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Direct link to the study: https://jpbs.hapres.com/htmls/JPBS_1766_Detail.html

I wanted to check the dosages they used. Looks like the review includes studies ranging from 5g/day to 20-25g/day.

(Typical dosage you'll see for daily use is 5 grams)


Just in case anyone is thinking about trying it: 25g seems pretty high. It’s worth it to review what that means for the rest of your body before starting this regime. Kidneys are really useful organs to have working.

This is a myth, its not bad for your kidneys. The reason this gets spread is because you will have higher levels of creatine in your urine if your Doctor tests your urine for kidney function, which indicates kidney disease.

However, If you reveal to that doctor that you're supplementing Creatine it will not be concern them.


My dad's GP didn't know about this, and despite my dad saying "it's fine, I'm taking creatine", sent him for a kidney check-up. Then they found an unrelated tumor on the ultrasound. Seems to be benign and hopefully all will be well. If so, creatine saved his life ;)

> creatine saved his life

Or more correctly, the myth saved his life.

Perhaps sometimes we should listen to conspiracy theorists. /s


Creatinine not Creatine

I've even had doctors unaware that the regular eGFR tests needs to be adjusted for body mass to be remotely accurate if you're bigger than average - e.g. lifting weights or obese. Couple that with creatine and you get some "fun" moments when your doctor tries to gently break to you how messed up they think your kidneys are. The first time I had that I'd warned my doctor ahead of time to expect elevated creatinine, and he still freaked out.

This has been my understand as well. I have CKD and my doctors have always been chill about it as long as I stop taking it about a week before having blood work done.

EDIT: I don't do 25g though... sounds like a lot...


You're lucky your doctor is aware of it. I've had several who did not understand, and insisted creatine must be dangerous if it elevated creatinine levels, and/or didn't understand the effects.

If your egfr is above 80 it’s you won’t notice it. But CKD is a late in life problem so you are basically making your end of life worse by making your kidneys work harder now. You might as well take up smoking: claiming it doesn’t hurt now is a lot different to 20 years of constant use.

At the risk of sounding stupid. Doesn’t this mean it would mask actual kidney disease? So you’d be ignoring potential warning signs.

There is a much more accurate test called Cystatin C that can be used instead, and it isn't subject to being thrown off by creatine, muscle mass, etc.

IF you tell your doc, they can adjust their interpretation of the test.

Edit: see comment below (i.e. better to stop taking creatine at least a week before a test).


If you have a good dr they'll just ask you to stop taking it for two weeks, then do a blood test.

creatinine != creatine

It's pretty clear they understand that. Creatinine is, however, the waste product of creatine. So the more creatine you consume, the more creatinine is in and discharged from your system.

Precisely and correctly as they said, normal eGFR presumes average musculature and average creatine consumption. If either of these out of the norm, eGFR becomes inaccurate and potentially flagging false positives for damage. Creatinine, the waste product of creatine, raises in a way that can get confused with kidney damage, which is precisely how the confusion about it causing kidney damage or being bad if you have a compromised kidney came about.

In some studies, people with CKD actually improved with creatine supplementation, though notably this was not people with PKD where it could increase cyst growth.


I started taking creatine after trying to clarify which one of those was which and found the dearth of negative consequences

Careful.

Creatine metabolizes into creatinine which is major indicator of kidney function because not being able to clear creatinine means your kidneys aren’t working. Adding more creatinine to your system decreases your ability to clear it leading to fatigue, edema, high blood pressure etc.

So it isn’t bad for your kidneys: it is bad for everything else.


Creatinine can be an indicator that your kidneys are not working well. It's a cheap red flag that can be screened for in a common blood test. But if heightened creatinine is a result of one's creatine supplementation, then there are none of the downsides associated with kidney disease.

Creatinine itself doesn't cause fatigue, edema, or high blood pressure. Kidney disease does.


Except many many many decades of research has not shown any of that to be true.

I'm not aware of any evidence that creatine harms the kidneys if your kidney function is remotely normal. You'd probably want to check with your doctor if your kidney function is already compromised.

Creatine supplementation will freak out a lot of doctors if they're not warned of it ahead of time, though, and sometimes you'll even need to explain to them that they will see elevated levels of creatinine on the tests and it won't be an accurate predictor of kidney function.

If you're supplementing with creatine and need your kidneys tested it's easiest to stop a couple of weeks before, or ask for a Cystatin C test and make sure they use the relevant adjustments for body mass as well if you e.g. lift weights - I've more than once had doctors imply they were worried I had kidney disease because they were entirely unaware of the effects both creatine and large body pass has on the regular tests.


