Depression Inflammation Link

September 30, 2011 Written by JP    [Font too small?]

There are a great many diseases and disorders that come mind when pondering the topic of inflammation. Typically, depression isn’t included in that rather lengthy list. A new review compiled by researchers from the Emory University School of Medicine postulates that there’s reasonable cause to do so. The authors of the paper note that “individuals with major depressive disorder (MDD) demonstrate increased levels of a variety of peripheral inflammatory biomarkers”. If this emerging theory is justified, how can patients and physicians use this information to help alleviate poor mood states? One of the most promising, natural candidates is fish oil.

The omega-3 fatty acids in fish, namely DHA and EPA, are known to decrease pro-inflammatory cytokines present in a variety of diseases, including arthritis. What’s more, reducing inflammation via fish oil supplementation has recently been shown to blunt stress-induced anxiety. But, supplementing with just any fish oil may not be the optimal approach. A recent meta-analysis in the Journal of Clinical Psychiatry recommends looking for omega-3 supplements that contain a minimum of 60% EPA (eicosapentaenoic acid). A daily dosage of up to 2,200 mg of EPA daily is also singled out as important. A separate review from August 2011 revealed similar findings with respect to fish oil therapy in those with bipolar disorder or manic depression. This is not to say that DHA or docosahexaenoic acid is not significant or valuable in it’s own right. For instance, a current study appearing in the British Journal of Nutrition cites that while EPA-rich fish oil was more effective at reducing depressive symptoms, DHA-rich fish oil alone improved cognitive performance (verbal fluency) and “self-reported physical health” in a group of seniors.

Even with all of this encouraging scientific data, it still may be too soon for many conventional psychiatrists to recommend EPA to depressed patients. However, because of fish oil’s other health benefits and relative safety, I would argue that it’s worth considering prior to any future mainstream consensus.

Note: Please check out the “Comments & Updates” section of this blog – at the bottom of the page.

You can find the latest research about this topic there!To learn more about the studies referenced in today’s column, please click on the following links:

Study 1 – Is Depression an Inflammatory Disorder? (link)

Study 2 – Omega-3 Fatty Acids in Juvenile Idiopathic Arthritis: Effect On (link)

Study 3 – Omega-3 Supplementation Lowers Inflammation and Anxiety in Medical (link)

Study 4 – Meta-Analysis of the Effects of Eicosapentaenoic Acid (EPA) in Clinical … (link)

Study 5 – Omega-3 for Bipolar Disorder: Meta-Analyses of Use in Mania and (link)

Study 6 – Effects of N-3 Fatty Acids, EPA v. DHA, On Depressive Symptoms (link)

Study 7 – Fatty Acids From Fish: the Anti-Inflammatory Potential of Long-Chain (link)

Daily EPA Supplementation May Improve Depressive Symptoms

Source: J Clin Psychiatry. 2009 Dec;70(12):1636-44. (link)

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Posted in Alternative Therapies, Mental Health, Nutritional Supplements

24 Comments & Updates to “Depression Inflammation Link”

  1. Orna Izakson, ND, RH (AHG) Says:

    Another great one, JP.

    Question: Aren’t EPA and DHA supposed to interconvert? Obviously there are issues going from ALA to EPA/DHA (as you point out in one of the other articles I’m belatedly reading), but what about between EPA and DHA? I ask this from a practical prescribing standpoint. There are all sorts of products on the market with different levels of this or that, targeting specific people with specific health challenges. I’d just as soon give everyone a good, high-dose fish oil and avoid the hype. Your thoughts?

  2. JP Says:

    Thank you, Orna. Much appreciated! 🙂

    Exactly how much DHA increases EPA is hard to say. One examination states the following:

    “…the estimated extent of DHA retroconversion to EPA was 11.3 and 12.0%, based on the serum and platelet analyses, respectively.” * *

    Generally speaking, a 2:1 to 3:2 ratio of EPA:DHA seems to be a reasonable middle ground, IMO. This would achieve or surpass the above stated depression guidelines, while at the same time allowing enough DHA to (likely) afford some cardiovascular and neurological benefits.

    The fish oil I’m currently using provides a 2:1 ratio (EPA/DHA) along with some added vitamin D.

    Be well!


  3. Orna Izakson, ND, RH (AHG) Says:

    Thanks, JP, that really helps. The fish oil I use is 3:2, but I do tend to dose it high.

  4. JP Says:

    Update: Glucosamine & chondroitin lower systemic inflammation …

    PLoS One. 2015 Feb 26;10(2):e0117534.

    Randomized trial of glucosamine and chondroitin supplementation on inflammation and oxidative stress biomarkers and plasma proteomics profiles in healthy humans.

    BACKGROUND: Glucosamine and chondroitin are popular non-vitamin dietary supplements used for osteoarthritis. Long-term use is associated with lower incidence of colorectal and lung cancers and with lower mortality; however, the mechanism underlying these observations is unknown. In vitro and animal studies show that glucosamine and chondroitin inhibit NF-kB, a central mediator of inflammation, but no definitive trials have been done in healthy humans.

