Introduction
Lemon Balm, scientifically known as Melissa officinalis, is a versatile herb with a rich history in traditional and modern herbal medicine. A member of the Lamiaceae family, lemon balm has been cherished for centuries and stands as a promising herbal option for pediatric medicine due to its gentle yet effective calming properties. In this article, we will explore the world of lemon balm, uncovering its historical significance, active constituents, and diverse applications in health and wellness, particularly for pediatric medicine.
Historical use of lemon balm
Lemon balm has a deep-rooted legacy in traditional medicine, tracing back over 2000 years and originating with the Greeks and Romans.1,2 The Greek Polymath Theophratus mentioned it in his Historia Plantarum around 300 BC, calling it “honey-leaf.” In Iranian folk medicine, its leaves are cherished for their digestive, sedative and analgesic properties.3 Dioscorides (40-90 CE), the father of pharmacology, introduced the medicinal properties of lemon balm in De Materia Medica, stating “A decoction of the leaves is good for those touched by scorpions, or bitten by harvest spiders or dogs.”1 Introduced formally into Europe in the 7th century, lemon balm found favor among herbalists, writers and philosophers in the Middle Ages. Arabic literature in the 15th century reveals historical insight into Lemon balm’s neuropsychiatric uses.2 While cultivated to attract bees and believed to keep them in gardens, historical records also reveal its use in treating bee stings.4 In European Traditional Medicine, Melissa officinalis was employed as a remedy for memory, cognition, insomnia, anxiety, depression, heart palpitations, and stimulating appetite.1,4,5 Early immigrants carried Lemon balm to North America, utilizing it for potpourri and as a lemon substitute in jams and jellies. By the early 1800s, Lemon balm seeds were regularly advertised in newspapers and eventually became a staple in herbal gardens across the US.6 Lemon balm, with its extensive history spanning civilizations and continents, continues to be revered in traditional medicine for its diverse therapeutic properties, leaving an enduring legacy that transcends over two millennia.
Active chemical constituents of lemon balm
Melissa officinalis’s therapeutic potential lies in its array of active chemical constituents, including terpenes, flavonoids, and phenolic compounds.
The active constituents of Melissa officinalis are primarily found in its leaves. These constituents include volatile compounds, terpenoids, as well as polyphenolic compounds like rosmarinic acid, caffeic acid, protocatechuic acid, rhamnocitrin and luteolin.5 Its essential oil, which contains citronella and geranial, imparts the delightful lemony scent associated with the plant. In contrast to other plants within the Laminacea family, Melissa officinalis contains notably low oil content, yet this constituent significantly contributes to its pharmacologic effects.7 Comparatively, research on the non-volatile components of Melissa officinalis is sparse. However, existing studies highlight flavonoids like quercetin and luteolin as contributors to its antioxidant properties, while phenolic compounds such as rosmarinic acid enhance its anti-inflammatory and antimicrobial effects.7
| Terpenoids | Oleanolic acid, betulinic acid, ursolic acid |
| Phenolic acids | Rosmarinic acid, caffeic acid, protocatechuic acid, caftaric acid, chologenic acid, ferulic acid, gentisic acid, p-coumaric acid |
| Flavonoids | Apigenin, rutin, cynaroside, isoquercitin, quercetin, luteolin, rhamnocitrin daidzein, hyperoside, kaempherol, myricetin, quercetrol |
| Volatile compounds | E-caryophyllene, caryophyllene oxide, citronella, geranial, geranyl acetate, neral, a-cadinol, a-copaene, b-caryophyllene |
| Other compounds | Lignin, polysaccharaides, alpha-cellulose, tannins |
Safety of lemon balm (Melissa officinalis) and considerations for infants, children, in pregnancy and lactation
Melissa officinalis is generally regarded as safe for most individuals. However, as with any herbal remedy, some precautions should be considered. Allergic reactions may occur in individuals with hypersensitivity to plants in the Lamiaceae family.
Pregnancy: Category B2. A retrospective observational study published in 2015 cited Melissa officinalis as one of the most commonly used medicinal herbs during pregnancy without correlated adverse outcomes.8 Further research has revealed lemon balm to be effective and safe in reducing severity of pain after birth.9
Lactation: Likely compatible. While there is evidence suggesting galactogogue activity in Lemon balm, no data currently exists on the excretion of Lemon balm components into breastmilk, or its safety and efficacy for nursing mothers and infants.10 However, historically and in contemporary research (see below), lemon balm has been safely and effectively administered alongside other herbs for various infant treatments and is likely not to be harmful with usual maternal doses. Given it’s extensive historical use, the main concern for pediatric clinicians is precise dosing to ensure safety and efficacy.
