The Hunger Games Reviewing the Evidence on Intermittent Fasting Monique Piderit, RD (SA) @MoniquePiderit
Outline 1. Defining Intermittent Fasting Calorie restriction vs. Intermittent Fasting Different types of Intermittent Fasting 2. Natural Models to Study Intermittent Fasting Animal Models Dutch Famine Ramadan 3. The Physiology of Intermittent Fasting Epilepsy Cancer Type II Diabetes Cardiovascular disease Mood Disorders Weight loss 4. Applying IF in Dietetic Practice
Calorie Restriction vs. Intermittent Fasting Calorie Restriction (CR) Method of energy deprivation TE by 20 50% of needs Frustration, adherence differs Seimon et al, 2015; Johnstone t al, 2014; Meo et al, 2015 Intermittent Fasting (IF): Significant energy restriction (75 90%) on 1 3 days per week (i.e. fasting days) with ad libitum food consumption on non-restricted days (i.e. fed days) Barnosky et al, 2014; Skazniek-Wikiel et al, 2014
Studies in Animal Models Significantly extended reproductive health into advanced age. Higher survival rates of offspring and sustained fertility. Skaznik-Wikiel and Polotsky, 2014 Food restriction (without malnutrition) extends average and maximal lifespan. Physiologically younger than ad libitum fed animals. Prevent chronic disease in rodents. Improved insulin sensitivity. Reduced oxidative stress. Enhanced immunity. Animals are leaner, less body fat and smaller. Lifespan extended and increases progressively as caloric intake reduced. Rizza et al, 2014; Skaznik-Wikiel and Polotsky, 2014
Different Methods of Intermittent Fasting The 16/8 Method: Fast for 16 hours, Eat for 8 hours The 5/2 Diet: Eat for 5 days, Fast 2 days per week Eat-Stop-Eat: Do a 24-hour fast, 1-2 x per week Alternate Day Fasting: Fast every other day (75% of TE) Warrior Fast: Fast in the day, eat huge meal at night Spontaneous Fast: Skip meals (as and when convenient)
Ramadan as a model to study IF The 16/8 Method: Fast for 16 hours, Eat for 8 hours Al Jazeera Website, May 2017
Ramadan Muslims fast from food and drink from sunrise until sunset. Not a continual fast but provides insight into short-term food restriction in healthy humans. Total daily energy intake is not decreased: Reduced kj intake in first week but increase thereafter. Comparable levels of energy intake before, during and after Ramadan No changes in body weight Adults are capable of making compensatory changes in food intake in response to a short term fast in order to maintain weight. Jonstone et al, 2014; Meo et al, 2015
The Dutch Famine Retrospective studies on the infamous Dutch famine: 1944-1945 Daily rations: 400 800 kcal per day for 5 6 months in morbidity and mortality Lumey and Van Poppel, 1994 Women in early gestation: Higher overall adult, CVD, cancer and breast cancer mortality risk Children: Increased CHD risk in adulthood Van Abeelen et al, 2012
Physiological Benefits of Intermittent Fasting Cardiovascular system Metabolic fuel BP HR Fat oxidation CHO oxidation De Azevedo et al 2013 Gene Expression Metabolic/ Inflammatory Cell survival Sirt2 and Sirt1 Glucose Insulin TG HDL IL-6, TNF-α, CRP
Epilepsy and seizures Type 2 Diabetes Mood disorder Sleep Weight Loss CVD Cancer Longevity
Epilepsy and Intermittent Fasting Anticonvulsant properties of ketones. Ketogenic diet to mimic metabolic changes of starvation: o 24-hour fast o Total calories restricted to 80 90% of needs. o Fat : protein 2:1 to 4:1. Energy restriction reduces seizures in animals: o inflammation neuronal excitability o glucose levels releases of ATP adenosine stabilises neuronal membranes and increases seizure threshold o sirtuin expression neuroprotection IF may be expected to reduce seizures in those with epilepsy. Hartman et al, 2013; Yuen and Sander, 2014; Maalouf et al, 2009
Mood, Depression, Pain and Intermittent Fasting More participants in IF group reported hunger and/or preoccupation with food, as well as decreases in hunger and uncontrolled eating with concomitant increase in fullness, satisfaction and restrained eating. Seimon et al, 2015 CR group reported bad temper. Harvie et al, 2011 No difference in mood, vigor, self-reported tension, depression, or anger. Harvie et al, 2013 Mood enhancement and substantial pain relief in those with chronic pain. Michalsen, 2010 Significant decreases in tension, anger, confusion and total mood disturbance in aging men. No significant changes in mean depression score Hussin et al, 2013
Positive energy balance in adult increases adiposity and contributes to risk of developing several cancers. Weight loss lowers this risk Longo and Fontana, 2010; Calle and Kaaks, 2004 Excessive energy and protein intake before puberty causes rapid growth and early menarche is linked to breast cancer in adult life. Berkey et al, 2000 FM, fasting insulin, insulin sensitivity: effect of IF and CR on these diabetic risk factors comparable. Unclear whether IF elicits comparable improvements in diabetes risk indicators compared to CR. Barnosky et al, 2014 CRONIes have total cholesterol, LDL, TG, blood pressure, fasting glucose and CRP. Beneficial effects on cardiovascular disease related to high quality diets (no refined CHO, eliminated processed foods, low GI food). Fontana et al, 2004-2010
