Monday, December 15, 2014

Fish/Fish Oil: Miscellaneous Benefits

Fish Oil Reduces Inflammation

Scientists have provided new evidence that using more fish oil than vegetable oil in the diet decreases the formation of chemicals called prostanoids, which, when produced in excess, increase inflammation in various tissues and organs. The results, by William L. Smith, Professor and Chair of Biological Chemistry at the University of Michigan, Ann Arbor, and colleagues, may help in designing new anti-inflammatory drugs with fewer side effects than the ones currently available.

“Prostanoids help control blood pressure, fight allergies, and modulate inflammation, but too much of them – especially those made from vegetable oils – can also lead to increased pain, swelling, and redness in various tissues,” Smith says. “Our study shows that prostanoids made from fish oil are less effective at causing pain and swelling than those made from vegetable oil and that adding fish oil to the diet decreases the amount of prostanoids made from vegetable oil.”

The new study, to be published in the August 3, 2007 issue of the Journal of Biological Chemistry was selected as a “Paper of the Week” by the journal’s editors, meaning that it belongs to the top one percent of papers reviewed in significance and overall importance.

Smith and colleagues looked at the mutual effects of both oils by changing their respective amounts in cultured cells. As expected, a relative increase in fish oil lowered the amount of prostanoids from vegetable oil, although not always in the expected proportions.

Both fish and vegetable oils are converted into prostanoids through chemical reactions that are aided by enzymes called cyclo-oxygenases (COX), two types of which – COX-1 and COX-2 – are involved in the reactions. The scientists showed that, in reactions involving COX-1, when more fish oil is present, it preferentially binds to COX-1, thus limiting vegetable oil’s access to this enzyme. But in reactions involving COX-2, increasing the amount of fish oil did not change the way it binds to COX-2, so a significant portion of vegetable oil was still converted to prostanoids.

“This was completely unexpected,” Smith says. “This new result shows that COX-2 does not ‘prefer’ fish oil to vegetable oil. Regardless of the amount of extra fish oil that we added, COX-2 still helped convert all the vegetable oil available.”

This finding reveals for the first time a limit to how the body naturally regulates levels of prostanoids produced by fish and vegetable oil. If both oil types are present in the body, levels of prostanoids from fish oil will, in general, be higher than those coming from vegetable oil, but mechanisms such as the one involving COX-2 can counter this trend.

The researchers are now investigating why COX-1 and COX-2 act differently. One possibility is that since COX-2 has two binding sites, it can bind to both fish and vegetable oils. When fish oil binds to one of the two sites, it may prepare the other site to bind more easily to vegetable oil, a process called allostery.

Smith and his colleagues hope that by further investigating how prostanoids are regulated in the body, they can design potential drugs that bind to COX-2 and decrease levels of the vegetable oil prostanoids.

“The drugs that are currently used to inhibit COX-1 and COX-2 provide relief from the symptoms of inflammation and pain, but they still have many side effects,” Smith says. “By better understanding how prostanoids work at the cellular level, we hope to find new ways to regulate inflammation and create better anti-inflammatory drugs.”

Omega-3: Intervention for childhood behavioral problems?

At the forefront of a field known as "neurocriminology," Adrian Raine of the University of Pennsylvania has long studied the interplay between biology and environment when it comes to antisocial and criminal behavior. With strong physiological evidence that disruption to the emotion-regulating parts of the brain can manifest in violent outbursts, impulsive decision-making and other behavioral traits associated with crime, much of Raine's research involves looking at biological interventions that can potentially ward off these behavioral outcomes.

A new study by Raine now suggests that omega-3, a fatty acid commonly found in fish oil, may have long-term neurodevelopmental effects that ultimately reduce antisocial and aggressive behavior problems in children.

He is a Penn Integrates Knowledge Professor with appointments in the School of Arts & Sciences and the Perelman School of Medicine.

Along with Raine, the study featured Jill Portnoy a graduate student in the Department of Criminology, and Jianghong Liu, an associate professor in the Penn School of Nursing. They collaborated with Tashneem Mahoomed of Mauritius' Joint Child Health Project and Joseph Hibbeln of the National Institute on Alcohol Abuse and Alcoholism.

