[Skip to Content]
[Skip to Content Landing]

Effect of Multinutrient Supplementation and Food-Related Behavioral Activation Therapy on Prevention of Major Depressive Disorder Among Overweight or Obese Adults With Subsyndromal Depressive SymptomsThe MooDFOOD Randomized Clinical Trial

Educational Objective
To learn about nutritional interventions for the prevention of major depressive disorder.
1 Credit CME
Key Points

Question  What is the effect of multinutrient supplementation and food-related behavioral activation therapy on prevention of a new episode of major depressive disorder among overweight or obese adults with subsyndromal depressive symptoms?

Findings  In this 2 × 2 factorial randomized clinical trial that included 1025 adults, there was no significant difference in episodes of major depressive disorder over 1 year of follow-up with multinutrient supplementation vs placebo (54 [10.5%] vs 51 [9.9%]) or with food-related behavioral activation therapy vs no therapy (48 [9.4%]) vs 57 [11.1%]).

Meaning  These findings do not support the use of multinutrient supplementation or food-related behavioral activation therapy for prevention of major depressive disorder.

Abstract

Importance  Effects of nutritional interventions on the prevention of major depressive disorder (MDD) in overweight adults are unknown.

Objective  To examine the effect of 2 nutritional strategies (multinutrient supplementation, food-related behavioral activation therapy) and their combination for prevention of a new MDD episode in overweight adults with subsyndromal depressive symptoms.

Design, Setting, and Participants  This multicenter 2 × 2 factorial randomized clinical trial included overweight adults (body mass index, 25-40) with elevated depressive symptoms (Patient Health Questionnaire-9 [PHQ-9] scores ≥5) and no MDD episode in the past 6 months from 4 European countries. A total of 1025 adults were randomized (July 30, 2015-October 12, 2016) and followed up for 1 year (October 13, 2017).

Interventions  Daily multinutrient supplements (1412-mg omega-3 fatty acids, 30-μg selenium, 400-μg folic acid, and 20-μg vitamin D3 plus 100-mg calcium) vs placebo and 21 individual or group therapy sessions vs none (blinded to researchers) for 1 year. Participants were allocated to placebo without therapy (n = 257), placebo with therapy (n = 256), supplements without therapy (n = 256), and supplements with therapy (n = 256).

Main Outcome and Measures  Cumulative 1-year onset of MDD via the Mini International Neuropsychiatric Interview at 3, 6, and 12 months. Logistic regression using effect-coded variables (−1 indicating control, 1 indicating intervention) evaluated intervention effects both individually and in combination (interaction) on MDD onset.

Results  Among 1025 participants (mean age, 46.5 years; 772 women [75%]; mean BMI, 31.4), 779 (76%) completed the trial. During the 12-month follow-up, 105 (10%) developed MDD: 25 (9.7%) patients in the placebo without therapy, 26 (10.2%) in the placebo with therapy, 32 (12.5%) in the supplement without therapy, and 22 (8.6%) in the supplement with therapy group. None of the treatment strategies affected MDD onset. The odds ratio (OR) for supplements was 1.06 (95% CI, 0.87-1.29); for therapy, 0.93 (95% CI, 0.76-1.13); and for their combination, 0.93 (95% CI, 0.76-1.14; P for interaction, .48). One person in the supplementation with therapy group, died. Twenty-four patients in each of the placebo groups and 24 patients in the supplementation with therapy group were hospitalized, and 26 patients in the supplementation-only group were hospitalized.

Conclusions and Relevance  Among overweight or obese adults with subsyndromal depressive symptoms, multinutrient supplementation compared with placebo and food-related behavioral activation therapy compared with no therapy did not reduce episodes of major depressive disorder during 1 year. These findings do not support the use of these interventions for prevention of major depressive disorder.

Trial registration  ClinicalTrials.gov Identifier: NCT02529423

Sign in to take quiz and track your certificates

Buy This Activity
Article Information

Corresponding Author: Marjolein Visser, PhD, Department of Health Sciences, Faculty of Science and Amsterdam Public Health research institute, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, the Netherlands (m.visser@vu.nl).

Accepted for Publication: January 28, 2019.

Author Contributions: Dr Bot had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Bot, Brouwer, Roca, Kohls, Penninx, Watkins, van Grootheest, Cabout, Gili, Visser.

