Time-restricted eating reshapes gene expression throughout the body

https://www.sciencedaily.com/releases/2023/01/230103133742.htm

by lxm • 3 years ago

150 86 3 years ago

sciencedaily.com

sandermvanvliet• 3 years ago

* in mice

mrandish2• 3 years ago

Notes:

- In mice.

- Tested 16:8 pattern.

- Sustained consistently for nine weeks.

- No exploration in this study of the effects and/or benefits from the gene expression.

N=1 but I've been doing ~16:8-ish along with strict keto for the past five years and the net benefits for me have been transformative in fitness (Weight: -100+ lbs, BMI: Obese->Fit), long-term health (A1C, LDL/HDL, Trigs, BP, resting heart rate all from bad to great), cognitive acuity and emotional stability. First 12 weeks required serious effort/focus to transition habits, palette and metabolism (must RTFM and be rigorous) but after that it's been surprisingly easy to sustain long-term, requiring no will power or conscious effort.

Other surprising experiential learnings: Dietary intake impacts long-term mental/emotional states FAR more than I ever suspected. Food & taste prefs I had since childhood are not innate. Many things I loved no longer even taste good. Hunger pangs and cravings are driven by my blood sugar cycle. Once I stabilized that I no longer get hungry or feel food deprived/obsessed. (<--- all N=1 of course.)

yonibot• 3 years ago

N=1 and also probably too many variables to learn from this - keto itself is already a massive lifestyle intervention. Did you restrict calories as well? Exercise?

TedDoesntTalk4• 3 years ago

most everyone sees body changes when using time-restricted eating WITHOUT any dietary changes. There’s no need to go keto like OP to see results.

mrandish2• 3 years ago

I started IF only after I had been doing keto for about six weeks. At that point it was frankly easy because I wasn't getting hungry or having cravings anymore. I can't tease out how much IF contributed but I'd already lost a remarkable amount of weight on just keto. In general, I'd recommend only making one significant change at a time.

Calorie tracking and restriction pretty much comes with strict keto. Transitioning to keto rigorously requires detailed tracking of every molecule that goes in your mouth (with a food scale and measuring cups), at least for the first 12 weeks. I tracked constantly for about 6 mos until it was automatic for me and I knew every food and portion I typically encounter at a glance. It's hard at first but only tracking part way is the #1 reason for failing to get results.

I didn't do any exercise at all while losing weight, in fact while changing diet I was more sedentary than my usual slug-like activity level due to work and life factors. For me, exercise has always been hard, unpleasant and inevitably makes me hungrier. N=1 but that's what worked best for me and my weight loss was dramatic and super fast (>100 lbs in 8 mos).

karim79• 3 years ago

Out of curiosity, and if you don't mind me asking, what is your daily carb intake while doing keto?

hellosputnik• 3 years ago

Is your 16:8 restricted to a full meal or did you consume or drink anything outside of the 16:8? After-work drinks? Coffee?

TedDoesntTalk4• 3 years ago

black coffee and plain tea are acceptable according to everything I’ve read, probably because they are close to 0 calories and certainly not nutritional calories if >0. So I drink them. Unfortunately there’s no way to know if you’re still in a fasted state after that coffee. You can test blood sugar with a pinprick and that is a marker, but not a guarantee.

To summarize: absolute safest is water only.

throwawaycities• 3 years ago

There are also studies showing both keto diets and fasting can alter the microbiome and attributed changes in gene expression to changes in the microbiome.

sometimesno• 3 years ago

16:8 is utterly unremarkable. A huge percent of people skip breakfast and then have dinner before 8pm. This is a normal, bog standard eating pattern.

snozolli• 3 years ago

In my experience, it's exceptional in America. This may be due to constant indoctrination that "breakfast is the most important meal of the day". Also, modern food processing has put all sorts of late-night snacks at our fingertips.

fbdab103• 3 years ago

If you mean a full meal, sure. However, I suspect the majority of people enjoy some calories pretty early in the day. Sugary coffee/tea, cereal bar, bagels or other grab and go snacks.

