Effect of Time-Restricted Feeding on Fat Loss and Cardiometabolic Risk Factors in Overweight Adults

Time-restricted feeding (TRF) is a novel type of intermittent fasting that involves eating within a daily period of 10 hours or less, followed by fasting for at least 14 hours daily. Several studies in rodents report that TRF reduces body weight, improves blood sugar control, and reduces the risk of cardiovascular disease-even when food intake is matched to the control group or no weight loss occurs. Preliminary evidence suggests that TRF may also increase weight loss, fat loss, and reduce the risk of diabetes and cardiovascular disease in humans. This study will test whether TRF enhances fat loss and increases weight loss in adults with obesity, relative to conventional dieting alone. In addition, this study will determine whether TRF reduces risk factors for type 2 diabetes and cardiovascular disease and will measure the feasibility and acceptability of TRF. In conjunction with the parent study described above, four ancillary studies will be conducted: Effect of weight loss on nitrogen metabolism and bacteria in the mouth. The primary endpoints for this ancillary study are plasma and salivary nitrate and nitrite, and the secondary endpoints are salivary nitrate reductase activity and salivary bacterial abundance. Effect of weight loss on several biomarkers related to kidney stones. The primary endpoint for this ancillary study is urinary oxalate, and the secondary endpoints are urinary citrate, chloride, sodium, potassium, calcium, phosphorus, uric acid, and creatinine. Effect of meal timing on blood pressure regulation and kidney function. The primary endpoints of this ancillary study include urinary aldosterone excretion, sodium, potassium, and endothelin, whereas the secondary endpoints include nitric oxide and albumin. Additional exploratory endpoints include renal injury markers (KIM-1, nephrin, and urine albumin-to-creatinine ratio), measures of reactive oxidative stress (e.g., hydrogen peroxide and TBARs), and urinary exosomes. Urine will be analyzed in 12-hour bins to determine how meal timing affects differentially affects these endpoints during the daytime and nighttime. The effects of weight loss on these endpoints may also be considered. Validation of a meal timing questionnaire to assess the distribution of food intake throughout the day.

Percent of weight lost as fat, as measured by dual-energy X-ray absorptiometry (DXA). Lean mass retention will be quantified as 100% minus percent of weight lost as fat (i.e., is measured in the same units).

Changes in total fat mass, lean mass, bone mass, and regional values (kg), as measured by DXA. (This will be secondary to the assessment of fat loss and lean mass retention as specified above.)

Total cholesterol (mg/dl), LDL cholesterol (mg/dl), HDL cholesterol (mg/dl), and triglycerides (mg/dl)

Hunger and fullness as measured by Likert (1-5 scale) and visual analog scales (a 0-100 scale, with 0 meaning "Not at all" and 100 meaning "Extremely")

Start and stop times and mid-points of daily eating in clock time, as assessed by the daily adherence survey

Distribution of calories eaten across the day in % per time period, as measured by a novel questionnaire that is being validated

Presence and degree of breakfast and nighttime eating, as measured by a novel questionnaire that is being validated

Depression as measured by the Patient Health Questionnaire-9. (Each question is scored on a 0-3 scale, where 0 means "Not at all" and 3 means "Nearly every day." Answers to each question are tallied to create a single composite score of depression from 0-27, with higher values meaning more depressive symptoms.)

Mood states as measured by the Profile of Mood States (a 5-point scale with 1 meaning "Not at all" and 5 meaning "Extremely"). This study is particularly interested in the scores for anxiety and related moods.

Sleep quality, as assessed by the Pittsburgh Sleep Quality Index (PQSI) (This study will use the Global PQSI score, which ranges from 0-21, where higher values correspond to worse sleep quality.)

Restrained, emotional, and external eating, as measured by the Dutch Eating Behavior Questionnaire. (Individual questions are scored on a 5-point scale ranging from "Never" to "Very often," and composite scores for restrained, emotional, and external eating are tabulated, with higher numbers reflecting more of each trait.)

Loneliness, as measured by the UCLA Loneliness Scale (a 3-point scale with 1 meaning "hardly ever" and 3 meaning "often")

Intervention satisfaction and barriers and facilitators of adherence, as measured by qualitative exit interview

Social life and daily habits, as measured by the frequency of occurrence of social activities (5- and 8-point rating scales)

24-hour urinary oxalate, citrate, sodium, calcium, chloride, potassium, and creatinine, as measured in mg/day

Inclusion Criteria: Are a new patient at the UAB Weight Loss Medicine Clinic Aged 25-75 years old BMI between 30-60 kg/m2 (inclusive) Weigh less than 450 lbs Wake up regularly between 4-9 am on most days. Exclusion Criteria: Diagnosed with diabetes, have an HbA1c of ≥6.5%, or are on diabetes medication On weight loss medication Addition of or withdrawal from a chronic medication within the past 10 weeks Clinically significant laboratory abnormality (e.g., abnormal hemoglobin levels) Significant gastrointestinal disease, major gastrointestinal surgery, or gallstones Significant cardiovascular, renal, cardiac, liver, lung, adrenal, or nervous system disease that might compromise the participant's safety or data validity Evidence of cancer (other than non-melanoma skin cancer) within the last 5 years Unstable psychiatric, sleep, or circadian conditions (common conditions such as sleep apnea and depression are acceptable as long as they are stabilized and not rapidly worsening) Lost or gained more than 5 lbs of weight in the past month Currently perform overnight shift work more than once per week on average Regularly eat within a less than 10-hour period each day Regularly eat dinner before 6 pm Traveled more than two time zones away in the two months prior to enrolling in the trial Will travel more than one time zone away during the study Pregnant or breastfeeding

Jamshed H, Steger FL, Bryan DR, Richman JS, Warriner AH, Hanick CJ, Martin CK, Salvy SJ, Peterson CM. Effectiveness of Early Time-Restricted Eating for Weight Loss, Fat Loss, and Cardiometabolic Health in Adults With Obesity: A Randomized Clinical Trial. JAMA Intern Med. 2022 Sep 1;182(9):953-962. doi: 10.1001/jamainternmed.2022.3050.

Allaf M, Elghazaly H, Mohamed OG, Fareen MFK, Zaman S, Salmasi AM, Tsilidis K, Dehghan A. Intermittent fasting for the prevention of cardiovascular disease. Cochrane Database Syst Rev. 2021 Jan 29;1(1):CD013496. doi: 10.1002/14651858.CD013496.pub2.