    METHODS: We conducted a randomized, double-blind, placebo-controlled, cross-over study to assess the effects of glucosamine hydrochloride (1500 mg/d) plus chondroitin sulfate (1200 mg/d) for 28 days compared to placebo in 18 (9 men, 9 women) healthy, overweight (body mass index 25.0-32.5 kg/m2) adults, aged 20-55 y. We examined 4 serum inflammatory biomarkers: C-reactive protein (CRP), interleukin 6, and soluble tumor necrosis factor receptors I and II; a urinary inflammation biomarker: prostaglandin E2-metabolite; and a urinary oxidative stress biomarker: F2-isoprostane. Plasma proteomics on an antibody array was performed to explore other pathways modulated by glucosamine and chondroitin.

    RESULTS: Serum CRP concentrations were 23% lower after glucosamine and chondroitin compared to placebo (P = 0.048). There were no significant differences in other biomarkers. In the proteomics analyses, several pathways were significantly different between the interventions after Bonferroni correction, the most significant being a reduction in the “cytokine activity” pathway (P = 2.6 x 10-16), after glucosamine and chondroitin compared to placebo.

    CONCLUSION: Glucosamine and chondroitin supplementation may lower systemic inflammation and alter other pathways in healthy, overweight individuals. This study adds evidence for potential mechanisms supporting epidemiologic findings that glucosamine and chondroitin are associated with reduced risk of lung and colorectal cancer.

    Be well!


  5. JP Says:

    Update 05/18/15:

    J Korean Acad Nurs. 2015 Apr;45(2):221-30.

    Effect and Path Analysis of Laughter Therapy on Serotonin, Depression and Quality of Life in Middle-aged Women.

    PURPOSE: This study was done to examine how laughter therapy impacts serotonin levels, QOL and depression in middle-aged women and to perform a path analysis for verification of the effects.

    METHODS: A quasi-experimental study employing a nonequivalent control group and pre-post design was conducted. Participants were 64 middle-aged women (control=14 and experimental=50 in 3 groups according to level of depression). The intervention was conducted five times a week for a period of 2 weeks and the data analysis was conducted using repeated measures ANOVA, ANCOVA and LISREL.

    RESULTS: Results showed that pre serotonin and QOL in women with severe depression were the lowest. Serotonin in the experimental groups increased after the 10th intervention (p=.006) and the rise was the highest in the group with severe depression (p=.001). Depression in all groups decreased after the 5th intervention (p=.022) and the biggest decline was observed in group with severe depression (p=.007). QOL of the moderate and severe groups increased after the 10th intervention (p=.049), and the increase rate was highest in group with severe depression (p<.006). Path analysis revealed that laughter therapy did not directly affect depression, but its effect was indirectly meditated through serotonin variation (p<.001). CONCLUSION: Results indicate that serotonin activation through laughter therapy can help middle-aged women by lessening depression and providing important grounds for depression control. Be well! JP

  6. JP Says:

    Update 07/15/15:

    Eur Neuropsychopharmacol. 2015 Jun 20.

    Inflammation and clinical response to treatment in depression: A meta-analysis.

    The depressive state has been characterised as one of elevated inflammation, which holds promise for better understanding treatment-resistance in affective disorders as well as for future developments in treatment stratification. Aiming to investigate alterations in the inflammatory profiles of individuals with depression as putative biomarkers for clinical response, we conducted a meta-analyses examining data from 35 studies that investigated inflammation before and after treatment in depressed patients together with a measure of clinical response. There were sufficient data to analyse IL-6, TNFα and CRP. Levels of IL-6 decreased with antidepressant treatment regardless of outcome, whereas persistently elevated TNFα was associated with prospectively determined treatment resistance. Treatment non-responders tended to have higher baseline inflammation, using a composite measure of inflammatory markers. Our findings suggest that elevated levels of inflammation are contributory to treatment resistance. Combining inflammatory biomarkers might prove a useful tool to improve diagnosis and detection of treatment refractoriness, and targeting persistent inflammation in treatment-resistant depression may offer a potential target for the development of novel intervention strategies.

    Be well!


  7. JP Says:

    Update 07/15/15:

    Evid Based Complement Alternat Med. 2015;2015:783761.

    Effect of Astaxanthin Supplementation on Salivary IgA, Oxidative Stress, and Inflammation in Young Soccer Players.

    The physiologic stress induced by physical activity is reflected in immune system perturbations, oxidative stress, muscle injury, and inflammation. We investigated the effect of astaxanthin (Asx) supplementation on salivary IgA (sIgA) and oxidative stress status in plasma, along with changes in biochemical parameters and total/differential white cell counts. Forty trained male soccer players were randomly assigned to Asx and placebo groups. Asx group was supplemented with 4 mg of Asx. Saliva and blood samples were collected at the baseline and after 90 days of supplementation in preexercise conditions. We observed a rise of sIgA levels at rest after 90 days of Asx supplementation, which was accompanied with a decrease in prooxidant-antioxidant balance. The plasma muscle enzymes levels were reduced significantly by Asx supplementation and by regular training. The increase in neutrophil count and hs-CRP level was found only in placebo group, indicating a significant blunting of the systemic inflammatory response in the subjects taking Asx. This study indicates that Asx supplementation improves sIgA response and attenuates muscle damage, thus preventing inflammation induced by rigorous physical training. Our findings also point that Asx could show significant physiologic modulation in individuals with mucosal immunity impairment or under conditions of increased oxidative stress and inflammation.

