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

Dr. Satchin Panda (00:00:00)

• Dr. Satchin Panda is a professor and director of the regulatory biology laboratory at the Salk Institute.
• His lab has contributed to understanding circadian rhythms and made discoveries on how eating patterns impact health.
• Intermittent fasting, or time-restricted feeding, is a focus of Dr. Panda's research, affecting liver health, gut function, brain health, mood, and cognitive performance.
• Dr. Panda's work includes books "The Circadian Code" and "The Circadian Diabetes Code."

Time-Restricted Eating (TRE), Calorie Restriction (CR) & Health (00:07:24)

• Time-restricted feeding (TRE) and intermittent fasting are explored, including their prevalence in historic caloric restriction studies.
• Calorie restriction has shown longevity and disease prevention benefits but is difficult to maintain.
• TRE was studied in animals and found to provide health benefits without reducing daily calorie intake, leading to its adoption by humans.
• TRE involves confining eating to a consistent window of 8 to 12 hours, with some people experimenting with narrower windows.
• TRE and intermittent fasting often overlap in terms, but scientific literature typically associates intermittent fasting with reducing calories on certain days.
• In TRE studies, animals given the same amount of food within restricted hours showed health benefits.

Mealtimes & Circadian Clock (00:14:38)

• Consistent meal start times are linked to the internal circadian clock of cells and organs, influencing physiological processes.
• Circadian rhythms are sensitive to light, but feeding times can significantly tune clocks in the liver and other brain areas.
• Shifts in mealtimes can disrupt the body's internal clock, much like daylight saving changes, causing a feeling of being out of sync.
• Regularity in eating times is advised to sync the body's clocks for optimal food digestion, and changes should be gradual to allow for adjustment.
• Evidence suggests that starting and ending eating windows at consistent times facilitates the body's anticipatory functions for digestion.

Circadian Rhythm, Meal Anticipation, Digestion (00:21:34)

• Anticipatory signals in our body help us assimilate food by preparing digestive juices for food intake.
• An unprepared body, such as waking up to an alarm or during daylight saving time changes, can result in heart attacks and accidents due to lack of coordination and an unprepared heart.
• There are digestive rhythms, including intestinal peristalsis, which slow down at night after our last meal, leading to indigestion if we eat late at night.
• Late-night eating or eating at inconsistent times can cause both physical and cognitive strain the next morning, suggesting benefits to eating meals around the same time daily.

Breaking a Fast, Burning Fat (00:25:28)

• The concept of a fed versus fasted state is complex, as food digestion rates and resultant blood glucose levels vary.
• The definition of breaking a fast may differ based on whether there is a rise in blood glucose or irreversible molecular signals.
• The body initially burns glycogen when fasting, and then shifts to burning fat; the transition can be measured through the respiratory exchange ratio (CO2 to oxygen ratio).
• Mice experiments suggest even a small food intake can halt fat-burning processes and initiate carbohydrate metabolism.
• The notion of fat-burning is often misunderstood; low carbohydrate diets burn dietary fat, not necessarily more body fat, which is contrary to some nutrition debates online.
• Non-caloric food intake and its impact on fasting and metabolism is an area that requires more research.

CR, Time Restricted Eating, Circadian Rhythm & Longevity (00:34:04)

• A study published by Dr. Satchin and his colleagues investigated the impacts of caloric restriction (CR) and time-restricted eating on mice and the implications for lifespan extension.
• Their research suggests that CR, in which mice consume 20-30% fewer calories, extends lifespan if combined with time-restricted feeding, with meals being eaten within a limited period and then fasting for the remainder of the day, a schedule akin to OMAD (one meal a day).
• Joseph Takahashi's study using smart feeders analyzed whether the benefits of CR were due to reduced caloric intake or the timing of consumption.
• The experiment compared mice that ate fewer calories throughout the day and night (little fasting) versus mice that ate the same reduced calories but within a constrained time during their active phase (time-restricted feeding).
• Results showed that mice under CR without prolonged fasting lived 10% longer than controls. Mice on time-restricted CR lived 20% longer than controls when fed during the day and an impressive 35% longer when fed during their active phase at night, even when consuming the same number of calories.
• Surprisingly, traditional markers for longevity such as weight, body composition, hemoglobin A1c, glucose control, and cholesterol levels did not correlate with lifespan extension, suggesting that there may be undiscovered biomarkers involved.
• A human study reflected that time-restricted eating and caloric restriction had similar outcomes regarding weight loss, even when participants habitually ate within a 10-hour window.
• The research suggests that in mice, at least, optimal benefits for longevity are achieved with caloric restriction within a 12-hour feeding window, and extending or shortening the eating period does not have a significant impact on lifespan.
• The findings do not definitively extend to humans, and further investigation is needed to understand the effective feeding window for human longevity when practicing caloric restriction.

