2010-stannard.pdf: “Adaptations to skeletal muscle with endurance exercise training in the acutely fed versus overnight-fasted state”, Stephen R. Stannard, Alex J. Buckley, Johann A. Edge, Martin W. Thompson
1986-dohm.pdf: “Metabolic responses to exercise after fasting”, (1986-10-01; ):
Fasting before exercise increases fat utilization and lowers the rate of muscle glycogen depletion. Since a 24-h fast also depletes liver glycogen, we were interested in blood glucose homeostasis during exercise after fasting. An experiment was conducted with human subjects to determine the effect of fasting on blood metabolite concentrations during exercise. Nine male subjects ran (70% maximum O2 consumption) two counterbalanced trials, once fed and once after a 23-h fast. Plasma glucose was elevated by exercise in the fasted trial but there was no difference between fed and fasted during exercise. Lactate was statistically-significantly higher (P less than 0.05) in fasted than fed throughout the exercise bout. Fat mobilization and utilization appeared to be greater in the fasted trial as evidenced by higher plasma concentrations of free fatty acids, glycerol, and beta-hydroxybutyrate as well as lower respiratory exchange ratio in the fasted trial during the first 30 min of exercise. These results demonstrate that in humans blood glucose concentration is maintained at normal levels during exercise after fasting despite the depletion of liver glycogen. Homeostasis is probably maintained as a result of increased gluconeogenesis and decreased utilization of glucose in the muscle as a result of lowered pyruvate dehydrogenase activity.
Hormesis occurs when a low level stress elicits adaptive beneficial responses that protect against subsequent exposure to severe stress. Recent findings suggest that mild oxidative and thermal stress can extend lifespan by hormetic mechanisms. Here we show that the botanical pesticide plumbagin, while toxic to C. elegans nematodes at high doses, extends lifespan at low doses. Because plumbagin is a naphthoquinone that can generate free radicals in vivo, we investigated whether it extends lifespan by activating an adaptive cellular stress response pathway. The C. elegans cap’n’collar (CNC) transcription factor, SKN-1, mediates protective responses to oxidative stress. Genetic analysis showed that skn-1 activity is required for lifespan extension by low-dose plumbagin in C. elegans. Further screening of a series of plumbagin analogs identified three additional naphthoquinones that could induce SKN-1 targets in C. elegans. Naphthazarin showed skn-1-dependent lifespan extension, over an extended dose range compared to plumbagin, while the other naphthoquinones, oxoline and menadione, had differing effects on C. elegans survival and failed to activate ARE reporter expression in cultured mammalian cells. Our findings reveal the potential for low doses of naturally occurring naphthoquinones to extend lifespan by engaging a specific adaptive cellular stress response pathway.
2011-teng.pdf: “Efficacy of fasting calorie restriction on quality of life among aging men”, Nur Islami Mohd Fahmi Teng, Suzana Shahar, Zahara Abdul Manaf, Sai Krupa Das, Che Suhaili Che Taha, Wan Zurinah Wan Ngah
“Ageing and its implications”, (2010):
Ageing processes are defined as those that increase the susceptibility of individuals, as they grow older, to the factors that eventually lead to death. It is a complex multi-factorial process, where several factors may interact simultaneously and may operate at many levels of functional organization. The heterogeneity of ageing phenotype among individuals of the same species and differences in longevity among species are due to the contribution of both genetic and environmental factors in shaping the life span. The various theories of ageing and their proposed roles are discussed in this review.
Background: Asthma is an increasingly common disorder responsible for considerable morbidity and mortality. Although obesity is a risk factor for asthma and weight loss can improve symptoms, many patients do not adhere to low calorie diets and the impact of dietary restriction on the disease process is unknown.
Objective: A study was designed to determine if overweight asthma patients would adhere to an alternate day calorie restriction (ADCR) dietary regimen, and to establish the effects of the diet on their symptoms, pulmonary function and markers of oxidative stress and inflammation.
Methods: Ten subjects with BMI>30 were maintained for 8 weeks on a dietary regimen in which they ate ad libitum every other day, while consuming less than 20% of their normal calorie intake on the intervening days. At baseline, and at designated time points during the 8 week study, asthma control, symptoms and Quality of Life questionnaires (ACQ, ASUI, mini-AQLQ) were assessed and blood was collected for analyses of markers of general health, oxidative stress and inflammation. Peak Expiratory Flow (PEF) was measured daily on awakening. Pre and post bronchodilator spirometry was obtained at baseline and 8 weeks.
