
Fasting triggers stem cell regeneration of damaged, old immune system - adventured
http://news.usc.edu/63669/fasting-triggers-stem-cell-regeneration-of-damaged-old-immune-system/
======
SoftwareMaven
There is a lot of evidence beginning to emerge on the value of fasting. This
was once encoded in culture as almost every culture had some concept of
fasting. We lost so much knowledge when we let nutrition "science"[1]
completely overwhelm the wisdom of our ancestors.

On a personal note, I found fasting became much easier after I changed my diet
to be ketogenic. With a metabolism primed for burning fat for energy and not
subject to a blood sugar roller coaster, going a couple days without food is
more of a mental challenge than physical hunger.

1\. We've acted like nutrition can give the same cut and dry answers that
physics has, and the health of our population shows how well that has worked.
Worse, nutrition seems to be driven by egos and media in a way that is nothing
short of frightening.

~~~
DenisM
>health of our population shows how well that has worked

The average lifespan has gone up considerably in recent decades, and people
remain active longer than ever, i.e. people are gaining productive years, not
just end-of-life years.

In other words, "it" worked fairly well.

~~~
themgt
That is almost all due to medical, not nutritional science - antibiotics,
better surgeries, pharma, etc. Nutritional science has been an abysmal failure
for decades and is barely beginning to relearn many things "nutrional science"
itself intentionally threw away in favor of laughably simplistic ideas about
how the body works.

~~~
jfoutz
I'm going to go out on a limb and say medicine wasn't very effective pre 1900,
and furthermore the vast majority of life expectancy improvements were due to
clean water and enough food.

Historically, nutrition has saved a ton of lives. But, I'm with you, modern
"nutrition science" doesn't really deserve any credit for that.

~~~
kangax
And ironically, death rates from obesity just crossed those from hunger. The
abundance of food (or rather, abysmal diet culture) is now starting to hurt
us.

~~~
nightski
Sure but isn't it misleading to correlate high caloric intake with obesity? I
mean this CAN be the case, but the more weight I lose and the more I work out
- the more calories I actually consume.

~~~
kangax
I think it's safe to say that there's some sort of correlation, although of
course obesity is a complex issue.

Higher caloric intake is just part of equation. Sedentary life style,
increased stress, reduced sleep, "western" diet (highly inflammatory, with
poor nutrient density), craving-inducing food, and messed up intestinal flora
are just some of the things that likely contribute to obesity.

As someone who travels from US to Europe often, I always wonder what exactly
it is that causes such dramatic difference.

Is it gluten, that's been under scrutiny lately? It doesn't seem to be so,
since so many European countries are happily eating their bread. Although
European-favored sourdough has been shown to positively affect intestinal
flora through fermentation, unlike those puffy bread-like impostors you see in
commercial stores in US.

Lifestyle doesn't seem to differ much either, although Europeans definitely
have a more sacred and slower approach to meals, and there's less of that
"quick lunch in a rush" culture.

However, portion size and difference in cooking oils (olive in EU vs.
corn/cottonseed/canola/etc. in US) seem to stand out the most, and are
probably the biggest offenders. [1]

