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lemon balm

  • Lack of energy is a constant theme in the lives of countless Americans. For many, tiredness is so routine that they accept it as a natural state. Family and work by themselves are exhausting; unexpected demands or a restless night can deplete the remaining energy reserves. What is to be done? The American answer is caffeine. Pick your flavor: coffee (then more coffee), energy drinks (which flavor and how tall?), sodas (nothing beats caffeine plus sugar!) and the list goes on. The idea is that, if the metabolism is flagging whip it harder or, better yet, throw in a quick burst of energy from a simple carbohydrate. Caffeinate, crash, repeat (perhaps several times throughout the day), then start over the next morning.

    And start over we do. Ninety percent of all American adults ingest caffeine daily. It is the go-to stimulant of choice, so much so that for a while Wrigley was producing eight stick chewing gum packs each stick of which contained as much caffeine as half a cup of coffee. To be sure, it is not as if caffeine has no benefits. After all, people consume caffeine mostly to improve productivity and related outcomes, not for pleasure. But what if the lack of energy is really just the body's response to a lack of rest (sound sleep usually is an early casualty of too much caffeine) and to a failure to recover from demands placed on it day in and day out? Under such circumstances, the daily caffeine fix is always needed and creates the conditions of its own demand along with downsides. Fortunately, it is possible to get off this merry-go-round.

    Controlling Caffeine
    Researchers have often wondered why it is that tea, despite its caffeine content, tends to relax individuals without making them drowsy. Similarly, those engaging in meditation practices may drink tea to dispel mental sluggishness and yet not become mentally agitated, as is typical with the consumption of too much coffee. Black and green teas give somewhat different answers. Black tea, for instance, contains one or more compounds that open up the peripheral circulation and also reduce blood levels of cortisol, the stress hormone. Likewise, blood platelet activation, which is linked to blood clotting and to the risk of heart attack, was lower in the tea drinkers in a clinical trial and this group reported a greater degree of relaxation in the recovery period after a stressful task.1 This is good news for the 65 percent of adult Americans who suffer from daily stress. L-Theanine, found in green and oolong teas, is more complicated. In one trial in which caffeine (250 milligrams) increased self-rated alertness along with jitteriness and blood pressure, theanine (200 milligrams) antagonized the effect of caffeine on blood pressure, but did not significantly affect jitteriness, alertness or other aspects of mood.2 At a lower level of caffeine consumption (150 milligram), theanine (250 milligrams) actually further improved the normal cognitive benefits of caffeine.3 Affects on stress per se also are found with theanine, with the degree of benefit depending on conditions and individuals.

    Various tests have demonstrated the anti-stress effects of L-theanine. One of the more revealing of these experiments examined brain wave patterns after the ingestion of theanine. This research built on the knowledge that humans produce specific patterns of electrical pulses on the surface of the brain that mirror brain states. The four primary wave patterns are known as the alpha, beta, delta and theta (a, b, d and q) brain waves, representing, respectively, 1) relaxed wakefulness, 2) excitation, 3) sound sleep, and dozing sleep.4

    In one experiment, 50 women volunteers (aged 18–22 years old) were divided into high-anxiety and low-anxiety groups. Each group was given either 50 or 200 mg theanine in water once a week. Their brain waves were measured during the 60 minutes after ingestion. The measurements were repeated twice during a two-month test period. The results were a marked increase in a-waves starting roughly 40 minutes after ingestion. Researchers concluded that theanine rapidly enters the system when ingested and that it heightens the index of the brain wave that is known to be linked to a state of relaxed wakefulness. Researchers also have explored whether the response to theanine might be influenced by the level of anxiety found in test subjects. As might be expected, the greater degree of change is found in those manifesting high anxiety.

    Theanine appears to protect against certain so-called "excitotoxins." It modulates the motor-stimulation associated with caffeine and it inhibits some of the actions of norepinephrine in the central nervous system, for instance. In tests with gerbils, theanine protected against the destruction of neurons induced ischemia, a condition that can lead to a rapid increase in glutamate in neurons and result in the death of these cells. Theanine taken in the evening may support improved sleep quality not by sedation, but through anxiolysis.5 The other herbs mentioned below also tend to improve sleep quality at least in part through the same mechanism.

