Diet Quality as a Moderator of Response to Multinutrients for ADHD and Emotional Dysregulation: The MADDY RCT

OBJECTIVES: The Micronutrients for ADHD in Youth (MADDY) study was an 8-week double-blind RCT of broad spectrum multinutrients (BSMN) for ADHD with emotional dysregulation in children ages 6–12. Primary outcome Clinical Global Impressions-Improvement (CGI-I) showed 3 times as many responders with BSMN (54%) as placebo (18%). Since diet is the primary source of nutrients intake, and diet quality corresponds with nutritional outcomes, this study seeks to determine the role of baseline diet quality as a moderator of treatment response to test the hypothesis that those with poor diet quality should benefit more. METHODS: 124 children (69 BSMN, 55 placebo) in the intent-to-treat analysis had diet quality assessed by Healthy Eating Index-2015 (HEI-2015) component and total scores from the Vioscreen(TM) FFQ. Primary outcome was odds of treatment response, defined by a rating of 1 or 2 (very much or much improved) on CGI-I at week 8. Sensitivity analysis used CGI-I at week 8 as a dimensional outcome (from 1 = very much improved to 7 = very much worse). Logistic regressions were conducted for the primary analysis and linear regressions for the sensitivity analysis, with HEI scores entered as potential moderators. RESULTS: Total HEI-2015 score did not moderate treatment response [odds ratio = 1.00 (95% CI: 0.90,1.10), p = 0.994] or improvement [β= −0.01 (95% CI: −0.06,0.04), p = 0.655]. HEI component scores also did not moderate treatment response, though total vegetable intake moderated level of improvement [β= −0.48 (95% CI: −0.82, −0.13), p = 0.007]: those with higher vegetable intake showed greater improvement with BSMN but not with placebo. CONCLUSIONS: BSMN may benefit children with ADHD and irritability regardless of diet quality. The finding that higher baseline vegetable intake possibly predisposes to improvement with BSMN is puzzling and worth further exploration of potential mechanisms such that a higher vegetable intake may promote the absorption or utilization of the multinutrients. FUNDING SOURCES: This study was funded by Foundation for Excellence in Mental Health Care, Wells Fargo/Gratis Foundation, and CTSA award #s UL1TR002733, UL1TR002369.