    Be well!


  8. JP Says:

    Updated 08/06/15:

    Am J Clin Nutr. 2015 Aug;102(2):454-63.

    High glycemic index diet as a risk factor for depression: analyses from the Women’s Health Initiative.

    BACKGROUND: The consumption of sweetened beverages, refined foods, and pastries has been shown to be associated with an increased risk of depression in longitudinal studies. However, any influence that refined carbohydrates has on mood could be commensurate with their proportion in the overall diet; studies are therefore needed that measure overall intakes of carbohydrate and sugar, glycemic index (GI), and glycemic load.

    OBJECTIVE: We hypothesized that higher dietary GI and glycemic load would be associated with greater odds of the prevalence and incidence of depression.

    DESIGN: This was a prospective cohort study to investigate the relations between dietary GI, glycemic load, and other carbohydrate measures (added sugars, total sugars, glucose, sucrose, lactose, fructose, starch, carbohydrate) and depression in postmenopausal women who participated in the Women’s Health Initiative Observational Study at baseline between 1994 and 1998 (n = 87,618) and at the 3-y follow-up (n = 69,954).

    RESULTS: We found a progressively higher dietary GI to be associated with increasing odds of incident depression in fully adjusted models (OR for the fifth compared with first quintile: 1.22; 95% CI: 1.09, 1.37), with the trend being statistically significant (P = 0.0032). Progressively higher consumption of dietary added sugars was also associated with increasing odds of incident depression (OR for the fifth compared with first quintile: 1.23; 95% CI: 1.07, 1.41; P-trend = 0.0029). Higher consumption of lactose, fiber, nonjuice fruit, and vegetables was significantly associated with lower odds of incident depression, and nonwhole/refined grain consumption was associated with increased odds of depression.

    CONCLUSIONS: The results from this study suggest that high-GI diets could be a risk factor for depression in postmenopausal women. Randomized trials should be undertaken to examine the question of whether diets rich in low-GI foods could serve as treatments and primary preventive measures for depression in postmenopausal women.

    Be well!


  9. JP Says:

    Updated 11/10/15:

    J Evid Based Complementary Altern Med. 2015 Nov 5.

    Omega-3 Fatty Acids and Cholesterol Have a Main Role in Antidepression Diet of Iranian Traditional Medicine.

    Depression is one of the major health problems of our world. Recent studies have revealed the relationship between diet and depression. In Iranian traditional medicine, there is a therapeutic diet that is recommended in melancholic diseases like depression. One of the main components of this diet is meat. Meats are divided into 2 groups: recommended and abstinent. The aim of this study was to clarify the logic of this diet through comparing nutritional elements of the 2 groups with each other. For this purpose, prominent books on Iranian traditional medicine were searched for abstinent and recommended meats traditionally prescribed for depressed patients. The results of each group were compared with the other by using Mann-Whitney Test (SPSS version 16). The results showed that recommended meats contain higher amounts of polyunsaturated fatty acids (P = .01) especially omega-3 (P = .03). Both groups contain high amounts of cholesterol. Iranian traditional medicine recommends consumption of meats that contains cholesterol with omega-3 fatty acids in depression.

    Be well!


  10. JP Says:

    Updated 11/30/15:

    Phytother Res. 2015 Nov 27.

    The Role of Curcumin Administration in Patients with Major Depressive Disorder: Mini Meta-Analysis of Clinical Trials.

    Major depression is a common, recurrent, and chronic disease that negatively affects the quality of life and increases the risk of mortality. Several studies have demonstrated that curcumin, the yellow-pigmented substance of the turmeric, possesses antidepressant properties. The aim of this review is to meta-analytically assess the antidepressant effect of curcumin in patients with major depressive disorders. We extensively searched the literature until August 2015. The random-effect model was used to calculate the pooled standardized difference of means (SMD). Subgroup analyses were also performed to examine the effect of different study characteristics on the overall model. Six clinical trials met the inclusion criteria. Overall, curcumin administration showed a significantly higher reduction in depression symptoms [SMD = -0.34; 95% confidence interval (CI) = -0.56, -0.13; p = 0.002]. Subgroup analyses showed that curcumin had the highest effect when given to middle-aged patients (SMD = -0.36; 95% CI = -0.59; -0.13; p = 0.002), for longer duration of administration (SMD = -0.40; 95% CI = -0.64, -0.16; p = 0.001), and at higher doses (SMD = -0.36; 95% CI = -0.59, -0.13; p = 0.002). The administration of new formulation of curcumin (BCM-95) had non-significantly higher effect on depression as compared with the conventional curcumin-piperine formula. We conclude that there is supporting evidence that curcumin administration reduces depressive symptoms in patients with major depression.

    Be well!


  11. JP Says:

    Updated 03/18/16:

    Eur Arch Psychiatry Clin Neurosci. 2016 Mar 16.

