Abstract
Background: Diagnosis for anxiety disorders (global population ∼4%) typically relies on clinical interviews/subjective questionnaires. Functional/integrative health groups promote an anxiety biomarker (kryptopyrrole) reported to measure urinary pyrroles, with zinc and B6 as a suggested treatment. Evidence is limited, with no large-scale RCTs supporting claims made. This pilot study investigated those claims.
Methods: Seventy-seven females (assigned at birth), aged 20-71, participated in a 6-week double-blind randomised placebo-controlled trial investigating the efficacy of a daily intake of combined zinc (100 mg) and B6 (100 mg pyridoxine plus 50 mg pyridoxal-5-phosphate) for management of acute symptoms of generalized anxiety. Urine samples were analysed using a modified Ehrlich's test. Primary outcome measures: 1) Generalized Anxiety Disorders 7 scale (GAD-7); 2) Participant Global Impression–Improvement (PGI-I).
Results: Constrained longitudinal data analysis showed significantly greater reductions on the GAD-7 with zinc/B6 (4.15, 95%CI [2.52, 5.78], p < .0001, Cohen's d=0.78), with 62.2% of the treatment group versus 35.0% of the placebo group achieving a ≥6-point improvement (OR = 3.05, p = .02). There was also significantly greater mean improvement on the PGI-I with zinc/B6 (0.780, 95%CI [0.34, 1.22], p < .001, Cohen's d=0.59). Correlations between urinary pyrrole concentrations and GAD-7 were inconsistent across groups and time, with poor sensitivity (49%) and specificity (60%). Secondary outcome measures showed significant improvements on SPAI-18 (p < .01, d=0.68) and Profile of Mood Scores (p < .01, d=0.48) on treatment compared to placebo.
Conclusions: Kryptopyrrole is not a reliable biomarker for anxiety symptoms. A combined daily dose of zinc/B6 may reduce acute self-reported symptoms of generalized anxiety although caution is advised on long-term use.
Clinical trial registry title: Effect of zinc and B6 on individuals with anxiety: A double blind, randomised, placebo controlled trial. Registration number: ACTRN12619000067178.