Objectives and Study hypothesis
Based on the contextual information provided, the primary aim of this research endeavor is to assess the impact of a customized intermittent fasting regimen on various anthropometric parameters, namely BMI, FFM, body fat mass, and waist circumference. Additionally, the study aims to investigate the influence of this dietary intervention on appetite, food cravings, and eating habits among women who are classified as obese or overweight.
It is postulated that individuals who are categorized as obese or overweight are likely to exhibit elevated levels of appetite, disordered eating behaviors, and food cravings. It is hypothesized that implementing a modified intermittent fasting diet would be particularly beneficial for this specific population, offering substantial support in addressing these concerns.
Design
This research constitutes a randomized controlled parallel-group trial aimed at comparing the impact of a modified intermittent fasting diet and a daily calorie restriction diet on various factors including appetite, food cravings, eating behavior, and anthropometric indices in women who are classified as either overweight or obese. The research endeavor will be implemented at Shahid Beheshti Hospital situated in Kashan. The trial will be administered individually under the direction of the principal investigators. The scientific committee will assume the responsibility of supervising the study, particularly during instances of adverse events or when necessary. Kashan University of Medical Sciences will exercise oversight over the comprehensive execution of the trial. The study team will convene on a weekly basis to address and discuss any operational challenges encountered during the study. Given the limited number of patients involved in a single center, the inclusion of a Data Monitoring Committee (DMC) is deemed unnecessary. The selection of participants for this study will be carried out through random sampling from the Health Centers affiliated with Kashan University of Medical Sciences. The study will span a duration of 8 weeks. The participants will be allocated randomly into two groups, namely the daily calorie restriction group and the fasting group, based on specific criteria for inclusion and exclusion. The research protocol for this study has been granted approval by the Ethics Committee of Kashan University of Medical Sciences under the reference number IR.KAUMS.MEDNT.REC.1401.002, and it has also been registered with the Iranian Registry of Clinical Trials under the identifier IRCT20220522054958N2. Prior to the implementation of any study-related procedures, all participants will be required to provide written consent. In this study protocol, we employed the SPIRIT reporting guidelines. [16].
Study population
To conduct this study, we need to determine the sample size based on the waist-to-hip circumference ratio data of a previous study. In that study, the mean and standard deviation of waist-to-hip circumference ratio were 0.96 and 0.05 in the intervention group, and 0.99 and 0.02 in the control group. Taking into account a power of 80% and alpha error of 5%, we will need 27 women in each group. A total of fifty-four individuals will be recruited from the Health Centers affiliated with Kashan University of Medical Sciences, utilizing a simple random sampling technique in accordance with predefined inclusion and exclusion criteria. The eligible participants will be carefully matched based on their age and BMI, and subsequently allocated to either the "modified intermittent fasting" group or the "daily calorie restriction" group. Due to the interventional nature of the study, blinding procedures will not be implemented (Fig. 1).
Inclusion and exclusion criteria
The inclusion criteria for this study pertain to women aged between 18 and 50 years who fall within the overweight or obese category, with a BMI ranging from 25 to 40. On the other hand, the exclusion criteria include factors such as pregnancy or breastfeeding, the presence of chronic metabolic conditions like diabetes, the existence of cardiovascular disorders such as coronary heart disease and hypertension, gastrointestinal disorders, recent weight loss of at least 1 kg within the past three months, smoking or alcohol abuse, adherence to a specific diet or use of specific medications that may interfere with the trial process, as well as the presence of mental or psychological disorders. Furthermore, the predetermined criteria for terminating assigned interventions for participants in the trial encompass several factors. These factors include deviations in calorie intake that fall below 80% or exceed 110% of the recommended caloric intake, experiencing severe emotional distress throughout the course of the study, engaging in smoking or alcohol consumption, participant unwillingness to continue cooperation or non-adherence to the prescribed diet, presence of chronic conditions such as hypertension, cardiovascular disease, diabetes, or gastrointestinal ailments, and the occurrence of pregnancy or breastfeeding during the study period.
Study variables
The primary outcomes of this study revolves around examining the variations observed between the interventional groups in terms of alterations from baseline levels in several key variables. These variables include the Visual Analog Scales (VAS) for appetite, the Food Craving Questionnaire (FCQ), the Dutch Eating Behavior Questionnaire (DEBQ), BMI, and Fat-Free Mass (FFM). As secondary outcomes, the study will also explore changes in waist circumference and body fat mass.
