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Food Science

Anise

Potential Health Benefits

Singletary, Keith W. PhD

Author Information
doi: 10.1097/NT.0000000000000534
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Abstract

Anise (Pimpinella anisum L., family Apiaceae) is an aromatic annual herb native to the eastern Mediterranean region and western Asia (Figure 1) and cultivated in numerous regions such as southern Europe, northern Africa, South America, China, and Japan. Turkey, Egypt, and Spain are major exporters of this herb, whereas Russia, Spain, and Poland are major suppliers of its oil. The small fruit is incorrectly referred to as a seed. Nonetheless, the fruit is commonly known as aniseed, which when ripe and dried is the popular spice. Aniseed has a sweet, aromatic taste similar to licorice. The fruit and essential oil are used extensively as a flavoring ingredient in numerous foods, including baked goods, sweets, puddings, curries, and frozen dairy desserts, to name a few. The essential oil also is used in perfumes, lotions, soaps, cough preparations, and gum and oral health products. In the food industry, it acts as an antioxidant and preservative. In addition, aniseed is distilled with ethanol to yield distinctive, traditional alcoholic beverages such as anis, Arabian arak, French pastis, Greek ouzo, Russian allasch, Turkish raki, German küstennebel, Italian sambuca, and South American aguardiente.1–4 Combining water with these alcoholic beverages in mixed drinks creates a milky cloudiness. This is due to the precipitation of congeners and by-products of distillation that are most soluble in ethanol compared with ethanol and water. In regional foods, this spice is a part of, for example, German springerle or anise-flavored cookies. For these cookies, anise oil (1/2 tsp) or extract (1 tsp) can be added directly to the dough, or on the other hand, toasted aniseeds can be distributed on the cookie sheets before baking. Greek butter cookies (koulourakia), traditionally made for Easter and Christmas celebrations, include aniseed (1/2 tsp) and ouzo (1 tbsp) among its flavorings. Likewise, aniseed cookies found in bakeries throughout the Middle East are prepared with ground anise and fennel seeds and savored with a cup of tea or coffee. Preparation of Italian anisette biscotti calls for anise extract (2 tsp). Baked anise taralli bread containing lightly crushed aniseeds can be enjoyed throughout Italy, with each region contributing to distinctive variations in ingredients and final shapes. Traditional Italian sausage incorporates aniseed (1/2 tsp) among the approximately 12 spices combined in its preparation. Anise is not to be confused with the Magnoliaceae family member Chinese star anise (Illicium verum), the volatile oil from which closely resembles that of anise oil. Star anise seeds and pods (Figure 2) are both used in cooking. Compared with anise, star anise possesses a much more intense aromatic flavor that can easily overpower a dish. Thus, it is recommended that ground star anise seed be used in moderation and pods be removed before a food is finished cooking. Star anise is a contributor to Chinese and Vietnamese cuisine and is one of the constituents in Chinese 5-spice powder. The traditional Vietnamese dish beef pho adds star anise pods to the simmering broth. Chinese tea leaf eggs comprise hard-boiled eggs flavored with star anise pods as one of its spices. It should be noted that Chinese star anise is similar in appearance to Japanese star anise (Illicium anisatum) that can cause serious adverse effects and organ damage when mistakenly eaten.

F1
FIGURE 1.:
Anise plants and fruit.
F2
FIGURE 2.:
Star anise.

Depending on the region of cultivation and method of extraction, the main constituents of the essential oil of aniseed5–7 generally are trans-anethole (85%–95%), γ-himachalene (0.4%–8.2%), methyl chavicol or estragole (0.5%–5.0%), p-anisaldehyde (0%–5%), and pseudoisoeugenol-2-methylbutyrates (1.3%–3.0%) (Figure 3).

F3
FIGURE 3.:
Structures of anise phytochemicals.

In ancient times, aniseed was used to aid childbirth and stimulate milk production8 and continues to be recommended for diverse maladies in folk medicines. Primarily because of the presence of trans-anethole, the fruit and essential oil are used in traditional therapies, for example, for relief of coughs, respiratory congestion, migraines, gastrointestinal (GI) distress, and colic; treatment of skin infections; as tranquilizer and aphrodisiac; and to improve lactation.4,5,9–13 More recently, there are efforts to understand the efficacy of aniseed toward diabetes, dysmenorrhea, and menopausal hot flashes, as well as to clarify its antioxidant, anti-inflammatory, and antimicrobial properties.2–5 The present narrative review summarizes human and animal studies about the potential health benefits of aniseed and highlights areas for future research.