    Saffron for Replacing Jitters with Emotional Balance
    Although small amounts of caffeine, meaning usually less than 400 milligrams per day, for the vast preponderance of individuals provides mostly an upside with little downside, excessive caffeine can lead to anxiety, physical and emotional "jitters," as well as insomnia. For many, black, oolong and green teas are more gentle alternatives to the concentrated caffeine of coffee, yet coffee is a preferred beverage for many. Moreover, caffeine is added to so many other pick-me-ups that individuals often are unaware of how much they are consuming throughout the day. Several herbs and spices are useful remedies to this excess. Saffron is one of these.

    Saffron is far more than merely a spice that gives color to rice and paella along with a distinctive aromatic signature. Crocins are the source of saffron's coloring properties, whereas its aromatic aspects come from picrocrocins and safranal. Medical texts from ancient Egypt, Persia and the Roman Empire attest to healing properties, including pain relief and calming effects. Similarly, Chinese and Indian healing systems ascribe these and more benefits to saffron. Other healing aspects include the treatment of coughs, better movement of nutrients into tissues and aphrodisiac qualities.

    At least eleven clinical studies have evaluated saffron for its impact on aspects of emotional balance, such as anxiety and depression. In comparative clinical trials, saffron intake after one or two weeks has proven to be comparable in efficacy to the drugs fluoxetine and imipramine. The mechanism of action seems to be the regulation of neurotransmitters.6 Other conditions that have been explored clinically with saffron include erectile dysfunction, vision, Alzheimer's disease and cosmetic benefits. In general, it is thought that there is a complementary action from more than twenty-five active compounds in saffron to yield the demonstrated clinical effects. One special extract that has been extensively clinically tested gives benefits when ingested at the level of 30 milligrams per day.

    Lemon Balm's Calming Effects, Sleep Benefits
    Another useful traditional herb is lemon balm (Melissa officinalis L.). Since the 19th Century, it has been recognized as being soothing during stress and anxiety. Lemon balm contains hydroxycinnamic and rosmarinic acids. Studies have shown that lemon balm consumption increases sleep quality, reduces stress and improves mood.7 Clinical trials have demonstrated the effects of lemon balm extract on cognitive health. Lemon balm improves cognitive performance by enhancing memory and accelerating the visual information processing.8,9 One high quality and tested extract is recommended at an intake level of 600 milligrams per day.

    Blue Dogbane Is a Bane for Stress
    Apocynum venetum L., commonly known as Luobuma in China, is a traditional and popular Chinese herb with a long history of use as a medicine and tea, both in Chinese and Uygur medicine. In fact, Apocynum venetum L. is mentioned in the ancient Dun Huang Manuscripts (written in the 5th to early 11th centuries A.D.) as a powerful longevity tonic. It especially is useful in cases of hypertension and anxiety.10 Among its other notable benefits is support for sleep. According to the official Chinese Pharmacopoeia, the herb calms the liver, soothes the nerves, treats palpitations and improves insomnia. As a tea in China, it is used especially for the elderly as a sleep aid and to reduce high blood pressure. Indeed, a commercial Luoboma "antihypertensive tea" is available commercially in the western province of China. Care should be taken to not confuse it with Indian Hemp (I), Apocynum androsaemifolium, poacynum pictum, I, or the blue dogbane native to Texas. Chinese White and Pink Dogbanes are inferior substitutes often presented as the same plant.

    Anxiety afflicts more than forty million Americans, hence is hardly a minor issue. As already explored above, caffeine and "energy" drinks aggravate anxiety, jitteriness and blood pressure. The exact mechanisms of blue dogbane's action, which likely are multiple, only partially have been elucidated. For instance, the herb inhibits superoxide generated from both the NADPH oxidase and the xanthine/xanthine oxidase systems in the arteries. The upshot of these actions is that there is more nitric oxide (NO) available locally to relax the vessels.11 Rather than taking multiple grams of L-arginine to provide a building block precursor for the production NO, just a little bit of this herb prevents the excessive destruction of NO and achieves the same benefit. The vasculature dilation effects of the blue dogbane extract, including in the brain, can be considerable. The benefits for relaxation, cortisol and stress reduction are significant. Clinical work indicates that the extract induces deeper sleep, meaning that it makes sleep more restful.12

