Please select the eligibility criteria that correspond to the clinical trial below.
Title: The Effect of Intermittent Energy Restriction Using Meal Replacements in Overweight Chinese Subjects: a Pilot Randomized Control Trial
Brief Summary: Background and Aims: The "5:2 diet", a form of intermittent energy restriction, has been popularized in Europe and USA. The rationale behind this approach is that two days of dieting is potentially more achievable, yet long enough to reduce overall weekly energy intake. However, this specific approach is lacking in evidence. Therefore, we are keen to investigate the effectiveness of this form of intermittent energy restriction compared with a control intervention (providing dietary and exercise advice only), in overweight, Chinese subjects, for an intervention period of 12 weeks.

Design and Methods: This will be a randomized controlled trial, with 15 subjects in each arm, for an intervention period of 12 weeks. Subjects randomized to the treatment group will take three packets of a meal replacement product (Optifast®) per day during two consecutive fasting days, and take a healthy balanced diet that meet estimated energy requirements for the remaining five days. Subjects randomized to the control group will be given general diet advice and allowed to eat ad libitum throughout the study period. Measurements and laboratory tests will be done at baseline, 4 weeks and 12 weeks. Adherence to the dietary interventions will be assessed at 4 weeks and 12 weeks using 7-day food diaries.

Significance: This will be the first study looking at an Asian population and will serve as a pilot towards a larger randomized trial. If this approach is found to be safe, effective and easier to adhere compared to the traditional continuous energy restriction, then it will be a very valuable option in the treatment of obesity, which has become an increasing problem globally including Singapore.


Options:
A: Inclusion Criteria:

* Ability to provide informed consent.
* Chinese. (Both parents must be Chinese)
* Age above 21 years old. This study will focus only on adult subjects, and 21 years old is chosen as the age cut off, as it is the recognised legal age of independent consent.
* BMI ≥ 25 kg/m2

Exclusion Criteria:

* Pregnant, or any possibility of being pregnant (based on last menstrual period).
* Lactation.
* Age above 70 years old and/or suffering from cancer, diabetes, or any major cardiovascular disease, respiratory, psychiatric or musculoskeletal morbidity.
* Currently dieting or losing weight
* Unable to tolerate or complete two consecutive days of fasting during a two-day trial before recruitment.
* Unwilling to be randomised into intervention or control group.
B: Inclusion Criteria:

* Ability to provide informed consent
* Baseline brachial flow-mediated dilation (FMD) \< 6%Δ (rationale: non-invasive screening to ensure exclusion of subjects with exceptionally high baseline endothelial function.
* Ability to perform motor and cognitive tests (e.g., can rise from a chair, walk for 2 min, climb 10 stairs)
* Women will be confirmed as postmenopausal (either natural or surgical) based on cessation of menses for \>1 year.

Exclusion Criteria:

* Ages \<55 years or ≥80 years
* Occupation that requires night-shift work or abnormal hours that would disrupt eating schedule
* Dietary habit of regularly skipping meals, already eating within a \~10 hour window, or any other form of restrictive eating.
* Unable to adhere to an 8 hour eating window for the length of the study period
* Participation in regular vigorous aerobic/endurance exercise (\>3 vigorous bouts/week)
* Not weight stable in the prior 3 months (\>2 kg weight change).
* Body mass index (BMI) \>40 kg/m\^2 (rationale: vascular function measurements can be inaccurate in severely obese subjects)
* Current smoking
* Diagnosis of a chronic clinical disease (e.g., coronary artery/peripheral artery/cerebrovascular diseases, diabetes, chronic kidney disease requiring dialysis, neurological disorders or diseases that may affect motor/cognitive functions \[multiple sclerosis, Parkinson's disease, polio, Alzheimer's disease, dementia or other brain diseases of aging\]), except hypertension and hyperlipidemia.
* Having unstable angina, acute myocardial infarction, coronary angioplasty, or aorto- coronary bypass surgery as defined by the occurrence of an event, symptom, surgery, or change in medication and/or dosage within 3 months prior to enrollment.
* Having thyroid disease that is not controlled by medications or \<3 month's use of a particular medication and/or dosage (rationale: uncontrolled thyroid diseases are associated with alterations in vascular function).
* Having past or present alcohol dependence or abuse, as defined by the American Psychiatry Association, Diagnostic and Statistical Manual of Mental Disorders
C: Inclusion Criteria:

1. The volunteer (male or non-pregnant female, any ethnicity) must be \>18 years of age.
2. The volunteer must either have a body mass index of 25.0-35.0 kg/m2 or the combination of a body mass index of 18.5-24.9 kg/m2 and two or more previously or currently measured symptoms of the metabolic syndrome (fasting glucose≥110 mg/dL, triglycerides≥150 mg/dL, high-density lipoprotein cholesterol\<40 mg/dL in males or \<50 mg/dL in females, systolic blood pressure≥130 mmHg or diastolic blood pressure≥85 mmHg, or waist circumference≥40 inches in males or ≥36 inches in females \[glucose and cholesterol levels may be self-reported\]).
3. The volunteer has not routinely participated in caloric restriction (deliberate limitation of caloric intake of \<80% than the FDA-recommended daily caloric intake) within the last 2 years, has not participated in extended fasting (\>12 hours at a time) for at least a year, and does not deliberately skip meals as a routine dietary practice.

Exclusion Criteria:

1. Body mass index \<18.5 or \>35 kg/m2.
2. Current active cancer treatment, treatment with immunosuppressive medications, or solid organ transplantation within 1 year.
3. Presence of immunosuppressive disease, myocardial infarction, peripheral vascular disease, or stroke within the past year.
4. Use of insulin.
5. Although it is unlikely fasting will harm the pregnant or lactating woman, the dietary restrictions placed on the participant for the duration of the study may conflict with dietary recommendations for pregnant or lactating women. Women of child bearing potential, therefore, will meet an exclusion if they become pregnant.
D: Inclusion Criteria:

* Females;
* Aged between 18 and 59 years old;
* Body mass index equal or greater 25 kg/m²;
* Agree to sign the informed consent.

Exclusion Criteria:

* Any chronic health conditions (e.g. chronic renal failure, autoimmune, heart, and liver disease);
* Thyroid diseases or medications for its treatment;
* Medications known to affect total energy expenditure;
* Use of steroids, immunosuppressants or non-steroidal anti-inflammatory drugs, weight-loss medications, oral hypoglycemic agents or insulin and any medications that influence metabolic and/or inflammatory parameters;
* Previous surgery for weight loss;
* Pregnancy or breast-feeding;
* Smoking;
* Alcohol use (\>2 doses/day).

Answer: A