METHODS

To provide evidence for potential health benefits of foods, ingredients, and plant constituents, data are gathered from a variety of scientific methods such as cell culture experiments, animal studies, and human clinical trials. Human studies are particularly important in determining public health recommendations, especially randomized controlled trials (RCTs) testing well-characterized treatments and applying appropriate statistical analyses. With this in mind, a search of the PubMed and Science Direct databases was conducted using terms that included Pimpinella anisum, aniseed, anise, anisoon, and anethole. Full reports of English-language publications and English-language abstracts of foreign-language articles from peer-reviewed journals were the primary sources of information. Although the quality of identified studies varied considerably, all relevant, published investigations were included in this overview so that the totality and diversity of information can be described, and issues for future research can be identified. Additional information was gleaned from bibliographies within these sources. Studies of aniseed as a component within multi-ingredient preparations were not included in this overview.

BIOAVAILABILITY

Little is known about the bioavailability of aniseed and its constituents. Such data are important, because any potential uses of aniseed to improve health are impacted by how much is consumed and the ultimate amount and form of its individual bioactive components in target tissues. This information also helps in discerning any negative effects of aniseed constituents and their metabolites in various organs. In contrast to aniseed, the disposition of trans-anethole has been investigated. In rats, trans-anethole is rapidly absorbed and distributed.14 In human volunteers (n = 5), trans-anethole (4-methoxy-propylbenzene) was randomly administered at doses of 1, 50, and 250 mg (0.01–5.0 mg/kg of body weight) with a 3-month interval between dosing.15 These doses represent a range of trans-anethole exposure from amounts from dietary intake (50 mg) to those levels (250 mg) consumed in several aniseed-containing drinks. The bulk of the metabolites was detected in the urine within 8 hours, and the main metabolites were 4-methoxy-hippuric acid and 4-methoxybenzoic acid. The dose administered did not affect rate or route of elimination, in contrast to that observed in animals. Similar results were observed in an extremely small human study (n = 2) in which 1-mg trans-anethole was given.16 In another small pilot study, serum levels of trans-anethole were determined in 1 volunteer provided anethole in ouzo at doses of 56.0, 93.4, and 168.1 mg separated by 7-day intervals.17 Within a 2-hour peak, serum levels of trans-anethole were 15.5, 25.7, and 73 ng/mL, respectively. When breastfeeding women were administered 100-mg trans-anethole, this chemical appeared in the milk at concentrations of 4.3 to 9.9 μg/L.18 Clearly, additional characterization of the systemic disposition of aniseed, as well as its extracts and major constituents, is needed after ingestion in foods and beverages.

HUMAN STUDIES

Human studies evaluating the influence of aniseed on several health conditions are few (Table 1). The reported RCTs mostly were conducted in 1 geographic region (8 reports from Iran), small (n = 20–47 subjects), and of short duration (4–6 weeks). Quality among studies varied, because some were not adequately blinded and statistical comparisons of outcomes between treatment and control groups were not always reported. Nonetheless, these trials provide preliminary evidence of potential actions of aniseed in modulating the signs and symptoms of diabetes, GI distress, sinusitis, migraines, and female disorders.

TABLE 1 - Effect of Aniseed Administration in Human Trials
Condition Anise Sample Dose/Duration Outcome Ref.
Type 2 diabetes Seed powder 5 g/d (n = 20), control (n = 20); 60 d Anise vs baseline:
↓FBG, ↓TG, ↓LDL, ↑HDL, plasma MDA, ↑serum CAT + GST + GSH, ↑serum ß-carotene + vitamin E + vitamin C
Control vs baseline:
↑FBG
NE: TC, TG, LDL, HDL.
Rajeshwari et al19
Dyspepsia Seed powder 9 g/d (n = 47), placebo (n = 60); 4 wk Anise vs baseline:
↑social + physical functioning, ↑vitality, ↓body pain
Placebo vs baseline:
Worsening physical + social symptoms
Ghoshegir et al20
Dyspepsia Seed powder 9 g/d (n = 47), placebo (n = 60); 4 wk Anise vs placebo:
↓epigastric discomfort + bloating, ↓epigastric and postprandial pain, ↓early satiety
NE:
Preprandial and postprandial nausea, morning nausea, vomiting
Ghoshegir et al21
Irritable bowel syndrome (IBS) Seed oil 600 mg/d (n = 38), placebo (n = 37); 4 wk Anise vs placebo:
↓abdominal pain, ↓bloating + reflux, ↓diarrhea, ↓constipation severity, ↓headache + tiredness, ↑subjective QOL scores
Azimi and Zahedi22
IBS-associated depression Seed oil 600 mg/d (n = 39), placebo (n = 38); 4 wk Anise vs placebo:
↓symptoms of mild to moderate depression
Mosaffa-Jahromi et al23
Migraine headaches Seed oil 2-cc oil-containing cream to forehead at migraine onset (n = 22), placebo cream (n = 10); 6 wk Anise vs placebo:
↓subjective headache scores, ↓frequency + duration of attacks
NE:
Headache intensity
Mosaffa-Jahromi et al24
Menopausal hot flashes Seed alcohol extract 0.99 g/d (n = 36), placebo (n = 36); 4 wk Anise vs placebo:
↓hot flash frequency + severity
Hawrelak et al25
Premenstrual syndrome (PMS) symptoms Seed alcohol extract 330 mg/d (n = 35), placebo (n = 32); −7 d to +3 d of menstrual cycle for 2 cycles Anise vs placebo:
↓PMS symptoms + intensity
Thompson Coon and Ernst26
Chronic rhinosinusitis without polyps Seed water extract 200 μg/nostril (n = 26), 1 fluticasone dose/nostril; per 12 h, 4 wk Anise or fluticasone vs baseline:
↓symptoms of sinonasal disorders, ↓inflamed mucosa
Anise vs fluticasone:
Improved scores for sinonasal outcomes test-22, improved rhinological symptoms, ↓psychological issues
Mosavat et al27
Duration of premature newborn tube feeding Seed oil Exposure to anise-containing olfactory pen 10 min before meals (n = 13), controls (n = 24) Anise vs controls:
Trend (P < .12) toward ↓duration tube feed and hospitalization
Post hoc analysis for newborn wt ≥ 2000 g: ↓ (P < .05) duration hospitalization
Nahidi et al28
Abbreviations: CAT, catalase; FBG, fasting blood glucose; GSH, reduced glutathione; GST, glutathione-S-transferase; HDL, serum high-density lipoprotein cholesterol; LDL, serum low-density lipoprotein cholesterol; MDA, malondialdehyde; NE, no effect; QOL, quality of life; TC, serum total cholesterol; TG, serum triglycerides; wt, weight.