    An interesting finding is that Apocynum venetum L. is a particularly rich source of isoquercitrin, the more active and much better absorbed form of the antioxidant quercetin. Some research suggests that Apocynum venetum L. is a safe alternative to St. John's Wort. Suggested consumption of the extract depends on its quality and the condition in mind; 50–150 milligrams represents typically suggested dosages.12

    Southern Ginseng
    Most Westerners have heard of ginseng and think that the Chinese name applies to only one species. However, in fact there are various "ginsengs" in Chinese medicine, each displaying particular benefits. Gynostemma pentaphyllum is "southern ginseng"; it also is called jiaogulan. It is considered to have powerful antioxidant and adaptogenic effects purported to increase longevity.13 The plant belongs to a family that includes cucumbers, gourds, and melons—its fruit is a small purple inedible gourd. It is little known in traditional Chinese medicine (TCM) because TCM is largely based on the dried materials that could be transported to the Imperial Court of the Chinese Emperors in Beijing. Research indicates significant effects of southern ginseng in the areas of blood glucose, improved insulin sensitivity, improved HbA1c (indicating improved glucose control in diabetics and reduced glycation) as well as other benefits.14

    Although local Chinese traditions long have reported adaptogenic effects, the impact of jiaogulan on stress and related conditions only recently has been explored by Western allopathic research. Nevertheless, a body of animal trials currently backs traditional uses to support human resilience to physical and mental challenges. For instance, a 2012 paper reports that oral administration of the ethanol extract of Gynostemma pentaphyllum can increase host defense in immunocompromised situations such as stress-induced immunosuppression.15,16 A report from the next year indicates that there are anxiolytic effects of an herbal ethanol extract from Gynostemma pentaphyllum in mice after exposure to chronic stress.17 In yet another model of chronic stress and related anxiety disorders in mice, gypenosides, proposed active ingredients in the herb, improved stress-induced anxiety disorders by modulating brain dopamine and serotonin activities and corticosterone levels.18 (Corticosterone in mice plays the same role as cortisol in humans.) Finally, a recent randomized, double-blind, placebo-controlled clinical trial lasting 12 weeks demonstrated that an extract of Gynostemma pentaphyllum led to significant decreases in total abdominal fat area, body weight, body fat mass, percent body fat, and body mass index. (BMI).19 It is likely that more than one mechanism of action was important in bringing about these clinical results.

    Magnesium
    Do not forget magnesium! An estimated 68 percent of Americans do not consume the recommended daily allowance for magnesium. Some attribute this to modern dietary patterns, such as a failure to consume green vegetables and less refined grains. Others have observed that reduced magnesium levels can be attributed to food refining, processing and the use of industrial fertilizers, which typically lack magnesium. Magnesium deficiency has been associated with poor sleep quality, muscle tension and anxiety. Raising tissue levels with oral supplementation of magnesium may promote more restful sleep and relaxation. Preferred forms include magnesium glycerophosphate, magnesium malate and magnesium threonate. Each of these forms exhibits special characteristics based on its ligand. Better results with magnesium supplementation are realized with chronic usage to build up tissue stores.

    Conclusion
    Too often, the demand for more energy really is just a symptom of inadequate rest and poor quality sleep. The majority of adults is chronically stressed and sleep deprived. Good sleep affects alertness, energy, creativity, indeed, mental and physical performance and productivity in general. The common solution to being tired and under-performing is to consume caffeine in the form of coffee and energy drinks. There are alternatives, however, to the "caffeinate, crash, repeat" model of daily existence. Some of these alternatives support the positive effects of caffeine while mitigating the side effects. Others moderate jitteriness and "wired" effects of stimulants by reducing the stress hormone release found with too much stimulation. A common benefit of this approach is to improve the ability to sleep without forcing slumber and to make the time spent sleeping more restful.

