Monday, December 15, 2014

Fish/Fish Oil: Mood and Anxiety Benefits

Omega-3 fatty acids in fish oil supplements fight depression

Patients with increased inflammation, including those receiving cytokines for medical treatment, have a greatly increased risk of depression. For example, a 6-month treatment course of interferon-alpha therapy for chronic hepatitis C virus infection causes depression in approximately 30% of patients.

Omega-3 fatty acids, more commonly known as fish oil, have a long list of health benefits, including lowering the risk of heart disease and reducing triglyceride levels. These nutritional compounds are also known to have anti-depressant and anti-inflammatory properties.

Despite some recent negative findings, as their tendency to increase the risk for prostate cancer was proven and some of the putative health benefits were not replicated in large trials, omega-3's remain of high interest to the depression field, where several studies have suggested benefits for depression and other psychiatric disorders.

This led a group of international researchers, led by senior author Dr. Carmine Pariante, to conduct a randomized, double-blind, placebo-controlled study in order to carefully evaluate the effects of omega-3 fatty acids on inflammation-induced depression.

They recruited 152 patients with hepatitis C to participate, each of whom was randomized to receive two weeks of treatment with EPA, DHA, or placebo. EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are the two main omega-3 fatty acids in fish oil supplements.

Following the two-week treatment, the patients received a 24-week course of interferon-alpha treatment and were evaluated repeatedly for depression.

The researchers found that treatment with EPA, but not DHA or placebo, decreased the incidence of interferon-alpha-induced depression in patients being treated for hepatitis C.

Pariante, a Professor at the Institute of Psychiatry, Psychology & Neuroscience at King's College London, added, "The study shows that even a short course (two weeks) of a nutritional supplement containing one such omega-3 polyunsaturated fatty acid (EPA) reduced the rates of new-onset depression to 10%."

In addition, both EPA and DHA delayed the onset of depression, and both treatments were well tolerated, with no serious side effects.

"These new data provide promising support for omega-3 fatty acids to prevent depression, complementing other studies where omega-3's were found to enhance antidepressant treatment," said Dr. John Krystal, Editor of Biological Psychiatry.

EPA is considered an "endogenous" anti-inflammatory, and in previous work, also published in Biological Psychiatry, these same authors found that subjects with low levels of endogenous EPA in the blood were at higher risk of developing depression. Therefore, the authors speculate that this nutritional intervention restores the natural protective anti-inflammatory capabilities of the body, and thus protects patients from new-onset depression when inflammation occurs.

Although further work is still necessary and the findings must be replicated, these data indicate that omega-3 polyunsaturated fatty acids may be effective in preventing depression in a group of patients at high-risk of depression because of increased inflammation.

The article is "Omega-3 Fatty Acids in the Prevention of Interferon-Alpha-Induced Depression: Results from a Randomized, Controlled Trial" by Kuan-Pin Su, Hsueh-Chou Lai, Hui-Ting Yang, Wen-Pang Su, Cheng-Yuan Peng, Jane Pei-Chen Chang, Hui-Chih Chang, and Carmine M. Pariante (doi: 10.1016/j.biopsych.2014.01.008). The article appears in Biological Psychiatry, Volume 76, Issue 7 (October 1, 2014), published by Elsevier.

Fish oil showed a marked reduction both in anxiety among a cohort of healthy young people

A new study gauging the impact of consuming more fish oil showed a marked reduction both in inflammation and, surprisingly, in anxiety among a cohort of healthy young people.

The findings suggest that if young participants can get such improvements from specific dietary supplements, then the elderly and people at high risk for certain diseases might benefit even more.

The findings by a team of researchers at Ohio State University were published (July, 2011) in the journal Brain, Behavior and Immunity. It is the latest from more than three decades of research into links between psychological stress and immunity.

Omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have long been considered as positive additives to the diet. Earlier research suggested that the compounds might play a role in reducing the level of cytokines in the body, compounds that promote inflammation, and perhaps even reduce depression.

