Effects of Two Weeks of 5:2 Intermittent Energy Restriction on Basal and Postprandial Metabolism
Condition: Weight Loss
MeSH terms: Weight Loss
Study type: Interventional

Summary: 
      Worldwide, a third of adults were overweight in 2016, and 13% were obese. Excess energy
      intake results in weight gain. Excess fat increases the risk of disease (eg. cardiovascular
      diseases, type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, dementia, certain
      cancers). Modest weight reduction (>5% of body weight) decreases the incidence and
      progression of many of these diseases. Daily energy restriction or continuous energy
      restriction (CER) involves diets that have a 500-600 kcal deficit per day resulting in
      sustainable weight loss. However, adherence is difficult. Diets following a 5:2 intermittent
      energy restriction (5:2 IER) pattern may be better. Approximately 75% energy restriction is
      maintained for 2 non-consecutive days/week and normal energy intake is consumed on the
      remaining 5 days of the week. Significantly reduced fasting insulin concentration and insulin
      resistance were shown in the 5:2 IER regimen compared with the CER regimen. In this study,
      normal-weight young participants will be recruited and 5:2 IER and CER will be compared over
      2 week periods. Subcutaneous continuous glucose monitoring (CGM) devices will be undertaken.
      An ad libitum pasta meal will be consumed by participants three hours after the ingestion of
      breakfast to evaluate the energy intake. Postprandial thermogenesis in response to the test
      drink will be evaluated.
    

Detailed description: 
      Once participants have consented to be screened, they will come to the lab for a medical
      screening. If the medical screening is satisfactory, all participants will be asked to
      undergo a one-week pre-study standardization period. Participants will be asked to maintain
      their normal dietary and physical activity patterns throughout this period. Participants will
      be asked to complete a 3-day food diary, which will be analyzed to evaluate their habitual
      food intake and temporal distribution of energy intake throughout the day. In addition,
      participants will be provided with and instructed on how to use, an Actiheart (a device that
      combines accelerometry with heart rate monitoring). This device will be placed on the
      participants' chest using two standard electrocardiogram (ECG) electrodes to record HR, heart
      rate variability and activity level (to allow estimation of total energy expenditure) for one
      week. Both items will be returned before the next visit, which will be the pre-intervention
      measurement. After the pre-intervention visit, participants will be then randomly assigned to
      two weeks of either (1) the CER of 20% restriction below their estimated requirement (~1600
      kcal) 7 days/week or (2) the 5:2 IER of 70% restriction (~600 kcal) delivered for two
      non-consecutive days/week and no restriction (so sufficient energy to meet their requirement)
      on the other 5 days/week. Seven days after the pre-intervention visit, participants will then
      start their 2-week intervention. A 7-day gap is designed in a bid to ensure both pre- and
      post-intervention measurements will be conducted during the second week of the follicular
      phase for females. The foods, drinks and overall energy restriction will be the same on each
      arm. Using estimated BMR based on the Henry equation and the individual daily physical
      activity level (PAL), estimated from the Actiheart during a one-week standardization period
      and the physical activity questionnaire, allowed the estimation of daily energy requirements
      for each subject using basal metabolic rate x PAL. Thus energy intake will be tailored to
      each participant's specific energy requirements. According to the suggestion from The
      Association of UK Dietitians, 2 non-consecutive ER days can be achieved on Day 1 and Day 4 of
      an IER week, thus the investigators will fix and prescribed the two ER days in a week with 3
      days apart.

      Food on intervention days will be prepared based on a 3-day sequence of menus to avoid
      boredom but be practical regarding the provision of foods. Each menu provides three meals/day
      to avoid confounding effects causing by altering meal frequency between the interventions.
      Three meals/day (and no snacks) is selected to make each eating incident acceptable on the
      most restricted day. Three meals with a macronutrient distribution of ~50% energy from
      carbohydrates, ~31% from fat and ~19% from protein will be prescribed. The distribution of
      energy across the day will be 25% of daily energy requirements from breakfast, 37.5% from
      lunch and 37.5% from the evening meal. To avoid confounding by altering the mealtime, and the
      period between which meals are consumed, breakfast will be instructed to be consumed between
      8 am-8:30 am; lunch between 1 pm-1:30 pm and evening meal between 6 pm-6.30 pm. Menu designed
      so that it could be proportionally increased and decreased depending on the intervention
      requirement and informed by cooking facilities available and optimizing food safety.
      Participants will be instructed to adhere to the prescribed meal plan and record their food
      intake by taking photos.

      On Day 7 of each experimental trial, participants will report to the unit in the morning
      after an overnight fast (~12h) for the assessment of body weight. The investigators will also
      use this visit to attach a subcutaneous continuous glucose monitoring (CGM) device, which
      will be placed on the abdomen to allow for the estimation of continuous blood glucose over
      the last 7 days of each trial. Also, the investigators will download the data from the
      pedometer and use it to assess compliance with the requirements of the study during the first
      week. CGM and pedometer will be removed upon arrival on the post-intervention visit.

      On the day after one week pre-study standardization period and the day after the 2-week
      intervention, the participants will be asked to attend the laboratory after an overnight fast
      to undergo a series of appetite and metabolic measurements in response to a standardised
      breakfast in the form of a milk-based test drink (in a volume of 10 kcal/kg body weight and
      energy distribution from the macronutrients will be 47.9 % carbohydrate, 35.1% fat, and 17%
      protein) and a subsequent ad libitum pasta lunch containing cheese, olive oil, and tomato
      sauce, which will provide 148.24 kcal/100g with 49.8%, 15.4% and 34.8% energy provided by
      carbohydrates, protein and fat, respectively.
    

Intervention name(s): 5:2 Intermittent energy restriction; Continuous energy restriction
Intervention type(s): Other; Other
Intervention description(s): Substantial (70%) energy restriction for 2 non-consecutive days/week interspersed with normal energy intake (isoenergetic) on the remaining 5 days of the week.; 20% energy restriction each day relative to the energy requirement.
Other intervention name(s): 5:2 IER; CER
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: obesity dietary restriction