High-Quality Diet Linked to Better Outcomes in Bipolar Disorder

Liam Davenport

October 12, 2018

BARCELONA, Spain — Diet quality and body mass index (BMI) may predict outcomes for patients with bipolar disorder (BD), new research suggests.

Results of a randomized controlled clinical trial showed that BD patients who received an adjunctive combination neutraceutical treatment that included the anti-inflammatory amino acid N-acetylcysteine (NAC) and who ate a higher-quality rather than a lower-quality diet had better outcomes.

A high-quality diet was one that included an abundance of fruits and vegetables, whereas poorer-quality diets included more saturated fat, refined carbohydrates, and alcohol.

"What we can see at this stage is that there seems to be some sort of combination between a better diet or noninflammatory diet and the combination treatment, although it wasn't consistent across all the parameters assessed," lead investigator Melanie M. Ashton, GDip, Deakin University, Geelong, Australia, said in a release.

These findings, which were presented at the 31st European College of Neuropsychopharmacology (ECNP) Congress, may imply that dietary advice should be included as a standard part of BD management.

Treatment "Shortfall"

Pharmacotherapies in BD often target symptoms of mania, which, the researchers point out, leaves a "potential shortfall in recovery" for those with depressive symptoms.

Underlying these symptoms are disturbances in neuroinflammation, mitochondrial activity, and neurotransmitters, as well as oxidative stress — processes that may potentially be modulated by diet quality. The investigators note that patients with BD often have poor-quality diets, and this may have an impact on treatment outcomes.

The aim of the research was to assess whether diet quality, dietary inflammatory index, and BMI predict treatment response. The trial included 133 BD patients who were randomly assigned to receive placebo, NAC alone, or a combination of mitochondrial activity–enhancing agents.

The combination treatment consisted of NAC, acetyl L-carnitine, ubiquinone, alpha lipoic acid, magnesium, alpha-tocopherol, cholecalciferol, retinyl palmitate, calcium ascorbate dehydrate, and vitamin B cofactors.

These cofactors included thiamine hydrochloride, nicotinamide, riboflavin, calcium panothenate, pyroxidine hydrochloride, biotin, folic acid, and cyanocabalamin.

BMI was measured at baseline. The patients were assessed every 4 weeks during the 16-week treatment period and again at a post-discontinuation visit at week 20.

Diet quality was determined by converting Food Frequency Questionnaire scores into an Australian Recommended Food Score and Energy-adjusted Dietary Inflammatory Index.

For the current analysis, the team assessed whether diet quality, dietary inflammation index, or BMI predicted week-20 scores on the following measures:

  • Montgomery-Åsberg Depression Rating Scale (MADRS);

  • Bipolar Depression Rating Scale (BDRS);

  • Clinical Global Impression–Improvement (CGI-I) scale;

  • Social and Occupational Functioning Scale (SOFAS); and

  • Longitudinal Interval Follow-Up Evaluation–Range of Impaired Functioning Tool (LIFE-RIFT), which examines the degree of functional impairment due to psychopathology.

Greater Improvement

Participants in the combined or NAC treatment groups who had a higher-quality diet experienced significantly greater improvements on both the CGI-I and BDRS than those with a low-quality diet or who were taking placebo (P < .05).

In addition, patients with a higher-quality diet, regardless of treatment arm, demonstrated significant improvements in MADRS scores in comparison with their counterparts who ate a low-quality diet (P < .05). There were no significant associations between diet quality and scores on either SOFAS or LIFE-RIFT.

The results also showed that those in the combination treatment group who also consumed a diet with low inflammatory potential demonstrated less impairment on LIFE-RIFT than the placebo group (P < .05).

Low dietary inflammatory potential was also associated with greater scores on SOFAS, regardless of the treatment received, in comparison with a proinflammatory diet (P < .05).

Scores on MADRS, CGI-I, and BDRS were not associated with dietary inflammatory index scores.

The team found that a lower BMI was associated with greater CGI-I scores over time in patients taking combination or NAC treatment vs placebo. By contrast, for those in the NAC group, a lower BMI was associated with greater improvements on MADRS vs placebo (P < .05 for both).

There were no significant associations between BMI and scores on SOFA, LIFE-RIFT and BDRS.

Results showed that after 16 weeks, diet quality had an impact on the response to treatment, including treatment of depression and bipolar depression, as well as clinician-rated scores. The inflammatory potential of the diets had an impact on the degree of functional impairment.

Patients' body mass index (BMI) also seemed to influence the degree of improvement, as measured by clinician-rated and depression scores.

Promising, but Early Days

The researchers caution that, although intriguing, the results should not be "overinterpreted."

"This study informs future researchers, indicating diet factors should be considered when assessing the efficacy of new treatments. In addition, this study should inform clinicians treating bipolar disorder to consider a patient's diet when prescribing pharmaceutical treatments," they note.

Ashton also noted in a release that although some of the study findings are statistically significant, "because the study wasn't specifically designed to test the effect of diet quality, inflammatory diets, and BMI on drug response in general, it is necessary to see the work replicated in a larger study before any firm conclusions can be formed."

The researchers are now studying the different outcomes in more detail. They are also studying the role inflammation plays in BD treatment outcomes, which is the favored explanation for the results.

"Diet quality, in particular the inflammatory capacity of a diet, and BMI of participants with bipolar disorder may predict response to treatment. Participants who have lower BMI may show greater clinician rated improvement when receiving the combination mitochondrial enhancing treatments. Further research is required for a more comprehensive assessment of diet quality and other common bipolar disorder treatments," the investigators conclude.

Commenting on the study, Eduard Vieta, MD, PhD, chair of the Department of Psychiatry and Psychology at the University of Barcelona Hospital Clinic, who was not involved in the study, noted in a release that the research "holds out the possibility that patients with bipolar disorder may benefit from a balanced diet.

"However," he added, "it is an early study, and we need more research before we can think whether this might affect clinical practice."

The study has been funded by NHMRC Project Grant, Deakin University, Australasian Society for Bipolar and Depressive Disorders/Lundbeck and Australian Rotary Health/Ian Parker Bipolar Research Fund.

M. Berk is a coinventor of two provisional agents regarding the use of NAC and related compounds for psychiatric indications, assigned to the Mental Health Research Institute. J. R. Herbert owns a controlling interest in Connecting Health Innovations, LLC (CHI), a company planning to license the right to his invention of the dietary inflammatory index from the University of South Carolina to develop computer and smartphone applications for patient counselling and dietary interventions in clinical settings. N. Shivappa is an employee of CHI. The other researchers and Dr Vieta have disclosed no relevant financial relationships.

31st European College of Neuropsychopharmacology (ECNP) Congress. Abstract P.039, presented October 7, 2018.

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