Summary

Depression affects women disproportionately compared with men, and symptoms of psychological distress may be particularly prevalent during the perimenopausal period. The current study of ethyl-eicosapentaenoic acid for the management of psychological distress among middle-aged women produced primarily negative results, which is consistent with other clinical trials of fish oil for depression. At this time, there is insufficient evidence to recommend fish oil for the treatment of depression.

Background

Depression is one of the most significant international public health problems today, and it affects women disproportionately. The lifetime prevalence of major depression among women varies widely with the population studied, but it is generally between 6% and 17%.[1] Depression is 1.5 to 3 times more common among women compared with men, and a report from the World Health Organization (WHO) identified depression as the leading cause of disease-related disability among women around the world, with rates of disability 50% higher than among men.[2]

While the gender difference in the prevalence of depression is evident by adolescence, the question of whether depression is particularly more common during perimenopause and menopause is controversial. Research suggests that rates of depressive symptoms increase in the year prior to and following women’s last menstrual period, with a peak prevalence of psychological distress in 28.9% of women in early menopause.[3] However, some epidemiologic studies have demonstrated no increase in the risk for depression among women at midlife, and there also does not appear to be an increased prevalence of depression in the postmenopausal vs premenopausal period.[4]

Women have many options to treat depression and its symptoms, but many women may prefer treatment that does not require a prescription. In one study from Finland, 35.4% of a large population-based sample reported the use of complementary and alternative medicine.[5] Women were more likely to use complementary medicine compared with men, and the presence of depression and anxiety disorders was positively associated with the use of complementary medicine as well.

One popular treatment women may consider for a variety of health benefits is fish oil, and fish oil has some evidence of efficacy in the treatment of depression. In a small study of patients with major depression, the addition of ethyl-eicosapentaenoic acid (E-EPA) to conventional antidepressant therapy significantly improved depression rating scores by week 3 compared with placebo.[6] On a larger scale, epidemiologic studies suggest that societies that consume higher amounts of fish and omega (n)-3 fatty acids have lower rates of depression.[7]

Current Trial

The current study examines the effects of E-EPA as monotherapy among middle-aged women with psychological distress. Women between the ages of 40 and 55 years were eligible for study participation. All participants had moderate-to-severe psychological distress, as measured by a score of 72 or less on the Psychological General Well-Being Schedule (PGWB). Women with severe depression were excluded from study participation, as were those who had been in menopause for over 5 years. However, women who met criteria for major depression were allowed into the trial.

Study participants were randomized to receive either E-EPA n-3 fatty acid supplementation or placebo as 500-mg capsules 3 times daily for 8 weeks. The study was double blind, and a small dose of regular fish oil was added to the placebo tablets to mimic any fish taste of the active treatment.

The main study outcome was the change in the PGWB. Researchers also followed multiple other depression rating scales.

One hundred twenty women underwent randomization, and 106 participants provided data at 8 weeks. The number of women dropping out of the study protocol was higher in the placebo compared with the E-EPA group.

Baseline data were similar when comparing randomized groups, except the percentage of women who met criteria for a major depressive episode was higher in the placebo (26.2%) compared with the E-EPA (22%) group. The mean age of participants was 48 years, and three quarters of the women had a college education or more. Nearly half of the women reported being physically active at least 3 times per week, and 20% were smokers.

Over 80% of participants took at least 80% of the study treatments, with no difference between treatment groups. Furthermore, blood tests confirmed that red blood cell concentrations of polyunsaturated fatty acids (PUFAs) increased in the E-EPA group and remained stable in the placebo group during the study period.

While 50% and 6% of women receiving E-EPA and placebo, respectively, noted a fishy taste of the capsule, there was no significant difference between groups in correctly guessing their assigned treatment. Beside the fishy taste, more women receiving E-EPA reported constipation as an adverse event during the study period.

Mean baseline scores on the PGWB indicated that 63.8% were under severe psychological distress, and 36.2% women were experiencing moderate distress. At 8 weeks, the PGWB score improved to a similar extent in both treatment groups. Similarly, the overall scores on the depression scales improved slightly in both the E-EPA and placebo groups.