wesapien• 3 years ago

That's the thing. Most people would greatly benefit from the unremarkable lifestyle change but a lot of people cannot do it due to reasons and a safety net.

kayoone2• 3 years ago

I had similar improvements without fasting and without keto. I do 16:8 on some days but it's mostly to help me manage my weight. I strongly believe most of the fasting benefits come from the fact that it makes managing weight easier. Calorie restriction and tracking my macros has helped me tremendously not only loosing weight but also understanding nutrition and what works for me and what doesn't. I am a 40 year old Software Engineer and fitter and stronger than I have ever been.

I do quite a bit of high intensity cardio (cycling) + weight training and my recovery and peak performance suffered a lot when I tried keto for a few weeks, it also tanked my hormone levels. I still focus my carb intake on times around training but generally don't restrict.

kbrisso• 3 years ago

You need to stay on it for months to become keto adapted. I would say 6 months minimum, after that the energy swings go away and you generally have a lot more energy. You can also add MCT oil. The problem with keto is eating enough calories.

galangalalgol2• 3 years ago

For me the benefits seem to be a lack of carb cravings, and my fullness indicator turned on for the first time in my life. That was with 20:4 though, and no keto.

layer8• 3 years ago

it also tanked my hormone levels.

How do you measure those?

mywacaday• 3 years ago

What RTFM do you recommend?

tomcam• 3 years ago

Are you available for a consultation? My contact is in my profile and of course I’m happy to pay.

croossin• 3 years ago

Agreed. Another additional benefit in my opinion is that when restricting your feeding window, it’s much easier to control cravings. When “free-eating”, it’s easy to just continue to snack.

TedDoesntTalk4• 3 years ago

How did you test your A1C?

fragmede• 3 years ago

They're available OTC, eg. https://www.walgreens.com/store/c/walgreens-at-home-a1c-test...

karaterobot• 3 years ago

One group was given free access to the food. The other group was restricted to eating within a feeding window of nine hours each day.

Small correction: 15:9 pattern, if this writeup is correct.

manmal2• 3 years ago

To give another N=1, I don’t feel good on a 16:8 split. At least not when the eating window starts at noon. Long term (18 months) this zapped my energy and I lost a lot of muscle. Yes, weight loss was phenomenal, but I gained all of that back in the phase of exhaustion that followed.

What has worked better for me was longer fasts, eg 48h, max once per week. And lately I‘ve been experimenting with skipping late dinner (no food after 6PM) which is kinda hard but seems to work for improved sleep and digestive health. I usually have visible bags under my eyes, those tend to be greatly reduced when I eat an early or no dinner.

notyourday• 3 years ago

Long term (18 months) this zapped my energy and I lost a lot of muscle. Yes, weight loss was phenomenal, but I gained all of that back in the phase of exhaustion that followed.

Muscle loss is an adaptation to loss of load on the muscle. Internet trope of "you lose muscle when you lose fat" is just that - a trope. If you were 100lb heavier, your muscles were loaded with extra 100lb. Should you lose the 100lbs, if you do not engage in the appropriate resistance exercises to provide equivalent of additional 100lb load, your muscle mass will decrease

Beaver117• 3 years ago

Also N=1, I did 16:8ish for a year and had no signficant change.

It wasn't until I changed the type of food I was eating and tracking calories that I lost weight. But I still do 16:8 often because its a habit now.

kaitai• 3 years ago

What's interesting to me is that there is strong support from data that skipping breakfast causes many people to eat more later, in particular eating more carbs/sugar/snack foods. I have to wonder to what extent a planned 16:8 window where you're conscious about having a good "break-fast" meal is different than simply running out of the house without a meal plan in place. It is very clear from the data that simply "not eating breakfast" does not lead to better outcomes.

I also find it interesting that the gender of the mice was not specified. If we're talking about hormonal profile changes, this will matter. When intermittent fasting was very popular, a number of women in "the scene" with a vested interest in making IF work noted that while initially it was great, they eventually started experiencing adverse effects, and often felt better on a 14:10 window instead.

