Review of the Uses, Chemistry, and Pharmacology of Lemon Balm

Lemon balm (Melissa officinalis, Lamiaceae) is widely used in European traditional medicine and Iranian traditional medicine (ITM) for various diseases, as well as being consumed as a salad vegetable and food flavoring. The authors searched unpublished old texts and several databases of published literature to review the botanical characteristics, traditional uses, phytochemistry, pharmacology, pharmacokinetics, and toxicity of lemon balm.

Lemon balm, also commonly known as balm and beebalm, is a perennial lemon-scented herb. The Eastern Mediterranean region, Western Asia, Southern Europe, Caucasus, and northern Iran are considered its areas of origin, but it grows worldwide. Its medicinal properties were first documented by Dioscorides (40-90 CE), who recommended a leaf decoction for spider, scorpion, and dog bites, and for amenorrhea, dysentery, mushroom poisoning, scrofulous tumors, and other indications. Paracelsus (1493-1541) prescribed lemon balm for nervous system disorders. Since 1984, it has been listed in the German Commission E monographs and is included in several pharmacopeias. In Danish folk medicine, lemon balm is used for sleeplessness caused by heartbreak or melancholy; in Austria, its essential oil (LBEO) is used for gastrointestinal, nervous, hepatic, and biliary problems. Lemon balm was used by Avicenna (981-1037) for all diseases caused by black phlegm and black bile. He attributed its antidepressant effects to its aroma. The plant has also been reported to be used as a cardiac and gastric tonic, memory enhancer, wound disinfectant, and for certain eye diseases. It is most often used in multiherb preparations, with varying dosages. It is a component of about 400 ITM medicinal preparations.

Lemon balm’s main active components are volatile compounds, triterpenes, and phenolics. LBEO, widely used in the pharmaceutical and food industries, is considered to be responsible for lemon balm’s antibacterial and antifungal effects. Obtained from fresh or dried flowers, leaves, and branches, LBEO is expensive due to its low yield; it comprises only 0.02-0.30% of plant material. While its composition varies by region and climate, most studies report that LBEO contains oxygenated monoterpenes, including the citral isomers geranial and neral, as well as citronellal, geraniol, and geranyl acetate. The main triterpenes in lemon balm are ursolic and oleanolic acids, with reported biological effects including antifungal, cytotoxic, and hemolytic activities. Antioxidant and antimicrobial effects also are attributed to its triterpenes. Phenolic compounds in lemon balm, including derivatives of benzoic and caffeic acids, likely exert antioxidant and free radical scavenging effects. Lemon balm’s rosmarinic acid (RA) component, with four hydroxyl groups, may be a stronger antioxidant than vitamin E or Trolox. Many flavonoids, including flavones, flavanones, flavonols, and flavanols, are found in lemon balm, with numerous biological effects.

Traditional uses of lemon balm have been supported by its pharmacological anxiolytic effects, possibly due to gamma-aminobutyric acid transaminase (GABA-T) inhibition and/or reduced levels of corticosterone. In vivo studies were supported by two human clinical trials; however, more randomized clinical trials (RCTs) are needed to better understand its mechanisms of action. While animal studies support lemon balm’s use as an antidepressant, studies to date used doses so large as to be unfeasible for clinical use. Antidepressive effects of lemon balm need more study, especially the monoamine oxidase A (MAO-A) inhibitory activity of compounds other than RA. Neuroprotective effects of various fractions of lemon balm have been demonstrated in vitro and in vivo, with significant protection against oxidative stress and amyloid beta (Aβ)-induced toxicity. Benefits to mood, cognition, and memory also have been supported in vitro, with acetylcholinesterase (AChE) inhibition seen as especially relevant. RCTs confirmed lemon balm’s benefit for some symptoms of Alzheimer’s disease and cognitive impairment. Lemon balm’s cardiovascular, cytotoxic, anti-inflammatory, antinociceptive, hypoglycemic, hypolipidemic, antioxidant, antimicrobial, antiviral, antispasmodic, antiangiogenic, and antiepileptic effects all have support in various research models, with the general proviso that many doses used in animal trials cannot realistically be applied in clinical practice. Results need to be supported using lower doses of lemon balm extracts.

There are few pharmacokinetic studies of lemon balm, with most focusing on its hydrocinnamic acid derivatives, especially RA, absorbed via paracellular diffusion. Much remains unknown about the bioavailability of lemon balm extracts and components. Microbial metabolites of RA may account for many of its activities. While lemon balm has been reported to be relatively well tolerated in humans when used for up to eight weeks, some adverse effects have been noted with both oral and topical administration. Care should be exercised with regard to high dosage or prolonged use until in-depth evidence from toxicity and dose-escalation studies are available. Current evidence suggests that a daily oral dose of 600 mg lemon balm extract is possibly safe and effective in treating memory, mood, and cognition problems, and topical formulations containing 1% lemon balm are effective in treating very early stages of herpes simplex virus 1 and 2.