Interventions
The schematic representation of the intervention procedure in this study is presented in Fig. 2. A total of 54 participants will be recruited from the Health Centers affiliated with Kashan University of Medical Sciences, utilizing a Simple Random Sampling method that adheres to the predefined inclusion and exclusion criteria. Following the baseline assessments, participants will be assigned to either the "modified intermittent fasting" group (intervention) or the "daily calorie restriction" group (control). Throughout the duration of 8 weeks, all participants will be instructed to adhere to their prescribed diet plan, which will be tailored to their respective group assignment and daily energy requirements. The estimation of individual energy requirements will be carried out using the Mifflin equation [17]. Both intervention groups will adhere to specific dietary compositions, with daily intake comprising 55% carbohydrates, 30% fat, and 15% protein in relation to their energy requirements. The modified intermittent fasting approach will entail alternating cycles of feeding and fasting, following an every-other-day pattern. On fasting days, participants will consume only 25% of the recommended calorie intake, while on feeding days, they will consume 100% of their calculated daily energy requirements. To ensure consistency, all fasting meals will be consumed as lunch between 12 pm and 2 pm, ensuring that each participant undergoes an equal duration of fasting. During fasting days, participants will have permission to consume non-caloric beverages like water, tea, and green tea, as well as coffee without sugar (limited to < 400 mg caffeine daily). Additionally, non-starchy vegetables such as lettuce, green leaf, cucumber, and tomato will be allowed. Adequate hydration will be encouraged by promoting the consumption of ample water.
On the days designated for feeding, participants will receive a dietary regimen that aligns with 100% of their individualized energy requirements. This regimen will encompass three primary meals and three snack intervals. Participants will be instructed to consume breakfast within the time frame of 6:00 and 8:00, followed by lunch between 12:00 and 14:00, and dinner between 19:00 and 21:00. Additionally, participants will be encouraged to incorporate three snack periods into their daily routine, with the first snack scheduled for 10:00, the second snack for 16:00, and the final snack for 22:00. Contrarily, the group assigned to daily calorie restriction will adhere to a dietary regimen that corresponds to 63% of their total energy requirement on a daily basis. This regimen will also consist of three main meals and three snack intervals. Similar to the modified intermittent fasting group, participants in the daily calorie restriction group will be instructed to partake in breakfast between 6:00 and 8:00, followed by lunch between 12:00 and 14:00, and dinner between 19:00 and 21:00. Additionally, they will be advised to consume their first snack at 10:00, the second snack at 16:00, and the final snack at 22:00.
Both the modified intermittent fasting and daily calorie restriction groups will be required to prepare all of their meals at home. These two groups will strictly adhere to their assigned diets for a duration of 8 weeks. Throughout the study period, participants in both groups will be instructed to maintain their regular physical activity levels. To address any inquiries or concerns, face-to-face and phone consultations will be conducted with a registered dietician. The extent of implementation adherence will be evaluated through the administration of a food record questionnaire every 2 weeks. Participants will be asked to complete this questionnaire for a total of 3 days per week: 2 weekdays and 1 day during the weekend. Adequate adherence will be determined if the calculated total caloric intake of participants falls within the range of 80–110% of the prescribed intake [18]. Participants will be explicitly instructed to refrain from engaging in any activities that could potentially interfere with the study, such as following a specialized diet, consuming specific supplements or medications. Researchers involved in the study will diligently monitor and evaluate any potential adverse events that directly relate to the study intervention. Continuous monitoring of the patients will be conducted. In the event of any adverse events, such as hypoglycemia or headaches, occurring during the study, they will be promptly reported to the Kashan University of Medical Sciences and the Ethics Committee of Kashan University of Medical Sciences. The managing physician will oversee the appropriate management of these events, and the associated costs will be covered by the trial funding.
A comprehensive depiction of the study's design, interventions, as well as the scheduled assessments, can be found in Fig. 1 (participants, interventions, analysis) and Fig. 2 (intervention flow chart). These visual representations provide an organized overview of the study's structure, interventions, and the sequence of evaluations to be conducted.
Assessment of study variables
Analog Scale VAS: Visual
The purpose of employing this questionnaire is to assess the appetite of the participant, encompassing dimensions such as hunger, satiety, satisfaction, and the individual's capacity to consume food. The questionnaire employs a linear scale to capture these variables, with the starting point representing an absence of the attribute under consideration, while the endpoint indicates its maximum extent. The scale is discretized into five distinct states, thereby enabling the quantification of the intensity of an individual's psychological experiences and serving as an indicator of their appetite [1]. The scale utilized in this study aims to assess the daily appetite of each subject by calculating the average score derived from a set of questions completed prior to the three primary meals of the day.