Yes, the labeling does caution against using it if you have kidney disease. Not sure how much of a risk there is if your kidneys are functioning normally. Maintaining good hydration is always a good idea.

I can second this, do NOT start at 25g of creatine. If you're too lazy to read the literature a friendly AI tool will summarize it.

If your intention is to take creatine long term, skip the loading phase.

It might take longer to see full effects, but who cares if you’re intending to take it indefinitely.


Most guidance I’ve seen says to start with a loading phase of 25-30g per day for several days, then go down to 5g per day maintenance.

The loading phase frankly was designed for studies. Studies are often short-term, say 6 weeks. You've got to get everyone's creatine supplies "loaded up" quickly in an effort to make sure the bulk of the study is on folks with relatively comparable creatine stores. The easiest way to do this is to have everyone do a loading phase to reach max intramuscular creatine concentration. It is not for the benefit of the study participants; it's for the benefit of the study.

We humans not in studies are generally looking for a health benefit, not max intramuscular creatine concentration as fast as possible at the price of side effects. We are optimizing for something different than study authors. 5 g is fine.


This sounds intense... I'm a small female and I recently started at 5g a day and now I've dropped down to 2g a day because even at just 5g I was getting signs of dehydration, despite tripling my water intake. It does seem to make a difference in my physical performance so I'm overall happy with it.

Also the NIH fact sheet for creatine specifically recommends against higher starting doses.


I did the 25g a day loading phase and I could not tell any sort of effect at all one way or another. I do lift either more weight or do more reps pretty much every time I work out now. What was repping to failure a month or two ago is not even a working set now.

Per day being a key part of that. 30g at once is going to give a good chunk of people pretty severe cramping or a trip to the bathroom.

I don't think you can even do 30g at once in terms of mixing it. Even 5g in water it seems like theres some that will just stay crashed out of solution no matter what. I have done 25g over the course of a day though for a week long loading phase, and didn't notice any ill effects.

I think a lot of the anecdata on creatine is probably from people misplacing confounding issues to the creatine use. People in this thread are talking about heart palpitations or trouble sleeping. Stressful days at work are enough to trigger that.


Creatine isn't water soluble. I just take a 5g scoop daily and wash it down with water. I could do 6 scoops in a row without problem, but not sure what the point would be. The latest research fits with the 5g/day no need to load.

When I first started taking creatine in the late 90s (it had already been heavily studied then as one of the only supplements that improved athletic performance), I would mix it with juice. There were some studies that sugar would help the uptake.


If you're too lazy to read the literature, then just don't take it.

Going to something that frequently hallucinates or misstates things to the point where it's "trust, but verify by reading the source" means you may as well just read the literature you'd have to verify the summary against anyway.


Also if you want to try creatine, after a week or so you'll probably gain 2-6 pounds of water weight. Don't be afraid of it, it's not real weight, and will go away within a week or two after stopping it.

if you take it right before bed it'll make you dreams loads and sleep haaard, if you can get to sleep; the restless legs are a motherfucker.

Hei more than that - as an avid weed consumer - drugs are not dangerous by themselves especially when you don't like them - they are dangerous when you create space for them and get along with them. I like to believe weed is my little "cheat" - but i'd argue that any product is an abuse on a daily basis - so taking creatine once in a while might be fun to try out - but i would warn about anything on the spectrum of "regime" that plan for a daily basis etc... especially as you rightfully justified, without a doctor or an expert being able to know what effect this is going to have on a said person.

You need creatine to live. Your body typically makes enough from protein to survive (vegetarians and vegans might need extra vigilance here).

This is just taking more to optimize performance.

It's not the same.


right...

https://www.google.com/search?q=artificial+creatine+side+eff...

kidney damage. liver damage. kidney stones. weight gain. bloating. dehydration. hair loss. muscle cramps.

The fact that you estimate weed as a drug is correct - the fact that you don't realize that everything is basically a drug depending on the amount an potency is worrying.


Water is bad for you if you drink too much.

Yes because taking advice to medicine itself everyday based on an online entrepreneur forum to "boot-yourself" is 100% a good advice that you should take blindly without taking a notice on what you are doing.

You are so right.


> based on an online entrepreneur

Creatine is one of the most studied supplements over the last 30+ years. First, it is proven to work for athletic performance and second, it's relatively safe. The AI overview of your Google link even says no evidence of serious harm. If people have underlying health issues and/or they take way more than recommended there can be side effects - just like anything else we put in our bodies.


I use it as a supplement because I do weightlifting. 5g/day. I did 20g/day for a week once, and didn't notice it made any difference, so I'm back to 5g now. In terms of stuff like memory, mood, etc. I can't say it's made any improvement but the idea that it might be helping prevent decline is nice.

