Dr. Satchin Panda: Intermittent Fasting to Improve Health, Cognition & Longevity

Intermittent Fasting and Time Restricted Feeding

• Intermittent fasting: various types of fasting, embedded in the history of caloric restriction 
  • 100 years ago, reducing calorie intake in rats led to longer lifespans
  • Idea: reducing daily calorie intake by 20% could lead to longer life by preventing age-​​related diseases and promoting repair mechanisms
  • Difficult to count and maintain reduced calories every day
• Every other day feeding in mice and rats 
  • Led to similar health improvements as continuous calorie restriction
  • Idea: humans could eat less for one or two days a week, leading to the 5:2 diet (eat for five days, reduce calories for two days)
  • Intermittent fasting: people fast periodically

Defining Fasting and Time Restricted Feeding

• Fasting: not eating for a certain period of time
• Time restricted feeding: eating within a specific window of time each day 
  • Everyone does this to some extent, as they don’t eat while sleeping
• Intermittent fasting covers many types of fasting, while time restricted feeding is a more specific term

Dr. Sachin Panda’s Research

• Dr. Panda’s laboratory focuses on the impact of intermittent fasting and time restricted feeding on mental health, physical health, and human performance
• His lab has made critical discoveries in how patterns of eating over time impact biology and health 
  • Pioneered discoveries related to intermittent fasting and time restricted feeding
• Dr. Panda has authored several books on the topic, including The Circadian Code and The Circadian Diabetes Code

Post-​​Mortem Human Retina Research

• Dr. Panda’s lab has also conducted research on post-​​mortem human retina

  • Potential for transplants to rescue vision in the blind
  • More details may be discussed later in the podcast
    Intermittent Fasting and Time Restricted Feeding

• Intermittent fasting: umbrella term for reducing calorie intake for one or more days in a week or month

• Time restricted feeding: confining all energy intake from solid and liquid food within a consistent window of 8–12 hours 
  • Originated from the science of circadian rhythm
  • Body has an internal timetable in every cell and organ
  • Circadian clocks are sensitive to light, which is the most dominant time giver
  • Changing feeding time can tune our liver clock and other parts of the brain
  • Consistency in feeding window helps the body anticipate and prepare for food intake

Anticipatory Signals and Health Benefits

• Anticipatory signals are important for waking up, digestion, and overall health 
  • Example: waking up to an alarm clock when the body is not prepared can lead to sleepiness, heart attacks, and car accidents
• Digestive system has rhythms, such as peristaltic action in the intestine 
  • Slows down at night, a few hours after the last meal
  • Eating late at night can lead to poor digestion and food hangovers
  • Healthy food at the wrong time can have negative effects

Consistency in Feeding Window

• Consistency in the feeding window helps the body’s anticipatory signals function properly 
  • Allows the body to be prepared for digestion and other physiological processes
• Changing the feeding window by even an hour can cause the body to take a day to catch up 
  • Example: traveling across time zones can cause jet lag and feelings of grogginess

• Maintaining a consistent feeding window can lead to better digestion, sleep, and overall health
  Intermittent Fasting and Time Restricted Feeding

• Benefits of eating first and last bite of food at the same time each day

• Different foods digest at different rates, affecting blood sugar levels
• Fasted state vs. fed state: how to define and measure them

Fasting and Blood Sugar

• Breaking a fast depends on the rise in blood glucose and molecular signals downstream
• Consuming a small amount of sugar may break a fast, but could return to a fasted state after physical activity
• Fasted state vs. fed state depends on the individual’s metabolism and activity levels

Fasted vs. Fed State in Mice

• Mice can switch from burning body fat to carbohydrates quickly after consuming food
• Indirect calorimetry measures oxygen and carbon dioxide to determine if the body is burning glucose or fat as an energy source
• Mice can return to a fasted state after consuming a small amount of food and engaging in physical activity

Caloric Restriction and Time Restricted Feeding

• Caloric restriction experiments often involve giving animals a reduced amount of food at one time
• Animals consume the reduced food within a few hours, leading to a long fasting period
• Question: Is the benefit of caloric restriction due to reduced calorie intake or time restricted feeding?

