Investigating the association between the symptoms of women with Fibromyalgia, Digestive function, and markers of the microbiota of the Gastrointestinal Tract (The FIDGIT Study): study protocol.

BACKGROUND: Fibromyalgia a common idiopathic condition affecting around 1.4% of adults globally. Its signature symptom is chronic widespread pain, with a constellation of somatic and psychological symptoms. Fibromyalgia is associated with significant reductions in quality of life, yet to date there is no biochemical marker for its diagnosis. Previous studies have indicated a strong association with gastrointestinal dysfunction, and more recently, alterations to the gut microbiome. No studies have examined the inter-relationship between fibromyalgia, gastrointestinal dysfunction, and the microbiome. This prospective observational case-controlled study will gather data on gastrointestinal function, dietary intake, fermentation patterns of ingested carbohydrates, and symptoms commonly associated with fibromyalgia. These will be evaluated alongside human gene expression and metatranscriptomic analysis of the oral and faecal microbiome. METHODS: Adult women aged ≥18 years diagnosed with fibromyalgia and/or meeting ACR 2016 criteria, and healthy family or age-matched controls will be recruited from the community. From consenting participants, we will collect detailed survey information and samples of blood, urine, stool, saliva, and breath. DISCUSSION: This is the first prospective study examining interactions between digestive function, human gene expression, and the gut microbiome together with general, and fibromyalgia-specific, symptoms experienced by New Zealand women. This exploration will allow an in-depth understanding of clinically relevant factors that are associated with fibromyalgia and will guide further research and contribute to improved management of this poorly understood condition. TRIAL REGISTRATION: The study was approved by the New Zealand Health and Disability Committee (HDEC) (ref: 20/CEN/197) and registered with the Australia and New Zealand Clinical Trials Registry (ANZCTR), registration number ACTRN12620001337965. Written consent will be obtained after providing participants with detailed information about the procedures. Access to data will be restricted to the immediate research team, and all samples and survey data will be deidentified and coded before analysis.

Persisting Cancer in Black Salve Treated Skin Lesions: Results of a Large 5 Year Retrospective Analysis of Australian Histopathology Specimens.

BACKGROUND: To date there has been minimal research on the use of black salve escharotics. Whether cancer persistence is a frequent finding in treatment areas, the types of lesion being treated by patients, whether rural patients are more likely to use black salve and whether current government prevention initiatives are succeeding are all issues needing investigation. METHODS: This study was a large national retrospective black salve pathology case series from 2015 to 2019. Five private pathology companies with 1471 collection centers located in 5 of the 8 Australian states and Territories provided de-identified skin pathology report information where black salve treatment had been documented in the pathology request. RESULTS: Over the 5-year period 409 patients had treated 475 lesions with black salve. Benign lesions were present at the treatment site in 18% of cases; persisting cancer was found in 34.2% of the remaining black salve treated areas. The majority of treatment areas were located on the head and neck. Black salve caused necrosis of normal tissue when treating benign lesions, refuting claims of cancer specificity. Likelihood of black salve use increased with rurality based on Modified Monash (MM) scores. Black salve use, despite regulatory efforts, appears to be increasing with specimen numbers more than doubling from 2015 to 2019. CONCLUSIONS: Patients undergoing histopathological assessment of black salve treatment areas have high rates of cancer persistence. Patients are applying black salve to benign lesions and lesions in cosmetically sensitive areas. Rural patients have higher proportional rates of black salve use. The increasing incidence of black salve pathology specimens suggests current Australian black salve public health initiatives are failing.

Understanding of black salve toxicity by multi-compound cytotoxicity assays.