    References:

    1. Steptoe A, Gibson EL, Vuononvirta R, Williams ED, Hamer M, Rycroft JA, Erusalimsky JD, Wardle J. The effects of tea on psychophysiological stress responsivity and post-stress recovery: a randomised double-blind trial. Psychopharmacology (Berl). 2007 Jan;190(1):81-9. Epub 2006 Sep 30. Erratum in: Psychopharmacology (Berl). 2007 Jan;190(1):91.
    2. Rogers PJ, Smith JE, Heatherley SV, Pleydell-Pearce CW. Time for tea: mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together. Psychopharmacology (Berl). 2008 Jan;195(4):569-77.
    3. Haskell CF, Kennedy DO, Milne AL, Wesnes KA, Scholey AB. The effects of L-theanine, caffeine and their combination on cognition and mood. Biol Psychol. 2008 Feb;77(2):113-22.
    4. Juneja LR, Chu D-C, Okubo T, Nagato Y, Yokogoshi H. L-Theanine––a unique amino acid of green tea and its relaxation effect in humans. Trends in Food Science & Technology 1999;10:199-204.
    5. Rao TP, Ozeki M, Juneja LR. In Search of a Safe Natural Sleep Aid. J Am Coll Nutr. 2015;34(5):436-47.
    6. https://www.naturalproductsinsider.com/whitepapers/2016/09/safrinside.aspx
    7. Cases J, Ibarra A, Feuillere N, Roller M, Sukkar S. Pilot trial of Melissa officinalis L. leaf extract in the treatment of volunteers suffering from mild-to-moderate anxiety disorders and sleep disturbances. Mediterranean journal of nutrition and metabolism. 2011; 4(3): 211-8.1.
    8. Scholey A, Gibbs A, Neale C, et al. Investigation of a Melissa officinalis special extract on Cognition II: Human study - Lemon balm extract administered in confectionary bars. Agro FOOD Industry Hi Tech2015; 26(2): 12-4.
    9. Kennedy D, Wake G, Savelev S, et al. Modulation of mood and cognitive performance following acute administration of single doses of Melissa officinalis (Lemon balm) with human CNS nicotinic and muscarinic receptor-binding properties. Neuropsychopharmacology 2003; 28(10): 1871-81.
    10. Xie W, Zhang X, Wang T, Hu J. Botany, traditional uses, phytochemistry and pharmacology of Apocynum venetum L. (Luobuma): A review. J Ethnopharmacol. 2012 May 7;141(1):1-8.
    11. Lau YS, Ling WC, Murugan D, Kwan CY, Mustafa MR. Endothelium-Dependent Relaxation Effect of Apocynum venetum Leaf Extract via Src/PI3K/Akt Signalling Pathway. Nutrients. 2015 Jun 30;7(7):5239-53.
    12. Yamatsu A, Yamashita Y, Maru I, Yang J, Tatsuzaki J, Kim M. The Improvement of Sleep by Oral Intake of GABA and Apocynum venetum Leaf Extract. J Nutr Sci Vitaminol (Tokyo). 2015;61(2):182-7.
    13. Blumert, Michael; Jialiu Liu. Jiaogulan: China's "Immortality" Herb. (2003: Badger, CA: Torchlight Publishing.)
    14. https://examine.com/supplements/gynostemma-pentaphyllum/
    15. Im SA, Choi HS, Choi SO, Kim KH, Lee S, Hwang BY, Lee MK, Lee CK. Restoration of electric footshock-induced immunosuppression in mice by Gynostemma pentaphyllum components. Molecules. 2012 Jun 25;17(7):7695-708.
    16. Shang X, Chao Y, Zhang Y, Lu C, Xu C, Niu W. Immunomodulatory and Antioxidant Effects of Polysaccharides from Gynostemma pentaphyllum Makino in Immunosuppressed Mice. Molecules. 2016 Aug 19;21(8).
    17. Choi HS, Zhao TT, Shin KS, Kim SH, Hwang BY, Lee CK, Lee MK. Anxiolytic effects of herbal ethanol extract from Gynostemma pentaphyllum in mice after exposure to chronic stress. Molecules. 2013 Apr 12;18(4):4342-56.
    18. Zhao TT, Shin KS, Choi HS, Lee MK. Ameliorating effects of gypenosides on chronic stress-induced anxiety disorders in mice. BMC Complement Altern Med. 2015 Sep 14;15:323.
    19. Park SH, Huh TL, Kim SY, Oh MR, Tirupathi Pichiah PB, Chae SW, Cha YS. Antiobesity effect of Gynostemma pentaphyllum extract (actiponin):
    20. a randomized, double-blind, placebo-controlled trial. Obesity (Silver Spring). 2014 Jan;22(1):63-71.
  • Lemon balm (Melissa officinalis) is one of those herbal medicines that have been in use for thousands of years. Steeped in wine, lemon balm was used in ancient Greek and Roman cultures for various medicinal purposes, including the treatment of wounds and to treat venomous bites and stings.1 These same uses also occurred in traditional Indian medicine.2 Furthermore, old European medical herbals report its memory-improving properties.3 Modern uses tend to be more in the area of lemon balm’s calming effects, as well as its properties in soothing gastrointestinal complaints, although there has been some research in the area of cognitive function and antioxidant protection against radiation. This article will discuss the internal uses of lemon balm.