I've found it helps cognitively if under a lot of stress and/or sleep deprived. If I'm not especially stressed and am well rested, I don't know that I notice any difference.

Its changed my life. Im also a long time vegan with MTHFR gene mutations and sleep issues though.

For vegans, creatine is among the recommended supplements, because the amount that is produced internally is insufficient for most people, so they need some extra amount in food. (The same is true for a few other substances, e.g. choline, taurine, menaquinone.)

I also take some creatine, for this reason.


I've heard others say it helps with mood, energy, depression, etc. and if that's the case for some people then great. I don't notice it myself but that's just me. Not everyone has the same body chemistry.

Did you try higher dose. You need to take 0.35g/kg body weight for effects on brain, atleast thats the doses that are usually used in the studies. I believe your body will distribute it to your muscles before any goes to the brain, so you need to take a dose that will saturate your muscles and then have extra left over. I take 25grams whereas the usually reccomend daily dose is 5grams

I did a week trial at 20 or 25g/day once. This was after being on the standard weightlifter's 5g/day for a while so muscles should have been fairly saturated. Didn't notice any effect. 0.35g/kg dose seems like way more than our bodies would have ever had even in a prehistoric hunter's diet. For me that would be 30g/day.

I also have MTHFR gene mutations and sleep issues.

What exactly helped you?


As a vegan you dont get any creatine since you're not eating meat, so your body has to make it itself, which requires a ton of methylation and if you're like me and have bad genes for methylation your body had a hard time with it as it is. So by supplmenting creatine you're reducing some of that burden.

As far as sleep goes, high dose creatine has been studied to have an extermely positive effect on brain function during sleep deprevation, better than stimulants/caffine

I think the prescribed dosing for creatine and sleep deprevation is 0.35g per KG, much higher than the typically recommended dose of 5gs a day for muscle. The positive effects on the brain come at much higher doses. Which is perfectly safe for your kidneys, this is a myth (as long as you dont already have poor kidney function).

https://www.nature.com/articles/s41598-024-54249-9

https://pubmed.ncbi.nlm.nih.gov/16416332/


Also note, that if someone is going to start taking creatine they need to up their hydration - likely a lot.

That’s a pretty amazing acronym if real

Say MTHFR one more time, I dare you.

Never heard of the acronym though so not sure what the mutation implies.


For lifting you hit a saturation point quickly where your muscles will only hold so much of it. Not sure if there is an equivalent for any brain related effects.

I'm sure there's something for the brain too. The thing is, there's a floor for the brain. If your muscles aren't saturated already and you don't "megadose" (from a muscle perspective) then you won't see any cognitive effects it seems.

>CONFLICTS OF INTEREST

DC has conducted industry-sponsored research involving creatine supplementation and received creatine donations for scientific studies and travel support and speaking honoraria for presentations involving creatine supplementation at scientific conferences and on social media. In addition, DC serves on the Scientific Advisory Board for Alzchem and Create (companies that manufacture creatine products) and as an expert witness/consultant in legal cases involving creatine supplementation. NF declares no conflicts of interest

A nice unbiased study, I may as well ask Exon Mobil for their opinion on climate change at this point


High dosage is not for your daily intake

It’s called a loading phase to quickly saturate the tissues i.e for a week or so for someone who never took the creatine. You can absolutely skip this.

I wouldn’t go higher than 10g daily on a regular basis.

I personally take 7.5g for the last couple of years.


The entire point is that >10G is justified if you're going for cognitive effects. For muscles you don't need to go above 5G. For brain, >15G.

For now there are zero studies that I know of that support this.

The only ones are for sleep deprived.


There are a number of studies on the topic of varying quality but I think that's besides the point.

> It’s called a loading phase

This is not about a loading phase. "It's called a loading phase" indicates that the reason you would take high doses is for the muscular saturation that some people think is required. You're right that you can absolutely skip the loading phase, but that's not the point. The point is that you would take the higher dose for the cognitive effects.


Replace "war crimes" with "hardware" and it's an equally good reason not to invest.

They're valued like software companies, but they have terrible margins compared to software. Investors haven't figured out how to value these companies.


> ChatGPT is a word now.

Many people I know have started simply calling it "Chat".

"I had Chat help me write this" (I didn't, I promise)

They own "chat.com", I think OpenAI should pull the trigger and move to the shorter domain and finish the rebrand.


What are streamers going to call their audience now?

This is what scares me about people raising insanely large $10 million seed rounds. It's too much runway. Takes too long to fail.