Despite these negative main results, E-EPA was more successful in improving both psychological distress and depression scores in the subgroup of women without a major depressive episode. However, placebo therapy was associated with better performance compared with E-EPA among women with major depression.

Commentary

The study discussion focuses on the benefit of E-EPA among women without major depression, although this ignores the fact that this was a largely negative trial. E-EPA failed to improve the main study outcome compared with placebo, and placebo was actually more effective than E-EPA among women with major depression. This latter result particularly calls into question any benefit of E-EPA in this population.

The negative results of this trial are consistent with larger studies of fish oil for depression. In one 12-week trial comparing EPA and docosahexaenoic acid (DHA) with placebo among 218 patients with mild to moderate depression, the active treatment was not associated with improved mood, mental health, or cognitive function outcomes.[8] In addition, another trial by Grenyer and colleagues[9] of 83 patients receiving oral antidepressants failed to demonstrate any benefit of fish oil supplementation compared with placebo, despite evidence of good compliance with study treatment. Finally, a trial of EPA plus DHA among 302 community-dwelling older adults failed to improve depression scores or mental well-being compared with placebo.[10] In this trial, both low-dose and high-dose fish oil supplementation were ineffective after a fairly long (26 weeks) intervention.

There are mixed results in reviews of supplementation with PUFAs for depression. One review published in 2006 noted that EPA improved depression in 4 of 7 randomized trials.[11] In all of the positive trials, EPA was added to existing antidepressant or mood-stabilizing medications. Another systematic review of 18 randomized controlled trials found limited effects of PUFAs on depression and significant heterogeneity of results due to publication bias in the accumulated scientific literature.[12] Finally, a meta-analysis from 2007 found that omega-3 PUFAs did have a significant antidepressant effect among patients with either depression or bipolar disorder.[13] However, study heterogeneity and publication bias precluded the researchers from recommending omega-3 PUFAs to treat depression.

Depression and depressive symptoms are frequently comorbidities associated with other chronic disease, particularly among middle-aged and older adults. Many adults consume fish or take fish-oil supplements to reduce lipid levels, which is well supported in the scientific literature. EPA appears most effective in reducing triglyceride levels, with minimal effects on low- and high-density lipoprotein cholesterol.[14] This treatment can improve the rate of cardiac events, and the prospect of combination treatment with fish oil and a medication from the statin class of drugs appears particularly promising. A trial of EPA combined with a statin with 4.6 years of follow-up demonstrated that combination treatment was associated with a significant 19% reduction in major coronary events compared with statin treatment alone.[15] In addition, fish oil has a modest effect in reducing blood pressure among patients with hypertension, and it has been demonstrated to reduce morning stiffness and the number of painful joints among patients with rheumatoid arthritis.[14]

Fish oil also appears safe and is generally well-tolerated. Patients should certainly consider making fish a regular part of their diet, provided that they avoid consuming large quantities of fish associated with high levels of mercury. Fish oil supplements are another viable treatment option, particularly for patients at higher risk for cardiovascular disease. However, the current study and collective body of research do not provide the level of evidence necessary to recommend fish oil to improve mood, whether for the management of psychological distress or major depression.

SOURCE: MedScape

The strength of evidence linking eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to a reduced risk of coronary heart disease was “remarkable”, they said, prompting them to recommend a DRI of between 250 and 500mg/day.

In 2002, the US Institute of Medicine (IOM) concluded that there was insufficient evidence to define DRIs for EPA and DHA. The current review, based on a workshop organized last year by the Technical Committee on Dietary Lipids of the International Life Sciences Institute of North America, was designed to examine new data that have emerged since 2002.

The workshop aimed to examine evidence of the benefits of EPA and DHA on coronary heart disease (CHD), cancer and cognitive decline.

In a supplement published this year in The Journal of Nutrition and based on the workshop conclusions, the scientists stated that while evidence was clear for the benefits of EPA and DHA for reducing the risk of CHD, there was not enough consistent evidence on the benefits of the omega-3s for cognitive health and cancer reduction.

