Creatine did not stop muscle shrinking inside a cast in the two trials that scanned it. Six small studies suggest the question may be what happens after the cast comes off

Anyone who has had a limb in a cast knows how thin it looks when the cast comes off. Creatine monohydrate has a solid record for adding to the gains from resistance training, so it is a natural thing to wonder about during an injury. Researchers from universities in the UK and Canada, with one in the US, went looking for every placebo-controlled trial that tested it during enforced rest. Their systematic review appeared in Experimental Physiology on 29 October. From 100 publications they ended up with six trials, 118 people in all, published between 2001 and 2018.

The most consistent result concerns the loss itself. Two trials measured the thigh muscle directly with imaging, and creatine made no difference in either: quadriceps area fell 5.6% with creatine and 5.5% with placebo after one week in a cast, and 11.0% against 9.4% after two weeks. Two other trials did favour creatine, with leg lean mass down 5.6% against 8.9%, and arm lean mass up 0.9% against down 3.7%. But those relied on bioelectrical impedance and DXA, which the reviewers point out can be swayed by shifts in body water and cannot separate small changes in muscle from other lean tissue. Their reading is that the favourable numbers should not be taken as muscle saved.

Strength and endurance gave a split answer. The three leg trials that tested performance generally found no protection. Two arm trials looked better, and one was striking: elbow strength fell by about 4% with creatine against about 20% with placebo. That trial had seven participants, all men, and was one of the two the reviewers flagged for some concerns about bias. The other arm trial's endurance result narrowly missed significance (p = 0.073). The reviewers say the evidence is too thin to tell whether arms and legs truly respond differently.

Rehab is where creatine looks more interesting, and where the reviewers are most careful. In three trials, 59 people in total, people returned to structured resistance training after the cast. Each trial reported at least some better results with creatine: in one, thigh muscle area regrew by up to 21.3% against 14.3%. Yet not every measure moved, since maximal knee strength recovered about equally in two of them. A fourth trial, with a week of ordinary recovery and no training, found no difference. The authors do not claim a benefit here, only that creatine may influence some measures and that larger trials are needed. Nearly everyone studied was a healthy young adult or teenager, with average ages from 15 to 24, so the trials say little about the older or chronically ill patients who lose the most muscle and recover the slowest.