Gender, Hormones & CR; Relative Energy Deficient in Sports (REDS) (00:47:20)

• Experiments on intermittent fasting have primarily been conducted on male mice, but new NIH guidelines mandate examining both male and female subjects due to emerging sex-based differences in results.
• In humans, restricting eating to short windows can lead to involuntary caloric reduction, posing risks if energy expenditure exceeds intake.
• Relative Energy Deficient in Sports (REDS) impacts athletes, causing issues like amenorrhea in females and adverse bone health in both genders.
• REDS can lead to psychological problems too, such as depression or anxiety, highlighting the risk of excessive time-restricted eating.
• The lab is currently developing a mouse model of REDS for more detailed study.

Physical Activity, Nutrition & Feeding Window (00:52:40)

• Studies on individuals with 4-6 hour eating windows show benefits, but these are carefully monitored to avoid excessive weight loss.
• An 8-10 hour eating window might be ideal, extending up to 12 hours for active individuals as it aligns with benefits seen in mouse models.
• A study using the myCircadianClock app with groups following standard nutrition or a 12-hour restricted eating window showed comparable weight and health improvements, suggesting benefit in the timing.
• Individuals following a 12-hour eating window avoided negative REDS outcomes and didn't necessarily eat higher-quality foods but matched the health benefits of the traditional nutrition group.
• For those combining physical exercise and better nutrition, a 12-hour window may prevent REDS and promote longevity, as observed in mice studies.

Nutrition Timing, Quality & Quantity; Low-Carbohydrate Diet (00:59:04)

• Reports describe greater weight loss with low carbohydrate diets combined with time-restricted feeding, despite similar caloric intake across different diet structures.
• Nutritional timing, quality of diet, and dietary timing synergistically influence weight loss efficacy.
• The focus is shifting toward understanding why a significant portion of the population successfully maintains a healthy weight.
• Observations during the pandemic showed divergent tendencies with some people neglecting health while others focused more on fitness.
• Maintaining consistent meal timing daily may improve other health aspects, like sleep patterns and alertness.

Caffeine, Nighttime Socialization, Fire, Breakfast (01:03:00)

• The main timekeepers for the human system include feeding, light, activity, social connection, and temperature.
• Timing for beginning and stopping feeding is central and acts as an anchor point for health, with a focus on the impact of nutrition quality and quantity.
• Mental and gut health can be affected by the timing and content of meals, specifically relating to caffeine intake.
• Caffeine on an empty stomach can exacerbate acid reflux and heartburn or trigger anxiety and panic attacks.
• Humans have used controlled fire for approximately 100,000 to 200,000 years to extend evening activities, leading to social and cultural development.
• Nighttime activity has evolved from fireside gatherings to modern socialization with technology, maintaining our circadian inclination to socialize in the evening.
• Coffee consumption initially started as an evening activity and evolved into a morning beverage to promote wakefulness, especially in Turkey.
• Turkish coffee culture influenced the introduction of food before coffee to prevent gastric distress, inadvertently creating the breakfast routine.
• Today, the sequence of eating before consuming caffeine is recommended for better health, aligning with the historical context and breakfast customs in certain cultures.
• The speaker, Dr. Satchin Panda, Personalizes his caffeine intake by having coffee after breakfast, suggesting it may align better with natural waking processes.

Circadian Rhythm, “Night Owls” & Genetics (01:16:20)

• Humans manage various activities between sunset and bedtime that can greatly impact health.
• There's a difference in cognitive function between morning and evening due to varying levels of neurotransmitters.
• Horacio de la Iglesia's field research shows that Argentinian communities without electricity go to bed within a short time frame, usually 3-3.5 hours after sunset, and get up around sunrise.
• The concept of being a "night owl" or a "morning person" may not apply in communities that follow natural light patterns.
• Dr. Satchin Panda's personal experience suggests that lifestyle changes can transition a "night owl" to more traditional sleep patterns.
• Camping studies indicate that exposure to natural light and activity can reset our internal clocks and persist even after returning to artificial light environments.
• Familial Advanced Sleep Phase Syndrome is an example of a strong genetic predisposition affecting sleep patterns due to mutations in clock genes like Period2.

Morning vs. Nighttime Discussions, “Me Time” (01:26:37)

• Morning discussions tend to focus on work and problem-solving, whereas evening activities are more personal and expressive.
• During the evening, known as "me time," individuals engage in activities that allow them to express themselves and relax.
• The difference in conversational themes may suggest that social media time should be limited in the evening to promote interaction and constructive activities with others.
• The discussion highlights the importance of circadian rhythms, sleep-wake activity, and human evolution in relation to time-restricted feeding and personal time management.

