
Metformin Promises to Extend Life for a Nickel a Pill - deegles
https://www.wired.com/story/this-pill-promises-to-extend-life-for-a-nickel-a-pop/
======
pavement

      In 2014 alone, Americans filled 76.9 million 
      prescriptions for metformin, and some of those 
      prescriptions went to Barzilai himself. (He’s 
      been taking the drug since he was diagnosed 
      with prediabetes around six years ago.)
    

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

    
    
      Metformin is in the biguanide class. It 
      works by decreasing glucose production by 
      the liver and increasing the insulin 
      sensitivity of body tissues.
    
      The most serious potential side effect of 
      metformin use is lactic acidosis; this 
      complication is very rare, and the vast 
      majority of these cases seem to be related to 
      comorbid conditions, such as impaired liver or
      kidney function, rather than to the metformin 
      itself.

------
roceasta
_> You could also be able to shrink the suffering and enormous expense that
accompanies cancer, heart disease, dementia, and all the other plagues of
growing old._

No. It could at best defer the health costs. We need to stop being passive
about this and embrace the idea of (1) life extension technologies for those
who want, (2) assisted suicide for those who don't.

When this philosophical shift happens we can get much more serious about life
extension research and mental well-being (purpose; reasons to live) and reduce
the vast expenditures on palliative care for those who are merely waiting
around to die.

------
Joyfield
But holy DAMNED does it give diarrhea. (Diabetic here, not using it since a
couple of years)

~~~
nikolay
Yeah, but only to 20% of those who try it. For them, there's a slow release
version, but I don't think it's widely available - I tried finding Glucophage
SR in Europe with no success!

Anyway, I'm among the lucky 80% of those without side effects. I'm not
diabetic; I take it for biohacking reasons.

~~~
SwellJoe
"I'm not diabetic; I take it for biohacking reasons."

Did you just say to your doctor, "Hey, doc, I'm trying to live forever here,
can you hook me up with some metformin?"

I often wonder about this, when it comes to folks using drugs for off-label
purposes. I know there are doctors that are amenable to prescribing things
like anti-depressants on patient request, but a diabetic drug seems a harder
sell.

~~~
nikolay
Many anti-aging doctors prescribe it to non-diabetics. I personally buy it in
Eastern Europe without a prescription with no issue. I know all the side
effects such as potential Vitamin B12 deficiency, lactic acidosis, etc.

------
dpeterson
From reading the article, it seems the health benefits may, primarily, be
attributed to having lowered blood sugar? I've also seen a number of
references saying just eating less has the ability to extend life. So, could
it be that sugar, in general, is really really bad for us? If you don't have
diabetes, could you get the same benefits Metformin provides simply cutting as
much sugar out of your diet as possible? The article reads like a distraction
for the masses from the research being done for billionaires to extend their
lives. "Hey, don't feel so bad about all the billionaires working on super
fancy life extending treatments you can't afford. You can take a cheap little
pill to live longer too."

~~~
Asooka
Yes, yes, yes, yes, and yes. If you manage to just cut out all fructose from
processed sources (i.e. fruits are ok, anything containing table sugar -
glucose+fructose, or high-fructose-corn-syrup is out), you'll be much better
off than most people. Also don't forget to eat flax seed to keep your
omega-6:omega-3 ratio close to optimal, and take your vitamins.

But even then, metformin might help you live even longer and better. More
studies needed.

And even _then_ , these are just things to keep your body's own systems
functioning optimally. I can't imagine what real anti-aging drugs might do.

------
reasonattlm
The results for metformin in animal studies are all over the map, with many
studies showing no results on life span or health span. A great many people
have taken metformin for a long time with no great and obvious results. Short-
lived species have far more plastic life spans in response to metabolic
adjustment in comparison to humans; the two most reliable and sizable effects
on mice (growth hormone receptor knockout and calorie restriction) do not have
similarly sizable effects in humans. Laron syndrome sufferers and calorie
restriction practitioners do not live significantly longer than others.

The one and only reason why metformin is getting into trials is as a political
lever to get the FDA to acknowledge aging as a medical condition with defined
causes for which treatments will be approved. Metformin couldn't really be
rejected in the way the FDA likes to reject a lot of things because it is so
widely used and has been so widely used for a long time.

