1.
Low omega-3 polyunsaturated fatty acids predict reduced response to standard antidepressants in patients with major depressive disorder.
Cussotto, S, Delgado, I, Oriolo, G, Kemper, J, Begarie, D, Dexpert, S, Sauvant, J, Leboyer, M, Aouizerate, B, Martin-Santos, R, et al
Depression and anxiety. 2022
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Plain language summary
Major depressive disorder (MDD) is a leading cause of disability, and antidepressant drug treatment is only effective in over half of patients with a high prevalence of treatment resistance. The importance of nutrition in mental health is gaining recognition. Omega-3 is an essential polyunsaturated fatty acid (PUFA) vital for anti-inflammatory processes and brain integrity. In the absence of the body's ability to make Omega-3, it or its precursors must be acquired from the diet. Yet altered metabolic pathways can hamper the process and the adequate balance with PUFA Omega‐6 is also crucial, as elevated levels of Omega-6 are linked to several diseases. An extensive amount of research suggests that higher Omega-3 levels reduce the occurrence of depression. Yet results using just Omega-3s for depression have been varied. This European-wide study sought to investigate how the PUFA status could affect the clinical response to treatment with antidepressants. 60-adults with an average age of 41 with major depressive disorders received antidepressive treatment. Their red blood cell fatty acids content was determined, and at the end of the 8-week trial treatment responders and non-responders were identified. Findings affirmed the existing knowledge that depressive symptoms are strongly associated with PUFA status. Patients who did not respond to treatment showed low levels of Omega-3 and an unfavourable ratio of Omega-3 to Omega-6 at the start of treatment. Higher levels of Omega-3 fatty acid of DHA seemed to produce a better clinical response to treatments than the Omega-3 of EPA. The authors discussed some potential mechanisms and suggested that PUFA intake and metabolism could be a potential tool for the management of treatment-unresponsive patients with depression. This review highlights the clinical importance of considering PUFA status and metabolism in the support of major depressive disorders.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Healthy eating such as that with low omega-6 diets has more than a physiological result on the human body and carries significant biochemical consequences when the omega-6 to omega-3 ratio is deemed to be ‘high’.
- The result of this research has pharmaceutical implications - if the findings could be imparted to the general public in layman’s terms, practitioners could empower individuals to take greater control of their mental health through more naturalistic means, i.e., optimised nutrition.
- There are wider cognitive considerations of healthy eating beyond that of treating Major Depressive Disorder due to implicated blood-brain-barrier effects, as concluded in this study.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Sixty adults suffering from major depressive disorder (MDD) were recruited into a multicenter study assessing the impact of baseline polyunsaturated (PUFA) levels on responsiveness to antidepressants. Neuropsychiatric evaluations producing MADRS (Montgomery Åsberg Depression Rating Scale) scores at baseline, four weeks and again at eight weeks, were performed. The pre-recorded baseline PUFA levels were then used as an associative and predictive indicator when viewing the end point scoring of participants, thus categorising into responsive and nonresponsive strata.
Of those with low omega-3 and high omega-6 to omega-3 ratio at baseline, there was increased association with ‘non-responsive’ classification at end point (week 8). Participants were deemed ‘non-responsive’ to anti-depressant treatment when scores at week 8 failed to demonstrate ≥50% reduction in MADRS scoring.
Clinical practice applications:
- Clinicians could monitor MDD within at-risk-groups, such as those who are overweight (mean BMI of ALL study participants was 24.20 kg/m2 with a standard deviation of 4.21) or those experiencing an inflammatory state with blood-brain-barrier involvement, as part of a mental ill-health prevention programme.
- When presenting with symptoms of major depressive disorder and prescribing antidepressants, clinicians could recommend increasing consumption of foods high in omega-3 and/or querying the patient about their dietary habits.
- Article supports recommendations for an increase in the consumption of omega-3 rich foods amongst the general population to prevent or intervene in cases of major depressive disorder.
- Wider cognitive implications beyond major depressive disorder in the presence of low omega-3, such as cognitive decline as seen with dementia, theorised due to altered blood-brain-barrier (Cussotto et al., 2022; Gustafson et al., 2020).
Considerations for future research:
- Repeated studies, with normalised distribution of antidepressant and sample size by country, with greater geographic inclusion, along with age categorisation. The broader geographic inclusion is necessary to rule out cultural diets as a confounding variable. An example of how different cultural diets could influence the results, which has potentially been highlighted in this study, is the more predominant consumption of a Mediterranean diet which may have been the case for the participants from Spain or, as could also be the case, an underlying vitamin D deficiency of the participants from Germany.
