Differences between Japan and Taiwan in the treatment of pregnant women with depressive symptoms by omega-3 fatty acids: An open-label pilot study.

OBJECTIVES: Although safe approaches for improving depression in pregnancy are required and the efficacy of omega-3 polyunsaturated fatty acids (PUFAs) has been suggested, the amount of supplemental omega-3 PUFAs has varied among previous studies and adequate amount might be different among countries. The aim of this pilot study is to explore the feasibility of using 1800 mg of omega-3 PUFAs supplementation for our future double-blind, placebo-control trial, and to clarify the clinical difference and the similarity between two sites of Japan and Taiwan. METHODS: Pregnant women between 12 and 24 weeks' gestation with depressive symptoms were recruited. Participants were supplemented daily with omega-3 PUFAs capsules containing 1206 mg eicosapentaenoic acid and 609 mg docosahexaenoic acid for 12 weeks. The primary outcome was change in total score on the 17-item Hamilton Rating Scale for Depression (HAMD) at 12 weeks after supplementation. RESULTS: Eight pregnant women in Japan and five in Taiwan participated in the study. A substantial proportion of pregnant women reported high consumption of omega-3 supplements and dietary fish were excluded in Taiwan rather than in Japan sites. The decrease in HAMD score from baseline to 12 weeks after the start of the intervention was significantly larger in Japanese participants than in Taiwanese participants (Wilcoxon rank sum test; P = 0.045). DISCUSSION: The improvement of depressive symptoms was smaller at the Taiwan site than at the Japan site. Differences in psychopathology of recruited participants identified by self-rating scales might affect the degree of population heterogeneity and the treatment efficacy. A randomized-controlled trial is needed to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01948596.

Plasma levels of n-3 fatty acids and risk of coronary heart disease among Japanese: The Japan Public Health Center-based (JPHC) study.

BACKGROUND AND AIMS: Higher intake of fish or n-3 polyunsaturated fatty acids (PUFAs) has been associated with reduced risk of coronary heart disease (CHD). However, it is unclear whether increased blood levels of n-3 PUFAs are associated with reduced risk of CHD in the Japanese population. METHODS: The relationship between circulating levels of n-3 PUFAs (eicosapentaenoic acid + docosapentaenoic acid + docosahexaenoic acid) and risk of CHD was examined in a nested case-control study among participants in the Japan Public Health Center (JPHC)-based Study Cohort. Plasma n-3 PUFA phospholipid levels were measured at baseline by gas chromatography in 209 cases with CHD and 418 controls matched for sex, age, date of blood draw, time elapsed since last meal before blood collection, and study location. The CHD cases (n = 209) comprised 168 cases of myocardial infarction and 41 of sudden cardiac death, otherwise classified as 157 non-fatal and 52 fatal coronary events, respectively. Mean duration of follow-up was 13.5 years. RESULTS: Multivariate conditional logistic analysis showed no significant association between n-3 PUFAs and risk of total CHD. The odds ratio (OR) for the highest versus lowest quartiles of plasma n-3 PUFAs was 0.79 (95% confidence interval [95% CI]: 0.41-1.51, p for trend = 0.51). Subtype analysis of CHD revealed that the multivariate ORs for the highest versus lowest quartiles for n-3 PUFAs were 0.91 (95% CI: 0.43-1.89, p for trend = 0.90) for myocardial infarction, 0.08 (95% CI: 0.01-0.88, p for trend = 0.04) for sudden cardiac death, 0.89 (95% CI: 0.42-1.89, p for trend = 0.97) for nonfatal coronary events, and 0.12 (95% CI: 0.02-0.75, p for trend = 0.03) for fatal coronary events. CONCLUSIONS: Plasma n-3 PUFA levels were not associated with risk of total CHD but were inversely associated with risks of sudden cardiac death and fatal coronary events among middle-aged Japanese individuals.

Limited effect of omega-3 fatty acids on the quality of life in survivors of traumatic injury: A randomized, placebo-controlled trial.