These findings add momentum to the drive to establish an omega-3 DRI, a move that has long been supported by the research community and the food and dietary supplement industries.

Heart disease

The scientists reviewed over 15 prospective cohort studies in generally healthy populations, a retrospective case-control study of sudden cardiac death, four large randomized controlled trials with fish or fish oil in patients with and without known heart disease, and several in vivo and animal experimental studies.

This evidence indicates that modest EPA and DHA consumption “markedly” reduces the risk of cardiac death, they said.

“The quality, strength, and concordance of this evidence are remarkable, meeting and indeed generally exceeding those for any other dietary factor for which a DRI has been set based on reducing risk for chronic disease, including saturated fat, dietary cholesterol, salt, and dietary fiber,” they wrote.

“For primary prevention of cardiac death, the leading cause of death in both men and women in the United States and nearly all other developed nations, current evidence supports a DRI for EPA1DHA between 250 and 500 mg/d.”

However, the scientists found that evidence was “more modest” for the effects of long-chain polyunsaturated fatty acids (PUFA) on other cardiovascular risks, including blood pressure, resting heart rate, triglyceride levels and heart rate variability.

Cognitive and cancer benefits

The review also included emerging data on the cognitive and cancer benefits of EPA and DHA.

The evidence for protective effects of omega-3 long chain PUFA from fish on risk of dementia is “promising but limited”, said the scientists.

Epidemiological evidence suggests positive benefits of one fish meal per week on the risk of Alzheimer’s disease, dementia, and cognitive decline. In addition, the animal evidence and biologic plausibility support a protective relation of omega-3 long-chain PUFA on neurodegeneration of the brain with aging. However, tissue DHA levels do not seem to be consistently lower in Alzheimer’s disease or any form of cognitive decline associated with aging, said the scientists.

“Several primary and secondary prevention trials are in progress in the United States and Europe that will greatly inform the field. Further research is necessary to examine the effects of different dose levels, benefits of DHA, EPA, and ALA, and the importance of relative intakes of [omega-3] vs. [omega-6] fatty acids”.

In relation to the cancer benefits of omega-3s, the researchers concluded that “there are no clear relations between dietary intakes of EPA and DHA and risk for cancer.”

Source:
Towards Establishing Dietary Reference Intakes for Eicosapentaenoic and Docosahexaenoic Acids
The Journal of Nutrition
First published online February 25, 2009; doi:10.3945/jn.108.101329.
Authors: William S. Harris, Dariush Mozaffarian, Michael Lefevre, Cheryl D. Toner, John Colombo, Stephen C. Cunnane, Joanne M. Holden, David M. Klurfeld, Martha Clare Morris, and Jay Whelan

The departments of Psychiatry and Obstetrics and Gynecology gynecology at Saint-François d’Assise Hospital (Centre Hospitalier Universitaire de Québec) Canada investigated the effects of enriched ethyl-eicosapentaenoic acid (E-EPA) omega-3 fatty acid supplementation with those of placebo on hot flashes (HFs) and distress among middle-aged women.

Women were considered for participation if they were between 40 and 55 years of age and had hot flushes and moderate to severe psychological distress. A total of 120 women were randomly assigned to E-EPA or placebo for 8 weeks.

Hot Flashes
At baseline, the average number of hot flushes was 2.8 per day. After 8 weeks, the frequency and score decreased significantly in the E-EPA group compared with the placebo group. Frequency of hot flushes declined by a mean of 1.58 per day in the E-EPA group and by 0.50 per day in the placebo group.

“Supplementation with E-EPA omega-3 fatty acid reduced HF frequency and improved the HF score relative to placebo. These results need to be confirmed by a clinical trial specifically designed to evaluate HFs in more symptomatic women”, the authors conclude.

Psychological Distress
Psychological distress (PD) and depressive symptoms are commonly observed during menopausal transition. Studies suggest that omega-3 (n-3) fatty acids may help alleviate depression. The objective of tris trial was to compare (E-EPA) supplementation with placebo for the treatment of PD and depressive symptoms in middle-aged women.

