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By Michael D. Cirigliano, MD, FACP and Philippe O. Szapary, MD
Inflammatory skin conditions and systemic processes are often seen and treated in clinical practice. Although usually not life threatening, conditions such as eczema, dermatitis, and oral mucositis can lead to significant morbidity and make life miserable.
Treatment of these medical conditions may involve the use of either topical or systemic steroids and non-steroidal anti-inflammatory agents, all of which have significant side effects. Despite the lack of clinical trial data, chamomile has been used historically as an anti-inflammatory, antispasmodic, and calming agent.1 In fact, chamomile sales exceeded $8.3 million in Germany alone in 1996, making it one of the most popular (and all-purpose) herbal therapies in the world.
Chamomile (Matricaria recutita), also known as German chamomile, belongs to the Asteraceae family and is an annual herbaceous plant indigenous to Europe and Western Asia.2 Roman chamomile (Chamaemelum nobile) represents another popular plant type from the same family.2 Although German chamomile accounts for a majority of sales and scientific study, both have been used as medicinal plants for centuries.2
The name chamomile comes from the Greek chamos meaning on the ground and Greek melos meaning apple—indicative of chamomile’s aroma which resembles that of apples.2 Flower heads of the plant are harvested in summer during the beginning of flowering when essential oil content is highest.2
The medicinal use of chamomile dates back to the Egyptians who "dedicated chamomile to their gods and to the sun, due to its power to cure agues [fever]."3 Chamomile later was used by Sir William Culpeper who recommended it as an anti-inflammatory and digestive aid.2 The German phrase for chamomile, alles zutraut, or "cure all," attests to the high regard for chamomile in that country.4 Today, chamomile is most commonly used for wound healing, to treat inflammatory skin conditions, and as a food additive. It is also commonly used for minor digestive disorders and as a mild sedative.
The therapeutic actions of chamomile derive from compounds contained in its essential oil, derived from its flower head.1 Constituents of the essential oil possessing the principal anti-inflammatory and antispasmodic properties include the terpenoids (a-bisabolol oxide A, a-bisabolol oxide B, ()-a-bisabolol, farnesene, and cham-azulene [a breakdown product of matricine]).5 Other active constituents of the plant include flavonoids, most notably apigenin and luteolin, along with coumarins (herniarin), amino acids, and tannins.
Mechanism of Action
Chamomile compounds exhibit numerous pharmacological properties. Anti-inflammatory effects have been demonstrated from both whole alcoholic extracts as well as individual constituents isolated from them. Most studies, however, have found that the whole extracts were more active than their individual constituents.6 Constituents of chamomile act mainly on the inflammatory mediators of the arachidonic acid cascade, probably by inhibition of 5-lipooxygenase and cyclooxygenase.6 In animal models, bisabolol effectively reduced inflammation and arthritis and has reduced healing time of cutaneous burns.7
Chamazulene exerts anti-inflammatory and anti-allergic activity. Several flavonoid components (including apigenin and luteolin) also exert anti-inflammatory properties and have been noted in vitro to have anti-inflammatory potencies similar to that of low-dose indomethacin.1
Finally, reported antispasmodic and sedative activity of chamomile extracts8 may derive from the action of apigenin, which binds to central benzodiazepine receptors.9
There are numerous animal studies evaluating the anti-inflammatory effects of chamomile extracts and specific components. In a study utilizing 1 ml of chamomile extract containing 50 mg of a standardized dry product, mice were exposed to topical croton oil applied to the ear to induce edema.10 Controls were compared to mice given chamomile extract, 0.75 mg hydrocortisone, and benzydamine, a non-steroidal anti-inflammatory agent. Chamomile extract was found to reduce edema nearly as well as benzydamine but less than hydrocortisone. Another study of experimentally induced ear edema in mice utilized the flavonoid apigenin, which also was found to be effective.11
In addition, essential oil of chamomile was found to be comparable to papaverine in reducing experimentally induced spasm of isolated guinea pig small intestine resulting in decreased tonus and peristalsis.12 These effects were found to be dose dependent. Specific components, including ()-a-bisabolol and apigenin, were found to have the most significant effects. Additionally, ()-a-bisabolol was noted to inhibit the occurrence of stomach ulceration following administration of indomethacin, stressful stimuli, or alcohol to rats.13
Chamomile extract has been evaluated in a number of clinical trials. Most have involved the use of chamomile topically to aid and prevent mucositis and dermatitis. In the largest and most recent double-blind, randomized, placebo-controlled study (DBRCT), 164 patients receiving 5-fluorouracil-based chemotherapy were given chamomile or placebo mouthwash tid for 14 days.14 Results revealed no difference between chamomile and placebo.
