62 comments

[ 2.6 ms ] story [ 131 ms ] thread
> A number of treatments, from low-calorie diets to taking the drug metformin, are currently being investigated.

Everything I read about metformin is exciting: cheap, simple structure, causes weight loss, reduced all-cause mortality in diabetics (ie: they studied it long enough to make sure it works, not just to ensure it reduces blood sugar), reduces blood sugar without hypoglycemia and might prevent cancer.

Yes, I want to find a doc to prescribe me this and also understands the negatives. Why aren't there more docs doing this kind of stuff? Maybe bc it is not so simple?
Preventative pharmaceutical treatments are, culturally, a hard sell unless you have some documented risk factor better than "life".

But if you can find a provider that specializes in "anti-aging", it might be the first thing they reach for. Just don't buy into too much of what they say :)

I would say anti-cholesterol medications were vastly marketed/sold and prescribed to those likely to only benefit a bit. The "Number Needed To Treat" (NNT) was over 100 for most populations prescribed it. But at $1/day and several pharma companies manufacturing their versions, there was a lot of profit from influencing.

But metformin is cheaper than cheap, so that won't happen.

Mass vaccinations were (mostly) an easy sell when they prevented debilitating diseases that harm children (e.g. polio), but remain harder sells when the benefits are primarily for the old/already ill (e.g. flu vaccines).

The childhood mass vaccinations are individually and collectively effective with few doses and target epidemic diseases, some of which lead to a lifetime of diminished capacity.

The flu vaccine targets a potentially epidemic disease, which can be lethal, but doesn't often leave you with lifetime effects otherwise. Additionally, the vaccine has varied effectiveness from year to year, requires an annual dose. Annecdotally, I know if I get the flue vaccine, I'm going to feel shitty for a couple days; but I don't know that I've ever had the flu -- most of the seasonal illness I've had doesn't seem to match, and of course, you wouldn't know unless you were tested, and no doctor wants you to come in to get tested if you're doing OK at home.

i get the flu vaccine every year, and I got this year's shot 3 days ago. I had a sore arm for a couple of hours (from getting a shot in a muscle i think) that night and it was gone by morning.
Except in countries with socialised healthcare.
Even they will develop criteria for when they pay for an intervention or not.

Unfortunately, low-value but worthwhile endeavours often go unfunded or underpromoted because the infrastructure makes it too expensive.

Metformin is cheap and large tracts of the population may benefit from taking it proactively, but once you factor in the cost of MD visits for otherwise healthy people, the public benefit can swing into the negatives.

The side effects can be pretty nasty. I took it for 6 months and the stomach pain and diarrhoea never went away. Berberine however acts on the same pathways as metformin and doesn’t cause the side effects. As a bonus you don’t need a prescription to take it.
> stomach pain and diarrhoea never went away

I always wondered if that's what caused the weight loss: destabilization of the digestive system, so you grow to fear overeating/eating crap.

Dunno how one can say they work on the same pathways: we're not really sure how metformin does its thing.

Not necessarily as you describe it, but weight loss might be the result of the microbiota changes induced by metformin.

I never felt digestive issues when taking metformin, only a feeling of having less energy.

Black boxed. Lactic acidosis.
Please elaborate on both sentences, I don't understand.
See my above post. There was fear that metformin causes lactic acidosis because its predecessor compound did. But the evidence doesn't support that.

Black box warning: Some drug regulators put alerts in a black box on their packaging.

Unfortunately, these same regulators don't revisit these warnings, leading to 'alert fatigue'.

And with non-metformin therapies being far more profitable, the push to get rid of that unnecessary warning isn't there.

> Lactic acidosis.

That's debunked hysteria leftover from its predecessor compound. We've been giving metformin long enough to see that it isn't causing lactic acidosis.

> Pooled data from 347 comparative trials and cohort studies revealed no cases of fatal or nonfatal lactic acidosis in 70,490 patient-years of metformin use or in 55,451 patients-years in the non-metformin group.

