🎙 Huberman 041 - Effects of Fasting & Time Restricted Eating on Fat Loss & Health

High level conclusions

There actually is a perfect diet for you on a given day (but has to be tailored to your specific context - needs and goals)

When you eat is as important as what you eat

Health benefits from time restricted feeding occur because certain conditions are met in the brain and body for a certain amount of time

it is very important that the feeding window fall during the more active phase of one's day

• for humans, that's typically in the early part of the day, or the later part of the day, but not at night

Time restricted eating anchors the gene systems of the body and provides a more regular & stable circadian rhythm

• Light is the number 1 driver of circadian rhythm, eating windows is number 2

the reason that the liver gets sick when you're eating too often is because inflammatory markers are increased

Major pillars:

1. Do not ingest any food in the first hour after waking
2. Do not ingest any food or liquid calories in the two (ideally three) hours prior to bedtime
   ~When to eat is governed by extending the natural fasting during sleep because fasted-states in sleep are extra helpful due to glymphatic and autophagic cleanup.
3. Create a narrower window than is comfortable (target 8hr likely means 10hr window in reality)
   ~People underestimate when they eat, so if you'd like to be on a 10 hour feeding window, then you should probably select an eight hour feeding window
   ~This takes into account the "fasted state" taper after that as you take your last bite or your last sip of calories. There's this time or taper before which you're actually in a fasted state

Fasting of any kind, does tend to enhance autophagy

when we eat, the clearance of that food from our gut, and the processes in our cells and organs, that are related to digestion, and the utilization of that food takes about five to six hours

as important as how long your feeding window is, is where that feeding window resides in each 24 hour cycle

There are ways to accelerate digestion / gastric emptying

• Light movement or exercise for 20-30 minutes after dinner

When we are in the fed state, we promote cellular growth, both good and bad (via the mTOR and PS6 pathways). When we are in the fasted state, we promote cellular repair (via NPK pathway).

Time restricted eating helps gut microbiome and may be helpful for irritable bowel syndrome and forms of colitis.

• Mechanism: Improve clock gene expression, which improves the mucosal lining of the gut, which reduces Lactobacillus (which, when in high levels, is correlated with metabolic disorders).
• Also stimulates the proliferation of beneficial gut microbiota that promote better intestinal function

Time restricted feeding may help non alcoholic fatty liver disease by increasing brown fat stores

• Brown fat is inversely correlated with non alcoholic fatty liver deposits. Mechanism not discussed in this episode.

Women that are ovulating and both men and women trying to get pregnant should not restrict below 8 hrs

• for women that are menstruating, there needs to be sufficient leptin signaling to the brain in order to maintain ovulation because of the way that the brain communicates with the pituitary in the ovaries.
• if you reduce food intake, either in total calories or in duration too much, you will suffer a drop in sperm counts fertility will drop and this makes sense the body is communicating to the brain whether or not conditions are suffering fish in the body to reproduce and to, presumably, and hopefully support the health and well being of those offspring

Things that break your fast

• Anything that involves sugars, particularly simple sugars
• Highly contextual based on when you last ate, what you ate

Considerations

Adherence - what diet is easier to follow

Athletic performance

• Increasing muscle mass suggested to eat earlier in the day because of Bmal gene more active earlier
• When to ingest protein does not depend on when one is doing resistance training

Mental performance

Shift / night workers

Typical eating schedules of the people around you (spouses, housemates, coworkers)

Some people do not do well on intermittent fasting either in terms of mood or hormone health.

Transition slowly over the course of 7-10 days by narrowing an hour a day until target.

• allow the hormone systems of your body including leptin, the hypocretin orexin system, which are systems within the body, that signal to the brain that food is about to come, allowing those systems to adjust so that you're not overwhelmingly hungry, irritable, and you're not throwing your whole hormone system out of whack

Open Questions

If wearing a continuous glucose monitor, what is the threshold for "fast broken"?

What turns on or off "sleep-related fasting"? If I fast for 2 hrs after waking, are those two hours in glymphatic clearing fasted state or is it the distinct waking fasted state?

Detailed Notes

[[UNVERIFIED]] [[📓 Fasting blood glucose as a predictor of mortality: Lost in translation]]

• Key findings - in humans, higher blood glucose is associated with mortality
• As people age, resting blood glucose goes & reductions in metabolism across lifespan are not nearly as robust as once thought
• unless there's something done to mitigate the increase in blood glucose associated with aging, almost everybody experiences a gradual but regular increase in resting blood glucose that predicts mortality.
• True for humans & primates, but exact opposite finding is true for mice --> be careful about extrapolating animal models to humans

[[UNVERIFIED]] [[📓 Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin SecretionThe DIETFITS Randomized Clinical Trial]]

• Key finding - no significant difference in weight change between people following a healthy low fat diet versus a healthy low carbohydrate diet with significantly more dietary fats in them
• For weight loss, specific diet is less important than number of calories burned is higher than the number of calories ingested