In contrast, a previously published case series revealed positive results. Ninety-eight patients were treated with chamomile oral rinse during head and neck irradiation and/or systemic chemotherapy.15 In this study, 20 patients treated with radiation and 46 patients receiving systemic chemotherapy were given prophylactic care using chamomile rinse. Thirty-two patients were treated after mucositis had already developed. With prophylactic use of chamomile, only one of the 20 patients receiving radiation therapy developed grade 3 mucositis in the final week of treatment and only 10 of the 46 patients receiving chemotherapy developed clinically significant mucositis. Of the 32 patients receiving chamomile therapy for existing mucositis, all noted immediate relief from discomfort and showed improvement.
In another DBRCT assessing effect on inflammation, 48 women who underwent surgery for local breast cancer were randomized to receive almond ointment or chamomile cream to the affected breast while undergoing radiation therapy.16 No statistically significant differences were noted between the two groups. Neither agent could prevent radiation-induced skin changes. Patients however preferred the chamomile cream because it was absorbed rapidly and did not stain.
Finally, a multicenter clinical trial found German chamomile to be 60% as active as low dose (0.25%) hydrocortisone when applied topically for atopic dermatitis.17
Chamomile’s effect as an antispasmodic has been evaluated in a DBRCT of 68 healthy, term infants (ages 2-8 weeks) with colic, which was defined as spells of unexplained irritability, agitation, fussiness, or crying, which lasted more than three hours a day, three times a week for at least three weeks. Infants were randomly assigned to receive an herbal tea containing German chamomile, vervain, licorice, fennel, and balm-mint, or placebo (hot water/glucose infusion). With every colic episode, each infant was offered 150 ml of herbal tea or placebo; each infant received no more than three doses per day. After seven days of therapy, colic symptom scores were 57% improved in the herbal tea group compared to 26% improvement with placebo (P < 0.01).18
Other human studies showing modest benefits from the use of chamomile for a variety of indications have been of poor methodological design and have lacked proper statistical power. One example is the often quoted study in which 12 hospitalized patients consumed two cups of chamomile tea while undergoing cardiac catheterization.19 The average cardiac index decreased minimally from 3.00 to 2.88 l/min/m2. Stroke index remained unchanged and a slight increase in the mean brachial artery pressure from 91 to 98 mm Hg was observed (P < 0.05). Interestingly, 10 minutes after the ingestion of the tea, 10 of 12 patients fell asleep. To date, no randomized trials investigating chamomile’s purported sedative effects have been published.
Adverse Effects and Interactions
Chamomile is generally regarded as safe (GRAS) by the FDA as a spice, seasoning, or flavoring agent. It is listed as a Class 1 herb by the American Herbal Products Association’s Botanical Safety Handbook, noting that it can be safely consumed when used appropriately. In animal studies, both the oral LD50 (dose lethal to 50% of the animals) and the dermal LD50 exceeded 5 g/Kg of body weight.8 An LD50 value in mice given oral chamomile has been documented to be 2.5 ml/Kg. Long-term oral administration of chamomile extracts to rats produced no teratogenicity or signs of changes in prenatal development. No drug-herb interactions have been associated with chamomile to date.6
Several cases of significant allergic reactions to chamomile have, however, been reported. One 35-year-old with a known history of ragweed/hay fever ingested one cup of chamomile tea and developed angioedema and subsequent anaphylaxis.20 In another case, a 54-year-old also developed an anaphylactic reaction after ingestion of chamomile tea.21 Both patients had a history of ragweed allergies; both responded quickly to standard treatment. Rare reports of contact dermatitis after topical application have been noted.8 Patients with known allergies to plants such as ragweed, asters, and chrysanthemums should avoid contact with chamomile products.8 In addition, whole chamomile may be contaminated with other related, more allergenic plants.
