The design of the CALERIE study paper provides a detailed description of CALERIETM 2’s aims. The following is a brief summary.
CALERIETM 2 tested effects of a two-year randomized clinical trial (25% CR vs. Ad Libitum (AL). The longer intervention period allowed the study to distinguish long-term CR effects after weight has stabilized from the acute effects of weight loss.
CALERIETM Phase 2’s specific primary aim was to test the hypothesis that CR in humans causes sustained metabolic adaptation as defined by:
- Reduction in core body temperature
- Reduced resting metabolic rate (RMR) corrected for changes in body composition
These metabolic adaptations to CR in laboratory animals were proposed to mediate its deceleration of aging changes. The sample size was specified in advance to provide robust statistical tests of these hypotheses.
CALERIETM Phase 2 secondary aims were to test the hypotheses that CR in humans:
- Reduces serum triiodothyronine (T3)
- Reduces inflammation as reflected by plasma concentrations of tumor necrosis factor-α a (TNF-α)
Both thyroid hormones and inflammatory mediators have been suggested to mediate aging changes and CR’s effects on them in laboratory animals.
In addition, numerous exploratory aims were pursued, including measurement of changes in
- risk factors for cardiometabolic diseases
- body composition and metabolism
- circulating levels of serum hormones, multiple inflammatory mediators, and growth factors
- indicators of mitochondrial function
- bone mineral density
- physical activity and physical function
- mood, cognition, and other psychological outcomes
The study also systematically assessed participant safety outcomes.