[HN Gopher] Diabetes Drug Metformin Reduces All-Cause Mortality ...
       ___________________________________________________________________
        
       Diabetes Drug Metformin Reduces All-Cause Mortality and Diseases of
       Aging (2017)
        
       Author : optimalsolver
       Score  : 94 points
       Date   : 2021-06-12 19:22 UTC (3 hours ago)
        
 (HTM) web link (pubmed.ncbi.nlm.nih.gov)
 (TXT) w3m dump (pubmed.ncbi.nlm.nih.gov)
        
       | cromwellian wrote:
       | My mother died from a combination of metformin and colchicine.
       | She had renal insufficiency, the FDA had warned not to prescribe
       | metformin to people with renal insufficiency, and it made her
       | kidneys worse. She had been taking daily low dose colchicine for
       | gout, but the worsened kidney function caused a poisonous level
       | of colchicine to build up. She vomited so much, she lost a too
       | much electrolytes and ended up in the hospital delirious. The
       | hospital thought it was a stroke and tested for that, eventually
       | ruling it out, but the time wasted on thinking it was a stroke,
       | obscured a growing instability in her kidneys, liver, thanks to
       | the insufficiency, colchicine, and bad electrolyte levels.
       | 
       | When they infused electrolytes, it swung the pendulum too far in
       | the other direction, and she suffered wild swings in blood levels
       | of potassium, etc. Eventually her kidneys and liver failed at the
       | same time, multiple organ failure, usually for someone in their
       | 60s is not survival. I watched her die slowly over a few days as
       | everything came crashing down.
       | 
       | Afterwards, I tried to get the hospital to conduct an autopsy to
       | show overdose of colchicine levels, but the pathology department
       | somehow "wasn't set up for that" and they said I'd have to send
       | her body to some specialist lab. I didn't want to cause anymore
       | pain with the family, so I opted to just bury her. But I
       | definitely see this as medical malpractice.
       | 
       | And it's a clear warning to not ignore FDA contraindication
       | warnings, even if your doctor apparently doesn't read up on the
       | latest research or alerts.
        
       | [deleted]
        
       | MengerSponge wrote:
       | The only miracle drugs that I know of are sleep, water, and
       | exercise. Even those have dose-related toxicities!
       | 
       | https://peterattiamd.com/metformin-and-exercise/
       | 
       | If you're healthy enough to exercise, that's probably more
       | effective. Apparently (I haven't tested myself, and I don't know
       | how thorough the literature is) metformin lowers your lactic
       | threshold, which reduces the total amount of work you can do in
       | that state.
       | 
       | Do cardio, sleep enough, avoid refined sugar and fats that are
       | solid at room temperature. More than that... godspeed
        
         | Filligree wrote:
         | > avoid refined sugar and fats that are solid at room
         | temperature.
         | 
         | This leaves, what, protein and starch? And cooking oil, I
         | suppose, but all forms of meat contain solid fats.
        
           | ansible wrote:
           | Some oils like rapeseed (canola) aren't that good for you
           | either.
        
             | fermentation wrote:
             | And coconut oil, which contains quite a bit of saturated
             | fat.
             | 
             | Edit: apparently coconut oil is supposed to be solid at
             | room temp. I should get an air conditioner
        
             | void_mint wrote:
             | These articles always bring up a lot of comments that use
             | the phrase "good for you" or "healthy", but in my
             | experience most of the time a person saying "___ is good
             | for you", they pretty much never quantify how or why.
             | 
             | Can you explain, in what capacity oils aren't "good for
             | you" ?
        
               | shaicoleman wrote:
               | I think the best talk of the health dangers of seed oils
               | is in the following video:
               | 
               | Dr. Chris Knobbe - 'Diseases of Civilization: Are Seed
               | Oil Excesses the Unifying Mechanism?' [1]
               | 
               | If you're short on time, you can skip directly to the
               | trials data section [2]
               | 
               | 1. https://youtu.be/7kGnfXXIKZM
               | 
               | 2. https://youtu.be/7kGnfXXIKZM?t=2020
        
               | void_mint wrote:
               | > in rats
               | 
               | So we're deriving that an entire class of foods aren't
               | "good for you", because of a specific outcome in a study
               | conducted on rats?
               | 
               |  _edit_
               | 
               | Also, the effect produced on the rats was weight gain. Is
               | all weight gain bad? Oils aren't "good for you" because
               | "weight gain"? So, if a person's goal was to gain weight,
               | would oils be "good for them"? And if yes, isn't this
               | just way too broad a statement ("oils aren't good for
               | you") to have any value?
        