    Calming Effects of Lemon Balm Anxiety disorders are common in many Western countries, and conventional drugs like benzodiazepines are often prescribed to relieve anxiety. However, these drugs have worrisome short-term and long-term side effects. Nervine herbs (herbs that quiet nervous excitement) have a long history of traditional use in relieving anxiety, insomnia, and mild depression. Case in point, lemon balm is often used as a mild mood elevator and calming herb in people with anxiety. It has been shown to improve attention and calmness in healthy volunteers,4 and reduce agitation in patients with mild to moderate Alzheimer’s disease (see discussion below under “Cognitive function”).5

    In a double-blind, placebo-controlled, randomized, balanced-crossover study,6 18 healthy volunteers received two separate single doses of a standardized lemon balm extract (300 mg, 600 mg) and a placebo, on separate days separated by a 7-day washout period to assess laboratory-induced psychological stress. The results showed that the 600 mg dose improved the negative mood effects of the stress, with significantly increased self-ratings of calmness. In addition, a significant increase in the speed of mathematical processing, with no reduction in accuracy, was observed after ingestion of the 300 mg dose.

    In Germany, lemon balm is licensed as a standard medicinal tea to help promote sleep. This is due to the fact that Germany’s Commission E (their version of the FDA for natural medicines) approved the use of lemon balm for nervous sleeping disorders.7 Likewise, ESCOP, the European Scientific Cooperative on Phytotherapy (an umbrella organization representing national herbal medicine or phytotherapy [aka, herbal medicine] associations across Europe), lists tenseness, restlessness and irritability among the uses for lemon balm.8 Furthermore, Health Canada has approved lemon balm for traditional use as an herbal medicine sleep aid (in cases of restlessness or insomnia due to mental stress).9 In addition, combining lemon balm with valerian root has also been shown to have benefit in sleep disorders. A combination of 80 mg lemon balm leaf extract and 160 mg valerian root extract three times daily improved the quality and quantity of sleep in healthy people,10 while the same dose once or twice daily decreased symptoms in children under age 12 years who have pathological restlessness.11

    Soothing gastrointestinal complaints
    As with its calming effects, in Germany lemon balm is also licensed as a standard medicinal tea for gastrointestinal tract disorders and approved by Commission E for functional gastrointestinal complaints.12 Similarly, ESCOP lists for symptomatic treatment of digestive disorders, such as minor spasms, among its internal uses.13 Also, Health Canada has approved lemon balm for traditional use as an herbal medicine to help relieve digestive disturbances, such as dyspepsia.14 The approved modern therapeutic applications for lemon balm are supportable based on its long history of use in well-established systems of traditional medicine, on phytochemical investigations, and on its documented pharmacological actions reported in in-vitro studies and in-vivo experiments in animals.15

    Lemon balm has also been used in clinical research along with other herbs for soothing gastrointestinal complaints. In one study, breast-fed infants with colic who were given 97 mg lemon balm, 164 mg fennel and 178 mg German chamomile twice daily for a week had reduced crying times compared to placebo.16 In another research, a 1 mL combination of lemon balm plus peppermint leaf, German chamomile, caraway, licorice, clown’s mustard plant, celandine, angelica, and milk thistle given orally three times daily over a period of four weeks to people with dyspepsia (i.e. indigestion) significantly reduced severity of acid reflux, epigastric pain, cramping, nausea, and vomiting compared to placebo.17

