theFRESHstudy: FRequency of Eating and Its Influence on Satiety and Health

This proposal will investigate whether eating frequency influences health. Evidence-based
recommendations are lacking for the optimal number of daily eating occasions. This is an
important area of research because over the past 40 years Americans' eating habits have
changed from three meals a day to a pattern whereby most people now have 6-8 daily eating
occasions. Apart from potential increases in total energy intake, frequent eating leaves
people in a constant postprandial state. This constant, modestly elevated glycemia disturbs
the normal glucose-insulin and counter-regulatory hormone network balance and also disturbs
downstream cell signaling pathways. A constant postprandial state may increase systemic
inflammation and cause numerous other metabolic disturbances. As a result, eating frequency
(EF) may be associated with risk of diet-related chronic diseases such as cardiovascular
disease, cancer and diabetes, which are the major causes of morbidity, mortality and health
care costs in the U.S. To better understand this phenomena the investigators propose a
randomized, cross-over clinical trial to test a low-EF eating pattern (three eating
occasions/day) vs. a high-EF eating pattern (six eating occasions/day) in relation to
inflammation, an adipokine and appetite. The investigators hypothesize that compared to
eating three times/day, eating six times/day will increase biomarkers of systemic
inflammation, will decrease a beneficial adipokine and will increase both biomarkers and
self-reported measures of appetite. The investigators will test their hypothesis with these
specific aims: 1) To test the effects of low vs. high eating frequency on inflammatory
biomarkers (fasting high-sensitivity C-reactive protein, Interleukin-6 and tumor necrosis
factor-α,) and a beneficial adipokine (adiponectin); 2) To test the effects of low vs. high
eating frequency on appetite [daily ratings of perceived appetite and serial ratings during a
six-hour appetite testing session] and biomarkers involved in appetite regulation and food
intake (leptin, ghrelin, peptide YY, and cholecystokinin). The investigators will enroll n=50
males and females who are normal weight, overweight or obese. Participants will complete two
3-week long isocaloric intervention periods in random order [low EF (three eating
occasions/day) and high EF (six eating occasions/day)]. Participants will be free-living and
eating their own food using study-provided structured meals plans. Study staff will provide
on-going support and instruction to maximize adherence to the protocol. Fasting blood samples
will be collected at the beginning and end of each study phase. The investigators will test
for the intervention effect by using the GEE modification of linear regression to compare
mean biomarker response (intervention effect) for each study phase. On the last day of each
intervention period, participants will complete 6-hour appetite testing sessions where two
test meals will be provided in the low-EF phase and four test meals will be provided in the
high-EF phase. Serial appetite ratings and bloods will be collected to assess perceived
appetite and hormones of appetite and satiety. Results from this investigation will be used
to form guidelines for eating frequency in the context of an overall healthy diet.

Inclusion Criteria:

- Normal, overweight and obese males and females

- BMI = 18.5-24.9 and 28.0-40.0 kg/m²

- Ages 18-50 years

- Live in Seattle, WA

Exclusion Criteria:

- Pregnant women

- Presence of diseases requiring dietary modification, including physician diagnosed
cardiovascular disease or diabetes mellitus, use of medications that may impact study
results including non-steroidal anti-inflammatory drugs (NSAIDS)

- Abnormal fasting glucose (>100 mg/dL)

- History of disordered or restrained eating and severe food restrictions

- Individuals with BMI ≥ 40 kg/m2