Caloric Restriction vs. Time Restricted Feeding in Mice

• Jota Kahassi’s lab published a study showing that most calorie restrictions create a condition of time restriction
• Experiment involved giving mice small meals throughout the day and night, with no fasting period

• Aimed to determine if the benefits of caloric restriction were due to reduced calorie intake or time restricted feeding
  Mouse Study on Time Restricted Feeding and Longevity

• Mice fed ad libitum lived a certain number of days

• Mice on caloric restriction (CR) with food distributed throughout 24 hours lived 10% longer
• Mice on CR with food restricted to daytime (active cycle) lived 20% longer
• Mice on CR with food restricted to nighttime (when they’re supposed to eat) lived 35% longer 
  • No difference in body weight and composition across all groups

Human Study on Time Restricted Feeding and Weight Loss

• Participants habitually ate within a 10-​​hour window
• Two groups: CR within a 10-​​hour window and CR within an 8‑hour window
• No difference in weight loss between the two groups 
  • Not surprising due to only a 2‑hour difference

Mouse Study on Different Feeding Windows

• Mice allowed to eat a sub-​​caloric diet within a 2‑hour or 12-​​hour window
• No change in longevity between the two groups 
  • Suggests that for mice, a 12-​​hour window provides the best benefit for longevity

Sex Differences in Time Restricted Feeding Studies

• Many mouse experiments only done in male mice
• NIH now requires sex as a biological variable in grant applications
• Differences between male and female mice observed in time restricted feeding studies

Human Feeding Window Duration

• Can’t conclude whether a 4, 6, 8, or 12-​​hour feeding window is best for humans
• People may inadvertently reduce calorie intake with shorter feeding windows due to gut volume

• One meal per day can lead to gastric distress and reduced energy levels
  Energy Intake and Relative Energy Deficit in Sports (REDS)

• People may reduce energy intake and increase physical activity

  • Can lead to adverse effects in the long term
• REDS: Relative Energy Deficit in Sports 
  • Experienced by nearly 40% of athletes, both male and female
  • Can lead to amenorrhea (loss of menstrual cycle) in females
  • Common but not normal or optimal for health
• REDS also affects bone health 
  • Long-​​term energy deficit can lead to loss of bone mass and increased risk of injury
• REDS can disrupt the HPG (hypothalamus-​​pituitary-​​gonadal) and HPA (hypothalamus-​​pituitary-​​adrenal) axes 
  • Can lead to depression, anxiety, and bipolar-​​like symptoms
  • Serious issue that needs further study

Time-​​Restricted Eating and Health

• Studies show benefits of 4–6 hour time-​​restricted eating for weight loss in healthy individuals 
  • However, not recommended for everyone due to potential risks
• 8–10 hour eating window may be ideal for most people 
  • Can be extended to 12 hours for physically active individuals
• 12-​​hour eating window can help maintain weight and improve health 
  • Combining with exercise and good nutrition can help avoid REDS

Low Carbohydrate Diet and Time-​​Restricted Eating

• Recent study showed greatest weight loss with low carbohydrate diet combined with time-​​restricted eating 
  • Same calories across groups
• Suggests that quality, quantity, and timing of calories all matter for weight loss and health
• Low carbohydrate diet may be beneficial for some individuals, especially when combined with time-​​restricted eating

Maintaining Healthy Body Weight

• 40% of people maintain a healthy body weight 
  • Majority are aware of their calorie intake and food quality
• Focusing on the reasons why people maintain a healthy weight can provide insights into effective strategies for weight management

• Pandemic may have influenced people’s eating habits and weight management
  Pandemic Impact on Health and Fitness

• People’s health and fitness were affected differently during the pandemic

  • Some gained weight, while others got more into fitness
  • Bimodal distribution of health outcomes

Time Restricted Feeding and Health Benefits

• Starting and stopping eating at consistent times each day can have additional benefits 
  • Improved sleep
  • More predictable shifts in alertness and sleepiness
  • Better ability to predict when to exercise

Circadian Biology and Timekeepers

• Main timekeepers for our system: 
  • Feeding
  • Light activity
  • Social connection
  • Temperature

Mental Health, Gut Health, and Caffeine

• Caffeine can trigger anxiety, panic attacks, and acid reflux 
  • Drinking coffee on an empty stomach can worsen these conditions
• People with anxiety or acid reflux should consider when they consume caffeine

