2 2. Material and Methods 2.1. Subjects and Eligibility Criteria. Infants aged 15 to 60 days, exclusively breastfeeding and treated at Instituto de Medicina Integral Professor Fernando Figueira (IMIP), Recife, Brazil, between March 2011 and December 2011, were eligible for the study entry. Infantile colic was characterized according to Wessel et al. [3] criteria: paroxysmal attacks of irritability, restlessness, or crying for at least three hours a day, and occurring more than three days a week for a period of three weeks. Complete physical examination was performed on all infants routinely to exclude other possible crying reasons. Exclusion criteria were illiterate mothers, living outside the metropolitan region of Recife, prema- turity or low birth weight (<2,500 g), failure to thrive, gastrointestinal disorders, and currently infectious, allergic or metabolic disease. Children were also excluded if they were receiving some type of treatment (drug, herbal products or chiropractic manipulation). Primary outcomes were evaluated by mother’s opinion about responses to the treatment, number of daily episodes of colic, and time spent crying, measured by a chronometer. Secondary outcomes were number of milk regurgitation, vomiting, diarrhea, constipation, and drowsiness. All children’s parents signed the consent form. This study was approved by the Ethical Committee in Research at IMIP (CEP/IMIP, number/09). 2.2. Study Intervention. This study was carried out using a crossover double-blind design. Each child underwent an intervention for 14 days. The infants were ﬁrstly randomized in two groups to receive formulation of leaves of the Mentha piperita (liquid drops; 1 drop per Kg body weight) or simethicone (liquid drops; 2.5 mg per Kg body weight) daily for a period of 7 days. After the ﬁrst 7 days of study and a period of wash out for 3 days, all the children had their medication alternated and were followed for more 7 days. Repeated visits were scheduled for the seventh and seventeenth days after the ﬁrst visit. On the seventh day visit, the medication was returned to the hospital and another pair of medication were distributed. When patients did not return to the hospital on the seventh day, a home visit was conducted by a researcher. During wash out period, the parents were oriented to use paracetamol for colic treatment. During visits, the infant was clinically examined. Mentha piperita and simethicone were identical in weight, smell, color, taste, and package. The drugs were arranged in numbered pairs, and were randomly designated by letters A or B. All researchers and parents were unaware of the treatment administered. The allocation sequence and randomization list were computer-generated using the “Ran- domized” program (http://www.randomized.com/). Parents ﬁlled out a daily structured form with notes on the number and time of crying episodes, administration of medications, and unintended eﬀects. A chronometer was previously provided to the parents to determine the crying time of their children. In order to determine the sample size, a preliminary trial was performed with 15 children to evaluate the average Evidence-Based Complementary and Alternative Medicine and variance of the diﬀerence in infantile colic frequency between Mentha piperita and simethicone. The sample size calculation was based on the ﬁnding of 50 minutes diﬀerence between groups in reduction of crying time, which was considered a clinically relevant diﬀerence. Considering a signiﬁcance level set at 0.05 and a power of 80% and an estimated standard deviation in groups of 50 minutes, 22 patients would be necessary. Presuming a loss of 30% of the sample, the number was increased to 30 participants. 2.3. Statistical Analysis. The Mann-Whitney and chi-square tests were used to compare continuous variables and cate- gorical variables, respectively. The proportions of patients with eﬀective and ineﬀective responses in each group were compared using the chi-square test. In all comparisons it was provided with a P value <0.05 as statistically signiﬁcant. Data were expressed as means and ranges. All the analysis was performed by SPSS 12 software (SPSS Inc, Chicago, IL). 3. Results Among 313 infants studied, 30 (7.7%) were diagnosed with infantile colic. Three of them were excluded based on the exclusion criteria, and the remaining were randomized. After the beginning of the trial, no parental withdrawal occurred. There was no adverse eﬀect due to the interventions in the present study protocol. 30 infants aged 8 to 56 days (33 ± 11.1) were studied. The average weight and height were 4.650 g (±415) and 54.2 cm (±3.0), respectively. The maternal age ranged from 14 to 32 years (22.7±5.4) and they had 10.4 years (±2.5) of schooling. All mothers had received prenatal care and 16 (53.3%) had undergone cesarean section. At baseline daily episodes of infantile colic were 3.9 (±1.1) and the mean of crying time per day was 192 minutes (±51.6). At the end of the study (17 days) daily episodes of colic fell to 1.6 (±0.6) and the crying duration decreased to 111 (±28) minutes. All mothers reported decrease of frequency and duration of the episodes of infantile colic and there were no diﬀerences between responses to Mentha piperita and simethicone (Table 1). 4. Discussion The prevalence of infantile colic in this study (7.7%) was similar to other studies [1, 7, 8]. The responses to both treat- ments, Mentha piperita and simethicone, did not show statis- tical diﬀerences according to parents evaluation. All parents reported lower frequency and duration of infantile colic in their children during the period of the study. Unintended eﬀects were not observed in this present study. Although there is still some controversy, clinical trials have shown that simethicone, an over-the-counter drug, is safe and helps to control infantile colic [17–19]. We did not ﬁnd studies with the same objectives to ours to compare results. The antispasmodic activity of Mentha piperita has been tested mainly in animals and the spasmolytic eﬀect of peppermint oil on the intestinal musculature appears to involve calcium