               | shaicoleman wrote:
               | Indeed, not all animal trials are valid in humans, and
               | your skepticism is warranted.
               | 
               | In the rest of the video he discusses how it affects
               | human health, along with the data to support that
               | assertion.
               | 
               | It's seed, vegetable and hydrogenated oils that are bad
               | for you and are correlated with obesity, heart disease,
               | diabetes and cancer.
               | 
               | Coconut oil, olive oil and butter are fine.
        
           | ivankolev wrote:
           | The dose makes the poison. Everything in excess is
           | detrimental.
        
           | basch wrote:
           | >refined sugar
           | 
           | I wouldn't personally consider rolled oats, rolled barley, or
           | rolled rye to be refined sugars, nor are they quite in the
           | white rice, potato, corn, flour starch category, despite
           | flattening a "grass seed/fruit" being a type of "processing."
           | 
           | Furthermore, oversimplifying food advice tends to leave out
           | conversation of how food breaks down. The main ways are time,
           | grinding, heat, fermentation. Fermentation gets a bit of an
           | asterisk at the end of hard rules lists. They may say no
           | dairy but then exempt fermented dairy. Lactofermentation of
           | oats will be less starchy than uncooked oats.
        
           | throwaway34241 wrote:
           | Well, there's a bit more variety there than cooking oil - I
           | think the "healthy fat" category usually includes nuts,
           | avocados, olive oil, salmon, etc. I don't think chicken
           | (including the skin) is supposed to be bad either. [1]
           | 
           | From my understanding of the available evidence, these fats
           | are supposed to be more healthy than other animal fats /
           | butter (saturated fat). [2] Whether saturated fats are bad or
           | not depends on what you compare them to - they seem less
           | healthy than say, olive oil, but might win out over refined
           | carbs. And the most clearly bad one is trans fat which has
           | the strongest evidence against it.
           | 
           | [1] https://www.hsph.harvard.edu/nutritionsource/2012/06/21/a
           | sk-...
           | 
           | [2] https://www.hsph.harvard.edu/nutritionsource/what-should-
           | you...
        
         | lambdaba wrote:
         | Avoiding "solid fats" aka saturated fats is bad advice. The
         | science behind saturated fats being harmful has been debunked
         | and even some government agencies have rescinded the
         | recommendation to avoid them.
         | 
         | On the contrary, it's the liquid fats that are more often
         | harmful, especially linoleic acid (aka omega-6).
        
           | myfavoritedog wrote:
           | Isn't it amazing how they can make such confident
           | recommendations about these dietary issues without having the
           | data (real data, not some bs study) to back it up? They end
           | up reversing themselves over and over, utterly destroying
           | societal trust in the field of dietary medicine.
        
         | void_mint wrote:
         | > avoid refined sugar and fats that are solid at room
         | temperature.
         | 
         | Why?
        
       | rscho wrote:
       | This whole comment section is totally delusional regarding the
       | reliability of medical statistics and preliminary data in life
       | science. It's funny (and sad) to see people easily disparaging
       | "state-of-the-art treatments" be so prone to experiment on
       | themselves with moonshot claims.
        
         | [deleted]
        
         | gremloni wrote:
         | No matter what, the underlying reality, is that there are
         | certain chemical you can take in the right amount per person to
         | give you the best health possible. We might not be there for a
         | while but studies help us in that direction.
        
           | rscho wrote:
           | Yes, I agree. But not all studies. There is a substantial
           | proportion of studies that are just statistical noise, and a
           | smaller but still substantial part that are outright fraud.
           | 
           | However, individual experiments are not studies in the
           | academic sense. Especially if they are not formally reported
           | so that the experience is not lost in time.
        
         | myfavoritedog wrote:
         | For decades, we were told that the food pyramid was the ideal
         | healthy diet and that dietary fat was the enemy. It was all
         | bullshit.
         | 
         | Eggs are healthy, eggs are unhealthy, eggs are really
         | unhealthy, eggs are healthy, eggs are really healthy.
         | 
         | I had trained medical professionals tell me twenty years ago
         | that I was going to ruin my kidneys with my low-carb dieting.
         | Twenty years later, I'm still keeping the weight off and
         | medical science has started to catch up to what I knew just by
         | experimenting on myself with moonshot claims.
         | 
         | The biggest problem with medical science (just look at how
         | COVID issues were butchered by politics and celebrity), is that
         | they refuse to just say, "We don't really know." Because all
         | too often, they have no clue. But they are trained to come up
         | with answers and sound confident about it.
        
