
New report on the cellular effects of a calorie-restricted diet in rats - conse_lad
https://www.salk.edu/news-release/eat-less-live-longer/
======
adamgluck
The only reason a study like this works is because it takes place in a
controlled environment where they can actually starve the rats (or sometimes
make genetic changes that reduce the rats hunger.)

Study after study and clinical experience shows that low calorie diets are
really hard for humans “in the wild” to maintain in practice. People who are
on them constantly complain of hunger (in the mid-20th century these were
actually called “semi-starvation” diets), and go back to their previous weight
as soon as they are done. That’s why a lot of modern dieting has oriented
around low carb / high fat because it means that you get enough calories, but
the composition of your macronutrients causes you to lose weight. You don’t
have to go as low as Keto to get these effects (that’s 5-10% carbs) and
certainly don’t need to entirely cut out fruit, etc. And the results have been
observed clinically for 100+ years.

This, however, hasn’t prevented academic nutritionist after academic
nutritionist from pushing these narratives without any clinical experience.
Can you imagine being at least a little hungry for 20 years... the equivalent
time span in humans to get the effect reserved here in rats? That’s insane.
And, more bluntly, probably not doable.

If you’re skeptical of this try dropping your caloric intake by 30% for two
weeks and tell me how you feel :)

~~~
silviogutierrez
To echo other replies, ketogenic and other diets diets with specific protocols
(IF) do work, but primarily for behavioral reasons. That is, you’re just not
that hungry. Or if you eliminate an entire meal (IF), you ”save” a ton of
calories.

Yes there are subtleties around actual macronutrient composition and gut
flora, but the effect appears to be minimal. Find a keto person eating 5000
calories of bacon per day and I guarantee they’re not losing weight.

For what it’s worth: I’m a big fan of keto for cuts.

~~~
adamgluck
This actually isn’t entirely true. You’re operating under the “energy in-
energy out” theory of weight loss, but human regulation of body fat is more
complicated than that.

Specifically, we store energy in adipose tissue in the form of body fat after
a meal (think of it like storing data on disk) and then when we are low on
energy we burn that fat (load that data “in-memory”). However, a lot regulates
when we burn fat. Blood sugar and insulin levels signal to the body not to
burn fat and those come directly from carbohydrates. Additionally,
carbohydrates are the initial energy source that is turned to fat. So with no
carbs all your body knows how to do is burn fat for energy, and no additional
intake of carbs means that there is no excess energy to store as fat to begin
with. So, actually, even with a 5000 calorie diet you might see some weight
loss... because your body has literally nothing (no carbs) to store as fat.

However, keto and low carb diets do have the benefit of the fact that they are
entirely sustainable (unless you’re really addicted to bread) so I agree in
that way they are behavioral :P

~~~
pen2l
> You’re operating under the “energy in-energy out” theory of weight loss, but
> human regulation of body fat is more complicated than that.

I hear the "energy in-energy out" being dismissed like this often, and while I
do agree with you that our bodies are more complex than that, I want to say
that in practice this adage more or less just works, indeed to the degree that
it's valuable to have in common knowledge to inspire folks to lose fat.

Particularly, if you want to lose fat, you reduce your caloric intake (and
what you are consuming, shoot for higher protein intake and lower carb
intake). In addition to this, do some aerobic exercises. This is really it. If
you do this you're nearly guaranteed to lose fat. I did this, my peers did
this, it's really simple, the only hard part is finding the motivation to
start and having faithful long-term committal to a routine.

~~~
PeterisP
The thing is that "energy in-energy out" works if you make some changes while
keeping everything else constant.... and we're really, really bad at keeping
everything else constant.

Add extra activity, and the natural effect will be an increased appetite
that'll nudge you to eat more calories - and it's not a given the effect of
that extra activity will be a calorie deficit, the increase in appetite can
easily be _more_ than what you spent in those exercises.

If you _try_ to reduce caloric intake, that's a very different beast than
actually reducing caloric intake - if you try to reduce caloric intake by
skipping carbs at lunch, it can result in reduced activity (so less calories
out) and a strong nudge to "cheat" at other meals or snacks; and again it's
plausible to get to a situation where the unintended compensation is larger
(and opposite) than the behavior modification that you made.

 _That_ is the problem with the "energy in-energy out" model - one does not
simply change the 'energy in' or 'energy out' part and expect that other
things will stay constant either magically or through sheer willpower.