The future of human longevity is not tinkering with metabolism to try to push
it to be a little more like calorie restricted metabolism. That is a waste of
time and effort. It is enormously expensive to carry out the work to try to
understand metabolism well enough to adjust it safely. Hell, look at the past
20 years of work on calorie restriction: how much has been spent, how many
man-years focused on it, and the research community is still only scratching
the surface on how to induce similar effects via therapies.

Yet there is another approach, one that is far more cost-effective in time and
money. Repair the causes of aging. Look at removal of senescent cells: in a
bare few years, and at far less cost than has been spent on calorie
restriction mimetic development, researchers have demonstrated robust effects
and reversal of numerous age-related conditions in mice. Unlike metformin and
similar drugs, the results are consistent, sizable, and produce rejuvenation
in old individuals, not just a slight slowing of aging.

There is an enormous difference between the bad way forward (typified by
metformin) and the good way forward (typified by senolytics). In the former we
all die on the same schedule as our parents and grandparents. In the latter we
can gain decades or more of additional healthy life.

~~~
deegles
Could you post some links? Any idea when these therapies will hit human
trials?

~~~
reasonattlm
And further, whenever anyone turns up to say "metformin is great", just point
them at the studies showing that aspirin does a fair job of extending healthy
life span in a variety of laboratory species. Arguably the aspirin life span
studies show more consistent results than metformin, though there are fewer of
them. And we all know what aspirin does for human life span.

For senolytic therapies, look at Unity Biotechnology's pharmaceutical trials
starting this year, Oisin Biotechnologies' gene therapy approach, SIWA
Therapeutics with an antibody approach. There are a dozen or so candidate
drugs worth looking at, in addition to the non-drug approaches.

If you have the connections you can order any of the various senolytic
pharmaceuticals today and try them. Though this would be unwise for the
chemotherapeutics with animal data, since they are not friendly compounds, and
worth waiting for a year or two to see how more targeted things like FOXO4-DRI
work out in human tests. A year or two from now will be a great time for self-
experimentation on this front, given the range of candidates and the size of
the effects in mice where there is data. Today the situation is in an awkward
state where some of the easier pharmaceuticals to handle are either going to
have tiny effects or have no animal data, while the others still need human
data. Still, I would expect medical tourism to flourish for these things quite
soon: the drugs are cheap, the beneficial effects sizable.

~~~
wavefunction
I'm allergic to aspirin so an alternative is nice.

~~~
Aron
You got Samter's like me (AERD)? No fun.

------
stupidcar
While I'm certain it's a very respectable school, "Albert Einstein College of
Medicine in the Bronx" sounds like the place a sitcom character pretending to
be a doctor would invent as their alma mater.

~~~
arkades
It's pretty solid and, for medical residencies, its internal medicine program
routinely draws from the same pool of applicants as MGH, NYP, and Sinai.

It's a pretty solid program all around.

(I didn't go there, but know plenty of folks that did.)

------
rscho
As an MD, I find those "take this miraculous drug we've known for years and
live long" fads pretty ridiculous. People are far too confident in medical
"research". If you know some statistics, read medical papers before bed and
have a good laugh!

------
nikolay
Dr. Ward Dean is a huge supporter of taking Metformin and it fits his
Neuroendocrine Theory of Aging [1] [2]. You can watch a short video about it
here [3].

[1]: [http://warddeanmd.com/articles/neuroendocrine-theory-of-
agin...](http://warddeanmd.com/articles/neuroendocrine-theory-of-aging-
chapter-1/)

[2]: [http://warddeanmd.com/articles/neuroendocrine-theory-of-
agin...](http://warddeanmd.com/articles/neuroendocrine-theory-of-aging-
chapter-2/)

[3]:
[https://www.youtube.com/watch?v=5bdoiHdhjbM](https://www.youtube.com/watch?v=5bdoiHdhjbM)

------
pbarnes_1
If you don't manage taking metformin with large enough meals etc, you get
wonderful "metformin moments" (i.e. uncontrollable diarrhea like you've got
food poisoning).

Gotta weigh up those risks. :)

~~~
nikolay
Only 20% of patients get this and for them, there's the sustained/extended
release version - Metformin ER, or Glucophage SR/XR.

