Fasting Rediscovered… The Science of not

Mark Jabro, MD Metabolic definition of Fasting

The beginning of ketogenesis and the depletion of glycogen is the beginning of fasting. Fasting is Ancient

• Humans evolved with fasting and feasting • Famine was a regular occurrence in ancient times • Religious observances Fasting/Intermittent

• Time restricted feeding (TRF) • 16:8 • 24 • Restrictive eating time window • Modified fasting 5/2 • 2 consecutive days of calorie restriction (low calorie intake) • Extended/Periodic Fasting • 3-5 days or longer to deplete glycogen stores and begin ketogenesis • Alternate Day Fasting • Full day fast followed by normal eating next day

Meal Frequency

• Has increased overtime, from 3 to 6 meals per day. • Continuous eating during waking hours

• 1960s study-showed frequent smaller meals better

• Epidemiological Study- 1.5 times more likely to be /obese with frequency of 5 or more per day vs 3 or fewer. What to “eat” during a fast

• Classic water fasting • Conventional advice is more “comfortable” • Coffee, tea, broth/electrolytes No proven best way to fast

• Multiple variables • Percent calorie reduction • 50-75-100% (pure water fast) • How long? • hours to days • How often to cycle • Alternate day, weekly, monthly, quarterly

• Which is best? Why Fast

• Survival Gene Activation • Brain-Body increase efficiency and self protective • Fasting is stress on the body. Gene expression is altered to protect from this stress. • Decreased /improved biomarkers • Saves Time and Money Misconceptions of fasting

• Fasting = • Fasting is volitional • Body enters starvation mode • shuts down and prevents fat burning • Muscle Loss • 2016 study 8 wks 16/8 TRF + resistance training preserved muscle mass • is the most important meal of the day. • Breakfast is not essential for weight control • Controlled trials do not show weight difference Challenges of Fasting • Not appropriate with active eating disorders • , binge eating, bulimia • Uncomfortable • Exercise requires more planning • Social Factors • Impromptu happy hour, dinner with friends Weakness of Observational Studies Because of their passive nature and lack of constants, observational longitudinal studies have less ability to detect causal relationships than do controlled trials.

When evidence from multiple observational studies is consistent the association is more likely to be real. What is the important for ?

• Dated Concepts • Calorie counting and exercise. • What should I eat? Low fat • How much should I eat? calories

• New Concepts • Diet composition, timing and good genes. • When should I eat? • Should I eat at all? Circadian Rhythm Asynchrony leads to

• Multiple body clocks • Brain, gut, kidney, and liver

• Master clock is Suprachiasmatic Nucleus (SCN) • Dysregulation of circadian rhythm is linked to obesity • Eating before bedtime is not a good idea • Sleep deprivation and timing of eating are important • Diet is a key extrinsic cue interacting with intrinsic clocks TRF and Circadian Rhythms based on Dr. Panda’s research • TRF limiting calorie intake. 8-12 hours • Focus on when to eat and not just what and how much to eat. • Digestive clock • Activates with consumption • Stand by mode when processing is complete • Repairs occur when system is not processing Time Restricted Feeding is a Preventative and Therapeutic Intervention against Diverse Nutritional Challenges (Dr. Panda, 2014)

• Mice restricted to different feeding intervals • 8, 9, 12, 15 hours eating window • One group had access to 24 hours • Calorie intake comparable in all cohorts

• Mice with the most restricted eating window performed best on fitness tests. • Mice restricted to 12 hours or less were protected from obesity, metabolic disease and inflammation vs control.

Take away: TRF is a behavioral intervention De-emphasizes calorie intake Results: Attractive and easily adoptable lifestyle modification. protects against weight gain and metabolic Eating during consistent time periods each day is helpful for keeping biological rhythms in sync which can help with preventing metabolic disease and chronic diseases related to obesity Intermittent calorie restriction

• 5:2 or 2 day diet aka intermittent energy restriction (IER) • Calorie restricted, low carb diet • 2 consecutive days each week • More practical than total fasting

• Short term human studies (Dr. Michelle Harvie) • Benefits include weight loss and improvement in metabolic disease markers • Negative: does not allow cells to enter a fasting state Periodic Fasting/Extended Fasting

Limiting calories between 3-5 days or longer

Valter Longo, PHD, USC Longevity Institute • Deplete glycogen stores and begin ketogenesis • Destruction and removal of damaged cells during fasting • Replacement of functional cells during refeeding

Created Fasting Mimicking diet (FMD) to limit calories between 770 and 1,110 a day.

Longo’s Human study, February 2017, results: • Improvement in body weight, waist circumference and BMI • Improvement in absolute total body and trunk fat • Improvement in risk factors for aging and disease Guides to Fasting • Jason Fung, MD – Intensive Dietary Management program in Toronto. The Complete Guide to Fasting. • Excellent Resource for what is fasting, why it is important, and how to fast in a way that improves your health. Guiding a Patient through Fasting

• Success is dependent upon • Fasting is safe for anyone persistence, reproducibility and without preexisting medical comfort. conditions and good health • 100% compliance is not • Physician supervision should be considered for patients required with metabolic disease and • Adjust TRF to the daily social diabetes schedule • Waves of are transient • Focus on time interval first and and will pass then once mastered then • Proper hydration is important optimize diet composition also supplement with • Calorie counting only important electrolytes for breaking through plateaus • If uncontrollable hungry or severe weakness then eat. “They should moreover, eat only once a day” -Hippocrates Obesity Fact-BMI

• Body Mass Index: kg/m2 • Introduced by a Belgian Mathematician • Early 19th century • Designed as a quick and easy way to measure obesity in the general population to assist gov in resource allocation. • Obesity is defined as fat excess not weight excess • BMI does not measure fat and does not differentiate between visceral and subcutaneous. • It is accurate in assessing disease risk and easy to measure Obesity Fact: Risk

55% of all cancer in Women and 24% in men are associated with overweight and obesity.

Breast, colon, endometriosis, esophageal, prostate, thyroid, kidney , pancreas, gallbladder

Take away: Body fat reduction is anti cancer.