    Adjuvant thiamine improved standard treatment in patients with major depressive disorder: results from a randomized, double-blind, and placebo-controlled clinical trial.

    Given that antidepressants (ADs) work slowly, there is interest in means to accelerate their therapeutic effect and to reduce side effects. In this regard, thiamine (vitamin B1) is attracting growing interest. Thiamine is an essential nutrient, while thiamine deficiency leads to a broad variety of disorders including irritability and symptoms of depression. Here, we tested the hypothesis that adjuvant thiamine would reduce depression, compared to placebo. A total of 51 inpatients (mean age: 35.2 years; 53 % females) with MDD (Hamilton Depression Rating Scale score (HDRS) at baseline: >24) took part in the study. A standardized treatment with SSRI was introduced and kept at therapeutic levels throughout the study. Patients were randomly assigned either to the thiamine or the placebo condition. Experts rated (HDRS) symptoms of depression at baseline, and after 3, 6, and 12 weeks (end of the study). Between baseline and the end of the study, depression had reduced in both groups. Compared to placebo, adjuvant thiamine improved symptoms of depression after 6 week of treatment, and improvements remained fairly stable until the end of the study, though mean differences at week 12 were not statistically significant anymore. No adverse side effects were reported in either group. Results suggest that among younger patients with MDD adjuvant thiamine alleviated symptoms of depression faster compared to placebo. Importantly, improvements were observed within 6 weeks of initiation of treatment. Thus, thiamine might have the potential to counteract the time lag in the antidepressant effects of ADs.

    Be well!


  12. JP Says:

    Updated 03/130/16:

    Transl Psychiatry. 2016 Mar 15;6:e756.

    Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder.

    Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been proposed as (adjuvant) treatment for major depressive disorder (MDD). In the present meta-analysis, we pooled randomized placebo-controlled trials assessing the effects of omega-3 PUFA supplementation on depressive symptoms in MDD. Moreover, we performed meta-regression to test whether supplementation effects depended on eicosapentaenoic acid (EPA) or docosahexaenoic acid dose, their ratio, study duration, participants’ age, percentage antidepressant users, baseline MDD symptom severity, publication year and study quality. To limit heterogeneity, we only included studies in adult patients with MDD assessed using standardized clinical interviews, and excluded studies that specifically studied perinatal/perimenopausal or comorbid MDD. Our PubMED/EMBASE search resulted in 1955 articles, from which we included 13 studies providing 1233 participants. After taking potential publication bias into account, meta-analysis showed an overall beneficial effect of omega-3 PUFAs on depressive symptoms in MDD (standardized mean difference=0.398 (0.114-0.682), P=0.006, random-effects model). As an explanation for significant heterogeneity (I(2)=73.36, P<0.001), meta-regression showed that higher EPA dose (β=0.00037 (0.00009-0.00065), P=0.009), higher percentage antidepressant users (β=0.0058 (0.00017-0.01144), P=0.044) and earlier publication year (β=-0.0735 (-0.143 to 0.004), P=0.04) were significantly associated with better outcome for PUFA supplementation. Additional sensitivity analyses were performed. In conclusion, present meta-analysis suggested a beneficial overall effect of omega-3 PUFA supplementation in MDD patients, especially for higher doses of EPA and in participants taking antidepressants. Future precision medicine trials should establish whether possible interactions between EPA and antidepressants could provide targets to improve antidepressant response and its prediction. Furthermore, potential long-term biochemical side effects of high-dosed add-on EPA supplementation should be carefully monitored.

    Be well!


  13. JP Says:

    Updated 05/08/16:

    Psychiatry Res. 2016 Apr 26;241:47-54.

    Exercise improves physical and psychological quality of life in people with depression: A meta-analysis including the evaluation of control group response.

    Exercise has established efficacy as an antidepressant in people with depression. However, few meta-analyses have assessed the effects of exercise across different domains of Quality of Life (QoL) in people with depression. Furthermore, there has been no previous meta-analysis of control group response in relation to QoL in exercise trials for depression. Randomized Clinical Trials(RCTs) were initially identified from a Cochrane review, and those including QoL assessments were included in the analysis. Search of major electronic databases were conducted to identify RCTs that compared the exercise effects on QoL versus control condition in people with depression. A random effects meta-analysis was employed to evaluate the Standardized Mean Difference (SMD). Six RCTs were included. Exercise significantly improved physical and psychological domains and overall QoL. Effects on social relationship and environment domains were not significant. No significant control group response was found for any domain or overall QoL. Exercise can be considered as a therapeutic strategy to improve physical and psychological domains and overall QoL of people with depression, with no effect evident across the social and environmental domains. The lack of improvement among control groups reinforces the role of exercise as a treatment for depression with benefits to QoL.

    Be well!


  14. JP Says:

    Updated 09/17/16:

    Lipids Health Dis. 2016 Sep 15;15(1):156.

    Association between frequency of fried food consumption and resilience to depression in Japanese company workers: a cross-sectional study.