- Novel studies for assessing diet against mood could be beneficial to fully apply the findings of this study to clinical practice applications and that of the practice of nutritional therapists. The thinking here is the potential for anti-inflammatory foods inducing better mood results through gut-brain axis links and resultant influence on microbiome.
Abstract
BACKGROUND Major depressive disorder (MDD) is characterized by a high rate of treatment resistance. Omega (ω)-3 polyunsaturated fatty acids (PUFAs) were shown to correlate with depressive phenotype both in rodents and in humans. However, few studies to date have investigated the role of PUFAs in antidepressant response. The primary aim of this study was to assess the link between baseline PUFA composition and changes in depressive symptoms as well as antidepressant response in a multicenter study of depressed patients. METHODS Sixty depressed adults who met criteria for MDD according to DSM-IV-TR were recruited. Neuropsychiatric evaluations occurred at baseline and after 4 and 8 weeks of treatment with standard antidepressants, including escitalopram (N = 45), sertraline (N = 13) and venlafaxine (N = 2). At study endpoint, patients were stratified into responders (R) or non-responders (NR) based on their MADRS (Montgomery-Åsberg Depression Rating Scale) score. Baseline PUFA levels were assessed and their association with clinical response was determined. RESULTS Lower ω-3 PUFA levels were associated to worse baseline symptomatology. Baseline levels of PUFAs were significantly different between R and NR, with R exhibiting lower docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and ω-3 index; and higher ω-6/ω-3 ratio than NR before the start of antidepressant treatment. DHA levels as well as the ω-3 index and ω-6/ω-3 ratio significantly predicted response to antidepressants at study endpoint. CONCLUSIONS These results show that baseline levels of PUFAs predict later response to standard antidepressants in depressed subjects. They suggest that PUFA intake and/or metabolism represent a novel modifiable tool for the management of unresponsive depressed patients.
2.
Consumption of 85% cocoa dark chocolate improves mood in association with gut microbial changes in healthy adults: a randomized controlled trial.
Shin, JH, Kim, CS, Cha, L, Kim, S, Lee, S, Chae, S, Chun, WY, Shin, DM
The Journal of nutritional biochemistry. 2022;99:108854
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Free full text
Plain language summary
Disturbances in a person’s mood interrupts their personal well-being and the ability to participate in social interactions, leading to physical health problems such as chronic diseases. The role of diet as a mood regulator has received a great deal of interest. Certain dietary components have been shown to reduce anxiety and depression and improve quality of life. The aim of this study was to investigate the effects of dark chocolate intake on mood in everyday life, with special emphasis on the gut-brain axis. This study is a randomized controlled trial. Participants who met the criteria for eligibility were randomly assigned to one of three groups: (1) control group (CON, n=14); 2) 85% cocoa chocolate group (DC85, n=18); and 3) 70% cocoa chocolate group (DC70, n=16). Results show that daily intake of dark chocolate significantly reduced negative affect in the DC85, but not in the DC70. Furthermore, gut microbial diversity was significantly higher in DC85 than the CON. Authors conclude that dark chocolate has prebiotic effects by restructuring the diversity and composition of the gut microbiome, which may in turn improve mood via the gut-brain axis.
Expert Review
Conflicts of interest:
None
Take Home Message:
- To highlight the potential benefits of high cocoa content dark chocolate in relation to mental states
- To promote more awareness of how dietary habits may impact emotional wellbeing
- To emphasise the importance of microbiota and the gut-brain axis regarding dietary habits.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background
The authors highlight that dark chocolate has been continually identified for its effects on mood. However, there is a dearth of evidence concerning the emotional impact of daily consumption of dark chocolate. Hence, the impact of dark chocolate consumption on daily mood, focusing on the gut-brain axis, is being investigated in this study.
Objectives
- To evaluate the correlation between the effect on emotional state after consuming dark chocolate and the gut microbiota in healthy adults
- To identify alterations in the composition and diversity of the microorganisms in the gastrointestinal tract on account of dark chocolate intake.
Study Design
A randomised controlled trial was performed at Seoul National University from July to December 2017, This involved. consumption of two types of dark chocolate (70% and 85% cocoa content). Subjects in the treatment groups were blinded although investigators and the control cohort were unblinded.
Participants
117 individuals were screened. However, 48 healthy males and females aged 20-30 years were eligible at baseline.