40 publications Original studies RCT, pilot studies Duration ranged: 2 104 weeks Excluded Ramadan Normal weight Overweight Obese Mixed
Mechanisms of weight loss Ketogenic Diets Reduction in appetite: Satiety of protein. Effect on appetite control hormones. Appetite suppression of ketones. Reduction in lipogenesis and increased lipolysis Greater metabolic efficiency in consuming fats Increased metabolic costs of gluconeogenesis and the thermic effect of protein Paolo, 2014
Ketones in Intermittent fasting Ketosis appears to provide a plausible explanation for the suppression of appetite. Changes in gut function alter appetite-regulating hormones: CCK, ghrelin, peptide YY. Appetite increased during first few days of fasting before ketone level raised Minimum 2 3 weeks to induce ketosis Paoli, 2014 Production of ketones: β-oxidation in the liver of FFA. Alternate fuel source (derived from fat) when glucose in short supply. Very low energy diets (i.e. IF) and LCHF diets can both cause ketosis, but LCHF result in several fold higher circulating levels of ketones. Further studies should investigate the minimum level of ketosis required to achieve appetite suppression during ketogenic weight loss diets as this could enable greater variety of healthy carbohydrate-containing foods into the diet. Gibson et al, 2015
Weight Loss and Intermittent Fasting 25 obese post-menopausal women Body weight, waist circumference, %BF and FM decreases significantly but similarly (IF versus CR) Most improvements occurred in first 5 weeks of both intervention groups. Arguin et al, 2012 12 lean men and 12 lean women for three days IF: Evidence that men lose more weight than women After the fast, subjects consumed less energy. IF is a viable weight loss strategy or normal weight and overweight individuals who aim to lose moderate amounts of weight (5 6 kg) within a short period of time (12 weeks) Johstone et al, 2015 54 obese women IF combined with CR is an effective strategy for weight loss in obese women. Klempel et al, 2012
Weight Loss and Intermittent Fasting Effective method for weight loss (37 of 40 publications) BMI Waist circumference Fat Mass Fat free mass Very low dropout rate High patient compliance Better adherence Learn to deal with feelings of hunger, important skill in achieving and maintaining weight loss De Azevedo et al, 2013; Seimon et al, 2015; Thom et al, 2017
In the short term, intermittent energy and carbohydrate restriction is superior to daily energy restriction. (3 months) Harvie et al, 2013 Alternate day fasting did not produce superior adherence, weight loss or weigh maintenance versus calorie restriction. (12 month study period) Trepanowski et al, 2017 [CR and IF] equally effective for decreasing body weight and fat mass, but IF may be more effective for the retention of muscle mass. (review) But Wait Varady, 2011 Diets highly variable with respect to energy intake, macronutrient distribution, timing of the feast versus fast. Research on time-restricted feeding is limited and clear conclusion cannot be made. Tinsley and La Bounty, 2015 Study sample sizes small. Significance of results questioned Further clinical studies essential to test the effectiveness of IF in preventing and controlling metabolic and cardiovascular disease. De Azevedo et al, 2013 Lack of long term follow up Intermittent fasting thus represents a valid- albeit apparently not superior- option to continuous energy restriction Animal for studies weight loss. Seimon et al, 2015 Drop out rates high: 38% - 64%
Physical Activity with Intermittent Fasting When IF combined with exercise, even greater weight loss achieved (±3kg more compared to IF alone). Seimon et al, 2015. Greater reductions in %FM Reduced emotional eating. Decreased hunger. Decreased drive to eat. Increase fullness and satisfaction. Are the changes related to ketosis? Bhutani et al, 2013
Applying IF to Practice Combination of CR and IF IF short term (3 months) vs. CR long term To induce ketosis, 2 3 weeks Evaluate nutritional consequences of energy restriction What about fasting from a food group for a certain amount of time? Experiment with meal times Is breakfast skipping similar to IF? Breakfast skipping and exclusion of late eating result in reduction of voluntary kj intake. Skipping BF can be as metabolically beneficial as excluding a late meal Perhaps once in a while an inter-meal interval is long enough to allow ketosis to initiate lipolysis and lower energy intake. Zilberter and Zilberter, 2014
Growth hormone Enhances lipoprotein lipase expression Anabolic effect of protein metabolism Antagonist to insulin action Insulin Regulates carbohydrate and lipid metabolism Stimulates lipogenesis Represses lipolysis and proteolysis Vijayakumar et al, 2011
(Intermittent) Fasting from Carbohydrates If GH blocks insulin action in fatty tissue, then could fasting from carbohydrates (which stimulate insulin) for 12 hours help with weight loss? Related to kilojoule restriction as well as GH-mediated induction of insulin resistance Ghrelin stimulates GH but increases food intake and decreases lipid utilization Vijayakumar et al, 2011; Hassouna et al, 2010
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Thank You! @MoniquePiderit monique@nutritionalsolutions.co.za Monique Piderit Registered Dietitian