A two year randomized controlled trial of human caloric restriction: feasibility and effects on predictors of health span and longevity

Authors: RAVUSSIN, ERIC - Pennington Biomedical Research Center; REDMAN, LEANNE - Pennington Biomedical Research Center; ROCHON, JAMES - Duke Clinical Research Institute; DAS, SAI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; FONTANA, LUIGI - Washington University School Of Medicine; KRAUS, WILLIAM - Duke Clinical Research Institute; ROMASHKAN, SERGEI - National Institute On Aging (NIA, NIH); WILLIAMSON, DONALD - Pennington Biomedical Research Center; MEYDANI, SIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; VILLAREAL, DENNIS - Washington University School Of Medicine; SMITH, STEVEN - Pennington Biomedical Research Center; STEIN, RICHARD - Washington University School Of Medicine; SCOTT, TAMMY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; STEWART, TIFFANY - Pennington Biomedical Research Center; SALTZMAN, EDWARD - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; KLEIN, SAMUEL - Washington University School Of Medicine; BHAPKAR, MANJU - Duke Clinical Research Institute; MARTIN, CORBY - Pennington Biomedical Research Center; GILHOOLY, CHERYL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; HOLLOSZY, JOHN - Washington University School Of Medicine; HADLEY, EVAN - National Institute On Aging (NIA, NIH); ROBERTS, SUSAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Gerontology Medical Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/5/2015
Publication Date: 9/1/2015
Citation: Ravussin, E., Redman, L.M., Rochon, J., Das, S.K., Fontana, L., Kraus, W.E., Romashkan, S., Williamson, D.A., Meydani, S.N., Villareal, D.T., Smith, S.R., Stein, R.I., Scott, T.M., Stewart, T.M., Saltzman, E., Klein, S., Bhapkar, M., Martin, C.K., Gilhooly, C.H., Holloszy, J.O., Hadley, E.C., Roberts, S.B. 2015. A two year randomized controlled trial of human caloric restriction: feasibility and effects on predictors of health span and longevity. Journal of Gerontology Medical Science. 70(9):1097-1104.

Interpretive Summary: An ad libitum diet is one in which food intake is self-regulated or freely chosen. Long-term caloric restriction (CR), defined as a reduction in energy intake by a specified amount below ad libitum intake, increases life span and health span in many species. To determine CRs feasibility, safety, and effects on predictors of longevity, disease risk factors, and quality of life in non-obese young to middle age humans, 218 persons were randomized to a two-year intervention designed to achieve 25% CR or to ad libitum diet (AL). Compared to AL, CR had larger decreases in cardiometabolic risk factors and in daily energy expenditure adjusted for weight change, without adverse effects on quality of life. Sustained CR is feasible in non-obese humans. The effects of the degree of CR in this study on reported predictors of human survival (e.g., daily energy expenditure and thyroid function) and chronic disease risk factors suggest potential favorable effects on aging related outcomes that could be elucidated by further human studies.

Technical 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 CRs feasibility, safety, and effects on predictors of longevity, disease risk factors, and quality of life in non-obese humans aged 21-51 years, 218 persons were randomized to a two-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 alpha (secondary); and exploratory physiological and psychological measures. Results: Body mass index averaged 25.1 (range: 21.9 - 28.0 kg/m2). 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 alpha 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.