Diabetes

Specifically, aniseed powder (5 g/d) was provided to subjects (n = 20) with type 2 diabetes mellitus for 60 days.19 This daily dose of aniseed powder is considerably more than from typical consumption of several portions of anise-containing foods. Compared with baseline values, administration of aniseed was associated with a significant decrease in fasting blood glucose concentrations and in blood levels of both total cholesterol and triglycerides. Moreover, blood levels of oxidative stress biomarkers decreased, and those of antioxidant factors increased. In contrast, for those subjects in the control group, compared with baseline, fasting blood glucose increased and total cholesterol and triglyceride levels were unchanged at 60 days.

Dyspepsia and Inflammatory Bowel Syndrome

In a different investigation, aniseed powder (9 g/d) was administered to patients with functional dyspepsia for 4 weeks.20,21 Compared with placebo, those receiving aniseed reported significantly less epigastric discomfort and bloating, epigastric and postprandial pain, and early satiety. Prevalence of nausea and vomiting was not changed. Furthermore, in the subjects administered aniseed powder, the quality of life was significantly improved as measured by self-reported increases in social and physical function, general health, and vitality. As recommended in a recent systematic review of Persian traditional medicines for functional dyspepsia,22 additional mechanistic insights are needed, such how aniseed affects the rate of gastric emptying and antrum contractions, regulation of GI motility, modulation of gastric mucosal inflammatory factors, and prevalence of Helicobacter pylori infection. Aniseed oil as an enteric capsule (AnisEncap) was given orally (600 mg/d) to individuals (n = 38) with irritable bowel syndrome (IBS) for 4 weeks in a 3-armed, double-blind, placebo-controlled trial.23,24 Detailed descriptions of demographic data and basic characteristics of participants were provided. Compared with the placebo group (n = 37), those given the oil reported significantly lower rates of diarrhea, bloating, reflux, severity of constipation, and abdominal pain, which were improvements that continued for an additional 2-week follow-up period after cessation of dosing. For 75% of patients, there were no IBS symptoms at the end of the 4-week treatment period, compared with 35% of control subjects (P < .001). In addition, aniseed oil intake resulted in significantly decreased symptoms of mild to moderate depression in those individuals with IBS and a significant increase in quality-of-life scores. Of interest, in this trial, aniseed oil treatment was superior in decreasing IBS symptoms compared with those in the third arm (n = 33) administered Colpermin IBS relief capsules (containing 566-mg peppermint oil). This superior performance of aniseed oil is significant, because peppermint essential oil is a commonly recommended remedy that is both effective and well tolerated in the short-term management of IBS, compares favorably with other potential IBS treatments,25 and consistently demonstrates benefits in treating nonulcer dyspepsia.26 Thus, further characterization of the efficacy of aniseed in alleviating IBS is warranted.