[1] [http://chriskresser.com/how-too-much-omega-6-and-not-
enough-...](http://chriskresser.com/how-too-much-omega-6-and-not-enough-
omega-3-is-making-us-sick)

~~~
kaitai
There are a number of reports claiming that wheat strains in the US and Europe
are quite different, with differing gluten levels. The US has certainly
pioneered the breeding of high-gluten wheats, as they're better for processed
goods.

Unfortunately, I can't find a reference with any science.

Certainly in Scandinavia wheat does not play the primary role that it does in
the US. Rye, barley, and oats are common in the diet. How many Americans,
though, have eaten 100% rye bread even once in their lives?

------
exratione
The paper, which is open access and worth reading (skip to the discussion at
the end if a layperson).

[http://dx.doi.org/10.1016/j.stem.2014.04.014](http://dx.doi.org/10.1016/j.stem.2014.04.014)

The more interesting part of this to my eyes was the material difference
between 24 hour and 72 hour fasting in human chemotherapy patients, in that
the former didn't do anything to the measure of immune cell populations and
the latter did. Intermittent fasting is nowhere near as well studied as
calorie restriction at this point in time, so it is interesting to see these
mechanisms emerge.

Now this is chemotherapy immune suppression, not aging immune dysregulation.
I'll be mildly surprised to see the exact same result in people with age-
damaged immune systems, as the character of the damage is very different. The
animal results for aging rather than chemotherapy here are intriguing but
that's all. There's still a lot of work to be done to arrive at the level of
comfort with this effect that exists for other aspects of calorie restriction
or intermittent fasting.

But given that (a) obtaining human data on fasting and immune cell population
in old people is a comparatively low cost study to put together, and (b) the
group involved here seems to have a good flow of funding to study intermittent
fasting in a broader context, I'd expect to see that data emerge at some point
in the next few years.

~~~
Florin_Andrei
> _The more interesting part of this to my eyes was the material difference
> between 24 hour and 72 hour fasting in human chemotherapy patients, in that
> the former didn 't do anything to the measure of immune cell populations and
> the latter did._

If you do zero-calorie fasting, there are some important changes around or
after day 3. Hunger disappears. Metabolism is low, muscles are relaxed. The
mind tends to more easily stay focused on a single topic. There's a sense of
clarity and ease, and an odd kind of energy. It's quite a contrast with the
increasingly frantic frustration prior to this time.

This is all from a subjective standpoint, of course, but it's well correlated
by most people who have done it. It seems quite obvious that there are major
changes around day 3. I'd love to see more data from studies.

------
rawland
My humble summary based on superficial reading of the paper:

    
    
      * Prolonged fasting = Eating NOTHING for 48-120 hr.
    
      * BENEFICIAL effect started on cycle 4 (day 39).
    
      * 1 Cycle = 2-4d fasting&chemo; 8-10d recovery.
    
      * Prolonged fasting enhances cellular resistance to
        toxins in mice and humans.
    
      * Glycogen depletion required => switch to fat/ketone
        bodies-based catabolism (!!!).
    
      * They have no idea, what the effects on blood are
        in detail.
    
      * At the beginning WhiteBloodCell count went down.
    
      * After 6 cycles things stabilized.
    
    

Article related paper: [http://www.cell.com/cell-stem-
cell/abstract/S1934-5909(14)00...](http://www.cell.com/cell-stem-
cell/abstract/S1934-5909\(14\)00151-9)

Interesting figures from the paper:
[http://www.cell.com/cms/attachment/2014950454/2036225024/gr1...](http://www.cell.com/cms/attachment/2014950454/2036225024/gr1.jpg)

------
wpietri
One of the things I've been up to the last couple years is reducing the
divergence between my life and the conditions I probably evolved for. E.g.,
much less processed food, reduced use of artificial light that diverges from
the normal day/night cycle, more frequent modest physical exercise, very low
sugar consumption, way less alcohol and caffeine. To me it feels a lot like
when I'm debugging a system and am trying to get back to a baseline by
eliminating complicating factors.

Lately I've been wondering about fasting in that context. Not eating
occasionally was presumably pretty normal for our ancestors. Have other self-
hackers here experimented with this?

~~~
niels_olson
I've been eating one meal a day for 2.5 years now. More about that here

[http://nielsolson.us/blog/2012/08/28/my-
diet/](http://nielsolson.us/blog/2012/08/28/my-diet/)

------
rdmcfee
I don't know that the biological benefits of fasting are associated directly
with cultural fasting patterns in our ancestry.

I suspect they're more linked with our ancestral hunter-gatherer traits. It
seems logical that early humans would go periods of time without eating while
hunting, then consume a large amount of protein and fat in a short period of
time.

Religious and cultural fasting, however, would likely have not occurred until
the development of language which is estimated at 20k-50k years ago. That's
not a particularly long time on an evolutionary scale.

