Intermittent fasting increases hippocampal neurogenesis in mice
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
> Adult hippocampal neurogenesis is a process that describes the generation of new functional DGCs from adult neural stem cells through the amplification of intermediate progenitors and neuroblasts, as well as the integration of these new neurons into the existing neural circuits.
Source: https://www.nature.com/articles/s41380-018-0036-2#:~:text=Ad....
Anyone care to ELI5 please?
The cells in our body are continuously replaced throughout our life, with the exception of our brain cells. For many many years we believed that mammals didn't create new brains cells in adulthood. You were born, your brain grew and developed as you became an adult, and then you were done.
About 20 years ago we realized that that was mostly true, but small parts of the brain continued to produce neurons through adulthood. This happens in two important parts of the brain:
- the hippocampus, which is associated with memory
- the olfactory bulb, which is associated with sense of smell (and memories related to it).
Humans have a relatively weak sense of smell, and if we create new neurons in the olfactory bulb it's much less than other mammals.
The process is convoluted, but small regions of the brain create those new neurons and they migrate through fluid-filled holes in your brain - most die, but a small % survive and incorporate themselves into that brain structure. The key thing to realize is that neurogenesis accounts for a tiny fraction of the neurons in our brain, and yet it's still an important process.
So why does adult neurogenesis matter, and what does it do for us? Neurogenesis is tied to our ability to learn and form new memories. So, if it's impaired, our ability to learn is reduced. There are tons of things that impact it - age, sleep levels, exercise, among others.
In the lab I worked at, we used to induce a form of brain damage to rats which greatly impaired neurogenesis, then run them through mazes, which they did quite poorly at.
We took some of those same brain-damaged rats and had them run in exercise wheels for two weeks, and they were suddenly doing just fine at maze tasks. When we stained and looked at their brain, their neurogenesis rate was back up to (or even above) normal levels.
We've known for a long time that exercise is great for your health, and there's a growing body of evidence that the same is true for intermittent fasting. What's interesting is that it's not just good for your overall body health, but both can help keep your brain working optimally by increasing neurogenesis and BDNF (which protects your existing neurons).
Even if we had confidence that adult neurogenesis occurs in humans, we can't really expose humans to a stimuli, kill them and then do a BrdU stain, so it's difficult to know how well any rat study translates over to humans.
What about teeth?
To me the premise that the possibility of changing my brain through fasting is unquestionably a silver bullet free of tradeoffs is suspect. Or to put it another way, the fact that fasting had a particular effect does not imply that effect is a positive one.
Furthermore, hunger is a strong motivation toward behaviors that are ethically suspect in its absence. A full belly is a rung up Maslow’s hierarchy.
People who spend their days starving mice at scale have incentives to interpret that starvation in positive ways. It would be hard to rationalize starvation and vivisection otherwise and still consider one’s life choice reasonable and ethical. Hence, I am skeptical of acting in the ways an optimistic interpretation of the report suggests. YMMV.
Presumably neurogenesis is occurring all the time and is restricted to a small set of regions in the brain and the new neurons form in just those very strict set of regions. Those neurons are not moving to the neocortex, just a few millimeters within the dentate gyrus. That is to say even robust neurogenesis is not likely to change your mind, cognitive experience, personality or intelligence in any measurable way.
But the parent comment is unfair insofar as scientists don't randomly chose to food deprive or "vivisect" animals because they think it's intrinsically fun. Running these experiments requires a huge amount of annoying busy work that I can't imagine anyone choosing to do without being paid or having some other motive.
In particular, the reason intermittent fasting is studied is because there's a large and increasing body of research that suggests that it may be of benefit to a wide variety of health measures.
The business of cutting apart animals and looking at the insides claim revealed knowledge isn’t new. The Romans called it “haruspicy” and also built wealthy bureaucratic institutions in service of narratives useful to the powerful.