    Cognitive function
    Some laboratory research has shown that lemon balm has cholinergic-binding properties, which means that it may have some of the cognitive and memory promoting effects of the neurotransmitter acetylcholine. To test this hypothesis, a randomized, placebo-controlled, double-blind, balanced-crossover study18 was conducted to investigate the effects of lemon balm on cognition and mood in 20 healthy, young participants. Single doses of 300, 600 and 900 mg of lemon balm extract (or matching placebo) were used at 7-day intervals. Cognitive performance was assessed immediately prior to dosing and at 1, 2.5, 4 and 6 hours thereafter. Results demonstrated improvements in cognitive function, as well as “calmness” at the earliest time points by the lowest dose, while “alertness” was significantly reduced at all time points following the highest dose. Overall, these results suggest that low doses of lemon balm may enhance calmness and high doses may have a mild sedative effect. A follow-up study showed essentially the same results.19

    In addition, a 4-month, parallel group, placebo-controlled trial20 was undertaken to assess the efficacy and safety of lemon balm extract (60 drops/day) in 42 patients with mild to moderate Alzheimer’s disease. The results were that lemon balm extract produced a significantly better outcome on cognitive function than placebo, and those using lemon balm had significantly less agitation than those in the placebo group.

    Antioxidant protection against radiation
    Radiology staffs are exposed to persistent low-dose radiation during work. Consequently, a study21 was conducted to determine the capability of lemon balm tea to improve oxidative stress status in 55 radiology staff members. They were asked to drink lemon balm tea (made from a tea bag with 1.5g lemon balm leaf) for 30 days. Results showed that the lemon balm tea resulted in significant improvements in plasma levels of the antioxidant enzymes catalase, superoxide dismutase, and glutathione peroxidase. It also promoted a marked reduction in plasma DNA damage and lipid peroxidation. The researchers concluded that lemon balm tea markedly improved oxidative stress condition and DNA damage in radiology staff.

    Dosage forms
    Lemon balm can be used in the following dosage forms, using the following dosages:

    Form

    Dosage

    Brewed herbal tea:

    1.5g lemon balm leaf, 1 - 3 times per day1

    Fluid extract:

    2 - 4g dried equivalent, 1 - 3 times per day (1:1, 45% ethanol, 2 - 4 ml or 60 drops)2,3

    Tincture:

    0.4 - 1.2g dried equivalent, 1 - 3 times per day (1:5, 45% ethanol, 2 - 6 ml)4

    Standardized extract:

    80 - 97mg in combination with other herbs (as previously described)5,6,7,8

    In the case of its use as a calming agent as well as its properties in treating gastrointestinal complaints, administering lemon balm as a brewed herb offers the additional benefit of delivering the herb as a warm beverage, adding to its soothing qualities