------
soneca
Somewhat tangential. I often see people treating different diet restrictions
that make you healthier as if they were competitors. Low carb/high fat, versus
low calories, versus intermittent fasting. They imagine the different
orientations as startups in a winner-takes-all market and pump their preferred
one _against_ the others.

I think a better way to frame a healthy diet is that you should aim to follow
all three and realize that they (obviously) help each other work. These are
collaborative orientations, not competitive.

You can control i) what you eat (low carb/high fat), ii) when you eat
(intermittent fasting), and iii) how much you eat (low calories).

You should be following at least one of them at all times, two of them often,
all three of them sometimes.

~~~
jjallen
Totally agree. Each diet may affect different pathways; we probably want to
engage in all of them to a degree.

Recently I have been pondering how we should eat if higher protein increases
all-cause mortality and higher carb diets increase all-cause mortality, so
I've come up with my seasonality hypothesis: basically we would experience
periods of lower carb or lower protein diets historically, which would engage
each of these various beneficial pathways we have.

For instance, and this is my hypothesis: we wouldn't eat wooly mammoth for
breakfast lunch and dinner every day, we would eat nothing but it for three
days, once a month. Dense carbs would come sporadically ("yay, we found a bee
hive" twice a year) and fruits (carbs) would blossom in either only spring or
fall.

~~~
tsimionescu
While you are possibly correct that those may be somewhat realistic historic
diets, why do you think they would be favorable to a longer, healthier life?

Evolution doesn't generally optimize for longevity, it only optimizes for
reproduction. The lifespan of most animals in the wild is much shorter than
what can be achieved with a carefully controlled diet.

~~~
visarga
Humans have a long childhood and even the availability of the grandparents can
increase the chances of survival of the child. So we adapted to live longer.

~~~
Nasrudith
Reminds me of cephalopods and their outright suicidal reproduction in
contrast. It involved a specific gland and when removed they would starve
themselves to death anyway.

Granted it is a very different niche in the ecosystem but it hints that it is
a matter of self-perpetuation where longer lifespan in this case is a side
effect.

------
ruminasean
I've done strict calorie tracking for restriction, keto as well as IF.

The best I've ever felt was keto, the easiest for me to adhere to was calorie
tracking. It's marginally harder if you eat out a lot, but if you cook for
yourself and can throw everything on a food scale for a week or so until you
get an idea of what's servings of your most commonly-eaten foods looks like,
tracking calories made losing weight for me and reducing my daily eating
almost comically easy. There's a switch in my brain somewhere that works
really well when I have to enter the calories of everything that goes in my
mouth into an app....suddenly that cookie or those chips that were so hard to
resist aren't a thing for me at all....my brain manages to yell "200 calories
for THAT?? Nope." I found myself eating more at the end of the day just to hit
my total calories and macros.

~~~
lmilcin
The easiest way I found to stay on a diet as a lifestyle (instead of dieting
for a bit and then stopping and regaining the weight) is alternate day
fasting.

I found I can't just decide never again to eat the things I like and never
again feel sated. Feeling hungry constantly isn't exactly my idea for the rest
of my life.

Alternate day fasting lets me survive a day with no calories knowing that the
next day I can be sated and eat (almost) whatever I want.

I have also found that when I eat every other day I put much more attention to
what I eat on those days -- I mean, if I just did not eat yesterday and I
won't eat tomorrow I want to eat well today. Even if I am going to eat sweets
-- I will try to go for something better and not feed myself with garbage.

I also found that alternate day fasting is good willpower training. Being able
to restrict myself from eating for an entire day somehow trains me to be
better at other things that require willpower.

~~~
war1025
So are you saying that you continually eat only every other day? Or is this
just something you do time to time? Curious as much as anything. How long have
you been doing this?

~~~
lmilcin
I have lost 25kg (55 pounds) over a course of a year. Half of that was
intermittent fasting (one day eating for about 10 hours, then no calories for
the rest, about 38 hours) but accounts for 3/4 of results.

When not eating I would not eat or drink anything that has any calories in it.
I typically drink water, black coffee or green tea.

I have also tried longer fasts from time to time (2-7 days typically, 2 weeks
once) and then I would supplement with vitamins, l-tryptophan and lean
broth/bone broth in moderate quantities (a cup a day), just for safety and
general well-being (l-tryptophan is precursor to serotonin and mildly anti-
depressant).

Intermittent fasting is hard at the beginning but after about 2 weeks I get
used to new regime. It seems it is the same every time I start it anew. It
might be getting easier but I think that's because I already know what to
expect.

Also, when intermittent fasting it is much easier to start longer fast. I
find, when fasting for more than 2 days first two days to be the hardest.

------
grandmczeb
Since people are sharing anecdotes I might as well share mine. I’ve personally
tried IF, keto, calorie counting, and various combinations of all three. I’ve
only ever lost weight when doing some form of calorie counting, and since
that’s easiest for me without putting other restrictions on my diet, I’ve
settled on just tracking calories long term.