           | rscho wrote:
           | There are many things I don't know. However, here's one thing
           | I know to be true: individual experiments do not make for
           | population-level generalizations. Additionally, dieting by
           | reducing or even excluding a single well-known food category
           | when there are many more left appears as less radical than
           | taking a pill that will rebalance your whole metabolism,
           | don't you think?
           | 
           | Regarding the "we really don't know" part: one can observe
           | that people here are basing their own shamanic medicine on
           | what they read in scientific papers, suddenly pretending that
           | those papers can be trusted while they'll disparage the
           | theories of clinical practitioners as being old-fashioned and
           | manipulative. Well, it happens that many of those theories
           | are based upon lots and lots of research and certainly more
           | so that the "fad of the day" is. And yes, those theories are
           | often refuted after years of clinical application, which does
           | not bode well for experiments based on "few papers shamanic
           | medicine".
        
           | jopsen wrote:
           | > just say, "We don't really know."
           | 
           | That is what OP says.
           | 
           | What we open see is that "we don't know" is often equated
           | with "does not work".
           | 
           | (I guess that also very frequently how it works out)
        
         | [deleted]
        
       | healthnut99 wrote:
       | The only way to get a reliable answer at this point appears to be
       | a large, randomized trial - the TAME trial
       | (https://www.afar.org/tame-trial) was supposed to have started in
       | 2020. Although the official website doesn't say so, I found
       | various articles in the press from late 2019 which said they had
       | raised all the $75 million they needed for it (for example, see
       | https://www.longevity.technology/worlds-first-anti-aging-tri...).
       | After that, it has been radio silence from them - no website
       | updates, no press releases. Although their website says they have
       | clinical sites set up, I haven't been able to find the clinical
       | trials.gov entry for it. I even sent an email to the PI Nil
       | Birzalai (at Montefiore in NYC) a few weeks ago to find out more,
       | but didn't get a response. Does anyone know whether that trial
       | even got off the ground?
        
       | Afforess wrote:
       | Gwern did some analysis and determined that the ROI for Metformin
       | vs the cost is positive for 45+ and older.
       | 
       | https://www.gwern.net/Longevity#metformin
        
       | macinjosh wrote:
       | It certainly is a powerful pharmaceutical. It can impact aquatic
       | life that live in treated waste water effluent.
       | 
       | "Emerging wastewater contaminant metformin causes intersex and
       | reduced fecundity in fish."
       | 
       | https://www.sciencedirect.com/science/article/pii/S004565351...
        
         | 8note wrote:
         | If you're already kind of old, you maybe don't want more kids
         | anyways?
        
         | wetpaws wrote:
         | human life > fish life
        
           | simcop2387 wrote:
           | Yes and no. If that's literally allmit does and it doesn't do
           | it to an extreme amount i'd have no issues with it, but it
           | also points to it possibly causing other effects that we need
           | to be looking for and studying so we don;t get caught unaware
           | of it destroying ecosystems that we depend on for our lives
           | too. You have to remeber that we don't exist in isolation
           | drom the environment and if it causes that in fish, it might
           | be causing other problems in us, or in plants and animals
           | that we depend on directly or indirectly.
        
           | baliex wrote:
           | We're all living in the same (complex!) ecosystem. It's
           | possible that the fish you're relegating to be less important
           | than you are somehow benefiting you in some indirect way
        
           | [deleted]
        
       | drcode wrote:
       | I have been taking metformin for anti-aging purposes for about 6
       | months now. I decided to take it mainly because the risks are
       | small, and I wanted to counter the natural bias on these sorts of
       | things, which always leans towards "doing nothing".
       | 
       | By taking metformin, it means I have a personal stake in the
       | developoment of anti-aging medicines and have a reason to
       | evaluate any newer options that appear (since there may be a
       | reason to switch metformin to another treatment) I feel like
       | taking metformin makes me less biased when it comes to evaluating
       | treatments in the field, even if I think the efficacy of
       | metformin is still an open question.
       | 
       | In terms of side effects, I have noted mild gastric upset (I
       | actually wonder if this is part of its mechanism of action,
       | making you less hungry in this way) but little impact on exercise
       | (I take it even on days that I exercise, and I have a fairly
       | heavy exercise routine)
        