    BACKGROUND: Long-chain n-3 and n-6 polyunsaturated fatty acids (LC n-3/n-6 PUFA) play important roles in emotional regulation. We previously reported an association between fish consumption, which is major source of LC n-3 PUFA, and resilience to depression, where resilience is the ability to cope with stress in the face of adversity. Although the traditional Japanese dietary pattern of high fish consumption is associated with low depressive symptoms, the current Japanese diet pattern has become westernized. Westernized diets contain excessive amounts of LC n-6 PUFA due to high intake of vegetable oils commonly used in fried food and are associated with risk of depression. The aim of this study was to examine the association between frequency of fried food consumption and resilience to depression.

    METHODS: Participants were 715 Japanese company workers. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to measure depressive symptoms, and the 14-item Resilience Scale (RS-14) was used to measure resilience. Frequency of fish and fried food consumption was assessed using a self-report questionnaire based on the Food Frequency Questionnaire. Regression analyses using Preacher and Hayes’ bootstrap script were used to adjust for demographic factors, frequency of physical exercise, and fish consumption.

    RESULTS: Significant associations were identified between frequency of fried food consumption and total CES-D score (path c, B = 0.72; P < 0.01), between frequency of fried food consumption and total RS-14 score (path a, B = -1.73, P < 0.01), and between total RS-14 score and CES-D score (path b, B = -0.35; P < 0.01). The association between fried food consumption and total CES-D score was not significant when we controlled for RS-14 score. Bootstrapping results showed that there was a significant positive indirect association between frequency of fried food and CESD score through RS-14 (95 % bias-corrected and accelerated confidence interval = 0.34 to 0.92). CONCLUSION: Frequency of fried food consumption was associated with lower resilience to depression. Further nutritional interventional studies to increase resilience and prevent depression are warranted. Be well! JP

  15. JP Says:

    Updated 09/27/16:

    Prostaglandins Leukot Essent Fatty Acids. 2016 Mar;106:19-25.

    Polyunsaturated fatty acids moderate the effect of poor sleep on depression risk.

    Although potentially modifiable risk factors for interferon-alpha (IFN-α)-associated depression (IFN-MDD) have been identified, it is not currently known how they interact to confer risk. In the present study we prospectively investigated interactions among poor sleep quality, high-stress, pre-existing depressive symptoms, and polyunsaturated fatty acid status. Non-depressed hepatitis C patients (n=104) were followed prospectively during IFN-α therapy. IFN-MDD occurs in 20-40% of patients and was diagnosed using the Structured Clinical Interview of DSM-IV (SCID-IV), with incidence examined using Cox regression. Baseline Pittsburgh Sleep Quality Inventory (PSQI), Perceived Stress Scale (PSS), Beck Depression Inventory (BDI), and a range of plasma long-chain fatty acid levels were measured (gas chromatography) – focusing on the ratio of arachidonic acid (AA) to docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) (AA/EPA+DHA). The AA/EPA+DHA ratio (Β=0.40 ± 0.16; p=0.006), PSQI (Β=0.12 ± 0.04; p=0.001), PSS (Β=0.07 ± 0.02; p<0.001), and baseline BDI (Β=0.05 ± 0.02; p<0.001) each individually predicted IFN-MDD incidence. In step-wise Cox regression eliminating non-significant variables, two interactions remained significantly predictive: PSQI*AA/EPA+DHA (p=0.008) and PSS*AA/EPA+DHA (p=0.01). Receiver Operator Curves (ROC) were used to examine the specificity and sensitivity of IFN-MDD prediction. When sleep was normal (PSQI<5), AA/EPA+DHA was strongly predictive of IFN-MDD (AUC=91 ± 6; p=0.002). For example, among those with AA/EPA+DHA less than the median (4.15), none with PSQI<5 developed depression. Conversely, neither PSS nor PSQI was statistically associated with depression risk in those with an elevated AA/EPA+DHA ratio. These data demonstrate that the AA/EPA+DHA ratio moderates the effect of poor sleep on risk for developing IFN-MDD and may have broader implications for predicting and preventing MDD associated with inflammation.

    Be well!


  16. JP Says:

    Updated 02/27/17:

    Nutr Neurosci. 2017 Feb 22:1-5.

    Adjunctive low-dose docosahexaenoic acid (DHA) for major depression: An open-label pilot trial.

    OVERVIEW: Whilst the majority of evidence supports the adjunctive use of eicosapentaenoic acid (EPA) in improving mood, to date no study exists using low-dose docosahexaenoic acid (DHA) alone as an adjunctive treatment in patients with mild to moderate major depressive disorder (MDD).

    METHODS: A naturalistic 8-week open-label pilot trial of low-dose DHA, (260 mg or 520 mg/day) in 28 patients with MDD who were non-responsive to medication or psychotherapy, with a Hamilton Depression Rating Scale (HAM-D) score of greater than 17, was conducted. Primary outcomes of depression, clinical severity, and daytime sleepiness were measured.