Impacts on number of calories burned

• amount of exercise
• type of exercise
• basal metabolic rate

• ~non-exercise induced thermogenesis (if people bounce around a lot and fidget a lot, they can burn anywhere from 800 to 2000 calories per day)

• metabolic factors
• hormones

• ~thyroid
• ~insulin
• ~growth hormone
• ~sex steroids (testosterone and estrogen)

During puberty

• Increase in sex steroid, growth, and other hormones
• much of caloric intake is directed to protein synthesis for production of bones, muscle, and other tissue

Eating and not eating create certain conditions in the body

• When you eat

• ~Blood glucose will go up
• ~Insulin levels will go up

• ~~How much glucose and insulin go up depends on what you eat --> simple sugars > complex carbohydrates > fibrous carbohydrates > protein > fat
• ~~Also depends on personal health (i.e. diabetes or insulin insensitivity)

• When you don't eat

• ~blood glucose and insulin go down
• ~GLP-1 (Glucagon-like peptide 1) go up

[[UNVERIFIED]] [[📓 Time-Restricted Feeding without Reducing Caloric Intake Prevents Metabolic Diseases in Mice Fed a High-Fat Diet]]

• mice that ate a highly palatable high fat diet, a great tasting diet, but only during a restricted feeding window of each 24 hour cycle, maintained or lost weight over time, whereas mice that ingested the same diet, same amount of calories, but had access to those calories around the clock gained weight became obese and quite sick
• Those so called clock genes underwent a very regular entrainment a locking in to the proper 24 hour schedule

• ~peaks in these clock genes became very regular, and the dips in these clock genes became very regular --> led to host of positive health effects

• ~~reduction in fatty deposits on liver

• when mice ate whenever they wanted across the 24 hour cycle, these clock genes became really out of whack --> led to negative health effects

• one of the bad things that happens is that the liver suffers - their livers got very sick fatty deposits in the liver

80% of the genes in your body and brain are on a 24 hour schedule

the reason that the liver gets sick when you're eating too often is because inflammatory markers are increased

[[UNVERIFIED]] [[📓 Time-restricted Eating for the Prevention and Management of Metabolic Diseases]]

• because we are fasting during sleep, it's very clear that it's best to extend the sleep related fast, either into the morning, or to start it in the evening
• something special about the fasting that occurs during sleep, because it's associated with a number of processes that relate to the so called glymphatic system, the movement of lymph like fluids and other fluids through the brain and kind of sweeping out garbage disposal if you will a clearing out of the metabolic debris and some of the autophagy that's associated with bad processes in the brain
• if people follow time restricted feeding schedule for long periods of time. So 60 days or longer, there's some metabolic changes in the way that people metabolize energy that do seem to shift the system toward more fat loss relative to burning of other tissues when in a state of caloric restriction, and I want to say when in a state of caloric restriction

at least three factors that are going to govern how quickly you transition from ingesting food to a fasted state

• Size of the meal (large -> slower gastric emptying)
• How much fat (more fat -> slower gastric emptying)
• Liquid vs. solid (solid -> slower gastric emptying)

short feeding windows of say four to six hours do produce a number of positive health effects

• increases insulin sensitivity
• but hard to adhere and folks seem to overeat in that window
• However, they either produce no change in body weight, or they tend to produce even increases in body weight

Generally, 8 hr window > 4-6 hr > 1 meal per day

[[UNVERIFIED]] [[📓 Distribution of dietary protein intake in daily meals influences skeletal muscle hypertrophy via the muscle clock]]

• there's better or enhanced protein synthesis early in the day because of the expression of one of these particular clock genes called Bmal

• ~B Mel regulates a number of different protein synthesis pathways within muscle cells, such that eating protein early in the day supports muscle tissue maintenance and or growth
• ~However, it's very interesting that it doesn't matter when the resistance training the load bearing exercise occurs in the 24 hour cycle. So whether or not in other words, people are training early in the day, or they're training late in the day.

You should allow yourself a transition period of anywhere from one week to 10 days, in which you shift your feeding window by about an hour each day or so.

One of the findings that's really been important to note is that almost every individual has a lot of drift in when that eating window resides in their 24 hour period in particular on the weekends.

When the feeding window shifts, it can cause disruptions in the circadian rhythm that take 2-3 days to recover from

blood glucose levels will actually increase if high intensity interval training is performed early in the day, and will decrease if high intensity interval training is performed later in the day.

There exist chemicals that are glucose disposal agents (i.e. prescription Metformin or over the counter Berberine) but use with caution as they can cause rapid glucose drops and trigger hypoglycemia

If you want to monitor more closely, there are continuous blood glucose monitors that sync with a phone app

When we are fasted, we tend to reduce the activity of a particular protein called mTOR. mammalian target of rapamycin mTOR is very active in cells while they are growing. phospho mTOR and PS six are reduced by fasting.

And when we fast, we see increases in sales of things like AMPK. The sirtuins things like transcription factors like Fox, oh, ATF and ketones, or ketone bodies

we have cell growth pathways involving mTOR and P SX. And we have cell repair and cell shrinkage processes that are associated with NPK.

