Fontana · Proceedings of the National Academy of Sciences of the United States of America 2004 · observational case-control study · n=36

Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans.

Cited 907 times in the scientific literature.

Level 4 - case-series / case-control

Case-control study comparing self-selected individuals on long-term caloric restriction to matched controls.

PubMed 15096581 · doi:10.1073/pnas.0308291101 · record verified 2026-08-30

What was done

Researchers evaluated 18 individuals who had practiced caloric restriction to slow aging for an average of 6 years and 18 age-matched healthy individuals consuming typical American diets. Measurements included body composition, serum lipids and lipoproteins, fasting plasma glucose and insulin, blood pressure, high-sensitivity C-reactive protein, platelet-derived growth factor AB, and carotid artery intima-media thickness. Medical records prior to caloric restriction were also reviewed.

What was found

The caloric restriction group was leaner than the comparison group with lower body mass index (19.6 +/- 1.9 vs. 25.9 +/- 3.2 kg/m(2)) and percent body fat (8.7 +/- 7% vs. 24 +/- 8%). Total cholesterol, low-density lipoprotein cholesterol, total-to-HDL cholesterol ratio, triglycerides, fasting glucose, fasting insulin, C-reactive protein, platelet-derived growth factor AB, and blood pressure were markedly lower, and HDL cholesterol was higher in the caloric restriction group (exact values not provided in the abstract). Carotid artery intima-media thickness was approximately 40% lower in the caloric restriction group.

Why it matters

This study provides evidence that prolonged caloric restriction in humans is associated with favorable cardiovascular risk profiles and reduced carotid artery intima-media thickness.

Limits

The study is limited by a small sample size (36 participants), non-randomized observational design, self-selected dietary intervention, and reliance on surrogate markers rather than hard cardiovascular outcomes.

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