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      Obesity, cancer risk, and time-restricted eating

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          Abstract

          Obesity and the associated metabolic syndrome is considered a pandemic whose prevalence is steadily increasing in many countries worldwide. It is a complex, dynamic, and multifactorial disorder that presages the development of several metabolic, cardiovascular, and neurodegenerative diseases, and increases the risk of cancer. In patients with newly diagnosed cancer, obesity worsens prognosis, increasing the risk of recurrence and decreasing survival. The multiple negative effects of obesity on cancer outcomes are substantial, and of great clinical importance. Strategies for weight control have potential utility for both prevention efforts and enhancing cancer outcomes. Presently, time-restricted eating (TRE) is a popular dietary intervention that involves limiting the consumption of calories to a specific window of time without any proscribed caloric restriction or alteration in dietary composition. As such, TRE is a sustainable long-term behavioral modification, when compared to other dietary interventions, and has shown many health benefits in animals and humans. The preliminary data regarding the effects of time-restricted feeding on cancer development and growth in animal models are promising but studies in humans are lacking. Interestingly, several short-term randomized clinical trials of TRE have shown favorable effects to reduce cancer risk factors; however, long-term trials of TRE have yet to investigate reductions in cancer incidence or outcomes in the general population. Few studies have been conducted in cancer populations, but a number are underway to examine the effect of TRE on cancer biology and recurrence. Given the simplicity, feasibility, and favorable metabolic improvements elicited by TRE in obese men and women, TRE may be useful in obese cancer patients and cancer survivors; however, the clinical implementation of TRE in the cancer setting will require greater in-depth investigation.

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          Most cited references215

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          Understanding the Warburg effect: the metabolic requirements of cell proliferation.

          In contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, a phenomenon termed "the Warburg effect." Aerobic glycolysis is an inefficient way to generate adenosine 5'-triphosphate (ATP), however, and the advantage it confers to cancer cells has been unclear. Here we propose that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass (e.g., nucleotides, amino acids, and lipids) needed to produce a new cell. Supporting this idea are recent studies showing that (i) several signaling pathways implicated in cell proliferation also regulate metabolic pathways that incorporate nutrients into biomass; and that (ii) certain cancer-associated mutations enable cancer cells to acquire and metabolize nutrients in a manner conducive to proliferation rather than efficient ATP production. A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer.
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            Exercise Guidelines for Cancer Survivors

            The number of cancer survivors worldwide is growing, with over 15.5 million cancer survivors in the United States alone-a figure expected to double in the coming decades. Cancer survivors face unique health challenges as a result of their cancer diagnosis and the impact of treatments on their physical and mental well-being. For example, cancer survivors often experience declines in physical functioning and quality of life while facing an increased risk of cancer recurrence and all-cause mortality compared with persons without cancer. The 2010 American College of Sports Medicine Roundtable was among the first reports to conclude that cancer survivors could safely engage in enough exercise training to improve physical fitness and restore physical functioning, enhance quality of life, and mitigate cancer-related fatigue.
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              Overweight, Obesity, and Mortality from Cancer in a Prospectively Studied Cohort of U.S. Adults

              The influence of excess body weight on the risk of death from cancer has not been fully characterized. In a prospectively studied population of more than 900,000 U.S. adults (404,576 men and 495,477 women) who were free of cancer at enrollment in 1982, there were 57,145 deaths from cancer during 16 years of follow-up. We examined the relation in men and women between the body-mass index in 1982 and the risk of death from all cancers and from cancers at individual sites, while controlling for other risk factors in multivariate proportional-hazards models. We calculated the proportion of all deaths from cancer that was attributable to overweight and obesity in the U.S. population on the basis of risk estimates from the current study and national estimates of the prevalence of overweight and obesity in the U.S. adult population. The heaviest members of this cohort (those with a body-mass index [the weight in kilograms divided by the square of the height in meters] of at least 40) had death rates from all cancers combined that were 52 percent higher (for men) and 62 percent higher (for women) than the rates in men and women of normal weight. For men, the relative risk of death was 1.52 (95 percent confidence interval, 1.13 to 2.05); for women, the relative risk was 1.62 (95 percent confidence interval, 1.40 to 1.87). In both men and women, body-mass index was also significantly associated with higher rates of death due to cancer of the esophagus, colon and rectum, liver, gallbladder, pancreas, and kidney; the same was true for death due to non-Hodgkin's lymphoma and multiple myeloma. Significant trends of increasing risk with higher body-mass-index values were observed for death from cancers of the stomach and prostate in men and for death from cancers of the breast, uterus, cervix, and ovary in women. On the basis of associations observed in this study, we estimate that current patterns of overweight and obesity in the United States could account for 14 percent of all deaths from cancer in men and 20 percent of those in women. Increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites. Copyright 2003 Massachusetts Medical Society
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                Author and article information

                Contributors
                nwebster@health.ucsd.edu
                Journal
                Cancer Metastasis Rev
                Cancer Metastasis Rev
                Cancer Metastasis Reviews
                Springer US (New York )
                0167-7659
                1573-7233
                19 August 2022
                19 August 2022
                2022
                : 41
                : 3
                : 697-717
                Affiliations
                [1 ]GRID grid.410371.0, ISNI 0000 0004 0419 2708, VA San Diego Healthcare System, ; San Diego, CA USA
                [2 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Department of Medicine, Division of Endocrinology and Metabolism, , University of California, ; La Jolla, San Diego, CA USA
                [3 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Moores Cancer Center, , University of California, ; La Jolla, San Diego, CA USA
                Article
                10061
                10.1007/s10555-022-10061-3
                9470651
                35984550
                a705f358-cd67-421e-a6e3-b5e4efd949cb
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 12 April 2022
                : 9 August 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100007316, Division of Cancer Prevention, National Cancer Institute;
                Award ID: CA196853
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
                Award ID: HL141999
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100009012, Veterans Affairs San Diego Healthcare System;
                Award ID: BX004848
                Award ID: BX005224
                Award Recipient :
                Categories
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                © Springer Science+Business Media, LLC, part of Springer Nature 2022

                Oncology & Radiotherapy
                obesity,metabolism,cancer,dietary interventions time-restricted feeding

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