The current obesity epidemic is a major public health concern. Many people are looking for effective ways to lose weight, especially after gaining weight during the pandemic. While continuous energy restriction (CER) is a common approach, intermittent energy restriction (IER) strategies like intermittent fasting (IMF) and time-restricted feeding (TRF) are gaining popularity.
This article explores various weight loss strategies, focusing on intermittent energy restriction (IER) methods and comparing them to traditional continuous energy restriction (CER). We will delve into the science behind these approaches, examine their effectiveness, and provide practical tips for implementation.
Understanding the Obesity Epidemic and Traditional Weight Loss Methods
The obesity epidemic is staggering in terms of its magnitude and public health impact. In developed countries, healthy weight individuals (body mass index (BMI) of 18.5-25 kg/m2) are now the minority. Medical spending attributable to overweight and obesity has been estimated to be over 90 billion dollars in the Unites States alone.
Reducing daily calorie intake is the most widely prescribed strategy to induce weight loss. Current guidelines recommend continuous energy restriction (CER; a daily energy deficit of ~500 or 750 kcals, or a 30% restriction from baseline energy requirements), along with a comprehensive lifestyle intervention, as the cornerstone of obesity treatment. On average, this approach produces modest weight loss (5-10% sustained for ≥1 year). The magnitude of weight loss with CER is minimally influenced by variations in diet macronutrient content, especially during long-term follow-up.
Regardless of diet and macronutrient content, adherence to CER typically declines within 1-4 months. As a result, the majority of individuals who lose weight with CER regain significant weight within 1 year. Because of the relative ineffectiveness of traditional CER approaches for achieving and sustaining weight loss, there has been increased interest in identifying alternative dietary weight loss strategies.
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Intermittent Energy Restriction (IER): An Alternative Approach
One such approach is prolonging the fasting interval between meals (i.e., intermittent energy restriction, IER). The premise of this approach is that individuals do not fully compensate during fed periods for the energy deficit produced during extended periods of fasting between eating bouts. Furthermore, these regimens may be easier to adhere to and maintain over time than CER. Finally, IER may lead to metabolic adaptations that favor a greater loss of fat mass, the preservation of lean mass, and a greater ability to sustain weight loss.
Various IER regimens have gained popularity in recent years as strategies for achieving weight loss and other metabolic health benefits. These paradigms involve recurring periods with little or no energy intake (e.g., 16-48 h), with intervening periods of ad libitum food intake. Studies in rodents have demonstrated that IER strategies such as intermittent fasting (IMF; ≥60% energy restriction on 2-3 days per week, or on alternate days) and time-restricted feeding (TRF; limiting the daily period of food intake to 8-10 h or less on most days of the week) exert beneficial effects on the body composition, energy expenditure, and substrate oxidation. However, clinical studies comparing weight loss with IER regimens to traditional CER in adults with overweight and obesity are limited.
Types of Intermittent Energy Restriction (IER)
A major problem in the field is a lack of standardization of terminology to describe different intermittent energy restriction paradigms. Mattson et al. [15,19] have used intermittent fasting as the umbrella term to define “eating patterns in which individuals go extended time periods (e.g., 16-48 h) with little or no energy intake, with intervening periods of normal food intake, on a recurring basis”. They further “distinguish studies of short-term frequent fasting periods from studies of less frequent but longer fasting periods” by using the term periodic fasting (PF) to refer to IMF regimens with periods of fasting lasting from 2 to as many as 21 or more days. The term time-restricted feeding (TRF) is used as a subcategory of IMF to describe “an eating pattern in which food intake is restricted to a time window of 8 h or less every day”. The categorization of TRF as a type of IMF diet is problematic because TRF is fundamentally different from a complete day of fasting or even a modified fast day (generally defined as a day on which individuals consume up to 25% of daily energy needs). As will be discussed below, TRF is simply an appropriate eating pattern (eat during the day and not at night) that humans have veered away form in the past several decades. Rodent studies have shown that reducing the daily eating duration has beneficial effects on weight, body composition, and metabolism. Importantly, these effects are seen even without a reduction in daily energy intake.