Women with moderate-to-severe PD (n = 120) were randomly assigned to receive 1.05 g E-EPA/d plus 0.15 g ethyl-docosahexaenoic acid/d (n = 59) or placebo (n = 61) for 8 wk. The main outcomes were 8-wk changes in PD scores [Psychological General Well-Being Schedule (PGWB)] and depressive scales [20-item Hopkins Symptom Checklist Depression Scale (HSCL-D-20) and the 21-item Hamilton Depression Rating Scale (HAM-D-21)].

At baseline, women with PD were mildly to moderately depressed, and 24% met the major depressive episode (MDE) criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. After 8 wk, outcomes improved in both groups, but no significant differences were noted between them. Differences in adjusted 8-wk changes between the E-EPA group with MDE (n = 13) and the placebo group (n = 16) were not significant.

“To our knowledge, this is the first trial of n-3 supplementation in the treatment of PD and depressive symptoms in middle-aged women. In women with PD without MDE at baseline, the 8-wk changes in PD and depressive scales improved significantly more with E-EPA than with placebo”, the authors write (2).

This trial was registered at Controlled Clinical Trials under ISRCTN69617477.

Lucas M, Asselin G, Mérette C, Poulin MJ, Dodin S. Effects of ethyl-eicosapentaenoic acid omega-3 fatty acid supplementation on hot flashes and quality of life among middle-aged women: a double-blind, placebo-controlled, randomized clinical trial. Menopause. 2008 Nov 20. Abstract

Lucas M, Asselin G, Mérette C, Poulin MJ, Dodin S. Ethyl-eicosapentaenoic acid for the treatment of psychological distress and depressive symptoms in middle-aged women: a double-blind, placebo-controlled, randomized clinical trial. Am J Clin Nutr. 2008 Dec 30. PubMed

The study was carried out by the oesophageal research group at Trinity College Dublin and St James’s Hospital. A randomised controlled trial showed omega-3 fatty acids given as part of an oral nutritional supplement resulted in the preservation of muscle mass in patients undergoing surgery for oesopahageal cancer, a procedure normally associated with significant weight loss and quality of life issues.

The trial was designed by Professor John V Reynolds, Professor of Surgery at Trinity College Dublin and St James’s Hospital, Dublin, and Dr Aoife Ryan PhD, a research dietitian at St James’s Hospital, Dublin*.

Omega 3 fats are essential fats found naturally in oily fish, with highest concentrations in salmon, herring, mackerel, and sardines. Recently food manufacturers have begun to add omega 3 to foods such as yogurt, milk, juice, eggs and infant formula in light of a body of scientific evidence which suggests that they reduce cardiovascular disease risk, blood pressure, clot formations, and certain types of fat in the blood.

Previous studies had found that nutritional supplements containing one form of omega 3 fat, eicosapentaenoic acid (EPA), significantly reduced weight loss among inoperable cancer patients. The researchers hypothesised that a nutritional supplement rich in calories and a high dose of EPA would stem the debilitating weight loss seen in patients following oesophageal surgery. The group chose to study patients undergoing surgery for oesophageal cancer as this surgery is one of the most stressful and serious operations a patient can undergo.

Professor John V Reynolds, Professor of Surgery at TCD and St James’s Hospital and the lead researcher on the study said: “There are almost 450 new cases of oesophageal cancer diagnosed every year in Ireland and Ireland has one of the highest rates of oesophageal cancer in Europe. An increasing number of patients are treated with chemotherapy alone or in combination with radiation therapy before they undergo surgery. The surgery is a serious operation lasting several hours and can take weeks to recover from surgery and up to six months to recover pre-illness quality of life. Weight loss is extremely common both before and especially after this type of surgery, and any approach that can preserve weight, in particular muscle weight and strength, may represent a real advance”.

