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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #331730
Title: Effects of 2-year calorie restriction on circulating levels of IGF-1, IGF-binding proteins and cortisol in non-obese men and women: a randomized clinical trial

Author
item FONTANA, LUIGI - Washington University
item VILLAREAL, DENNIS - Washington University
item DAS, SAI KRUPA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item SMITH, STEVEN - Pennington Biomedical Research Center
item MEYDANI, SIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item PITTAS, ANASTASSIOS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item KLEIN, SAMUEL - Washington University
item BHAPKAR, MANJUSHRI - Duke Clinical Research Institute
item ROCHON, JAMES - Duke Clinical Research Institute
item RAVUSSIN, ERIC - Pennington Biomedical Research Center
item HOLLOSZY, JOHN - Washington University

Submitted to: Aging Cell
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/15/2015
Publication Date: 2/1/2016
Citation: Fontana, L., Villareal, D.T., Das, S., Smith, S.R., Meydani, S.N., Pittas, A.G., Klein, S., Bhapkar, M., Rochon, J., Ravussin, E., Holloszy, J.O. 2016. Effects of 2-year calorie restriction on circulating levels of IGF-1, IGF-binding proteins and cortisol in non-obese men and women: a randomized clinical trial. Aging Cell. 15:22-27.

Interpretive Summary: Experimental and epidemiological studies indicate that insulin like growth factor (IGF)-1 and its binding proteins play a role in the biology of aging and in the pathogenesis of several common cancers. Young onset calorie restriction (CR) in rodents decreases serum IGF-1 concentration and increases serum corticosterone levels, which have been hypothesized to play major roles in mediating its anti cancer and anti aging effects. However, little is known about the effects of CR on the IGF-1 system and cortisol in humans. To test the sustained effects of CR on these key hormonal adaptations, we performed a multicenter randomized trial of a 2-year 25% CR intervention in 218 non obese young and middle aged (20 to 50 yr age range) men and women. Weight loss averaged 7.6 plus or minus 0.3 kg over the 2-yr period of which 71% was fat mass loss. CR did not have an effect on IGF1 levels, but caused a significant 21% increase in serum IGF-1 binding protein, resulting in less availability of IGF-1. Serum cortisol concentrations were slightly but significantly increased after 1 year, but not 2 years of CR. We conclude that in contrast to rodents, humans do not respond to CR with a decrease in serum IGF-1 concentration or with a sustained and biological relevant increase in serum cortisol. However, CR causes a reduction in IGF-1 bioavailability by substantially and persistently increasing IGF-1 binding protein in young and middle aged lean or slightly overweight men and women. More studies are needed to understand the biological implications of these metabolic adaptations on cancer risk, health and longevity, and whether or not other nutritional interventions (e.g. protein restriction or intermittent fasting) reduce serum IGF1 concentration in humans.

Technical Abstract: Young-onset calorie restriction (CR) in rodents decreases serum IGF-1 concentration and increases serum corticosterone levels, which have been hypothesized to play major roles in mediating its anti-cancer and anti-aging effects. However, little is known on the effects of CR on the IGF-1 system and cortisol in humans. To test the sustained effects of CR on these key hormonal adaptations, we performed a multicenter randomized trial of a 2-year 25% CR intervention in 218 non-obese (body mass index between 22 to 27.8 kg/m2) young and middle-aged (20 to 50 yr age range) men and women. Average CR during the first 6-months was 19.5 +/- 0.8% and 9.1 +/- 0.7% over the next 18 months of the study. Weight loss averaged 7.6 +/- 0.3 kg over the 2 yr-period of which 71% was fat mass loss (p<0.0001). Average CR during the CR caused a significant 21% increase of serum IGFBP-1 and a 42% reduction in IGF-1:IGFBP 1 ratio at 2 yrs (p<0.008), but did not change IGF-1 and IGF-1:IGFBP-3 ratio levels. Serum cortisol concentrations were slightly but significantly increased by CR at 1-yr only (p=0.003). CR had no effect on serum concentrations of PDGF AB and TGFbeta-1. We conclude, on the basis of the present and previous findings, that, in contrast to rodents, humans do not respond to CR with a decrease in serum IGF-1 concentration or with a sustained and biological relevant increase in serum cortisol. However, long-term CR in humans significant and persistently increases serum IGFBP-1 concentration.