> There was no difference in lactate levels, either as mean treatment levels or as a net change from baseline, for metformin compared to non-metformin therapies.

https://www.ncbi.nlm.nih.gov/pubmed/20393934

In other words, you may find a few case reports of patients taking metformin having LA, but that's because you can have LA without metformin.

Metformin damages the liver as a side effect.
Can you provide your source? This one says otherwise, I'm really interested in your source as someone taking M daily:

https://www.ncbi.nlm.nih.gov/pubmed/20452916

I don’t think there is any evidence for it damaging the liver. It does have effects on it (the liver does create glucose after all), but nothing I’ve seen says it damages the liver in normal dosages.
To be fair, I'm sure there's a research paper for anything, that suggests it might prevent cancer.
That’s why I liked that they followed patients on it long enough to demonstrate reductions in all-cause mortality.

A lot of studies don’t go that far, which makes you wonder if the intervention is providing overall benefit.

Quite a bit of evidence, particularly for lower BMI and lower blood glucose decreasing cancer rates.

"I liked that they followed patients on it long enough to demonstrate reductions in all-cause mortality"

Isnt that a very low bar? If I'm understanding you correctly that's only ruling out things like saying smoking reduces prostate cancer.

Couldn't you say the exact same thing about regular exercise? And it has minimal side effects, unlike this medication.
Nope. At least not for me. My blood sugar was too high and rising. I exercised all the time and ate a low carb diet. My blood sugar continued to rise, but the spikes were only while I was sleeping.

My doctor gave me a prescription, my blood sugar immediately went down and stayed down, and in four months I had lost 25 pounds. I don't feel hungry all the time (a problem that got a lot worse when I cut down on carbs). I don't think there's anything I could have done naturally to prevent diabetes.

This sounds like one of the billion things correlated with having less money.

https://www.citylab.com/life/2012/03/why-people-cities-walk-...

I'm not surprised with the London result - they seem the fastest walkers to me.
Geoffrey West, former theoretical physicist now at the Santa Fe Institute, found many scaling laws in biology, cities, businesses, and more. One was that people's walking speed scales with city size.

Fascinating results.

Here's a short article about his book, Scale: https://blogs.sciencemag.org/books/2017/07/11/a-physicist-pr.... He's spoken with TED too: https://www.ted.com/talks/geoffrey_west_the_surprising_math_....

Here are my podcast episodes with him, where he describes his findings: http://joshuaspodek.com/guests/geoffrey-west.

(I'm a former physicist too who walks fast at 48.)

Full article is available at the Journal of the American Medical Association's website:

https://jamanetwork.com/journals/jamanetworkopen/fullarticle...

An interesting take-away not mentioned in the BBC write-up is that the researchers found significant effects as early as three years old, suggesting causal factors found in early childhood or a genetic origin. Perhaps sedentary behavior early in life has long-lasting effects for the CNS?

> Lifelong compromised brain health—including poor neurocognitive functioning as early as age 3 years and childhood-to-adulthood decline in cognitive functioning—was associated with slower gait at midlife.

This is possible but I'd really like to see twin studies to confirm it, with differences in activity levels between the twins as the variable.

I would suspect there is a genetic mechanism at play too, but at this point I'm spitballing.

At the risk of sounding like confirmation bias, I have found many relatives and friends to adhere to this kind of simple rule. The more agile and active you in middle age, the better your sleep quality probably is, and both of these are a proxy for how well you will age, apart from genes.
A researcher from the University of California, San Francisco posed this trivia question at a Q&A event on healthspan... At age 65, what single factor most accurately predicts the likelihood you'll live to age 100. The answer was walking speed (faster is better). He said that this has been shown in multiple studies, but they weren't sure why. Sorry, I don't have a source.
So, if you feel older than you really are, walk faster. Problem solved. Got it.
correlation vs causation. If you walk slowly you won't be able to figure it out.
My point, albeit made sarcastically, is maybe some people just like to walk slowly. I was taught as a young man that walking slowly is a sign of wisdom and confidence. It means you know where you are going, you left on time, and you're not in a hurry.
Study link: https://jamanetwork.com/journals/jamanetworkopen/fullarticle...

