Creatine and Endometriosis: What the Research Says

If you've spent any time in fitness spaces, you've probably seen creatine everywhere — in gym bags, on supplement shelves, in threads about muscle recovery and brain fog. And if you have endometriosis, you might have wondered whether it's safe to take, whether it could help with the fatigue that makes some days feel impossible, or whether it's just another supplement that doesn't really apply to you. Here's the thing: creatine and endo is actually a research question now, and the findings are not what most people in the fitness world are talking about. Two recent studies — one published in Advanced Science in 2024 and another in Reproduction in 2025 — looked specifically at creatine and endometriosis tissue, and what they found is genuinely important for anyone with endo who is considering supplementing. It's not a simple story, and it doesn't mean creatine is poison, but it does mean the "creatine is universally great" narrative has a major asterisk when endo is in the picture. This article is going to walk through what creatine actually is, what those studies found, what the broader metabolic research on endo tells us, and what any of it means for your actual life. No hype in either direction. Just what the papers say, what we don't know yet, and how to think about it.

What creatine actually does in the body

Creatine is a compound your body makes naturally — mostly in the liver and kidneys — and you also get it from meat and fish. About 95% of your body's creatine is stored in muscle, where it helps regenerate ATP, which is basically your cells' energy currency. When you're lifting weights or sprinting or doing anything that demands short bursts of power, creatine is part of what keeps your muscles going. The reason people supplement with it is that oral creatine (usually creatine monohydrate) can increase the amount stored in your muscles beyond what diet and your body's own synthesis provides. That translates to better performance in high-intensity exercise, faster recovery, and — more recently — some evidence for cognitive benefits, particularly under sleep deprivation or mental load. For most healthy people, it's one of the most studied and well-tolerated supplements out there. That context matters, because the concern here is not about creatine as a general health risk — it's about something much more specific to endo tissue.

What the 2024 and 2025 studies actually found

Ok so here's what they actually found, and it's worth reading carefully. A 2024 paper in Advanced Science ⁵ looked at how creatine affects endometriosis lesions at a cellular level. The researchers found that endo lesions actively accumulate creatine, and that creatine appears to help those lesions survive by making them resistant to ferroptosis — a form of regulated cell death. In normal circumstances, ferroptosis is one of the ways the body eliminates damaged or abnormal cells. The study found that creatine suppresses a protein called PrP (cellular prion protein), and that this suppression interferes with the ferroptosis pathway, essentially helping endo cells dodge a mechanism that might otherwise clear them. Then a 2025 paper in Reproduction ¹ went a step further and looked at how creatine affects the immune environment around endo lesions — specifically peritoneal macrophages, which are immune cells that live in the abdominal cavity and play a major role in whether endo progresses or gets contained. What they found:

Endometriosis (EM) is a chronic inflammatory disease with unclear pathogenesis, in which peritoneal macrophages play a pivotal role. This study demonstrates that creatine (CR) induces M2 polarization of peritoneal macrophages, promoting angiogenesis, fibrogenesis and lesion progression in EM, offering new insight into potential therapeutic strategies.

Chen SM, Liu YK, Ma XQ, et al. — Creatine promotes endometriosis progression by inducing M2 polarization of peritoneal macrophages. Reproduction (Cambridge, England), 2025. View paper →

. The study showed that creatine was driving those macrophages toward what's called M2 polarization — a pro-healing, anti-inflammatory state that sounds good in isolation, but in the context of endo lesions, is actually problematic. M2-polarized macrophages promote angiogenesis (new blood vessel growth, which feeds lesions) and fibrogenesis (the formation of scar tissue and adhesions) ¹. To put that plainly: the research suggests that creatine, in the peritoneal environment of people with endo, may be helping lesions grow a blood supply and form adhesions, while simultaneously helping endo cells resist the kind of cell death that might otherwise limit lesion progression. These are mouse model and cell culture findings with some human tissue data. They are not yet clinical trials in humans taking creatine supplements. That distinction matters — we'll come back to it.

The broader metabolic picture: endo and energy

This creatine story doesn't come out of nowhere. There's been growing interest in the metabolic environment of endo for several years, and it's been clear for a while that endo tissue behaves differently from normal endometrial tissue at the energy level. A 2019 study using a nonhuman primate model ² looked specifically at mitochondrial function in endo tissue versus healthy endometrium. The premise is worth understanding:

Endometriosis is the growth of uterine lining (endometrium) outside of the uterus. In other chronic inflammatory diseases, mitochondrial dysfunction is suspected of playing a role in disease pathogenesis.

Atkins HM, Bharadwaj MS, O'Brien Cox A, et al. — Endometrium and endometriosis tissue mitochondrial energy metabolism in a nonhuman primate model. Reproductive biology and endocrinology : RB&E, 2019. View paper →

. The study found differences in oxidative phosphorylation — the process cells use to generate energy — between endo lesions and normal tissue, suggesting that endo tissue has a distinct metabolic signature. A 2017 study ³ adds another layer. It used MRI spectroscopy to measure metabolite levels in the eutopic endometrium (the endometrium inside the uterus, not the lesions) of people with endometriomas, and found that creatine levels in the endometrium changed significantly after endometrioma removal. Specifically,

Compared to preoperative peak values, significantly decreased NAA, Lac, and Cr1 signals were noted in patients undergoing endometrioma surgery.