Contemporary interest in fasting research is helpful to those who find advantage in moralizing upon obesity. Intermittent fasting is a virtue reserved for those with food security. It’s attractive to people whose socio-economic status insures that going hungry is a choice and a display of will power. Not weakness. The conclusion that it makes such people smarter is self serving.
The preponderance of health evidence is that starvation is detrimental to human health and creates long term cognitive problems. But lab mice are an industrial product and labs are industrial institutions and the money keeps flowing so long as the results are acceptable to those providing it. That’s the way it has been for millennia.
>We evaluated the impact of 3 months of IF (12, 16, and 24 hr of food deprivation on a daily basis)
We were upstairs when we realized it was the first ice cold night of the year.
So we went down and mice are cuddled in the cold , and apparently out of food.
Someone decided fruit loops mixed in with mouse food was a good idea. One mouse went and ate. Other one was clearly in roughed shap.
First mouse took a fruit loop, walked it over, and kept putting it against the others mouth. After couple minutes she started eating.
The sheer empathy of one mouse helping another still gets to me.
They both were fine after eating and being moved to a warm spot.
For those interested here is a great interview with David Sinclair, Harvard Researcher on aging:
I'm not against doing these kinds of studies on mice but the only conclusion you can really get is that we should do longer studies on animals that are closer to humans or on humans themselves.
Most probably, weight loss will be less than pound in water calorie restriction.
Also, there was studies on Ramadan fasting and they've found almost two fold increase of serum brain-derived neurotrophic factor at the end of fast. Level of BDNF correlates with neuroneogenesis in brain.
Sadly, leap seconds are rare.
12 is better than, say, 8 or 6 (e.g., snacking at night).
Curious how your experience compares to your pre-IF state 5+yrs ago?
BMI 18-19 for reference.
Would you mind sharing your BMI from before IF? Also curious if you feel IF is better than the alternatives (e.g., Keto, which for me has been the "easiest" of the effective diets)
I did have a really good experience doing long fasted running in the morning. At first I couldn't go three miles without breakfast. But eventually I could do twelve straight out of bed and feel great.
As I understand, fasting trains your body to supply blood glucose from fat stores, which breaks your brain's craving for sugary foods- which are a crutch for getting your blood sugar up. (Remember, your brain runs mainly on blood glucose)
Keto does the same thing a different way. But to me IF is way easier and healthier. (I strive to eat a Mediterranean style diet which ain't Keto!)
I would say the experience for me is really good- as long as I avoid the cliff, which is what I was warning about. Basically, just don't try to get all extreme thinking longer fasts are always better.
Stay up all night playing factorio. No food, of course, because you're in a middle of a refactor and you can't be bothered to eat. Crash in the afternoon and sleep until midnight. There you go, easy mode health++, apparently.
Generally for health you aim for a longer fast with perhaps social break nights. But whatever works.
given different metabolism speed and body energy stores depletion rate that would translate into days for humans.
Sidenote: it is not a good thing to torture animals.
I did a water only fast which is documented here: https://news.ycombinator.com/item?id=16533514
The mental benefits in terms of ability to concentrate are hard to put into words. It's different than with micro-dosing which gives you a false sense of your abilities. The long fast showed me what kind of energy gets unlocked when we feel like we're close to snuffing it. It's like the body gets ready for a final push so that you can hunt and find food. I stopped doing these crazy type of diets after discovering IF.
IF gives me a similar result (the highs and lows on the graph are less extreme but at least it's sustainable) without landing myself in hospital (in retrospect the kidney stones were most likely legacy/cruft that needed to be refactored anyway, and who knows what kind of cancers or other long term illnesses my body "ate" while I pushed him that hard). I understand this is all pretty mental to read but back in 2013 there was no IF and all I had was the theory that dogs and rats that were kept on an IF survived longer.
!!!
