In previously trained adults, performing resistance training with 0–1 repetitions in reserve (RIR) for 5 weeks results in a small but statistically significant decrease in distal vastus lateralis muscle cross-sectional area, whereas training with 4–6 RIR results in a larger decrease, though the difference in change between the two training conditions is not statistically significant.

When muscles are trained very close to failure, the cells inside them experience prolonged stress from buildup of waste products and energy depletion. This stress causes the nerve signals to the muscle to change, making the smaller, slower muscle fibers fire more often even at low effort. Over time, this constant overuse without full recovery leads to a slight breakdown of muscle tissue, shrinking the muscle slightly — and this happens similarly whether training is done very close to failure or stopped earlier, because both still push the muscle into enough stress to trigger this response.