Dr. Satchin Panda my most favorite research scientists of all time!
This one is about circadian rhythms and “Time-Restricted-Eating:”
This episode is a round 2 episode with none other than Dr. Satchin Panda of the Salk Institute! While discussion with Dr. Panda invariably leads to eating behaviors, his deep background in circadian biology always tends to lend new and insightful perspectives. There’s a good reason for this! It’s an area he has made deep contributions to, especially through the discovery of melanopsin, which is a photopigment found in the eye that, rather than forming images, is specialized for communicating information about time-of-day to the “master oscillator” of circadian rhythm, the suprachiasmatic nucleus.
In the first episode with Dr. Panda, we were introduced to a new paradigm for eating known as time-restricted eating. Time-restricted eating, on the surface, shares many characteristics with an idea many of you may be more familiar with known as intermittent fasting. The difference, however, is that Dr. Panda’s concept of time-restricted feeding has some degree of focus on the effect of poorly timed consumption food (or even xenobiotics) can have on the subtle behavior of our tissues. At nearly two hours of dialog, this episode touches on a lot of material, but also has a special focus on practical implementation of time-restricted eating, featuring a few of the most frequent questions that came after the first conversation. To see a list of these questions, scroll through the timeline below and look for timepoints with the heading “practical implementation.” (SPOILER: Yes, we cover black coffee!)
In addition, we dive into lots of interesting new territory as well, including…
- How human anecdote and animal evidence suggests time-restricted feeding may be especially useful for gut-related issues, including inflammatory bowel disease and acid reflux.
- The fascinating way Dr. Panda is using human anecdote from his trial to ask new scientific questions he wouldn’t think to ask and then going back to animal data to figure it out and how this unique approach forms a sort of closed loop pattern: animal → human feedback → back to animal for mechanism.
- How labs doing caloric restriction research may have actually been reaping the benefits of time-restricted without realizing it as an incidental to their experimental design.
- The revelation that 70% of FDA drugs are subject to circadian effects and are either less effective or more effective at certain times of the day.
- The effect melatonin has on the pancreatic production of insulin and the insight this lends to why we should probably stop eating at least 2-3 hours before we go to bed.
- The bizarre way circadian rhythms affects everything from susceptibility to UV damage to recovery from surgery to cancer risk (at least if you think the World Health Organization knows what they’re talking about).
Learn more about Dr. Satchidananda Panda:
Participating in the mobile app-based time-restricted eating study:
If this podcast inspires you to give time-restricted eating a try, don’t let your data go to waste! Dr. Panda’s mobile app-based study of time-restricted eating is now accepting an international cohort. For those of you that are at least 18 years of age or older, you can sign-up by visiting myCircadianClock.org.
Participation is pretty simple, but, as mentioned in the video there are a few good rules of thumb:
- Don’t start the habit right away. Track what your existing eating habits are first! This is important for the 2-week baseline needed for their research.
- After you figure out what your eating window has been up until now, choose a new time window that you think you can reasonably adhere to for at least 12 weeks. This is about how long it takes to form a new habit anyway!
- If you feel like you’ve got the hang of it, stick with it! At the very least, try to submit a picture of your first meal and your last meal every day and your bodyweight once per week. By submitting your first and last meal, they’re able to use the timestamps associated with these pictures to know how closely you’re adhering to your self-selected intervention.
By following these basic rules of thumb, you’re helping Satchin’s group out and probably getting a little bit healthier in the process! Not a bad deal, right?
In this approximately 2-hour conversation, Dr. Panda and I discuss….
- 00:00:00 - Brief recap of the broad discussion from the first conversation Rhonda had with Dr. Panda.
- 00:01:35 - Some of the animal evidence of the effects of maintaining a 9-12 hour eating window, which includes: effects on glucose metabolism, lipid profiles, favorable changes in lean muscle mass, and gene expression.
- 00:02:51 - American Heart Association meta-analysis concluded limiting the number of hours of eating during the day or maintaining overnight fasting (e.g. time-restricted feeding) was beneficial for maintaining cardiovascular health. Study.
- 00:04:36 - Adopting a time-restricted feeding paradigm (by not eating later than 5, 6, or 7 PM) often results in an incidental reduction of caloric intake, which, while not a goal of time-restricted feeding, may actually be helpful for those with metabolic syndrome and obesity.
- 00:05:58 - Rodent models for metabolic syndrome, when subjected to a conservative time-restricted feeding regimen, generally don’t become lean, however, their blood biomarkers (glucose, cholesterol, triglycerides) regress back to an almost normal range even in the context of a low-quality diet.