~~~
leetrout
I have a lot of success with high fat / high protein diets because they let me
function better with lower calories.

I subscribe to the church of keto / slow carb in broad strokes. I think there
is a hormonal element that we don’t fully appreciate that relates to our
ability to lose weight effectively.

My frustration with pure calories in / calories out is the rumination I do
with how much calories we really extract from certain foods. I am convinced
(as some science agrees) 100 calories of sugar and 100 calories of bacon
aren’t handled the same. I also wonder about how some people must have faster
digestive systems and if it moves through faster are you still extracting the
same calories as someone else...

~~~
didibus
From what I understand, 100 calories of bacon and 100 calories of sugar is the
same. Though there are other compounds in those that may trigger effects in
your body.

That said, how calories are measured is from an average approximation. It is
true that different people may yield slightly more or less calories from the
same foods. Calories are what your body extracts from the food post digestion.

That said, I've never seen strong indicators that the maximum and minimum are
that far apart. So it could be that you are a huge outlier and your body
extracts way more calories from food A then the average person, or way less.
But I think those chances are slim, that is, for you to be such an outlier.

------
0xcde4c3db
Do we actually know whether these effects are triggered by calorie restriction
in general, as opposed to restriction of some specific nutrient that's
happening incidentally to the calorie restriction protocol? I seem to remember
some reports from ~10 years ago that protein restriction, and possibly even
restriction of specific amino acids, has shown similar effects.

~~~
jostmey
I think it’s very clear that is the calorie restriction that’s increasing
lifespan. It’s worked across many studies on almost every organism tested

~~~
ip26
Have we ever gotten clarity on whether these are starvation diets pushing the
subjects below what would normally be considered healthy weight? Vs reining in
over-eating behavior?

E.g. if we imagine running this on humans, are we talking about a BMI of 20,
or 16?

------
ip26
Many of the observed effects at least distantly remind me of the known effects
of exercise.

I wonder if there's an intersection, e.g. without adjusting your eating
habits, exercise results in an _effectively_ calorie-restricted diet?

If there is no intersection, I wonder which is more valuable than the other?
Not much exercise is going to be happening on a starvation diet.

~~~
Gibbon1
I think during physical work your muscles consume glucose. Potentially large
amounts. The liver gives up it's stores of glycogen. Afterwords the liver will
efficiently take up glucose to replenish it's stores of glycogen. I think that
dynamic is a lot better than the insulin mediated glucose to fat conversion
dynamic you get with sedentary people.

------
timwaagh
I don't think I'm mentally capable of following this kind of diet for a very
long time. It just makes you hungry and less productive. It also weakens you
in terms of physical strength.

~~~
ed_balls
That's why I go to gym at least 3 times a week. I build muscle to increase my
"static" calories burn - and obviously burn calories while lifting weight. I
kicked sugar as well.

------
hprotagonist
especially in lab rats, the null hypothesis is that lab rats eat too much and
too regularly.

this may or may not generalize.

------
chubot
I watched part of Aubrey de Gray on Joe Rogan yesterday. He said that fasting
(which is caloric restriction if not identical to it) has a smaller effect on
lifespan for animals of greater mass:

Roughly

\- worm: 5x longer lifespan by fasting

\- mouse: 50% longer

\- dog: 10% longer

\- human: 1-2% longer

I'd be interested to hear support or refutations of this. It seems like
something that should be pretty well studied by now.

------
bigbee
Original title: “Eat less, live longer Salk scientists show how caloric
restriction prevents negative effects of aging in cells”

What it should have been: Are you a lab rat? Eat less, live longer! Salk
scientists show how caloric restriction prevents negative effects of aging in
cells _of rats_

------
acd
I have read that calorie restriction can "reset" the immune system. How do you
eat calorie restricted diet without getting very thin?

If you eat 30% less than you should calories do you not eventually get so thin
that you die from under nutrition?