~~~
Florin_Andrei
I agree that we're probably adapted, in our biology, to re-occurring intervals
of food scarcity. I would not be surprised at all if it turned out that our
bodies actually function better on that sort of regime (eat at will for a
while, then forego all caloric intake for a brief period).

I wonder if this was noticed at the dawn of civilization, and then got
codified into religion and so on.

~~~
rdmcfee
Yeah it's interesting how ancient cultures seemed to have (by trial and error
I suppose) incorporated specific behaviors into their culture which, in
hindsight, solve a particular problem that can be scientifically identified.

An example I love is the Canadian Inuit who traditionally ate no vegetables
for 10+ months of the year without developing scurvy. The tradition of eating
raw whale blubber and fish (including the broth) preserved the vitamin C and
minerals from the mea, while eating cooked meat without broth drastically
reduces mineral and vitamin intake.

------
ihnorton
Some similar intermittent fasting studies related to autophagy and mTOR
(rather than PKA in top article):

[http://www.ncbi.nlm.nih.gov/pubmed/20534972](http://www.ncbi.nlm.nih.gov/pubmed/20534972)

[http://www.nature.com/nature/journal/v468/n7327/full/nature0...](http://www.nature.com/nature/journal/v468/n7327/full/nature09584.html)

------
awolf
From an evolutionary standpoint periods of famine were certainly a selective
pressure for our ancestors. It could make sense that prolonged periods of no-
food are not only something our bodies have adapted to survive, but have
adapted to thrive upon as part of their natural cycle.

~~~
jostmey
Sorry for being nit-picky. It is not that we evolved to thrive during periods
of famine. It is that we did not evolve under conditions where resources were
plentiful. That is why so many people die from heart conditions brought on by
excessive eating. The machinery in our body is simply insufficient to deal
with the excess cholesterol.

~~~
libria
He's saying that even when people are universally weakened by starvation, the
other mutations that exhibit advantages (a regenerative immune system in this
case) are rewarded with further generations. I think "evolved to thrive in
famine" is fair to say.

~~~
Florin_Andrei
Evolved to thrive on abundance of resources on the long-term, punctuated by
brief intervals of scarcity.

------
tokenadult
Let's look at what the submitted article, which is a press release from a
university, says. "In both mice and a Phase 1 human clinical trial, long
periods of not eating significantly lowered white blood cell counts. In mice,
fasting cycles then 'flipped a regenerative switch,' changing the signaling
pathways for hematopoietic stem cells, which are responsible for the
generation of blood and immune systems, the research showed."

What's good about this line of research is that it is trying to show whether
or not an observation found in a model animal will also be found in human
patients. As preliminary research, this will have to be replicated by other
researchers before we can rely on this finding (NOT extended fully to human
patients in the current study) to guide treatment of human patients.

This is good news that people are investigating this issue. Once there has
been a thorough review article on this issue published in a different journal
by a different author, summing up several well designed studies, then we will
really have something to talk about here on Hacker News.

I should comment on some of the other comments here. One very tricky problem
in studies of human nutrition is that there isn't a good model organism for
nutrition and its effect on human health. The study reported here, just like
most medical intervention studies, begins in a mouse model. Mice are well
understood organisms and their similarities to and differences from human
beings for many medical treatments are well understood. Mice are not a
particularly good model for nutrition studies, however, because mice are
rodents (part of a clade of obligate herbivores) while human beings are
primates (part of a clade of facultative omnivores). Moreover, human beings,
the current species _Homo sapiens,_ have evolved with co-evolution of the gut
in the environment of the cultural practice of cooking food.[1] Cooking is a
human cultural universal. No other animal lineage has evolved in a similar
environment, so no animal provides a fully suitable model for studies of human
nutritional interventions.