In a double-blinded randomised control trial, the gold standard in medical research, patients awaiting oesophagectomy surgery were randomly assigned to treatment and control groups. While both groups received a 240ml nutritional supplement twice daily starting five days before surgery (which was identical in calories, protein, micronutrients and flavor), patients in the treatment group received an enriched formula with omega 3 (2.2 gram EPA/day). Immediately following surgery, the supplement was given through a feeding tube for 14 days while patients recovered in hospital. Once patients could resume oral feeding, they continued drinking the supplement until 21 days post surgery.

Results:

The oesophageal research group at Trinity College Dublin and St. James’s Hospital found that patients given the standard feed (without omega 3) suffered clinically severe weight loss post surgery - losing an average of 4 lbs of muscle mass post surgery, where as in the omega 3 group patients maintained all aspects of their body composition

Commenting on the significance of the results, Dr Aoife Ryan said: “The results were extraordinary in the sense that no previous nutritional formulation had revealed such an outcome, with supplemented patients maintaining all aspects of their body composition in the three weeks following surgery. Patients given the standard supplement without omega 3 lost a significant amount of weight comprising 100% muscle mass. In fact 68% of patients suffered ‘clinically severe’ weight loss post surgery in the standard group (without omega 3) versus only 8% in the omega 3 group. The significant finding was that the patients did not lose just fat, as one would expect with weight loss, but instead they depleted their muscle stores significantly. Research has shown that a loss of 5lbs of weight produces significant effects on quality of life and a patient’s ability to mobilise and perform simple activities of daily living. Losing 4 lbs of muscle is even more significant”.

Professor John Reynolds said: “Omega 3 enriched nutrition appears to prevent loss of muscle mass by reducing the amount of inflammatory markers in the blood - this means the metabolism is not as stressed as it usually is post surgery. We also saw that the omega 3 group was less likely to have a fever in the first week post surgery which points to the ability of omega 3 to suppress inflammation. Looking at their blood tests omega 3 fed patients had much lower ‘inflammatory compounds’ circulating in their blood which points to the ability of omega 3 to reduce inflammation”.

Using specialised nutritional feeds with a highly purified form of EPA, the researchers were able to administer a dose of omega 3 that was much higher than that typically found in food. They noted that treatment with omega 3 enriched supplement is only slightly more expensive than traditional nutritional therapy, and previous studies have yielded significant cost-savings in the form of fewer complications following surgery using immuno-nutrition feeds similar to this. “Initial treatments like this may be cost-effective for our cash-strapped health care system”, said Dr Ryan.

Commenting in an accompanying editorial in the Annals of Surgery Dr Michael Meguid, Professor of Surgery at State University of New York noted: “This study is a significant step forward because it underscores the message to surgeons of the importance of using omega 3 based nutrition as an adjunct therapy started at least 5 days before surgery. It should no longer be a surgeon’s preference, but the standard of expected norm for the practice of elective complex gut cancer surgery”.

In conclusion, Professor John Reynolds said: “This study has provided an interesting insight into how nutritional therapy can positively impact on the major stress of cancer surgery. More studies need to be done, in particular to address whether such approaches lead to more rapid recovery of quality of life, reduce complications, and improve outcomes. Throughout cancer care, many patients undergoing therapy nowadays have a combination of surgery, chemotherapy and radiation therapy, and studies addressing whether nutritional supplementation with omega 3 for the entire duration of treatment should be considered. Finally, we do not expect these findings are unique to cancer surgery, and similar benefits may accrue to patients needing complex surgical care for non-cancer problems, for instance liver transplantation or major cardiac surgery.”

SOURCE: http://www.tcd.ie/

(CNN) — The benefits to humans of omega 3 fatty acids in fish oils are well documented, but a new study has found that fish oils can have a wider benefit to the environment — by reducing the amount of methane produced by cows.

The report produced by University College Dublin found that by including two percent fish oil in the diet of cattle they achieved a reduction in the amount of methane released by the animals.

Lowering methane emissions is important for the environment, as the gas given off by farm animals is a major contributor to greenhouse gas levels.

More than a third of all methane emissions, around 900 billion tonnes every year, are produced by methanogen bacteria that live in the digestive systems of cattle, sheep and goats.

By volume, methane is 20 times more powerful at trapping solar energy than carbon dioxide making it a potent greenhouse gas.