Agree with you on the last paragraph re: your experiences. I've needed to substantially change what I eat due to some health challenges, and blood sugar is huge. Protein in the morning (rather than something like oatmeal) is key for me. A dozen eggs a week and my hereditarily-high cholesterol went down, too. Sorry oatmeal folks!

esperent• 3 years ago

there is strong support from data that skipping breakfast causes many people to eat more later, in particular eating more carbs/sugar/snack foods.

There's a big difference between skipping breakfast one time and habitually skipping breakfast. The body adapts. You no longer feel hungry in the mornings and you develop new eating patterns - since most people doing IF are focused on health, these are likely to be healthy eating patterns that don't include lots of sugary snacks. Apparently this adaptation takes the form of the liver learning not to expect breakfast after waking and producing glucose at that time, although I have not personally checked the research on this.

I've been doing IF 16:8 for about a year now. I rarely eat processed sugar (except a good croissant a few times a week). Even some fruits like ripe mango taste too sweet to me now.

From personal experience and discussing this with other people, if your fear is that you'll end up getting so hungry that you'll stuff your face with junk, it's not a valid fear beyond the first week. To avoid this I would suggest easing into it. Eat breakfast an hour later for a few days, then two hours later, and finally combine it with lunch.

kuhewa2• 3 years ago

I think it was 15:9 and since it is in mice it's hard to say but I reckon thats the equivalent of more like 24+ hour fasts in humans.

Rury• 3 years ago

I have been doing similar for about 3 years now, with similar results, but one thing that has been problematic with for me... is my bowel movements just don't seem to function well when I'm doing keto. The only thing that seems to fix them is milk+cereal... (fiber from veggies don't seem to quite cut it). So I kind of alternate between periods of keto, and a normal diet. How do you do strict keto?

justinlloyd2• 3 years ago

Very low carb keto is known to stop you up, if that is what you are referring too. I didn't get any issues, but I kept my carbs a little higher than my wife who regularly did have issues. A small glass of salty water fixes it. Don't venture too far from a bathroom after ingesting.

justinlloyd2• 3 years ago

N = 1. 18:6 for me. 2PM to 8PM, with occasional falling off the wagon due to social obligations or just simply forgetting to eat and then realizing I need to eat. I have noticed if I eat sugary snacks with my last meal that I get ravenously hungry much earlier the next day. There are some days where I unintentionally forget to eat until 4PM or so.

I tried 16:8 but it never seemed to have any effect on weight loss for the 2PM to 10PM range. And my weight would creep up with that regimen. I suspect that might be related to late night hormonal changes in the human body preventing the digestion of certain types of food. I should try a 16:8 with 12PM to 8PM at some point and track the results.

cush• 3 years ago

There's an excellent Huberman Lab episode that covers various studies on time restricted eating for both mice and humans. There's a high focus on cognitive, health, and sleep benefits in humans.

https://hubermanlab.com/effects-of-fasting-and-time-restrict...

sidcool2• 3 years ago

Does restricted time eating mean intermittent fasting?

SavageBeast• 3 years ago

Presuming you read the linked study but more or less (and this is argument fuel among The Faithful here ), "time restricted eating" spoken of here is Intermittent Fasting. The "restriction" here is that not a single calorie of anything is consumed outside of an 8 hour window and the 16 remaining hours in the day are nothing but water. Some people even like to do a 18:6 split too.

The hacks in this style of eating is that once you stop putting calories in your mouth, your insulin levels drop and that makes the fat cells in the body more willing to allow lipids into the bloodstream where the liver can make Ketones out of them - hence the term "ketosis" is often seen when reading about intermittent fasting.

There are also small studies, I'd call them anecdotal yet still informative, that demonstrate a raise in GH in response to an IF style eating pattern. Leptin sensitivity/resistance is also positively impacted by this eating style.

