Health for life

The omega 3 fatty acids in fish oil have long been thought to protect against cardiovascular disease—so much so that the American Heart Association currently recommends eating at least two servings of fish a week, particularly fatty varieties rich in omega 3s. However, the mechanism behind this protective effect still remains a mystery.

In a new study, scientists led by Jason R. Carter of Michigan Technological University shed light on this phenomenon by providing evidence that fish oil might specifically counteract the detrimental effects of mental stress on the heart. Their findings show that volunteers who took fish oil supplements for several weeks had a blunted response to mental stress in several measurements of cardiovascular health, including heart rate and muscle sympathetic nerve activity (MSNA), part of the "fight or flight" response, compared to volunteers who took olive oil instead. The results may explain why taking fish oil could be beneficial to the heart and might eventually help doctors prevent heart disease in select populations.

The article is entitled "Fish Oil and Neurovascular Reactivity to Mental Stress in Humans." It appears in the May edition of the American Journal of Physiology – Regulatory, Integrative, and Comparative Physiology, published by the American Physiological Society. It is available online at http://bit.ly/10j0CSS

Methodology

Carter and his colleagues worked with 67 adult volunteers. At the beginning of the study, each volunteer underwent a battery of tests to assess cardiovascular function, including heart rate, blood pressure, MSNA, and blood flow through the forearm and calf. These tests were performed first when the volunteers were at rest, and then again while they were performing a mental arithmetic test while the investigator encouraged them to hurry, a situation designed to induce acute mental stress. The study subjects were then nearly equally assigned to take either 9 grams of fish oil per day or 9 grams of olive oil, a placebo that hasnt been shown to have the same beneficial cardiovascular effects as fish oil. None of the volunteers were aware of which supplement they were taking. After 8 weeks of this intervention, the study subjects underwent the same tests again.

Results

The researchers found that test results didnt change between the two groups of study subjects when they were at rest. However, results for the volunteers who took fish oil and those who received the placebo differed significantly for some of the tests during the mental stress. Those in the fish oil group showed blunted heart rate reactivity while they were stressed compared to those who took olive oil. Similarly, the total MSNA reactivity to mental stress was also blunted in the fish oil group.

Importance of the Findings

These results show that fish oil could have a protective effect on cardiovascular function during mental stress, a finding that adds a piece to the puzzle on why taking fish oil helps the heart stay healthy, the authors suggest. Future studies might focus on the effects of taking fish oil for longer time periods and examining this effect on older populations or people with cardiovascular disease.

"Overall," the study authors say, "the data support and extend the growing evidence that fish oil may have positive health benefits regarding neural cardiovascular control in humans and suggest important physiological interactions between fish oil and psychological stress that may contribute to disease etiology."

Eating fish may reduce the risk of heart attack, but it is important to steer clear from the type of fish that contains the most amounts of mercury, according to experts from Umeå University in Sweden.

The researchers have worked together with teams from Finland and other countries in order to assess whether the advantages of heathy fatty acids outweigh the risks of mercury proportion.

Previous research has said that individuals who consume fish have a decreased risk of heart disease, compared to those who eat none or very little. However, certain types of fish carry pollutants from the environment, which can be detrimental to the health of humans.

Methyl mercury, which can be found in many types of fish, may actually raise the risk of cardiovascular disease. Theore, consuming fish with a lot of mercury, or with ample amounts of pollutants, can severely increase the risk of heart problems. However, if people are too health conscious of fish, they increase their risk of the disease because they are not receiving the benefits of healthy fish.

A recent study said that tuna, which has high levels of mercury, should be given to children less often.

The current research, which will be published in the October 2012 issue of American Journal of Clinical Nutrition (AJCN), was carried out with the intention of finding a middle point between not eating any fish and eating too much, or types that are unhealthy.

The authors analyzed why heart attack risk is linked to the amount of mercury and omega-3 fats in the body due to fish consumption. They did so by measuring hair and blood samples of volunteers who had been involved in other trials in eastern Finland and northern Sweden. The blood samples of the Swedes were taken from the Medical Biobank in Umeå. Researchers compared blood from the patients who had suffered a heart attack after their check-up appointments and those who remained in good health with no heart attacks.