- 00:07:28 - Explanation for how time-restricted feeding actually relates to our circadian rhythm and Dr. Panda’s qualitative description of “health.” Note: thinking from the paradigm of circadian rhythm is actually an important distinction between Dr. Panda’s work on time-restricted feeding and conventional intermittent fasting protocols.
- 00:08:51 - 10-14 hours of fasting when we get up in the morning means that we have given our gut “rest” because it has a period of not processing food. Moreover, having 3-4 hours of fasting before bed can help with sleep in the evening.
- 00:10:19 - Ad libitum feeding, when compared to a calorically and nutritionally identical but time-constrained feeding pattern of 8 to 10 hours (depending on the trial), reveals that time-restricted feeding is a consistently healthier pattern, according to animal research.
- 00:11:35 - Time-restricted eating is easy to implement because most of us are already used to having to synchronize some of our daily activities to the clock. For example : when we wake or when we get to work or leave our place of employment.
- 00:12:18 - Sometimes Dr. Panda’s group has to adjust the eating window by a half hour or an hour (from 8 to 9-hours of feeding per day, for example) in order to ensure that the time-restricted group still consumes the same calories, but small changes like this has a mostly negligible effect on the benefits.
- 00:12:50 - Dr. Panda’s group has tested the concept of cheat weekends : In experiments where mice are allowed ad libitum eating times (usually eating over 12 hours per day) but only on the weekend, mice still experienced benefits from time-restricted eating.
- 00:13:33 - Dr. Panda discusses his time-restricted feeding schedule, which starts at around 7 or 8 in the morning and ends around 5 or 6 in the evening.
- 00:14:12 - Anecdote: eating a diet that is low in high glycemic index foods and simple sugars and higher in fiber and/or slightly higher in protein is associated with less hunger when eating in a time-restricted fashion.
- 00:17:20 - After ~5 weeks of habituation to time-restricted feeding, users participating in the myCircadianClock trial via the mobile app tend to report that cheating gives them what might be colloquially referred to as a “food hangover.”
- 00:18:51 - Dr. Panda explains some of the benefit to the distributed mobile app trial design he employs through myCircadianClock.org: it’s naturally more inclusive design that has a greater degree of geographic diversity than even the most well-funded conventional trials… and also includes >shift workers, which would often be excluded from clinical trials.
- 00:22:03 - Feedback from mobile app trial participants actually sometimes lead to novel questions entering into animal trial design. User reports relief from immune-related disease → new focus of inquiry for animal research → reductions in systemic inflammation as a mechanistic explanation.
- 00:22:59 - Observations surrounding effects of time-restricted feeding on inflammatory bowel disease is one unique example of this “closed loop” pattern of scientific inquiry (animal → human feedback → back to animal for mechanism) is a unique opportunity the Panda group has due to their ability to solicit direct user feedback from participants of their mobile app trial.
- 00:25:10 - Discussing the effect of time-restricted feeding on systemic inflammation.
- 00:26:08 - Time-restricted feeding as an opportunity for night-time repair that may prevent gut leakiness (or “gut permeability”), which is an important source of systemic inflammation.
- 00:26:58 - Timing of macronutrients that may differentially affect gut permeability.
- 00:28:09 - The gut lining as one of the most important interfaces in which our interact with the environment, which emerging evidence is showing to be governed by circadian clocks from the oesophagus to the cecum, including the gut microbiome.
- 00:28:57 - Time-restricted feeding promotes the rhythmic changes in gut microbiota populations that are supposed to occur throughout the day, increasing healthy diversity.
- 00:30:36 - Shift workers are a population that seem to be predisposed to gut-related issues and this may make them especially well-suited to a time-restricted feeding intervention.
- 00:31:07 - Potential implications for acid reflux: animal research has shown that time-restricted feeding has an affect on the proton pump responsible for the acidification of the stomach, reducing its expression in the gut. This proton pump is also the target of therapeutic drugs for the treatment of acid reflux.
- 00:34:02 - Uber and Lyft drivers are often a type of shift work that may not be classified as such. Similarly, the family members of shift workers also adopt a lifestyle that unintentionally takes on characteristics of shift work as well. Dr. Panda’s group refers to this second order effect as secondhand hand shift workers. Using these broader definitions of shift work, Dr. Panda estimates upwards of 30% to 40% of the population may have shift work for at least a few months or years over the course of their lives.
- 00:36:01 - Shift work has been associated with cardiovascular disease, diabetes & obesity. Study.
- 00:36:45 - The #1 cause of on-duty mortality in firefighters, a type of shift work, is heart disease and stroke. Study
- 00:37:13 - The World Health Organization has categorized shift work as a potential carcinogen. 2007 press release. >Study: Shift work and breast cancer risk.