If you want to go down a rabbit hole and really geek all the way out on a topic, theres a lot out there to sort through, debunk and sort into useful information. I encourage you to give it a look.

EDIT: For extra credit - it's natural to look at Fasted Training in the same context. The hack here is that when you train at near peak low insulin levels ( or near peak anyhow which takes about 14h of fasting ) your body will suffer in terms of absolute performance but if done correctly you can train burning mostly fat. Theres as much on this subject to sort through as the first one. A whole host of hormonal and health benefits are purported here and I can say from experience I believe most of them having seen it myself.

cycomanic2• 3 years ago

EDIT: For extra credit - it's natural to look at Fasted Training in the same context. The hack here is that when you train at near peak low insulin levels ( or near peak anyhow which takes about 14h of fasting ) your body will suffer in terms of absolute performance but if done correctly you can train burning mostly fat. Theres as much on this subject to sort through as the first one. A whole host of hormonal and health benefits are purported here and I can say from experience I believe most of them having seen it myself.

I've done quite a bit of fasted training, but can't say I have seen a huge effect myself. That said, I was very fit at the time, most studies have been done on untrained subjects AFAIK. There are also studies that show that base metabolic rate increases after fasted training, but for men only while it decreases for women, which would be counterproductive if they would want to loose weight.

The main problem with most of the studies is that they have been done with very small study populations.

sidcool2• 3 years ago

Thanks for the detailed response. Are the advantages of fasting well researched?

enkid• 3 years ago

Intermittent Fasting can include fasting for longer periods, including days at a time.

mhaberl• 3 years ago

yes, but only for a short time, usually 16-20h long fasts.

Some people do fasts that last for multiple days, usually 3-7 days - this not I.F.

cycomanic2• 3 years ago

I have seen IF described as both in a day and in a week. Supposedly the effects are very similar as well.

zargon• 3 years ago

A lot of people (including me in the past) have used the term intermittent fasting to describe this, but it's not a good label for this. Intermittent fasting should describe protocols where one fasts for at least a full day. If one is eating daily but only during certain hours, it's better described as time-resricted eating. It's also possible to do both time-restricted eating and intermittent fasting.

pammf2• 3 years ago

I’ve been doing intermittent fasting for 2 years. Did a bunch of different protocols and eventually settled on ~18:6. Lost around 15kgs (from 105 to 90) and as a nice “side effect” got rid of all skin problems that I’d had during the previous 10 years or so. Today I don’t preach it anymore cause I got tired of debating whether it was healthy or not but I definitely recommend to everyone that’s truly interested in giving it a try.

piqi3• 3 years ago

...got tired of debating whether it was healthy or not...

I've had a similar experience. "unhealthy" seems to often be used in place of "not normal."

I don't blame them. Advertising has been pushing "normal" food choices for 100+ years. Social gatherings are focused too much on eating. People are shamed for being "skin and bones."

I've been doing it for more than 10 years. I never get hunger pangs. I don't feel the need to eat something before leaving the house, or stopping at a drive-thru while out. I'm able to make better food choices. It doesn't mean I starve myself, or abstain from eating lunch/dinner with friends. I get all necessary calories for whatever my goals are (ie fat loss, maintenance, or weight gain).

Constant calorie intake from accessible food products designed to sit on store shelves for months should be considered not normal and unhealthy.

birdyrooster• 3 years ago

I mean some people look unhealthfully slim like they would starve if there was too much snow or they couldn't leave their house for a protracted time.

red-iron-pine• 3 years ago

People are shamed for being "skin and bones."

In all of western and handful of middle eastern countries I've lived in, I've never once seen people say that except in jest; e.g. imitating the Concerned Italian Mother or Babushka, etc.

With the exception of 2-3 very skinny coder-types, pretty much everyone I met could have lost 3kg and still looked fine, and most of them (myself included) could probably stand to lose 5kg or more. Pretty much everyone I met in Dubai and the US was fat as fuck; little more reasonable in Canada, Australia, and France. Asia was still pretty lean, but getting bigger.