Disclaimer: this is the most extreme one I ever done so please don't start out with this if you want to try... try 7 days or 2 weeks are enough time to do some extreme diet. But don't go overboard - which is way too easy after 2 weeks because you'll be so high on your own achievement and you won't feel hunger. It'll feel like you're able to continue for 2 or 3 months. (you won't). the key is in recognizing this and to quit regardless! Also knowing your own body is key. E.g. if you do sports and have a 20 year history of pushing yourself to extremes probably yes. But I understand why doctors bail and give the "blanket advise" that this is irresponsible.
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- It is not stated if the diets are isocaloric or hypocaloric; probably because it wasn't measured. Timing restrictions and calorie restrictions are two different stressors on the body, and all else being equal stress is positively correlated with neurodegenerative effects. It might as well be only isocaloric intermittent fasting is indicative of BDNF increase and hippocampal neurogenesis.
- Fasting time is a very specific slice of the circadian rhythm; between 15:00–07:00, so this study is only skipping dinner and not breakfast. This is important because body has different stress responses early in the morning (we wake up with higher cortisol levels) and our insulin mechanism also reacts differently to food deprivation based on time of the day.
- Limits of animal models already mentioned, and I think it is particularly compounded around the concerns around timing and bioeconomics of growing brain regions. Mice and humans have similar encephalization quotients, but size of neural cells are constant between both, so is the cost to create or upkeep them. Same concern goes for the number of days of energy each animals bodies can store. So the underlying calculus to make new brain cells or not might be vastly different. For example maybe humans need to undergo a much longer (e.g. multiday) fast before this effect kicks in.
Can you provide some references to this?
I often read these threads about fasting/intermittent fasting on HN and see a lot of nitpicking about flaws in the study.
Given that almost all studies tend to fall between "no effect" or "clear positive effect" of fasting on health, do we have enough evidence to say "fasting is good for your health?" I still believe there's value in further research to nail down exactly how and how much, but curious if we can make the overall statement confidently.
It seems balance and "do what works for you" would be the recommendation.
If you can successfully pull it off, there's substantial evidence it is generally beneficial. But I have a genetic disorder that impairs fat processing (so I had no real fat stores to draw on while fasting) and I began fasting or semi fasting while homeless at times when I was too broke to afford food.
Initially, it was extremely hard on me. I routinely threw up on fasting days and usually managed to get something into me so was really only light rationed, not actually fasting. It took years for me to get well enough for fasting to stop being horrible torturous drama and I still have extremely severe diarrhea when I resume eating.
Second, there is a thing called Refeeding Syndrome that can occur when you break a fast. It can be deadly.
I think it benefits a lot of conditions, but if you have a condition, it's also potentially dangerous to try it and we need to get a lot more savvy about how people with conditions can safely try it.
With asking around about Refeeding Syndrome and some best practices for how to effectively break a fast plus some experience, breaking a fast has gotten to be a lot easier on me.
I could have potentially died from fasting and it likely wouldn't have been blamed on fasting. My condition is serious enough they would have blamed my condition.
But it has proven beneficial and I hate it less than I used to.
There is a reboot procedure for getting the system going again. After a 3-day fast, mine was something like this:
Turmeric and ginger Tea
+ 30 minutes
bone broth
+ 30 minutes
sauerkraut
+ 30 minutes
almonds / pumpkin seeds / sunflower seeds
+ 45 minutes
avocado
+ 30 minutes
soup (bone broth / chicken broth, kale, tofu, chard, napa)
+ 45 minutes
yogurt
nuts / seeds ... beef bowl for dinner (rice, onions, simple vegetable side)
The logic behind this is that the turmeric and ginger causes a (very mild) inflammatory response in the stomach. It gets the body "ready" for food again.
The bone broth supplies a very mild, easily digestible form of protein that resupplies immediate deficits. Sauerkraut supplies good digestive bacteria to rebuild your population of digestive helpers. This helps prevent diarrhea, though not entirely.
