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Fennel

Scientific Name(s): Foeniculum vulgare Mill.
Common Name(s): Bitter fennel, Carosella, Common fennel, Finocchio, Florence fennel, Garden fennel, Large fennel, Sweet fennel, Wild fennel

Clinical Overview

Use

Fennel has been used as a flavoring agent, a scent, and an insect repellent, as well as an herbal remedy for poisoning and GI conditions. It has also been used as a stimulant to promote lactation and menstruation as well as to improve symptoms in postmenopausal women. However, clinical evidence to support the use of fennel for any indication is limited.

Dosing

Fennel seed and fennel seed oil have been used as stimulant and carminative agents in doses of 5 to 7 g and 0.1 to 0.6 mL, respectively. Oral essential fennel oil (30%) capsules and fennel extract vaginal cream (5%) have been used to improve symptoms in postmenopausal women at 200 mg/day and 5 g/day, respectively.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

There are documented adverse reactions and emmenagogue effects. Avoid use.

Interactions

One study suggested that the fennel constituent 5-methoxypsoralen has the ability to inhibit cytochrome P450 3A4. Therefore, fennel should be used cautiously with medications requiring this isoenzyme as a substrate.

Adverse Reactions

Fennel may cause photodermatitis, contact dermatitis, and cross reactions. The oil may induce reactions, such as hallucinations and seizures. Four case reports of premature thelarche (breast development) in girls have been reported with the use of fennel. Poison hemlock may be mistaken for fennel.

Toxicology

Fennel oil is genotoxic in the Bacillus subtilis DNA repair test. Estragole, present in the volatile oil, has caused tumors in animals.

Botany

Fennel (synonyms Foeniculum officinale All., Anethum foeniculum) is an herb native to southern Europe and Asia Minor. It is also cultivated in the United States, Great Britain, and temperate areas of Eurasia. All parts of the plant are aromatic. When cultivated, fennel stalks grow to a height of approximately 1 m. Plants have finely divided leaves composed of many linear or awl-shaped segments. Grayish compound umbels bear small, yellowish flowers. The fruits or seeds are oblong ovals about 6 mm long and are greenish or yellowish brown in color with 5 prominent dorsal ridges. The seeds have a taste resembling that of anise. Besides F. vulgare, Foeniculum dulce (carosella) is grown for its stalks, while F. vulgare var azoricum Thell. (finocchio) is grown for its bulbous stalk bases. A number of subspecies have been identified, adding to the potential confusion surrounding the terminology of these plants.

History

According to Greek legend, man received knowledge from Mount Olympus in the form of a fiery coal enclosed in a stalk of fennel. The herb was known in the ancient Chinese, Indian, Egyptian, and Greek civilizations, and the Roman scholar Pliny (AD 61-113) recommended it for improving eyesight. The name foeniculum is from the Latin word for fragrant hay. During the Middle Ages, wealthy people routinely added the seed to fish and vegetable dishes, while the poor reserved its use for fasting days as an appetite suppressant. The plant was introduced to North America by Spanish priests, and the English brought it to their early settlements in Virginia.2 All parts of the plant have been used for flavorings, the stalks have been eaten as a vegetable, and the seeds have served as a traditional carminative. Fennel has been used to flavor candies, liqueurs, medicines, and food; its use is especially favored for pastries, sweet pickles, and fish. The oil can be used to protect stored fruits and vegetables against growth of toxic fungi.3 Beekeepers have grown it as a honey plant.2 It is a purported antidote to poisonous herbs, mushrooms, and snakebites4 and it is also thought to be useful in treating gastroenteritis and indigestion, in stimulating lactation, as an expectorant, and as an emmenagogue.1 Tea made from crushed fennel seeds has been used as an eyewash.2 Powdered fennel is said to drive fleas away from kennels and stables.3

Chemistry

Fennel seeds contain between 3% and 6% of an essential oil and approximately 20% of a fixed oil composed of petroselinic acid, oleic acid, and tocopherols. The essential oils of sweet and bitter fennel contain up to 90% trans-anethole, up to 20% fenchone, and small amounts of limonene, camphor, alpha-pinene, and about 6 additional minor volatile compounds.5 Sweet fennel contains derivatives of caffeic acid and hydroxybenzoic acid.6 The fruit (seeds) and leaves contain a number of flavonoid compounds, including quercetin 3-glucuronide, isoquercetin, kaempferol 3-glucuronide, and kaempferol 3-arabinoside. Low concentrations of isorhamnetin glycosides are found in the leaves.7