Empirical evidence is divided on whether n-3 polyunsaturated fatty acid levels are associated with quality of life (QOL). This study investigated the effects of docosahexaenoic acid (DHA) supplementation on QOL in survivors of traumatic injury. In this secondary analysis of a double-blind, randomized controlled trial, we recruited 110 trauma patients (82% men; mean age, 39.6 years) in an intensive care unit. Fifty-three received DHA-rich supplements and 57 received placebo for 12 weeks. We used the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) to assess QOL at the end of intervention. DHA did not significantly affect any QOL domain on the SF-36 after 12 weeks. In the DHA group, changes in the erythrocyte levels of eicosapentaenoic acid (EPA) + DHA and EPA were positively correlated with the SF-36 mental component. DHA did not influence QOL of trauma patients, but increased EPA levels during the trial were associated with better QOL in patients receiving omega-3.

Effects of omega-3 polyunsaturated fatty acids on psychophysiological symptoms of post-traumatic stress disorder in accident survivors: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Psychophysiological symptoms (e.g., pounding heart) are known to be a prominent feature of post-traumatic stress disorder (PTSD). Although omega-3 polyunsaturated fatty acids (PUFAs) have a beneficial potential pharmacological effect of preventing these psychophysiological symptoms, no clinical data is yet available. Therefore, we conducted a randomized, double-blind, placebo-controlled trial of Japanese accident survivors. METHODS: A total of 83 participants received either omega-3 PUFAs (1470mg docosahexaenoic acid and 147mg eicosapentaenoic acid per day) or placebo within 10 days of the accidental injury. After 12-week supplementation, participants performed script-driven imagery of their traumatic event during monitoring of their heart rate and skin conductance. RESULTS: Analysis revealed that heart rate during both rest and script-driven imagery was significantly lower in the omega-3 group than the placebo group, whereas baseline heart rate was comparable between the two groups. LIMITATIONS: The present trial was conducted at a single-center in Japan and psychophysiological symptoms of PTSD in most participants were not serious. CONCLUSION: These findings suggest that post-trauma supplementation of omega-3 PUFAs might be effective for the secondary prevention of psychophysiological symptoms of PTSD.

The synchronized trial on expectant mothers with depressive symptoms by omega-3 PUFAs (SYNCHRO): Study protocol for a randomized controlled trial.

BACKGROUND: Maternal depression can be harmful to both mothers and their children. Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been investigated as an alternative intervention for pregnant women with depressive symptoms because of the supporting evidence from clinical trials in major depression, the safety advantage, and its anti-inflammatory and neuroplasticity effects. This study examines the efficacy of omega-3 PUFA supplementation for pregnant women with depressive symptoms in Taiwan and Japan, to provide evidence available for Asia. The rationale and protocol of this trial are reported here. METHODS: The Synchronized Trial on Expectant Mothers with Depressive Symptoms by Omega-3 PUFAs (SYNCHRO) is a multicenter, double-blind, parallel group, randomized controlled trial. Participants will be randomized to either the omega-3 PUFAs arm (1,200 mg eicosapentaenoic acid and 600 mg docosahexaenoic acid daily) or placebo arm. Primary outcome is total score on the Hamilton Rating Scale for Depression (HAMD) at 12 weeks after the start of the intervention. We will randomize 56 participants to have 90 % power to detect a 4.7-point difference in mean HAMD scores with omega-3 PUFAs compared with placebo. Because seafood consumption varies across countries and this may have a major effect on the efficacy of omega-3 PUFA supplementation, 56 participants will be recruited at each site in Taiwan and Japan, for a total number of 112 participants. Secondary outcomes include depressive symptoms at 1 month after childbirth, diagnosis of major depressive disorder, changes in omega-3 PUFAs concentrations and levels of biomarkers at baseline and at 12 weeks' follow-up, and standard obstetric outcomes. Data analyses will be by intention to treat. The trial was started in June 2014 and is scheduled to end in February 2018. DISCUSSION: The trial is expected to provide evidence that can contribute to promoting mental health among mothers and children in Asian populations. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02166424 . Registered 15 June 2014; University Hospital Medical Information Network (UMIN) Center: UMIN000017979. Registered 20 May 2015.

Change in blood levels of eicosapentaenoic acid and posttraumatic stress symptom: A secondary analysis of data from a placebo-controlled trial of omega3 supplements.