They found that while mercury content increased the chance of heart attack, omega-3 fatty acids decreased the risk. The researchers noted that higher risk of heart attack due to mercury consumption was only prevalent when there was a large amount of pollutants found in the body. If there was a high level of omega-3 fatty acids, the risk was low.

The findings suggest that it is important and beneficial to reach an equilibrium between healthy and unhealthy content found in fish. In this particular study, the environmental pollutant used was mercury. However, in regards to organic pollutants, such as dioxin and PCD, the results are the same. The authors note, though, that there has been no trial done thus far concerning these substances.

According to the Swedish National Food Agency, 2-3 servings of fish should be consumed per week. However, Swedes tend to eat predatory fish, which have a high amount of mercury and should not be eaten on a regular basis. In addition, a study conducted by the National Food Agency revealed that 7 out of 10 people in Sweden do not eat enough fish.

A 2011 study said that people who eat fish on a regular basis have lower blood glucose concentrations, and a lower risk of cardiovascular disease and type 2 diabetes. The researchers conclude that it is safe, as well as beneficial, to eat fish, but staying away from fish with high levels of pollutants is important in avoiding health problems.

Men with prostate cancer who ate a low-fat diet and took fish oil supplements had lower levels of pro-inflammatory substances in their blood and a lower cell cycle progression score, a measure used to predict cancer recurrence, than men who ate a typical Western diet, UCLA researchers found.

The findings are important because lowering the cell cycle progression (CCP) score may help prevent prostate cancers from becoming more aggressive, said study lead author William Aronson, a clinical professor of urology at UCLA and chief of urologic oncology at the West Los Angeles Veterans Affairs Medical Center.

"We found that CCP scores were significantly lower in the prostate cancer in men who consumed the low-fat fish oil diet as compare to men who followed a higher fat Western diet," Aronson said. "We also found that men on the low-fat fish oil diet had reduced blood levels of pro-inflammatory substances that have been associated with cancer."

This study appears in the early online edition of Cancer Prevention Research, a peer-reviewed journal of the American Association for Cancer Research.

This study is a follow-up to a 2011 study by Aronson and his team that found a low-fat diet with fish oil supplements eaten for four to six weeks prior to prostate removal slowed the growth of cancer cells in human prostate cancer tissue compared to a traditional, high-fat Western diet.

That short-term study also found that the men on the low-fat fish oil diet were able to change the composition of their cell membranes in both the healthy cells and the cancer cells in the prostate. They had increased levels of omega-3 fatty acids from fish oil and decreased levels of the more pro-inflammatory omega-6 fatty acids from corn oil in the cell membranes, which may directly affect the biology of the cells, Aronson said.

"These studies are showing that, in men with prostate cancer, you really are what you eat," Aronson said. "The studies suggest that by altering the diet, we may favorably affect the biology of prostate cancer."

The men in the previous study were placed into one of two groups, the low-fat fish oil diet or the Western diet. The Western diet consisted of 40 percent of calories from fat, generally equivalent to what many Americans consume today. The fat sources also were typical of the American diet and included high levels of omega-6 fatty acids from corn oil and low levels of fish oil that provide omega-3 fatty acids.

The low-fat diet consisted of 15 percent of calories from fat. Additionally, the men on this diet took five grams of fish oil per day in five capsules, three with breakfast and two with dinner, to provide omega-3 fatty acids. Omega-3 fatty acids have been found to reduce inflammation, and may be protective for other malignancies.

For this study, Aronson wanted to look at the potential biological mechanisms at work in the low-fat fish oil diet that may be providing protection against cancer growth and spread. They measured levels of the pro-inflammatory substances in the blood and examined the prostate cancer tissue to determine the CCP score.

"This is of great interest, as the CCP score in prostate cancer is known to be associated with more aggressive disease and can help predict which patients will recur and potentially die from their cancer," Aronson said.

Further, Aronson and his team analyzed one pro-inflammatory substance called leukotriene B4 (LTB4) and found that men with lower blood levels of LTB4 after the diet also had lower CCP scores.

"Given this finding, we went on to explore how the LTB4 might potentially affect prostate cancer cells and discovered a completely novel finding that one of the receptors for LTB4 is found on the surface of prostate cancer cells," Aronson said.

