Some strength athletes are convinced that they react badly to creatine. They fall ill more quickly when they use the most researched and most effective supplement to hit the market in the last twenty years. Are they imagining this? Perhaps not, cell studies done by immunologists at Creighton University suggest.
Toll-like receptors [TLRs] were the focus of the researchers' study, the results of which will be published soon in International Immunopharmacology. TLRs are receptors on the membrane of immune cells, which are capable of recognising pathogens. TLRs play an important role in the non-learning part of our immune system that we are born with, and they roll into action immediately when they discover pathogens or faulty substances produced by the body itself. This part of the immune system is also called the body's natural resistance.
Back in the seventies, researchers discovered that creatine has an anti-inflammatory effect. [Arch Int Pharmacodyn Ther. 1978 Feb; 231(2): 340-50.] The effect is so strong that researchers even attributed painkilling effect to creatine. If it weren't for the fact that creatine has been so well studied, you'd be forgiven for wondering whether the extra reps you manage on creatine were the result of its painkilling properties.
Because inflammation is closely bound up with the immune system, the immunologists at Creighton were curious to know whether creatine and its analogues have an effect on the immune system. They extracted macrophages from mice and exposed these in test tubes to creatine, creatinine and creatine ethyl ester. Macrophages are immune cells that fall under the natural resistance department. They literally gobble intruders up.
When the researchers added creatyl [CEE], creatine [CR] and creatinine [CRN] to the cells and waited 60 minutes, the production of the RNA for the TLRs decreased. The figure below shows the effect of the three analogues on the RNA for TLR-4. These are the instructions from the genetic material in the cells to make more TLR-4. At twenty and thirty minutes after being added, creatine ethyl ester boosts production, but this effect has worn off after 60 minutes.
The photos above show the cells where the TLRs have been made visible using dye. This was done 24 hours after exposure to creatinine, the waste product of creatine and creatine ethyl ester.
TLR-2 is a receptor through which macrophages recognise bacteria, viruses and fungi; TLR-3 is involved in protecting blood vessels against hardening; TLR-4 stimulates pain and inflammation processes and TLR-7 recognises the genetic material of viruses.
The researchers repeated their experiments with cells from mouse spleens, and obtained the same results. The spleen is the equivalent of the immune cells' barracks.
Three hours after a load of creatine molecules have entered your blood, half of them have already been converted into creatinine. It's not so much creatine users' creatine level but their creatinine level that is probably raised the whole day – certainly if they take several doses a day.
"It is tempting to speculate that the extended elevation in creatine levels in vivo negatively impacts the host's ability to respond to infections", the researchers write. "Future studies in the laboratory will focus on the impact of CR, CRN, and CEE in animal models of viral and bacterial infections."
Future studies. Aha. We'll be watching out for these.
Int Immunopharmacol. 2011 May 14. [Epub ahead of print].