Human nutrition studies are HARD, because they require minute-by-minute
monitoring of the subjects and exact measurements of food intake to gather
meaningful experimental data. (I recall a TV news report from the 1970s about
a human nutrition study in which the study volunteers, who of course were paid
for this, lived confined inside a lab in which lab technicians weighed all
their food to the nearest gram and controlled everything they could eat for
the duration of the experiment. Alas, I've never heard of results of that
study, perhaps because the sample size, with such an expensive procedure, was
too small to generate meaningful data.) Yes, let's see what nutritional
interventions do what for human beings, but let's be careful not to jump to
conclusions too soon, because careful data gathering on this topic is
especially difficult, and anecdotes crowd out data in most popular discussion
of this topic.

[1] [http://www.scientificamerican.com/article/cooking-up-
bigger-...](http://www.scientificamerican.com/article/cooking-up-bigger-
brains/)

[http://www.popsci.com/science/article/2012-10/eating-
cooked-...](http://www.popsci.com/science/article/2012-10/eating-cooked-food-
made-us-human-study-finds)

[http://www.smithsonianmag.com/science-nature/why-fire-
makes-...](http://www.smithsonianmag.com/science-nature/why-fire-makes-us-
human-72989884/)

~~~
Houshalter
Is calorie constriction considered nutrition? Of course animals will have
evolved different food requirements, but it seems like the basic mechanism of
responding to a lack of calories should be the same.

~~~
vanderZwan
It's not my field, but I would expect it to be. We don't ingest calories, we
ingest chemicals that we convert to energy. A term like "calorie constriction"
masks the complicated nutrition processes behind this.

~~~
collyw
yes, but if all you ingest is water, none of that will be converted to energy.
So eating a food with calories will have a quite different effect.

------
Yen
As someone who doesn't know very much about the immune system - I wonder if
this 'resetting' property could be used to treat allergies or other minor
autoimmune problems.

Also, I'd appreciate a medium-level overview of the immune system, if anyone
has a good link.

~~~
brm
As someone with an esophageal autoimmune response I'd be very curious to know
this as well.

~~~
niels_olson
ee?

~~~
brm
Yes though not a typical presentation of EE (EoE?). It ramped up dramatically
around my 24th birthday and appears to be connected with my body's response to
histamines. As such most doctors haven't known what to do with me and we've
been feeling our way blindly along. If fasting even partially resets immune
response i'd be interested.

------
coldcode
Fasting has always been a tradition in many religious groups. It would
interesting to study groups that fasted regularly to see what affect it had on
longevity.

~~~
jostmey
Calorie restricted diets have been extensively studied. Radically reducing
your food intake is about the only known way to seriously extend lifespan. The
trend holds true for virtually every multi-cellular organism ever tested under
laboratory conditions.

~~~
tiglionabbit
I wonder if that would still be true among animals that are allowed to eat
whatever they want to eat, and given plenty of space and others to interact
with.

I'm not positive, but I would bet that a big confounder to these results would
be that we are feeding all individuals in the study an unhealthy, unnatural
diet, isolating them, or causing stress. These factors could cause them to eat
too much.

~~~
jostmey
The data overwhelming supports the hypothesis that eating less extends
lifespan in model organisms. See:
[http://en.wikipedia.org/wiki/Calorie_restriction#Effects_of_...](http://en.wikipedia.org/wiki/Calorie_restriction#Effects_of_CR_on_life_span_in_different_organisms)

~~~
tiglionabbit
> "In contrast to the conclusions reached by the University of
> Wisconsin–Madison (WNPRC) study, a 2012 National Institute on Aging (NIA)
> study published in the journal Nature, concluded that a calorie restriction
> regimen did not improve survival outcomes whether implemented in young or
> older age rhesus monkeys.[49] A key difference between the WNPRC and the NIA
> studies is that the monkeys in the WNPRC study were fed a more unhealthy
> diet.[50]"

Perhaps I was right =]

------
mgulaid
I'll recommend fasting with fellow Muslim friends and co-workers for a day
during Ramadan. it is very rewarding and revealing about our daily routines
and eating habits. I enjoy high productivity during Ramadan, plus it is
healthy.