History of Nighttime Activity and Coffee

• Controlled use of fire is unique to humans 
  • Fire created an evening time for socializing, culture, politics, philosophy, and science
• Coffee was initially an evening activity 
  • Started in Istanbul in the mid-​​16th century
  • Sufi branch of Islam consumed coffee in the evening for singing and dancing
• Coffee became a morning drink to help stay awake for early morning prayers 
  • Turkish coffee is thick and strong, causing heartburn and acid reflux
  • Eating something before coffee became a way to prevent gastric distress, leading to the development of breakfast

Satchin Panda’s Morning Routine

• Wakes up around 6 am
• Starts first meal of the day around 8 am

• Has coffee after breakfast to avoid gastric distress
  Link Between Nighttime Socialization, Feeding, and Caffeine

• Nighttime socialization and feeding linked to caffeine consumption

• Regular blood work important for understanding and improving health
• Inside Tracker: personalized nutrition platform analyzing blood and DNA data 
  • Helps users understand their body and reach health goals
  • Provides actionable insights based on blood test results

Cultural Differences in Sleep Patterns

• Researcher studied African tribes and their nighttime conversations 
  • Found differences in topics discussed during daytime and nighttime
  • Nighttime discussions focused on matchmaking, politics, strategizing, singing, and dancing
• Evening activities between sunset and bedtime impact overall health

Sleep Patterns in Cultures Without Electricity

• Research by Horacio de la Iglesia on Argentinian Tobas tribe 
  • Tribe members consistently go to bed 3–3.5 hours after sunset
  • Sleep onset variability very small (15–30 minutes standard deviation)
  • No distinction between night owls and morning people in this context

Personal Experiences with Sleep Patterns

• Both the podcast host and guest experienced shifts in their sleep patterns over time 
  • In college and grad school, they considered themselves night owls
  • Later in life, they adapted to more “normal” sleep schedules
• Ken Wright Jr.‘s study on camping and sleep patterns 
  • Took lab members camping, exposed them to natural light and physical activity
  • Participants went to bed between 9–10:30 PM
  • Melatonin rhythms, cortisol rhythms, and sleep-​​wake rhythms persisted for several weeks after returning to artificial lighting environments

Genetic Influence on Sleep Patterns

• Some people may be genetically predisposed to certain sleep patterns 
  • Familial Advanced Sleep Syndrome: strong genetic phenotype causing early sleep onset
  • Mutation in the period 2 clock gene affects sleep patterns

• Nighttime discussions in tribes may differ from morning discussions

  • Morning discussions may focus on waking up and consuming caffeine
    Morning Discussions vs Evening Activities

• Morning discussions are mostly about work and daily tasks

  • Hunting, gathering, farming, meetings, problem-​​solving, etc.
• Evening activities are more about self-​​expression and entertainment 
  • Singing, dancing, socializing, relaxing
• People often seek “me time” in the evenings to express themselves or entertain themselves 
  • Switching roles between performing and observing

Circadian Rhythms, Sleep-​​Wake Activity, and Human Evolution

• Night owls may have different sensitivities to light 
  • Some people may be more sensitive to artificial light at night, shifting their circadian clock
• Teenagers are known to be more sensitive to light and stay awake later into the night 
  • Their sleep schedule is not reduced, but they struggle to wake up early for school

Sleep Before Midnight vs Sleep After Midnight

• Going to sleep within 3 hours of sunset may be better for circadian timing mechanisms 
  • Melatonin levels rise in the absence of bright light, preparing the body for sleep
  • Sleep debt may cause tension between circadian aspect and sleep needs
  • Restorative sleep may be more difficult to achieve when going to bed later

Shift Workers and Time Restricted Feeding

• Definition of shift work: staying awake for 2 or more hours during habitual sleep time (10 PM — 5 AM) 
  • Engaging in physical or intellectual activity during this time
  • Occurring once a week for 50 weeks can disrupt physiology, metabolism, behavior, and brain function
• Light exposure during shift work resets the circadian clock, causing it to constantly catch up 
  • Disruption lasts for the day of the shift and two days following
  • Body is not in sync with the clock for half of the week or year

Firefighters and Time Restricted Feeding Study

• Studied the impact of shift work on firefighters’ health and well-being 
  • Shift work disrupts circadian rhythms, sleep, and metabolism