“The fish oil affects the methane-producing bacteria in the rumen part of the cow’s gut, leading to reduced emissions,” said Dr Lorraine Lillis, one of the researchers, speaking at the Society for General Microbiology meeting in Harrogate, England.

“Understanding which microbial species are particularly influenced by changes in diet and relating them to methane production could bring about a more targeted approach to reducing methane emissions in animals.”

Approximately 50 percent of Irish agricultural methane emissions result from farm animals, which has led to suggestions that, to help combat global warming, the numbers of cattle, sheep and goats should be capped.

The researchers believe that it may not be necessary to limit the number of farm animals if their methane levels are reduced through diet.

SOURCE: CNN.com

In the study reported here, Dr. S. Wang and colleagues of Xi’an Jiaotong University in China, used pulse wave velocity to assess arterial elasticity in 43 overweight Chinese patients with hypertension who consumed fish oil or placebo supplements for 8 weeks. Daily n-3 LC-PUFA supplementation provided 900 mg/day of n-3 LC-PUFAs from salmon oil, containing 540 mg EPA and 360 mg DHA. Participants had a body mass index of ≥23 and systolic blood pressure ≥140 with diastolic pressure ≥90. Blood pressure control medications were suspended for 2 weeks prior to the study. Measures of pulse wave velocity, plasma lipids and blood pressure were obtained at baseline and after 56 days.

After 8 weeks of fish oil supplementation, there was a significant 21% increase in arterial elasticity, but no changes in the placebo group. Heart rate, systolic and diastolic blood pressures, plasma lipids and soluble vascular adhesion molecule-1 did not change significantly in either group during the study. As expected, n-3 PUFAs in serum fatty acids increased significantly only in the fish oil group, mainly at the expense of monounsaturated fatty acids.

The primary outcome in this study was a significant increase in arterial elasticity with the consumption of 900 mg/day of n-3 LC-PUFAs for 8 weeks. This change occurred despite the lack of change in blood pressure. Large artery elasticity has a genetic component, but is also blood pressure dependent, with decreased elasticity occurring at high blood pressure. However, hypertension triggers arterial hypertrophy, which reduces arterial stiffness. It is noteworthy that a significant reduction in arterial stiffness occurred in a relatively short time, 8 weeks, with a dose of n-3 LC-PUFAs that has been linked to reduced cardiovascular mortality in survivors of myocardial infarction. These results strengthen previous findings of improved arterial compliance with the consumption of n-3 LC-PUFAs, suggesting another way in which these fatty acids protect heart health.

SOURCE: PUFA Newsletter

This study reports the associations between changes in anger and anxiety scores and serum levels of EPA and DHA in 22 substance abusers who consumed about 3 g/day of n-3 LC-PUFAs or soybean oil for 3 months. The n-3 LC-PUFA capsules provided 2.2 g/day of EPA, 500 mg/day DHA, and 50 mg of n-3 docosapentaenoic acid and alpha-linolenic acid. Participants were enrolled in an outpatient substance abuse program in Brooklyn, New York, and were free of major psychiatric and physical illnesses and had liver function tests no greater than 1 SD above maximum normal values.

Participants completed a dietary history questionnaire and a modified version of the Profiles of Mood States questionnaire 1, 2 and 3 months following the start of the study and gave blood samples at the beginning and end of the study. Fatty acids were determined in plasma. The Profiles in Mood States includes scores for anger, anxiety, depression, vigor, confusion and fatigue. Eight patients received methadone treatment and 5 took antidepressants in stable doses throughout the study. Participants did not differ at baseline in body mass index, energy consumption or low intake of n-3 LC-PUFAs.

After 3 months of treatment, participants consuming the n-3 LC-PUFAs had a significant decline in their anger scores, whereas scores in those taking the placebo capsules increased slightly. Scores reached their maximum after 2 months of n-3 LC-PUFA consumption. Anger scores continued to decline throughout the 3-month period for those on the active n-3 LC-PUFA treatment. A similar pattern of significantly improved anxiety scores was observed for substance abusers consuming the n-3 LC-PUFAs, but scores were unchanged in those taking the placebo.