- 00:39:15 - The heterogeneity of the various type of shift work can make it difficult to identify which types are the most health compromising and may also influence the suitability of certain lifestyle intervention. For example: 24-hour shifts versus regular night shifts versus irregular shift work that may rotate between daytime and nighttime work depending on the calendar day or week.
- 00:40:56 - Relevant for shift workers: animal studies suggest that eating within a time window is superior to ad libitum feeding, even when the timing of that eating window is less than ideal (e.g. later in the day or evening).
- 00:42:49 - Early caloric restriction studies, due to the incidental constraints of experiment design and lab resources, actually followed a pattern that >share some qualities of shift work and time-restricted feeding : rodents were fed when they would usually be sleeping (in the mornings) and consumed all of their food within 2-3 hours instead of at random throughout the entire day.
- 00:44:34 - Animal evidence for shift workers suggest that a combination of caloric restriction, a healthy diet, and eating in a time window are probably all the current best options for mitigating deleterious effects.
- 00:45:31 - On delaying the eating window: starting the eating window earlier in the day is thought to be beneficial due to enhanced insulin sensitivity earlier in the day. Dr. Panda gives his thoughts on how to setup your own n=1 experiment using just a glucometer.
- 00:47:48 - Melatonin, which begins to rise, on average, 2-3 hours before our habitual sleep time, binds to receptors in the pancreas to tell it to stop producing insulin. That means eating within this window of time (just before bed) can result in higher blood glucose as we rest, which is another potential problem with a later eating window.
- 00:49:10 - This relationship between insulin and melatonin was initially unearthed by the observation made by genome-wide association studies (GWAS) that some people with certain polymorphisms in melatonin had a greater risk of diabetes and obesity. Melatonin receptors in the pancreas turned out to be this missing link. Study.
- 00:50:06 - Opinion : An eight hour window starting at noon is still much better than random eating over a greater than 12 hour window.
- 00:50:51 - When healthy adults eat meals that are identical in terms of both their macronutrient and caloric content at breakfast, lunch, or dinner, the postprandial glucose increase is lowest after breakfast and highest after dinner even though the meals were 100% identical. Study.
- 00:51:18 - Dr. Panda introduces the concept of “evening diabetes”: some people can show a healthy fasting blood glucose in the mornings, but then defy expectations by showing very poor response to a post-prandial glucose test in the evenings.
- 00:51:56 - Differentiating between the various types of fasting.
- 00:52:59 - Somatic and qualitative sensations that help define the boundaries between types of fasting: early feelings of lightness, eventual headache (24+ hours).
- 00:53:41 - Formation of a certain threshold of circulating ketone bodies may also be a useful milestone (this transition may sometimes be accompanied by a headache).
- 00:54:47 - The three foundations of health that inform the Panda group’s lifestyle guidelines: sleep, nutritional food & physical activity.
- 00:55:58 - The difference between time-restricted eating and prolonged fasting is that time-restricted eating is fundamentally one of simple daily maintenance. >It represents a bare minimum that is not too dissimilar from brushing your teeth .
- 00:56:26 - Dr. Panda likens a prolonged water fast of 4-5 days to being more like a regular trip to the dentist. Anecdotally, Satchin does this type of long fast once per year. Article about his personal fasting habits and those of others in the field.
- 00:56:50 - An important distinction between time-restricted eating is that it can be a lifestyle that is usable by anyone, whereas prolonged fasting is not accessible to all populations and may require medical supervision.
- 00:58:57 - Liver glycogen begins to deplete at 10 hours and adipose tissue begins to release fatty acids and production of ketone bodies begins to ramp up. Study.
- 00:59:14 - Rhonda mentions cytosolic protein deacetylation, which is in an important autophagy signal. Learn more deep biology of autophagy in this episode.
- 00:59:48 - By ignoring circadian rhythm, many labs that have done work looking at fasting and caloric restriction may assume valid data to be artifact or noise. This has probably lead research groups to gravitate towards researching the effects of longer fasting protocols where the signal is stronger .
- 01:01:17 - In contrast, the Panda group asks questions like whether or not ketone bodies rise reproducibly everyday around the same time… and then proceed to test this with a time course over a series of set intervals (e.g. every hour). After confirming that this does happen to a small degree, they then begin to ask the question of whether or not there might be some important but subtle tissue-specific benefits to this type of biological rhythm or, conversely, consequences to its disruption.
- 01:02:54 - Autophagy gene expression oscillates on a 24-hour pattern and disruption of circadian clock genes has a direct effect on this autophagy activity. During the fasting phase this gene expression is activated in the liver. Study.
