Walford · The journals of gerontology. Series A, Biological sciences and medical sciences 2002 · longitudinal case series · n=8

Calorie restriction in biosphere 2: alterations in physiologic, hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period.

Cited 304 times in the scientific literature.

Level 4 - case-series / case-control

Single-arm longitudinal case series with pre- and post-intervention measurements and no concurrent control group.

PubMed 12023257 · doi:10.1093/gerona/57.6.b211 · record verified 2026-08-30

What was done

Eight crew members (four men and four women; seven aged 27 to 42 and one aged 67, including two study authors) were sealed inside Biosphere 2 for two years. For seven eighths of that period, they consumed a low-calorie (1750-2100 kcal/d), nutrient-dense diet primarily composed of vegetables, fruits, nuts, grains, and legumes (approximately 12% protein, 11% fat, and 77% complex carbohydrates). Fifty physiological, hematological, hormonal, and biochemical variables were measured before entry, at multiple time points inside, and four times during the 30 months after exiting, using Bayesian statistical analysis to compare inside versus outside values.

What was found

Participants experienced an overall weight loss of 17 +/- 5%, mostly in the first 8 months. BMI decreased by 19% in men and 13% in women. Systolic blood pressure decreased by 25% and diastolic blood pressure decreased by 22%. White blood cell count decreased by 31%. Insulin decreased by 42%, T3 decreased by 19%, blood sugar decreased by 21%, and cholesterol decreased by 30%. Changes were also reported for rT3, cortisol, glycated hemoglobin, androstenedione, thyroid-binding globulin, renin, and transferrin.

Why it matters

This study demonstrates that prolonged, nutrient-dense calorie restriction in humans produces multi-system physiological and biochemical changes that parallel those observed in calorie-restricted animal models.

Limits

The sample size was very small (n = 8) and included study authors. The study lacked an external parallel control group to separate diet from other enclosure factors such as physical workload and atmospheric conditions. Long-term clinical disease outcomes and longevity were not assessed.

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