Psychological stress has repeatedly been shown to increase cytokine production so the researchers wondered if increasing omega-3 might mitigate that process, reducing inflammation.

To test their theory, they turned to a familiar group of research subjects – medical students. Some of the earliest work these scientists did showed that stress from important medical school tests lowered students’ immune status.

“We hypothesized that giving some students omega-3 supplements would decrease their production of proinflammatory cytokines, compared to other students who only received a placebo,” explained Janice Kiecolt-Glaser, professor of psychology and psychiatry.

“We thought the omega-3 would reduce the stress-induced increase in cytokines that normally arose from nervousness over the tests.”

The team assembled a field of 68 first- and second-year medical students who volunteered for the clinical trial. The students were randomly divided into six groups, all of which were interviewed six times during the study. At each visit, blood samples were drawn from the students who also completed a battery of psychological surveys intended to gauge their levels of stress, anxiety or depression. The students also completed questionnaires about their diets during the previous weeks.

Half the students received omega-3 supplements while the other half were given placebo pills.

“The supplement was probably about four or five times the amount of fish oil you’d get from a daily serving of salmon, for example,” explained Martha Belury, professor of human nutrition and co-author in the study.

Part of the study, however, didn’t go according to plans.

Changes in the medical curriculum and the distribution of major tests throughout the year, rather than during a tense three-day period as was done in the past, removed much of the stress that medical students had shown in past studies.

“It may be too early to recommend a broad use of omega-3 supplements throughout the public, especially considering the cost and the limited supplies of fish needed to supply the oil,” Belury said. “People should just consider increasing their omega-3 through their diet.”

“These students were not anxious. They weren’t really stressed. They were actually sleeping well throughout this period, so we didn’t get the stress effect we had expected,” Kiecolt-Glaser said.

But the psychological surveys clearly showed an important change in anxiety among the students: Those receiving the omega-3 showed a 20 percent reduction in anxiety compared to the placebo group.

An analysis of the of the blood samples from the medical students showed similar important results.

“We took measurements of the cytokines in the blood serum, as well as measured the productivity of cells that produced two important cytokines, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFa),” said Ron Glaser, professor of molecular virology, immunology & medical genetics and director of the Institute for Behavioral Medicine Research.

“We saw a 14 percent reduction in the amounts of IL-6 among the students receiving the omega-3.” Since the cytokines foster inflammation, “anything we can do to reduce cytokines is a big plus in dealing with the overall health of people at risk for many diseases,” he said.

While inflammation is a natural immune response that helps the body heal, it also can play a harmful role in a host of diseases ranging from arthritis to heart disease to cancer.

While the study showed the positive impact omega-3 supplements can play in reducing both anxiety and inflammation, the researchers aren’t willing to recommend that the public start adding them to the daily diet.

"It may be too early to recommend a broad use of omega-3 supplements throughout the public, especially considering the cost and the limited supplies of fish needed to supply the oil,” Belury said. “People should just consider increasing their omega-3 through their diet.” Some of the researchers, however, acknowledged that they take omega-3 supplements.

Omega-3 Consumed During Pregnancy Curbs Postpartum Depression Symptoms

Fish has long been considered in myriad cultures to be "brain food," but only recently has bona fide science begun to support this deep-rooted belief. Researchers now know that the omega-3 fatty acids found in oily fish such as salmon and herring may play a critical role in both development and maintenance of the brain and nerves. Although sufficient amounts of these long-chain fats can be synthesized endogenously by most adults, experts recommend that pregnant women and infants get additional amounts of these compounds from their diets.

This, combined with research suggesting that these fats play a critical role in cognitive and visual development during early life, has prompted much research and product development aimed at pregnant women and newborn infants. Studies have also suggested that higher consumption of certain omega-3 fatty acids may also benefit adult mental health as well -- for instance, as it might relate to lower risk for depression.

