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Comment by WhitneyLand

4 months ago

The article made up the claim it’s not from the paper itself.

There was some improvement in cognitive scores, but no placebo group. Without a placebo group, there are a lot of explanations for the data.

>> Recently, a pilot study (single-arm) by Smith et al., recruited 20 patients (73 years of age) with AD and provided them with 20 grams/day of CrM for 8 weeks [20]. Serum creatine levels were increased at weeks 4 and 8 (p < 0.001), and total brain creatine levels (as measured by H-MRS) increased by 11% (p < 0.001). Clinically, there were demonstrated improvements in cognition on global (p = 0.02) and fluid composites (p = 0.004), as well as List Sorting (p = 0.001), Oral Reading (p < 0.001) and Flanker tests (p = 0.05).

Yeah 20 patients is not a lot. I'm inferring this is a pre-post test. However some of those p-values are pretty good (.001 on reading and and sorting). Very promising pilot study but not conclusive imo.

  • 19 patients completed, according to the article.

    And List Sorting, Oral reading, and Flanker only? The first and last are part of global and fluid composites, so those have to be excluded from comparison. That leaves us with 3 improved scores out of 12 tests. So 9 did not improve, or got worse. Figure 3 (of the original article) shows that the changes aren't big. Just "significant". Since the participants were in the early stages of dementia, this seems well within expectations.

    So I can't see those numbers as impressive.

  • I wouldn't even call it "promising but inconclusive" so much as "not conclusively a dead-end for further research". In a single-arm open-label study, with no blinding, both the participants and the researchers know who's getting what. You need a placebo and double-blinding for comparison against the active group and to adjust for any ways in which the researchers may have unwittingly influenced the results. (Or perhaps even wittingly, when there are conflicts of interest. I spent half a minute looking up this study and didn't see any statement attesting that there were none.)

    • Worse: go look at the MMSE. I bet that, at least for patients with reasonably functional memory, taking the MMSE and then taking it again a few weeks later from the same examiner will tend to improve the score the second time.

    • One study rarely makes or breaks anything. Creatine has lots of studies going back 10-20 years.

  • .001 for creatine levels isn't surprising; that's a lot of creatine. I'd explain the cognitive tests with the practice effect, because it is unlikely that creatine had such a massive effect and we only discover it now.

    • I hear about tech bros taking creatine these days with the tone of voice that they use to talk about microdosing. So I can’t imagine it having zero effect.

      What I worry about more is that it has more to do with fixing a deficiency. That being deficient in creatine causes a cognitive loss more than supplementing causes a boost.

      3 replies →

Yes, I can't find a 30%-slowdown number either.

I'll add to this: the referenced trial occurred over 8 weeks, so even if we stipulate that the improvements in cognition (which are dubious, as tgv points out in this comment: https://news.ycombinator.com/item?id=48347906) are due to treatment rather than some other effect, we don't know that the effect is disease-modifying as opposed to symptomatic. As with acetylcholinesterase inhibitors, it may just be having a cognition-enhancing effect which, nevertheless, does not alter the underlying disease trajectory (i.e. just shifting the declining trajectory up vertically by a constant amount), and might revert shortly after discontinuing use of the drug.

A controlled trial, over a much longer duration, and ideally with a wash-out period, would be necessary to identify a disease-modifying effect.

FWIW creatine is "one of the most studied supplements for muscle and strength".

But at the same time "creatine’s brain benefits aren’t as exciting as social media makes them out to be. The research at this point just doesn’t support the hype".

Source: https://physiqonomics.com/creatine-cognitive-performance/

  • I think people often overestimate the effects of these things. It absolutely works for muscle growth but it's not like a steroid or something. Similarly there is enough evidence to suggest that it actually does have some small effect on cognition; I remember a study 10 years ago showing that in people who are creatine deficient (vegans) it improved cognition scores. But it's not going to be a huge effect for someone whose not deficient in some way.

    It would actually make sense that as you age and eat less you might get creatine deficient so sure. I don't think it's bullshit, but it's not going to be a huge noticeable effect either.

    All of this reminds me of people who don't weight lift "because they don't want to get built." They somehow think you lift some weights and boom you're looking like Arnold. No, it doesn't work that way.

> Without a placebo group...

You just needed to read the next paragraph:

"The 2026 multicenter placebo-controlled trial extending this work..."

I think you're right.

Confusingly they reference a 2026 article (which isn't included in their citation list) that allegedly includes "placebo-controlled trial", but I think it might just be [0], which is based on the same single-arm trial. If they do have a paper using a placebo-controlled trial, they should definitely include that citation.

[0] https://pmc.ncbi.nlm.nih.gov/articles/PMC12927926/

Normally I wouldn't ask this, but having seen the effects of Alzheimer's I must ask: is there any evidence that taking creatine will harm my brain?

Let's be real: I take a lot of edibles. I smoke sometimes on a hike. Every once in a while I get a Guiness and a gyro. My health is by no means perfect, and if I'm willing to take in literal poison (yes, alchohol is that dangerous that I say such things even about my precious Guiness).

Anyways, for years I've been mostly skeptical of vitamins. I've heard a megadose of Vitamin C can shorten the symptoms of a cold, but a "megadose" is relatively small enough that just some OJ can do that, no need for pills.

But if I'm not giving up my Guiness and gyros, I probably should be willing to be more flexible about my "no vitamins or weird supplements rule".

So TL;DR: Let's flip this around: What are the risks of creatine, presuming a safe supply chain? (It's legal where I am as far as I know, which I'm a fan of for most things since then you can get a receipt and there will be some authority that investigates if you're unlucky to get a "bad batch".)

  • Creatine is one of the most studied supplements in fitness and i don't think there ever was evidence it was harmful.

    Then again supplements mostly create expensive pee.

  • No sure about brain harm. But I used creatine for a few months and I got cramps in an intensity like I never experienced before. I then decided it was not worth it for a few watts of cycling FTP increase. So I would not consider it harmless for everbody, but this sideeffect seems pretty rare.

  • There are scattered reports from people who take it and feel worse. Some don’t notice until they run out or forget to take it for a few days and realize their mood improves.

    This happens with a lot of popular supplements. I don’t know how common it is, but it’s a thing that happens. There are proponents of every supplement who will tell you it’s perfectly safe and any negative effect is due to impurities or your imagination, but there are a lot of reports from people who believe it’s helping until they stop, and are surprised that they feel better without.

  • Long term studies haven't shown any harm. I've taken 30g a day for well over a year now for both the physical performance and the cognitive benefits. I had brain fog following a bad COVID infection which this has helped with. My family also has a history of Alzheimer's and dementia (both sides), I figure it can't hurt.

    The only side effects I've encountered have been mild GI discomfort, and that only rarely (mostly when restarting after a vacation etc-- I drop the routine when I travel). Roughly similar to having a morning coffee at its worst.

    I've found I get much thirstier when on this high of a dose. If you're not already a big water drinker I'd definitely invest in a nice insulated bottle to drag around.

They also quote a follow up study that sounds more compelling:

> The 2026 multicenter placebo-controlled trial extending this work enrolled 240 participants with early Alzheimer’s... The intervention group showed slower decline on standard cognitive scales by about 30% versus placebo.

But there's no such study in the references section. Not sure what's going on there but I want to see the data before I believe this.

I also noted the lack of a placebo group.

Give them sugar pills and call them smart pills and their test scores will also improve.

That said, I work out daily and only just discovered the well researched and proven benefits of creatine on that front, so now I'm going to try it.

I can't speak for the Alzheimer piece, but there are other studies about supporting the brain.

Worth looking at the range of studies as well.