Uses and Pharmacology

Antimicrobial activity

Fennel has demonstrated inhibitory effects on the growth of Bacillus amyloliquefaciens.24 Bacteriostatic effects against Escherichia coli, Staphylococcus epidermidis, and Saccharomyces cerevisiae have also been demonstrated.25 In an in vitro study, F. vulgare exerted antifungal effects against Candida albicans.26 Additionally, the essential oil and hexane extract of Florence fennel and anethole exerted antimicrobial effects against probiotic bacteria.27

Because of the association of Helicobacter pylori with gastritis, peptic ulcer, and gastric cancer, in vitro experimentation was conducted in H. pylori-infected gastric epithelial cells with 24 medicinal plants indigenous to Pakistan to evaluate their effect on secretion of IL-8 and generation of reactive oxygen species (ROS) in order to assess anti-inflammatory and cytoprotective effects. Although no significant direct cytotoxic effects on the gastric cells or bactericidal effects on H. pylori were found, fennel seed extract was observed to have mild and moderate inhibitory activity on IL-8 at 50 and 100 mcg/mL, respectively, and significant suppression on ROS generation in H. pylori-infected gastric cells (P < 0.01).46

Acaricidal activity

Animal data

Oil derived from F. vulgare fruit demonstrated acaricidal activity against Dermatophagoides farinae and Dermatophagoides pteronyssinus (house dust mites). The median lethal dose (LD50) for the oil was 119 and 103 mg/m2 for D. farinae and D. pteronyssinus, respectively.

Twelve volatile compounds were identified from the oil of Foeniculum fruits. The main constituents were trans-anethole (53.2%), anisaldehyde (0.7%), beta-asarone (0.9%), beta-caryophyllene (1.1%), p-cymene (3.1%), estragole (12.7%), (+)− fenchone (14.2%), d-limonene (0.7%), 1,5,8-p-menthatriene (0.6%), alpha-pinene (0.8%), gamma-terpinene (0.7%), and thymol (1.4%). The compound most toxic against both species was p-anisaldehyde. Further research is needed to determine any safety issues for the use of F. vulgare in humans.10

Clinical data

There are no clinical data regarding the use of fennel for acaricidal activity.

Anti-inflammatory effects

Animal data

In mice, a F. vulgare fruit methanol extract at a dose of 200 mg/kg caused inhibition of paw edema (69%). Ear edema was also reduced by 70%. These results suggest that F. vulgare fruit methanolic extract may act on the cyclooxygenase and lipoxygenase pathways.12

Clinical data

A study compared the effect and potency of mefenamic acid and an extract of fennel (2% concentration) for the treatment of primary dysmenorrhea in 30 women. Mefenamic acid was more potent than fennel on the second and third days of menstruation (P ≤ 0.05). However, on the other days, the difference was not significant. With the doses prescribed, no complications were reported in the mefenamic acid treatment cycles (250 mg every 6 hours). However, 5 participants (16.6%) withdrew from the study because of fennel's odor, and one subject reported a mild increase in the volume of her menstrual flow during the fennel treatment cycle.13 A Cochrane systematic review and meta-analysis of dietary supplements for primary dysmenorrhea identified only low or very low quality studies with very small sample sizes. No consistent evidence of effectiveness was found for the treatment of primary dysmenorrhea with fennel compared to placebo or no treatment; however, no difference was identified between fennel compared to mefenamic acid (1 randomized clinical trial, n = 59). Dosages and formulations varied widely.45

Chronic constipation

In a randomized, placebo-controlled, single-blinded, crossover study of 20 patients with chronic constipation, use of a tea containing F. vulgare, Sambucus nigra, Cassia augustifolia, and Pimpinella anisum was associated with improvements in colonic transit time as well as number of bowel evacuations, with the latter effects beginning during the second day of therapy.15

Enhancement of transdermal drug delivery

Animal data

In animal studies, pretreatment of the skin with several essential oils increased the flux values of trazodone. Pretreatment with a solution containing 10% fennel oil in propylene glycol showed an enhancement ratio of 9.25 compared with the control. The incorporation of fennel in the transdermal device also produced an increase in the flux of trazodone but less of an increase than when the skin was pretreated.14

Clinical data

There are no clinical data regarding the use of fennel for enhancement of transdermal drug delivery.