Chamomile has other effects. Excessive use of chamomile may result in mild gastroparesis and emesis.8 Chamomile should not be used in the eyes because of residual alcohol content. Although low doses of ()-a-bisabolol have been administered orally to pregnant rats with no reported effects on the fetus, use of chamomile by pregnant and lactating mothers should be avoided.6 Chamomile has been reputed to affect the menstrual cycle. Teratogenicity studies in vitro have been documented for ()-a-bisabolol with oral toxicity at high doses; a dose of 3 ml/Kg has been found to increase the number of fetuses reabsorbed and to reduce body weight at birth.5
Formulations and Dosing
Although available products may contain either German chamomile or Roman chamomile, the majority of studies performed both in animals and humans involved the product Kamillosan®.6 Manufactured by Chemie-werke Homburg Pharmaceuticals in Frankfurt, this product has been marketed since 1921 and utilizes a German chamomile extract.6
In addition to teas, tinctures, liquid extracts, salves, creams, and capsules, chamomile is often added to soaps and perfumes, given its pleasant smell.8 Historical use as a compress, rinse, and gargle continues today. Because it is approved as a food additive by the FDA, chamomile is also commonly added to herbal beverages. Several commercial preparations are available in the United States. (See Table 1.)
|Table 1-Selected physiological measures, MS exercise group|
|Physical work capacity (W x min)||913||1351|
|Shoulder flexion (newtons)||165||183|
|Knee extension (newtons)||255||289|
|Adapted from: Petajan JH, et al. Impact of aerobic training on fitness and quality of life in multiple sclerosis. Ann Neurol 1996;39:432-441.|
According to the German Commission E, dosing of chamomile as a tea means pouring 150 cc of boiling water over 3 g dry weight of fresh or dried flower heads and steeping for 5-10 minutes.1 Foster recommends steeping a gallon of flowers in 30 gallons of hot water for a soothing, antihemorrhoidal bath. Many chamomile preparations are standardized to contain a minimum value of chamazulene and a-bisabolol; in the German pharmacopeia, the crude drug must contain at least 0.4% volatile oil. Unfortunately, there is no universally accepted standardization of chamomile products.
Although published, randomized controlled trials have revealed conflicting results regarding efficacy, chamomile appears to have potential for adding to currently available treatments for a number of commonly encountered conditions, including inflammatory skin conditions. Certainly DBRCTs are needed to establish efficacy. As an FDA approved food additive and as a substance generally regarded as safe, chamomile’s risk of significant toxicity appears very low, with several notable exceptions.
Given its long history of use, apparent safety, and documented bioactivity in animal studies, consideration might be given to using chamomile extract for mild skin irritation and inflammation, mild anxiety/insomnia, and intestinal colic symptoms. Chamomile creams might also be considered for mild skin irritation. Pregnant and lactating women and patients with known allergies to ragweed and other members of the Asteraceae family should avoid chamomile.
a. tea containing German chamomile alone.
b. tea containing Roman chamomile alone.
c. tea containing a combination of herbs.
d. No benefit from herbs was noted.
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3. Grieve M. A Modern Herbal. London: Penguin Books; 1931.
4. Foster S, Tyler VE. Tyler’s Honest Herbal. 4th ed. Binghamton, NY: The Haworth Herbal Press; 1999.
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9. Viola H, et al. Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects. Planta Med 1995;61: 213-216.
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11. Yasukawa K, et al. Effect of chemical constituents from plants on 12-O-tetradecanoylphorbol-13-acetate-induced inflammation in mice. Chem Pharm Bull 1989;37:1071-1073.
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13. Szelenyi I, et al. Pharmacological experiments with compounds of chamomile. III. Experimental studies of the ulcerprotective effect of chamomile. Planta Med 1979;35:218-227.
14. Fidler P, et al. Prospective evaluation of a chamomile mouthwash for prevention of 5-FU-induced oral mucositis. Cancer 1996;77:522-525.
15. Carl W, Emrich LS. Management of oral mucositis during local radiation and systemic chemotherapy: A study of 98 patients. J Prosthet Dent 1991;66:361-369.
16. Maiche AG, et al. Effect of chamomile cream and almond ointment on acute radiation skin reaction. Acta Oncol 1991;30:395-396.
17. Aergeerts P, et al. Vergleichende pruufung von kamillosan crème gegenuber steroidalen externa in der erhaltungstherapie von ekzemerkrankungen. Z Hautkr 1985;60:270-277.
18. Weizman Z, et al. Efficacy of herbal tea preparation in infantile colic. J Pediatr 1993;122:650-652.
19. Gould L, et al. Cardiac effects of chamomile tea. J Clin Pharmacol 1973;13:475-479.
20. Benner MH, Lee HJ. Anaphylactic reaction to chamomile tea. J Allergy Clin Immunol 1973;52: 307-308.
21. Casterline CL. Allergy to chamomile tea [letter]. JAMA 1980;244:330-331.