Results: Nine of the subjects adhered to the diet and lost an average of 8% of their initial weight during the study. Their asthma related symptoms, control and QOL improved statistically-significantly, and PEF increased statistically-significantly, within 2 weeks of diet initiation; these changes persisted for the duration of the study. Spirometery was unaffected by ADCR. Levels of serum β-hydroxybutyrate were increased and levels of leptin were decreased on CR days indicating a shift in energy metabolism towards utilization of fatty acids and confirming compliance with the diet. The improved clinical findings were associated with decreased levels of serum cholesterol and triglycerides, striking reductions in markers of oxidative stress (8-isoprostane, nitrotyrosine, protein carbonyls, and 4-hydroxynonenal adducts) and increased levels of the antioxidant uric acid. Indicators of inflammation, including serum tumor necrosis factor-α and brain-derived neurotrophic factor, were also statistically-significantly decreased by ADCR.
Conclusions: Compliance with the ADCR diet was high, symptoms and pulmonary function improved, and oxidative stress and inflammation declined in response to the dietary intervention. These findings demonstrate rapid and sustained beneficial effects of ADCR on the underlying disease process in subjects with asthma, suggesting a novel approach for therapeutic intervention in this disorder.
[Keywords: AQLQ, isoprostanes, peak expiratory flow, protein carbonyls, nitrotyrosine, BDNF, spirometry, tumor necrosis factor, oxidative stress]
2015-brandhorst.pdf: “A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan”, Sebastian Brandhorst, In Young Choi, Min Wei, Chia Wei Cheng, Sargis Sedrakyan, Gerardo Navarrete, Louis Dubeau, Li Peng Yap, Ryan Park, Manlio Vinciguerra, Stefano Di Biase, Hamed Mirzaei, Mario G. Mirisola, Patra Childress, Lingyun Ji, Susan Groshen, Fabio Penna, Patrizio Odetti, Laura Perin, Peter S. Conti, Yuji Ikeno, Brian K. Kennedy, Pinchas Cohen, Todd E. Morgan, Tanya B. Dorff, Valter D. Longo
Importance: Alternate-day fasting has become increasingly popular, yet, to date, no long-term randomized clinical trials have evaluated its efficacy.
Objective: To compare the effects of alternate-day fasting vs daily calorie restriction on weight loss, weight maintenance, and risk indicators for cardiovascular disease.
Design, Setting, and Participants: A single-center randomized clinical trial of obese adults (18 to 64 years of age; mean body mass index, 34) was conducted between October 1, 2011, and January 15, 2015, at an academic institution in Chicago, Illinois.
Interventions: Participants were randomized to 1 of 3 groups for 1 year: alternate-day fasting (25% of energy needs on fast days; 125% of energy needs on alternating “feast days”), calorie restriction (75% of energy needs every day), or a no-intervention control. The trial involved a 6-month weight-loss phase followed by a 6-month weight-maintenance phase.
Main Outcomes and Measures: The primary outcome was change in body weight. Secondary outcomes were adherence to the dietary intervention and risk indicators for cardiovascular disease.
Results: Among the 100 participants (86 women and 14 men; mean [SD] age, 44  years), the dropout rate was highest in the alternate-day fasting group (13 of 34 [38%]), vs the daily calorie restriction group (10 of 35 [29%]) and control group (8 of 31 [26%]). Mean weight loss was similar for participants in the alternate-day fasting group and those in the daily calorie restriction group at month 6 (-6.8% [95% CI, -9.1% to -4.5%] vs -6.8% [95% , -9.1% to -4.6%]) and month 12 (-6.0% [95% , -8.5% to -3.6%] vs -5.3% [95% , -7.6% to -3.0%]) relative to those in the control group. Participants in the alternate-day fasting group ate more than prescribed on fast days, and less than prescribed on feast days, while those in the daily calorie restriction group generally met their prescribed energy goals. There were no statistically-significant differences between the intervention groups in blood pressure, heart rate, triglycerides, fasting glucose, fasting insulin, insulin resistance, C-reactive protein, or homocysteine concentrations at month 6 or 12. Mean high-density lipoprotein cholesterol levels at month 6 significantly increased among the participants in the alternate-day fasting group (6.2 mg/dL [95% , 0.1-12.4 mg/dL]), but not at month 12 (1.0 mg/dL [95% , -5.9 to 7.8 mg/dL]), relative to those in the daily calorie restriction group. Mean low-density lipoprotein cholesterol levels were significantly elevated by month 12 among the participants in the alternate-day fasting group (11.5 mg/dL [95% , 1.9-21.1 mg/dL]) compared with those in the daily calorie restriction group.
Conclusions and Relevance: Alternate-day fasting did not produce superior adherence, weight loss, weight maintenance, or cardioprotection vs daily calorie restriction.
Trial Registration: clinicaltrials.gov Identifier: NCT00960505.