Methods and compositions are provided for increasing responsiveness to therapeutic metalloproteases including increasing and/or maximizing responsiveness and preventing botulinum and tetanus toxin resistance due to a functional deficiency of zinc. Also provided are methods for zinc replacement or supplement in lacking individuals comprising the administration of a zinc supplement for a loading period and/or administration of a phytase supplement together with the zinc supplement. Also provided are methods for standardization of botulinum toxin potency assays that provide for greater certainty and margins of safety in the use of products from different manufacturers.