Infants and children: Likely safe in appropriate doses. See above, precise dosing is necessary to ensure safety and efficacy.
Lemon balm in clinical and naturopathic medicine
Melissa officinalis’s (MO) role in naturopathic pediatric medicine is significant due to its diverse therapeutic applications. It has been used to treat a range of conditions for adult and pediatric patients including digestive issues, infections, anxiety, depression, insomnia, palpitation, hypertension, dementia, infantile colic, bruxism, metabolic problems, and sexual disorders. 11
Pediatric Specific Research for Lemon Balm (Melissa officinalis)
Restlessness & difficulty sleeping:
In a 2006 open, multicenter study, the effectiveness of a combined valerian and Melissa officinalis preparation was assessed in 918 children < 12 years of age experiencing restlessness and nervous dyskoimesis. The study revealed a significant reduction in symptom severity, particularly in core symptoms like dyssomnia with an 80% improvement and restlessness (70.4% improvement). Both parents and investigators rated the treatment as effective (60.5% and 67.7%, respectively), and it was well-tolerated with no medication-related adverse effects.12
Hyperactivity and concentration deficits
Likewise, a 2014 observational study reported similar outcomes. In this study, 169 primary school children <12 years of age, experiencing hyperactivity and decreased concentration (not meeting ADHD criteria), were treated with valerian root and Melissa officinalis extracts. The treatment led to significant reduction in symptoms of poor focus, hyperactivity and impulsiveness. Parents also reported improvements in social behavior, sleep, and overall symptom burden.13
Infantile colic
A 2017 randomized control trial of 176 infants with colic showed that a preparation containing chamomile, Melissa officinalis, and tyndallized Lactobacillus acidophilus HA122 as well as Lactobacillus Reuter DSM 17938, resulted in significantly lower daily crying time when compared to Simethicone, a common medication for gas and stomach relief.14
Teeth grinding
In a trial of 52 children with possible sleep bruxism, homeopathic Melissa officinalis, Phytolacca decandra (PD), and their combination were tested in four 30-day phases. All treatments, including placebo, led to significant reductions in bruxism compared to baseline. Melissa officinalis (MO) performed better than PD (p=0.018) and similarly to MO + PD (P= 0.724), slightly outperforming Placebo (p= 0.050). However, neither sleep diary nor anxiety scale outcomes changed with any treatment.15
PMS
Three studies involving high school-aged girls investigated the effect of Melissa officinalis on premenstrual syndrome symptoms over three menstrual cycles. In the first study published in 2015, 1200 mg Melissa officinalis resulted in significant reduction of PMS symptoms (p<0.001) with an overall decrease in PM intensity in the intervention compared to placebo (42.56 + 15.73 before the intervention and changed to 32.72 ± 13.24, 30.02 ± 12.08, and 13.90 ± 10.22 after three months).16 A followup study by the same authors published in 2017 showed 600 mg Melissa officinalis capsules and care education led to significant reductions in physical, psychological and social PMS symptoms compared to placebo.17 In the third study, 600 mg Melissa officinalis capsules alone revealed significantly lower psychosomatic symptoms (p <0.001), anxiety and sleep disorders (p<0.001) and social function disorders (p=0.021) compared to placebo.18
Acne vulgaris
Hydroalcoholic and hydrodistillation of Melissa officinalis were utilized in a 2018 study examining efficacy on acne in 20 participants aged 15-31 years old. Both extracts showed significant improvement in skin pore conditions, acne infections and hypersecretion of sebaceous glands.19
Viral infections
Studies showcasing Melissa officinalis’s antiviral properties against infections like influenza and Enterovirus71 are particularly relevant for children who are more susceptible to such viruses. The observed effect of lemon balm on mood and sleep in adults may suggest avenues for pediatric mental health interventions. Furthermore, lemon balm’s use in managing dysmenorrhea could be relevant for adolescent girls experiencing menstrual pain. Lemon balm’s implications for cardiovascular health and metabolic markers could open possibilities for managing cardiovascular risks in children with relevant conditions.
While direct studies in pediatric populations are essential, drawing insights from adult-focused research could pave the way for tailored treatments for various pediatric health conditions using Melissa officinalis.
