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A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity.

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26187233
PMC4841173
The journals of gerontology. Series A, Biological sciences and medical sciences
Sept. 1, 2015
Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts.
Triiodothyronine, Young Adult, Basal Metabolism, Longevity, Caloric Restriction, Body Temperature, Tumor Necrosis Factor-alpha, Feasibility Studies, Blood Glucose, Energy Intake, C-Reactive Protein, Weight Loss, Male, Lipids, Blood Pressure, Time Factors, Adult, Middle Aged, Humans, Female
P30 DK098722, U24 AG047121, U01 AG020480, U01 AG022132, U01AG020487, U01AG020478, U01AG020480, U01AG022132, U01 AG020487, U01 AG020478
Meydani SN, Scott TM, Stewart TM, Stein RI, Bhapkar M, Kraus WE, CALERIE Study Group, Rochon J, Gilhooly CH, Redman LM, Romashkan S, Fontana L, Klein S, Villareal DT, Holloszy JO, Martin CK, Ravussin E, Williamson DA, Smith SR, Roberts SB, Das SK, Saltzman E, Hadley EC
Ravussin E, Redman LM, Rochon J, Das SK, Fontana L, Kraus WE, Romashkan S, Williamson DA, Meydani SN, Villareal DT, Smith SR, Stein RI, Scott TM, Stewart TM, Saltzman E, Klein S, Bhapkar M, Martin CK, Gilhooly CH, Holloszy JO, Hadley EC, Roberts SB, CALERIE Study Group. A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity. The journals of gerontology. Series A, Biological sciences and medical sciences 2015 Sep.

Abstract

BACKGROUND: Caloric restriction (CR), energy intake reduced below ad libitum (AL) intake, increases life span in many species. The implications for humans can be clarified by randomized controlled trials of CR. METHODS: To determine CR's feasibility, safety, and effects on predictors of longevity, disease risk factors, and quality of life in nonobese humans aged 21-51 years, 218 persons were randomized to a 2-year intervention designed to achieve 25% CR or to AL diet. Outcomes were change from baseline resting metabolic rate adjusted for weight change ("RMR residual") and core temperature (primary); plasma triiodothyronine (T3) and tumor necrosis factor-α (secondary); and exploratory physiological and psychological measures. RESULTS: Body mass index averaged 25.1 (range: 21.9-28.0 kg/m(2)). Eighty-two percent of CR and 95% of AL participants completed the protocol. The CR group achieved 11.7±0.7 %CR (mean ± standard error) and maintained 10.4±0.4% weight loss. Weight change in AL was negligible. RMR residual decreased significantly more in CR than AL at 12 months (p = .04) but not 24 months (M24). Core temperature change differed little between groups. T3 decreased more in CR at M12 and M24 (p < .001), while tumor necrosis factor-α decreased significantly more only at M24 (p = .02). CR had larger decreases in cardiometabolic risk factors and in daily energy expenditure adjusted for weight change, without adverse effects on quality of life. CONCLUSIONS: Sustained CR is feasible in nonobese humans. The effects of the achieved CR on correlates of human survival and disease risk factors suggest potential benefits for aging-related outcomes that could be elucidated by further human studies.