It was published in the Journal of Child Psychology and Psychiatry.

When Raine was a graduate student, he, his advisor and colleagues conducted a longitudinal study of children in the small island nation of Mauritius. The researchers tracked the development of children who had participated in an enrichment program as 3-year-olds and also the development of children who had not participated. This enrichment program had additional cognitive stimulation, physical exercise and nutritional enrichment. At 11 years, the participants showed a marked improvement in brain function as measured by EEG, as compared to the non participants. At 23, they showed a 34 percent reduction in criminal behavior.

Raine and his colleagues were interested in teasing apart the mechanisms behind this improvement. Other studies suggested the nutritional component was worth a closer look.

"We saw children who had poor nutritional status at age 3 were more antisocial and aggressive at 8, 11 and 17," Raine said. "That made us look back at the intervention and see what stood out about the nutritional component. Part of the enrichment was that the children receiving an extra two and a half portions of fish a week."

Other research at the time was beginning to show that omega-3 is critical to brain development and function.

"Omega-3 regulates neurotransmitters, enhances the life of a neuron and increases dendritic branching, but our bodies do not produce it. We can only get it from the environment," Raine said.

Research on the neuroanatomy of violent criminals suggested this might be a place to intervene. Other brain-imaging researchers have shown that omega-3 supplementation increases the function of the dorsolateral prefrontal cortex, a region Raine found to have higher rates of damage or dysfunction in criminal offenders.

Raine's new study featured a randomized controlled trial where children would receive regular omega-3 supplements in the form of a juice drink. One hundred children, aged 8 to 16, would each receive a drink containing a gram of omega-3 once a day for six months, matched with 100 children who received the same drink without the supplement. The children and parents in both groups took a series of personality assessments and questionnaires at the start.

After six months, the researchers administered a simple blood test to see if the children in the experimental group had higher levels of omega-3 than those in the controls. They also had both parents and children take the personality assessments. Six months after that, the researchers had parents and children take the assessment again to see if there were any lasting effects from the supplements.

The assessments had parents rate their children on "externalizing" aggressive and antisocial behavior, such as getting into fights or lying, as well as "internalizing" behavior, such as depression, anxiety and withdrawal. Children were also asked to rate themselves on these traits.

While the children's self-reports remained flat for both groups, the average rate of antisocial and aggressive behavior as described by the parents dropped in both groups by the six-month point. Critically, however, those rates returned to the baseline for the control group but remained lowered in the experimental group, at the 12-month point.

"Compared to the baseline at zero months," Raine said, "both groups show improvement in both the externalizing and internalizing behavior problems after six months. That's the placebo effect.

"But what was particularly interesting was what was happening at 12 months. The control group returned to the baseline while the omega-3 group continued to go down. In the end, we saw a 42 percent reduction in scores on externalizing behavior and 62 percent reduction in internalizing behavior."

At both the six- and 12-month check-ins, parents also answered questionnaires about their own behavioral traits. Surprisingly, parents also showed an improvement in their antisocial and aggressive behavior. This could be explained by the parents taking some of their child's supplement, or simply because of a positive response to their child's own behavioral improvement.

The researchers caution that this is still preliminary work in uncovering the role nutrition plays in the link between brain development and antisocial behavior. The changes seen in the one-year period of the experiment may not last, and the results may not be generalizable outside the unique context of Mauritius.

Beyond these caveats, however, there is reason to further examine omega-3's role as a potential early intervention for antisocial behavior.

"As a protective factor for reducing behavior problems in children," Liu said, "nutrition is a promising option; it is relatively inexpensive and can be easy to manage."

Pregnant women not getting enough omega-3, critical for infant development

Alberta Pregnancy Outcomes and Nutrition (APrON) is a birth cohort involving over two thousand women and their infants from Calgary and Edmonton that was funded by Alberta Innovates Health Solutions and includes researchers at the University of Alberta and the University of Calgary. The main objective of APrON is to understand the relationship between maternal nutrient status during pregnancy and maternal mental health and child health and development. 

As part of the project, the APrON team studied the first 600 women in the cohort during and after their pregnancy to see whether they were consuming enough omega-3 long chain polyunsaturated fatty acids (omega 3-LCPUFA) to meet current recommendations. The team has just published (March 2015) heir results in the journal Applied Physiology, Nutrition, and Metabolism.