- 01:04:50 - The effect of circadian disruption on the ability to tolerate DNA damage from ultraviolet (UV) radiation and how hair follicles, one of the most rapidly dividing cells, may resist cancer by being especially good at repair thanks to its strong circadian rhythm. Study.
- 01:06:26 - Radiation tolerance and repair: mice receiving a dose of radiation in the morning lose much more hair than if they’d been administered the dose in the evening (only 15% loss at 8PM vs. 85% loss from an 8AM dose). Interestingly, this dose of radiation is similar to what may be used clinically in radiation treatment. Study.
- 01:07:46 - Recovery from surgery: in mouse studies, improved recovery from a partial hepatectomy (resection of the liver) is also associated with an evening surgery. Study.
- 01:08:47 - Time-restricted feeding reduces tumor growth in mice. Study.
- 01:09:08 - Breast cancer patients that practice time-restricted eating by fasting for 13-hours overnight had a 36% reduced incidence of breast cancer recurrence. Study. Interview with this study’s author Dr. Ruth Patterson.
- 01:09:52 - Time-restricted feeding and coffee : the somewhat definitive answer on whether or not we should drink coffee outside of our fasting window and why the time-restricted feeding guidelines have this distinction from the popular 16:8 intermittent fast protocols. myCircadianClock caffeine article. Relevant studies: 1, 2.
- 01:16:14 - Omitting black coffee and tea during fasting addresses certain important ambiguities surrounding metabolism and the initiation of digestive activity, however, at least one time-restricted eating study did still show positive results even without this guideline. Study.
- 01:16:54 - Increases in protein deacetylation (an autophagy signal) have been observed in association with coffee polyphenol consumption. Study. Interview with author Dr. Guido Kroemer.
- 01:17:58 - Practical implementation: Thoughts on stevia usage while in the fasting window. Note: Stevia is a special type of sweetener called a nonnutritive sweetener, which has properties distinct from those of artificial sweeteners.
- 01:21:06 - Practical implementation: Should nutritional supplements be taken outside of the eating window?
- 01:22:40 - Practical implementation: Does evening weight training or exercise offset the detrimental effects of a late night meal?
- 01:23:57 - A shorter time-restricted feeding window of 8 to 9 hours has been shown to enhance endurance performance in animal studies, which may be associated with the increase in circulating ketones also observed. Study.
- 01:26:08 - Exogenous ketone supplements have been shown to improve endurance in human athletes. Study.
- 01:27:16 - Animal studies of time-restricted feeding show improvements in lean muscle mass in mice restricted to a feeding window of 8 to 9 hours, but this wasn’t observed in the group receiving the “unhealthy diet.” This increase in lean muscle mass was also associated with an increase in a transcriptional coactivator that functions as the master regulator of mitochondrial biogenesis known as PGC-1alpha. Study.
- 01:30:06 - Practical implementation: Should we avoid brushing our teeth or using mouthwash outside of the eating window?
- 01:31:30 - Practical implementation: At what stage (developmentally) can children or adolescents safely begin practicing time-restricted eating?
- 01:33:03 - Children with a highly regular bedtime schedule and evening meal were shown to be protected from obesity 5 to 7 years later. Study.
- 01:35:00 - Practical implementation: Should we think about meal frequency within our eating window?
- 01:39:47 - Practical implementation: Should pharmaceuticals be taken outside of the eating window?
- 01:40:06 - Transcription factors controlling the enzymes that degrade xenobiotics, such as cytochrome P450s, are strongly circadian and even used as reporters in circadian studies. This has practical implications like the fact that pharmaceutical drugs may be more effective depending on the time of day that they are administered. Study.
- 01:42:36 - Nearly 70% of FDA approved drugs have their intended targets cycling in accordance with a circadian rhythm. This suggests that better drug timing may be of great relevance to medicine in the near future. Study.
- 01:43:56 - Dr. Panda totally wants to have researchers in the antarctic and/or astronauts on the space station participate in his time-restricted feeding trial. Know any?
- 01:45:56 - Effect of long-term shift work on brain aging. Study #1: 10 years of shift work experience an extra 6 years of brain aging compared to age-matched controls. Study #2 : making animals eat when they should be sleeping it disrupts hippocampal function and long-term potentiation.
- 01:46:38 - Future research questions: measuring effects of time-restricted eating on brain memory & learning parameters and also neurodegenerative disease progression in animal models.
- 01:48:15 - Sleep cleans broken down metabolic products via the glymphatic system.
- 01:50:11 - Closing discussion: information on Dr. Panda’s mobile app based study.