Light Sensitivity & “Night Owls”; Puberty, Melatonin (01:30:08)

• People's sensitivity to light varies, possibly due to genetics, with some more affected by artificial light at night which can shift their circadian rhythm.
• Blue light sensors in eyes, called the intrinsically photosensitive retinal ganglion cells (ipRGCs), affect sensitivity to light and sleep patterns.
• Individuals can have varying levels of light sensitivity, altering their sleep-wake cycle, especially noticeable after puberty when teens become more sensitive to light.
• The notion that sleep before midnight is more restorative than sleep after midnight is not fully understood, but avoiding bright light at night and allowing melatonin levels to rise can lead to better sleep preparation.
• Sleep quality may also be compromised by the tension between circadian rhythms and sleep debt.

Shift Workers, Health & Disease (01:36:05)

• Shift workers, defined by staying awake during habitual sleep times, frequently experience disrupted metabolism, brain function, and an increased burden of disease.
• It is difficult to include shift workers in clinical trials due to their irregular schedules and potential resistance to certain interventions or medications.
• Up to 50% of the adult population may be living a shift worker-like lifestyle due to varying schedules and responsibilities.
• Shift work is associated with higher risks for diseases such as high blood pressure, high cholesterol, gastrointestinal problems, inflammation, cancer, and diabetes.
• Lifestyle changes are difficult for shift workers due to their schedules and exhaustion, and their health metrics can resemble pre-diabetic conditions after just a few disrupted nights.
• Even dim artificial light during sleep can negatively affect morning blood glucose levels.
• Beyond formal shift workers, many people function as shift workers by engaging in activities that disrupt their normal sleep patterns, potentially affecting up to half of the population.

Artificial Lights, Young Adults & Sleep, Metabolic Dysfunction (01:45:43)

• High school students and college students, such as those at UCSD, typically go to bed around midnight, with very few going to bed before this time.
• A study from the University of Washington revealed that young people tend to stay up later in winter than in summer due to artificial lighting, contrary to what one might assume.
• Increased consumption of coffee and hot chocolate in the evening during winter may also contribute to delayed sleep onset.
• The shift to digital assignments and midnight submission deadlines during remote learning has further encouraged students to stay up late.
• There is a need to re-evaluate educational policies and practices, such as assignment deadlines, to mitigate these issues.
• Obesity and metabolic dysfunction have increased globally, with lack of activity and late eating habits potentially contributing to these issues.
• The 'Freshman 15' is a term referring to college students gaining weight in their freshman year, potentially linked to late class schedules and eating times.
• Revisiting academic schedules and submission deadlines could be beneficial in addressing these health concerns.

Firefighters, Sleep & TRE; Cardiovascular Health, Blood Glucose (01:50:59)

• Discussion on the benefits of being active and consuming food mostly in the early part of the day to improve sleep and overall health.
• Morning sunlight exposure is critical, regardless of cloud cover, for health and maintaining circadian rhythm.
• The study on firefighters focuses on addressing the absence of research on shift workers who are at high risk for health issues including metabolic disease, cancer, and dementia.
• Firefighters, who often have disrupted schedules, experience a high incidence of heart attacks, strokes, and cancer, partly due to their exposure to carcinogens during fires.
• The study conducted in collaboration with Dr. Pam Taub at UCSD investigated the feasibility of firefighters adhering to a 10-hour time-restricted eating (TRE) schedule, even with challenging 24-hour shifts.
• Participants of the study included 155 firefighters; half followed a Mediterranean diet and the other half combined the Mediterranean diet with a 10-hour TRE.
• The study found that most firefighters were able to maintain the TRE schedule at least five days a week.
• Results showed a significant reduction in LDL particle size and number, indicating a lower risk for atherosclerosis for those following the TRE.
• Firefighters with high blood pressure experienced a significant reduction akin to the effects of antihypertensive drugs.
• Firefighters starting with high blood sugar, particularly pre-diabetics, managed their blood glucose better on the TRE schedule.
• Results also reveal that shift workers struggle more to manage blood glucose due to their irregular schedules.
• The study suggests that maintaining a consistent meal schedule could serve as an anchor point for shift workers who have little control over their sleep patterns.

Shift Workers & Sleep; Alcohol & Caffeine (02:05:18)

• Shift workers like firefighters, unlike other night workers, often have a chance to sleep during their shifts, reducing their sleep debt during the day.
• Different types of shift workers such as nurses or truck drivers remain awake the whole night and need specific studies to find out what strategies work best for them.
• Nutrition quality tends to improve in shift workers who follow a time-restricted eating pattern, including an increase in fruits, vegetables, and olive oil.
• Shift workers generally rely on alcohol to wind down after shifts and caffeine to start the day, leading to poor health outcomes.
• A reduction in alcohol intake was noted among shift workers who followed a time-restricted eating plan, in contrast to those on a standard Mediterranean diet.
• Research indicates that significant health risks, including cancer, metabolic, sleep disruption, and anxiety, arise from alcohol consumption exceeding two drinks per week.
• The widespread consumption of alcohol, despite its known health risks, is surprising, as it is often incorrectly seen as harmless as caffeine.