BACKGROUND: Black salve is a controversial complementary and alternative medicine (CAM) associated with skin toxicity and skin cancer treatment failures. Black salve formulations vary between manufacturers and contain a number of botanical and synthetic constituents. The skin cancer cytotoxicity of a number of these constituents has not been assessed to date. The alkaloids from the rhizomes of Sanguinaria canadensis, a key black salve ingredient, have had their single compound cytotoxicity assessed; however, whether they possess synergistic cytotoxicity with other compounds has not been studied and is of direct clinical relevance. This research aimed to improve our understanding of the skin cancer cytotoxicity of black salve constituents. METHODS: The cytotoxicity of individual and combination black salve constituents were assessed against the A375 melanoma and A431 squamous cell carcinoma cell lines. Cytotoxicity was determined using the Resazurin assay with fluorescence measured using a Tecan Infinite 200 Pro Microplate reader, compound cytotoxicity being compared to that of the topical cancer therapeutic agent, 5- fluouracil. Docetaxal was used as a positive control. Dunnetts p value was used to determine whether significant synergistic cytotoxicity was present. RESULTS: Sanguinarine was the most cytotoxic compound tested with a 24-hour IC50 of 2.1 µM against the A375 Melanoma cell line and 3.14 µM against the A431 SCC cell line. All black salve constituents showed greater cytotoxicity against the two skin cancer cell lines tested than the skin cancer therapeutic 5-Fluouracil with 24 hours of compound exposure. Chelerythrine and minor Quaternary Benzophenanthridine Alkaloids (QBAs) present in black salve, at concentrations not having a cytotoxic effect by themselves, boosted the cytotoxic effects of sanguinarine. This could be a synergistic rather than additive cytotoxic effect although the synergistic effect was cell line and concentration dependent. CONCLUSIONS: Black salve contains several cytotoxic compounds, a number of which have been found to possess synergistic cytotoxicity for the first time against skin cancer cell lines. In addition, these compounds together increase the overall cytotoxic effect. Assessing multi-compound cytotoxicity in herbal medicine can provide additional information about both their therapeutic and toxicity potential. As black salve is currently being used by patients, further cytotoxicity work should be undertaken to assess whether synergistic cytotoxicity exists when tested in normal skin cells.

Zinc for the prevention or treatment of acute viral respiratory tract infections in adults: a rapid systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To evaluate the benefits and risks of zinc formulations compared with controls for prevention or treatment of acute viral respiratory tract infections (RTIs) in adults. METHOD: Seventeen English and Chinese databases were searched in April/May 2020 for randomised controlled trials (RCTs), and from April/May 2020 to August 2020 for SARS-CoV-2 RCTs. Cochrane rapid review methods were applied. Quality appraisals used the Risk of Bias 2.0 and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Twenty-eight RCTs with 5446 participants were identified. None were specific to SARS-CoV-2. Compared with placebo, oral or intranasal zinc prevented 5 RTIs per 100 person-months (95% CI 1 to 8, numbers needed to treat (NNT)=20, moderate-certainty/quality). Sublingual zinc did not prevent clinical colds following human rhinovirus inoculations (relative risk, RR 0.96, 95% CI 0.77 to 1.21, moderate-certainty/quality). On average, symptoms resolved 2 days earlier with sublingual or intranasal zinc compared with placebo (95% CI 0.61 to 3.50, very low-certainty/quality) and 19 more adults per 100 were likely to remain symptomatic on day 7 without zinc (95% CI 2 to 38, NNT=5, low-certainty/quality). There were clinically significant reductions in day 3 symptom severity scores (mean difference, MD -1.20 points, 95% CI -0.66 to -1.74, low-certainty/quality), but not average daily symptom severity scores (standardised MD -0.15, 95% CI -0.43 to 0.13, low-certainty/quality). Non-serious adverse events (AEs) (eg, nausea, mouth/nasal irritation) were higher (RR 1.41, 95% CI 1.17 to 1.69, NNHarm=7, moderate-certainty/quality). Compared with active controls, there were no differences in illness duration or AEs (low-certainty/quality). No serious AEs were reported in the 25 RCTs that monitored them (low-certainty/quality). CONCLUSIONS: In adult populations unlikely to be zinc deficient, there was some evidence suggesting zinc might prevent RTIs symptoms and shorten duration. Non-serious AEs may limit tolerability for some. The comparative efficacy/effectiveness of different zinc formulations and doses were unclear. The GRADE-certainty/quality of the evidence was limited by a high risk of bias, small sample sizes and/or heterogeneity. Further research, including SARS-CoV-2 clinical trials is warranted. PROSPERO REGISTRATION NUMBER: CRD42020182044.