BACKGROUND: Eicosapentaenoic acid (EPA) is suggested to be protective against posttraumatic stress disorder (PTSD) from two observational studies. We previously conducted a randomized controlled trial and found no effect of docosahexaenoic acid (DHA) for prevention of PTSD. This secondary analysis aimed to determine whether change in blood levels of EPA is associated with PTSD symptoms. METHODS: The percentages of EPA, DHA, and arachidonic acid (AA) were measured in erythrocyte membranes at baseline and posttreatment in 110 participants with severe physical injury who were randomly assigned to receive either a daily dose of 1,470mg DHA and 147mg EPA or of placebo for 12 weeks. Associations between change in erythrocyte fatty acid levels during the trial controlling for each baseline level and PTSD severity at 12 weeks were analyzed by treatment arm. RESULTS: In the omega3 supplements arm, changes in EPA+DHA (p=.023) and EPA (p=.001) as well as the EPA:AA ratio (p=.000) and EPA: DHA ratio (p=.013) were inversely correlated with PTSD severity. Change in AA was positively correlated with PTSD severity (p=.001). LIMITATION: This trial was conducted at a single-center in Japan and PTSD symptoms in most participants were not serious. CONCLUSIONS: Increased erythrocyte level of EPA during the trial was associated with low severity of PTSD symptoms in patients receiving omega3 supplements.

Medicines and Vegetable Oils as Hidden Causes of Cardiovascular Disease and Diabetes.

BACKGROUND: Positive associations have been observed between cardiovascular disease (CVD) and type 2 diabetes mellitus (DM), but their causal relationship has not been clarified. Nevertheless, guidelines from relevant medical societies recommend using cholesterol lowering medication (statin) for both types of patients. Medicines with several different action mechanisms have been developed, and the effectiveness of different lifestyle modifications has been studied extensively for the prevention of DM, which was successful in improving clinical marker status in relatively short-term treatments, but none have been shown to be effective in improving long-term outcomes (mortality from CVD and all causes). SUMMARY: Statin-induced suppression of prenyl intermediates in the cholesterol biosynthetic pathway has been linked to stimulated atherosclerosis and heart failure. On the other hand, certain types of vegetable oil and hydrogenated oil shortened the survival of stroke-prone spontaneously hypertensive rats by decreasing platelet number, increasing hemorrhagic tendency and damaging kidney functions, which could not be accounted for by their fatty acid and phytosterol compositions. These vegetable oils and medicines such as statin and warfarin share, in part, a common mechanism to inhibit vitamin K2-dependent processes, which was interpreted to lead to increased onset of CVD, DM, chronic kidney disease, bone fracture and even mental disorder. Impaired vitamin K2-dependent processes by some types of vegetable oils and medicines, but not plasma high low density lipoprotein cholesterol, were proposed as the cause of CVD, DM and other lifestyle-related diseases. High n-6/n-3 fatty acid ratio of ingested foods, but not animal fats, was emphasized to be another risk factor for many of the diseases described above. KEY MESSAGES: To date, no randomized controlled trials (RCTs) have been performed to prove the above interpretation. However, the opposite types of RCT trials have been performed by increasing the intake of high-linoleic vegetable oils and reducing that of animal fats, which resulted in increased CVD and all-cause mortality. The amounts of these vegetable oils to exhibit adverse effects in animal studies are not huge (<6 energy %), which should not be overlooked nor disregarded.

Fatty acid composition and fatty acid binding protein expression in the postmortem frontal cortex of patients with schizophrenia: A case-control study.

BACKGROUND: Abnormal levels of n-3 polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), have been found in the postmortem frontal cortex, particularly the orbitofrontal cortex, of patients with schizophrenia. Altered mRNA expression of fatty acid binding protein (FABP) 5 and FABP7 has likewise been reported. METHODS: This study investigated whether PUFAs in the frontal cortex [Brodmann area (BA) 8] and mRNA expression of FABP3, 5, and 7 were different between patients with schizophrenia (n=95) and unaffected controls (n=93). RESULTS: In contrast to previous studies, no significant differences were found in DHA between the groups. Although arachidonic acid (AA) levels were significantly decreased in the schizophrenia group, no association was found between AA and schizophrenia on logistic regression analysis. Only FABP3 expression was significantly lower in the schizophrenia group than in the control group. Significant inverse associations were seen between only two saturated fatty acids, behenic acid and lignoceric acid, and FABP3 expression. CONCLUSIONS: We found no evidence that major PUFA levels in BA8 are involved in the etiology of schizophrenia. Although FABP3 expression was not correlated with any of the major PUFAs, it might play a novel role in the pathology of BA8 in a subset of patients with schizophrenia.

