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      Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease

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          Abstract

          Calorie restriction or changes in dietary composition can enhance healthy aging, but the inability of most subjects to adhere to chronic and extreme diets, as well as potentially adverse effects, limits their application. We randomized 100 generally healthy participants from the United States into two study arms and tested the effects of a fasting-mimicking diet (FMD)—low in calories, sugars, and protein but high in unsaturated fats—on markers/risk factors associated with aging and age-related diseases. We compared subjects who followed 3 months of an unrestricted diet to subjects who consumed the FMD for 5 consecutive days per month for 3 months. Three FMD cycles reduced body weight, trunk, and total body fat; lowered blood pressure; and decreased insulin-like growth factor 1 (IGF-1). No serious adverse effects were reported. After 3 months, control diet subjects were crossed over to the FMD program, resulting in a total of 71 subjects completing three FMD cycles. A post hoc analysis of subjects from both FMD arms showed that body mass index, blood pressure, fasting glucose, IGF-1, triglycerides, total and low-density lipoprotein cholesterol, and C-reactive protein were more beneficially affected in participants at risk for disease than in subjects who were not at risk. Thus, cycles of a 5-day FMD are safe, feasible, and effective in reducing markers/risk factors for aging and age-related diseases. Larger studies in patients with diagnosed diseases or selected on the basis of risk factors are warranted to confirm the effect of the FMD on disease prevention and treatment.

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          Most cited references20

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          Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies.

          The purpose of this research was to assess the association between the metabolic syndrome (MetSyn) and cardiovascular events and mortality by meta-analyses of longitudinal studies. Controversy exists regarding the cardiovascular risk associated with MetSyn. We searched electronic reference databases through March 2005, studies that referenced Reaven's seminal article, abstracts presented at meetings in 2003 to 2004, and queried experts. Two reviewers independently assessed eligibility. Longitudinal studies reporting associations between MetSyn and cardiovascular events or mortality were eligible. Two reviewers independently used a standardized form to collect data from published reports. Authors were contacted. Study quality was assessed by the control of selection, detection, and attrition biases. We found 37 eligible studies that included 43 cohorts (inception 1971 to 1997) and 172,573 individuals. Random effects meta-analyses showed MetSyn had a relative risk (RR) of cardiovascular events and death of 1.78 (95% confidence interval [CI] 1.58 to 2.00). The association was stronger in women (RR 2.63 vs. 1.98, p = 0.09), in studies enrolling lower risk (<10%) individuals (RR 1.96 vs. 1.43, p = 0.04), and in studies using factor analysis or the World Health Organization definition (RR 2.68 and 2.06 vs. 1.67 for National Cholesterol Education Program definition and 1.35 for other definitions; p = 0.005). The association remained after adjusting for traditional cardiovascular risk factors (RR 1.54, 95% CI 1.32 to 1.79). The best available evidence suggests that people with MetSyn are at increased risk of cardiovascular events. These results can help clinicians counsel patients to consider lifestyle interventions, and should fuel research of other preventive interventions.
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            Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan.

            Most animals alternate periods of feeding with periods of fasting often coinciding with sleep. Upon >24 hr of fasting, humans, rodents, and other mammals enter alternative metabolic phases, which rely less on glucose and more on ketone body-like carbon sources. Both intermittent and periodic fasting result in benefits ranging from the prevention to the enhanced treatment of diseases. Similarly, time-restricted feeding (TRF), in which food consumption is restricted to certain hours of the day, allows the daily fasting period to last >12 hr, thus imparting pleiotropic benefits. Understanding the mechanistic link between nutrients and the fasting benefits is leading to the identification of fasting-mimicking diets (FMDs) that achieve changes similar to those caused by fasting. Given the pleiotropic and sustained benefits of TRF and FMDs, both basic science and translational research are warranted to develop fasting-associated interventions into feasible, effective, and inexpensive treatments with the potential to improve healthspan.
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              Prevalence of the Metabolic Syndrome Among US Adults

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                Author and article information

                Journal
                101505086
                36963
                Sci Transl Med
                Sci Transl Med
                Science translational medicine
                1946-6234
                1946-6242
                11 October 2019
                15 February 2017
                28 October 2019
                : 9
                : 377
                : eaai8700
                Affiliations
                [1 ]Longevity Institute, School of Gerontology, and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
                [2 ]Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
                [3 ]Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
                [4 ]Department of Internal Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
                [5 ]Department of Internal and Complementary Medicine, Charite University Medical Center, 10117 Berlin, Germany.
                [6 ]Department of Clinical Medicine, Sapienza University, 00185 Rome, Italy.
                [7 ]FIRC Institute of Molecular Oncology, Italian Foundation for Cancer Research Institute of Molecular Oncology, 20139 Milan, Italy.
                Author notes
                []Corresponding author. vlongo@ 123456usc.edu

                Author contributions: V.D.L., M.W., T.E.M., and T.D. designed the clinical trial. M.W., K.H., and T.D. supervised the clinical trial. J.B. and M.S. contributed to patient recruitment and supervision. S.B., H.M., C.W.C., E.G., S.G., and W.J.M. performed data analysis. S.B. and V.D.L. wrote the paper. All authors discussed the results and commented on the manuscript.

                [*]

                These authors contributed equally to this work.

                Article
                PMC6816332 PMC6816332 6816332 nihpa1054235
                10.1126/scitranslmed.aai8700
                6816332
                28202779
                69e53b9a-f95e-490d-9d9d-bd79a079b07f
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