------
Evgeny
I believe that is the link to the original study:

[http://www.cell.com/cell-stem-
cell/pdf/S1934-5909(14)00151-9...](http://www.cell.com/cell-stem-
cell/pdf/S1934-5909\(14\)00151-9.pdf)

------
themgt
You know I've had a hunch for a while there must be something to these "detox"
diets where you just eat a bunch of carrots or whatever. I think it's
increasingly clear collateral fasting is the answer. The gimmick is "it's the
carrots", the reality is you're inducing an extended fasting state which has
all kinds of beneficial impacts on the body.

The science is increasingly clear that humans should be putting their body in
a fasting state far more often and for far longer than we in the decadent west
do.

------
corysama
Wonder if you can approximate the effect with regular blood donations? It's my
understanding that regular blood donations are a good idea for males because
it helps clear out old red blood cells with iron buildups. Clearing out old
white blood cells could be yet another motivator.

~~~
chrisBob
Are we likely to resume using leaches as a standard medical technique?

~~~
araes
You joke, but I have a condition where my iron content builds up relatively
quickly, and the best thing they've still figured out as a cure is blood
letting.

~~~
escherplex
These are just nervous jokes following the ongoing demise of antibiotics. But,
having to resort to venipuncture for treatment of hemochromatosis must be
tough. Hope your phlebotomist also prescribed some chelating agents to reduce
frequency of treatment.

~~~
araes
Luckily they caught it relatively early on because a family member had it, so
its been semi-easy to manage.

------
achille2
Can someone with access to the original paper kindly lookup specifically how
long each fast lasted and how often?

The article is a bit vague: _periods of no food for two to four days at a time
over the course of six months_

------
kumarski
I asked a question on quora regarding the difference between successful animal
clinical trials and humans

[http://www.quora.com/Clinical-Trials/What-are-examples-of-
dr...](http://www.quora.com/Clinical-Trials/What-are-examples-of-drugs-that-
showed-promising-results-in-clinical-lab-animal-trials-and-failed-miserably-
in-human-trials)

------
TheSpiceIsLife
Certain body systems only activate certain processes when the body isn't
processing food. Firstly, the gut _is_ an immune organ. Think of it this way:
this inside of the digestive system is technically outside the body. It is a
continuous tube mouth to anus, and functions as an interface between the
outside world and systemic circulation - both blood and lymphatic. The gut has
GALT - Gut-Associated Lymphoid Tissue [1]. Lymphatic tissue _is_ an immune
system _organ_ and a waste disposal system [2].

It's important to note that all (most) fats are first absorbed by the GALT
(specically Lacteals [3]), where it then takes some time to enter blood
circulation - the Thorasic Duct [4] (largest lymph vessel) drains in to the
Subclavian Vein [5] - so any fat soluble toxins (as in, fat soluble non-
nutrients and / or outright toxic molecules) are absorbed by the GALT and
removed by white blood cells. _Only_ when this system _isn 't_ being stressed
by our regular (and typically poor) food intake can the immune system attend
to it's ordinary tasks of dealing with regular cellular waste products.

Aditionally, Caffeine consumption reduces immune activity [6]. Alcohol
(ethanol) is a Type 1 / Group A carcinogen [7] - why doesn't alcohol packaging
state this in the same way cigarette packaging does (in Australia, at least).