• Results may be applicable to other shift workers and those with disrupted sleep schedules
  Shift Work and Its Effects on Health

• One in five working adults are considered shift workers (nurses, doctors, firefighters, bakers, truck drivers, service industry)

• College students, new moms, food delivery and rideshare drivers also experience shift work lifestyle
• Approximately 50% of the adult population experience shift work lifestyle at any given time
• Shift workers carry a disproportionately heavier burden of disease (high blood pressure, high cholesterol, gastrointestinal problems, chronic inflammation, colon cancer, diabetes)
• Clinical trials often exclude shift workers due to their disrupted schedules and potential resistance to medications or lifestyle interventions

Impact of Shift Work on Sleep and Metabolism

• High school and college students often go to bed around midnight or later, disrupting their circadian rhythm
• Even five days of living like a shift worker can cause blood glucose levels to read as prediabetic
• Dim light exposure during sleep can disrupt morning blood glucose levels
• Shift work lifestyle may contribute to the obesity crisis, along with other factors like processed foods and lack of activity

Potential Solutions for Shift Work Lifestyle

• Revisit deadlines and schedules in educational institutions to encourage healthier sleep patterns
• Focus on being active and eating primarily during the early part of the day
• Encourage morning sunlight exposure, even in areas with less sunlight during certain times of the year

• Time-​​restricted feeding is just one aspect of circadian health; addressing sleep, exercise, and socialization within the context of a healthy circadian rhythm is also important
  Firefighter Study on Time-​​Restricted Eating

• Firefighters and shift workers often excluded from studies

  • Less than 50 studies focused on improving health of shift workers
• Study aimed to test feasibility of 10-​​hour time-​​restricted eating for firefighters 
  • Collaborated with Dr. Pam TOBB and San Diego Fire and Rescue Department
  • Goal: maintain consistent eating schedule between work and non-​​work days
• Researchers lived the life of a firefighter to understand their culture 
  • Experienced frequent nighttime disruptions due to 911 calls
• Study design:
  • 150 firefighters recruited, half assigned to Mediterranean Diet
  • 75 assigned to 10-​​hour time-​​restricted eating, choosing their own consistent 10-​​hour window
  • Aimed for at least 5 days of adherence per week

• Results:

  • No significant difference in weight loss between groups
  • Time-​​restricted eating group saw significant change in VLDL particle size and number 
    • Reduced risk for atherosclerosis
  • Firefighters with high blood pressure saw significant reduction in systolic and diastolic blood pressure 
    • Comparable to taking an antihypertensive drug
  • Pre-​​diabetic firefighters better managed their blood glucose
  • Study highlights the potential benefits of time-​​restricted eating for shift workers and the general population
    Effects of Shift Work on Blood Sugar Regulation

• Multiple middle-​​of-​​the-​​night wakings can lead to blood sugar regulation issues

  • Especially if people stare at screens during these wakings
• Regulating blood sugar better is important for overall health

Morning Sunlight Viewing and Regular Meal Schedules

• Keeping a regular meal schedule every day (5 out of 7 days) can help regulate sleep and blood sugar 
  • Aim for a great night’s sleep 80% or more of the nights of your life
• When one can’t reliably control their sleep-​​wake cycle, maintaining a regular meal schedule becomes even more important

Firefighters and Shift Work

• Firefighters work 24-​​hour shifts and have opportunities to sleep between calls 
  • Different from nurses and healthcare workers who stay awake throughout the night
• Time-​​restricted feeding may not have the same effects on other shift workers 
  • Need to consider work schedules, breaks, and other factors

Time-​​Restricted Feeding and Alcohol Consumption

• Many shift workers rely on alcohol at night and caffeine in the morning to cope with their schedules
• Time-​​restricted feeding can lead to a significant reduction in alcohol intake 
  • Alcohol can disrupt health, sleep, and increase anxiety even at low levels of consumption

Time-​​Restricted Feeding for Men, Women, and Children

• Provided that the feeding window is not shorter than 12 hours, time-​​restricted feeding can be used by men, women, and children 
  • In a study, mice on time-​​restricted feeding had changes in gut microbiome, excreted more fat and sugar, and had increased brown fat activity

My Circadian Clock App

• Developed to help people track their eating habits 
  • Users take a picture of their food and save it in the app