Honeybee products for the treatment and recovery from viral respiratory infections including SARS-COV-2: A rapid systematic review.

BACKGROUND: This rapid review systematically evaluated the effects of honeybee products compared to controls for the prevention, duration, severity, and recovery of acute viral respiratory tract infections (RTIs), including SARS-CoV-2, in adults and children. METHODS: Cochrane rapid review methods were applied. Four English databases plus preprint servers and trial registries were searched for randomized controlled trials (RCTs). The evidence was appraised and synthesized using RoB 2.0 and GRADE. RESULTS: 27 results were derived from 9 RCTs that included 674 adults and 781 children. In hospitalized adults with SARS-CoV-2, propolis plus usual-care compared to usual-care alone reduced the risk of shock, respiratory failure and kidney injury and duration of hospital admission. Honey was less effective than Guaifenesin for reducing cough severity at 60-minutes in adults with non-specific acute viral RTIs. Compared to coffee, honey plus coffee, and honey alone reduced the severity of post-infectious cough in adults. Honey reduced the duration of cough in children compared to placebo and salbutamol; and the global impact of nocturnal cough after one night compared to usual-care alone and pharmaceutical cough medicines. CONCLUSION: More studies are needed to robustly assess honeybee's role in SARS-CoV-2 and non-specific viral respiratory infections. PROTOCOL REGISTRATION: PROSPERO: CRD42020193847.

Hydrogen-methane breath testing results influenced by oral hygiene.

The measurement of hydrogen-methane breath gases is widely used in gastroenterology to evaluate malabsorption syndromes and bacterial overgrowth. Laboratories offering breath testing provide variable guidance regarding oral hygiene practices prior to testing. Given that oral dysbiosis has the potential to cause changes in breath gases, it raises concerns that oral hygiene is not a standard inclusion in current breath testing guidelines. The aim of this study was to determine how a pre-test mouthwash may impact hydrogen-methane breath test results. Participants presenting for breath testing who had elevated baseline gases were given a chlorhexidine mouthwash. If a substantial reduction in expired hydrogen or methane occurred after the mouthwash, breath samples were collected before and after a mouthwash at all breath sample collection points for the duration of testing. Data were evaluated to determine how the mouthwash might influence test results and diagnostic status. In 388 consecutive hydrogen-methane breath tests, modifiable elevations occurred in 24.7%. Administration of a chlorhexidine mouthwash resulted in significantly (p ≤ 0.05) reduced breath hydrogen in 67% and/or methane gas in 93% of those consenting to inclusion. In some cases, this modified the diagnosis. Mean total gas concentrations pre- and post-mouthwash were 221.0 ppm and 152.1 ppm (p < 0.0001) for hydrogen, and 368.9 ppm and 249.8 ppm (p < 0.0001) for methane. Data suggest that a single mouthwash at baseline has a high probability of returning a false positive diagnosis. Variations in gas production due to oral hygiene practices has significant impacts on test interpretation and the subsequent diagnosis. The role of oral dysbiosis in causing gastrointestinal symptoms also demands exploration as it may be an underlying factor in the presenting condition that was the basis for the referral.

Corrigendum to "Choose your shortcuts wisely: COVID-19 rapid reviews of traditional, complementary and integrative medicine" [Integr Med Res 2020; 9: 100484].

[This corrects the article DOI: 10.1016/j.imr.2020.100484.].

A systematic review of the association between fibromyalgia and functional gastrointestinal disorders.

