1.
Autophagy and intermittent fasting: the connection for cancer therapy?
Antunes, F, Erustes, AG, Costa, AJ, Nascimento, AC, Bincoletto, C, Ureshino, RP, Pereira, GJS, Smaili, SS
Clinics (Sao Paulo, Brazil). 2018;73(suppl 1):e814s
-
-
-
Free full text
Plain language summary
Autophagy is a cellular mechanism that removes unnecessary or dysfunctional components and is being studied intensively with regards to chronic disease, including cancer. Dietary restriction, as in intermittent fasting, is thought to activate autophagy. The authors review the literature and possible mechanisms for autophagy in cancer, noting that autophagy can both suppress and support cancer development and growth. It appears that fasting in combination with cytotoxic drugs elicits differential responses in normal and cancer cells, whereby normal cells prioritise maintenance pathways and inactivate growth factor signalling when nutrients are absent, whilst cancer cells, do not inhibit stress resistance pathways, thus becoming vulnerable to cytotoxic treatment Preclinical studies on calorie restriction or intermittent fasting in combination with chemo- and/or radiotherapy have found beneficial effects in animal and in vitro studies. There are a number of clinical human trials underway, but only two completed pilot trials, which showed promising results with reducing side effects and increasing efficacy of the chemotherapeutic drugs through intermittent fasting.
Abstract
Cancer is a leading cause of death worldwide, and its incidence is continually increasing. Although anticancer therapy has improved significantly, it still has limited efficacy for tumor eradication and is highly toxic to healthy cells. Thus, novel therapeutic strategies to improve chemotherapy, radiotherapy and targeted therapy are an important goal in cancer research. Macroautophagy (herein referred to as autophagy) is a conserved lysosomal degradation pathway for the intracellular recycling of macromolecules and clearance of damaged organelles and misfolded proteins to ensure cellular homeostasis. Dysfunctional autophagy contributes to many diseases, including cancer. Autophagy can suppress or promote tumors depending on the developmental stage and tumor type, and modulating autophagy for cancer treatment is an interesting therapeutic approach currently under intense investigation. Nutritional restriction is a promising protocol to modulate autophagy and enhance the efficacy of anticancer therapies while protecting normal cells. Here, the description and role of autophagy in tumorigenesis will be summarized. Moreover, the possibility of using fasting as an adjuvant therapy for cancer treatment, as well as the molecular mechanisms underlying this approach, will be presented.
2.
Serum Polychlorinated Biphenyls Increase and Oxidative Stress Decreases with a Protein-Pacing Caloric Restriction Diet in Obese Men and Women.
He, F, Zuo, L, Ward, E, Arciero, PJ
International journal of environmental research and public health. 2017;14(1)
-
-
-
Free full text
Plain language summary
Weight loss (WL) diets lower heart disease risk factors, and protein-pacing calorie restriction (P-CR, more than 25% of calories from protein) is one of the most efficacious interventions to treat obesity. During fat loss polychlorinated biphenyls (PCBs) are released into the blood stream and can disrupt metabolic and endocrine function in humans, having an adverse effect on health. The primary aim of this study was to compare changes in serum PCBs and oxidative stress biomarkers between obese men and women following a short-term P-CR diet. Participants, who were all overweight or obese, followed a P-CR WL diet which included 1 day per week of intermittent fasting (less than 330-430 kcal/day) for 12 weeks, a protein drink and a protein bar were provided. After the initial 12 weeks, participants self-selected to either continue with the P-CR diet or follow an approved “heart healthy” diet (HH) for one year. Laboratory tests were done at baseline, week 12 and at the end of the study (64 weeks). Weight loss was observed in the initial 12 weeks and was accompanied with an increase in PCBs, with no difference between men and women. Oxidative stress markers were decreased and total antioxidant capacity (TAC) was increased. After 64 weeks changes in circulating PCBs were higher in those who lost more body weight and fat. PCBs decreased more in the HH group than the P-CR group, which was associated with an increase in weight in the HH group. No significant difference was found in terms of oxidative stress and antioxidant status between P-CR and HH group. The authors concluded that a P-CR diet is an effective dietary intervention to induce weight loss, as well as mobilise stored PCBs and improve redox status.
Abstract
The purposes were to compare the effects of a: (1) 12-week P-CR weight loss (WL) diet (Phase 1) between obese men and women and; (2) 52-week modified P-CR (mP-CR) vs. heart healthy (HH) weight maintenance (WM) diet (Phase 2) on serum PCBs and oxidative stress biomarkers (thiobarbituric acid reactive substances, TBARS; total antioxidant capacity, TAC) in 40 obese participants (men, n = 21; women, n = 19). Participants received dietary counseling and monitoring of compliance. PCBs, TBARS, and TAC were assessed at weeks -1 (CON), 12 (WL), and 64 (WM). Following WL (Week 12), concomitant with reductions in TBARS (0.24 ± 0.15 vs. 0.18 ± 0.11 µM; p < 0.01), PCB serum concentrations (86.7 ± 45.6 vs. 115.6 ± 65.9 ng/g lipid; p < 0.01) and TAC (18.9 ± 2.6 vs. 19.9 ± 2.3 nmol/mL; p < 0.02) were increased similarly in men and women. At the end of WM (Week 64), a significant effect of time × group interaction was observed for % change in PCB 170 and 187; whereby mP-CR values were higher compared to HH (PCB170: 19.31% ± 26.48% vs. -6.61% ± 28.88%, p = 0.02; PCB187: -3.04% ± 17.78% vs. -21.4% ± 27.31%, p = 0.04). PCB changes were positively correlated with TBARS levels (r > 0.42, p < 0.05) and negatively correlated with body weight, fat mass, and abdominal fat (r < -0.46, p < 0.02). Our results support mobilization of stored PCBs as well as enhanced redox status following a 12-week P-CR WL diet. Additionally, a 52-week mP-CR WM diet demonstrated an advantage in preventing weight gain relapse accompanied by an increase in circulating PCBs compared to a traditional HH diet.