It took me 4 years of working on 3 different startups, with 2 different set of cofounders, before I landed on the idea/business that finally became successful.

Two of those failed companies were part of YC. Thank god every investor turned us down. It allowed us to shut down and move on to the next idea way faster.

Edit: If you're a founder sitting on a giant bank account with a startup that you're losing faith in... remember you aren't obligated to spend all that money. Investors will respect you for returning the money and admitting it's time to try something else.


Until it gets stuck on a far away AP because it was the first AP to come online the last time the network rebooted.

Not sure if roaming is actually the fix for this problem. For whatever reason my Ring cameras just love connecting to the worst and most far away AP in my house.


Not sure how widely available this feature is, but the unifi controller software for the popular Ubiquiti APs lets you bind individual client devices to specific APs such that they can only connect to the ones you choose.

I had to solve a similar issue for some crap IoT lights that would join the incorrect AP after a power cut every time.

> https://community.ui.com/questions/Lock-Client-to-Specific-A...


This, of course, breaks clients that try to connect to the loudest RSSI when the loudest RSSI that they hear is not the one that is chosen.

Yet to encounter this side effect. So far every crappy wifi device I've tried has obliged.

Don't want to name drop, but this is unfortunately a real phenomenon.

for static clients that works well, though you can usually set a min rssi and get the same benefit without so much clicking.

That works for fixed devices like a TV, but also tends to shrink the effective coverage area of the wireless network as a whole.

That can mean that the portable wifi speaker-widget (which itself doesn't need much bandwidth) might go from working fine on the back deck or well-enough about anywhere else in the yard, to not working at all outside.


> That works for fixed devices like a TV, but also has the effect of shrinking the effective coverage area of the wireless network as a whole.

Which is normally a good thing to push the clients to roam to a better AP, OR you walked out of the building and want you phone to disconnect. But yes, does impact overall coverage area size.


That only works if there's a better AP to roam to. It's often very easy to add more APs indoors; but hanging them outside is a whole different animal.

Meanwhile: As a practical matter, shrinking coverage means "Hey, honey! I fixed the TV!" gets met with a response like "Oh, so that's why I can't listen to Audible on the veranda anymore!" :)


Experimentally probe: say you "fixed" something when you haven't touched anything and see what responses you get.

Obviously only if your honey is the type that enjoys being experimented upon (So long as it isn't mean, I like thoughtful attention like that, but some might not).


I dare to say that most people I've cohabitated with were not like you, and that this would have been a fine way to play things out if they were.

I find it funny that the one device in my household which will not roam between APs is the Nintendo Switch.

My nintendo switch doesn't roam either. Usb wired ethernet at the dock.

> Coding agents really did change everything. These are tools which burn vastly more tokens

The assumption here is that this is a positive thing.

But this very well could end up being a major negative long term by increasing the cost per user, reducing margins.

More usage = more cost = less profit.

It's not obvious that more usage is good. It's only good if revenue per user increases more than cost does. I'm skeptical about that.


> It's only good if revenue per user increases more than cost does.

That's why it's so important for these labs that they're selling API tokens for more than the compute+energy costs needed to generate them.

Every indicator I've seen is that they do have a positive margin on that. If they don't, they're screwed.


No this is not what matters.

The customers of these tokens need to see returns on their projects that exceed the cost of financing.

Laying people off only goes so far.

If enough said firms don’t see enough value given the price of frontiers they will cancel and consume open source. This is the risk the frontier labs are exposed to.


What's an example of an indicator? Genuinely curious!

Insider tips from Google and AWS telling me that they run inference at a profit (though that was over a year ago now).

Dario telling Dwarkesh three months ago that they have a margin on inference: https://www.dwarkesh.com/p/dario-amodei-2?timestamp=3528.0


Unless your insider is the CFO, I wouldn’t trust these sources to have the access, knowledge, or insight to determine whether they’re running inference at a profit.

Simple test: can they get their hands on a data center contracts and financials?

Search isn’t anywhere near as high profile as the profitability of AI inference, and yet, even aspects of the Search org were walled off from the rest of the company such that other employees couldn’t see what we see.


I don't think the fact that inference runs at a profit is a particularly deeply kept secret inside these companies.

It might be worth keeping it secret from the staff if they were running at a loss.


Are these sources not incentivized to say exactly this, regardless of whether it's true?

The insiders tips? I don't think so, they were people I trust.

They had all the incentive in the world to say "I'm not going to talk about that."


> half-alive state

The brain can't be "half-alive" after you've died.


> I do not think we understand consciousness enough to rule out what those brains are experiencing.

