Micronutrients Absorbed via the Oral Mucosa Reduce Irritability and Anger but Not Stress in University Students During COVID-19: A Randomized Placebo-Controlled Trial

Abstract

Research has shown micronutrient capsules can reduce stress in clinical and nonclinical recipients. However, as individuals can struggle with taking capsules, the objective of this double-blind, randomized placebo-controlled trial was to investigate the efficacy and safety of treating stress and well-being using an alternative delivery methodology: a powder that is absorbed via the oral mucosa. Seventy-two mild–severely stressed students, assessed using the Depression Anxiety Stress Scale–21 (DASS-21), were randomized to placebo or micronutrients and took one powder pouch per day for 4 weeks. Seven (10%) dropped out with no group differences. Symptoms of stress, depression, anxiety, irritability, anger, sleep, diet, and side effects were measured with online questionnaires every 2 weeks. There were no group differences on the primary outcome measures of stress (DASS-21; d = 0.15, p =.525) and self-reported improvement (Modified Clinical Global Impressions–Improvement scale), with 17.1% of the micronutrient and 16.2% of the placebo group identifying themselves as “much” to “very much” improved. However, the micronutrient group experienced statistically significantly greater reduction in irritability (d = 0.54, p =.024) and anger (d = 0.62, p =.011) relative to placebo, measured with the Affective Reactivity Scale and the Abbreviated Profile of Mood States, respectively. No group differences were found on remaining measures, with both groups showing significant improvements. There were significantly more headaches and drowsiness reported in the micronutrient group. Belief in treatment assignment was significantly correlated to self-reported improvement (r = −0.247, p =.049). To conclude, the micronutrients were no better than placebo in reducing stress; nonetheless, the significant benefit on irritability requires further research.