• Study with 156 participants found that people eat a median of 7 times per day

  • Top 10% of participants ate 12 times per day
    Irregular Eating Patterns and Meal Skipping

• Many people have irregular eating patterns

  • Breakfast at different times each day
  • Dinner times vary, sometimes eating late at night
• 50% of adults eat within a 15-​​hour window 
  • Only 10% eat within a conventional 12-​​hour window
• Snacking has increased, often outside of regular meal times 
  • Dinner often delayed, especially for those who prepare their own meals

Sleep Recommendations for Children and Teenagers

• Children and teenagers should sleep between 9–11 hours 
  • Growth hormone production and growth occur during sleep
• 90% of high school students are chronically sleep deprived 
  • Due to device usage, homework, and other factors

Circadian Rhythms and Meal Timing

• Shifting meal times by several hours can cause “metabolic jet lag” 
  • Short-​​term effects may not be noticeable, but long-​​term consequences are unknown
• Body weight and composition are not always accurate markers of health 
  • Acid reflux, depression, anxiety, and high LDL can affect people with low body fat

Fasting and Health Benefits

• Complete fasting has been practiced in many religions for cleansing purposes 
  • Studies show health benefits from fasting, including every other day eating
• Fasting clinics in Germany supervise patients during extended fasts 
  • Patients consume minimal calories and receive necessary micronutrients and electrolytes
• Fasting may have a positive impact on brain health and mental health 
  • Treatment-​​resistant depression and anxiety could potentially benefit from fasting
  • More research needed on the gut-​​brain axis and the effects of fasting on mental health

Fat Fasting

• Some people try to limit blood glucose by only eating mainly fats

  • Healthy fats like avocados, olive oils, nuts, and some animal fats
  • Aim to keep blood glucose low while also practicing time-​​restricted eating
  • More research needed to determine the effectiveness and potential benefits of this approach
    Low Carbohydrate Diet and Health

• Restricting feeding times and keeping blood glucose lower can be beneficial

• Concerns about long-​​term effects on islet cells in the pancreas that produce insulin 
  • Disuse or unuse of muscles can lead to muscle atrophy
  • Unclear if long-​​term low carbohydrate diet impacts islet cells
• True ketogenic diet: less than 10% of calories from carbohydrates, not high in protein
• Liver reacts dramatically to lifestyle changes

Metformin and Berberine

• Metformin and Berberine: drugs that lower blood glucose 
  • Mimic fasting state
  • Metformin activates AMP kinase, a sensor in cells that senses fasting state
  • Berberine is a tree bark extract that lowers blood glucose
• Metformin and rapamycin shown to extend mouse lifespan and improve health 
  • Rapamycin reduces mTOR activation
• Calorie restriction study: mice given food as a lump sum, essentially doing time restriction 
  • Mice naturally have high levels of AMP kinase and low levels of mTOR activity during fasting
• Metformin and rapamycin may mimic fasting state, leading to benefits seen in studies
• Time of day may impact effectiveness of metformin and rapamycin 
  • Evening metformin may trigger fasting state earlier
  • mTOR activation may be better if taken during the evening or morning before a meal

Berberine Experiences

• Berberine can flatten blood glucose response when taken with carbohydrates 
  • Can cause hypoglycemia when taken without carbohydrates
• Circadian effects not considered in personal experiences

Circadian Rhythms and Metabolism

• Nuclear hormone receptors, master regulators of metabolism, have circadian patterns 
  • Circadian rhythms exist for food-​​seeking behavior, eating, and fasting
  • Metabolic regulators also have circadian rhythms or diurnal cycles
• Fat oxidation should be in opposite phase with feeding

• Salk Institute: groundbreaking work on circadian rhythms and metabolism
  Podcast Discussion with Dr. Sachin Panda

• Grounded in science, actionable ideas

• Dozens of tools and considerations for shift workers and non-​​shift workers
• Importance of light and activity for circadian rhythm
• Firefighter study: relevance to the general population
• Dr. Panda’s work: animal and human studies, focus on human health
• Links to Dr. Panda’s books and apps for further learning

Dr. Panda’s Contributions

• Conducts both animal and human studies
• Focuses on circadian rhythm and its alignment with internal clock and habits
• Developed My Circadian Clock app (research-​​facing)
• Developed On Time Health app (available on Apple App Store)