StefanWestfal• 3 years ago

I tried it for some time but felt cranky in the morning until I ate at lunch time. How was your experience regarding cravings, hunger and mood changes over time when starting your fasting?

gavinray• 3 years ago

Not the poster but the hunger lessens after the first few weeks as you adapt to it, or at least that's my experience

I start to dread eating a bit now because I get tired/sleepy after I do. I want to eat because I'm hungry but mentally feel clearer if I don't.

arcturus172• 3 years ago

Not OP, but I've done ~16:8 intermetinent fasting (aka skipping breakfast) many times during my life, and have almost always experienced morning crankiness like you.

At times I've felt the crankiness has been good; the increased aggression has led to some really productive mornings. The flip side of the coin is that it sometimes also leads to negative thoughts and feelings of pessimism until I eat.

I prefer to have a more stable mood so what I'm doing as of late is drinking a protein shake with oat milk for breakfast and a high-quality multi-vitamin. The crankiness completely goes away and mental acuity is still high. It's still excellent for weight control since it's a ~200kcal breakfast that is digested very fast. Arguably better for recovery too since I practice sports every day. It's definitely not IF but it's been serving me well.

I'm also experimenting with a ~24h fast once a week, from Sunday lunch to Monday lunch, but don't have enough experience to know what it's doing for me yet.

wpietri3• 3 years ago

For what it's worth, I can happily do IF if I eat from 7a-1p, but I'm miserable if I do 12p-6p. I got super grouchy in the 10a-12p range and if anything that got worse over the month I tried it.

matwood• 3 years ago

I was a religious breakfast eater. Would often wake up because I was hungry. The first few weeks of IF was rough, but the hunger eventually passed. My energy levels also dipped, but then went way up. I try to do all my deep work and exercise before my first feeding of the day because of how sharp I feel.

3ish years in I feel great, and routinely get comments how 'in shape' I look. I also try to weight train every day and train BJJ a few times/week.

Other things I've learned personally is if I eat poorly the night before (lots of sweets or something), I am more likely to feel a bit of hunger the next morning. Normally I don't really feel hungry though, and if I'm busy I can go right through lunch without noticing.

pammf2• 3 years ago

I only had cravings while doing the 36 hours fasting, which I don’t do regularly anymore. It was usually during dinner time (rest of the family was having dinner normally) and what I tried to do was to distract myself with something else (work, book, movie, etc.). I never really had problems during other periods of the day.

What I’d suggest is to experiment a bit, perhaps in your case skipping dinner is easier than skipping breakfast. Or try to start by simply not having snacks and gradually increase the intervals between meals.

mlboss• 3 years ago

It took me around 2 months to get adjusted to it. Also, I lost a lot of hair during the initial months. It is a big shock for body to get adjusted after a life long breakfast eating habit.

The advantage is that I no longer get hungry. Ever. If skip lunch I might feel weak by evening but never hungry. You develop this super power against food. You can choose what and when to eat and not give in to whatever is available.

nobaddays• 3 years ago

Yeah my doctor always tells me to intermittent fast, ie stop eating at 8ish pm and have breakfast at 10am.

andy_ppp3• 3 years ago

A mouse only lives 5 years so if we scale everything based on this to humans you’d have to be fasting for 16h * (80 years / 5 years) = 256h or nearly 11 days. You could be damn sure doing this regularly your gene expression would change. Of course basing the scaling this way is completely ridiculous but no less ridiculous than inferring anything about humans from the original study.

ford• 3 years ago

I see where you're coming from, but just because mice don't live as long as humans doesn't mean all biological processes happen 16x as fast. They don't defecate 16x as often as humans or sleep 16x per day.

