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THE EFFECT OF FENNEL (FOENICULUM VULGARE) Irina Alexandrovich, MD, Olga Rakovitskaya, MD, Elena Kolmo, MD, Tatyana Sidorova,MD, Sergei Shushunov, MD Irina Alexandrovich, MD, Department of Pediatrics, St.
of colic in the treatment group compared with the control group Petersburg Medical Academy of Postdoctoral Education,
[Absolute Risk Reduction (ARR) = 41% (95% CI 25 to 57), Number St. Petersburg, Kirochnaya, Russia. Olga Rakovitskaya, MD,
Needed to Treat (NNT) = 2 (95% CI 2 to 4)]. Side effects were not Department of Pediatrics, St. Petersburg Pediatric Medical
reported for infants in either group during the trial. Academy, St. Petersburg, Litovskaya, Russia. Kolmo EA,
Conclusion • Our study suggests that fennel seed oil emulsion is
MD, Department of Pediatrics, St. Petersburg Medical
superior to placebo in decreasing intensity of infantile colic. Academy of Postdoctoral Education. Petersburg,
Kirochnaya, Russia. Tatyana Sidorova, MD, Department of
Pediatrics, St. Petersburg Medical Academy of Postdoctoral
Education, St. Petersburg, Kirochnaya, Russia. Sergei
Shushunov, MD, Department of Pediatrics, University of
Illinois College of Medicine at OSF St. Francis Medical
Infantile colic is a frequent cause for visits to a pediatri- cian and to the emergency room. Despite its benign,natural course, colic carries a substantial psychological,emotional, and physical burden for parents. Infantile Center, Peoria, Illinois.
colic can lead to unnecessary hospitalizations, interfere with parent-child bonding, cause strain in a marriage, and in Context • Despite its benign, natural course, colic is a significant
problem in infants and imparts a psychological, emotional, and The purpose of this study was to evaluate the clinical efficacy physical burden to parents. Dicyclomine hydrochloride is the only of a standardized preparation of fennel. We hypothesized that pharmacological treatment for infantile colic that has been consis- infants with colic who received fennel seed oil emulsion would: tently effective. Unfortunately, 5% of infants treated with dicy- 1. Have significantly shorter cumulative crying, and clomine hydrochloride develop serious side effects, including 2. Relief of colic symptoms at a rate greater than infants death. Fennel seed oil has been shown to reduce intestinal spasms and increase motility of the small intestine. However, there havenot been any clinical studies of its effectiveness. Background
Objectives • To determine the effectiveness of fennel seed oil
Infantile colic is a self-limiting condition of undetermined etiology. Various mechanisms of colic, including food allergies, Design • Randomized placebo-controlled trial.
formula intolerance, immaturity of gastrointestinal (GI) tract, Settings • Two large multi-specialty clinics.
excessive gas formation, and intestinal cramping, have been Subjects • 125 infants, 2 to 12 weeks of age, who met definition of colic.
hypothesized, but none of them proven. It is possible, that the Intervention • Fennel seed oil emulsion compared with placebo.
etiology of colic is multifactorial. Since colic does not carry a Outcome measure • Relief of colic symptoms, which was defined
biological marker, diagnosis of colic is clinical and is usually as decrease of cumulative crying to less than 9 hours per week. made when an infant meets Wessel criteria: crying for 3 hours Results•The use of fennel oil emulsion eliminated colic, according
or more a day, for at least 3 days a week.2 Wessel criteria, first to the Wessel criteria, in 65% (40/62) of infants in the treatment published in 1954, remains the most widely-used measure to group, which was significantly better than 23.7% (14/59) of infants diagnose colic, despite the fact that the validity of Wessel crite- in the control group (P<0.01). There was a significant improvement The typical therapeutic interventions offered to parents fall into 1 of 4 categories: dietary, physical, behavioral, and Reprint requests: InnoVision Communications, 169 Saxony Rd, Suite 104, Encinitas, CA 92024; pharmacological. Many dietary interventions have not proven phone, (760) 633-3910 or (866) 828-2962; fax, (760) 633-3918; e-mail, alternative.therapies@innerdoorway.com. to be effective. Use of hypoallergenic formulas may offer help ALTERNATIVE THERAPIES, July/AUG 2003, VOL. 9 NO. 4 The Effect of Fennel Seed Oil Emulsion in Infantile Colic to some patients.4 Physical and behavioral interventions haveproven to be ineffective and impractical.5-8 Pharmacological compounds used to treat colic include phenobarbital, alcohol,sedatives, simethicone, dicyclomine, and others. Only dicy-clomine hydrochloride, an anticholinergic agent with antispas-modic activity, has been consistently effective in treating infantile Excluded (n = 24) Parents refusedto participate colic. Unfortunately, 5% of treated infants develop side effects,including breathing difficulties, muscular hypotonia, apnea,seizures, syncope, asphyxia, and coma. Several cases of death have been reported in infants taking dicyclomine,9,10 making thiscompound unpopular among pediatricians.