Dr. Michelle Price Judge, a faculty member at the University of Connecticut School of Nursing, is keenly interested in how omega-3 fatty acids consumed during pregnancy impact both maternal and infant health. She has demonstrated previously that maternal consumption of docosahexaenoic acid (DHA; a prominent omega-3 fatty acid) during pregnancy gives infants a developmental advantage even 9 months after they are born. These findings prompted her to consider the benefits that DHA could holistically have on the maternal-infant dyad. Specifically, might greater omega-3 fatty acid intake during pregnancy lower risk for postpartum depression, a condition that leads to a multitude of problems including interruptions in maternal-infant attachment and subsequent impairments in later infant development?

As part of the scientific program of the American Society for Nutrition, results from this study were presented at the Experimental Biology 2011 meeting in Washington, DC.

To answer this question, Dr. Judge oversaw a randomized, double-blind, placebo-controlled dietary intervention trial in which 52 pregnant women took either a placebo (corn oil) or a fish oil capsule containing 300 milligrams of DHA 5 days each week from 24-40 weeks of pregnancy. This is the amount a woman would consume if she ate about ½ serving of salmon. It is noteworthy that dietary DHA intake during pregnancy has been estimated to be 50-70 milligrams of DHA daily: a mere fraction of the 200 milligrams daily that is considered optimal during pregnancy by most experts. Using the Postpartum Depression Screening Scale developed by her colleague and coauthor Dr. Cheryl Beck, Judge was able to categorize postpartum women as having negligible depressive symptoms, significant symptoms of postpartum depression, or being "positive" for this condition. The Postpartum Depression Screening Scale also assisted the research team in discerning between several symptoms specific to the disorder including sleeping/eating disturbances, anxiety, emotional liability, confusion, loss of self, guilt, and thoughts of suicide.

Although the study did not have enough women to investigate if fish oil consumption resulted in a lower incidence of diagnosable postpartum depression, women in the treatment group had significantly lower total Postpartum Depression Screening Scale scores, with significantly fewer symptoms common to postpartum depression. For example, compared to those in the control group, women in the fish oil group were less likely to report symptoms related to anxiety and loss of self.

Judge and coworkers concluded "DHA consumption during pregnancy -- at levels that are reasonably attained from foods -- has the potential to decrease symptoms of postpartum depression." Why is this important? For starters, some experts estimate that postpartum depression affects a whopping 25% of new mothers. And healthcare providers agree that this condition can have devastating consequences, not only for the women experiencing it but also for their children and family.

The bottom line? Although larger-scale intervention studies will be needed to better understand the mechanisms and magnitude by which fish oil consumption can improve postpartum mental health, women would be wise to eat at least a serving of high-omega-3 fish 2-3 days per week. Although fish oil supplements may be more acceptable to some women, the real thing is clearly the more nutritious option as a serving of fish is also protein- and mineral-rich. Clearly, fish as a "brain food" is gaining the nod from not only from the general public, but scientists as well. 

Omega-3s boost mood and behavior 
Omega-3 fatty acids, found in fatty fish like salmon, are associated with increased grey matter volume in areas of the brain commonly linked to mood and behavior according to a University of Pittsburgh study.

Findings were presented by Sarah M. Conklin, Ph.D., postdoctoral scholar at the Cardiovascular Behavioral Medicine Program in the department of psychiatry at the University of Pittsburgh, at the American Psychosomatic Society’s Annual Meeting, (2007) held in Budapest, Hungary.

Animal research has shown that raising omega-3 intake leads to structural brain changes. In a separate study presented by Dr. Conklin at the society’s meeting last year, Pitt researchers reported that people who had lower blood levels of omega-3 fatty acids were more likely to have a negative outlook and be more impulsive. Conversely, those with higher blood levels of omega-3s were found to be more agreeable and less likely to report mild or moderate symptoms of depression. In the study being presented today, the researchers sought to investigate if grey matter volume was proportionally related to long-chain omega-3 intake in humans, especially in areas of the brain related to mood, helping them attempt to explain the mechanisms behind the improvement in mood often associated with long-chain omega-3 intake.