Do you think there is 0 signal about potential impacts on humans from testing on mice? How would you prefer research be done with a similar cost, ability to control variables, & level of ethics?

andy_ppp3• 3 years ago

I think the extrapolations you’ve made from my comments are fighting an argument I’ve not made and am not interested in having because I’m not a scientist working on these things. What I’ve tried to explain in my comment is that we do not know how the metabolism of a mouse doing 16:8 relates to a human being. No more and no less, we simply do not know how to do that mapping and trying to draw conclusions about humans from this specific study is fairly futile because of this (unless they are using some methodology I’m not aware of)!

kuhewa2• 3 years ago

Not 16x, but a 15 hour mouse fast definitely doesn't translate to diel IF type pattern in humans. There's a signal here sure but it probably corresponds to fasts of more than a day.

aquafox2• 3 years ago

Actually C57 black 6 mice (the ones used in the study), only live 2.5 - 3 years.

aquafox2• 3 years ago

Computational biologist with >5 years experience in analyzing RNAseq data like the one in the paper: I find 80% of genes being differentially expressed very hard to believe. You usually see such strong effects only when there are other sources of variation not being controlled for (e.g. batch effects) or when inducing an unphysiological state (e.g. treating with a cytotoxic drug).

manmal2• 3 years ago

Have you considered that 16h for a mouse might, from a metabolic POV, be comparable to 4+ days in humans? That’d be quite the intervention.

331c8c71• 3 years ago

I think they are overselling... Not clear to me how they treated the multiple testing across 22 tissues - gene expression measurements across different tissues in a single mouse are clearly not independent from each other.

A total of 15,430 genes were DE in at least one tissue, but only 816 and 1,335 genes were differentially up- or downregulated, respectively, by TRF in ≥5 tissues

dukeofdoom• 3 years ago

I tried this. Ended up thinking about food too much until 1 pm. But I might try it again.

LAC-Tech• 3 years ago

Try having an early dinner rather than skipping breakfast. I've been doing it this month, going alright.

halfjoking• 3 years ago

Best trick IMO is to take prebiotic fiber while fasting.

That way your gut bacteria gets fed and doesn’t get desperate to tell your brain you’re starving.

Personally I don’t feel ketogenic state is reached from 16 hours. Feels like I need at least 24 hours, but usually do 36. Only thing I need other than water is electrolytes. I would get bad headaches without my mineral/pink salt.

shagie• 3 years ago

Another approach that had some popularity a bit ago was "VB6" - Vegan Before Six (pm).

Mark Bittman's VB6 Diet - https://www.webmd.com/diet/a-z/mark-bittman-vb6-diet

Vegan by Day, Glutton by Night? Thinking About VB6 - https://www.bittmanproject.com/p/236239_vegan-by-day-glutton...

You can find other posts of people trying it.

siliconc0w• 3 years ago

Metabolism for mice doesn't directly translate to humans, their metabolisms are a lot faster. I think the formula is roughly 7 times, so this is just above two days of fasting for humans. Which I'm sure would be fantastic for your health but pretty hard to do.

TRF has had mixed research results vs normal calorie restriction - sometimes leading to a drop of muscle - but it's a bit hard to tell since the studies are not consistent about monitoring protein intake or weight training which is generally necessary to avoid muscle loss when doing any sort of weight lost protocol. I think the latest research is skipping dinner is generally better (eTRF).

torusenthusiast• 3 years ago

For posters who do time restricted eating, how do you deal with the panicked/dizzy feeling you often get when not eating for long periods. Does that eventually go away with IF, or do you just get used to it?

lockyc• 3 years ago

Electrolytes.

You probably need at least more sodium.

https://old.reddit.com/r/fasting/wiki/fasting_in_a_nutshell/...

spirit557• 3 years ago

That's from low blood pressure and/or electrolyte imbalance. So drink more fluid supplemented with electrolytes. You can also take a spoonful of a pure fat like coconut oil or ghee in the morning or in between a meal to help with any hunger pain.

You don't faint from low blood sugar, you faint from low blood pressure. If you were losing consciousness from low blood sugar you're gong to start convulsing and having seizures, afaik.

In normal homeostasis, insulin lowers blood sugar as needed and glucagon raises it. There is always a balance being made between the two I believe.

Time-restricted eating reshapes gene expression throughout the body

Related Stories