Various carminative plants have been used to relieve infantile colic, including catmint, chamomile, lemon balm, Allocated to standard intervention Allocated to placebo intervention dill, caraway and fennel. Among these plants, fennel is the most frequently recommended. The beneficial effect of fennel is attributed to its volatile oil (the highest concentration of which is found in seeds). Animal experiments have demon- Did not receive standard intervention Did not receive placebo intervention strated that fennel seed oil reduces intestinal spasms and increases motility of the small intestine.11, 12 Although theseanimal studies are old, they are important to our understand-ing of the physiologic effect of fennel. This effect of fennelseed oil on GI smooth muscle shown in animal studies poten-tially explains the beneficial effect of fennel in infantile colic. Because over-the-counter (OTC) preparations of fennel are not standardized to have a consistent concentration of fen- nel seed oil, the inconsistency in the concentration of oil makes it difficult to obtain an effective and reproducible response. This factor may explain why only 1 clinical studyhas supported the use of fennel for infantile colic.13 The prepa-ration in our study was a stable emulsion of 0.1 % of fennelseed oil in water with an addition of emulsifying agent. Institutional review boards at all settings approved this trial.
We conducted a double blind, randomized, placebo-controlledtrial to determine the therapeutic effect of fennel seed oil prepa- Figure 1 Flow Diagram of Subject Progress Through the
ration on infants with colic. A total of 125 infants, ranging in age from 2 weeks to 12 weeks, diagnosed with colic, wereenrolled in our study at 2 large multi-specialty clinics of Kalinindistrict of St. Petersburg, Russia. Infants were included in thestudy if they met the criteria offered by Wessel et al, which received a water emulsion of 0.1% fennel seed oil and 0.4% defined colic as a period of unexplained irritability; agitation; polysorbate-80. The control group [26/59 (44%) males and and crying, lasting longer than 3 hours per day and at least 3 33/59 (56%) females] received a placebo, which consisted of days per week, and continuing for more than 3 weeks in 0.4% polysorbate in water. The fennel preparation and the severe cases.2 Excluded from the study were premature placebo appeared identical on visual examination and were bot- infants; infants with chronic or acute illnesses; infants gain- tled in plastic 6 oz (180 mL) nursing bottles by a laboratory ing less than 30 grams a day over a period of 1 week prior to technician. Randomization was achieved by a computer-gener- the study; infants who received any medication; and infants ated number using Microsoft Excel (Microsoft, Redmond, WA). with an estimated cumulative crying time of less than 9 hours There was no significant difference between the 2 groups per week. Infants enrolled into the study were not tested for according to gender, age, birth number, hours spent crying, and milk allergy, and continued their diets. The infants were indi- the feeding method. (Table 1) The treatment group of 65 infants vidually randomized into 2 groups. (See Figure 1.) The treat- received fennel seed oil emulsion. The control group of 60 infants ment group [29/62 (47%) males and 33/62 (53%) females] received placebo. A pharmacist dispensed both the fennel prepa- The Effect of Fennel Seed Oil Emulsion in Infantile Colic ALTERNATIVE THERAPIES, JULY/AUG 2003, VOL. 9, NO. 4 59 ration and the placebo into quantities sufficient to last one week.
his parents failed to complete the diary. Because of a reloca- The pharmacist was unaware of which parents received the prepa- tion, 2 infants (twins) in the treatment group were lost to fol- ration. Parents were instructed to administer a minimum of 5 mL low-up. One infant in the control group was withdrawn from and a maximum of 20 ml of either fennel seed oil emulsion, or the study because of a severe cold. No difference was found placebo up to 4 times a day, orally before meals, and at the onset of between the 2 groups in frequency and volume of consumed colic episodes. In addition, parents were instructed to limit con- fennel seed oil emulsion or placebo (Table 2). There was no sumption to about 12 mL/kg/day, which would provide about 12 significant difference in cumulative crying between the 2 mg/kg/day of fennel seed oil. This amount of oil has been shown groups prior to the trial, but there was a significant decrease in animal experiments to be well below the toxic levels and was in cumulative crying in infants in the treatment group. based on our observations that infants have different degrees of There was a significant improvement of colic in the treat- acceptance of the emulsion and tend to take variable quantities of ment group compared with the control group. The use of fen- the emulsion during the day. This limited consumption effectively nel oil emulsion, based on the Wessel criteria,2 eliminated decreased the daily dose variability.