Researchers interviewed 55 healthy adult participants to determine their average intake of long-chain omega-3 fatty acids. Grey matter volume was evaluated using high-resolution structural MRI. The researchers discovered that participants who had high levels of long-chain omega-3 fatty acid intake had higher volumes of grey matter in areas of the brain associated with emotional arousal and regulation – the bilateral anterior cingulate cortex, the right amygdala and the right hippocampus.

While this finding suggests that omega-3s may promote structural improvement in areas of the brain related to mood and emotion regulation – the same areas where grey matter is reduced in people who have mood disorders such as major depressive disorder – investigators note that more research is needed to determine whether fish consumption actually causes changes in the brain.

Fish intake associated with boost to antidepressant response
 Up to half of patients who suffer from depression (Major Depressive Disorder, or MDD) do not respond to treatment with SSRIs (Selective Serotonin Reuptake Inhibitors). Now a group of Dutch researchers have carried out a study which shows that increasing fatty fish intake appears to increase the response rate in patients who do not respond to antidepressants. This work was presented at the October 2014 European College of Neuropsychopharmacology congress in Berlin.
According to lead researcher, Roel Mocking (Amsterdam):
"We were looking for biological alterations that could explain depression and antidepressant non-response, so we combined two apparently unrelated measures: metabolism of fatty acids and stress hormone regulation. Interestingly, we saw that depressed patients had an altered metabolism of fatty acids, and that this changed metabolism was regulated in a different way by stress hormones".
The researchers were looking at the relationship between depression and fatty acids, and various hormones, including the stress hormone cortisol. They took 70 patients with depression and compared them to 51 healthy controls, by measuring their fatty acid levels and cortisol levels. They then gave the depressed patients 20mg of an SSRI daily for 6 weeks, and in those who did not respond to the SSRIs the dose was gradually increased up to 50mg/day. Fatty acid and cortisol levels were measured during the trial.
They found that the MDD patients who didn't respond to the SSRI also tended to have abnormal fatty acid metabolism, so they checked the dietary habits of all those taking part in the trial. Fatty fish is rich in fatty acids, such as the well-known Omega-3 DHA. So the researchers looked at the amount of fatty fish in the diet of all involved in the trial. They categorised the patients into 4 groups, according to their fatty fish intake, and they found that those who took the least fish tended to respond badly to anti-depressants, whereas those who had most fish in the diet responded best to anti-depressants. Those who ate fatty fish at least once a week had a 75% chance of responding to antidepressants, whereas those who never ate fatty fish had only a 23% chance of responding to antidepressants. Roel Mocking continued:
"This means that the alterations in fatty acid metabolism (and their relationship with stress hormone regulation) were associated with future antidepressant response. Importantly, this association was associated with eating fatty fish, which is an important dietary source of omega-3 fatty acids. These findings suggest that measures of fatty acid metabolism, and their association with stress hormone regulation, might be of use in the clinic as an early indicator of future antidepressant response. Moreover, fatty acid metabolism could be influenced by eating fish, which may be a way to improve antidepressant response rates".
"So far this is an association between fatty acids in blood and anti-depressant response; so it's not necessarily a causal effect. Our next step is to look at whether these alterations in fatty acid metabolism and hormonal activity are specific for depression, so we are currently repeating these measurements in patients with post-traumatic stress disorder and schizophrenia".
ECNP President, Professor Guy Goodwin (Oxford) said:

'Understanding non-response to treatment with SSRIs remains an important known unknown. There is already an intriguing association between eating fish and general health. The present study, while preliminary, takes the story into the realm of depression. Larger scale definitive studies will be of considerable interest".

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