BackgroundProlonged fasting in which only water is consumed for 2 days or more has been shown to reduce pro‐growth signaling, activate cellular protection mechanisms and promote protection against cancer, diabetes, heart disease and neurodegenerative diseases. Since prolonged fasting is difficult for most human subjects, we developed a Fasting Mimicking Diet (FMD) which is a low calorie, low protein, plant‐based meal plan for 5 continuous days. During periods of low calorie intake, the body enters a protected mode, removes damaged cells and tissues, and undergoes self‐repair.Methods100 participants without a diagnosed medical condition in the preceding six months were enrolled based on Inclusion criteria (generally healthy adult volunteers, 18–70 years of age, body mass index: 18.5 and up). This study is designed as a randomized cross‐over trial, includes two arms: Control and multi‐cycle special 5‐day dietary regimen (Diet, 3 cycles). We evaluated the effects of the FMD on risk factors and markers for aging, cancer, metabolic syndrome and cardiovascular diseases.ResultsFor all subjects who completed 3 FMD cycles (combining both FMD arms), body weight, BMI, total body fat, trunk fat, absolute lean body mass, waist circumference, IGF‐1, systolic and diastolic blood pressure, total cholesterol and LDL were significantly reduced (P<0.05) and relative lean body mass (p=0.0002) was increased.ConclusionsFMD cycles are effective in improving an array of metabolic markers/risk factors associated with poor health and aging and in contributing to the treatment and prevention of multiple age‐related diseases.Support or Funding InformationFunding was provided by the USC Edna Jones chair fund. Dr. Mack's contributions were provided through the Southern California Clinical and Translational Science Institute (SCCTSI) supported by NIH ULTR001855