Acquisition, analysis, or interpretation of data: Bot, Brouwer, Kohls, Penninx, Watkins, van Grootheest, Cabout, Hegerl, Gili, Owens, Visser.

Drafting of the manuscript: Bot, Roca, Kohls, Gili, Owens, Visser.

Critical revision of the manuscript for important intellectual content: Brouwer, Kohls, Penninx, Watkins, van Grootheest, Cabout, Hegerl, Gili, Owens, Visser.

Statistical analysis: Bot, Watkins, Owens.

Obtained funding: Brouwer, Penninx, Gili, Visser.

Administrative, technical, or material support: Kohls, Penninx, Watkins, van Grootheest, Cabout, Owens, Visser.

Supervision: Bot, Brouwer, Roca, Kohls, Penninx, Watkins, Hegerl, Gili, Owens, Visser.

MooDFOOD Prevention Trial Investigators: We thank further all nonauthor members of this trial: Bep Verkerk, post-BSc (data manager, GGZ inGeest Specialized Mental Health Care, Amsterdam, the Netherlands), Nadine Paans, MSc (field center therapist and research assistant, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands), Carisha Thesing, MSc (field center therapist, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands), Deborah Gibson-Smith, MSc (field center research assistant, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands), Melany Horsfall, MSc (field center coordinator, GGZ inGeest Specialized Mental Health Care, Amsterdam, the Netherlands), Lena Weiss, MSc (field center research assistant, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands), Amy Romijn, PhD (field postdoctoral research associate, University of Exeter, Exeter, United Kingdom), Hannah Bunce, MSc (field center associate research fellow), Owain Winfield, BSc (research therapist, University of Exeter, Exeter, United Kingdom), Harriet Bunker-Smith, MSc (field center associate research fellow, University of Exeter, Exeter, United Kingdom), Fern Durbridge, BSc (field center associate research fellow, University of Exeter, Exeter, United Kingdom), Caterina Versari Molinares, MSc (research intern, University of Exeter, Exeter, United Kingdom), Atikah Sapar, BSc (research intern, University of Exeter, Exeter, United Kingdom), Miquel Tortella, PhD (field center coinvestigator, UIB, Palma de Mallorca, Spain), Clara Homar Covas, MSc (field center research and therapist, UIB, Palma de Mallorca, Spain), M. Angeles Pérez-Ara, PhD (field center research assistant, UIB, Palma de Mallorca, Spain), Adoración Castro Gracia, MSc (field center research assistant, UIB, Palma de Mallorca, Spain), José Luis Reig, MSc (field center therapist, UIB, Palma de Mallorca, Spain), Jana Hoesel (field center study nurse, ULEI, Leipzig, Germany), Ezgi Dogan, MD (field center research fellow, ULEI, Leipzig, Germany), Sabrina Baldofski, PhD (field center therapist, ULEI, Leipzig, Germany), and Nicole Mauche, MSc (field center therapist). All members of the trial were staff members at the respective institutions and received no further compensation.

Conflict of Interest Disclosures: Dr Roca reported receiving grants from the European Union and research funding from Janssen and Lundbeck outside the submitted work. Dr Penninx reported receiving grants from Janssen Research and Boehringer Ingelheim. Dr Watkins reported receiving royalties for a therapy manual in Behavioural Activation/Cognitive Behavioural Therapy from Guilford Press; and honorarium for running workshops in his rumination-focused cognitive behavioral therapy from different national cognitive behavioral therapy organizations worldwide. Dr Hegerl reported receiving personal fees from Lundbeck, Janssen Pharmaceutica, Servier, Bayer Pharma, and Medice.

Funding/Support: Funding for this article was provided by the European Union FP7 MooDFOOD Project Multi-country Collaborative Project on the Role of Diet, Food-related Behavior, and Obesity in the Prevention of Depression (grant agreement 613598). This work is supported in the United Kingdom by the National Institute for Health Research (NIHR), through the Primary Care Research Network and the NIHR Exeter Clinical Research Facility.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement 4

Additional Contributions: We thank Mohammod Mostazir, MSc (College of Life and Environmental Sciences, University of Exeter) for his assistance with the CACE analyses, and Adriaan Hoogendoorn, PhD (GGZ inGeest Specialized Mental Health Care, Amsterdam, the Netherlands) for his advice for the statistical analyses. Neither received compensation for their roles.