------
nikolay
You need to supplement with calcium and B-12 [1], though... but B-12
supplementation causes cancer [2]. Oh, well...

[1]: [https://selfhacked.com/blog/uses-benefits-
metformin/](https://selfhacked.com/blog/uses-benefits-metformin/)

[2]:
[https://news.ycombinator.com/item?id=15099760](https://news.ycombinator.com/item?id=15099760)

------
myth_drannon
A really great podcast on the subject by Tim Ferris (I think it's one of his
best). They also talk about Metformin

[https://tim.blog/2016/10/20/my-life-extension-pilgrimage-
to-...](https://tim.blog/2016/10/20/my-life-extension-pilgrimage-to-easter-
island/)

------
caycep
Granted, you'd get a huge increase in survival signal just by reducing
everyone's diabetes, but maybe I'm just being cynical...

(i guess since this is HN the solution would be to design a statistical model
that corrects for anti diabetic effect to try and demonstrate non-diabetic
related anti-aging effects...)

~~~
SwellJoe
Given how many people in the western world are pre-diabetic due to diet and
lifestyle, maybe curing that would be a miraculous result in and of itself.

I mean, it wouldn't directly help those of us who aren't on that path, but in
terms of general societal health and average lifespan, it still seems pretty
great. I like it when people don't die. It could potentially save all of us
some money, too.

------
snikeris
Anyone taking this off-label?

~~~
hendersoon
When a type 2 diabetic enters remission after losing weight and/or gastric
bypass, they are typically kept on metformin forever, because it's cheap and
they obviously have a risk factor for diabetes. Metformin is very, very widely
prescribed.

That said, lactic acidosis, while rare, can actually kill you. So I wouldn't
take metformin without consulting a doctor.

------
gscott
The older I get, the more I want the blood of teens.

~~~
JohnTHaller
It's a great emo band name.

~~~
api
"The Blood Boys"

Best punk band name EVER.

------
candiodari
Warning: metformin works by interfering with the mechanism cells use to, well,
essentially request food. Whilst yes, chronically working on too little energy
has been proven to extend lifespans, you will not like the side effects.

For one it makes you stupid. Obviously it interferes with everything requiring
effort, from running to sex.

There are cell types in your body that will, when faced with an energy
shortage simply consume themselves. Usually, this means trading a sudden death
for permanent damage, for example heart muscle cells. This means that when
faced with an energy shortage they will kill themselves. An overdose of
Metformin can cause this to occur on a large scale and when that happens, your
life is somewhere between over and very short.

Do not take any medication without being aware of the side effects and getting
advice from a doctor (and let me spoil the surprise: your doctor will advise
against both metformin and calorie restriction. He will be happy to prescribe
you a placebo. You would be surprised how calming taking one can be)

There are other treatments that extend life, like taking aspirin daily, and
other metabolism blockers, anti inflammatories and blood thinners. All come at
a serious cost (DO NOT take aspirin daily unless you're happy to bleed to
death with any major injury) which makes a lot of sense if you think about it.

~~~
SwellJoe
"For one it makes you stupid. Obviously it interferes with everything
requiring effort, from running to sex."

Fasting (one way to alter insulin sensitivity without drugs) has been reported
to increase focus and energy. I have been doing intermittent fasting (16 hour
fast/8 hour feast, with an occasional 24 hour fast) for the past four or five
months (I started logging my results about 3 months ago, but I started before
that in an imprecise sort of way). I haven't noticed a significant change
either way. I feel fine, with normal levels of energy and the like. I don't
_think_ I'm stupider because of it, though I probably ought to do some A/B
testing to be sure.

I've never taken metformin, and haven't done any real research beyond reading
the article and the Wikipedia page about it, so I don't really know what it
does to someone, but as I understand it sounds like your main concern is the
effect on insulin sensitivity. But, insulin sensitivity seems to be a major
factor in weight and health, and growing evidence suggests that actions
improving it also improve general health.

I'm not saying you're wrong, just that I don't think it's reasonable to
dismiss it or to assume the most simplistic explanation of how the body works
(e.g. glucose makes brains smarter, or glucose makes bodies energetic) is the
correct or complete one.

