Effects of Intermittent Versus Continuous Energy Restriction on Metabolic Adaptation in Women With Obesity

One of the major challenges for treating obesity is to maintain a weight reduced state on the long term due to the high rate of weight regain. Therefore, the aim of this study is to evaluate the effects of an intermittent versus a continuous energy restriction in body composition (body weight, fat mass and fat-free mass) and metabolic adaptation, in women with obesity.

Literature is full of lifestyle interventions aimed for weight loss (WL) in several populations. However, one of the major challenges for treating obesity is WL maintenance on the long term due to the high rate of weight regain.

The reduction of the resting metabolic rate (RMR) is one of the identified aspects regarding compensatory metabolic alterations. After a WL intervention, decreases in RMR are mainly explained by the loss of fat-mass (FM) and fat-free mass (FFM). However, some authors showed that these reductions tend to be higher than predicted (explained by FM and FFM loss), a phenomenon called "metabolic adaptation" (MA). MA has been studied as a possible barrier to WL, WL maintenance and may contribute to weight regain. However, its relevance on long-term WM has been recently questioned. It is known that in order to lose weight, a negative energy balance (EB) must be achieved, meaning when EE surpasses the energy intake (EI). However, this negative EB may be achieved through several strategies, by changing the EI (energy restriction (ER)) and/or EE (increasing physical activity).

Regarding EI strategies, continuous energy restriction (CER) is the most common nutritional strategy for WL, consisting in a daily energy restriction according to one's specific needs. However, some concern has been pointed out regarding this widely used strategy, once it evolves several behavioural, metabolic and endocrine responses that may contribute to therapeutic adherence, undermining WL and its maintenance. On the other hand, intermittent energy restriction (IER) has been recently suggested as an alternative to CER. IER consists in interspersing periods of ER with periods of neutral EB, called "refeed" or "diet breaks" during the WL phase. Energy restriction is followed by several adaptive responses, namely endocrine, including thyroid, appetite regulation and steroid hormones, influencing the energy expenditure (EE), body composition and satiety. Therefore, understanding how hormones may influence RMR and as a consequence, AT, it´s crucial to a better understanding.

According to the literature, compensatory metabolic responses following ER and WL can be reversed following a 7-to-14-day period of energy balance post-weight loss. Therefore, considering that the length of the nutritional intervention for WL may benefit a reduction, we consider relevant to study other ER designs/patterns, namely 2 weeks in ER interspersed with 1 week in EB, comparing to a CER. Taking into account this therapeutic as a potential opportunity for the obesity's treatment, this paper describes the protocol for a randomized controlled trial (RCT), which targets to evaluate the effects of an IER (alternating 2 weeks of ER with 1 in neutral EB), comparing to a CER. This trial aims: a) to compare the effects of a IER vs CER strategy on body composition variables (body weight, fat mass and fat-free mass) and in metabolic adaptation and, b) to understand if participants will be able to maintain a reduced weight state after 12 months (successful weight-loss maintenance), in both groups.

Eligibility Criteria:
Inclusion Criteria:

* Women
* BMI ranging between 30 and 39.9 kg/m2
* Age between 20-45 years
* Weight stable in the last 6 months (less than 5% weigh variation)
* Inactive (less then 150 min/week of moderate physical activity or 75 min/week of vigorous physical activity
* Living in Lisbon Metropolitan Area and being able to drive to Faculty of Human Kinetics and Germano de Sousa Laboratory (Algés)
* Available to be randomized to any of the trial groups (CER or IER)
* Willing to commit with the assigned group protocol, including the nutritional intervention and lifestyle recommendations, as well as being available for participation in all evaluation moments.

Exclusion Criteria:

* Previous or present health disorders: cancer, autoimmune, cardiac, psychiatric, kidney and liver disease (except liver steatosis), diabetes, chronic intestinal inflammatory disease, or other medical conditions known to affect energy balance homeostasis
* Menopause
* Hormonal or thyroid disorder
* Medications that promote weight gain or alter energy balance, including corticosteroids, antidepressants, anxiolytics, mood-stabilizing, and antipsychotics
* Medications or dietary supplements for weight-loss in the past 3 months
* Pregnant for the past 6 months or breastfeeding
* Planning to get pregnant in the next 2 years or getting pregnant during the study
* Current consumption of more than 14 alcoholic drinks per week or other substance abuse, and/or current acute treatment or rehabilitation program for alcohol/substance abuse
* Surgery or in hospital admission for the last month
* Positive for Covid-19 in the past 3 months or testing positive during the intervention phase of the study