    RESULTS: After 8 weeks, 54% of patients had a ≥50% reduction on the HAM-D, and 45% were in remission (HAM-D ≤ 7). The eta-squared statistic (0.59) indicated a large effect size for the reduction of depression (equivalent to Cohen’s d of 2.4). However confidence in this effect size is tempered due to the lack of a placebo. The mean score for the Clinical Global Impression Severity Scale was significantly improved by 1.28 points (P < 0.05). Despite a significant reduction in the HAM-D score for middle insomnia (P = 0.02), the reduction in excessive daytime somnolence on the total Epworth Sleepiness Scale (ESS) did not reach significance. No significant adverse reactions to DHA were found. CONCLUSION: Within the major limits of this open-label pilot study, the results suggest that DHA may provide additional adjunctive benefits in patients with mild- to -moderate depression. Be well! JP

  17. JP Says:

    Updated 09/01/17:

    J Educ Health Promot. 2017 Aug 9;6:76.

    Effect of yoga training on inflammatory cytokines and C-reactive protein in employees of small-scale industries.

    OBJECTIVE: The present study intends to see the effect of yoga practices on lipid profile, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and high-sensitivity-C-reactive protein (hs-CRP) among apparently healthy adults exposed to occupational hazards.

    MATERIALS AND METHODS: In the present study, 48 participants aged 30-58 years (41.5 ± 5.2) who were exposed to occupational hazards were randomized into two groups, that is, experimental and wait-list control. All the participants were assessed for lipid profile, IL-6, TNF-α, and hs-CRP at the baseline and after completion of 3 months of yoga training intervention. The experimental group underwent yoga training intervention for 1 h for 6 days a week for 3 months, whereas control group continued with their daily activities except yoga training. Data analysis was done using statistical software SPSS Version 20.0. Data were analyzed using paired t-tests and independent t-test.

    RESULTS: The results of within group comparison revealed highly significant changes in cholesterol (P < 0.001), high-density lipoprotein (P < 0.001), low-density lipoprotein (LDL)(P < 0.01), hs-CRP (P < 0.01), IL-6 (P < 0.001), and TNF-α (P < 0.001) in experimental group. Comparison between experimental and control group revealed significant changes in cholesterol (P < 0.01), LDL (P < 0.05), IL-6 (P < 0.01), TNF-α (P < 0.01), and hs-CRP (P < 0.01). CONCLUSION: A yoga-based lifestyle intervention seems to be a highly promising alternative therapy which favorably alters inflammatory markers and metabolic risk factors. Be well! JP

  18. JP Says:

    Updated 12/08/17:

    Nutr Neurosci. 2017 Dec 7:1-14.

    A Mediterranean-style dietary intervention supplemented with fish oil improves diet quality and mental health in people with depression: A randomized controlled trial (HELFIMED).

    OBJECTIVES: We investigated whether a Mediterranean-style diet (MedDiet) supplemented with fish oil can improve mental health in adults suffering depression.

    METHODS: Adults with self-reported depression were randomized to receive fortnightly food hampers and MedDiet cooking workshops for 3 months and fish oil supplements for 6 months, or attend social groups fortnightly for 3 months. Assessments at baseline, 3 and 6 months included mental health, quality of life (QoL) and dietary questionnaires, and blood samples for erythrocyte fatty acid analysis.

    RESULTS: n = 152 eligible adults aged 18-65 were recruited (n = 95 completed 3-month and n = 85 completed 6-month assessments). At 3 months, the MedDiet group had a higher MedDiet score (t = 3.95, P < 0.01), consumed more vegetables (t = 3.95, P < 0.01), fruit (t = 2.10, P = 0.04), nuts (t = 2.29, P = 0.02), legumes (t = 2.41, P = 0.02) wholegrains (t = 2.63, P = 0.01), and vegetable diversity (t = 3.27, P < 0.01); less unhealthy snacks (t = -2.10, P = 0.04) and red meat/chicken (t = -2.13, P = 0.04). The MedDiet group had greater reduction in depression (t = -2.24, P = 0.03) and improved mental health QoL scores (t = 2.10, P = 0.04) at 3 months. Improved diet and mental health were sustained at 6 months. Reduced depression was correlated with an increased MedDiet score (r = -0.298, P = 0.01), nuts (r = -0.264, P = 0.01), and vegetable diversity (r = -0.303, P = 0.01). Other mental health improvements had similar correlations, most notably for increased vegetable diversity and legumes. There were some correlations between increased omega-3, decreased omega-6 and improved mental health. DISCUSSION: This is one of the first randomized controlled trials to show that healthy dietary changes are achievable and, supplemented with fish oil, can improve mental health in people with depression. Be well! JP

  19. JP Says:

    Updated 03/20/18:

    Nutr Res. 2018 Feb 13.

    A diet high in carotenoid-rich vegetables and fruits favorably impacts inflammation status by increasing plasma concentrations of IFN-α2 and decreasing MIP-1β and TNF-α in healthy individuals during a controlled feeding trial.