BACKGROUND: Fibromyalgia and functional gastrointestinal disorders (FGID) including irritable bowel syndrome (IBS) are common conditions presenting in clinical settings and are more prevalent in women. While the relationship between IBS and fibromyalgia has been demonstrated, a review of the prevalence of the broader group of FGID in adults with fibromyalgia has not been undertaken. The aim of this review was to systematically review the published literature, identifying the comorbidity of FGID in people with fibromyalgia, and to discuss the clinical implications, limitations of current research and areas of interest for future research. METHODS: Medline, Embase, CINAHL and Web of Science were searched during June 2019. Results were screened for original research articles meeting established criteria for identification of FGID in adults diagnosed with fibromyalgia. RESULTS: A total of 14 studies involving 1340 adults with fibromyalgia, 363 healthy controls and 441 adults with other pathologies were included in this review. Only 1 of the 14 studies included surveyed the full range of FGID . Functional gut disorders were matched to Rome II criteria for reporting and comparison. In addition to increased abdominal pain and functional bloating or gas, IBS of mixed-pattern and constipation-types appear to be more prevalent than diarrhoea-predominant IBS in adults with fibromyalgia. CONCLUSION: This review confirms previous reports that IBS is common in people living with fibromyalgia and suggests that IBS-mixed and constipation types predominate. An association with a range of FGID other than IBS is suggested, but data are limited. Research exploring the association between fibromyalgia and functional gastrointestinal dysfunction beyond IBS are warranted.

Zinc for the prevention and treatment of SARS-CoV-2 and other acute viral respiratory infections: a rapid review.

BACKGROUND: The global COVID-19 pandemic has prompted an urgent search for interventions to prevent and treat SARS-CoV-2. Higher risk of infection and adverse outcomes coincide with populations with chronic diseases and elderly who are at risk of zinc deficiency. Through several mechanisms zinc may prevent, reduce severity and duration of symptoms. METHOD: An a priori protocol was registered with PROSPERO on 27th April 2020 (CRD42020182044). Eight databases (one Chinese) and four clinical trial registries (one Chinese) were searched for randomised and quasi-randomised controlled trials (RCTs), evaluating single or adjunct zinc against placebo or active controls, for prevention and/or treatment of SARS-CoV-2, other coronaviruses or related infections. RR constraints included not searching bibliographies or contacting authors, single reviewers with calibration and second reviewer checking, meta-analyses and quality appraisal of critical and study primary outcomes only and reporting results as they became available. RESULTS: 118 publications of 1,627 records met the inclusion criteria (35 Chinese and 83 English publications), 32 for prevention, 78 for treatment and 8 for both. Four RCTs specific to SARS-CoV-2 are ongoing; two are investigating zinc for prevention and two for treatment. As of 7 July 2020, no results were available. A wide range of zinc forms, including nasal spray/gel, lozenges, liquid, tablets and intramuscular were investigated. CONCLUSION: Currently, indirect evidence suggests zinc may potentially reduce the risk, duration and severity of SARS-CoV-2 infections, particularly for populations at risk of zinc deficiency including people with chronic disease co-morbidities and older adults. Direct evidence to determine if zinc is effective for either prevention or treatment of SARS-CoV-2 is pending. In the interim, assessing zinc status of people with chronic diseases and older adults, as part of a SARS-CoV-2 clinical work-up, is reasonable as both groups have a higher risk of zinc deficiency/insufficiency and poorer outcomes from SARS-CoV-2.

Choose your shortcuts wisely: COVID-19 rapid reviews of traditional, complementary and integrative medicine.

