Re: Proprietary Spearmint Extract Improves Working Memory in Subjects with Age-associated Memory Impairment

Spearmint (Mentha spicata, Lamiaceae) Age-associated Memory Impairment Working Memory Date: 02-28-2018 HC# 021851-587 Herrlinger KA, Nieman KM, Sanoshy KD, et al. Spearmint extract improves working memory in men and women with age-associated memory impairment. J Altern Complement Med. 2018;24(1):37-47. Age-associated memory impairment (AAMI) is a normal part of aging; nonetheless, slowing this decline improves quality of life. Spearmint (Mentha spicata, Lamiaceae) aerial parts contain polyphenols such as rosmarinic acid (RA) and salvianolic acid, which have anticholinesterase, antioxidant, and anti-inflammatory activity in neuronal cells. It has been hypothesized that spearmint can improve cognitive function. Using traditional breeding techniques, lines of spearmint that produce significantly higher levels of bioactive polyphenols have been developed. A proprietary dried aqueous extract of these spearmint chemotypes improved learning and memory in a mouse model of aging.1 In an open-label 30-day study of healthy, older adults with self-reported memory impairment, the polyphenol-rich extract was well-tolerated and improved cognitive performance.2 The purpose of this randomized, double-blind, placebo-controlled study was to evaluate the effect of this proprietary spearmint extract on cognitive performance, sleep, and mood in healthy, older subjects with AAMI. Healthy subjects (n = 90, 50-70 years) with AAMI according to National Institute of Mental Health criteria (≥25 on the Memory Assessment Clinic Scale Questionnaire [MAC-Q], ≤29 on the Verbal Paired Associates [VPA] I and/or ≤9 on VPA II of the Wechsler Memory Scale IV, and ≥24 on the Mini-Mental State Exam [MMSE]) were recruited from the local community of Addison, Illinois, from August 2013 through January 2014. Included subjects had a body mass index between 18.5 and 35.0 kg/m2, had at least a high school diploma, were willing to maintain their habitual diet and exercise routines, and were willing to maintain consistent sleep duration the evening before study visits. Excluded subjects met the following criteria: had clinically significant abnormal laboratory test results; history or presence of cancer, except nonmelanoma skin cancer; history or presence of clinically important cardiac, renal, hepatic, endocrine, pulmonary, biliary, gastrointestinal, pancreatic, or neurologic disorders; had a history of alcohol or substance abuse within the previous 12 months; had a history of depression within the past 24 months or used psychotropic medications within 1 month of screening; had a history of heavy smoking (>1 pack/day) within the past 3 months; had heavy caffeinated beverage consumption (>400 mg caffeine/day) within the past 2 weeks; were pregnant, lactating, or planning to be pregnant during the study period or of childbearing potential and unwilling to use a medically approved form of contraception; had an occupation that resulted in disruption of sleep-wake cycles; used medications or supplements known to alter cognitive function within the past 2 weeks; or an inability to complete or understand the cognitive function practice tests. Subjects received either placebo (cellulose) or 600 mg/day or 900 mg/day spearmint extract for 90 days. The proprietary spearmint extract (Kemin Foods, L.C.; Des Moines, Iowa) contained ≥14.5% RA and 24% total polyphenols. Cognition was assessed on days 0, 45, and 90 with the Cognitive Drug Research (CDR) System, which is a validated instrument. Mood was assessed with the Profile of Mood States (POMS) questionnaire on days 0 and 90. Sleep was assessed with the Leeds Sleep Evaluation Questionnaire (LSEQ) on days 0 and 90. Before and during all test visits, subjects were instructed to avoid vigorous physical activity for 24 hours, alcoholic beverages for 24 hours, caffeine for 10-14 hours, and tobacco (Nicotiana tabacum, Solanaceae) use for 1 hour. Compliance was excellent (≥98.1% for all groups). One subject in the placebo group and 2 subjects in the 600-mg spearmint group discontinued the study due to adverse effects (AEs). Only 1 AE (heartburn) was considered probably related to the 600-mg spearmint treatment. At 90 days, there were overall treatment effects in working memory and spatial working memory for subjects supplemented with spearmint. Pairwise comparisons between groups showed that subjects taking 900 mg spearmint had a significantly greater improvement (22%) in quality of working memory compared with a 5% improvement in the 600-mg spearmint group (P = 0.021) and 7% improvement in the placebo group (P = 0.047). Also, subjects taking 900 mg spearmint had a significantly greater improvement (17%) in spatial working memory compared with a 3% improvement in the 600-mg spearmint group (P = 0.017) and 6% improvement in the placebo group (P = 0.046). There were no other significant improvements in cognitive performance. Of the 7 mood factors assessed, there were significant overall treatment effects for the vigor-activity factor (P = 0.039) and the composite total mood disturbance (TMD) (P = 0.037) after 90 days of spearmint supplementation. However, pairwise comparisons between groups for the vigor-activity factor showed a trend towards significance only for the 900-mg group versus placebo (P = 0.065). Similarly, for the TMD, pairwise comparison showed a trend towards significance only for the 900-mg group versus placebo (P = 0.083). There were no significant improvements in the other mood factors. Significant overall treatment effects were observed in subjective ratings of ease of getting to sleep (P = 0.017) and behavior following wakefulness (P = 0.042) for subjects supplemented with spearmint. Pairwise comparisons indicated that the 900-mg spearmint group had significantly improved ability to get to sleep compared with placebo (P = 0.005). Pairwise comparisons showed a significant improvement in behavior following wakefulness in the 900-mg versus the 600-mg group (P = 0.014) but not versus placebo (P value not reported). There were no significant differences among groups in quality of sleep or ease of awakening from sleep. In summary, subjects with AAMI taking 900 mg/day of the proprietary spearmint extract for 90 days had significantly improved working memory, spatial working memory, and self-reported ability to get to sleep. There were overall spearmint treatment effects for vigor-activity, TMD, and behavior after waking, with trends towards statistical significance compared to placebo. Also, 900 mg/day spearmint for 90 days was well tolerated in this population. This study bears repeating with a larger population (this study had 30 subjects/group), for a longer duration (age-related cognitive impairment increases over time), with additional measures of cognitive function, and possibly with a higher dose. The study was funded by Kemin Foods, L.C. The authors have either received research funding from or are employees of Kemin Foods, L.C. —Heather S. Oliff, PhD References 1Farr SA, Niehoff ML, Ceddia MA, et al. Effect of botanical extracts containing carnosic acid or rosmarinic acid on learning and memory in SAMP8 mice. Physiol Behav. 2016;165:328-338. 2Nieman KM, Sanoshy KD, Bresciani L, et al. Tolerance, bioavailability, and potential cognitive health implications of a distinct aqueous spearmint extract. Functional Foods in Health and Disease. 2015;5(5):165-187.