ALA reduces platelet turnover and TACE-mediated GPIb shedding. Plasma glycocalicin (a marker for platelet turnover) as well as the glycocalicin index (A-B; n = 17; P < .001) were significantly decreased in mice fed the high-ALA diet. GPIb cleavage after platelet activation with 0.5 and 1 U/mL thrombin was monitored by flow cytometry of washed platelets. Results are expressed as percentage of fluorescence vs resting state (C; n = 10; *P = .027; **P = .003). In the presence of the specific TACE inhibitor TAPI-1 or the broad metalloprotease inhibitor GM6001, cleavage was completely abrogated (C; n = 5). Addition of the p38 specific inhibitor SB203580 (at concentrations of 20 and 40 μM) blunted the difference between low- and high-ALA platelets, indicating that the TACE inhibition by ALA is p38 dependent (D; n = 8; *P < .05).