Omega-3 LCPUFA include eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). A source of these is required during pregnancy for fetal and placental development and is critical for the development of the infant, particularly for brain development.

The American Dietetic Association along with Dietitians of Canada recommends that all healthy adults including pregnant and lactating women consume at least 500 mg/day of omega-3 LCPUFA. The European Commission and the International Society for the Study of Fatty Acids and Lipids (ISSFAL) specifically recommends that pregnant and lactating women consume a minimum of 200 mg DHA per day.

The women from this group of APrON participant lived in Edmonton and Calgary. The team found that the majority of participants, despite a high level of education and income, were not meeting these recommendations for omega-3 LCPUFA during pregnancy and lactation.

According to the study: "Only 27% of women during pregnancy and 25% at three months postpartum met the current European Union (EU) consensus recommendation for DHA. Seafood, fish and seaweed products contributed to 79% of overall n-3 long chain polyunsaturated fatty acids intake from foods, with the majority from salmon. Results suggest that the majority of women in the cohort were not meeting the EU recommendation for DHA during pregnancy and lactation."

The current study found women who took a supplement containing DHA were 10.6 and 11.1 times more likely to meet the current EU consensus recommendation for pregnancy and postpartum, respectively. Recommendations could also be met by following the Health Canada recommendation to consume one to two portions per week of fish high in omega-3 fatty acids.

The results of this also study suggests that nutritional counseling and education about benefits of a supplement source of LCPUFA should extend beyond pregnancy as 44% percent of the women in the cohort who reported taking a supplement during pregnancy were no longer taking these supplements when breast feeding at three months postpartum.

The current study provides useful information for health practitioners and for future interventions (dietary or supplement recommendations) aimed at helping women obtain LCPUFA in their diet to ensure they are able to meet the needs of their infants.

The amount of omega-3 docosahexaenoic acid (DHA) in a mother’s milk is the strongest predictor of test performance

You are what you eat, the saying goes, and now a study conducted by researchers at UC Santa Barbara and the University of Pittsburgh suggests that the oft-repeated adage applies not just to physical health but to brain power as well.

In a paper published in the early online edition of the journal Prostaglandins, Leukotrienes and Essential Fatty Acids, the researchers compared the fatty acid profiles of breast milk from women in over two dozen countries with how well children from those same countries performed on academic tests.

Their findings show that the amount of omega-3 docosahexaenoic acid (DHA) in a mother’s milk — fats found primarily in certain fish, nuts and seeds — is the strongest predictor of test performance. It outweighs national income and the number of dollars spent per pupil in schools.

DHA alone accounted for about 20 percent of the differences in test scores among countries, the researchers found.

On the other hand, the amount of omega-6 fat in mother’s milk — fats that come from vegetable oils such as corn and soybean — predict lower test scores. When the amount of DHA and linoleic acid (LA) — the most common omega-6 fat — were considered together, they explained nearly half of the differences in test scores. In countries where mother’s diets contain more omega-6, the beneficial effects of DHA seem to be reduced.

“Human intelligence has a physical basis in the huge size of our brains — some seven times larger than would be expected for a mammal with our body size,” said Steven Gaulin, UCSB professor of anthropology and co-author of the paper. “Since there is never a free lunch, those big brains need lots of extra building materials — most importantly, they need omega-3 fatty acids, especially DHA. Omega-6 fats, however, undermine the effects of DHA and seem to be bad for brains.”

Both kinds of omega fat must be obtained through diet. But because diets vary from place to place, for their study Gaulin and his co-author, William D. Lassek, M.D., a professor at the University of Pittsburgh’s Graduate School of Public Health and a retired assistant surgeon general, estimated the DHA and LA content — the good fat and the bad fat — in diets in 50 countries by examining published studies of the fatty acid profiles of women’s breast milk.

The profiles are a useful measure for two reasons, according to Gaulin. First, because various kinds of fats interfere with one another in the body, breast milk DHA shows how much of this brain-essential fat survives competition with omega-6. Second, children receive their brain-building fats from their mothers. Breast milk profiles indicate the amount of DHA children in each region receive in the womb, through breastfeeding, and from the local diet available to their mothers and to them after they are weaned.