References
1.
Kessler  RC, Wang  PS.  The descriptive epidemiology of commonly occurring mental disorders in the United States.  Annu Rev Public Health. 2008;29:115-129. doi:10.1146/annurev.publhealth.29.020907.090847PubMedGoogle ScholarCrossref
2.
Vos  T, Flaxman  AD, Naghavi  M,  et al.  Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010.  Lancet. 2012;380(9859):2163-2196. doi:10.1016/S0140-6736(12)61729-2PubMedGoogle ScholarCrossref
3.
Cuijpers  P, Beekman  ATF, Reynolds  CF  III.  Preventing depression: a global priority.  JAMA. 2012;307(10):1033-1034. doi:10.1001/jama.2012.271PubMedGoogle ScholarCrossref
4.
Molendijk  M, Molero  P, Ortuño Sánchez-Pedreño  F, Van der Does  W, Angel Martínez-González  M.  Diet quality and depression risk: a systematic review and dose-response meta-analysis of prospective studies.  J Affect Disord. 2018;226:346-354. doi:10.1016/j.jad.2017.09.022PubMedGoogle ScholarCrossref
5.
Paans  NPG, Bot  M, van Strien  T, Brouwer  IA, Visser  M, Penninx  BWJH.  Eating styles in major depressive disorder: Results from a large-scale study.  J Psychiatr Res. 2018;97:38-46. doi:10.1016/j.jpsychires.2017.11.003PubMedGoogle ScholarCrossref
6.
Jacka  FN, O’Neil  A, Opie  R,  et al.  A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’ trial).  BMC Med. 2017;15(1):23. doi:10.1186/s12916-017-0791-yPubMedGoogle ScholarCrossref
7.
Parletta  N, Zarnowiecki  D, Cho  J,  et al.  A Mediterranean-style dietary intervention supplemented with fish oil improves diet quality and mental health in people with depression: A randomized controlled trial (HELFIMED).  Nutr Neurosci. 2017;1-14. doi:10.1080/1028415X.2017.1411320PubMedGoogle Scholar
8.
Opie  RS, O’Neil  A, Itsiopoulos  C, Jacka  FN.  The impact of whole-of-diet interventions on depression and anxiety: a systematic review of randomised controlled trials.  Public Health Nutr. 2015;18(11):2074-2093. doi:10.1017/S1368980014002614PubMedGoogle ScholarCrossref
9.
Milaneschi  Y, Hoogendijk  W, Lips  P,  et al.  The association between low vitamin D and depressive disorders.  Mol Psychiatry. 2014;19(4):444-451. doi:10.1038/mp.2013.36PubMedGoogle ScholarCrossref
10.
Sarris  J, Murphy  J, Mischoulon  D,  et al.  Adjunctive nutraceuticals for depression: a systematic review and meta-analyses.  Am J Psychiatry. 2016;173(6):575-587. doi:10.1176/appi.ajp.2016.15091228PubMedGoogle ScholarCrossref
11.
Mocking  RJT, Harmsen  I, Assies  J, Koeter  MWJ, Ruhé  HG, Schene  AH.  Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder.  Transl Psychiatry. 2016;6(3):e756. doi:10.1038/tp.2016.29PubMedGoogle ScholarCrossref
12.
Okereke  OI, Singh  A.  The role of vitamin D in the prevention of late-life depression.  J Affect Disord. 2016;198:1-14. doi:10.1016/j.jad.2016.03.022PubMedGoogle ScholarCrossref
13.
Milaneschi  Y, Simmons  WK, van Rossum  EFC, Penninx  BW.  Depression and obesity: evidence of shared biological mechanisms.  Mol Psychiatry. 2019;24(1):18-33. doi:10.1038/s41380-018-0017-5PubMedGoogle ScholarCrossref
14.
Roca  M, Kohls  E, Gili  M,  et al; MooDFOOD Prevention Trial Investigators.  Prevention of depression through nutritional strategies in high-risk persons: rationale and design of the MooDFOOD prevention trial.  BMC Psychiatry. 2016;16(1):192. doi:10.1186/s12888-016-0900-zPubMedGoogle ScholarCrossref
15.
Kroenke  K, Spitzer  RL, Williams  JBW.  The PHQ-9: validity of a brief depression severity measure.  J Gen Intern Med. 2001;16(9):606-613. doi:10.1046/j.1525-1497.2001.016009606.xPubMedGoogle ScholarCrossref
