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Comment by kherud | Hacker News Reader

Feedback about creatine often seems mixed. Many love it, but many also report problems. Just in this thread there are people talking about heart palpitations and sleep problems. I have the theory that these side effects and mixed experiences come from impurities of lesser quality products. Apparently there are mostly two sources: Creatine mono-hydrate which mostly comes from China and "creapure", which is a patented formula known for its purity. Does anyone have insight into how substantiated this theory is? How likely are negative effects because of pollutants/impurities?

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> Creatine mono-hydrate which mostly comes from China and "creapure", which is a patented formula known for its purity.

Creapure sells Creatine Monohydrate not a proprietary form of creatine [1]. The higher end in creatine is Creatine HCL which is more expensive but more water soliable, easier on the stomach, and requires a smaller dose.

In terms of creatine manufactured in the Western World:

* CON-CRĒT manufactures creatine in the US, they produce Creatine HCL.

* Creapure manufactures creatine in Germany. They produce Creatine Monohydrate.

There are also a variety of brands that import creatine and run various tests to ensure quality.

[1] https://www.creapure.com/en/creapure/what-is-creapure/

Weird, I’ve heard the HCL is harder on the stomach. I’ve actually never met anyone who uses monohydrate that reports any gastric issues whatsoever.

Stomach issues are a frequently reported side effect of Creatine Monohydrate [1].

The general school of thought behind the belief 'Creatine HCL is easier on the stomach" is:

1) HCL is much more water soluble and (likely) is more easily digested.

2) less creatine HCL stays undigested.

3) the dose needed is smaller.

4) anecdotes seem to support HCL being easier to digest.

To the best of my knowledge, there are no peer reviewed studies of monohydrate vs HCL that look to establish which is easier on the stomach.

[1] https://www.mdpi.com/2075-4663/14/4/137

The abstract you linked, pasted below, seems to say otherwise. Placebo groups report same SE frequency.

“Across 684 randomized controlled trials, reported SEs were infrequent. Although dose and duration tertiles were statistically associated with study-level side effect reporting, the effect sizes were uniformly small, events were infrequent, and the reported symptoms were primarily mild and nonspecific. No consistent exposure–response pattern indicative of clinically meaningful risk was observed. Adjusted logistic regression and frequency-based analyses showed no consistent dose- or duration-dependent increase in SE risk, with placebo groups often reporting similar or greater SE frequencies at the study-reporting level. CrM appears to be well-tolerated and, at the study-level, does not increase the risk of gastrointestinal, renal, liver, musculoskeletal, or other SEs compared to placebo, even at high doses or longer durations.”

What I got from the linked review is:

1) Creatine is safe, "creatine supplementation is safe across a range of doses, durations, and populations according to human trials".

2) Stomach issues are a commonly reported side effect, "Gastrointestinal issues were the most frequently reported side effect... Most notably, gastrointestinal distress is a commonly reported side effect, and those supplementing with creatine may need to divide the dose into smaller boluses to alleviate it; however, it is worth noting that this side effect was not persistent"

3) It is not clear if the side effects are caused by creatine, many of the issues can be explained by baseline issues rather than caused by creatine, "No consistent or clinically meaningful dose-dependent increases in side-effect reporting were observed across models; even at higher doses and prolonged durations, reporting remained low and largely comparable to placebo at the study level"

On the sleep deprivation topic, adenosine buildup in the brain is, along with melatonin, one of the brain's core sleep mechanisms. As you expend energy during the day, adenosine builds up, so your brain has an idea of how long you've been awake.

Creatine recycles adenosine back into ATP, so less adenosine builds up. The amount of creatine you find in foods naturally is way less than the amount people are supplementing with.

So it makes sense physiologically why mega doses of creatine might negatively affect sleep.

As with anything in medicine, if it was that straightforward, someone would've already discovered that right now. Human physiology (and biology in general) is such a messy field that the simple act of using isolated facts very rarely gives useful insights.

So creatine adds the phosphates back to the adenosine? However, it's a good reason to exercise. Burn the phosphates from ATP and be left with adenosine, which as you say promotes sleep.

However, I don't think it is so much of a signal of your brain having an idea of how long you've been awake, that's the circadian cycle. I always looked at adenosine as a driver of sleep need. If you burned this much ATP, we're going to need to recover. Seems like an elegant process.

> "creapure", which is a patented formula known for its purity

You mean known for its branding. Most people have never heard of creapure and those who do haven't tested it for purity.

There are several studies of Creapure and other brands. Most of the studies done on CM use the Creapure brand.

https://pmc.ncbi.nlm.nih.gov/articles/PMC9761713/

https://pubmed.ncbi.nlm.nih.gov/35268011/

Some people simply don’t digest the monohydrate form well. I get all of the symptoms you list.

The HCL form is more expensive, but does wonders for me. None of the negative side effects.

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