Future research needs include mechanisms of action, efficacy, and proper dosages for other ethnomedical uses of lemon balm, as well as proof-of-concept clinical trials evaluating its usefulness as an adjunct to conventional treatment for depression. In vitro studies reveal lemon balm’s inhibition of several human cancer cell lines, but a great deal of research needs to be conducted before any clinical applicability could be assessed.

Supplementation with Lemon Balm Leaf Powder Improves Lipid Profiles in Patients with Borderline Hyperlipidemia

Jandaghi P, Noroozi M, Ardalani H, Alipour M. Lemon balm: A promising herbal therapy for patients with borderline hyperlipidemia—A randomized double-blind placebo-controlled clinical trial. Complement Ther Med. 2016;26:136-140.

Hyperlipidemia is a risk factor for cardiovascular disease. The current treatment options for hyperlipidemia are not always effective and are often associated with adverse side effects. Studies suggest that lemon balm (Melissa officinalis, Lamiaceae) may be a safer and more effective treatment alternative. The aim of this parallel, randomized, double-blind, placebo-controlled, clinical trial was to explore the effects of lemon balm supplementation on the lipid profiles of patients with borderline hyperlipidemia.

This study was conducted at Ansari Hospital in Tehran, Iran, between January and July 2014. Male and female patients (age range, 25-65 years) were included if they had at least 1 of the following: serum total cholesterol, 200-260 mg/dL; low-density lipoprotein (LDL), 100-160 mg/dL; and serum triglycerides, 150-300 mg/dL. Patients were excluded if they were smokers, had any health conditions/complications, were intolerant to lemon balm, or consumed any medications that would interfere with the outcome of the study.

Patients were randomly divided into 2 different groups and instructed to consume 2 capsules containing 500 mg of lemon balm leaves (collected and prepared in Tehran, Iran; MO group) or a placebo (500 mg of starch powder; P group) 3 times a day (after consuming a meal) for 2 months. Both capsules were the same size, shape, and color. The chemical profile of the lemon balm leaves was evaluated using gas chromatography and mass spectrometry. Patients were instructed to visit Ansari Hospital twice per month to be monitored and ensure compliance. They were told not to change their diet and to avoid physical activity and other similar products during the study.

Patients were interviewed at the beginning of the study to obtain demographic data. At the beginning and end of the intervention period, body measurements, a 24-hour dietary recall questionnaire, a physical activity questionnaire, and a blood sample (after fasting) were obtained from the patients. Lipid profiles and liver enzymes were evaluated from the blood samples.

A total of 64 patients participated in the study (32 in each group). A few patients discontinued the study (2 in the P group and 3 in the MO group). The only adverse effects reported were headaches (n=1) and dizziness (n=1) in the MO group and dizziness (n=1) in the placebo group. There were no significant differences between the 2 groups in terms of patient demographics and daily dietary intake (except for saturated fatty acids, P<0.05).

At the end of the study, total cholesterol was significantly reduced for both the MO group (P=0.000) and the P group (P=0.03) compared to baseline, but these effects were not significantly different between the 2 groups (P=0.27). At the end of the study, there were no significant differences found between the groups for high-density lipoprotein (HDL), triglycerides, fasting blood glucose, body mass index, or physical activity. By the end of the study, LDL was significantly decreased in the MO group (P=0.002) and significantly increased in the P group (P=0.8); the difference between the 2 groups was significant (P=0.02). The LDL:HDL ratio significantly increased only for the P group (P=0.003). There were no significant effects on liver enzymes, with the exception of aspartate transaminase (AST), which was significantly increased in the P group (P=0.003) but not in the MO group (a significant difference was found between the groups, P=0.009).

The results of this 2-month study indicate that consumption of lemon balm leaf powder significantly lowered LDL and the liver enzyme AST compared to a placebo treatment. Such outcomes suggest that lemon balm supplementation is both safe and effective for patients with mild hyperlipidemia. Although the lipid profiles did not improve to the extent that they did in a study that used lemon balm essential oils, the authors suggest that this is a safer form of supplementation.1 The authors also suggest that larger and longer trials with mechanistic investigations are needed to confirm the safety and efficacy of this supplement.

Aqueous Lemon Balm Extract Alleviates Benign Heart Palpitations

Alijaniha F, Naseri M, Afsharypuor S, et al. Heart palpitation relief with Melissa officinalis leaf extract: double-blind, randomized, placebo-controlled trial of efficacy and safety. J Ethnopharmacol. 2015;164:378-384.