    The health benefits of vegetable and fruit (VF) intake include benefits for diseases that have an inflammatory component, although the relationship between VF intake and systemic inflammatory status is unclear due to the lack of comprehensive analysis of inflammatory markers in most studies. Therefore, our hypothesis was that the consumption of carotenoid-rich vegetables and fruits in the diet would have a beneficial effect on systemic inflammation status. In this study, we determined the association between varying doses of carotenoid-rich VF intake, plasma carotenoids, and a broad array of markers including 26 cytokines and high-sensitivity C-reactive protein. Data were derived from a single-arm controlled clinical feeding trial in which healthy, nonobese individuals received a low-carotenoid prescription for 6 weeks and then consumed a provided high-VF diet for 8 weeks. Proinflammatory cytokines and plasma carotenoids were measured at baseline, at 6 weeks, and at the end of the 8-week feeding period. Maximum likelihood estimation was used to calculate overall correlations between total plasma carotenoid concentrations and the cytokines. Plasma carotenoids decreased during the low-carotenoid treatment and increased during the feeding treatment. Of the inflammatory markers measured, we found increased plasma concentrations of interferon α-2 (P = .003) and decreased macrophage inflammatory protein-1β (P = .027) and tumor necrosis factor-α (P = .012) after consumption of the carotenoid-rich diet. These results indicate that consumption of VF may be important in the maintenance of beneficial inflammatory homeostasis.

    Be well!


  20. JP Says:

    Updated 04/28/18:

    Molecules. 2018 Apr 24;23(5).

    Dietary Polyphenol Intake and Depression: Results from the Mediterranean Healthy Eating, Lifestyle and Aging (MEAL) Study.

    Background: The epidemiological evidence for a relation between dietary polyphenol intake and depression is limited. Therefore, the aim of this study was to assess the association between habitual dietary intake of total polyphenols, their classes, subclasses and individual compounds and depressive symptoms among the participants of the Mediterranean healthy Eating, Lifestyle and Aging (MEAL) study. Methods: Demographic and dietary characteristics of 1572 adults living in southern Italy were analyzed. Food frequency questionnaires and Phenol-Explorer were used to calculate habitual dietary intakes of polyphenols. The Center for Epidemiologic Studies Depression Scale (CES-D-10) was used as screening tool for depressive symptoms. Multivariate logistic regression analyses were used to test associations and were expressed as odds ratio (OR) and 95% confidence intervals (CI). Results: A total of 509 individuals reported having depressive symptoms. Based on multivariate logistic regression analyses, total polyphenol intake was not associated with depressive symptoms. After adjustment for potential confounding factors, dietary intake of phenolic acid (OR = 0.64, 95% CI: 0.44, 0.93), flavanones (OR = 0.54, 95% CI: 0.32, 0.91), and anthocyanins (OR = 0.61, 95% CI: 0.42, 0.89) showed significant inverse association with depressive symptoms, when comparing the highest with the lowest quartile. Moreover, flavanones and anthocyanins, were associated with depressive symptoms in a dose-response manner. Among individual compounds, inverse association was observed for quercetin (OR = 0.53, 95% CI: 0.32, 0.86) and naringenin (OR = 0.51, 95% CI: 0.30, 0.85), for the highest versus lowest quartile of intake. When taking into consideration the major sources of the polyphenols, only citrus fruits and wine consumption was inversely associated with depressive symptoms (Q4 vs. Q1: OR= 0.51, 95% CI: 0.35, 0.75; Q4 vs. Q1: OR = 0.53, 95% CI: 0.38, 0.74, respectively). Conclusions: Higher dietary intake of flavonoid may be inversely associated with depressive symptoms. Further studies are needed to definitively confirm these observed associations.

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  21. JP Says:

    Updated 06/22/18:

    Iran J Public Health. 2018 Apr;47(4):575-583.

    Long Chain n-3 Fatty Acids Improve Depression Syndrome in Type 2 Diabetes Mellitus.

    Background: Type 2 diabetes mellitus (T2DM) is commonly associated with depressive symptoms, which affect prognosis and quality of life. We investigated the antidepressant effects of n-3 fatty acids (n-3FAs) monotherapy (without conventional antidepressants) for T2DM patients with mild to moderate depressive symptoms.

    Methods: A 10-wk, placebo-controlled, double-blind, parallel-group (1:1 ratio) randomized trial of n-3FAs (2700 mg/day EPA: DHA ratio=2) versus placebo in 88 Iranian diabetic patients with mild to moderate depression based on Beck Depression Inventory II (BDI-II-PERSIAN) was conducted. This study started from July 2014 to January 2015 in Tehran University of Medical Sciences, Tehran, Iran. The primary event was defined as worsened, non-changed, or inconsiderably improved depression (<5 unit decrease in BDI-II-PERSIAN depression scores after treatment) ( Identifier: NCT02261545).

    Results: Randomly, 44 T2DM patients were treated with n-3FAs supplements and 44 cases received placebo (three patients discontinued). n-3FAs could significantly protect patients against the aforesaid event and exhibit satisfactory prevention (number needed to treat with 95% confidence interval: 2.52, 1.71-4.74). No serious adverse reactions were reported.

    Conclusion: n-3FAs supplementation had significant antidepressant effects in T2DM patients with mild to moderate depressive symptoms, not confounded by metabolic factors and disease duration.

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  22. JP Says:

    Updated 01/08/19:

    J Affect Disord. 2018 Dec 26;246:586-594.

    Gut permeability and depressive symptom severity in unmedicated adolescents.