~~~
0xcde4c3db
It was 30% below a "normal diet" (presumably some reference diet for lab
rats), not 30% below maintenance. Weight loss wouldn't continue indefinitely.

------
djohnston
so how does this translate to my day to day?

can i skip breakfast and eat whatever i want for 6-8 hours, ala IF?

does the window of consumption not matter, and i just need to eat fewer
calories on the day?

~~~
TheRealSteel
I don't have any formal education on this topic, but I did lose a bunch of
weight and keep it off, partly thru intermittent fasting, so I can offer
anecdotal evidence.

For me, simply, it's easier to eat less calories if I intermittent fast. For
some reason, if I don't eat breakfast or lunch, I find my hunger is actually
sometimes _lower_ , and I don't need to eat a bigger dinner to make up for it.

Certainly eating low-g.i\high-carb foods seems to make me get hungry again
very easily.

I also had really good luck with keto, and sometimes a combination of both.

I believe the reason is something to do with blood sugar and insulin not
spiking as much, but I'm not a biologist in the slightest.

~~~
paulcarroty
Eat less & eat often - doctor recommended me once. And its works fine. He also
said fasting and "don't eat breakfast or lunch" are destructive, regular
feeding matters.

~~~
TheRealSteel
I don't believe the research and evidence are going that way.

That being said, I will concede that specifically for some (not all) people
with some eating disorders, restricting intake can be detrimental to recovery
as it increases the chance of a binge later in the day. If you have binge
eating disorder, be aware of that if you're considering intermittent fasting.

~~~
nmfisher
> That being said, I will concede that specifically for some (not all) people
> with some eating disorders, restricting intake can be detrimental to
> recovery as it increases the chance of a binge later in the day. If you have
> binge eating disorder, be aware of that if you're considering intermittent
> fasting.

This is exactly why I don't do that well with fasting, and I don't even have
an eating disorder. With anything more than 16:8, it's very easy for me to
start binge eating, so the whole thing becomes counterproductive.

Every time I seriously lose weight (usually twice a year, once after winter
and once after Christmas), it's eating small, high protein/low-carb meals
every 3 hours or so. That puts just enough volume into my stomach to keep the
hunger pangs at bay.

------
zackmorris
I wish that it was possible to do a caloric restriction study on people who
work out. I spent most of my 20s eating roughly twice as much as average and
hitting the gym 3-4 times per week and I never felt better, especially after
20 rep squat sessions that naturally raise hormones like testosterone and HGH.

I occasionally cut calories to lose weight or train my metabolism to be
"ready" for emergency situations (which was honestly camping or going broke,
not exactly military excursions), but in my experience it basically felt like
death. Like I could feel my body catabolizing muscle and I had flu-like
symptoms if I took it too far for too many weeks.

Anecdotally, my parents' boomer generation felt that bodybuilding was
generally a waste of time. If you watch old movies from the 60s and 70s,
people were especially lean. And then unfortunately juicers in the 70s, 80s
and 90s ruined the reputation of bodybuilding so everyone figured that being
strong meant taking steroids. It's only been in the last 5-10 years or so that
I've noticed a resurgence in natural bodybuilding (check out Jeff Nippard,
Steve Cook and Mike O'Hearn for examples of what's possible natty).

So personally I really feel that lifting weights from about 15-16 years of age
for life probably replicates many of the health effects of calorie
restriction. Like, Arnold Schwarzenegger did some of his best work in his 40s
when he was in better shape than most people in their 20s. Many athletes in
their 70s and 80s look like they're 50.

An untrained human bench presses about 100 pounds. When I was growing up, a
300 pound bench was considered mastery. Today with YouTube and better workout
programs and supplements, that's probably 400-500 pounds. I personally would
choose to have 3-5 times average strength (anything above 4 is metahuman IMHO)
rather than spend my life at a withered calorie restricted strength of 1/2.

Of course ethically, it would be better for the planet if nobody worked out I
guess. That's a separate discussion though, and I feel that some of the
downside could be alleviated if the extra calories came from relatively benign
sources like rice and beans. So my question is, is this all just vanity? Or
would a diet/exercise approach be comparable to calorie restriction?

~~~
jotm
Seems to me like working out you just naturally need more calories. So it's
the same thing - you use more calories than you eat. Like how Michael Phelps
are something ridiculous like 10,000 calories a day while training.

