Treatment response to supplemental nutrients for ADHD is independent of diet quality: the MADDY Study RCT

ABSTRACT

Objectives

The 8-week Micronutrients for ADHD in Youth (MADDY) randomized controlled trial (N = 126, age 6–12) of broad-spectrum multinutrients for ADHD with emotional dysregulation found 3 times as many responders with multinutrients (54%) compared to placebo (18%) by Clinical Global Impression-Improvement (CGI-I). Our primary aim for this analysis tests the hypothesis that those with poor overall diet quality at baseline benefit more. The second aim is to explore whether specific components of diet quality moderate treatment response.

Methods

124 children (69 multinutrients, 55 placebo) had diet quality assessed using the Healthy Eating Index-2015 (HEI-2015). For each potential moderator, the outcome CGI-I at week 8 (RCT-end), was modeled two ways: (1) as a dichotomous variable: responder/non-responder, with responders defined by a rating of 1 or 2 ‘very much’ or ‘much improved,’ all else equals non-responder using logistic regression, and (2) as a dimensional improvement outcome from 1 = very much improved to 7 = very much worse, using linear regression.

Results

HEI-2015 total score did not moderate treatment response [odds ratio = 1.00 (95% CI: 0.90,1.10), p = 0.984] or improvement [β = −0.01 (95% CI: −0.06,0.04), p = 0.648]. However, total vegetable intake moderated level of improvement in exploratory analysis [β = −0.48 (95% CI: −0.82, −0.13), p = 0.007]: those with higher baseline vegetable intake showed greater benefit from multinutrients compared to placebo.

Conclusions

Multinutrients may benefit children with ADHD and irritability regardless of overall diet quality. The finding that higher baseline vegetable intake may improve response to multinutrients deserves further exploration, including dietary effect on gut microbiota and absorption of multinutrients and parental factors.

KEYWORDS:

• Dietary quality
• ADHD
• children
• mental health
• healthy eating index
• vitamins
• minerals
• nutrients
• moderator

Acknowledgements

The authors wish to acknowledge our study participants, the study staff, and student researchers, as well as our funders.

Disclosure statement

Dr. Arnold has received research funding from Axial, Forest, Lilly, Noven, Otsuka, Shire, Supernus, Roche, Yamo, and YoungLiving (as well as NIH and Autism Speaks); has consulted with Pfizer, Tris Pharma, and Waypoint; and been on advisory boards for Arbor, Ironshore, Otsuka, Pfizer, Roche, Seaside Therapeutics, Shire. The other authors declare that the research was conducted without any conflict of interest.

Additional information

Funding

The study was funded through a grant from the Foundation for Excellence in Mental Health Care (FEMHC), and donations from FEMHC, the Wells Fargo/Gratis Foundation and the Nutrition and Mental Health Research Fund in Canada. The project was supported by the National Center for Advancing Translational Sciences awards UL1TR002733 (OSU) and UL1TR000128 (OHSU). Similarly, NIH-NCCIH5R90AT008924 funds to the National University for Natural Medicine and NIH-NCCIH T32 AT002688 to Oregon Health & Science University also supported the project. The study funders had no role in the design or reporting of the study. The research was performed with approval from the Oregon Health & Science University (OHSU; #16870) and the Ohio State University (OSU; #2017H0188) Institutional Review Boards and the Conjoint Health Research Ethics Board at the University of Calgary (protocol code #17-0325).

Notes on contributors

Lisa M. Robinette

Lisa Robinette, MS is a PhD student in the Interdisciplinary PhD in Nutrition Program, OSU

Irene E. Hatsu

Irene E. Hatsu, PhD is an Associate Professor of Human Nutrition at the Department of Human Sciences, OSU.

Jeanette M. Johnstone

Jeanette Johnstone, PhD is an Assistant Professor in Child and Adolescent Psychiatry, OHSU

Alisha M. Bruton

Alisha Bruton, ND, MS is a research scientist in the Department of Psychiatry, OHSU.

Brenda M.Y. Leung

Brenda Leung, PhD is an Associate Professor of Public Health in the Faculty of Health Sciences, University of Lethbridge, and holds the Emmy Droog Chair in Complementary and Alternative Healthcare

L. Eugene Arnold

L. Eugene Arnold, MD is a Professor Emeritus of Psychiatry & Behavioral Health, OSU.