12-Hour Feeding Window for Adults & Children, Sleep (02:09:15)

• Time-restricted feeding is beneficial for men, women, and children if the feeding window is at least 12 hours.
• Studies in mice have shown that time-restricted feeding changes the gut microbiome, affecting how much fat and sugar are absorbed.
• The liver's cholesterol metabolism changes under time-restricted feeding, leading to alteration in bile acid excretion.
• Generous funding from philanthropists has been crucial for pioneering studies in time-restricted feeding.
• An app was developed to track eating habits, revealing that most people eat more frequently than the conventional three times a day, often snacking multiple times.
• It was discovered that around 50% of adults eat within a 14-hour 45-minute window, and only about 10% eat within a 12-hour window as commonly perceived.
• Children and teenagers require 9-11 hours of sleep, and therefore should have a 12-hour feeding window that aligns with sleep recommendations.

Meal Timing (02:22:10)

• The practice of skipping meals within a feeding window can fit into many lifestyles but might introduce what is referred to as 'metabolic jet lag.'
• Constantly changing meal times could cause potential long-term health effects that are not yet fully understood.
• Meal timing and its effect on health is an emerging field of research, with current knowledge largely based on mouse studies and the need for more substantiated human studies.
• While body weight is often thought to indicate health, other factors like mood disturbances or LDL cholesterol levels are also important and can be influenced by meal timing.

In summary, time-restricted feeding within a 12-hour window appears beneficial for health across all ages. However, irregular meal timings and frequent snacking beyond this window are prevalent. The impact of meal timing and structure on metabolism and health is an active area of research.

“Complete Fast”, Longer Fasts, Physical Health & Mental Health (02:25:20)

• Complete fasting has a significant body of literature supporting its health benefits.
• Practices of complete fasting span various religions and are believed to cleanse the body.
• Health advantages have been observed with alternate-day eating in both mice and humans.
• There are clinics in Germany where strict supervised fasting is conducted for weight loss and other health benefits, providing just minimal calories through a small bowl of soup.
• It is suggested that periodic fasting could potentially impact brain health, potentially helping with treatment-resistant depression, due to the gut-brain axis.

“Fat Fasting”, Blood Glucose & Insulin (02:28:12)

• Fat fasting focuses on consuming fats to keep blood glucose low, sometimes in conjunction with time-restricted feeding.
• There is an emphasis on the spikes in blood sugar and the pancreas's role in insulin production.
• The long-term effects of a low-carbohydrate diet on the pancreas's insulin-producing cells are unknown.
• The researchers acknowledge that insulin and insulin-like growth factors have positive effects on muscle synthesis, tissue repair, and possibly cognition.

Fasting, Metformin, Rapamycin & Longevity; Human Applicability? (02:31:57)

• Metformin and rapamycin are thought to increase longevity by mimicking the fasting state and reducing mTOR activity, which has been demonstrated to extend lifespan and improve health in mice.
• There are concerns about the implications of these substances for human longevity, considering they mimic fasting and their effects may not directly translate from mice to humans.
• Anecdotal instances of varying effects of metformin at different times of the day suggest that timing might influence the drug's efficacy in glucose level management.
• Exercise and metabolic reactions to lifestyle changes highlight the adaptability of human tissues like the liver and muscle.
• Personal experience with berberine points out its ability to affect blood glucose levels differently depending on carbohydrate intake, with potential risks of hypoglycemia.

Circadian Rhythm & Metabolism (02:39:14)

• The expression of nuclear hormone receptors, crucial for regulating metabolism, follows a circadian pattern in various tissues.
• Metabolism itself is closely tied to the circadian rhythm, with the inherent routine of food-seeking, eating, and fasting being integral to daily metabolic regulation.
• Discussion of the research environment and collaboration at the Salk Institute highlights the innovative work being done in the field of circadian rhythms and metabolism.

Ontime Health App, Circadian Clock App (02:41:36)

• Appreciation was expressed for the detailed discussion of actionable health and science-based ideas.
• Many individuals might recognize themselves as shift workers due to their habits related to light and activity.
• The discussion highlighted a firefighter study relevant to both firefighters and the general population.
• Dr. Panda was commended for conducting both animal and human research with a focus on human health amidst competitive funding.
• Tools and resources such as the Ontime Health app, books on health and diabetes, and links to Dr. Panda's work were offered to listeners.
• The Ontime Health app is accessible in Apple's App Store and aims to balance feeding, fasting, activity, and sleep through circadian rhythm alignment.
• The effort to communicate complex science to the public was acknowledged as critical, particularly in today's rapidly advancing scientific landscape.