The study was done in NZ in Dunedin. I wonder how much difference/coorelation there is between locales. I've found that Wellingtonians walk very fast in general - I thought I was a fast walker always passing people in San Francisco, but when I moved to Wellington everybody was passing me.

It's amazing that the Dunedin Study is still producing results like this. I wonder why longitudinal studies are not more common now, given that these 900 people have been such a deep source of knowledge.
Well it helps when the wind is pushing you along.
Interesting.

I always thought fast walking was related to city size. In average towns I'm a fast walker, when I go to medium cities I'm an average walker, and in London I'm a slow walker.

I wonder if it's another correlated factor? Usage of public transport?

Maybe you were just passing the tourists.
This shit will not replicate. Classic p-value hacking, if not total fiction, dreamt up to pad chum buckets. It is junk science to the core. I'd bet one thousand dollars that another researcher could wrangle contradictory data with a diametrically opposed result.

This trash infotainment has been selected because it is inconsequential to the point of being astrology. No individual can take this "discovery" and apply it to their daily life, but most importantly, it's been selected such that should any moron try it out on their own, they won't be able cause harm. Perfect fodder for the BBC nanny state media.

So... what's your sign?

Is this just a general position or do you have concerns with this specific study?

I tend to be reflexively skeptical of results like this as well - but I also have a lot of time for results from the Dunedin study. Long-term studies are great and we (society, science) should do more of them.

Reminds me of the article about "cancer-prone personalities" finally being classified as junk science which just dropped off the hn frontpage.

We really should be more generous with the word bullshit.

Your whole post is just an empty argument from authority.

Who are you and why should we just believe what you are saying any more then the study?

”Even at the age of 45, there was a wide variation in walking speeds with the fastest moving at 4m/s at top speed (without running).”

4m/s? That’s 14,4 km/hour. They must have met a racewalker (https://en.wikipedia.org/wiki/List_of_world_records_in_maste... says the world record for 45 year old for 5k is 20:28:28. That’s almost exactly that speed)

I can surely imagine those walking at those speeds to be healthier than average.

Looks like they edited their article:

> Even at the age of 45, there was a wide variation in walking speeds with the fastest moving at 2m/s at top speed (without running).

I suspect they were mixing units and someone got it wrong. As noted elsewhere, the article is now edited, but it's worth noting that 2 m/s (the value now quoted) is a little over 4 mph.
It's not so difficult to walk at those paces. The difficult part comes in with the length and abiding by the rules and regulations.
This reminds me of the “surprising” finding that ability to stand from seated partition without using your hands is associated with dramatically lower chance of dying within 5 years. Of course, this is because anyone likely to die of old age within 5 years is unlikely to be that spry.
Correlation doesn't equal causation, in either direction.

It's fashionable to downplay the physical these days, but I think it's reasonable to hypothesize that if you don't maintain your muscle, you reduce quality of life AND increase mortality risk significantly.

It’s much worse if you can’t maintain your muscles, rather than just don’t. And older people have a lot of reasons that can happen (my dad degraded like this quickly from cancer we didn’t know about at the time).
I walk slower because I have smaller legs.

Pff, but then I can swim faster than quite a lot of younger people, for longer, and daily.

And run.

WTF.

well I walk much slower since I walk with small children and I guess it took its toll on even when I walk alone. what's the point reversing to your regular high speed when later you need to drag with children? it's just easier to get used to lower speed. many people at 45 could still have like 5yo child (2nd) or even younger or was the study done only on childless people?
Sounds like it's a good sign that at 45, I am still annoyed by how slowly everybody else is walking.