Migraine Headaches and Sinusitis

Aniseed oil incorporated into a cream was applied for 6 weeks to the temporal and forehead regions of individuals (n = 22) experiencing migraine headaches.27 Compared with users of a placebo cream, treatment with aniseed oil-containing cream significantly decreased the frequency and duration of attacks, although the severity of attacks was not mitigated. In another study, individuals (n = 26) having chronic rhinosinusitis without polyps28 were instructed to apply nasal drops containing 200 μg of a water extract of aniseed in almond oil to each nostril every 12 hours for 4 weeks. Another group of patients nasally administered the corticosteroid drug fluticasone. When outcomes from the aniseed extract treatment and fluticasone dosing were examined, both aniseed extract and fluticasone significantly improved sinonasal symptoms and significantly decreased inflamed paranasal sinus mucosa as measured with computed tomography scans. Of interest, when these 2 groups were compared, the aniseed-containing drops were significantly more effective than fluticasone in decreasing rhinological symptoms.

Hot Flashes and Premenopausal Syndrome

In 2 trials, alcohol extracts of aniseed powder were investigated. In 1 trial, the extract (990 mg/d) was given for 4 weeks to subjects (n = 36) experiencing menopausal hot flashes.29 Compared with controls, there was a significant lowering in the severity and frequency of hot flashes. Notably, this beneficial response continued for another 2 weeks post intervention. Future studies should compare the actions of these traditional medicines to the efficacy of accepted hormonal replacement therapies and clarify possible mediators of the changes in intensity and severity of hot flashes, such as levels of estradiol, estrone, follicle-stimulating hormone, and sex hormone–binding globulin. In another study, an alcohol extract (330 mg/d) was given orally to college-aged women (n = 35) for 7 days before and 3 days after each of 2 menstrual cycles.30 Compared with placebo, aniseed treatment significantly decreased the symptoms and intensity of premenopausal syndrome. As noted in a recent review of aniseed's effects on female disorders,8 most clinical trials evaluated aniseed in combination with different plant materials. Thus, human investigations examining the individual efficacy of aniseed as well as its oil and extracts on various female conditions such as pain after childbirth, menstruation pain, polycystic ovary syndrome, hot flashes, and menopause-related depression are needed.8

Infant Transition to Breastfeeding

Finally, in a novel trial involving premature newborns in Belgium,31 infants were exposed to an aniseed-containing olfactory stimulus 10 minutes before feeding tube-provided meals to determine whether this brief stimulus would lead to a more rapid switch to satisfactory maternal breastfeeding. Compared with controls, there was a trend (P < .12) toward a shorter length of tube feeding and subsequent duration of hospitalization. In a post hoc analysis of newborns admitted weighing 2000 g or more, the hospital stays of those administered the olfactory stimulus were significantly shortened, compared with controls. It should be noted that, in these diverse clinical trials, the doses and durations of aniseed, aniseed oil, and extract treatments were not associated with significant adverse effects.

ANIMAL STUDIES

A few animal studies (Table 2) provide consistent support for the effects of aniseed reported in clinical trials. In some cases, the aniseed phytochemical trans-anethole was tested in similar animal models. For example, different doses of aniseed powder (10% w/w diet), essential oil (25–200 mg/kg/d, intraperitoneal), and alcohol extract (0.125-0.5 mg/kg/d, intraperitoneal) were shown to modulate aberrant levels of blood lipids but were less consistent in changing blood glucose concentrations.42–45 With regard to trans-anethole, oral dosing of diabetic rats ameliorated hyperglycemia by altering key enzymes of carbohydrate metabolism, improving hepatic and muscle glycogen status, and normalizing pancreatic histology, compared with controls.64 Ten animal investigations32–41 demonstrated the capacity of aniseed to suppress seizures, lessen pain, and modulate mood, in part through inhibiting oxidative stress and inflammation in the brain and restoring normal brain cellular architecture. In some cases, efficacy was similar to that of standard drugs used as positive controls. Similarly, trans-anethole was reported to correct behavioral deficits and demonstrate antinociceptive and anxiolytic properties in animals.65–70 In contrast, in one study of mice dosed with 1 to 2 g/kg of an aqueous extract of aniseed, an impairment of learning was observed.41 For these animal studies, aniseed and trans-anethole were frequently administered pharmacological doses by intraperitoneal injection or intragastric intubation. Additional animal experiments are needed in which neurological and behavioral outcomes following dietary supplementation of aniseed are determined. Despite the preliminary and limited nature of this current evidence, additional support from dietary studies could justify exploring the antidepressant and analgesic properties of aniseed in humans.

