Effect of Dietary Zinc and Phytase Supplementation on Botulinum Toxin Treatments

April 2012 | Volume 11 | Issue 4 | Original Article | 507 | Copyright © April 2012


John C. Koshy MD,1 Safa E. Sharabi MD,1 Evan M. Feldman MD,1 Larry H. Hollier, Jr MD,1 James R. Patrinely MD,1-4Charles N. S. Soparkar MD PhD 1-4

1Department of Plastic Surgery, Baylor College of Medicine, Houston, TX 2Department of Ophthalmology, Baylor College of Medicine, Houston, TX 3Department of Head and Neck Surgery, MD Anderson Cancer Center, Houston, TX 4Department of Ophthalmology, The Methodist Hospital, Houston, TX 5 Department of Ophthalmology, Weill Cornell University, Houston, TX

Abstract
Purpose: To determine whether oral zinc supplementation might affect the efficacy and duration of botulinum toxin treatments.
Methods: In a double-blind, placebo-controlled, crossover pilot study, we examined the efficacy of three botulinum toxin preparations (onabotulinumtoxinA, abobotulinumtoxinA, and rimabotulinumtoxinB) following oral supplementation with zinc citrate 50 mg and phytase 3,000 PU, zinc gluconate 10 mg, or lactulose placebo in individuals treated for cosmetic facial rhytids, benign essential blepharospasm, and hemifacial spasm.
Results: In seventy-seven patients, 92% of subjects supplemented with zinc 50 mg and phytase experienced an average increase in toxin effect duration of nearly 30%, and 84% of participants reported a subjective increase in toxin effect, whereas no significant increase in duration or effect was reported by patients following supplementation with lactulose placebo or 10 mg of zinc gluconate. The dramatic impact of the zinc/phytase supplementation on some patients' lives clinically unmasked the study and prompted an early termination.
Conclusions: This study suggests a potentially meaningful role for zinc and/or phytase supplementation in increasing the degree and duration of botulinum toxin effect in the treatment of cosmetic facial rhytids, benign essential blepharospasm, and hemifacial spasm.

J Drugs Dermatol. 2012;11(4):507-512.

INTRODUCTION

Botulinum toxins (BTXs), a family of zinc-dependent metalloproteases, play an expanding role in the management of many medical and aesthetic conditions. While generally effective for most patients, BTX therapeutic efficacy is well known to vary widely, not only among individuals, but also from treatment to treatment for a single individual, and certain demographic variables, such as age over 64 years, are associated with a profoundly diminished BTX effect.1,7,8,13
Due to the obligate requirement of zinc for BTX function, and the fact that commercial preparations of BTXs exclude zinc addition, a person's zinc status may be an important variable in BTX clinical effect.
Profound zinc deficiency in childhood can be blatant,24but less severe deficiencies in adulthood may be subtle. While the exact prevalence of zinc deficiency is unknown due in large part to poor correlation of serum and urine levels with tissue and intracellular concentrations and overall elemental zinc effect,11,28concern over suspected widespread marginal zinc status is growing.5,17,20,26 For example, in the United States (U.S.), roughly half of persons over age 50 consume less zinc than federally recommended, 4 and nearly 30% of these individuals may show overt signs of zinc deficiency.23
Zinc levels are dependent upon many factors aside from zinc dietary intake including dietary phytates (Table 1), a family of phosphorous-containing compounds that block zinc absorption (Table 2).18A relatively low zinc/high phytate diet may be increasingly prevalent in the U.S., especially among fixed-budget elderly avoiding expensive meats, the weight- and cholesterolconscious, and vegetarians. Phytases, a family of enzymes that degrade phytates, are known to increase zinc absorption when consumed with zinc and phytates.2,15
Zinc homeostatic mechanisms maintain tissue levels for only brief periods, and individuals may become relatively zinc deficient quickly.14 Although the effects of BTX treatments may last months, the zinc-dependent proteolytic activity of BTXs occurs before the toxins are degraded within hours of administration.
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