Background: With the emerging global popularity of botulinum neurotoxin (BoNT), both for aesthetical and medical purposes, there is a rising need for achieving better outcomes. The aim of this narrative review was to comprehensively cover the effect of BoNT, as well as its possible interactions with everyday mineral and vitamin supplementation. Results: It is well established that BoNT exerts its paralytic effects through zinc-dependent cleavage of SNARE proteins, blocking acetylcholine release at the neuromuscular junctions. However, after meticulous research of the available literature regarding the effect of oral supplementation on BoNT, there is very scarce data. The effect of zinc supplementation on the duration and effectiveness of BoNT in some facial applications was studied in a couple of clinical studies; however, systematic reviews indicate inconsistent results. Copper acts as a noncompetitive inhibitor, potentially antagonizing BoNT in animal models. Magnesium and calcium exhibit theoretical synergistic or compensatory roles via neuromuscular transmission modulation but lack clinical validation. Vitamin B complex shows no interference in rat studies and vitamin D influences baseline muscle strength and dosing needs, while vitamin E increases bruising risk but not efficacy. Conclusions: Even though zinc supplementation holds promise for potentiating BoNT effects, evidence for both zinc and other supplements remains speculative or contradictory, underscoring the need for randomized controlled trials to develop evidence-based guidelines. Clinicians should assess patient supplementation status pre-treatment to optimize outcomes and minimize complications, particularly advising against high-dose vitamin E peri-procedurally.
Puizina et al. (2026) studied this question.