~~~
1024core
What do you consider "fasting"? No food at all? What about drinks like
coffee/tea? How about water?

Just curious about fasting, need to get into it.

~~~
SwellJoe
There's quite a bit of information out there about the various sorts of
intermittent fasting people are doing. Some people do longer, less frequent,
fasts. Some people combine it with other diets.

My intermittent fasting looks like this:

For eight hours from midday until evening (the exact times shift a little
based on my waking and sleeping schedule; 2PM to 10PM is a pretty common
schedule for me), I eat like a responsible adult. Minimal junk food, desserts
in moderation, try to make my meals balanced, don't eat too much sugar or
simple carbs. I don't deny myself anything I crave, generally speaking, but I
try not to eat garbage. I am also a vegetarian, occasional vegan, but I've
been doing that for 23 years...it is unrelated to my current diet and fasting.

During the other 16 hours of the day, I eat nothing and drink nothing with
calories. I drink water and unsweetened green tea (iced or hot depending on
the weather; right now, it's summer and I'm in Texas, so it's iced tea). I
don't drink coffee, but I normally don't drink coffee so that's not a change.
Some people who fast drink coffee without sugar or dairy; I assume it has no
or very few calories.

I never stop drinking water and don't know of any evidence that supports
dehydration as a beneficial practice. I'm not seeking spiritual enlightenment
or going on a hunger strike, I'm trying to maintain good health as I age.

The goal of intermittent fasting (as practiced by the folks I pay attention
to) is to force your body to improve insulin sensitivity and to reduce caloric
intake by 20-30% without having to count calories or give up favorite foods.

I don't know if it's the optimal practice, but it seems to be working OK for
me, so far. I have lost about 15 pounds (and I'd lost about 5 pounds before
that on a reduced calorie diet), which averages out to a little less than a
pound every week since I started. Weight loss has slowed somewhat in the past
month or so. I have begun lifting weights a couple times a week, though, so
that may be offsetting my weight loss with regained muscle.

You probably need to come up with a fasting schedule that works for you and
fits your existing daily routine. Skipping breakfast was easiest for me, and I
know I have trouble sleeping well when I'm hungry, so eating late in the day
is the right schedule for me. 16/8 is a reasonable balance, for me, as well. I
find it's really quite easy to maintain; I go to bed two or three hours after
my evening meal and then sleep through the next eight hours of the fast. Then
I've only got five or six hours to go after I wake up before eating. I sip tea
through that time, and most days barely notice my hunger.

I don't know if I'll do this forever but, assuming evidence continues to mount
about the benefits of caloric restriction and improved insulin sensitivity, it
seems like I'll keep at it for the foreseeable future.

~~~
jff
> For eight hours from midday until evening (the exact times shift a little
> based on my waking and sleeping schedule; 2PM to 10PM is a pretty common
> schedule for me), I eat like a responsible adult. Minimal junk food,
> desserts in moderation, try to make my meals balanced, don't eat too much
> sugar or simple carbs. I don't deny myself anything I crave, generally
> speaking, but I try not to eat garbage.

So if you shift your example schedule two hours back to 12PM-8PM, isn't that
just saying "I don't eat breakfast any more"? Lunch at noon, dinner at 6, a
snack in between meals, and dessert at 7:30 would fit all the criteria you
laid out, and indeed is something I end up doing pretty frequently, just
without a faddish name like "intermittent fasting".

~~~
SwellJoe
I call it that, too, in the very comment you've replied to: "Skipping
breakfast was easiest for me".

The faddish name makes it easy to google for research on the topic. You can,
of course, call it whatever you like. I'm not advocating anything, I'm just
sharing what I'm doing.

That said, the name does have useful meaning and context. "Fasting" hints at
the metabolic response you're trying to achieve with the practice, in a way
that maybe saying "skip breakfast" doesn't. And, the word "fasting" has
thousands of years of history, which can also be mined for information; it's
even part of the word, "breakfast".

"Skip breakfast" leaves room for "but, I had a donut at the 10AM meeting".

