Does creatine do anything to your immune system?
Creatine affects immune cells, but whether that turns out well or badly depends strongly on the situation. For healthy older adults who also do strength training there is a cautiously positive signal; if you have endometriosis or a certain type of cancer, the context is more complex and consulting your doctor is advisable.
Creatine affects immune cells, but the effect is not simply 'better' or 'worse'. The key lies in how creatine directs a specific type of immune cell, the macrophage. In cell and animal research, creatine switches macrophages from an aggressive, pro-inflammatory mode of behaviour to a calming, repair-oriented one. Whether that is beneficial or harmful depends entirely on the situation.
In older adults with an average age of 68, creatine (3 grams per day) combined with strength training was found to lower the inflammatory markers IL-6 and TNF-alpha and to reduce oxidative stress. Creatine without training already had a smaller but measurable effect on TNF-alpha and on a measure of cell damage caused by free radicals. This is the only randomised experiment in this selection. Two authors have financial ties to the manufacturer of the creatine used, which adds a caveat to this finding.
There are also less favourable contexts. In women with endometriosis, an elevated creatine concentration was found in peritoneal macrophages. There, creatine steered macrophages precisely toward that calming M2 profile, which promoted blood vessel formation and scar tissue and thus appeared to worsen the disease. In oesophageal cancer, the same switch to M2 macrophages was found, leaving the tumour better protected against the body's own immune defences. In mouse models, creatine did something different: it strengthened the attacking capacity of killer immune cells against tumours and increased the effect of cancer immunotherapy. However, this has not yet been studied in humans.
The overarching message is that creatine does not one-sidedly boost or suppress the immune system. It disrupts a specific switch in immune cells, and whether the outcome is positive or negative depends on the context: healthy older adults doing exercise, endometriosis, or a tumour are fundamentally different situations. For the average healthy adult, the lower inflammation seen with use combined with training represents a cautiously positive signal, but this is based on a single study with a commercial caveat.
The evidence rests on a combination of cell and animal research, several reviews, and one randomised experiment involving 103 older adults. The mechanistic insights (the switch in macrophages) are relatively well supported by non-human research. The randomised experiment in older adults is the only one that can establish cause and effect in humans with any degree of certainty, but two authors have financial ties to the creatine manufacturer. Effects in children have barely been studied. The findings in endometriosis and oesophageal cancer are based on tissue analyses, not experiments.