General Research for Lemon Balm (Melissa officinalis)
Hand-Foot-Mouth Disease, COVID-19 and Other Viral Infections
Enteroviruses: Enterovirus71 is a significant cause of Hand, Foot and Mouth Disease in young children, occasionally leading to severe complications and, rarely, death. A 2017 investigation of Melissa officinalis (MO) was conducted by Sin-Guang Chen et al., which found the concentrated methanolic extract from MO inhibited plaque formation, viral protein synthesis, and cytopathic effects in EV71-infected cells. Rosmarinic acid was identified as an active component that demonstrated inhibition of viral attachment, reduction in protein cleavage and modulation of cellular processes, suggesting its potential therapeutic use against EV71 infection.20
COVID-19: The research on Melissa officinalis’s antiviral properties gained increased attention during the SARS-V-COVID-19 pandemic. In docking experiments, Prasanth and colleagues discover that three phytoconstituents from Melissa officinalis, including luteolin-7-glucoside-3’-glucuronide, melitric acid-A, and quadranoside-III, exhibited strong binding affinity and stability with COVID-19’s primary protease and spike protein.21 These findings align with earlier work by Elekofehinti et al., which found that melitric acid A and salvanolic acid A showed higher binding affinity to COVID-19’s main protease compared to lopinavir and ivermectin, as assessed using AutodockVina and XP docking algorithms.22
Influenza: A 2016 study found that Melissa officinalis (MO) essential oil, containing monoterpenaldehydes citral a and citral b, inhibits influenza virus replication through multiple mechanisms including masking the host cellular surface protein, intracellular steps, and direct virucidal effect by structural damage.23 Furthermore, this research found that combining MO with oseltamivir, an antiviral medication commonly used to treat influenza, enhanced the drug’s effectiveness, even at low concentrations.23 Similar encouraging results were seen in research evaluating the efficacy of MO extract against influenza subtype H1N1 in cell culture.24
Herpes simplex virus: A 2004 study published in Phytomedicine demonstrated inhibition of HSV-2 replication from the application of non-toxic concentrations of Melissa officinalis (MO) volatile oils, indicating the presence of anti-HSV-2 substance.25 MO extract has further demonstrated potent virucidal activity against HSV-1, even at very low concentrations (1.5 ug/ml) by hindering HSV-1 attachment to host cells and direct viral damage.26,27 These findings suggest MO to be a promising candidate for potential topical therapeutic applications against recurrent herpes infection.
A 2018 study published by Geuenich et al demonstrated that aqueous extracts of Melissa officinalis displayed potent and concentration-dependent activity against HIV-1 by affecting free virions, reducing HIV-1 entry and hindering early stages of infection.28
Other Antimicrobial Effects
Multiple studies on Melissa officinalis (MO) have highlighted its potent antibacterial and antifungal properties. Essential oils show strong antimicrobial effects against various bacteria, including Salmonella typhimorium, Escherichia coli, Listera monocytogenes and Staphylococcus aureus.11 Additionally, MO has demonstrated high sensitivity against E. coli ATCC25922 and a multiresistant strain of Shigella sonei IPH-MR.11
Moreover, MO essential oil has displayed significant antifungal properties, particularly against Trichophyton tonsurans and various Candida strains.11
Mood and Sleep Disorders
Anxiety: A 2007 in vitro study aimed to evaluate the impact of various botanicals on primary brain enzymes responsible for GABA metabolism and, thus, anxiety management. Among the tested extracts, Melissa officinalis exhibited significant inhibition of GABA transaminase (GABA-T) activity.29 Another randomized clinical trial study with 36 burn patients admitted to Shahid Motahari Burn Hospital in 2013, patients who consumed Melissa officinalis tea exhibited a significant reduction in anxiety (P=0.023) and depression (P = 0.002) compared to the control group. Moreover, the Melissa officinalis tea group also experienced improved sleep quality (P= 0.031).30
In a 2019 double-blind RCT involving 80 post-coronary artery bypass surgery patients, the impact of administering 1.5g powdered Melissa officinalis three times daily was assessed. After the seven-day intervention, the group receiving Melissa officinalis exhibited significantly reduced anxiety scores (P=0.001) and improved sleep quality (P<0.001) compared to placebo. This treatment notably reduced anxiety levels by 49% and improved sleep quality by 54% in these patients.33
A 2022 in vivo study found that Melissa officinalis essential oil resulted in a significant reduction in motor impairment associated with acute anxiety in mice as well as inhibition of ileum contraction and a decrease in atria contraction frequency and force. Notably, the study indicated that the anxiety-reducing effects were not associated with acetylcholinesterase inhibition. Instead, the observed effects of the oil, including those of its primary constituent, citronella, appeared to be linked to potential alterations in voltage-gated Ca2+ channel or muscarinic receptors.34
A 2019 study with 96 patients in a cardiac care unit, aromatherapy using Melissa officinalis extract for 30 minutes twice daily during three consecutive days revealed significantly lower anxiety score post-intervention (p<0.05)38.
