tildesley and associates carried out 2 crossover studies of sage oil in normals—one with a pseudo-randomized design in 20 volunteers and another doubleblind, placebo-controlled investigation in 24 additional subjects. A computerized cognitive test battery was administered 4 times over a 6-hour period to assess immediate and delayed verbal recall abilities before and after sage oil ingestion. One hour after oral administration, a dose of 50 mL of sage oil was reportedly associated with a statistically significant change from baseline in immediate verbal recall performance relative to placebo. Effects at other times and doses were not consistently observed across trials. No adverse effects were observed in normals with single doses up to 150 mL.
Perry and colleagues reported results of an open-label trial in 11 patients with mild-to-moderate AD who initially received 50 mL per day of sage oil and were titrated over 3 weeks to 50 mL t.i.d. Outcome was assessed at 6 weeks using the Folstein Minimental State (MMSE) examination, a computerized cognitive test battery and the Neuropsychiatric Inventory. No significant changes were observed in immediate recall, delayed recall, or the MMSE. The NPI and tests of attention and vigilance were reported to improve after 6 weeks of treatment with sage oil. Two patients with a past history of hypertension experienced significant increases in blood pressure during the trial. The study also examined the degree of peripheral red blood cell acetylcholinesterase (AChE) inhibition brought about by sage oil treatment and found a 14% inhibition of AChE at 150 mL/d. Perry et al found the results encouraging and expressed the belief that further studies are warranted to establish the value of sage oil as a treatment for AD.
Commentary
While it is encouraging to see herbal medicines being investigated with rigorous clinical scientific methodology, these studies fall short of supporting their conclusions concerning the value of sage oil in improving human cognition. In the trials involving normal adults, baseline memory performance was substantially lower in the sage oil-treated arms than with placebo. This difference in memory performance at baseline was actually greater than the magnitude of the reported change in memory performance after treatment. Although such baseline differences can be adjusted for analytically, the reported changes in memory performance with 50 mL doses of sage oil could well represent regression to the mean rather than a true biological effect.
The open-label trial is clearly inadequate to establish whether sage oil is beneficial in the treatment of AD patients. The duration was too short, especially since AD clinical trials frequently show a placebo effect at 6 weeks. This is particularly problematic in an open-label study with an exceedingly small number of subjects and an accordingly greater potential for biased outcome. The 14% inhibition of AChE observed in this study indicates relatively weak cholinesterase inhibition relative to approved AD treatments. Despite Perry et al’s contention that sage oil is a more benign intervention than currently available AD therapies, the occurrence of treatment-related hypertension in 2 of 11 AD patients receiving sage oil at doses of 150 mL per day suggests that this herbal preparation is not without potential side effects.
Unquestionably, sage can add to the taste of turkey stuffing, stews, and salads. The medicinal value of sage oil, however, remains to be determined. — Norman Relkin, MD, PhD, Associate Professor of Clinical Neurology and Neuroscience, New York Presbyterian Hospital-Cornell Campus, Assistant Editor, Neurology Alert.
In 1597, the herbalist John Gerard reported that an extract of the sage plant, is singularly good for the head and brain and quickeneth the nerves and memory. More than 400 years later, British investigators have put Gerards observation to the test by examining the effects of an essential oil derived from Spanish sage on memory in normal volunteers and patients with Alzheimers disease.
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