colic in 65% (40/62) of infants in the treatment group, which Neither the observing pediatrician, nor parents were aware of was significantly better than 23.7% (14/59) of infants in the the content of the bottles. Each family received a diary with control group (P<0.01) (Table 2). [Absolute Risk Reduction instructions to enter data on a daily basis of all episodes of colic, (ARR) = 41% (95% CI 25 to 57), Number Needed to Treat number of night awakenings, amount of consumed emulsion or (NNT) = 2 (95% CI 2 to 4)]. NNT is 1 of many ways to repre- placebo, and frequency of administration. All episodes of infant sent the results from clinical trials. NNT is an expression of crying lasting longer than 15 minutes were recorded, and cumula- the number of patients a clinician would need to treat to pre- tive crying for a week was calculated. Diaries were entered for 21 vent 1 additional adverse outcome or attain 1 additional bene- days: 7 days prior to the trial, during the 7-day trial, and 7 days fit. The NNT is calculated as the inverse of the absolute risk after the trial. A pediatrician examined each child prior to, during, reduction. For the purposes of this research, these results sug- and after the trial. The data were entered into a computerized gest that a physician would need to treat between 2 to 4 spreadsheet by a blinded researcher. Significance between the infants with fennel seed oil for the 7-day period to show a groups was assessed using the Student t-test. P value less than 0.05 reduction in colic symptoms using Wessel criteria. was considered significant. Continuous variables were reported as The ARR is the difference between the proportion of events in mean ± 1 standard deviation. Relief of colic symptoms was defined the control group and the proportion of events in the intervention as reduction of cumulative crying to less than 9 hours a week. group; or for this research, the difference in the risk of the outcome(reduction in the symptoms of colic) between children treated with fennel seed oil and those receiving placebo. The ARR is commonly A total of 121 infants completed the study. One infant in conceptualized as the absolute benefit of an intervention. For this the treatment group was withdrawn from the study because research, 41% of infants were spared the outcome of continued colic TABLE 2 Results in Fennel Treatment and Control Groups of
TABLE 1 Characteristics of Fennel Treatment and Control Groups
Treatment
Control Group
Statistical
Treatment Group Control Group Statistical
Criteria
Significance
Criteria
Group n=62
n=62
n=59
Significance
* Relief of Colic Symptoms is defined as decrease of cumulative crying to less than 9 hours ALTERNATIVE THERAPIES, July/AUG 2003, VOL. 9 NO. 4 The Effect of Fennel Seed Oil Emulsion in Infantile Colic as a result of having received fennel seed oil.
A significant placebo effect was observed in our study, Side effects were not noted in infants in either group dur- and was comparable to the placebo effect reported by Weizman et al in their study.13 The authors speculated that thecontrol group mothers received the same amount of attention Discussion
as mothers of the treatment group; but, control group moth- This was the first clinical study to demonstrate that stan- ers received more attention than would be expected had their dardized fennel seed oil emulsion is effective in reducing the children not participated in the study. This may support pre- intensity of infantile colic. Although favorable results have been vious observations that there could be a link between colic reported in animal studies, there is a lack of clinical research in and the psychological state of the mothers. Such a finding pro- the use of fennel seed oil emulsion to effectively treat infantile vides indirect support for the hypothesis that a vicious circle colic. The postulated mechanism in the pathogenesis of colic plays a role in the pathogenesis of colic in which the infant’s may be a spasm of the intestinal smooth muscles. The therapeu- crying leads to a negative emotional response from the moth- tic effect of fennel seed oil may be secondary to a spasmolytic er, which in turn, aggravates the symptoms of colic. It would action. The spasmolytic action of fennel seed oil may be be interesting to know if improvement of colic with effective explained by the similarity of the chemical structure of anethole, treatment leads to a corresponding positive change in the which is the main ingredient in fennel seed oil to dopamine. This emotional status of infants’ mothers.
similarity may result in the binding of anethole to dopaminergic Our experience suggests that fennel seed oil emulsion is receptors. The fennel plant has a complex mix of chemicals, superior to placebo in reducing the intensity of infantile colic. many of which are biologically active. The content of biological-ly-active compounds fluctuates from 1 batch of raw material to Acknowledgments
another. A standardized fennel preparation guarantees that This study was supported by institutional funds. The fennel seed oil emul- these biologically-active compounds are present in a fixed con- sion and placebo were provided by Lev Laboratories (Glencoe, IL). Theauthors extend their thanks to Dr Al Torres for his editorial input.
centration. The safety of fennel seed oil emulsion has not beendocumented. However, it has been shown that undiluted fennel References
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The Effect of Fennel Seed Oil Emulsion in Infantile Colic ALTERNATIVE THERAPIES, JULY/AUG 2003, VOL. 9, NO. 4 61

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