Insomnia: An in vivo study aimed to assess the hypnotic effects of several plant extracts (200, 400 and 800 mg/kg) in mice found that, compared to control, Melissa officinalis reduced sleep onset by 24.7%, 27.5% and 51.2% and prolonged sleep duration by 37.9%, 68.7% and 131.7% respectively. Combining L. angustifolia and Melissa officinalis extracts showed an additive effect, suggesting their potential usefulness in addressing insomnia.31
Mixed anxiety, depression and insomnia: In a double-blind randomized placebo controlled clinical trial published in Integrative Medicine Research in 2018, authors M. Ranjbar, et al., reported the impact of a herb combination (Melissa officinalis, Nepeta menthoides Boiss. & Bushes) on anxiety and depression among 67 individuals with insomnia. After four weeks, the herbal treatment group showed improvement in insomnia severity, anxiety and depression compared to placebo (P = 0.008, 0.005, and < 0.001 respectively).32
In a double-blind, placebo-controlled clinical trial involving 80 patients with chronic stable angina(CSA), an 8-week supplementation with 3g of Melissa officinalis significantly reduced depression, anxiety, stress and sleep disturbances compared to the placebo group. These findings suggest that Melissa officinalis supplementation may offer potential benefit in alleviating emotional and sleep-related issues in CSA patients.35
Depression: In an 8-week randomized, double-blind clinical trial involving 45 adult outpatients diagnosed with major depression, Melissa officinalis ( 2g), Lavandula angustifolia (2g), and fluoxetine (20mg) were compared for their efficacy in treating mild to moderate depression. Assessment using the Hamilton Rating Scale for Depression at weeks 0, 2, 4, and 8 revealed that both Melissa officinalis and L. angustifolia demonstrated effectiveness comparable to fluoxetine in managing mild to moderate depression. Notably, no significant differences were found between the three groups (F = 0.131, df = 2,42, p = 0.877).37
A study, published in 2020, explored the impact of a blend of L-theanine, Magnolia offcinalis and Melissa officinalis (TMM) on mood disorders through in vivo and in vitro analysis. Through animal models, TMM showcased strong anxiolytic and antidepressant properties. Additionally, in vitro tests revealed TMM’s ability to protect neurons from excitotoxicity, suggesting potential neuroprotective qualities. Notably, TMM seemed to operate through a mechanism distinct from traditional benzodiazepines, indicating a novel approach to addressing mood disorders. The study also indicated a possible involvement of the endocannabinoid system in TMM’s effects, as evidenced by reduced efficacy in the presence of cannabinoid receptor type 1 (CB1) antagonists.39
Cardiovascular and Metabolic Disorders
Cardiac arrythmias and cardiac protection: Melissa officinalis (MO) has shown promising cardiovascular effects in preclinical animal studies, including anti-arrhythmogenic, hypotensive, and vasorelaxant properties. While some benefits, like the reduction of heart palpitations, have been observed in humans, the underlying mechanisms involve Melissa’s antioxidant and anti-inflammatory properties, receptor activation, and inhibition of calcium channels and are attributed to the chemical constituent, rosmarinic acid.5
Heart palpitations: In a 2015 double-blind, randomized controlled trial assessing heart palpitations, eligible participants were randomly assigned to either a 14-day regimen of 500 mg of Melissa officinalis leaf extract twice a day or a placebo. Assessments were based on patient diaries and self-reported questionnaires, focusing on palpitation frequency and intensity. Secondary outcomes evaluated psychiatric symptoms before and after the intervention. The results highlighted a significant reduction in palpitation frequency and lowered anxiety among those taking Melissa officinalis extract compared to the placebo, with no observed serious side effects.43
Diabetes: In a 2018 study published in Complementary Therapies in Medicine, a randomized double-blinded clinical trial investigated the impact of 700 mg/d Melissa officinalis compared to placebo over 12 weeks in type 2 diabetic patients aged 20-60 years old. Results indicated significant differences in serum Apo A-I, TC/HDL-c, and LDL-c/HDL-c in the Melissa officinalis group compared to placebo (p<0.05).47
In a 2019 study with dyslipidemic adult diabetic patients, those who took 500 mg Melissa officinalis capsules twice daily for 2-3 months experienced a notable reduction in serum triglyceride levels (P = 0.04) compared to placebo. Additionally, they showed a significant decrease in both systolic and diastolic blood pressure (p= 0.02). No significant metabolic changes were observed compared to the control group.48