Background: The COVID-19 pandemic has led to an explosion of rapid reviews geared towards providing time sensitive answers for clinical and policy decision-makers. Rapid reviews (RRs) strike a balance between rigour and rapidity to minimise bias and optimise transparency within specified constraints. Methods: This review article appraised the methods and reporting standards of a convenience sample of RR protocols and RRs of COVID-19 clinical management questions, published in the first six-months of 2020. Inclusion criteria were all RR protocols evaluating traditional, complementary, and integrative medicine (TCIM) registered on PROSPERO, and all RRs indexed on PubMed or published on the Oxford COVID-19 Evidence Service. A purpose-specific 9-item reporting checklist reflecting recommended minimum requirements for RRs was applied. Findings were synthesised and narrated in the context of methodological considerations for conducting and reporting RRs of TCIM. Results: Included studies were five RR protocols of TCIM and 16 RRs, of which five considered TCIM. Wide variations in RR methods were proposed or applied, as were the reporting standards. All five RRs that evaluated TCIM had the lowest reporting standards that limited reproducibility and transparency. Despite accepted recommendations, most RRs did not publish a protocol. Conclusions: We propose that specific research disciplines, such as TCIM, have a uniqueness that may lead to unacceptable outputs if minimum methodological standards are not applied. The recommended minimum requirements will optimise the credibility of rapid reviews of TCIM and limit the risk of prematurely disregarding a potentially effective intervention.

Determining the association between fibromyalgia, the gut microbiome and its biomarkers: A systematic review.

BACKGROUND: The association between fibromyalgia and irritable bowel syndrome is well-established. Alterations in the composition and diversity of the gut microbiome in irritable bowel syndrome have been reported, however, this association is poorly understood in fibromyalgia. Our aim was to summarise the research reporting on the gastrointestinal microbiome and its biomarkers in people with fibromyalgia. METHODS: A systematic review of published original research reporting on the gastrointestinal microbiota and its biomarkers in adults with a diagnosis of fibromyalgia was undertaken. RESULTS: From 4771 studies, 11 met our inclusion criteria and were separated into four main groups: papers reporting Helicobacter pylori; other gut bacterial markers; metabolomics and other biomarkers, which included intestinal permeability and small intestinal bacterial overgrowth. CONCLUSION: The results suggest there is a paucity of quality research in this area, with indications that the gut microbiota may play a role in fibromyalgia within the emerging field of the gut-musculoskeletal axis. Further investigations into the relationship between the gut microbiota, gut dysfunction and fibromyalgia are warranted.

Reply to "Comment on: A Systematic Review of Organic Versus Conventional Food Consumption: Is There a Measurable Benefit on Human Health? Nutrients 2020, 12, 7".

We would like to thank Di Renzo et al [...].

Western herbal medicines in the treatment of irritable bowel syndrome: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy of Western herbal medicines in the treatment of irritable bowel syndrome (IBS). DESIGN: A computer-based search of MEDLINE, EMBASE, CINAHL, AMED, GreenFILE, Health Source: Nursing/Academic Edition, and the Cochrane Library was conducted. A hand-search of the bibliographies of relevant papers and previous meta-analyses and reviews was also undertaken. Trials were included in the review if they were double-blind and placebo-controlled investigating the effects of Western herbal medicines on IBS-related symptoms or quality of life. There were no language restrictions. Eligibility assessment and data extraction were performed by two independent researchers. For herbal medicines where there was more than 1 trial of similar design, data were synthesised using relative risk of symptoms improving using the random effects model. RESULTS: Thirty-three trials were identified that met all eligibility criteria. Seventeen of these evaluated peppermint essential oil, fifteen other Western herbal medicines, and one trial evaluated peppermint oil in one arm and aniseed essential oil in the other arm. Eighteen different herbal preparations were evaluated in these trials. Data suggests that a number of Western herbal medicines may provide relief of IBS symptoms. Meta-analyses suggest that peppermint essential oil is both efficacious and well-tolerated in the short-term management of IBS. Aloe vera and asafoetida also demonstrated efficacy in reducing global IBS symptoms in meta-analyses. The herbal formulas STW 5, STW 5-II and Carmint, along with Ferula assa-foetida, Pimpenella anisum oil, the combination of Curcumin and Foeniculum vulgare oil, and the blend of Schinopsis lorentzii, Aesculus hippocastanum, and peppermint essential oil also demonstrated efficacy in rigorously-designed clinical trials. CONCLUSION: A number of Western herbal medicines show promise in the treatment of IBS. With the exception of peppermint essential oil, Aloe vera, and asafoetida, however, none of the positive trials have been replicated. This lack of replication limits the capacity to make definitive statements of efficacy for these herbal medicines.