The academic test results came from the Programme for International Student Assessment (PISA), which administers standardized tests in 58 nations. Gaulin and Lassek averaged the three PISA tests — math, science and reading ability — as their measure of cognitive performance. There were 28 countries for which the researchers found information about both breast milk and test scores.

“Looking at those 28 countries, the DHA content of breast milk was the single best predictor of math test performance,” Gaulin said. The second best indicator was the amount of omega-6, and its effect is opposite. “Considering the benefits of omega-3 and the detriment of omega-6, we can get pretty darn close to explaining half the difference in scores between countries,” he added. When DHA and LA are considered together, he added, they are twice as effective at predicting test scores as either is alone, Gaulin said.

Gaulin and Lassek considered two economic factors as well: per capita gross domestic product (a measure of average wealth in each nation) and per student expenditures on education. “Each of these factors helps explain some of the differences between nations in test scores, but the fatty acid profile of the average mother’s milk in a given country is a better predictor of the average cognitive performance in that country than is either of the conventional socioeconomic measures people use,” said Gaulin.

From their analysis, the researchers conclude that both economic wellbeing and diet make a difference in cognitive test performance, and children are best off when they have both factors in their favor. “But if you had to choose one, you should choose the better diet rather than the better economy,” Gaulin said.

The current research follows a study published in 2008 that showed that the children of women who had larger amounts of gluteofemoral fat “depots” performed better on academic tests than those of mothers with less. “At that time we weren’t trying to identify the dietary cause,” explained Gaulin. “We found that this depot that has been evolutionarily elaborated in women is important to building a good brain. We were content at that time to show that as a way of understanding why the female body is as evolutionarily distinctive as it is.”

Now the researchers are looking at diet as the key to brain-building fat, since mothers need to acquire these fats in the first place. 

Their results are particularly interesting in 21st-century North America, Gaulin noted, because our current agribusiness-based diets provide very low levels of DHA — among the lowest in the world. Thanks to two heavily government-subsidized crops — corn and soybeans — the average U.S. diet is heavy in the bad omega-6 fatty acids and far too light on the good omega-3s, Gaulin said.

“Back in the 1960s, in the middle of the cardiovascular disease epidemic, people got the idea that saturated fats were bad and polyunsaturated fats were good,” he explained. “That’s one reason margarine became so popular. But the polyunsaturated fats that were increased were the ones with omega-6, not omega-3. So our message is that not only is it advisable to increase omega 3 intake, it’s highly advisable to decrease omega-6 — the very fats that in the 1960s and ’70s we were told we should be eating more of.”

Gaulin added that mayonnaise is, in general, the most omega-6-laden food in the average person’s refrigerator. “If you have too much of one — omega-6 — and too little of the other — omega 3 — you’re going to end up paying a price cognitively,” he said.

The issue is a huge concern for women, Gaulin noted, because “that’s where kids’ brains come from. But it’s important for men as well because they have to take care of the brains their moms gave them.

 “Just like a racecar burns up some of its motor oil with every lap, your brain burns up omega-3 and you need to replenish it every day,” he said.

Fish and fatty acid consumption associated with lower risk of hearing loss in women

Study provides insights to possibly prevent or delay acquired hearing loss

Researchers at Brigham and Women's Hospital found that consumption of two or more servings of fish per week was associated with a lower risk of hearing loss in women. Findings of the new study Fish and Fatty Acid Consumption and Hearing Loss study led by Sharon G. Curhan, MD, BWH Channing Division of Network Medicine, are published online on September 10, 2014 in the American Journal of Clinical Nutrition (AJCN).

"Acquired hearing loss is a highly prevalent and often disabling chronic health condition," stated Curhan, corresponding author. "Although a decline in hearing is often considered an inevitable aspect of aging, the identification of several potentially modifiable risk factors has provided new insight into possibilities for prevention or delay of acquired hearing loss."

Although evidence suggests higher intake of fish and long-chain omega-3 polyunsaturated fatty acids (PUFA) may be associated with lower risk of hearing loss, prospective information is limited. This prospective study examined over time the independent associations between consumption of total and specific types of fish, long-chain omega-3 PUFA, and self-reported hearing loss in women.