16.
Sheehan  DV, Lecrubier  Y, Sheehan  KH,  et al.  The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10.  J Clin Psychiatry. 1998;59(suppl 20):22-33. http://www.ncbi.nlm.nih.gov/pubmed/9881538. PubMedGoogle Scholar
17.
Ekers  D, Webster  L, Van Straten  A, Cuijpers  P, Richards  D, Gilbody  S.  Behavioural activation for depression; an update of meta-analysis of effectiveness and sub group analysis.  PLoS One. 2014;9(6):e100100. doi:10.1371/journal.pone.0100100PubMedGoogle ScholarCrossref
18.
Rush  AJ, Gullion  CM, Basco  MR, Jarrett  RB, Trivedi  MH.  The Inventory of Depressive Symptomatology (IDS): psychometric properties.  Psychol Med. 1996;26(3):477-486. doi:10.1017/S0033291700035558PubMedGoogle ScholarCrossref
19.
Spitzer  RL, Kroenke  K, Williams  JBW, Löwe  B.  A brief measure for assessing generalized anxiety disorder: the GAD-7.  Arch Intern Med. 2006;166(10):1092-1097. doi:10.1001/archinte.166.10.1092PubMedGoogle ScholarCrossref
20.
EuroQol Group.  EuroQol—a new facility for the measurement of health-related quality of life.  Health Policy. 1990;16(3):199-208. doi:10.1016/0168-8510(90)90421-9PubMedGoogle ScholarCrossref
21.
Devlin  NJ, Shah  KK, Feng  Y, Mulhern  B, van Hout  B.  Valuing health-related quality of life: An EQ-5D-5L value set for England.  Health Econ. 2018;27(1):7-22. doi:10.1002/hec.3564PubMedGoogle ScholarCrossref
22.
de Lauzon  B, Romon  M, Deschamps  V,  et al; Fleurbaix Laventie Ville Sante Study Group.  The Three-Factor Eating Questionnaire-R18 is able to distinguish among different eating patterns in a general population.  J Nutr. 2004;134(9):2372-2380. doi:10.1093/jn/134.9.2372PubMedGoogle ScholarCrossref
23.
Garcia-Larsen  V, Luczynska  M, Kowalski  ML,  et al; GA2LEN-WP 1.2 ‘Epidemiological and Clinical Studies’.  Use of a common food frequency questionnaire (FFQ) to assess dietary patterns and their relation to allergy and asthma in Europe: pilot study of the GA2LEN FFQ.  Eur J Clin Nutr. 2011;65(6):750-756. doi:10.1038/ejcn.2011.15PubMedGoogle ScholarCrossref
24.
Wendel-Vos  GCW, Schuit  AJ, Saris  WHM, Kromhout  D.  Reproducibility and relative validity of the short questionnaire to assess health-enhancing physical activity.  J Clin Epidemiol. 2003;56(12):1163-1169. doi:10.1016/S0895-4356(03)00220-8PubMedGoogle ScholarCrossref
25.
Stunkard  AJ, Sørensen  T, Schulsinger  F. In: Kety  S, Roland  L, Sidman  R, Matthysse  S, eds.  Use of the Danish Adoption Register for the Study of Obesity and Thinness. The Geneti. New York, NY: Raven Press; 1983.
26.
Cuijpers  P, van Straten  A, Smit  F, Mihalopoulos  C, Beekman  A.  Preventing the onset of depressive disorders: a meta-analytic review of psychological interventions.  Am J Psychiatry. 2008;165(10):1272-1280. doi:10.1176/appi.ajp.2008.07091422PubMedGoogle ScholarCrossref
27.
van’t Veer-Tazelaar  PJ, van Marwijk  HWJ, van Oppen  P,  et al.  Stepped-care prevention of anxiety and depression in late life: a randomized controlled trial.  Arch Gen Psychiatry. 2009;66(3):297-304. doi:10.1001/archgenpsychiatry.2008.555PubMedGoogle ScholarCrossref
28.
Buntrock  C, Ebert  DD, Lehr  D,  et al.  Effect of a web-based guided self-help intervention for prevention of major depression in adults with subthreshold depression.  JAMA. 2016;315(17):1854-1863. doi:10.1001/jama.2016.4326PubMedGoogle ScholarCrossref
29.
