New treatment approaches are needed to prevent cognitive decline and dementia in the growing elderly population. Several traditionally used medicinal plants have been reported to enhance cognitive function and improve brain health through their antioxidant, anti-inflammatory, and neuroprotective properties. Among those plants are sage (Salvia officinalis, Lamiaceae), rosemary (Rosmarinus officinalis, Lamiaceae), and Melissa (lemon balm; Melissa officinalis, Lamiaceae). Although study findings support the traditional use of these plants individually for cognitive function, no study has examined the clinical effects of a combination of sage, rosemary, and Melissa (SRM) on memory. These authors conducted a randomized, double-blind, placebo-controlled pilot trial to evaluate the effects of an SRM combination on verbal recall in healthy participants.
The study was conducted at Dilston Physic Garden Centre and BodyWorks Therapy Center in Northumberland, United Kingdom (the dates of the study are not given) and included healthy participants who were aged 40 years or older and who had not been diagnosed with cognitive impairment or dementia. Two study visits, two weeks apart, took place at the BodyWorks Therapy Centre. The participants were randomly assigned to take 5 mL SRM ethanol extract or 5 mL placebo, diluted in warm water, two times daily for two weeks. At baseline and at the end of the two weeks of treatment, each participant completed a pencil-and-paper immediate and delayed word recall test. The number of words correctly recalled minus the number of words not correctly recalled was calculated for both immediate and delayed word recall. Changes from baseline and differences between the two groups were analyzed.
For the SRM preparation, fresh authenticated sage, rosemary, and Melissa were supplied by Rutland Biodynamics, Town Park Farm, in Brooke, United Kingdom. [Note: The plant parts used were not specified; traditionally the leaves of sage and rosemary are used but leaves and flowers of Melissa may be used together.] The plant materials were individually extracted, 0.5 g/mL in 45% ethanol, for three weeks in the dark at room temperature. Equal portions of the extracts were combined. The daily dose of 10 mL of extract was equivalent to a daily dose of 5 g original plant material. Phytochemical analysis revealed the main compound classes of the three extracts and the SRM combination to be flavones and their glycosides, diterpenoids, and rosmarinic acid. Diterpenoids were detected only in the sage and rosemary extracts and not in the Melissa extract. The placebo was 50% fresh garden myrrh (sweet cicely; Myrrhis odorata, Apiaceae) extract (similarly prepared). Additionally, garden myrrh extract was added as 10% of the volume of both preparations, and 1% Lyles Black Treacle (Waitrose Ltd., United Kingdom) was added as a colorant to both to create visual similarity.
A total of 45 participants were recruited and 44 completed the study, 22 in each group. Participants in the placebo group were on average 4.5 years younger than those in the SRM group; however, this did not reach statistical significance (P=0.11). At baseline, the performance of the placebo group on the word recall test was marginally better than that of the SRM group (P>0.05). The authors report that no significant changes were observed during the study in either group nor were differences between the two groups significant. Although, numerically, the SRM group tended to improve more in delayed word recall.
In a possibly post hoc analysis, participants were divided into two subgroups to analyze younger and older participants separately by using baseline performance as the covariate. In the younger subgroup (two males and 24 females), the ages were 43-62 years in the placebo group and 44-61 years in the SRM group. In the older subgroup (4 males and 14 females), the ages were 66-78 years in the placebo group and 63-80 years in the SRM group. In the younger subgroup taking SRM, significant improvement in delayed word recall was observed compared with younger subjects taking a placebo (P=0.0347). A 56% improvement in delayed recall (2.6 words) was observed in the SRM participants in this subgroup compared with baseline (P=0.0123). No improvement in word recall was observed in the older subgroup.
Treatment compliance, which was similar in the two overall groups, was slightly less in the older subgroup. No adverse effects were reported.
The authors suggest that the mechanisms behind the positive effects seen in this study are likely due to the anticholinesterase action of the plants and the interactions of their constituents. Other mechanisms of action of constituents present in the three extracts, including terpenoids and phenolics or their metabolites, may also be relevant, including cholinergic receptor activation; these constituents also appear to have anti-inflammatory, antioxidative, anti-amyloid, estrogenic, and neuroprotective actions, though some of these are less likely to be relevant to short-term effects.
These study results suggest that the SRM combination, taken at the selected dose and duration, is more effective than placebo in improving verbal episodic memory in healthy participants younger than 63 years, according to the authors. However, if the analysis of different age groups was a posthoc analysis, it requires confirmation in additional studies. “Short- and long-term supplementation with SRM extract merits more robust investigation as an adjunctive treatment for patients with Alzheimer’s disease and in the general aging population,” the authors conclude. Although in this study no benefit was observed in older participants, they suggest that a higher dose might be effective. Also, additional tests of cognitive function could be included in future studies. The older age group would appear to be the most relevant for these effects. Those elderly with early signs of memory problems should perhaps be the target group for future studies.
This research was supported by the Ross Menzies Herbal Clinic, BodyWorks Therapy Centre, Wesnes Cognition Ltd, the Royal Botanic Gardens, Kew, and Dilston Physic Garden; authors were employed by the last four of these. Authors stated that they had no conflicts of interest.
Perry NSL, Menzies R, Hodgson F, et al. A randomized double-blind placebo-controlled pilot trial of a combined extract of sage, rosemary, and Melissa, traditional herbal medicines, on the enhancement of memory in normal healthy subjects, including the influence of age. Phytomedicine. January 2018;39:42-48. doi: 10.1016/j.phymed.2017.08.015.