Benign heart palpitations—the feeling of a rapid, pounding, or fluttering heart—can cause distress and disability. Currently, available therapies are not very effective and have unwanted side effects. In traditional Iranian medicine, lemon balm (Melissa officinalis, Lamiaceae) leaf extract is used as a heart tonic and to help ease tension, restlessness, and irritability. According to the authors, no clinical trials evaluating lemon balm as a treatment for heart palpitations have been published. Hence, the purpose of this randomized, double-blind, placebo-controlled study was to evaluate the efficacy of lemon balm in relieving benign heart palpitations.

Adults (n = 71, aged 18-60 years) with an “unpleasant sensation in the heart or awareness of heartbeat” were recruited at the outpatient clinic of the cardiology department at Shahid Mostafa Khomeini Hospital in Tehran, Iran, from November 2012 to May 2013. Included patients had palpitations as their main complaint for ≥ 3 months. Excluded patients had intellectual disability, psychosis, or other serious psychiatric disorders; organic heart disease; a serious chronic disease; endocrine problems; were pregnant; were lactating; or consumed beta-blockers, antidepressants, anxiolytics, hypnoinducers, or sedatives 10 days before study commencement. Patients received placebo or 1000 mg lemon balm extract/day for 2 weeks. Lemon balm dried leaf was purchased from the farm of Zardband Pharmaceutical Co.; Gonbad, Iran. The material was authenticated and a voucher specimen was filed at the herbarium of the Traditional Medicine and Materia Medica Research Center, Shahid Beheshti University of Medical Sciences; Tehran, Iran. “Quality control tests were done according to British Pharmacopea [sic] (2009).” A lyophilized aqueous extract of 100 g lemon balm leaves was prepared, yielding 20.9 g (20.9%) dried extract. This procedure “was done proportionally to obtain the required amount of dried extract for 28 patients … .” Capsules were filled with 500 mg of the dried extract. The placebo was breadcrumbs filled in identical capsules. Patients were instructed to take 1 capsule in the morning and 1 capsule in the evening.

Palpitations are a subjective complaint, and there is no accurate tool to make quantitative measurements. There are no validated patient-reported outcome instruments available. The primary outcome measures were a change in the frequency and intensity of the palpitation episodes over 24 hours. Each day, patients completed a questionnaire about their symptoms and an adverse effects form. Patients started monitoring the palpitations 1 week before treatment began to offset the increased attention to heartbeats, which could create bias. Psychiatric symptoms were measured with the General Health Questionnaire-28 (GHQ-28) at baseline and after treatment. Blood was drawn before and after treatment to monitor safety.

Baseline demographic and physical characteristics such as blood pressure and heart rate were similar between groups. Only 5 patients were diagnosed with a cardiac disorder as the cause of palpitations. Panic disorder, which can cause palpitations, occurred in 66.6% of the placebo group and 71.4% of the lemon balm group. Tea (Camellia sinensis, Theaceae), coffee (Coffea arabica, Rubiaceae), and cigarette consumption, which can cause heart palpitations, were used at a similar rate in both groups. In both groups, 85% of the patients had moderate to much distress about the palpitations. The mean duration of occurrence of palpitation episodes was 65 months in the placebo group and 60 months in the lemon balm group. Eight patients in each group discontinued treatment (reasons not reported), so 27 placebo and 28 lemon balm patients were included in the final analysis.

After treatment, the lemon balm group had 36.8% fewer palpitation episodes compared to baseline (P < 0.0001), while no significant change was seen in the placebo-treated patients; the difference between the groups was significant (P = 0.01). Both groups had a significant decrease in intensity of palpitations; there was no significant difference between groups. Anxiety and insomnia after treatment were significantly decreased in the lemon balm group compared to baseline (P = 0.004), but not in the placebo group. (The P value for the difference between groups was not reported.) There were no clinically significant adverse effects and no significant changes in laboratory parameters. The lemon balm group had a significant increase in appetite compared with the placebo group. There were no other significant differences in frequency of adverse effects.

The authors conclude that 2 weeks of treatment with lemon balm safely and significantly decreased frequency of episodes and anxiety in patients with benign heart palpitations likely caused by psychological factors. Acknowledged limitations of this study are the short duration of treatment, only 1 dose was evaluated, the sample size was small, and detailed psychological evaluations of anxiety and depression were not conducted. The authors point out that lemon balm has many other clinically demonstrated benefits and that these results support the prescriptions that the renowned Persian physician Avicenna made over 1,000 years ago—that lemon balm is beneficial for heart conditions and mental health. Although aqueous lemon balm extract has been reported to reduce heart rate without changing contractile force in rats, no effect on heart rate was detected in this relatively small study. Larger trials of longer duration are warranted to confirm these findings and to further evaluate the effect on heart rate, as well as to determine whether treatment effect varies with the clinical presence and severity of panic disorder or anxiety.