Other potential Thrive Action - cold exposure to increase brown fat stores

• cold exposure of anywhere from one to three minutes, two or four times per week, or maybe even 10 minutes two to four times per week can increase brown fat stores

time restricted feeding also seems to positively increase brown fat stores probably because of the way that brown fat stores relate to epinephrine and adrenaline which tend to go up when we're fasted

[[UNVERIFIED]] [[📓 Time-restricted eating effects on performance, immune function, and body composition in elite cyclists: a randomized controlled trial]]

• there were some positive effects on their performance related to time restricted eating
• time restricted eating caused a decrease in free testosterone
• They had significant reductions in serum cortisol
• But in fact, because cortisol is lower, it may mean that the effects of testosterone or the reduction in testosterone is offset

insulin is a hormone and time restricted feeding seems to have very positive effects on overall insulin profiles and so forth

Thus far, at least in my awareness, there isn't any quality, clinical peer reviewed study on that yet, for sake of dementia, although I await those studies

alternate day fasting has gotten the so called Safe bill of health this has been written up meaning that people didn't suffer bone loss, they didn't suffer any major detrimental effects

• can produce more rapid effects on weight loss and reductions in blood glucose than time restricted feeding

one of the aspects of fasting that have drawn a lot of people to time restricted feeding and fasting is the clarity of mind

[[📓 Effects of 8-hour time restricted feeding on body weight and metabolic disease risk factors in obese adults: A pilot study]]

• eight hour time restricted feeding produces a mild caloric restriction and weight loss without calorie counting

turns out that it drives more fat loss by way of increasing hepatic lipase

• increases the enzyme that metabolizes fat for lipolysis and energy production, and reduces something called scidac ci d c, which is a lipid droplet associated, and lypolosis inhibitor now

extended periods of time restricted feeding, meaning eight hour feeding window or 10 hour feeding window that's obeyed for several months or more, seems to allow the system to shift toward burning more fat, or rather, using a higher percentage of fat when in a caloric deficit

drinking water will not break your fast drinking tea will not break your fast drinking coffee provided it is black coffee will not break your fast

artificial sweeteners or non artificial plant based sweeteners like stevia break a fast this will vary somewhat, and I have to say the data on this are somewhat mixed

• I think it's fair to say that in moderation, the plant based non sugar sweeteners like stevia, in particular, stevia seem to have a minimal impact on overall blood glucose
• when consumed in excess, that those might have some detrimental effects on the gut microbiome

cinnamon is even a mild glucose disposal agent that can actually reduce blood glucose, lemon and lime juice, believe it or not, can lower blood glucose

Many people find that the kind of lightheadedness, the shakiness, that's accustomed with having slightly low blood sugar can be offset by taking a half teaspoon or so of sea salt, or even just a tiny pinch of salt and putting into some water and drinking it

salt water actually has a mild effect as a glucose disposal agent, but it has a stabilizing effect on blood volume. And so because sodium brings with it water, and the so called osmolarity of your blood in your body depends on the salt levels in your blood and brain and body

• This is especially true for people that are using caffeine. Because when you ingest caffeine you actually excrete a lot of water has a diuretic effect. And with that water goes salt so it actually causes you to excrete sodium

Where you can't imagine going another five minutes before eating something suddenly you feel okay. And that has to do with a lot of the effects of blood volume caused by ingesting salt in the appropriate amounts.

Zero app that makes it very easy to mark when you're beginning your feeding window

Turns out that when you go in a sauna because you dehydrate you're losing water. I wasn't drinking water and you're dropping a lot of water The concentration of sugar in your blood actually goes up.

Papers referenced

[[📓 Fasting blood glucose as a predictor of mortality: Lost in translation]]

[[📓 Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin SecretionThe DIETFITS Randomized Clinical Trial]]

[[📓 Time-Restricted Feeding without Reducing Caloric Intake Prevents Metabolic Diseases in Mice Fed a High-Fat Diet]]

[[📓 Time-restricted Eating for the Prevention and Management of Metabolic Diseases]]

[[📓 Distribution of dietary protein intake in daily meals influences skeletal muscle hypertrophy via the muscle clock]]

Unclear reference

• A recent study that was published in cell reports medicine just a couple of weeks ago, tested the hypothesis whether or not the gut microbiome, or so called brown fat tissue is impacted. The liver health and in particular, non alcoholic fatty liver disease. The short takeaway from this study is that contrary to what was previously thought, the gut microbiome, while very important for a number of other processes in the body, doesn't seem to be related to this non alcoholic fatty liver disease. This is surprising to people or should be to those of you that have been following the gut microbiome literature.

[[📓 Time-restricted eating effects on performance, immune function, and body composition in elite cyclists: a randomized controlled trial]]

[[📓 Effects of 8-hour time restricted feeding on body weight and metabolic disease risk factors in obese adults: A pilot study]]

Tools referenced

https://www.mycircadianclock.org/

https://www.zerofasting.com/