Docosahexaenoic acid for selective prevention of posttraumatic stress disorder among severely injured patients: a randomized, placebo-controlled trial.

OBJECTIVE: Docosahexaenoic acid (DHA) might help prevent or attenuate posttraumatic stress disorder (PTSD) symptoms. We examined the efficacy and safety of DHA for preventing PTSD (DSM-IV) after severe accidental injury. METHOD: From December 2008 to August 2013, we conducted a randomized, double-blind, placebo-controlled trial of 110 accident-injured patients consecutively admitted to an intensive care unit of the National Disaster Medical Center in Tokyo, Japan. All patients were taught about their psychological reactions to accidental injury for 20 minutes and were randomly assigned to receive 1,470 mg/d of DHA plus 147 mg/d of eicosapentaenoic acid (EPA; n = 53) or placebo (n = 57) for 12 weeks. The primary outcome was total score on the Clinician-Administered PTSD Scale (CAPS) at 3-month follow-up. Secondary outcomes included PTSD diagnosis (full-blown or partial PTSD). Adherence to the interventions was assessed by erythrocyte fatty acid composition. RESULTS: At 3 months, the CAPS total score revealed no differences between the 2 groups (10.78 in the DHA group vs 9.22 in the placebo group; n = 100; P = .572). We found that 11.1% of the DHA group and 5.5% of the placebo group developed PTSD. The erythrocyte level of DHA and EPA in the DHA group was significantly elevated compared to the placebo group (P < .01). CONCLUSIONS: Docosahexaenoic acid supplementation was not superior to placebo for the secondary prevention of PTSD symptoms at 3 months after severe accidental injury. The efficacy of a different ratio of DHA and EPA and higher doses of omega-3 fatty acids as secondary prevention of PTSD remains to be determined. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00671099.

Fatty acid composition of the postmortem prefrontal cortex of patients with schizophrenia, bipolar disorder, and major depressive disorder.

Postmortem brain studies have shown abnormal levels of n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid, in the frontal cortex (particularly the orbitofrontal cortex) of patients with depression, schizophrenia, or bipolar disorder. However, the results from regions in the frontal cortex other than the orbitofrontal cortex are inconsistent. In this study we investigated whether patients with schizophrenia, bipolar disorder, or major depressive disorder have abnormalities in PUFA levels in the prefrontal cortex [Brodmann area (BA) 8]. In postmortem studies, fatty acids in the phospholipids of the prefrontal cortex (BA8) were evaluated by thin layer chromatography and gas chromatography. Specimens were evaluated for patients with schizophrenia (n=15), bipolar disorder (n=15), or major depressive disorder (n=15) and compared with unaffected controls (n=15). In contrast to previous studies, we found no significant differences in the levels of PUFAs or other fatty acids in the prefrontal cortex (BA8) between patients and controls. Subanalysis by sex also showed no significant differences. No significant differences were found in any individual fatty acids between suicide and non-suicide cases. These psychiatric disorders might be characterized by very specific fatty acid compositions in certain areas of the brain, and BA8 might not be involved in abnormalities of PUFA metabolism.

Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms.

In contrast to the current belief that cholesterol reduction with statins decreases atherosclerosis, we present a perspective that statins may be causative in coronary artery calcification and can function as mitochondrial toxins that impair muscle function in the heart and blood vessels through the depletion of coenzyme Q10 and 'heme A', and thereby ATP generation. Statins inhibit the synthesis of vitamin K2, the cofactor for matrix Gla-protein activation, which in turn protects arteries from calcification. Statins inhibit the biosynthesis of selenium containing proteins, one of which is glutathione peroxidase serving to suppress peroxidative stress. An impairment of selenoprotein biosynthesis may be a factor in congestive heart failure, reminiscent of the dilated cardiomyopathies seen with selenium deficiency. Thus, the epidemic of heart failure and atherosclerosis that plagues the modern world may paradoxically be aggravated by the pervasive use of statin drugs. We propose that current statin treatment guidelines be critically reevaluated.

Mead acid (20:3n-9) and n-3 polyunsaturated fatty acids are not associated with risk of posterior longitudinal ligament ossification: results of a case-control study.

