Effect of slow-release [beta]-alanine tablets on absorption kinetics and paresthesia

Issue Title: Carnosine in Exercise and Disease Oral [beta]-alanine ([beta]A) doses larger than 800 mg commonly result in unpleasant sensory symptoms (paresthesia). However, the association of form (pure vs. slow-release) with side-effects has not been fully described. The aim of this single-blinded, randomized three-arm clinical trial was to compare plasma kinetics and symptoms following [beta]A bolus administration in solution or in slow-release tablet form. Eleven healthy adults ingested 1.6 g of a pure [beta]A reference solution (REF), 1.6 g in slow-release [beta]A tablets (TAB) or a placebo (PLA) after an overnight fast. During the next 6 h, urinary and plasma [beta]A concentrations were measured and questionnaires about intensity, nature (pins and needles, itching, flushing, irritation, numbness, soreness), and spatial distribution of unusual sensations were filled in. TAB resulted in a smaller peak plasma concentration than REF (82 vs. 248 [mu]mol L^sup -1^, p < 0.001), delayed time to peak (1.0 vs. 0.5 h, p < 0.01) no difference in area under the curve, reduced loss in urine (202 vs. 663 [mu]mol, p < 0.0001), and improved retention (98.9 vs. 96.3%, p < 0.001). Symptoms described as "pins and needles" were perceived rapidly on the skin of the arms and trunk after REF (T ^sub max^ = 15 min) and their time course nearly mimicked plasma concentrations. Maximum intensity scores were weaker with TAB ("very low") than with REF ("low", p < 0.001), while TAB and PLA did not differ with respect to side-effects. In summary, ingesting 1.6 g [beta]A in slow-release tablets rather than pure in solution results in slower absorption kinetics, improved whole body retention and sensory side-effects that cannot be differentiated from PLA.