Almonds, pumpkin seeds, sunflower seeds (preferably unsalted) begin supplying dense packets of minerals. Don't have too much, but a few handfuls will be a good start.
Avacado! Calories (from good fat) and minerals, and more fiber.
The soup is the first serious nourishment. The tofu, chard, kale, and napa provide a range of good stuff. Protein from the tofu, and more minerals and fiber from the leafy greens. Lightly salted broth, (a mix of bone broth and chicken broth for flavor) is also good.
Yogurt (active culture) provides calcium and fat, and another excellent boost to helper bacteria.
More snacking on the nuts and seeds as you like...
A light dinner of thin slices of ribeye with onions and soy sauce over rice, and a nice cruciferous vegetable blanched, dressed with a touch sesame oil and salt.
Rebooted!
The waits in between are important, as is continued hydration along the way.
All that said, many of the benefits you supposedly get from 3-day / 5-day fasts, can be had from reduced calorie diets.
Try resuming with an at least slightly green banana. It's a really effective tool vs. diarrhea in general, but I've found it to also be a great restart after fasting.
I would say 16 hours for a mouse is probably more like 7 plus days without food for a Human.
I’ve always been curious if a long fast would clear up random stuff like knee pain (or even gum disease)
My only regret is that I wasn't able to have someone doing a study or researching fasting monitor and harvest the wealth of information that was available.
These days I maintain 172 lbs with time delayed eating (18/6) and a clean diet.
I've done 48 hour fasts. The major thing that keeps me from doing it longer is that it's really hard to do while also socializing.
Can you provide a citation for this?
The effects of fasting on the human body are... fastinating! (Sorry!)
I hate black coffee so I’m not sure what I could do.
I don’t feel like eating after dinner and I don’t feel hungry in the morning.
You’d think there would be something calorie free to make coffee taste good.
It’s hard with a family though if they’re on different schedules.
My approach was that the kids ate things I wouldn’t and so it wasn’t difficult for me to be present and not eat.
And pedagogically it was apparently better than eating, say, just salad or a minuscule serving of the meal, as their mother was concerned about modeling behavior that might encourage diet pathologies (e.g. anorexia).
There are lots of definitions of fasting and it’s not perfectly understood which consequences line up with which behaviors.
It’s pretty clear things are different once you break down the different ideas of “fast” and build it back up. In a dry fast, nothing enters your body except air. Now switch to a water fast and your stomach and kidneys are going to start doing something with that water. Have some coffee and now your liver is processing that caffeine and other chemicals. Add some calories (milk) and more organs are doing more. And then once you get past 500 calories in a day, you’re not really fasting by just about any definition.
So your coffee is doing something, the milk is doing something, but I don’t think it’s perfectly clear what happens at each threshold.
The coffee is fine though. Maybe try it iced?
Could someone explain what this tells us about 16 hour vs 24 hour intermittent fasting? Is one "better" than the other?
But only once every 16 hours, apparently.
Being past fifty might play into it.
I think about half the USRDA is about right for my caloric intake, though I've never consulted a nutritionist.
>Compared to AL [ad libitum, "at one's pleasure"] mice, IF12 [12 hour fast], IF16 [16 hour fast], and EOD [24 hour fast] tamice demonstrated significantly lower average body weight after 3 months of IF (Data not shown).
So this could be due to lower overall caloric intake.
Disclaimer. I looked at their charts but I didn’t completely understand.
https://journals.physiology.org/doi/full/10.1152/jn.00005.20...
Seems to get some portion of the benefits.
Seen it happen, it's real not pretty.
Several animal species, in times of hardship (like migration) reform their brains, by forgetting unimportant memories or reduce brain area dedicated to now unimportant skills. Quite similar to a stroke victim, that relearns speech, by "re-purposing" a different brain area.
Fasting indicates a food scarce environment, so the brain might do the same thing every body does - and reduce calorie consumption in all areas, including the brain. So the "reconnection" might just be a side-effect of the "down-sizing".