Ersahin A, Celik O, Acet M, et al. — Impact of Endometrioma Resection on Eutopic Endometrium Metabolite Contents: Noninvasive Evaluation of Endometrium Receptivity. Reproductive sciences (Thousand Oaks, Calif.), 2017. View paper →

reatine levels were observed post-surgery — suggesting that the presence of endometriomas is actively altering the metabolic environment of the uterine lining itself, including creatine metabolism. A 2020 study ⁴ looked at follicular fluid — the fluid surrounding eggs in the ovaries — and found that the metabolome (the full set of metabolites present) differs depending on the type of endo a person has. This is consistent with the idea that endo doesn't just affect the sites of visible lesions; it alters metabolic signalling across the pelvic environment. Taken together, these studies paint a picture of endo as a disease that fundamentally rewires how energy is managed and metabolites are distributed in the pelvis. Creatine is part of that picture — not as a random bystander, but as something endo tissue appears to actively concentrate and use.

What this doesn't tell us yet

Here's where I want to be honest about the gaps, because there are real ones.

• The 2024 ⁵ and 2025 ¹ studies were conducted in animal models and cell cultures, with some human tissue data. Neither study tracked what happened to people who took creatine supplements orally over time.

• We don't know whether oral creatine supplementation meaningfully raises creatine levels in peritoneal fluid or endo lesions specifically, or whether the body's normal regulation prevents that.

• We don't know the dose-response relationship — whether the concentrations used in the lab studies are comparable to what you'd get from a standard 3-5g daily supplement dose.

• There are no human clinical trials on creatine supplementation in people with endo. None. This is early-stage mechanistic research.

• The research on creatine and cognitive function, fatigue, and muscle recovery in people with chronic inflammatory conditions is separate from this, and hasn't been studied specifically in endo populations. The absence of clinical trial data means we are genuinely in "we don't know yet" territory when it comes to the real-world impact of creatine supplements on endo progression in living humans.

What the research actually says

Let's be clear about what the evidence actually is and isn't. The strongest signal comes from the two Chen et al. papers ¹⁵. The 2024 Advanced Science study ⁵ identified a specific mechanism: creatine suppresses PrP, which impairs ferroptosis in endo cells, making them harder to eliminate. The 2025 Reproduction study ¹ found that creatine in the peritoneal environment promotes M2 macrophage polarization, which in turn drives angiogenesis and fibrosis around lesions. Both studies used mouse models of endo alongside human tissue samples, which gives them more weight than purely in vitro work — but they are still not human clinical trials. The metabolomics studies ³⁴ support the broader point that creatine metabolism is altered in endo. The 2017 study ³ showed that endometrial creatine levels dropped after endometrioma resection, which implies that the presence of endo was influencing creatine distribution in the first place. The 2020 follicular fluid study ⁴ confirmed that the metabolic environment differs by endo phenotype, adding to the picture of endo as a disease that reshapes the biochemical of the pelvis. The mitochondrial study ² provides context for why energy metabolism matters in endo at all — it's not just about creatine, it's about the fact that endo tissue appears to handle energy production differently from healthy tissue, and that difference may be relevant to why lesions survive and grow. What the research does not show: - That taking creatine supplements causes endo to worsen in humans

• That people with endo who have been supplementing have higher disease burden
• That stopping creatine supplementation improves endo outcomes The research is early and mechanistic. It raises a legitimate concern. It does not, on its own, constitute a clinical recommendation to avoid creatine. But it does mean the question deserves serious attention, and it would be dishonest to brush it aside just because creatine has a good safety record in the general population.

What to do with this

So what do you actually do with this? If you're currently taking creatine and you have endo, this is worth bringing to your gynae — specifically your endo specialist if you have one, not just a general gyn who may not be across this research. Show them the Chen et al. papers ¹⁵ if you have to. This is a legitimate conversation to have, not a paranoid one. If you're considering starting creatine — for muscle recovery, brain fog, energy, whatever the reason — it's worth pausing until we have more clarity. The mechanistic evidence isn't conclusive, but it's specific enough that "probably fine" doesn't feel like a satisfying answer when the proposed mechanism involves lesion growth and ferroptosis resistance. If your reason for considering creatine is endo-related fatigue, there are other things worth investigating first: iron levels (especially if you're losing major blood), vitamin D, B12, and whether your sleep is being disrupted by pain. None of those are as simple as a supplement, but they're also not implicated in lesion progression. If you're an athlete or someone who trains seriously and creatine is a meaningful part of your performance protocol, this is genuinely hard. The honest answer is that we don't have enough evidence to say the risk is — but the mechanism identified in these studies is specific enough that I wouldn't personally feel comfortable supplementing with it until there's human clinical data. That's a personal call, not a medical directive. One thing that's clear from the metabolomics research ³⁴: the peritoneal and pelvic environment in endo is metabolically distinct from healthy tissue. Supplements that are well-studied in general populations haven't necessarily been studied in this specific context. Creatine is the most prominent example of that right now, but it's a broader principle worth keeping in mind.