Ossification of the posterior longitudinal ligament (OPLL) involves the replacement of ligamentous tissue with ectopic bone. Although genetics and heritability appear to be involved in the development of OPLL, its pathogenesis remains to be elucidated. Given previous findings that 5,8,11-eicosatrienoic acid [20:3n-9, Mead acid (MA)] has depressive effects on osteoblastic activity and anti-angiogenic effects, and that n-3 polyunsaturated fatty acids (PUFAs) have a preventive effect on heterotopic ossification, we hypothesized that both fatty acids would be involved in OPLL development. To examine the biological significance of these and other fatty acids in OPLL, we conducted this case-control study involving 106 patients with cervical OPLL and 109 age matched controls. Fatty acid composition was determined from plasma samples by gas chromatography. Associations between fatty acid levels and incident OPLL were evaluated by logistic regression. Contrary to our expectations, we found no significant differences between patients and controls in the levels of MA or n-3 PUFAs (e.g., eicosapentaenoic acid and docosahexaenoic acid). Logistic regression analysis did not reveal any associations with OPLL risk for MA or n-3 PUFAs. In conclusion, no potential role was found for MA or n-3 PUFAs in ectopic bone formation in the spinal canal.

The safety of fish oils for those whose risk of injury is high.

A diet rich in omega-3 polyunsaturated fatty acids (PUFAs) may decrease risk of cardiovascular disease by improving the blood lipid profile. The purpose of this review was to (1) determine if fish oil (omega-3) consumption increased the risk of hemorrhaging after a military injury and (2) whether an improvement in the omega-3 PUFA profile had an impact on survivability from military wounds. The authors found no evidence to contradict the existing U.S. Food and Drug Administration safety ruling that 3 g of omega-3 PUFA per day is generally regarded as safe. However, there is insufficient data with regard to the safety of consuming more than 3 g of omega-3 PUFA per day. More research is needed to safely recommend use of higher doses omega-3 PUFA.

Arachidonic acid supplementation does not affect N-methyl-N-nitrosourea-induced renal preneoplastic lesions in young Lewis rats.

Arachidonic acid (AA) is naturally found in human breast milk. AA, together with docosahexaenoic acid, is commonly added as a functional food ingredient to commercial infant formula worldwide, in accordance with the international standards of Codex Alimentarius. However, few studies of the possible renal carcinogenic effects of AA supplementation during neonatal life have been performed. The effect of dietary AA supplementation in dams during gestation and lactation was investigated on N-methyl-N-nitrosourea (MNU)-induced preneoplastic lesions in the kidneys of young Lewis rats. Dams were fed a 2.0% AA diet or a basal diet (<0.01% AA). At birth (postnatal day 0), male and female pups received a single intraperitoneal injection of 35 mg/kg MNU or vehicle. Renal morphology was examined after 7, 14, 21, 28 and 60 days. Histopathologically, renal preneoplastic lesions, such as nephroblastomatosis and mesenchymal cell proliferation, were found on day 60 in both the MNU-treated groups. There was no significant difference in lesion incidence of 38% in the basal diet group and 31% in the AA diet group. In conclusion, an AA-rich diet for dams during gestation and lactation does not modify MNU-induced renal preneoplastic lesions in their offspring.

Tachikawa project for prevention of posttraumatic stress disorder with polyunsaturated fatty acid (TPOP): study protocol for a randomized controlled trial.

BACKGROUND: Preclinical and clinical studies suggest that supplementation with omega-3 fatty acids after trauma might reduce subsequent posttraumatic stress disorder (PTSD). To date, we have shown in an open trial that PTSD symptoms in critically injured patients can be reduced by taking omega-3 fatty acids, hypothesized to stimulate hippocampal neurogenesis. The primary aim of the present randomized controlled trial is to examine the efficacy of omega-3 fatty acid supplementation in the secondary prevention of PTSD following accidental injury, as compared with placebo. This paper describes the rationale and protocol of this trial. METHODS/DESIGN: The Tachikawa Project for Prevention of Posttraumatic Stress Disorder with Polyunsaturated Fatty Acid (TPOP) is a double-blinded, parallel group, randomized controlled trial to assess whether omega-3 fatty acid supplementation can prevent PTSD symptoms among accident-injured patients consecutively admitted to an intensive care unit. We plan to recruit accident-injured patients and follow them prospectively for 12 weeks. Enrolled patients will be randomized to either the omega-3 fatty acid supplement group (1,470 mg docosahexaenoic acid and 147 mg eicosapentaenoic acid daily) or placebo group. Primary outcome is score on the Clinician-Administered PTSD Scale (CAPS). We will need to randomize 140 injured patients to have 90% power to detect a 10-point difference in mean CAPS scores with omega-3 fatty acid supplementation compared with placebo. Secondary measures are diagnosis of PTSD and major depressive disorder, depressive symptoms, physiologic response in the experiment using script-driven imagery and acoustic stimulation, serum brain-derived neurotrophic factor, health-related quality of life, resilience, and aggression. Analyses will be by intent to treat. The trial was initiated on December 13 2008, with 104 subjects randomized by November 30 2012. DISCUSSION: This study promises to be the first trial to provide a novel prevention strategy for PTSD among traumatized people. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00671099.