~~~
asdff
You can eat like a pig and perform de facto caloric restriction if you work
out hard enough. No need to subscribe to whatever diet religion is in vogue on
instagram; just burn more calories than you take in and you will loose weight.
It's a basic physics equation.

------
waterheater
I recently read a copy of Isaac Asimov's "The Chemicals of Life." Written in
1954, the book talks about how and why our bodies work. It hardly mentions DNA
and focuses on the larger structures of enzymes, proteins, vitamins, and
hormones. Some of the information is outdated in its presentation, but the
book still holds up in almost all areas. (Also, I had never realized Asimov
was a Professor of Biochemistry. He knew his stuff in this area.)

The first chapter of the book is titled, "The All-Important Protein." This
struck my 2020, DNA-oriented mind as an odd starting point, yet Asimov was
very clear: "all life is protein." The book is remarkably lucid, and here's
one of the best portions of the book:

"Suppose the food you ate contained very little fat. That wouldn't bother your
body a bit. It would take the carbohydrate you eat and turn it into fat. It
happens all the time. Everyone knows what starchy foods will do for the
waistline.

"If both fats and carbohydrates are low, the body is still not at a loss. It
can manufacture both out of the proteins of the diet.

"Where the body _does_ get stuck is in the case of a shortage of proteins. It
cannot manufacture proteins out of fats and carbohydrates. Proteins require
nitrogen, and neither fats nor carbohydrates have any. So proteins can only be
obtained for the body by making certain that protein is in the food. It is
impossible to live on a diet of starch, butter and sugar. You can get all the
energy you need, but you can't build tissue."

Asimov places heavy emphasis on the two primary categories of what our body
cannot naturally produce: essential amino acids and vitamins. Amino acids are
the building blocks of proteins. The human body cannot produce nine of these
amino acids, and we term these to be "essential" (Asimov said there were only
eight; the necessity of histidine for adults was not yet established in 1954.)
We must acquire the essential amino acids from a source outside our body. If
we don't acquire these essential amino acids, our bodies will fall apart.
Wikipedia says "protein deficiency has been shown to affect all of the body's
organs and many of its systems" [1]. Asimov later discusses the importance of
vitamins, or "atom groupings, which the body cannot make for itself and must
get from the food it eats." Without vitamins, we cannot produce certain
coenzymes and will fall ill and possibly die.

Essential amino acids and vitamins. I've been focusing my diet on the
acquisition of those in correct quantities. My diet-optimizing function seeks
to minimize sugar, maximize protein, and moderate the rest. So far, it seems
to be working well; I still build muscle at the gym and fat stays off. Wonder
if this is what keto basically optimizes for as well.

So many articles about bodily function I've seen online jump straight to
considerations of DNA. Certainly, this approach is more accurate, though I do
wonder if we the layperson are approaching health issues with too much detail.
To analogize to software, it's like we're trying to debug our complex C++
program by pouring over the binary. The issues are far more likely to be with
what we're putting in than what's already there.

Sources:

[1]
[https://en.wikipedia.org/wiki/Essential_amino_acid](https://en.wikipedia.org/wiki/Essential_amino_acid)

------
DoreenMichele
_“This gives us targets that we may eventually be able to act on with drugs to
treat aging in humans.”_

Oy. Why do we do this nonsense? Why can't it just be research that helps us
better understand how to eat healthy?

/pet peeve

~~~
Nasrudith
Two reasons. First the drug could provide better results than the most perect
diet it is worth researching period. It is under fewer constraints than an
organic system.

Second, because the theoretical good and the actual results don't align. We
could end many STDs by only monogamously coupling for a generation but that
isn't going to happen and virginity pledges haven't helped at all.

If "the right way" doesn't actually help in practice can it even be called
right?

~~~
DoreenMichele
The problem with virginity pledges is that it's a policy of "just don't find
any way whatsoever to meet your needs." Generally speaking, dietary advice
doesn't boil down to "All food: bad! People who eat are all going to hell!
Stop desiring food at all, you evil sinner you!"

I don't think research into how to eat well really compares one-for-one to
morality policies of "sex is always bad and we will allow for one and only one
right way to ever get laid while still making you feel like shit for wanting
it at all."