Interventions
- Subjects (n=16): Consumed 30g/day of 70% cocoa chocolate for 3 weeks
- Participants (n=18): Consumed 30g/day of 85% cocoa chocolate for 3 weeks
- Participants (n=14): The control group consumed no chocolate for 3 weeks.
Main Health Outcomes Measured
- Mood states were quantified via the Positive and Negative Affect Schedule in tandem with Microbiota analysis pre- and post-experiment
- Body composition analysis and dietary assessment were also conducted pre- and post-intervention
- Faecal 16S rRNA sequencing analysis of bacterial genomic DNA was conducted for the cohort who consumed 85% cocoa chocolate and the control arm to evaluate the association between the mood-altering effects of dark chocolate and the gut microbiota
- Statistical tests were performed based on intention-to-treat analysis. The Chi-squared test, Kruskal-Wallis test, one-way ANOVA, unpaired t-test and Mann-Whitney U test were employed for inter-group analysis. Spearman's correlation analysis was used to assess the association between gut microbiota composition and mood scores and P<.05 was considered statistically significant.
Results
- Daily intake of dark chocolate substantially diminished negative emotional states in the cohort consuming 85% cocoa content, but not in the 70% cocoa treatment arm
- Gut microbial diversity was substantially greater in the 85% cacao cohort than the control group (P<.05)
- Blautia obeum levels were significantly elevated and Faecalibacterium prausnitzii levels were decreased in the 85% cacao cohort than the control arm (P<.05).
- Furthermore, it was observed that changes in negative affect scores were inversely correlated with diversity and relative abundance of Blautia obeum (P<.05).
Conclusions
The observations suggest that consumption of dark chocolate with a higher cocoa content may induce prebiotic effects due to its capacity to restructure the diversity and composition of the gut microbiota. Furthermore, consuming dark chocolate with a higher cocoa might exert a positive effect on negative emotional states through the gut-brain axis.
Clinical practice applications:
- To inform practitioners of the benefits of 30g/day high (85%) cocoa chocolate consumption and its potential positive impact on mood through the gut-brain axis
- To educate clients regarding the potential benefits of daily high cocoa content chocolate consumption and its possible favourable effect on emotional states associated with gut microbiota.
Considerations for future research:
- More extensive research could investigate interventions of a longer period
- Further studies could evaluate if any difference exists between cocoa and cacao consumption and emotional states via the gut-brain axis, and the strength of any associations
- Interventions could investigate which strains of bacteria that high cocoa content dark chocolate may affect.
Abstract
Dark chocolate has long been recognized for its mood-altering properties; however, the evidence regarding the emotional effects of daily dark chocolate intake is limited. Therefore, we aimed to investigate the effects of dark chocolate intake on mood in everyday life, with special emphasis on the gut-brain axis. Two different dark chocolates (85% and 70% cocoa content) were tested in this study. In a randomized controlled trial, healthy adults (20-30 y) consumed either 30 g/d of 85% cocoa chocolate (DC85, n=18); 70% cocoa chocolate (DC70, n=16); or no chocolate (control group, CON; n=14); for 3 weeks. Mood states were measured using the Positive and Negative Affect Schedule (PANAS). Daily consumption of dark chocolate significantly reduced negative affect in DC85, but not in DC70. To assess the association between the mood-altering effects of dark chocolate and the gut microbiota, we performed fecal 16S rRNA sequencing analysis for the DC85 and CON groups. Gut microbial diversity was significantly higher in DC85 than CON (P<.05). Blautia obeum levels were significantly elevated and Faecalibacterium prausnitzii levels were reduced in DC85 compared to CON (P<.05). Furthermore, we found that the observed changes in negative affect scores were negatively correlated with diversity and relative abundance of Blautia obeum (P<.05). These findings indicate that dark chocolate exerts prebiotic effects, as evidenced by its ability to restructure the diversity and abundance of intestinal bacteria; thus, it may improve negative emotional states via the gut-brain axis.
3.
Gut feelings: A randomised, triple-blind, placebo-controlled trial of probiotics for depressive symptoms.