    OBJECTIVE: This study examined gut permeability in unmedicated adolescents with and without major depressive disorder.

    METHOD: Medically healthy, non-medicated, 12-17 year-old females in a major depressive episode (MDE) or healthy controls, without any psychiatric condition, were enrolled. They completed the Children’s Depression Rating Scale-Revised (CDRS-R) and underwent a clinical interview. Preejection period (PEP) and respiratory sinus arrhythmia (RSA) data were collected to measure autonomic nervous system activity. Following an overnight fast, participants ingested lactulose and mannitol and collected urine for 4 hours while still fasting, to examine gut permeability. Plasma cytokines (interleukin 1β, interleukin 6, and tumor necrosis factor α) were measured. Correlational analyses were used to examine the associations between relevant variables.

    RESULTS: 41 female participants (age: 14.8 ± 1.6 years, n = 25 with MDE) were enrolled. PEP, but not RSA, was inversely associated with neurovegetative symptom severity on the CDRS-R (r = -0.31, p < 0.06). In the 30 participants with gut permeability data, the lactulose to mannitol ratio (LMR) was significantly positively associated with depression severity, particularly neurovegetative symptom severity (r = 0.37, p < 0.05). Notably, the association between neurovegetative symptom severity and PEP was substantially reduced after adjusting for LMR. Additionally, depression severity was significantly associated with circulating cytokines. CONCLUSIONS: This is the first study to examine gut permeability in unmedicated adolescents, offering preliminary support for a mechanistic pathway linking sympathetic nervous system activation to increased gut permeability and activation of the innate immune system, likely contributing to the emergence of neurovegetative symptoms of depression. Be well! JP

  23. JP Says:

    Updated 01/14/19:

    Biol Res Nurs. 2018 Dec 20:1099800418820162.

    Impact of Yoga on Inflammatory Biomarkers: A Systematic Review.

    BACKGROUND: Many chronic conditions, including heart disease, cancer, and rheumatoid arthritis, are associated with underlying chronic inflammatory processes. Literature reviews have analyzed a variety of integrative therapies and their relationships with chronic inflammation. This systematic review is unique in reporting solely on yoga’s relationship with inflammation. Its purpose was to synthesize current literature examining the impact of yoga interventions on inflammatory biomarkers in adults with chronic inflammatory-related disorders.

    METHOD: Searches of several electronic databases were conducted. Inclusion criteria were (a) English language, (b) sample age >18 years old, (c) yoga interventions involving postures with or without yoga breathing and/or meditation, and (d) measured inflammatory biomarkers.

    RESULTS: The final review included 15 primary studies. Of these, seven were rated as excellent and eight as average or fair. There was considerable variability in yoga types, components, frequency, session length, intervention duration, and intensity. The most common biomarkers measured were interleukin-6 ( n = 11), C-reactive protein ( n = 10), and tumor necrosis factor ( n = 8). Most studies reported positive effects on inflammatory biomarkers ( n = 11) from baseline to post yoga intervention. Analysis of the dose showed higher total dose (>1,000 min) resulted in greater improvements in inflammation.

    CONCLUSION: This review suggests that yoga can be a viable intervention to reduce inflammation across a multitude of chronic conditions. Future studies with detailed descriptions of yoga interventions, measurement of new and well-established inflammatory biomarkers, and larger sample sizes are warranted to advance the science and corroborate results.

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  24. JP Says:

    Updated 03/21/19:

    Physiol Int. 2019 Mar 19:1-11.

    Pycnogenol supplementation as an adjunct treatment for antidepressant-induced sexual dysfunction.

    INTRODUCTION: Major depressive disorder is a serious mental disorder in which treatment with antidepressant medication is associated with incidence of adverse events, such as constipation, diarrhea, dry mouth, headache, insomnia, and sexual dysfunction (SDys). Escitalopram (ESC), an effective and safe selective serotonin reuptake inhibitor with good tolerability, was used in this study. In this study, we investigated the prospective effect of Pycnogenol (PYC), an antioxidant, anti-inflammatory, and vasodilator agent, on ESC-induced SDys.

    METHODS: This was a randomized, parallel, open-label study. Seventy-two outpatients of both genders with depression were randomized into two groups as follows: 37 patients from the ESC + PYC group took 50 mg of PYC per day for 4 months in ESC co-treatment, and 35 subjects from the ESC group took ESC only. Five patients dropped out and were excluded from the analysis. The participants were examined every month (visits 1-4).

    RESULTS: ESC use led to improvement of depressive symptoms and severity scored by standardized psychiatric tests. PYC co-treatment resulted in attenuation of SDys beginning at 1 month of treatment and continuing for two consecutive months. Furthermore, an increase in heart rate in the PYC group was registered.

    CONCLUSIONS: We propose that PYC-mediated SDys attenuation is based on its ability to improve endothelial functions by its antioxidant, anti-inflammatory, vasodilatory, and anticoagulant action. We assume that the action of PYC on heart rate is in accordance with the aforementioned vasodilatory action of PYC and consequent baroreflex-mediated heart rate response. PYC co-treatment reduced ESC-induced SDys and elevated heart rate.

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