1\. [http://en.wikipedia.org/wiki/Gut-
associated_lymphoid_tissue](http://en.wikipedia.org/wiki/Gut-
associated_lymphoid_tissue)

2\.
[http://en.wikipedia.org/wiki/Lymphatic_system](http://en.wikipedia.org/wiki/Lymphatic_system)

3\.
[http://en.wikipedia.org/wiki/Lacteal](http://en.wikipedia.org/wiki/Lacteal)

4\.
[http://en.wikipedia.org/wiki/Thoracic_duct](http://en.wikipedia.org/wiki/Thoracic_duct)

5\.
[http://en.wikipedia.org/wiki/Subclavian_vein](http://en.wikipedia.org/wiki/Subclavian_vein)

6\.
[http://www.sciencedirect.com/science/article/pii/S1567576904...](http://www.sciencedirect.com/science/article/pii/S1567576904001924)

7\.
[http://www.cancer.org/cancer/cancercauses/othercarcinogens/g...](http://www.cancer.org/cancer/cancercauses/othercarcinogens/generalinformationaboutcarcinogens/known-
and-probable-human-carcinogens)

Full Disclosure: this is my field of expertise, I hold an Advanced Diploma in
Clinical Nutrition from an Australian Nationally Accredit Training
organisation. I have been actively studying this field for over ten years.

Edit: link to my blog
[http://thecurrentstandard.wordpress.com](http://thecurrentstandard.wordpress.com)

------
noisy_boy
Aside from the non-sense of miracles etc., it has been a tradition in yogis in
India to fast regularly. Maybe the positive effects were observed/known even
in those older times.

------
mc_hammer
a lot of methods used by people throughout our history are no longer
considered "good" by western culture...

bath houses and sauna (sweat lodges also), fasting, fish and potatoe diets,
beer and wine consumption (maybe was not considered good, but was common)

all seem to have lost ground.

i could also argue that eating sushi or seaweed is on the list, also, peace
pipe (!), and 2-sleep days (sleep+"second sleep").

im currently leaning towards these being better for us that 9-5 coffee strung
out + staring at a lcd all day... by a lot

------
tiglionabbit
The article seems pretty obvious. If you don't eat food, your body will eat
itself. It would make sense for it to eat the worst cells first. Then when you
add new food into the system it can replace those cells.

Perhaps fasting was more common in the past, so it was a reliable trigger for
this behavior, and our bodies did not need to develop their own automatic
trigger. Why waste resources rebuilding things, after all?

------
jotm
So does working out - it's basically the same effect, only faster from what I
understand.

------
mingabunga
I've been eating 1 meal a day for the past 2.5 years and have not been sick
since (usually I'd get a few colds each year) plus I always feel great. I'd
like to think I'm getting the benefit of an improved immune system such as in
this article, but I guess time will tell.

------
andywood
Did you need to hear it from a non-monk? That's ok. That's totally fine. I
heard it from a holy man.

~~~
gwern
Given all the _other_ stuff monks and holy men say... yes.

~~~
andywood
We must discern ideas by the merit of the idea, yes?

Otherwise, Argument Against Authority ;)

~~~
gwern
No. Expertise and authority is an excellent way to evaluate claims. In this
case, monks and holy men have espoused so many crazy and harmful ideas over
the years that knowing they have endorsed [all kinds of fasting, not just the
ones being evaluated scientifically] is not useful because their endorsements
have no connection to the truth.

------
chrisBob
It probably just creates a slightly acidic environment. All you need to create
stem cells from adult human cells is a weak acid.

[http://www.nature.com/nature/journal/v505/n7485/full/nature1...](http://www.nature.com/nature/journal/v505/n7485/full/nature12969.html)

~~~
DenisM
Stop with the down-votes, you guys.

Had there been no references cited by chirsBob, this comment would be an
overall negative "hearsay"-type contribution, but the inclusion of a
reasonably reputable, if outdated, reference allowed others to point out the
paper retraction, and raised the overall quality of the discussion.

~~~
chrisBob
No, actually I submitted it knowing that the paper had been retracted, and was
stirring up trouble. The down votes are perfectly reasonable in this case.

I do appreciate the defense though as some times is is hard to tell which
posts were inaccurate by mistakes, and which were malicious. [edited to thank
the defending post]