       | birriel wrote:
       | Comparison of metformin and berberine based on Cochrane meta-
       | analysis:
       | 
       | https://www.youtube.com/watch?v=OPsMMfSQKQ0
        
         | clumsysmurf wrote:
         | Looked at berberine also, seems toxic to the liver.
         | 
         | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867333/
        
       | toddh wrote:
       | Metformin does have some long term issues. After 10 years it can
       | cause serious lower back pain. Not in everyone, but it's
       | something to be aware of.
        
       | api wrote:
       | Could this be replicating what fasting and caloric restriction
       | do?
        
         | nate_meurer wrote:
         | Yes, there's evidence for that. However the jury is still out
         | on whether metformin is a net benefit for people with healthy
         | insulin sensitivity. It appears there are negative effects:
         | 
         | Derek Lowe talks about the negative effects of metformin on
         | healthy people:
         | 
         | https://blogs.sciencemag.org/pipeline/archives/2019/06/24/me...
         | 
         | Peter Attia talks about the same, and some interesting other
         | considerations:
         | 
         | https://peterattiamd.com/191013/
        
           | birriel wrote:
           | Folks that take metformin for anti-aging usually take it on
           | exercise off-days. There was concern about lactic acidosis,
           | but it's beginning to become clear that it mostly arises in
           | patients with comorbidities.
        
           | dcolkitt wrote:
           | Metformin likely blunts the impact of high intensity
           | exercise. But for the 65% of people living sedentary or low
           | activity lives, it's a straight win. Even for those who are
           | consistent with physical fitness, the downsides can likely be
           | avoided by waiting a few hours after the morning exercise
           | session to dose.
        
             | electriclove wrote:
             | Right, and wouldn't the non extended release version work
             | well if taken at night and exercise in morning (or vice
             | versa).
        
         | 238475235243 wrote:
         | Yes. And keto, OMAD, etc... They all do the "same thing" in
         | reducing serum glucose and therefore all the downstream bad
         | things that happen.
         | 
         | Metformin forms the base plank of novel metabolic cancer
         | regimens too.
        
           | jcims wrote:
           | >Metformin forms the base plank of novel metabolic cancer
           | regimens too.
           | 
           | For which you'll likely have to lie to or find an alternative
           | oncologist who's willing to tolerate adjuvant therapies that
           | aren't 'standard of care'.
           | 
           | There are organizations that are developing protocols that
           | include metformin along with statins, anthelmintics and even
           | some antibiotics that are showing promise across a variety of
           | research and even some clinical trials to help fight cancer
           | through a number of mechanisms. Independently they are not
           | likely sufficient to beat cancer but may slow its roll
           | through the body of the patient.
        
             | CodeWriter23 wrote:
             | "alternative" practitioners have been keeping humans
             | healthy for several millennia prior to the existence of the
             | AMA and their so-called "standard of care".
        
               | oivey wrote:
               | Sure, but evidence from last several millennia also show
               | they haven't kept people healthy quite as long.
        
               | nojokes wrote:
               | Those so called alternative practitioners lack scientific
               | rigor, I am afraid of, or more likely just do not know
               | what they are doing. Exceptions exists of course.
        
               | hellbannedguy wrote:
               | The magic of placebo. Chiropractic school dropout, with
               | the bonus of having a ex girlfriend who was a Herbal
               | Doctor. A Naturopath? I forget.
               | 
               | What really sealed the deal was this one professor.
               | Attractive lady whom spoke like she was addressing the
               | United Nations. I still remember the time she told me to
               | show the class my Coccyx. I was relieve I had good
               | underware on.
               | 
               | Back to the most rediculious statement from the red
               | lipstick mouth of a PhD. (I comment on her appearance
               | because she was cute. So--please don't take it any other
               | way. I know there are people waiting to pounce.)
               | 
               | She stated,
               | 
               | "We have over 15 upper cervical techniques, and they All
               | work equally well." Studies, and Placebo Effect are
               | conviently never talked about at that school."
               | 
               | That said, I feel most modern medicine is not much
               | better.
               | 
               | Placebo rules in every healing art.
               | 
               | The kid in front of me, at Chiro school, was the spitting
               | image of health. I was actually jealous. He was getting
               | weekly adjustments. He was getting something called a
               | Rotary Adjustment.
               | 
               | He was biking with his wife, and father in-law on a sunny
               | Saturday. He stopped peddling, and fell over. Died of a
               | massive stroke, at 25.
               | 
               | While I'm here. Sharon Stone was a big Chiro fanatic. Out
               | of the blue she developed bilateral aneurisms, or tears?,
               | in her neck. A world renowned vascular surgeon happened
               | to be giving a talk at UCSF. The hospital asked him to
               | perform the delicate surgery. It was obviously
               | successful.
        