TABLE 2 - Effects of Aniseed Extracts in Animal Models
Condition Treatment Model + Outcomes Ref.
Sample Dose/Duration
Neural disorders Essential oil (EO) 0.25–1.0 mL/kg of body weight (i.p.), 30 min Mouse:
↓PTZ-induced + ↓electroshock-induced convulsions
↑Seizure threshold
↓Seizure spread
Pourgholami et al32
0.125–0.5 mL/kg (i.p.), 30 min Mouse:
↓Morphine-induced conditioned behavior
↓GABAergic activation
Sahraei et al33
0.5 mL/kg (i.p.), 30 min Rat:
↓Chemical-induced inflammation + nociception
Tas et al34
0.1–0.4 mL/kg (i.p.), 30 min Mouse:
↑Analgesic effect
Tas35
1–3 mL/kg (i.p.), 90 min Rat:
↓PTZ-induced seizure frequency + amplitude
↓Duration epileptiform burst discharges
↓Production dark neurons in hippocampus CA1 and CA3
Karimzadeh et al36
0.3 mg/kg/d (i.g.), 5 d Mouse:
↑Codeine analgesic effect
↑Midazolam-induced + diazepam-induced motor impairment
↓Pentobarbitol-induced sleeping time
↓Antidepressant effect imipramine + fluoxetine
Samojlik et al37
300 mg/kg (i.g.), 4 wk Rat:
↑Antidepressant activity
↑Cerebral + hippocampal levels SOD, GPx, GR, GST
↓Brain MDA + NO levels
Restore hippocampal cell architecture
El-Shamy et al38
Alcohol extract 50–200 mg/kg (i.p.), 30 min Mouse:
↑Antidepressant activity; comparable with fluoxetine
Shahamat et al39
100–200 mg/kg/d (i.g.), 21 d Mouse:
↑Antidepressant activity; comparable with paroxetine
↑Anxiolytic activity; comparable to bromazepam
Es-Safi et al40
Water extract 0.5–2.0 g/kg (i.g.), 30 min Rat:
↓Learning
NE: anxiety
Gamberini et al41
Blood lipid and glucose dysregulation EO 25–200 mg/kg/d (i.p.), 30 d Rat model NAFLD:
↓TC, ↓TG, ↓LDL, ↓ALT, ↓AST, ↓LPO, ↑HDL, ↓steatohepatitis
Asadollahpoor et al42
1 mL/kg/d (i.g.), 1 mo Rat (male):
↓BW, ↓TC, ↓TG, ↓LDL, ↓FBG, ↑HDL, ↓LH, ↓FSH, ↓T, ↓sperm count
NE: ALT, AST, creatinine, BUN
Helal et al43
Fruit powder 10% w/w diet
24 h, 7d
Rat:
24 h: ↓food intake
NE: NFBG, SI, H2O intake, urine output
7d: ↑BW, ↑NFBG
NE: food intake, SI, H2O intake, urine output
Parvinroo et al44
10-g/kg w/w diet
29 d
Quail:
↓TC
NE: TG
Christaki et al45
Alcohol extract 0.125–0.5 mg/kg/d (i.p.), 30 d Rat model NAFLD:
↓TC, ↓TG, ↓LDL, ↓ALT, ↓AST, ↓LPO, ↑HDL, ↓steatohepatitis
Asadollahpoor et al42
Toxic damage EO 20, 100 mg/kg/d (i.p.); 3 d Rat:
NE: CCl4-induced liver injury, AST, LDH, AST, GSH, TBARS
Jamshidzadeh et al46
100–300 mg/kg/d (i.g.), 7 d Rat:
↓Fava bean-induced liver damage + acute hemolytic anemia
↑Serum GSH
↓Serum TBARS
Koriem et al47
0.5 mL/kg/d (i.p.), 7 d Rat:
NE: CCl4-induced liver damage
↓Serum AST + ALT
Cengiz et al48
0.3 mL/kg (i.g.), 3 d Rat:
Small ↓ paraquat-induced lung damage
Cambar and Aviado49
0.5 mL/kg/d (i.p.), 2 mo Rat:
↓Aspartame (aspr)-induced neurotoxicity in Purkinje cells cerebral cortex
↓Prevalence aspr-induced abnormal granular cells + myelinated nerve fibers
Abdul-Hamid and Gallaly50
Fruit powder 2,4,6% w/w diet; 28 d Rat:
CCl4-induced liver AST + ALT
↓BW, ↓FBG, ↓TC, ↓TG, ↓LDL, ↓HDL
Aboelnaga51
Alcohol extract 100, 200 mg/kg/d (i.p.); 3 d Rat:
NE: CCl4-induced liver damage, AST, ALT, GSH, TBARS
Jamshidzadeh et al46
300 mg/kg/d (i.p.), 8 d Rat:
↓Gentamycin-induced kidney damage
