Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2024 Dec 4;16(23):4199.
doi: 10.3390/nu16234199.

Effects of Melissa officinalis Phytosome on Sleep Quality: Results of a Prospective, Double-Blind, Placebo-Controlled, and Cross-Over Study

Francesco Di Pierro  1   2   3 , Davide Sisti  4 , Marco Rocchi  4 , Annalisa Belli  4 , Alexander Bertuccioli  2   4 , Massimiliano Cazzaniga  2   3 , Chiara Maria Palazzi  2 , Maria Laura Tanda  5 , Nicola Zerbinati  1
Affiliations
Randomized Controlled Trial

Effects of Melissa officinalis Phytosome on Sleep Quality: Results of a Prospective, Double-Blind, Placebo-Controlled, and Cross-Over Study

Francesco Di Pierro et al. Nutrients. .

Abstract

Background: Melissa officinalis standardised extracts, characterised by the presence of hydroxycinnamic acids, have been experimentally demonstrated to be endowed with anti-anxiety and anti-insomnia pharmacological actions. These effects, probably attributable, at least in part, to the role played by rosmarinic acid on GABA-T, have not always been observed in a reproducible manner in humans, perhaps due to the poor bioavailability of these compounds.

Methods: as nutraceuticals and botanicals could be an alternative option to prescription medications for alleviating symptoms of mild anxiety and insomnia, we have verified in a prospective, double-blind, placebo-controlled, and cross-over study the supporting role on sleep quality played by a Melissa officinalis highly standardised extract, formulated as Phytosome™ (MOP) to improve the oral bioavailability of its active polyphenolic components.

Results: results showed a significant reduction in the ISI score in the treated group, with an average of 6.8 ± 4.1 compared to 9.7 ± 3.7 in the placebo group, indicating a significant reduction of 2.9 points (p = 0.003). The SWS phase duration increased by an average of 15%, while the REM phase decreased by 10%. Additionally, 87% of participants in the treated group reported improved sleep quality, compared to 30% in the placebo group, with significant differences measured by chi-square test (χ2(4) = 21.01, p = 0.0003), highlighting the effects due to Melissa officinalis L. No significant changes in physical activity or anxiety levels were observed.

Conclusions: these findings suggest that MOP may represent a natural and safe alternative to traditional pharmacological treatments for insomnia.

Keywords: GABA-T; hydroxycinnamic acids; oral bioavailability; rosmarinic acid.

PubMed Disclaimer

Conflict of interest statement

Author F.D.P. is the scientific director of Pharmextracta, Pontenure, Italy; Authors A.B. (Alexander Bertuccioli) and M.C. are Pharmextracta, Pontenure, Italy consultants. The other authors declare no conflicts of interest and no financial relationships.

Figures

Figure 1
Figure 1
Graphical illustration of temporal phases of intervention, in which the timing of administration for the International Physical Activity Questionnaire (IPAQ), State-Trait Anxiety Inventory (STAI), and Insomnia Severity Index (ISI) is outlined.
Figure 2
Figure 2
Graphical representation of the cross-over design in which “Group 1” represents the group that took MOP during the first two weeks and a placebo during the last two, while “Group 2” performed the opposite.
Figure 3
Figure 3
Flowchart of study participants. *: Treatment with MOP.
Figure 4
Figure 4
(a) shows a violin plot of International Physical Activity Questionnaire score, for which there are no significant differences between the two groups (p = 0.63); (b) shows linear regression lines regarding METs and ISI score.
Figure 5
Figure 5
Delta score of State-Trait Anxiety Inventory questionnaire considering state anxiety, trait anxiety, and the total score in the two groups.
Figure 6
Figure 6
Box-and-whisker plot of mean scores of Insomnia Severity Index questionnaire, in which “Group 1” represents the group that took MOP during the first two weeks and a placebo during the last two, while “Group 2” performed the opposite.
Figure 7
Figure 7
Changes in Insomnia Severity Index scores. It can be observed that there is an increase in the ISI score from treatment (T1) to placebo (C2). Conversely, in the lower part of the graph, it can be noted that in Group 2, the opposite occurred, with a decrease in the ISI score from the placebo period (C2) to the treatment period (T2).
Figure 8
Figure 8
Treatment effect of the four phases of sleep. Although no significant changes were observed in total sleep time and light sleep phase, significant changes were detected in SWS and REM sleep.
Figure 9
Figure 9
Time effect related to the four stages of sleep. No significant results were observed regarding the time effect, indicating no influence of the time factor on the interpretation of the results.
Figure 10
Figure 10
No significant results were observed regarding the carryover effect in any sleep phase. On the y-axis, the average time spent in each phase is shown, to be interpreted as follows: e.g., for X1.T: 1 = group considered; T = two weeks of treatment with MOP considered.
Figure 11
Figure 11
Subjective improvements in sleep quality expressed as a percentage.
See this image and copyright information in PMC

References

    1. Zam W., Quispe C., Sharifi-Rad J., López M.D., Schoebitz M., Martorell M., Sharopov F., Fokou P.V.T., Mishra A.P., Chandran D., et al. An Updated Review on The Properties of Melissa officinalis L.: Not Exclusively Anti-Anxiety. Front. Biosci.-Sch. 2022;14:16. doi: 10.31083/j.fbs1402016. - DOI - PubMed
    1. Soltanpour A., Alijaniha F., Naseri M., Kazemnejad A., Heidari M.R. Effects of Melissa officinalis on Anxiety and Sleep Quality in Patients Undergoing Coronary Artery Bypass Surgery: A Double-Blind Randomized Placebo Controlled Trial. Eur. J. Integr. Med. 2019;28:27–32. doi: 10.1016/j.eujim.2019.01.010. - DOI
    1. Cases J., Ibarra A., Feuillère N., Roller M., Sukkar S.G. Pilot Trial of Melissa officinalis L. Leaf Extract in the Treatment of Volunteers Suffering from Mild-to-Moderate Anxiety Disorders and Sleep Disturbances. Mediterr. J. Nutr. Metab. 2010;4:211–218. doi: 10.3233/s12349-010-0045-4. - DOI - PMC - PubMed
    1. Shakeri A., Sahebkar A., Javadi B. Melissa officinalis L.—A Review of Its Traditional Uses, Phytochemistry and Pharmacology. J. Ethnopharmacol. 2016;188:204–228. doi: 10.1016/j.jep.2016.05.010. - DOI - PubMed
    1. Petrisor G., Motelica L., Craciun L.N., Oprea O.C., Ficai D., Ficai A. Melissa officinalis: Composition, Pharmacological Effects and Derived Release Systems—A Review. Int. J. Mol. Sci. 2022;23:3591. doi: 10.3390/ijms23073591. - DOI - PMC - PubMed

Publication types

LinkOut - more resources