Promoting effect of arachidonic acid supplementation on N-methyl-N-nitrosourea-induced pancreatic acinar cell hyperplasia in young Lewis rats.

Arachidonic acid (AA) is naturally found in human breast milk. AA, together with docosahexaenoic acid, is commonly added as a functional food ingredient to commercial infant formula worldwide, in accordance with the international standard of Codex Alimentarius. However, few studies have been performed that are concerned with the possible carcinogenic effects of AA supplementation during neonatal life. The effect of dietary AA supplementation in dams, during gestation and lactation, was investigated in N-methyl-N-nitrosourea (MNU)-induced preneoplastic lesions in the exocrine pancreas of young Lewis rats. Dams were fed either an AA (2.0% AA) or a basal (<0.01% AA) diet. On postnatal day 0 (at birth), male and female pups received a single intraperitoneal injection of either 35 mg/kg MNU or vehicle. The morphology and proliferating activity of the exocrine pancreas were examined by proliferative cell nuclear antigen immunohistochemistry 7, 14, 21, 28 and/or 60 days post-MNU. Histopathologically, acinar cell hyperplasia (ACH) occurred in the MNU-treated groups 60 days after MNU injection, irrespecitive of whether the rats had been fed an AA diet. Morphometrically, the number and area of ACH per 1 mm(2) in MNU-treated rats increased significantly in the AA diet-fed rats, compared with basal diet-fed rats. The number of proliferative cell nuclear antigen-positive acinar cells in both the normal and hyperplastic areas of MNU-treated rats increased significantly in the AA diet-fed rats. In conclusion, providing dams with an AA-rich diet during gestation and lactation promotes MNU-induced pancreatic ACH in young Lewis rats.

Attenuating posttraumatic distress with omega-3 polyunsaturated fatty acids among disaster medical assistance team members after the Great East Japan Earthquake: the APOP randomized controlled trial.

BACKGROUND: On March 11, 2011, a magnitude 9.0 earthquake, the most powerful ever recorded in Japan, and a massive tsunami struck off the coast of the Sanriku region. A Disaster Medical Assistance Team, a mobile medical team with specialized training that is deployed during the acute phase of a disaster, was dispatched to areas with large-scale destruction and multiple injured and sick casualties. Previous studies have reported critical incident stress (i.e. posttraumatic stress disorder symptoms and depressive symptoms) among rescue workers as well as the need for screening and prevention for posttraumatic stress disorder. So far we have shown in an open trial that posttraumatic stress disorder symptoms in critically injured patients can be reduced by taking omega-3 fatty acids intended to stimulate hippocampal neurogenesis. METHOD/DESIGN: This study is designed to determine the effectiveness of attenuating posttraumatic distress with omega-3 polyunsaturated fatty acids among Disaster Medical Assistance Team members after the Great East Japan Earthquake, and is named the APOP randomized controlled trial which is currently ongoing. First, we will provide psycho-education on posttraumatic distress, which is common in responders to the Disaster Medical Assistance Team members deployed to the disaster area. Second, observational research will be conducted to evaluate critical incident stress following the completion of medical activities. Third, team members who provide consent to participate in the intervention research will be randomly divided into a group given an omega-3 fatty acid supplement and a group not given the supplements. Outcome will be evaluated at 12 weeks after the supplements are shipped to the team members. DISCUSSION: Measures that address critical incident stress in disaster responders are important, but there is no substantial evidence that links such measures with prevention of posttraumatic stress disorder. Thus, any confirmation through this study that the intake of omega-3 fatty acid supplements serves as a simple preventative measure for critical incident stress will be of great significance. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000005367.