Quality of life in people with ongoing symptoms of coeliac disease despite adherence to a strict gluten-free diet.

People with Coeliac disease who suffer persistent symptoms despite adherence to a gluten-free diet are at a greater risk of a reduced health related quality of life. The purpose of this paper is to report the quality of life experienced by this specific group of patients in Australia. A Coeliac Disease Specific Questionnaire (CDQ) was administered to 45 people who were enrolled in a clinical trial and reported persistent symptoms of Coeliac disease despite adherence to a strict gluten free diet. The clinical trial was based in New South Wales, Australia. The instrument used was a subscale and total scores of a CDQ measuring health related quality of life. At baseline the overall mean CDQ score was 147 ± 3.31 (optimum 196) consisting of 4 subscales; gastrointestinal 33 ± 0.88, emotional 32.9 ± 0.99, worries 39.8 ± 0.79 and social 41 ± 6.12 each with a potential score of 49. The health related quality of life of people reporting persistent symptoms of Coeliac disease despite adherence to a gluten free diet is sub-optimal with concerningly low scores for emotional quality.

Increased Posterior Cingulate Functional Connectivity Following 6-Month High-Dose B-Vitamin Multivitamin Supplementation: A Randomized, Double-Blind, Placebo-Controlled Trial.

B vitamins are essential for optimal brain and body function, and are particularly important for cortical metabolic processes that have downstream effects on mitigating oxidative stress. Oxidative stress has been linked to poor psychological outcomes including psychological distress, which has wide-reaching implications for the community and the workplace. Given work-related stress has been associated with poor mental health outcomes, high-dose B vitamin supplementation may be effective in improving brain function and psychological outcomes via attenuation of oxidative stress. This randomized, double-blind, placebo-controlled study investigated psychological outcomes following 6-month supplementation of a high-B-vitamin multivitamin in a large sample of healthy adults (n = 108, aged 30-70 years), as well as changes in default mode network functional connectivity in a subset of the original sample (n = 28). Improvements in occupational stress, general health, perceived stress, depressive symptoms, and mood profiles were identified for both active and placebo groups over time (p < 0.05 corrected). Seed-based functional connectivity analysis centered on the posterior cingulate cortex (PCC) showed that connectivity between the PCC and the caudate increased for the active treatment group, but decreased for the placebo group (p < 0.05 corrected). These findings reveal a substantial intervention effect for both active and placebo treatments, which could in part be associated with a placebo effect in subjective measures. There was, however, a significant treatment effect in the objective measure of functional connectivity, suggesting that reduced psychological stress and high-B-vitamin multivitamin supplementation may lead to an increase in DMN and caudate functional connectivity, which might reflect a strengthening of neurocircuitry within areas associated with reward and emotion at rest. Future studies should consider a placebo run-in methodology to reduce the placebo effect on the subjective measures of stress.

The State of the Evidence for Whole-System, Multi-Modality Naturopathic Medicine: A Systematic Scoping Review.