Menopausal symptoms

A triple-blind, randomized, placebo-controlled Iranian trial (n=79) found that 8-week supplementation with fennel capsules (200 mg/day; 30% essential fennel oil per 100 mg capsule) significantly improved menopausal symptoms compared to baseline and placebo in postmenopausal women who were in the first 5 years of the postmenopausal period. In the fennel group, 1 patient experienced a minor allergic reaction and 1 the feeling of severe heat, whereas 1 case of digestive problems was documented in the control group.47 Additionally, 5% fennel extract vaginal cream (one application of 5 g/day for 8 weeks) was observed to significantly improve symptoms of vaginal atrophy compared to placebo. In this double-blind controlled trial conducted in postmenopausal women, symptom improvement was seen in itching (P=0.017), dryness (P<0.001), pallor (P<0.001), dyspareunia (P<0.001), and the maturation vaginal index value (P<0.001). No adverse events were observed.48

The effect of fennel supplementation was also investigated for efficacy in managing anxiety and depression in postmenopausal women in a double-blind, randomized, placebo-controlled trial conducted in 60 women. After the 3-month intervention, women taking fennel 300 mg/day standardized to 21 to 27 mg anethole (100 mg 3 times daily) did not experience a significant change in anxiety or depression scores on either of the 2 scales utilized. Patients receiving fennel complained of frequent urination and spotting (n=2) whereas those on placebo experienced stomach ache (n=2).49

Repellent activity

Animal data

The repellent activity of constituents identified in F. vulgare against hungry female Aedes aegypti mosquitoes was compared with N,N-diethyl-m-toluamide (DEET) using skin and patch tests. With patch testing, responses varied according to the compound and dose. Fenchone caused 94% and 82% repellency at 0.01 and 0.005 mg/cm2. (E)-9-octadecenoic acid gave 91% repellency at 0.01 mg/cm2 and 73% repellency at 0.005 mg/cm2. At a dose of 0.2 mg/cm2, the repellent effects of a fenchone skin test were 100% and 32% with (E)-9-octadecenoic acid. The efficacy for fenchone was only 30 minutes, compared with more than 1 hour with DEET.11

Clinical data

There are no clinical data regarding the use of fennel for mosquito repellent activity.

Stimulant to promote lactation and menstruation

As an herbal medicine, fennel is reputed to increase milk secretion, promote menstruation, facilitate birth, ease the male climacteric, and increase libido. These supposed effects led to research on fennel for the development of synthetic estrogens during the 1930s. The principal estrogenic component of fennel was originally thought to be anethole, but it is now believed to be a polymer of anethole, such as dianethole or photoanethole.8

Animal data

An acetone extract of F. vulgare seeds had estrogenic effects on the genital organs of male and female rats.9

Clinical data

There are no clinical data regarding the use of fennel as a stimulant to promote lactation and menstruation.

Other uses

A systematic review suggests a potential role for fennel in the management of infantile colic symptoms.16

In a rabbit model, F. vulgare exerted oculohypotensive effects in both normotensive and glaucoma-induced models.17

The chief component of fennel, anethole, had anticarcinogenic and anti-inflammatory effects through modulation tumor necrosis factor–induced cellular processes.18 In a murine model, the tumor incidence was lower in mice with skin and forestomach papillomagenesis treated with fennel, suggesting a chemopreventive effect.19

In a murine model, fennel seed methanolic extract had anticancer effects against a breast cancer cell line (MCF7) and liver cancer cell line (HepG-2). Additionally, antitumor effects occurred through modulation of lipid peroxidation.20

The volatile oil of fennel increases the phasic contraction of ileal and tracheal smooth muscle in guinea pigs. The effect was generally greater with ileal muscle.21 Administration of the volatile oil to rats has exacerbated experimentally induced liver damage.22

