# Self-selected diet composition, adherence to caloric restriction, and cardiometabolic disease risk

> **NIH NIH R21** · TUFTS UNIVERSITY BOSTON · 2020 · $173,371

## Abstract

PROJECT SUMMARY
Calorie restriction (CR) is a promising nutritional strategy that has the potential to attenuate the risk of age-
related disease. The National Institutes of Health-funded CALERIE (Comprehensive Assessment of Long-term
Effects of Reducing Intake of Energy) was the first clinical trial to demonstrate the feasibility of achieving
sustained, moderate CR in healthy, non-obese adults. Remarkable reductions in cardiometabolic risk factors
were observed in the CR group compared with the ad libitum intake control group. Over the two-year study
period, participants were prescribed a caloric intake target but self-selected their diet, and notable variability
was observed in objectively measured adherence to CR. Examining diet composition during CR compared to
ad libitum intake will help identify factors that may contribute to this variability. Emerging evidence suggests
that the ratio of macronutrients in the diet plays an important and independent role in influencing health.
Studies in mice indicate that a low-protein, high-carbohydrate diet is associated with a longer healthspan. This
observation contradicts findings of greater satiety and lower energy intake associated with a higher protein
diet. As higher protein intake likely supports adherence to a CR regimen, further research is needed to
determine whether dietary composition can be optimized for both longer healthspan and CR adherence. The
proposed research directly contributes to the NIH FOA PA-18-824 and will use CALERIE data to evaluate the
effect of dietary composition on adherence to CR and resultant cardiometabolic disease risk factor
modification. The publicly available CALERIE database includes comprehensive measures of self-selected
diet composition, an objective measure of caloric intake, and a variety of health outcomes including
inflammatory and cardiometabolic risk factors. We will use the Geometric Framework for Nutrition (GFN), a
state-of-the-art analytical approach that can simultaneously evaluate multiple dietary components and
determine their associations with disease risk. Identifying these dietary factors has important implications for
optimizing adherence to CR and for the prevention and treatment of age-related chronic disease. We
hypothesize that dietary components associated with successful CR in a non-obese, disease-free population
will confer even stronger benefits in individuals at risk for cardiometabolic disease, such as populations with
overweight or obesity. Our long-term goal is for our results to inform dietary intervention strategies to facilitate
CR, attenuate cardiometabolic risk, and reduce the burden of age-related chronic disease.

## Key facts

- **NIH application ID:** 9993186
- **Project number:** 5R21AG064295-02
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** Sai Krupa Das
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $173,371
- **Award type:** 5
- **Project period:** 2019-08-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993186

## Citation

> US National Institutes of Health, RePORTER application 9993186, Self-selected diet composition, adherence to caloric restriction, and cardiometabolic disease risk (5R21AG064295-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9993186. Licensed CC0.

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