Intermittent Fasting (IMF)
Intermittent fasting (IMF) is characterized by recurring periods (e.g., 16-48 h) with little or no energy intake. Many variations have been used to study the effects of IMF on body weight, including:
- Alternate Day Fasting (ADF): Zero calorie intake on fast days.
- Alternate Day Modified Fasting: >60% energy restriction on fast days.
- Fasting or Modified Fasting on Two Days per Week (2DW).
- Periodic Fasting: Fasting for 2 to as many as 21 or more days. This IMF paradigm is acknowledged in the present review but will not be discussed as there are few studies in the literature.
Intermittent fasting regimens involve 60-100% energy restriction on fast days with ad libitum energy intake on fed days. Various IMF regimens have been proposed, with the most popular being alternate day fasting (ADF) and a regimen of fasting for two days per week (2DW). A common and appealing feature of IMF is that dieters do not have to restrict calories every day. Weight loss likely occurs because individuals do not fully compensate on non-fasting days for the calorie deficit that occurs on fasting days. Furthermore, the periodic nature of fasting may mitigate the constant hunger associated with CER. For example, several studies using a modified fasting paradigm (~25% of energy requirements on fast days) have shown that hunger decreases or remains unchanged from the baseline over an 8-12 week IMF intervention.
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Time-Restricted Feeding (TRF)
TRF refers to an eating pattern in which the food intake is restricted to a time window of 8-10 h or less every day. Recent studies in humans suggest that the median duration of eating is approximately 14.5 h per day, and the assumption that most individuals regularly undergo an “overnight fast” may thus be incorrect. Eating “around the clock” has been suggested to have detrimental effects on health and body weight, leading to a desire to study time-restricted feeding as a weight loss strategy. Limiting the eating duration may be an effective strategy to reduce the overall caloric intake; however, TRF does not necessarily have to involve caloric restriction. TRF is distinct from IMF because it involves an element of timing optimally aligned to the biological day.
Preclinical Studies: Insights from Animal Models
A key research question is whether IMF elicits benefits for body weight and peripheral/tissue-specific metabolism that are at least comparable to CER. This question is challenging to rigorously address in human clinical trials because of issues with adherence to energy intake prescriptions and the lack of a criterion method for measuring the actual free-living intake. In contrast, manipulating the energy intake and determining the actual intake can be accomplished with a high degree of accuracy in animal models.
Alternate day fasting has been the most thoroughly studied IMF protocol in laboratory rodents. A few studies have used a CER protocol for 3-6 consecutive days, followed by a ‘break’ period of ad libitum feeding (e.g., 4 days of a CER followed by 3 days of ad libitum feeding). However, for the purposes of this review, we will only consider preclinical studies of ADF as this protocol is most consistent with the definition of IMF that we have provided here and with previous definitions proposed by Mattson et al.
Compared to ad libitum fed animals, ADF appears to improve several circulating and tissue-specific biomarkers associated with the metabolic health status (for reviews, see refs [15,19]). In mice, ADF mitigates the adverse effects of ad libitum high-fat feeding, resulting in a lower fat mass, and thus reducing plasma glucose, insulin, and leptin levels, and improving glucose tolerance.
To our knowledge, only two preclinical studies (Anson et al. [34] and Mager et al. [33]) have performed head-to-head comparisons of ADF and CER regimens and measured longitudinal weight change and metabolic outcomes. Anson et al. [34] studied mice over a period of ~20 weeks assigned to one of four groups: mice fed ad libitum; mice provided ad libitum access to food every other day (i.e., ADF); mice provided with a limited daily food allotment of 60% of that eaten by the ad libitum fed animals (i.e., CER); and pair-fed mice that were provided a daily food allotment equal to the average daily intake of mice in the ADF group. The fourth group provided an opportunity to isolate the effects of total calorie intake versus ADF. Over ~20 weeks, the ADF mice compensated for periods of fasting by almost doubling the food intake on fed days, thus gaining weight at rates similar to the ad libitum-fed mice. As expected, the pair-fed mice gained an identical amount of weight to the ADF and ad libitum-fed mice, while the CER mice maintained a significantly lower weight. Interestingly, despite different body weights and levels of intake, fasting glucose and insulin concentrations were improved to a similar extent in the ADF and CER groups, an effect that was not observed in the pair-fed or ad libitum-fed mice.