↑Renal function
↑Kidney antioxidant levels
↓Kidney MDA
Changizi-Ashtiyani et al52
Water extract 250, 500 mg/kg (i.g.); 30 min Rat:
↓Ethanol- and indomethacin-induced gastric mucosa damage
↓Basal gastric secretion + acidity
↓Depletion of gastric wall nonprotein sulfhydryls
Al Mofleh et al53
500, 750 mg/kg/d (i.g.); 15 d Rat (Lead exposure during weaning):
500: ↓kidney LPO
750: ↑kidney catalase
NE: creatinine, urea
Amina and Nadia54
Hexane extract 100, 200 mg/kg/d (i.p.); 3 d ↓CCl4-induced liver damage
↓Serum ALT + LDH
↑Serum TBARS + GSH
Jamshidzadeh et al46
Wound healing Alcohol extract 10% topical cream, 21 d Rat:
↑Incision-induced wound contraction + scar-healing + reepithelization
↑Tissue maturity + remodeling
↓Inflammation + oxidative stress
Hashemnia et al55
Fruit polysaccharide fraction 5-mg/mL topical hydrogel, 7 d Mouse:
↑Laser-induced wound contraction
↑Collagen deposition
↑Reepithelization
↑Hydroxyproline content dermal cells
↓Inflammation
Ghlissi et al56
Miscellaneous EO 200, 400 mg/kg/d (i.g.); 15 d Mouse:
↓E2-induced PCOS ovarian cysts
↓E2-induced alterations in serum LH + E2
↓Abnormalities of ovarian primary, secondary + Graafian follicles + corpus luteum
Mahood57
Water extract 20–40 mL/L of 6% extract drinking fluid Chick:
↓Infectious bursal disease
NE: infectious bronchitis, Newcastle disease
Durrani et al58
0.5, 1.0 g/kg (i.g.); 13 d Rat (weaning):
↑Milk yield
↑Pup wt
Hosseinzadeh et al59
0.25–2.0 g/kg/d (i.g.), 2 wk Rat (normotensive:
↓SBP
Rat (spontaneous hypertensive):
↓SBP
Pontes et al60
Alcohol extract 0.5, 1.0 g/kg (i.g.); 13 d Rat (weaning):
↑Milk yield
↑Pup wt
Hosseinzadeh et al59
Fruit powder 10% w/w diet
24 h, 7 d
Rat:
24 h: ↓free triiodothyronine
NE: triiodothyronine
7d ↑triiodothyronine
NE: free triiodothyronine
Parvinroo et al61
7.5% w/w diet
12 wk
Rat:
↓E2-induced mammary cell proliferation
↓Circulating E2 + prolactin
NE: mammary ERα + CYP1A1/CYP1B1
Aqil et al62
10% w/w diet
3 mo
Lamb:
↑n-3 PUFA content
↑Oxidative stability
↑Sensory attributes
↓Meat atherogenic values
Bhatt et al63
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; BW, body weight; CA1, CA1 region of hippocampus; CA3, CA3 region of hippocampus; CCl4, carbon tetrachloride; CYP, cytochrome P-450; E2, estradiol; ERα, estrogen receptor-alpha; FBG, fasting blood glucose; FSH, follicle-stimulating hormone; GABA, gamma aminobutyric acid; GPx, glutathione peroxidase; GR, glutathione reductase; GSH, reduced glutathione; GST, glutathione-S-transferase; HDL, high-density lipoprotein cholesterol; i.g., intragastric; i.p., intraperitoneal; LDH, lactate dehydrogenase; LDL, low-density lipoprotein cholesterol; LH, luteinizing hormone; LPO, lipid peroxides; MDA, malondialdehyde; NAFLD, nonalcoholic fatty liver disease; NE, no effect; NFBG, nonfasting blood glucose; NO, nitric oxide; PCOS, polycystic ovary syndrome; PTZ, pentylenetetrazol; PUFA, polyunsaturated fatty acids; SBP, systolic blood pressure; SI, serum insulin; SOD, superoxide dismutase; TBARS, thiobarbituric acid reactive substances; TC, total cholesterol; T, testosterone; TG, triglycerides; wt, weight.