      References:
    1. Blumenthal M (ed) et al. Herbal Medicine: Expanded Commission E Monographs. Austin, TX: Integrative Medicine Communications; 2000:230–2.
    2. Nadkarni KM. Indian Materia Medica. Bombay: Popular Prakashan; 1976:786.
    3. Blumenthal M (ed) et al. Herbal Medicine: Expanded Commission E Monographs. Austin, TX: Integrative Medicine Communications; 2000:230–2.
    4. Abascal K, Yarnell E. Nervine herbs for treating anxiety Altern Compliment Ther. 2004 December:309–15.
    5. Akhondzadeh 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, randomized, placebo controlled trial. J Neurol Neurosurg Psychiatry. 2003 Jul;74(7):863–6.
    6. Kennedy DO, Little W, Scholey AB. Attenuation of laboratory-induced stress in humans after acute administration of Melissa officinalis (Lemon Balm). Psychosom Med. 2004 Jul-Aug;66(4):607–13.
    7. Blumenthal M (ed) et al. Herbal Medicine: Expanded Commission E Monographs. Austin, TX: Integrative Medicine Communications; 2000:230–2.
    8. ESCOP. Melissae folium. Monographs on the Medicinal Uses of Plant Drugs. Exeter, U.K. European Scientific Cooperative on Phytotherapy;1997.
    9. Monograph: Lemon Balm. Health Canada. Date Modified: 2008-3-17. Retrieved February 11, 2014 from http://webprod.hc-sc.gc.ca/nhpidbdipsn/monoReq.do?id=125&lang=eng.
    10. Cerny A, Shmid K. Tolerability and efficacy of valerian/lemon balm in healthy volunteers (a double blind, placebo-controlled, multicentre study). Fitoterapia 1999;70:221–8.
    11. Muller SF, Klement S. A combination of valerian and lemon balm is effective in the treatment of restlessness and dyssomnia in children. Phytomedicine 2006;13:383–7.
    12. Blumenthal M (ed) et al. Herbal Medicine: Expanded Commission E Monographs. Austin, TX: Integrative Medicine Communications; 2000:230–2.
    13. ESCOP. Melissae folium. Monographs on the Medicinal Uses of Plant Drugs. Exeter, U.K. European Scientific Cooperative on Phytotherapy;1997.
    14. Monograph: Lemon Balm. Health Canada. Date Modified: 2008-03-17. Retrieved February 11, 2014 from http://webprod.hc-sc.gc.ca/nhpidbdipsn/monoReq.do?id=125&lang=eng.
    15. Blumenthal M (ed) et al. Herbal Medicine: Expanded Commission E Monographs. Austin, TX: Integrative Medicine Communications; 2000:230–2.
    16. Savino F, Cresi F, Castagno E, et al. A randomized double-blind placebo-controlled trial of a standardized extract of Matricariae recutita, Foeniculum vulgare and Melissa officinalis (ColiMil) in the treatment of breast-fed colicky infants. Phytother Res 2005;19:335-40.
    17. Melzer J, Rosch W, Reichling J, et al. Meta-analysis: phytotherapy of functional dyspepsia with the herbal drug preparation STW 5 (Iberogast). Aliment Pharmacol Ther 2004;20:1279-87.
    18. Kennedy DO, Scholey AB, Tildesley NT, Perry EK, Wesnes KA. Modulation of mood and cognitive performance following acute administration of Melissa officinalis (lemon balm). Pharmacol Biochem Behav. 2002 Jul;72(4):953–64.
    19. Kennedy DO, Wake G, Savelev S, Tildesley NT, Perry EK, Wesnes KA, Scholey AB. Modulation of mood and cognitive performance following acute administration of single doses of Melissa officinalis (Lemon balm) with human CNS nicotinic and muscarinic receptor-binding properties. Neuropsychopharmacology. 2003 Oct;28(10):1871–81.
    20. Akhondzadeh 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, randomized, placebocontrolled trial. J Neurol Neurosurg Psychiatry. 2003 Jul;74(7):863-6.
    21. Zeraatpishe A, Oryan S, Bagheri MH, Pilevarian AA, Malekirad AA, Baeeri M, Abdollahi M. Effects of Melissa officinalis L. on oxidative status and DNA damage in subjects exposed to long-term low-dose ionizing radiation. Toxicol Ind Health. 2011 Apr;27(3):205–12.
    22. Monograph: Lemon Balm. Health Canada. Date Modified: 2008-03-17. Retrieved February 11, 2014 from http://webprod.hc-sc.gc.ca/nhpidbdipsn/monoReq.do?id=125&lang=eng.
    23. Monograph: Lemon Balm. Health Canada. Date Modified: 2008-03-17. Retrieved February 11, 2014 from http://webprod.hc-sc.gc.ca/nhpidbdipsn/monoReq.do?id=125&lang=eng.
    24. Akhondzadeh 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, randomized, placebocontrolled trial. J Neurol Neurosurg Psychiatry.2003 Jul;74(7):863–6.
    25. Monograph: Lemon Balm. Health Canada. Date Modified: 2008-03-17. Retrieved February 11, 2014 from http://webprod.hc-sc.gc.ca/nhpidbdipsn/monoReq.do?id=125&lang=eng.
    26. Cerny A, Shmid K. Tolerability and efficacy of valerian/lemon balm in healthy volunteers (a double blind, placebo-controlled, multicentre study). Fitoterapia 1999;70:221–8.
    27. Muller SF, Klement S. A combination of valerian and lemon balm is effective in the treatment of restlessness and dyssomnia in children. Phytomedicine 2006;13:383–7.
    28. Savino F, Cresi F, Castagno E, et al. A randomized double-blind placebo-controlled trial of a standardized extract of Matricariae recutita, Foeniculum vulgare and Melissa officinalis (ColiMil) in the treatment of breast-fed colicky infants. Phytother Res 2005;19:335–40.
    29. Melzer J, Rosch W, Reichling J, et al. Meta-analysis: phytotherapy of functional dyspepsia with the herbal drug preparation STW 5 (Iberogast). Aliment Pharmacol Ther2004;20:1279–87.
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