The parent edited their comment, wasn’t there when I replied. But if you believe your organs don’t die when you die, then don’t donate your organs?

> if you believe your organs don’t die when you die, then don’t donate your organs?

Because "I" don't know what "I" am.

Am I a brain? Am I a soul? Am I the universe?

I have no idea. Science currently has no idea. Religion is unprovable.

I want to donate my organs. If my death can bring life to others, it would be a truly amazing deed I could do.

On the other hand, if I am just a brain, I do not want to be locked into some sort of drugged, half-conscious state where I can't scream.


Um... I, 220% disagree with that statement. I did edit to fix a spelling mistake, I did not add/remove content...

I wish HN showed the edit history >:(


Yet, the metrics in the article are routinely ignored (or not tracked at all) by your typical PCP doctor.

I think more frequent and more thorough blood testing is something I'd love to see become more common place. Even if it's for no other reason than to know what your benchmark is so that if you have a health issue down the line, you know what your values were when you weren't sick.


If your PCP checks a CBC and a CMP, all of these metrics are there (which virtually 99% of PCP’s do yearly). Lipid panels are regularly checked, A1c is checked periodically if you have a diabetes risk, usually every 1 to 3 years based off USPSTF guidelines.

The only thing that is not regularly checked is a vitamin D level.

So unless you go to some quack MD who orders nothing (which is usually the exact opposite of what quack MDs do) you’re wrong.

Source: I’m a MD


You're right.

I was thinking of Lp(a), ApoB, A1c, cystatin c, GGT, and HS CRP.

I personally like getting those tested at least twice a year in addition to CBC/CMP/hormones/lipids.

I'm honestly surprised more doctors aren't ordering more advanced cardiac panels (specifically LP(a) and ApoB). Even though you can't do much about Lp(a), knowing you're genetically at risk can be a motivator to reduce other risk factors.


LBO's are like buying a rental property where the mortgage is approved based on expected future rental income from the property.

That's why the parent is saying "It is like paying for the company with the money from the company you are buying.".


LBOs are much worse than that. It's like buying a rental property where the mortgage is owed by the a shell corporation that owns the property. The shell corporation, not the purchaser, owes the debt.

It's like taking out a mortgage on a house, but letting the house owe the debt.


>It's like taking out a mortgage on a house, but letting the house owe the debt.

Isn't that a non-recourse loan, which in some states is the default for the initial loan to acquire the housel


When you put it like that, you make it sound reasonable! The house being collateral for the debt seems in a blurry way to be "the house owes the debt".

That's pretty blurry, though. Blurry enough that we don't distinguish between the collateral and the borrower.

Exactly. That is largely how commercial lending is underwritten: by ensuring the DSCR (debt service coverage ratio) is over 1.0.

Sure that is commercial lending.* And the acquirer owes the debt. But that's not how LBOs work. In an LBO the target owes the debt.

*Coverage of 1:1 is an accident waiting to happen, but otherwise sure.


That's not especially different from the typical LLC/SPE holding structure where individual properties in a large real estate portfolio are not held directly, but rather by a single-purpose entity that holds each property and then is owned by a larger but distinct entity. You don't want an issue in a single company/property to be able to take down your entire holding company. If someone will lend you money without cross-collateralization, why wouldn't you prefer that?

If PE firm A wants to buy company C using an LBO, it could do so by having C borrow money and then A purchase C, or by creating an entity B that borrows money and then purchases C. Whether B or C owns the debt doesn't change anything meaningful for A, and it's pretty clear that you're allowed to form company B (and really hard to imagine how you'd make that illegal without effects that would be worse than current).


>If someone will lend you money without cross-collateralization, why wouldn't you prefer that?

I would prefer that! I'd prefer even more strongly that the debt be owed by someone else entirely, so a default isn't associated with me at all. If you're up for it I'd also prefer to use your credit card number to buy stuff on Amazon. But for whatever reason the law doesn't always seem to follow my preference.

I'm sensitive to your point about restricting formation of new corps. The system can't just be changed randomly without extremely careful thought. And often not even then.


That's exactly HOW rental properties are (supposed to) be bought!

Most small-time single family landlords actually go above and beyond that and "pretend" the rental is a house they're buying to live in (or actually is, for a time) and get a "home owner's mortgage" which is even easier.

Large commercial real estate is sold and loaned based on future rental income, pretty formulaically.


Why?

You can seed the randomness are still having nonzero temperature.

Numerical instability can introduce randomness especially on GPU like hardware unless you’re very careful about how you write your algorithms.


In any batch inference environment that includes experts, expert routing may vary depending on what else is in the batch. For one thing.

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