Aniseed administration was investigated for preventing tissue damage due to diverse toxic insults.46–54 Results were inconsistent, possibly due, in part, to the specific aniseed fraction evaluated, different animal models and dosing regimens used, and the varied target organs and tissues assessed. In contrast, in animal models, trans-anethole protected against damage from multiple agents toward the liver, lung, and GI tract.71–79

Finally, compared with either agent alone,80 combining trans-anethole with the nonsteroidal anti-inflammatory drug ibuprofen produced synergistic suppression of inflammation in rats, suggesting that characterizing the targets for this synergism is warranted. In regard to female disorders, only a single animal study is available.57 It reported improvement in polycystic ovary syndrome symptoms and ovarian pathology after intragastric dosing of high levels of aniseed essential oil.

MECHANISMS

In animal models and in vitro assays, a variety of potential mechanisms of action were examined to understand aniseed's and trans-anethole's purported anticancer, anti-inflammatory, antidiabetes, and anti-neurodegenerative effects. The number of potential mechanisms is many, and the involvement of specific biological processes in improving outcomes depends on the animal disease model under investigation. General examples of some of these actions include altering the tissue expression and circulating levels of cytokines and chemokines, as well as of enzyme catalysts and chemical inhibitors of oxidative stress. Administration of aniseed and its constituents can alter hormone homeostasis. Complex and dose-dependent effects on transcription factors and cell-signaling pathways that control numerous physiological processes also were reported.5,81–84 Compared with animals, these processes in humans are generally unexplored.

SAFETY

Aniseed and aniseed oil are listed as generally recognized as safe by the US Food and Drug Administration (21 CFR 182.10, 182.20) when used at typical levels in foods.2 An expert panel of the Flavor and Extract Manufacturers Association determined a possible average daily intake value for aniseed that represents an exposure amount generally considered to be safe. For aniseed and anise oil, the amounts are 330.5 and 46.4 mg, respectively.85 According to Flavor and Extract Manufacturers Association data,85 usual amounts of anise oil present in several food categories (in parts per million [ppm]) include 426 ppm in alcoholic beverages, 162 ppm in baked goods, 182 ppm in chewing gum, 39 ppm in gelatin and puddings, 497 ppm in hard candy, and 510 ppm in soft candy.

Trans-anethole also is considered generally recognized as safe by the Flavor and Extract Manufacturers Association based on its typically low level of use as a flavoring agent (54 μg/kg/bw per day).86,87 Likewise, the Joint FAO/WHO Expert Committee on Food Additives determined that trans-anethole has no safety concerns at current levels of intake as a flavoring agent. The US Food and Drug Administration recommended an acceptable daily intake level for trans-anethole of 0 to 0.6 mg/kg/bw,14 and an acceptable daily intake value of 0 to 2 mg/kg/bw was recommended by the Joint FAO/WHO Expert Committee on Food Additives.88

Potential Toxicity

Excessive doses or frequency of intake of aniseed can produce adverse effects. For example, human ingestion of as little as 1 to 5 mL of aniseed essential oil can induce nausea, vomiting, and pulmonary edema.4 Seizures were temporarily induced in a 12-day-old infant who received multiple doses of undiluted aniseed oil by the parents as treatment for colic.89 A case report90 described severe coagulopathy, nonketotic hyperglycemia, and neurological symptoms in a 4-month-old infant treated for colic with a water extract of star anise and anise for 2 months. It should be noted that use of star anise in foods and folk medicines can be problematic if “false star anise” or Japanese star anise is mistakenly ingested. The dried fruit of Chinese star anise is a popular, widely used culinary ingredient. However, the dried fruit of Japanese star anise (or shikimi fruit) is similar in morphology to the Chinese plant but contains potent neurotoxins. Japanese star anise can be inadvertently ingested because of mistaken identity with Chinese star anise or when adulterated batches of Chinese star anise are used in food preparation. Digestion of false star anise has been associated with serious adverse events such as diarrhea, hallucinations, vomiting, and convulsions91–93

Aniseed may cause allergic reactions. Caution is warranted for those with hypersensitivity to trans-anethole, aniseed, or other spices in the Apiaceae family. Contact dermatitis and pulmonary distress after occupational exposure to trans-anethole and aniseed as well as consumer exposure to skin creams and oral health products were reported.94–102

Animal studies and in vitro assays indicate that aniseed oil and trans-anethole can affect circulating hormone levels and exhibit hormonelike activity, although results are not entirely consistent. For example, estrogenic effects and alterations in circulating testosterone and pituitary hormones were reported.3,13,43,57,61,62,82,103,104 In some cases, these changes were associated with lower sperm counts in male rats. An antifertility action also was observed in female rats administered oral anethole (50–80 mg/kg), although additional experimental confirmation of this is lacking.10,105 The relevance of these hormonelike actions to humans is unclear because the amounts typically consumed by humans in foods are lower. The relationship of extended use or higher intakes of aniseed on hormonal status and hormone therapies needs to be better understood.

