FB4 (Framingham, Boston, Bloomington, Birmingham, and Baylor)
FB4 (Framingham, Boston, Bloomington, Birmingham, and Baylor)
This study will evaluate the effects of dietary carbohydrate and sugar consumption,
 independent of energy content, on body fatness and metabolism in a rigorous feeding study.
Many people with obesity can lose weight for a few months, but most have difficulty
 maintaining weight loss over the long term. Extensive research has shown that weight loss
 elicits biological adaptations - including a decline in energy expenditure and an increase in
 hunger - that promote weight regain. However, this observation leaves unanswered why average
 body weight has recently increased among populations that are mostly genetically stable.
 According to the Carbohydrate-Insulin Model, increased consumption of processed carbohydrates
 during the low-fat diet era of the last 40 years has raised the average body weight being
 defended by biological mechanisms on a population basis. Specifically, the investigators
 hypothesize that diets high in total carbohydrate (with or without added sugar) acting
 through increased insulin secretion, alter substrate partitioning toward storage in body fat,
 leading to increased hunger, slowing metabolism, and accumulation of body fat.

 To test this hypothesis, the investigators plan a randomized-controlled feeding study
 involving 125 adults with obesity. During the run-in phase, participants will be given a
 hypocaloric very-low-carbohydrate (VLC) diet, with adjustment of energy intake to produce 15
 ± 3% weight loss over 3 to 4 months on an outpatient basis. After weight stabilization,
 participants will be admitted to a residential center for 13 weeks. During the first 3 weeks,
 energy intake and expenditure will be closely monitored during weight-loss maintenance. Then,
 energy intake will be individually "locked" at levels equal to energy expenditure and
 participants will be administered one of three randomly-assigned test diets for 10 weeks. The
 test diets include VLC, High Carbohydrate-Low Sugar (HC-LS), and High Carbohydrate-High Sugar
 (HC-HS).
Inclusion Criteria:

 -  Aged 18 to 50 years

 -  BMI ≥ 27 kg/m2

 -  Weight ≤ 350 lb

 -  Medical clearance from a primary care provider

 -  Willingness to follow a VLC weight-loss diet

 -  Willingness to reside in a research unit for 3 months and eat/drink only provided
 study foods and beverages

 -  No major food allergies or aversions

 -  Willingness to obtain seasonal flu shot or provide documentation of flu shot for
 current flu season (winter/spring cohort only)

 -  Willingness to discuss work options (e.g., remote work) with employer, and make
 appropriate arrangements prior to the Residential phase.

 Exclusion Criteria:

 -  Change in body weight ≥ 10% during prior 6 months

 -  Specialized diets (e.g., for medical or religious reasons)

 -  Chronic use of any medication or dietary supplement that could affect study outcomes
 (e.g., insulin, metformin, thyroxine)

 -  Current smoking (1 cigarette in the last week)

 -  Greater than moderate alcohol consumption (> 14 drinks/wk) or history of binge
 drinking (≥5 drinks in 1 day within past 6 months)

 -  Physician diagnosis of a major medical illness or eating disorder

 -  History of kidney stones

 -  Laboratory tests: ALT>2x upper limit; abnormal HgA1c; abnormal TSH; abnormal
 creatinine; abnormal uric acid (using the male upper limit for both sexes)

 -  Failed criminal offender background check or sex offender background check

 -  Use of recreational drugs

 -  Current diagnosis or history of kidney stones, gout, or gall stones; or removal of
 gall bladder

 -  Exercise restrictions or at high risk for complications during exercise

 Female-specific exclusion criteria:

 -  Menopausal

 -  Any change in birth control medication during the 3 months prior to enrollment

 -  Pregnancy or lactation during the 12 months prior to enrollment, or intent to become
 pregnant during study participation