When the investigators examined the relationship between the anger and anxiety scores at the end of the study with the percent change in plasma fatty acids over the 3-month study, they observed significant associations (Figure 1). Lower anger scores were associated with increased DHA, n-3 docosapentaenoic acid and total n-3 LC-PUFAs, but not with increased EPA concentrations. In contrast, reduced anxiety was associated with increased EPA, but not with changes in DHA. Changes in anger and anxiety scores were not associated with changes in any n-6 PUFAs.

It is worth noting that improved scores for anger and anxiety related to increased DHA and EPA, respectively, but neither behavior related to both DHA and EPA when these fatty acids were examined individually. However, both behaviors were significantly associated with increases in the total concentration of n-3 LC-PUFAs measured in µg/ml.

Only a few studies have reported an association between low plasma DHA and hostility in violent men and young urban males. Students under the stress of school exams who consumed 1.5 to 1.8 g/day of DHA exhibited no aggression against others compared with increased aggression observed in those taking a placebo. This study adds another link between DHA and aggressive behavior as reflected in anger scores.

As with anger, studies of anxiety and n-3 PUFAs are scarce. A few have suggested a link between increased anxiety and low levels of EPA or n-3 LC-PUFAs. The administration of a mixture of n-3 and n-6 PUFAs to anxious college students was associated with improved appetite, mental concentration and academic organization. Patients with social anxiety disorder had significantly lower concentrations of n-3 PUFAs compared with those not having this disorder. Moderate fish consumption (83 to 112 g/day or 3 to 4 oz/day) or n-3 LC-PUFA intake was associated with a significant 30% lower risk of incurring depression, anxiety or stress in a 2-yr prospective study of Spanish adults. The present report identified increased EPA specifically with improved anxiety scores and higher DHA with less anger.

 Although it may be tempting to suggest that EPA and DHA influence anxiety and anger behaviors through different mechanisms, and plausible explanations could be proffered, these specific associations need more robust confirmation before reaching firm conclusions. Investigation of EPA and DHA administered individually without the other would be useful across an array of mental disorders. This study supports others in demonstrating that anxious or angry substance abusers who have low blood levels of n-3 LC-PUFAs achieve significant improvements in their mental health when treated with a moderate dose of EPA and DHA. This finding could ease the mind and, one hopes, encourage additional research.

Buydens-Branchey L, Branchey M, Hibbeln JR. Associations between increases in plasma n-3 polyunsaturated fatty acids following supplementation and decreased anger and anxiety in substance abusers. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:568-575. [PubMed]

In this study, Shima Jazayeri and colleagues at the Tehran University of Medical Sciences in Iran sought to evaluate the effectiveness of fluoxetine (Prozac), EPA or a combination of them in patients with major depressive disorder as indicated by Hamilton Depression Rating Scale scores of 15 or greater. Patients did not have other psychiatric disorders or any other significant medical problems or substance abuse. They were not taking n-3 PUFA supplements nor eating more than one serving of fish/week. All participants were free of medication for at least 6 weeks prior to enrolment.

Sixty patients were recruited from referrals to the Roozbeh Psychiatric Hospital in Tehran and randomized to consume 20 mg of fluoxetine or 1 g EPA or a combination daily for 8 weeks. Each participant consumed either a fluoxetine placebo or a rapeseed oil placebo to mimic the type of capsules taken in each group. No placebo-only group was included for ethical reasons. Patients were assessed by the Hamilton Scales at baseline and every 2 weeks thereafter. Of the 60 patients enrolled, 48 completed at least 4 weeks of the study.