Data were from the Nurses' Health Study II, a prospective cohort study. In the study, 65,215 women were followed from 1991 to 2009. After 1,038,093 person-years of follow-up, 11,606 cases of incident hearing loss were reported. In comparison with women who rarely consumed fish, women who consumed two or more servings of fish per week had a 20 percent lower risk of hearing loss. When examined individually, higher consumption of each specific fish type was inversely associated with risk. Higher intake of long-chain omega-3PUFA was also inversely associated with risk of hearing loss.

"Consumption of any type of fish (tuna, dark fish, light fish, or shellfish) tended to be associated with lower risk. These findings suggest that diet may be important in the prevention of acquired hearing loss," stated Curhan.

Fish oil can boost the immune system

New research published in the Journal of Leukocyte Biology suggests that instead of suppressing the body's immune response, fish oil actually enhances the function of B cells

Fish oil rich in DHA and EPA is widely believed to help prevent disease by reducing inflammation, but until now, scientists were not entirely sure about its immune enhancing effects. A new report appearing in the April 2013 issue of the Journal of Leukocyte Biology, helps provide clarity on this by showing that DHA-rich fish oil enhances B cell activity, a white blood cell, challenging the notion that fish oil is only immunosuppressive. This discovery is important as it shows that fish oil does not necessarily reduce the overall immune response to lower inflammation, possibly opening the doors for the use of fish oil among those with compromised immune systems.

"Fish oil may have immune enhancing properties that could benefit immunocompromised individuals," said Jenifer Fenton, Ph.D., M.P.H., a researcher involved in the work from the Department of Food Science and Human Nutrition at Michigan State University in East Lansing, Michigan.

To make this discovery, researchers used two groups of mice. One group was fed a control diet, and the other was fed a diet supplemented with DHA-rich fish oil for five weeks. B cells were harvested from several tissues and then stimulated in culture. Researchers then looked for markers of B cell activation on the cell surface, B cell membrane changes, and B cell cytokine production. They found that DHA-enriched fish oil enhanced B cell activation and select antibody production, which may actually aid immune responses associated with pathogen clearance, while possibly dampening the totality of the inflammatory response.

"This work confirms similar findings on fish oil and B cells from our lab, and moves us one step closer to understanding the immune enhancing properties of EPA and DHA," said S. Raza Shaikh, Ph.D., a researcher also involved in the work from the Department of Biochemistry and Molecular Biology at East Carolina University.

Fish Oil Reduces Hospital Stays
A randomised controlled trial of fish oil given intravenously to patients in intensive care has found that it improves gas exchange, reduces inflammatory chemicals and results in a shorter length of hospital stay.

Researchers writing in BioMed Central's open access journal Critical Care (January , 2010) investigated the effects of including fish oil in the normal nutrient solution for patients with sepsis, finding a significant series of benefits.

Philip Calder, from the University of Southampton, UK, worked with a team of researchers to carry out the study in 23 patients with systemic inflammatory response syndrome or sepsis in the Hospital Padre Américo, Portugal. He said, "Recently there has been increased interest in the fat and oil component of vein-delivered nutrition, with the realization that it not only supplies energy and essential building blocks, but may also provide bioactive fatty acids. Traditional solutions use soybean oil, which does not contain the omega-3 fatty acids contained in fish oil that act to reduce inflammatory responses. In fact, soybean oil is rich in omega-6 acids that may actually promote inflammation in an excessive or unbalanced supply."

Calder and his colleagues found that the 13 patients in the fish oil group had lower levels of inflammatory agents in their blood, were able to achieve better lung function and left hospital earlier than the 10 patients who received traditional nutrition.

According to Calder, "This is the first study of this particular fish oil solution in septic patients in the ICU. The positive results are important since they indicate that the use of such an emulsion in this group of patients will improve clinical outcomes, in comparison with the standard mix."

Eating fish helps vs allergies
Women who eat fish during pregnancy may reduce the risk of their children developing asthma or allergic disease, suggests a new study presented at the American Thoracic Society 2007 International Conference, on Sunday, May 20.