A Food Craving Questionnaire is employed to gauge the intensity of food cravings on a multidimensional scale [19]. The present questionnaire comprises a total of 30 questions, utilizing a 6-point Likert scale that ranges from "never" to "always" for scoring the responses. FCQ encompasses several distinct factors, including: (i) the intention and planning associated with food consumption (e.g., "Food cravings consistently prompt me to strategize ways to obtain the desired food"), (ii) the anticipation of positive reinforcements derived from eating (e.g., "Eating what I crave brings about a sense of improved well-being"), (iii) the anticipation of relief from negative emotional states through eating (e.g., "Satisfying a craving often alleviates my feelings of depression"), (iv) the potential lack of control over eating when succumbing to food cravings (e.g., "If I indulge in what I crave, I frequently lose control and overeat"), (v) thoughts and preoccupation revolving around food (e.g., "When I experience a craving, my thoughts become consumed by the idea of consuming it"), (vi) the perception of cravings as a physiological state (e.g., "I tend to crave food when my stomach is empty"), (vii) the emotions that may be encountered prior to or during food cravings or eating (e.g., "My emotions frequently trigger a desire to eat"), (viii) environmental cues that may trigger food cravings (e.g., "Being in the presence of someone eating often stimulates my appetite"), and (ix) the experience of guilt resulting from food cravings (e.g., "Indulging in my cravings often leads to feelings of guilt and self-reproach"). Elevated scores on the questionnaire will signify a greater propensity for food cravings in the individual being assessed, while lower scores will indicate a lesser inclination towards such cravings [20].
Eating behavior
In order to assess eating behavior, DEBQ will be administered, consisting of a total of 33 questions. The questionnaire comprises three distinct subscales: emotional eating (relating to the consumption of food as a means of coping with negative emotions), external eating (associated with the consumption of food in response to external cues such as the aroma or visual stimuli), and restrained eating (pertaining to behaviors aimed at restricting food intake). The responses to these questions are measured on a 5-point Likert scale, ranging from 1 (never) to 5 (most of the time). The utilization of norms, Cronbach's alpha coefficients for internal consistency, and Pearson's correlation coefficients to evaluate interrelationships among the scales demonstrate that the subscales exhibit strong internal consistency and factorial validity [21].
Physical activity scale
The physical activity questionnaire employed in this study relies on the concept of metabolic equivalents (METs) to assess participants' physical activity levels. The questionnaire encompasses nine distinct activity levels, ranging from sleep and rest to high-intensity activities, with each level corresponding to a specific range of MET values, where lower MET values indicate lower intensity and higher MET values indicate higher intensity of physical activity [22].
Anthropometric indices
Height measurements will be obtained using a stadiometer with an accuracy of 0.5 cm. The weight of individuals, while wearing light clothing and without shoes, will be measured using a scale with an accuracy of 0.1 kg. Body Mass Index (BMI) will be calculated by dividing the weight in kilograms by the square of the height in meters. The waist-to-hip ratio will be determined by dividing the waist circumference by the hip circumference. Waist circumference will be measured at the midpoint between the iliac crest and the lowest rib, using a non-stretchable measuring tape, while the individual is in a state of normal expiration [23]. Additional anthropometric measures, including skeletal muscle mass and soft lean mass will be assessed using the Inbody770 model BPM040S12FXX. These anthropometric indices will be measured both at the commencement and conclusion of the study.
Baseline and evaluation visits:
The primary investigators will establish communication with potential candidates identified through health center consultations, inviting them to participate in the study. Subsequently, an interview will be scheduled with each participant, during which the study's objectives will be thoroughly explained. Participants will be provided with detailed information and, if they express their willingness to participate, they will be invited to sign the informed consent form. In order to monitor and assess participants' compliance with the prescribed diet, food record questionnaires will be administered at biweekly intervals. These questionnaires will be completed for a total of 3 days per week, consisting of two regular weekdays and one non-consecutive day. To provide ongoing support and motivation, researchers will maintain regular communication with participants through phone calls and visits, reinforcing the study protocols and encouraging adherence. Additionally, participants will be subject to regular monitoring via weekly phone interviews. In the event that participants discontinue or deviate from the intervention protocols for any reason, their data will still be included in the analysis using an intention-to-treat approach.
Statistical analysis
The outcomes will be presented as the mean ± standard deviation for quantitative variables, while frequency distribution will be used for qualitative variables. The normality of the data will be assessed using the Kolmogorov-Smirnov test. A chi-square test will be employed to compare qualitative data between the two groups. Differences in quantitative data between groups will be examined using an independent t-test. In cases where non-parametric assumptions are violated, the Wilcoxon test and paired t-test will be utilized to compare the means of quantitative variables within the group before and after the intervention, for non-parametric and parametric conditions respectively. The Mann-Whitney test and t-test will be employed to compare the means between the two groups, for non-parametric and parametric conditions respectively.
To assess the disparity in data changes between the two groups at the conclusion of the study, analysis of covariance (ANCOVA) will be employed. Adjusted p-values will be used for each statistical test to investigate the effects of the intervention, employing the Bonferroni correction to account for multiple outcomes. Multiple regression models and ANCOVA will be utilized to determine if specific variables serve as confounders for the treatment effect and if the treatment effect interacts with particular covariates. No interim analyses are planned to be conducted. Statistical significance will be determined by considering a p-value lower than 0.05. The data analysis will be carried out using the SPSS software.