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This is in contrast to a study conducted by Mager et al. [33] that reported unchanged glucose concentrations in Sprague-Dawley rats following a period of ADF, and reduced glucose concentrations in a group of rats following a 40% CER regimen. Similar to the results of Anson et al. [34], the body weight remained lower in the CER rats compared to the rats that received ADF.
An additional study worth noting (Gotthardt et al. [35]) compared ADF combined with either a low- or high-fat diet to groups of mice that were fed low- and high-fat diets ad libitum. This study is relevant to human weight loss because animals were placed into the diet groups after a period of weight gain. C57/BL6 mice were fed a high-fat diet (HFD; 45% fat) ad libitum for 8 weeks to promote an obese phenotype and mice were then divided into four groups that were either maintained for four weeks on an ad libitum high-fat diet (HFD), maintained on an ad libitum low-fat diet, received a high-fat diet every other day (ADF-HFD), or received a 10% low-fat diet every other day (ADF-LFD). At 4 weeks, body weights were significantly lower in the ADF-HFD group (~13% reduction) and ADF-LFD group (~18% reduction) compared with the HFD group. All three diet groups had a statistically similar energy intake during the intervention. Mice on the ADF-LFD maintained a ~12% higher lean mass over 4 weeks compared to the ad libitum LFD and HFD groups. Only the ADF-LFD group had improved glucose tolerance at 4 weeks compared to the other groups. Although a limitation of the study is that it lacked a diet-specific calorie-restricted group, the results suggest that the dietary macronutrient composition potentially modifies the metabolic response to ADF.
Taken together, the effects of ADF on body weight and glucose (at least in rodents) seem to depend on a number of factors, such as the energy and macronutrient content of the diet. Importantly, in contrast to humans, rodents fed normal chow every other day tend to fully compensate on fed days for the negative energy balance incurred on fast days [34] (see next section).
The lack of well-controlled preclinical studies comparing ADF to CER represents a key evidence gap that could be addressed in future studies by including both CER and ADF groups and ideally, animals pair-fed to the IMF group, as was done in the work conducted by Anson et al. [34]. Future studies should also carefully consider how the CER group receives its daily allotment of food. Calorically-restricted rodents tend to eat all of their food as soon as it is made available (e.g., 3-6 h time window) [36]. This is a confounding factor that adds a timing component to the reduction in calories and extends the fasting duration, potentially rendering the CER group indistinguishable from the ADF animals.
Time-Restricted Feeding (TRF) in Preclinical Studies
In contrast to IMF, there have been no preclinical studies directly comparing TRF regimens to CER in the context of weight loss, so it is unknown whether this form of IER differentially impacts metabolic responses to weight loss. Therefore, we will briefly address the studies that have examined metabolic responses to TRF compared to an energy-matched ad libitum feeding …
Practical Tips for Implementing Weight Loss Strategies
While the scientific research provides valuable insights, here are some practical tips for implementing weight loss strategies:
- Consult with a Professional: Before starting any weight loss program, especially IER, consult with a healthcare professional or a certified weight management consultant like Shari. They can help you determine the best approach for your individual needs and health status.
- Focus on a Healthy Food Relationship: The goal should be to develop a healthy relationship with food, not just to restrict calories.
- Consider the Diet Terminator Program: Shari and Dr. Patti have combined her Diet Terminator program with holistic products and services to create a program that helps people commit to a healthy food relationship and lifestyle while eliminating self-sabotage and detrimental patterns and habits.
- Start Slowly: If you're new to IER, start with a less restrictive approach like TRF with a 10-hour eating window and gradually reduce it.
- Prioritize Nutrient-Dense Foods: Focus on consuming whole, unprocessed foods like fruits, vegetables, lean proteins, and whole grains during your eating windows.
- Stay Hydrated: Drink plenty of water throughout the day, especially during fasting periods.
- Listen to Your Body: Pay attention to your hunger and fullness cues. Don't force yourself to fast if you're feeling unwell.
- Be Consistent: Consistency is key to success with any weight loss strategy.