Oil extracted from F. vulgare has a protective effect against the toxicity induced by carbon tetrachloride in rat livers. Although the responsible compound has not been identified, d-limonene and beta-myrcene have previously been shown to affect the liver.23

Fennel essential oil inhibited contraction of an isolated uterus that was induced by oxytocin and prostaglandin E2. The optimum dose of fennel essential oil was 100 mg/mL. Fennel essential oil may have a mechanism of action similar to that of diclofenac, although the exact mechanism of action of the oil is unknown.28

F. vulgare fruit methanolic extract may have immunosuppressive properties. Antiallergic activity (type IV) was tested using 2,3-dinitrofluoro-benzene–induced contact hypersensitivity reactions. F. vulgare fruit methanolic extract showed an inhibitory effect.29

Fennel inhibited rat lens and human recombinant aldose reductase; therefore, it may have a potential role in the management of diabetic complications.30

Fennel essential oil and anethole exerted antithrombotic effects in an experimental model in guinea pig plasma. Specifically, antiplatelet effects were found against arachidonic acid-, collagen-, ADP-, and U46619-induced aggregation. In rat aorta, fennel essential oil and anethole exerted nitric oxide-dependent vasorelaxation.31 Some data suggest a possible diuretic effect with fennel.32

Fennel has been shown to be effective in the treatment of hirsutism in women.33

Dosing

Fennel seed and fennel seed oil have been used as stimulant and carminative agents in doses of 5 to 7 g and 0.1 to 0.6 mL, respectively.29 Oral essential fennel oil (30%) capsules and fennel extract vaginal cream (5%) have been used to improve symptoms in postmenopausal women at 200 mg/day and 5 g/day, respectively.47, 48

Pregnancy / Lactation

There are documented adverse reactions and emmenagogue effects. Avoid use.34, 35

Interactions

One study suggests the constituent 5-methoxypsoralen contained in fennel has the ability to inhibit cytochrome P450 3A4.36 Therefore, cautious use of concomitant medications that require this isoenzyme as a substrate is warranted.

Adverse Reactions

Ingestion of fennel's volatile oil may induce nausea, pulmonary edema, seizures, and vomiting.37 One case report describes a 28-year-old woman with well-controlled epilepsy who experienced a generalized tonic-clonic seizure, remaining unconscious for 45 minutes, and involuntary diarrhea.38 Laxative and cholagogic properties have also been described.39 The oil's therapeutic use has occasionally induced epileptiform madness and hallucinations.3 The principal hazards with fennel itself are photodermatitis and contact dermatitis. Some individuals exhibit cross-reactivity to several species of Apiaceae, characteristic of the "celery-carrot-mugwort-condiment" cross-reactivity syndrome.40 Rare allergic reactions have been reported following ingestion of fennel.

Four case reports suggest that fennel tea given to infants for prolonged periods of time resulted in premature thelarche (breast development) in girls. All 4 subjects had serum estradiol levels 15 to 20 times higher than normal values for their ages. After stopping the ingestion, the premature thelarche resolved within 3 to 6 months.41 A survey of fennel samples in Italy found viable aerobic bacteria, including coliforms, fecal streptococci, and Salmonella species, suggesting the plant may serve as a vector of infectious GI diseases.42

Toxicology

Fennel oil was genotoxic in the B. subtilis DNA-repair test.43 Estragole, which is present in the volatile oil, caused tumors in animals. A serious hazard is that poison hemlock can easily be mistaken for fennel. Hemlock contains highly narcotic coniine, and a small amount of hemlock juice can cause vomiting, paralysis, and death.4

Animal studies have demonstrated toxic effects of fennel essential oil on fetal cells. However, no evidence of teratogenicity was seen.44

No pathological toxicity was seen in the organs of dead animals, indicating that death may be caused by the effects of metabolite imbalance or nervous system toxicity. The value of LD50 was 1,326 mg/kg.28

In a murine model, fennel seed methanolic extract at doses of 100 mg/kg did not result in any deaths. However, doses up to 500 mg/kg were associated with adverse effects, including loss of appetite and piloerection; a higher mortality rate was noted at 1,000 mg.20

References

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