A 12-week randomized, double-blind, clinical trial aimed to evaluate the effect of 700mg/d Melissa officinalis on adult patients with type 2 diabetes (n=31). The MO group reportedly showed improvements in serum FBS (p=0.007), HbA1c (p=0.002), B-cell activity (p=0.05), triglycerides (p=0.04), HDL-c (p=0.05), hs-CRP (p=0.001), and systolic blood pressure compared to placebo (p=0.04).49
Women’s Health
A systematic review utilizing electronic databases explored the therapeutic potential of Melissa officinalis for obstetric and gynecological health issues. Fifteen studies were included, showcasing Melissa officinalis’s efficacy in reducing pain during childbirth and primary dysmenorrhea, alleviating premenstrual symptoms and addressing postpartum blues. Reported side effects among intervention groups were mostly minor, including diarrhea, constipation, flatulence, stomach pain, and sleep disturbances, with many studies reporting no side effects.50
In a randomized controlled trial from 216, a group of ninety-three female university students joined a study examining the impact of Melissa officinalis on premenstrual syndrome (PMS) symptoms and quality of life. The participants who exclusively took MO experienced notable decreases in PMS symptoms and reported enhanced physical and psychological quality of life compared to those in the placebo group following the two-month intervention.51
There has been further research into the effects of Melissa officinalis on cognitive function and quality of life in alzheimer’s patients,52,53 as potential anti-convulsant therapy,54–56 for sexual dysfunction in women,57 inhibition of HSV-1 and HIV-1
Research Considerations
As practitioners of naturopathic and functional medicine, we’re well acquainted with the limitations in studies investigating botanical medicine. My review of research on Melissa officinalis (lemon balm) showed the usual trends: publication bias and methodological differences that challenge standardizing its dosage or use by conventional medical standards.
That said, lemon balms’ enduring legacy across over millennia celebrates its efficacy as a potent plant medicine. Its consistent use across time to aid with anxiety and sleep is particularly compelling, but the more varied research, such as its use as an antimicrobial, is ceaselessly intriguing. Furthermore, its established safety profile emboldens me to integrate lemon balm into tailored treatment plans for patients of all ages. It is imperative that we integrate historical wisdom with modern research to understand lemon balm’s potential.
As clinicians, we can use this research as a starting point to inform our clinical decisions, and should feel especially supported when considering the wealth of evidence to date on shared constituents in medicines similar to lemon balm. As I researched, I felt encouraged to see a recent surge in clinical trials and research published over the last 5 years and believe this signals a shift in scientific exploration, aiming not only to validate traditional and anecdotal evidence, but actively seeking lower-intervention solutions for disease. With the rise of antibiotic resistance and more families seeking out holistic care, incorporating lemon balm and other plant medicines into managing acute and chronic disease is a practical, not to mention cost-effective, solution for families and the healthcare system as a whole.
In conclusion
Melissa officinalis stands as a beacon in pediatric medicine, heralding a centuries-old legacy steeped in its gentle yet powerful therapeutic properties. Its rich historical roots spanning civilizations underscore its versatile applications in addressing various pediatric health concerns, from restlessness and hyperactivity to digestive issues and sleep disorders.
The herb’s safety profile positions Melissa officinalis as a promising botanical ally in pediatric care. Bridging historical reverence with modern evidence-based practice illuminates Melissa officinalis’s role as a gentle yet effective therapeutic option and plant ally, offering hope for tailored treatments in pediatric medicine.
References
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14. Martinelli M, Ummarino D, Giugliano FP, et al. Efficacy of a standardized extract of Matricariae chamomilla L., Melissa officinalis L. and tyndallized Lactobacillus acidophilus (HA122) in infantile colic: An open randomized controlled trial. Neurogastroenterol Motil. 2017;29(12). doi:10.1111/nmo.13145
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