Collins  LM, Dziak  JJ, Kugler  KC, Trail  JB.  Factorial experiments: efficient tools for evaluation of intervention components.  Am J Prev Med. 2014;47(4):498-504. doi:10.1016/j.amepre.2014.06.021PubMedGoogle ScholarCrossref
30.
Rubin  DB.  Multiple Imputation for Nonresponse in Surveys. New York, NY: Wiley; 2004.
31.
Twisk  JWR, Bosman  L, Hoekstra  T, Rijnhart  J, Welten  M, Heymans  M.  Different ways to estimate treatment effects in randomised controlled trials.  Contemp Clin Trials Commun. 2018;10(June):80-85. doi:10.1016/j.conctc.2018.03.008PubMedGoogle Scholar
32.
Morris  SB.  Estimating effect sizes from pretest-posttest-control group designs.  Organ Res Methods. 2008;11(2):364-386. doi:10.1177/1094428106291059Google ScholarCrossref
33.
Angrist  JD, Imbens  GW, Rubin  DB.  Identification of Causal Effects Using Instrumental Variables.  J Am Stat Assoc. 1996;91(434):444-455. https://dash.harvard.edu/handle/1/3382969. doi:10.1080/01621459.1996.10476902Google ScholarCrossref
34.
Emsley  R, Dunn  G, White  IR.  Mediation and moderation of treatment effects in randomised controlled trials of complex interventions.  Stat Methods Med Res. 2010;19(3):237-270. doi:10.1177/0962280209105014PubMedGoogle ScholarCrossref
35.
van Zoonen  K, Buntrock  C, Ebert  DD,  et al.  Preventing the onset of major depressive disorder: a meta-analytic review of psychological interventions.  Int J Epidemiol. 2014;43(2):318-329. doi:10.1093/ije/dyt175PubMedGoogle ScholarCrossref
36.
Rogers  PJ, Appleton  KM, Kessler  D,  et al.  No effect of n-3 long-chain polyunsaturated fatty acid (EPA and DHA) supplementation on depressed mood and cognitive function: a randomised controlled trial.  Br J Nutr. 2008;99(2):421-431. doi:10.1017/S0007114507801097PubMedGoogle ScholarCrossref
37.
Ford  AH, Flicker  L, Thomas  J, Norman  P, Jamrozik  K, Almeida  OP.  Vitamins B12, B6, and folic acid for onset of depressive symptoms in older men: results from a 2-year placebo-controlled randomized trial.  J Clin Psychiatry. 2008;69(8):1203-1209. doi:10.4088/JCP.v69n0801PubMedGoogle ScholarCrossref
38.
Okereke  OI, Cook  NR, Albert  CM, Van Denburgh  M, Buring  JE, Manson  JE.  Effect of long-term supplementation with folic acid and B vitamins on risk of depression in older women.  Br J Psychiatry. 2015;206(4):324-331. doi:10.1192/bjp.bp.114.148361PubMedGoogle ScholarCrossref
39.
Rayman  M, Thompson  A, Warren-Perry  M,  et al.  Impact of selenium on mood and quality of life: a randomized, controlled trial.  Biol Psychiatry. 2006;59(2):147-154. doi:10.1016/j.biopsych.2005.06.019PubMedGoogle ScholarCrossref
40.
Bellón  JA, Moreno-Peral  P, Motrico  E,  et al.  Effectiveness of psychological and/or educational interventions to prevent the onset of episodes of depression: A systematic review of systematic reviews and meta-analyses.  Prev Med. 2015;76(suppl):S22-S32. doi:10.1016/j.ypmed.2014.11.003PubMedGoogle ScholarCrossref
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_LoginSubscribe_Purchase
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_LoginSubscribe_Purchase
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right

Name Your Search

Save Search
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
jn-learning_Modal_SaveSearch_NoAccess_Purchase

Lookup An Activity

or

My Saved Searches

You currently have no searches saved.

With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Topics
State Requirements