Over the course of the 8-week study, all patient groups exhibited significant reductions in their Hamilton depression scores as early as 2 weeks from baseline. Scores for patients treated with fluoxetine or EPA did not differ throughout the study. At 4 and 6 weeks, those consuming both EPA and fluoxetine showed a significantly greater improvement in their Hamilton ratings (as determined by analysis of covariance) compared with either treatment alone. Depression scores continued to improve from the 4th to the 8th week. Response rates for achieving at least a 50% reduction in depression score were 50% for fluoxetine, 56% for EPA and 81% for those taking both fluoxetine and EPA. More adverse events occurred in the fluoxetine and combination groups than in the EPA group and ranged from gastro-intestinal effects, anxiety and decreased appetite to single reports of tremor, nightmare and constipation.

These results suggest a greater improvement in depression with the combination of EPA and fluoxetine, but the effects of either one alone may have been no different from a placebo, had there been one. Other studies have reported a placebo effect of trial participation. This study supports those that have reported significant improvement in depression using a modest dose (1 g/day) of EPA as an adjunct treatment to current medication.

SOURCE: Jazayeri S, Tehrani-Doost M, Keshavarz SA, Hosseini M, Djazayery A, Amini H, Jalali M, Peet M. Comparison of therapeutic effects of omega-3 fatty acid eicosapentaenoic acid and fluoxetine, separately and in combination, in major depressive disorder. Aust N Z J Psychiatry 2008;42:192-198. [PubMed]

Scientists from the University of Alaska Fairbanks and the Fred Hutchinson Cancer Research Center in Seattle report that the ratio between 15N and 14N is elevated in fish, and therefore levels of 15N could be a suitable measure for EPA and DHA intake.

Writing in the American Journal of Clinical Nutrition, they report that analysis of the 15N levels in red blood cells of Yup’ik Eskimos were “strongly correlated with red blood cell EPA and DHA”, and “also correlated with dietary EPA and DHA intake”.

“The results strongly support the validity of RBC {delta}15N as a biomarker of EPA and DHA intake. Because the analysis of RBC {delta}15N is rapid and inexpensive, this method could facilitate wide-scale assessment of EPA and DHA intake in clinical and epidemiologic studies,” they concluded.

Source: American Journal of Clinical Nutrition
March 2009, Volume 89, Number 3, Pages 913-919, doi:10.3945/ajcn.2008.27054 “Red blood cell {delta}15N: a novel biomarker of dietary eicosapentaenoic acid and docosahexaenoic acid intake”
Authors: D.M. O’Brien et al.

In Japan, mortality from stroke is more than twice that of US men and about 1.5 times higher for women. The risk is related mainly to hypertension and also to diabetes, hypercholesterolemia and smoking. In this analysis of the JELIS study participants, the authors investigated the occurrence of a first or subsequent stroke in both treatment groups. Overall, the incidence of stroke was low, 114 (1.3%) in the statin group and 133 (1.5%) in the statin plus EPA group. This difference between the two groups was not statistically significant.

To assess secondary prevention, the investigators examined the 5-year recurrence of stroke (for example, cerebral thrombosis, embolism or hemorrhage) in patients who had a previous stroke. There were 457 stroke patients in the control group and 485 in the EPA group. Stroke recurred in 48 controls (10.5%) and 33 EPA patients (6.8%), a significant 20% reduction in risk with EPA consumption.

This is the first study to report a significantly reduced risk of stroke recurrence with EPA. Although this investigation observed no effect of EPA on stroke prevention, one epidemiological study reported an inverse association between fish or omega-3 fatty acid consumption and the risk of stroke in women. Other epidemiological studies have not observed a relationship between fish consumption and stroke. As the authors noted, the plasma concentration of EPA (2.8 mol%) prior to supplementation was already 10-fold higher than in the US Caucasian population, yet a benefit of increased consumption was still observed. If validated in western populations with low fish consumption, this study suggests there may be substantial opportunity to lower the risk of recurrent stroke with EPA.

SOURCEL Tanaka K, Ishikawa Y, Yokoyama M, Origasa H, Matsuzaki M, Saito Y, Matsuzawa Y, Sasaki J, Oikawa S, Hishida H, Itakura H. Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K; JELIS Investigators, Japan. Reduction in the recurrence of stroke by eicosapentaenoic acid for hypercholesterolemic patients: subanalysis of the JELIS trial. Stroke 2008;39:2052-2058. [PubMed]