The SEATON study, conducted at the University of Aberdeen, UK, found that the children of mothers who ate fish once or more a week were less likely to have had eczema than children of mothers who never ate fish.

The study did not find any protective effect against allergic diseases from many other foods, including vegetables, fruit juice, citrus or kiwi fruit, whole grain products, fat from dairy products or margarine or other low-fat spreads.

The researchers studied 1212 children born to women who had filled out food questionnaires during their pregnancy. When the children were 5 years old, the mothers filled out a questionnaire about the children’s respiratory symptoms and allergies, as well as a questionnaire about their child’s food consumption.

The children were also given lung function and allergy tests. Previous studies in the same children have found evidence for protective effects of vitamin E and D and zinc during pregnancy in reducing the risk of children’s wheeze and asthma, notes researcher Saskia Willers, M.Sc. of Utrecht University in the Netherlands. If the new results are confirmed, she says, "recommendations on dietary modification during pregnancy may help to prevent childhood asthma and allergy."

Omega-3 fatty acids, especially DHA, are of significant value in the prevention of fatty liver disease

A study of the metabolic effects of omega-3 fatty acids, especially DHA, concludes that these compounds may have an even wider range of biological impacts than previously considered, and suggests they could be of significant value in the prevention of fatty liver disease.

The research, done by scientists at Oregon State University and several other institutions, was one of the first of its type to use “metabolomics,” an analysis of metabolites that reflect the many biological effects of omega-3 fatty acids on the liver. It also explored the challenges this organ faces from the “Western diet” that increasingly is linked to liver inflammation, fibrosis, cirrhosis and sometimes liver failure.

The results were surprising, researchers say.

Supplements of DHA, used at levels that are sometimes prescribed to reduce blood triglycerides, appeared to have many unanticipated effects. There were observable changes in vitamin and carbohydrate metabolism, protein and amino acid function, as well as lipid metabolism.

Supplementation with DHA partially or totally prevented metabolic damage through those pathways often linked to the Western diet – excessive consumption of red meat, sugar, saturated fat and processed grains.

The findings were published December, 2013 in PLOS One, an online professional journal.

“We were shocked to find so many biological pathways being affected by omega-3 fatty acids,” said Donald Jump, a professor in the OSU College of Public Health and Human Sciences. “Most studies on these nutrients find effects on lipid metabolism and inflammation.

“Our metabolomics analysis indicates that the effects of omega-3 fatty acids extend beyond that, and include carbohydrate, amino acid and vitamin metabolism,” he added.

Omega-3 fatty acids have been the subject of much recent research, often with conflicting results and claims. Possible reasons for contradictory findings, OSU researchers say, are the amount of supplements used and the relative abundance of two common omega-3s – DHA and EPA. Studies at OSU have concluded that DHA has far more ability than EPA to prevent the formation of harmful metabolites. In one study, it was found that DHA supplementation reduced the proteins involved in liver fibrosis by more than 65 percent.

These research efforts, done with laboratory animals, used a level of DHA supplementation that would equate to about 2-4 grams per day for an average person. In the diet, the most common source of DHA is fatty fish, such as salmon, mackerel or sardines.

The most recent research is beginning to break down the specific processes by which these metabolic changes take place. If anything, the results suggest that DHA may have even more health value than previously thought.

“A lot of work has been done on fatty liver disease, and we are just beginning to explore the potential for DHA in preventing or slowing disease progression,” said Jump, who is also a principal investigator in OSU’s Linus Pauling Institute.

“Fish oils, a common supplement used to provide omega-3, are also not prescribed to regulate blood glucose levels in diabetic patients,” he said. “But our studies suggest that DHA may reduce the formation of harmful glucose metabolites linked to diabetic complications.”

Both diabetes and liver disease are increasing steadily in the United States.

The American Liver Foundation has estimated that about 25 percent of the nation’s population, and 75 percent of those who are obese, have nonalcoholic fatty liver disease. This can progress to nonalcoholic steatohepatitis, cirrhosis and cancer.

This study established that the main target of DHA in the liver is the control of inflammation, oxidative stress and fibrosis, which are the characteristics of more progressively serious liver problems. Omega-3 fatty acids appear to keep cells from responding to and being damaged by whatever is causing inflammation.

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