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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #331729
Title: Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non obese humans

Author
item MEYDANI, SIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item DAS, SAI KRUPA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item PIEPER, CARL - Duke University Medical Center
item LEWIS, MICHAEL - University Of Vermont
item KLEIN, SAM - Washington University
item DIXIT, VISHWA - Pennington Biomedical Research Center
item GUPTA, ALOK - Pennington Biomedical Research Center
item VILLAREAL, DENNIS - Washington University
item BHAPKAR, MANJUSHRI - Duke University Medical Center
item HUANG, MEGAN - Duke University Medical Center
item FUSS, PAUL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item ROBERTS, SUSAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item HOLLOSZY, JOHN - Washington University
item FONTANA, LUIGI - Washington University

Submitted to: Aging
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/20/2016
Publication Date: 7/13/2016
Citation: Meydani, S.N., Das, S., Pieper, C.F., Lewis, M.R., Klein, S., Dixit, V.D., Gupta, A.K., Villareal, D.T., Bhapkar, M., Huang, M., Fuss, P.J., Roberts, S.B., Holloszy, J.O., Fontana, L. 2016. Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non obese humans. Aging. 8(7). doi:10.18632/aging.100994.

Interpretive Summary: Obesity and being overweight induces inflammation. Chronic inflammation has been shown to damage cells, and therefore plays a major role in developing age related diseases like cancer, heart disease and dementia. According to the Center for Disease Control (CDC), in 2010, seven out of ten causes of death were chronic disease, with heart disease and cancer attributed to 48 per cent of these deaths. After six weeks of baseline testing, which included metabolic measurements to determine their total daily energy output and blood collection to evaluate inflammation and immune system response, 220 eligible individuals were randomized into two groups. The control group maintained their normal diet for the duration of the study, while the test group was provided with support to maintain a high-satiety diet that restricted their calories by 25 percent including customized behavioral guidance. The test group was also given multivitamin and mineral supplements to prevent micronutrient malnutrition. The research team found that the test group had a significant and persistent reduction in inflammatory markers with no differences in other aspects of the immune responses such as response to vaccine, from the control group at the end of 24 months. However, while reduction in weight, fat mass, and other measurements were most pronounced at 12 months, they were not accompanied by the significant reduction indicators of inflammation until 24 months had passed in the study. This delay suggests that restricting calories for at least 24 months induces other mechanisms that may play a role in the reduction of inflammation without compromising the rest of immune system. These calorie restriction changes suggest a shift toward a healthy phenotype (the observable appearance of the body resulting from the interaction of its genetic makeup and the environment) given the established role of inflammation causing molecules and risk markers in the development of metabolic syndrome and age related diseases. This may be one of the most powerful non genetic interventions to slow aging, increase health span and the quality of lives in humans.

Technical Abstract: Calorie restriction (CR) inhibits inflammation and slows aging in many animal species, but in rodents housed in pathogen-free facilities, CR impairs immunity against certain pathogens. However, little is known about the effects of long-term moderate CR on immune function in humans. In this multi-center, randomized clinical trial to determine CR’s effect on inflammation and cell-mediated immunity, 218 healthy non-obese adults (20-50 y), were assigned 25% CR (n=143) or an ad-libitum (AL) diet (n=75), and outcomes tested at baseline, 12, and 24 months of CR. CR induced a 10.4% weight loss over the 2-y period. Relative to AL group, CR reduced circulating inflammatory markers, including total WBC and lymphocyte counts, ICAM-1 and leptin. Serum CRP and TNF-alpha concentrations were about 40% and 50% lower in CR group, respectively. CR had no effect on the delayed-type hypersensitivity skin response or antibody response to vaccines, nor did it cause difference in clinically significant infections. In conclusion, long-term moderate CR without malnutrition induces a significant and persistent inhibition of inflammation without impairing key in vivo indicators of cell-mediated immunity. Given the established role of these pro-inflammatory molecules in the pathogenesis of multiple chronic diseases, these CR-induced adaptations suggest a shift toward a healthy phenotype.