Chahwan, B, Kwan, S, Isik, A, van Hemert, S, Burke, C, Roberts, L
Journal of affective disorders. 2019;253:317-326
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Plain language summary
Depression is a debilitating psychiatric disorder that is the leading cause of disability world-wide. Multiple causes of depression have been identified, including genetic, neurological, inflammatory, personality, cognitive, and environmental factors. The aim of this study was to investigate the effectiveness of the multispecies probiotic Ecologic® Barrier for reducing symptoms in adults with mild to severe levels of depression. The study was a triple-blinded parallel, placebo-controlled randomised clinical trial. Participants were randomly allocated into two groups; probiotic and placebo. 71 participants with depressive symptoms were recruited and allocated sequentially over 12 months. Results indicate that all participants across both probiotic and placebo groups exhibited a reduction in depressive symptoms over the time-period of the trial. Thus, the routine involved with daily preparation and consumption of the probiotic and scheduled appointments, as well as involvement in these behaviours with the aim of seeking improvement in depressive symptoms had positive impacts on mood, irrespective of whether the probiotic or placebo was consumed. Authors conclude that their findings offer evidence to indicate that probiotic consumption can exert change on cognitive patterns associated with depression.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This study offers evidence to indicate that probiotic consumption can exert change on cognitive patterns associated with depression.
- The study suggests that probiotics, rather than having a direct effect on depressive symptoms, potentially act on immune system activity, inflammation and gut barrier integrity which contribute to the expression of depression.
- Probiotics may be a useful adjunct to potentiate the effects of other therapies, such as CBT.
- This study points to the validity of managing physical health as part of mental health treatment.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
With evidence suggesting that decreased gut barrier function and inflammation are correlated with depression, this study set out to determine the effect of consumption of probiotic supplements on depressive symptoms from a sample of 71 participants with depression. The study was a triple-blinded parallel, placebo-controlled randomised clinical trial conducted over 8 weeks in Australia. Pre and post intervention measures of symptoms and vulnerability markers of depression as well as gut microbiota were compared alongside psychological variables and gut microbiota composition to non-depressed, placebo and probiotic groups. All the clinical trial participants demonstrated an improvement in symptoms – participants in the probiotic group demonstrated a significantly greater reduction in cognitive reactivity compared with the placebo group. Probiotics did not significantly alter the microbiota of depressed individuals, however a significant correlation was found between Ruminococcus gnavus and one of the metrics for depression.
Clinical practice applications:
This study was small and carried out over a short period of time. While significant results were found, which signify potential considerations for clinical practice, the results from this study do not offer evidence that the probiotics used had a direct effect on depressive symptoms – they suggest that probiotics potentially act on cognitive processes contributing to depression which may include immune system activity, inflammation, and gut barrier integrity. Overall, this study offers evidence to indicate that probiotic consumption can exert change on cognitive patterns associated with depression. In clinical practice, probiotics may be a useful adjunct to potentiate the effects of therapies, such as CBT. Finally, the use of probiotics promotes the concept of managing physical health as part of mental health treatment.
Considerations for future research:
These preliminary results are promising and offer a number of future research and clinical avenues to build upon. The results do however, indicate that a longer trial may be needed to fully assess the effects of probiotics on mood and the mechanisms by which probiotics may be influencing this. The study also suggests that further research using a range of concentrations in a dose response study may be warranted to determine the optimal dose; a greater dose over a longer period may produce detectable changes in microbiota as well as further differences in psychological data.
Abstract
BACKGROUND Depression is the leading cause of disability worldwide; with evidence suggesting that decreased gut barrier function and inflammation are correlated with depressive symptoms. We conducted a clinical trial to determine the effect of consumption of probiotic supplements (Winclove's Ecologic® Barrier) on depressive symptoms in a sample of participants with mild to severe depression. METHOD 71 participants were randomly allocated to either probiotic or placebo, which was, consumed daily over eight weeks. Pre- and post-intervention measures of symptoms and vulnerability markers of depression as well as gut microbiota composition were compared. Clinical trial participants were also compared on psychological variables and gut microbiota composition to a non-depressed group (n = 20). RESULTS All clinical trial participants demonstrated improvement in symptoms, suggesting non-specific therapeutic effects associated with weekly monitoring visits. Participants in the probiotic group demonstrated a significantly greater reduction in cognitive reactivity compared with the placebo group, particularly in the mild/moderate subgroup. Probiotics did not significantly alter the microbiota of depressed individuals, however, a significant correlation was found between Ruminococcus gnavus and one depression metric. LIMITATIONS There was a high attrition rate, which may be attributed to weekly monitoring visits. Additionally, modulation of the gut microbiota may need more specific testing to distinguish subtle changes. CONCLUSIONS While microbiota composition was similar between all groups, probiotics did affect a psychological variable associated with susceptibility to depression. Further research is needed to investigate how probiotics can be utilised to modify mental wellbeing, and whether they can act as an adjunct to existing treatments.