The therapeutic use of anise alone is not supported by human clinical studies.13 Nonetheless, aniseed has a long history of use as a folk remedy during pregnancy, childbirth, and lactation and is considered safe when used at recommended dosages based on historical practices.3,8,10,87 Summaries of these traditional medicine usages are available from the European Medicines Agency describing dosing and restrictions.11–13 The range of doses recommended in these traditional remedies is broad. An example of usual preparation of an herbal tea is 1 to 3.5 g of crushed aniseed in 150-mL water, 3 times daily. Yet, clinical data examining dose-related effects on pregnancy of aniseed alone or in a mixture of plant materials are lacking. In 2 systematic reviews, long-term herbal remedy use among pregnant women in multiple countries was deemed safe for use during pregnancy as determined by the authors' analysis of the relevant literature, references and textbooks, and monographs.106,107 In contrast, a recent review108 concluded that any essential oil constituents present in the mother's circulation can be expected to reach the fetus and exert some level of potential adverse effect. In light of the lack of clinical evidence on reproductive toxicity of potentially harmful oil constituents, including trans-anethole, the author advised avoiding or restricting the use of these compounds and oils. Aniseed also is recommended in traditional therapies as a galactagogue, although no scientifically valid human studies have directly addressed the relationship between the amount and form of aniseed consumed and subsequent milk production. An herbal tea containing multiple herbs including aniseed consumed by exclusively breastfeeding mothers was reported in a small, manufacturer-sponsored, double-blind RCT to cause no adverse effects in their infants, compared with those women consuming lemon verbena tea.109 In this study, each tea bag contained 350-mg anise fruit and participants were requested to drink 3 to 5 cups per day. However, the amount of aniseed phytochemicals transferred to such teas and how much subsequently might be transferred in mother's milk are not known. In this regard, a recent study110 quantitated amounts of select phytochemicals transferred from raw plant materials to an herbal tea. For aniseed, 2 g of plant material containing 4.9 mg of trans-anethole was boiled in 250 mL (1 cup) of water for 5 minutes. In the resulting tea, a total of 1.5 to 1.6 mg of trans-anethole was available for consumption. It is known that trans-anethole is transferred to human milk when ingested by breastfeeding mothers, albeit in small amounts relative to the amount consumed.18 Concerns were raised about the safe use during lactation of herbal medicines and herbal teas that contain Apiaceae family herbs such as fennel and anise.111,112 The European Medicines Agency advised, in light of the absence of sufficient safety data, that the use of aniseed oil and alcohol extracts during pregnancy and lactation is not recommended, although aqueous extracts were allowed based on extensive traditional use. However, clinical data are lacking.11,13 Shortcomings in methodologies of completed clinical trials that examined aniseed as a complementary remedy for lactation have been discussed.113 In general, these concerns include lack of randomization, blinding, and controls, and small numbers of participants.

Drug Interactions

Reports from animal studies and in vitro assays indicate that aniseed and trans-anethole interact with drug-metabolizing enzymes. For example, a human equivalent dose of aniseed oil (0.3 mg/kg) administered to mice increased the analgesic effect of codeine, increased diazepam- and midazolam-induced motor impairment, altered the antidepressant action of imipramine and fluoxetine, and decreased pentobarbital-induced sleeping time.37 In another study, an opposite effect on pentobarbital-induced sleeping time occurred when the aniseed oil (50 mg/kg) was simultaneously injected (intraperitoneal) during pentobarbital dosing.114 Oral administration of aniseed oil to mice (0.3 mg/kg/d) for 5 days changed the bioavailability and pharmacokinetics of acetaminophen and caffeine.115 In a study with human liver microsomes,116 an alcohol extract of aniseed activated cytochrome P-450 2C9, suggesting that aniseed has the potential to alter the fate of medications metabolized by this enzyme. Examples of such drugs include the antiepileptic phenytoin, the anticoagulant warfarin, the angiotensin-II blocker losartan, and nonsteroidal anti-inflammatory drugs. The authors noted that this may be a particular concern for medications, such as warfarin, that have a narrow therapeutic index. In this regard, aniseed was identified as a possible naturally occurring coagulation inhibitor that may be capable of interacting with warfarin.117,118 The magnitude of any dose-response interactions of aniseed with drug metabolism is not well established and has, to date, not been confirmed in humans. In light of this preliminary evidence, additional scrutiny of any possible drug interactions after intake of different forms of aniseed is needed, and caution may be warranted for those consuming higher levels of trans-anethole–containing foods, beverages, or traditional remedies. This is an area that warrants additional research and clarity of evidence-based recommendations. Of note, aniseed supplements are available that, in some cases, recommend doses of up to 1350 mg/d.

SUMMARY AND CONCLUSIONS

Aniseed is widely used and considered safe when consumed in amounts normally encountered as a flavoring agent in diverse foods and beverages. Aniseed and its essential oil have an extensive history of inclusion in herbal remedies for a variety of health conditions. However, caution regarding medicinal use of higher amounts of aniseed is warranted for susceptible individuals such as pregnant and lactating women and infants. Thus, to provide evidence-based recommendations, clinical studies from high-quality RCTs are needed that clarify the bioavailability of the phytochemicals consumed in aniseed powder, oil, and extracts; that characterize dose-related and duration-associated physiological responses to aniseed intake; and that better illuminate potential adverse effects for individuals with a variety of health conditions.

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