             | rscho wrote:
             | And choloroquine! Let's not forget chloroquine. It can beat
             | anything.
        
             | 238475235243 wrote:
             | This is easy in the US, check out Care Oncology.
        
               | jcims wrote:
               | That's who we used, they made it very simple. Our
               | oncologist was not pleased though.
        
               | rscho wrote:
               | Haha. I'm so happy and relieved that I don't have to
               | practice in the US anymore.
        
       | clumsysmurf wrote:
       | Picture seems complicated
       | 
       | Our study, performed in C. elegans and human primary fibroblasts
       | shows that there is an age-related decrease in metformin
       | tolerance, which in later life leads to toxicity of all metformin
       | doses tested. This shows possible safety risks of late life
       | administration of metformin to individuals without diabetes,"
       | 
       | https://medicalxpress.com/news/2020-11-age-decisive-positive...
        
         | Nevermark wrote:
         | It would be interesting to know if lower doses were tolerated
         | better while still providing some benefit.
        
       | pochamago wrote:
       | My dad actually switched doctors because his original one refused
       | to prescribe metformin to anyone who wasn't fully diabetic
        
         | rscho wrote:
         | And rightfully so given the state of the evidence.
        
           | staticassertion wrote:
           | What would you consider satisfying evidence?
           | 
           | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839379/
           | https://pubmed.ncbi.nlm.nih.gov/31405774/
           | https://pubmed.ncbi.nlm.nih.gov/31954752/
           | https://ncbi.nlm.nih.gov/pmc/articles/PMC4287273/
        
             | rscho wrote:
             | Years and years of widespread clinical practice would be my
             | standard, but I'll make do with multiple large-scale
             | randomized studies AND precise guidelines if absolutely
             | necessary. As for evidence seeking, clinical research
             | happens to be part of my job so I don't really need
             | assistance, thanks.
        
               | staticassertion wrote:
               | That seems like a silly standard, but do you.
        
               | rscho wrote:
               | It's the standard of one particular professional with 15y
               | of clinical practice and research who's seen every kind
               | of manipulation and incompetence in medicine. But yeah,
               | it may be silly. We'll see about that in the coming
               | decades I guess.
        
               | staticassertion wrote:
               | I'm not planning to take metformin but it was discovered
               | a century ago and has been in use for half that time. A
               | quick look shows me that it's the 4th most prescribed
               | medication in the US. I find it hard to understand how
               | this would not satisfy "years and years of widespread
               | clinical practice", at least with regards to
               | understanding negative implications.
               | 
               | But as you said, you can do your own research, so I'll
               | leave things where they stand. You just sound more like
               | someone who's annoyed by pop-science more than someone
               | who actually has strong opinions about the article or
               | Metformin.
        
               | rscho wrote:
               | I am well aware of the downsides of metformin since
               | someone ends up in my ER because of it most weeks. So
               | you'll excuse me if an off-label and very new potential
               | indication is not an immediate go for me. When we want to
               | open a new indication for a particular drug, evaluation
               | of the risk-benefit ratio for this particular indication
               | has to be performed. There are many factors at play and
               | results are completely unpredictable.
               | 
               | As for the rest no, I'm all for pop-science because it's
               | what stimulates the interest of the masses. The problem
               | in my eyes is more that academic medical studies
               | available to the wider public are akin to a very sharp
               | saw, and people will get cut if they don't know what
               | they're doing.
        
               | staticassertion wrote:
               | Yeah I'd recommend you open up with information like that
               | in the future, just right off the bat. It's a lot more
               | interesting and at least somewhat useful.
        
         | [deleted]
        
       ___________________________________________________________________
       (page generated 2021-06-12 23:02 UTC)