OBJECTIVE: To summarize the current state of the research evidence for whole-system, multi-modality naturopathic medicine. DESIGN: A systematic search for research articles from around the world was undertaken using MEDLINE, Embase, CINAHL, AMED, and WHO regional indexes. Naturopathic journals and gray literature were hand searched. No language restrictions were imposed. INTERVENTIONS: All human research evaluating the effectiveness of naturopathic medicine, where two or more naturopathic modalities are delivered by naturopathic clinicians, were included in the review. Case studies of five or more cases were included. RESULTS: Thirty-three published studies (n = 9859) met inclusion criteria (11 American; 4 Canadian; 6 German; 7 Indian; 3 Australian; 1 United Kingdom; and 1 Japanese) across a range of mainly chronic clinical conditions. The studies predominantly showed evidence for the efficacy of naturopathic medicine for the conditions and settings in which they were based. CONCLUSIONS: To date, research in whole-system, multi-modality naturopathic medicine shows that it is effective for treating cardiovascular disease, musculoskeletal pain, type 2 diabetes, polycystic ovary syndrome, depression, anxiety, and a range of complex chronic conditions.

A Hierarchy of Healing: Origins of the Therapeutic Order and Implications for Research.

The philosophy, principles, and theories of naturopathic medicine include the six Principles of Naturopathic Medicine and the Therapeutic Order. Together these constructs, describe the core principles of the practice of naturopathic medicine, as established by thought leaders throughout the formation and development of the profession. The naturopathic medicine research agenda (NMRA) set forth recommendations for the codification of the foundational theories of naturopathic medical practice. The "Therapeutic Order, Whole-systems, Evidence-based Research Standards" (TOWERS) initiative is proposed with the primary objective to conduct the rigorous evaluation of the Principles of Naturopathic Medicine and the Therapeutic Order constructs. It is envisioned that this initiative will result in the development of an evidence-base concerning the clinical theory, philosophy and principles of whole-systems naturopathic medicine. After over one hundred years of professional organization and formal practice, there is a need to translate these empirically derived constructs into an evidence-informed theory of naturopathic medicine.

Chronic Psychological Stress Was Not Ameliorated by Omega-3 Eicosapentaenoic Acid (EPA).

Background: Chronic psychological stress and mental health disorders are endemic in Western culture where population dietary insufficiencies of omega-3 fatty acids (n-3FA) from seafood have been observed. Objective: This study was designed to test for a causal relationship between one of the most active components of fish oil, eicosapentaenoic acid (EPA), and chronic psychological stress. Method: A randomized double-blind, placebo-controlled clinical trial with parallel-assignment to two groups was designed (Trial Id: ACTRN12610000404022). The interventions were four EPA-rich fish oil capsules per day, delivering 2.2 g/d EPA (and 0.44 g/d DHA), or identical placebo (low-phenolic olive oil capsules with 5% fish oil to aid blinding). The primary outcome was the between-group difference on the Perceived Stress Scale (PSS-10) after 12 weeks supplementation. An a priori power analysis determined that group sizes of 43 would provide 80% power to detect a significant between-group difference of 12.5%, at α = 0.05. Ninety community members (64 females, 26 males) reporting chronic work stress were recruited via public advertising in northern NSW, Australia. Results: At baseline the omega-3 index (EPA + DHA as % to total fatty acids in red blood cell membranes) was 5.2% in both groups (SD = 1.6% control group; 1.8% active group). After supplementation this remained stable at 5.3% (SD = 1.6%) for the control group but increased to 8.9% (SD = 1.5%) for the active group, demonstrating successful incorporation of EPA into cells. Intention-to-treat (ITT) analysis found no significant between-group differences in PSS outcome scores post-intervention (b = 1.21, p = 0.30) after adjusting for sex (b = 2.36, p = 0.079), baseline PSS (b = 0.42, p = 0.001) and baseline logEPA [b = 1.41, p = 0.185; F(3, 86) = 8.47, p < 0.01, n = 89, R-square = 0.243]. Discussion: Treatment increased cell membrane EPA but, contrary to the hypothesis, there was no effect on perceived stress. Limitations included an imbalance of gender in groups after randomization (68% of the males were in the placebo group). While we found no significant interaction between sex and group on the outcome after adjusting for baseline PSS, larger studies with groups stratified for gender may be required to further confirm these findings. Conclusion: This study demonstrated that 2. 2 g/day of EPA for 12 weeks did not reduce chronic psychological stress.