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| Date: 12-31-2015 | HC# 071511-535 |
Noguchi-Shinohara M, Ono K, Hamaguchi T, et al. Pharmacokinetics, safety and tolerability of Melissa officinalisextract which contained rosmarinic acid in healthy individuals: a randomized controlled trial. PLoS One. 2015;10(5):e0126422. doi: 10.1371/journal.pone.0126422.
Rosmarinic acid (RA), a compound found in lemon balm (Melissa officinalis, Lamiaceae), has been reported to have promising effects against neurotoxic events occurring in Alzheimer's disease (AD). Although many studies have reported numerous biological effects of RA, the pharmacokinetic profile of this compound from lemon balm extracts has not been reported. The aim of this placebo-controlled, randomized trial was to evaluate the food-effect and safety of lemon balm extract (donated by Maruzen Pharmaceuticals Co., Ltd.; Hiroshima, Japan)containing 500 mg, 250 mg, and 100 mg of RA in healthy subjects.
Subjects were recruited from the Kanazawa University in Kanazawa, Japan. Exclusion criteria included dementia, pregnancy, health problems, allergies (e.g., to polyphenolics, food ingredients, or drugs), and consumption of any supplement containing RA 15 days prior to the study. A total of 11 subjects (8 men and 3 women; 20-31 years of age) were enrolled in 2 studies. In the first study, subjects underwent a 12-hour fast before consuming the RA supplement, whereas in the second study, subjects consumed the supplement 30 minutes after completion of a standardized low-polyphenol meal.
Subjects were also divided into 3 groups (A, B, and C in a 3 × 3 Latin square design). In each of these groups, subjects consumed the placebo and 2 out of 3 doses (500 mg, 250 mg, and 100 mg of RA) during 3 separate trial periods. Overall, a total of 9 subjects completed 1 of the 2 studies, and 7 subjects completed both. Each intervention was 10 days, which included a 7-day controlled diet period (low-polyphenolic diet) and a 3-day treatment period. The washout period between interventions was 10 days.
Subjects were provided with placebo capsules and capsules containing RA-enriched lemon balm extract. The RA-enriched capsules contained 185 mg lemon balm extract, 50 mg RA, 60 mg lactose, and 5 mg calcium stearate. The placebo capsules (donated by Maruzen Pharmaceuticals Co., Ltd.) contained 210 mg lactose, 35 mg caramel, and 5 mg calcium stearate. Subjects consuming the 100-mg, 250-mg, and 500-mg doses of RA consumed 2, 5, or 10 capsules of RA, respectively, to obtain the appropriate single dose.
Blood samples were collected at baseline and 0.25, 0.5, 1, 2, 3, 6, 24, 48 hours after intake of the RA supplement or placebo on each intervention day. Subjects were evaluated for body measurements, and blood samples were assessed for hematological parameters and other biochemical parameters. Any adverse events were self-reported.
Baseline characteristics were similar among all of the treatment groups. Only 1 subject dropped out of the study (from the 100-mg RA arm) due to problems that did not appear to be related to the study (lack of sleep). For all treatments, no significant differences were found for hematological parameters and indicators of liver and kidney function.
RA was not detected in blood samples of the placebo group subjects (fasted or fed). In the 100-mg RA arm,serum RA was also not detected in 4 of 6 subjects in a fasted state or in 5 of 6 subjects in a fed state. For the fasted state, the maximum concentration of total RA for the 250-mg and 500-mg doses of RA was 1 hour (72.22 ± 12.01 nmol/L and 162.20 ± 40.20 nmol/L, respectively). In the fed state, total RA was not detected in 5 out of 6 subjects with the 250-mg dose of RA, and maximum concentration of total RA for the 500-mg dose of RA was 3 hours (142.20 ± 45.20 nmol/L).
The mean values for the area under the curve for total RA and intact RA (AUCTotal, AUCIntact) for a 500-mg dose of RA in the fasted state were 2 times and 7.5 times greater, respectively, than the values for a 250-mg dose of RA. The mean values of the maximum serum concentration of total RA and intact RA for the 500-mg dose of RA in a fasted state were 2 and 4 times greater, respectively, than the values found for the 250-mg dose of RA. Overall, it was found that consuming food before intake of RA increased the AUC and delayed the time for the maximum serum concentration.
This study confirmed the safety and tolerability of lemon balm extract containing up to 500 mg of RA. In addition, a previous study has shown that a dose of RA from lemon balm extract (around 120 mg) significantly improved cognitive function in patients with mild to moderate AD.1 The authors suggest pharmacokinetic studies of RA should also be conducted in older populations that are more at risk for AD. This study provided valuable information about the effects that food may have on the pharmacokinetics of an RA-enriched lemon balm extract. The information will be useful for future clinical studies that evaluate the health effects of lemon balm products containing RA.
—Laura M. Bystrom, PhD
Reference
1Akhondzadeh S, Noroozian M, Mohammadi M, Ohadinia S, Jamshidi AH, Khani M. Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomised, placebo controlled trial. J Neurol NeurosurgPsychiatry. 2003;74(7):863-866.