Further studies are planned to determine the importance of this novel receptor in prostate cancer progression, Aronson said.

Based on the results of his research, Aronson has been funded to start a prospective, randomized trial at UCLA next year studying 100 men who have elected to join the active surveillance program, which monitors slow-growing prostate cancer using imaging and biopsy instead of treating the disease. Study volunteers will receive a prostate biopsy at the beginning of the trial and again at one year. The men will be randomized into a group that eats their usual diet or to a low-fat fish oil diet group. Aronson will measure markers in the prostate biopsy tissue to check for cell growth and CCP score.

Prostate cancer is a leading cause of death among men in the United States. Its estimated that more than 230,000 American men will be diagnosed with prostate cancer this year alone, with more than 29,000 dying from their disease.

Risk of dying from heart disease significantly lowered

Older adults who have higher levels of blood omega-3 levels—fatty acids found almost exclusively in fatty fish and seafood—may be able to lower their overall mortality risk by as much as 27% and their mortality risk from heart disease by about 35%, according to a new study from Harvard School of Public Health (HSPH) and the University of Washington. Researchers found that older adults who had the highest blood levels of the fatty acids found in fish lived, on average, 2.2 years longer than those with lower levels.

"Although eating fish has long been considered part of a healthy diet, few studies have assessed blood omega-3 levels and total deaths in older adults," said lead author Dariush Mozaffarian, associate professor in the Department of Epidemiology at HSPH. "Our findings support the importance of adequate blood omega-3 levels for cardiovascular health, and suggest that later in life these benefits could actually extend the years of remaining life."

The study—the first to look at how objectively measured blood biomarkers of fish consumption relate to total mortality and specific causes of mortality in a general population—appears online April 1, 2013 in Annals of Internal Medicine.

Previous studies have found that fish, which is rich in protein and heart-healthy fatty acids, reduces the risk of dying from heart disease. But the effect on other causes of death or on total mortality has been unclear. With this new study, the researchers sought to paint a clearer picture by examining biomarkers in the blood of adults not taking fish oil supplements, in order to provide the best assessments of the potential effects of dietary consumption of fish on multiple causes of death.

The researchers examined 16 years of data from about 2,700 U.S. adults aged 65 or older who participated in the Cardiovascular Health Study (CHS), a long-term study supported by the National Heart, Lung, and Blood Institute. Participants came from four U.S. communities in North Carolina, California, Maryland, and Pennsylvania; and all were generally healthy at baseline. At baseline and regularly during follow-up, participants had blood drawn, underwent physical examinations and diagnostic testing, and were questioned about their health status, medical history, and lifestyle.

The researchers analyzed the total proportion of blood omega-3 fatty acids, including three specific ones, in participants blood samples at baseline. After adjusting for demographic, cardiovascular, lifestyle, and dietary factors, they found that the three fatty acids—both individually and combined—were associated with a significantly lower risk of mortality. One type in particular—docosahexaenoic acid, or DHA—was most strongly related to lower risk of coronary heart disease (CHD) death (40% lower risk), especially CHD death due to arrhythmias (electrical disturbances of the heart rhythm) (45% lower risk). Of the other blood fatty acids measured—eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA)—DPA was most strongly associated with lower risk of stroke death, and EPA most strongly linked with lower risk of nonfatal heart attack. None of these fatty acids were strongly related to other, noncardiovascular causes of death.

Overall, study participants with the highest levels of all three types of fatty acids had a 27% lower risk of total mortality due to all causes.

When the researchers looked at how dietary intake of omega-3 fatty acids related to blood levels, the steepest rise in blood levels occurred when going from very low intake to about 400 mg per day; blood levels rose much more gradually thereafter. "The findings suggest that the biggest bang-for-your-buck is for going from no intake to modest intake, or about two servings of fatty fish per week," said Mozaffarian.

A Loyola University Chicago Stritch School of Medicine study suggests that omega-3 fish oil might help protect against alcohol-related dementia.

Previous studies have shown that long-term alcohol abuse increases the risk of dementia. The Loyola study found that in the brain cells of rats exposed to high levels of alcohol, a fish oil compound protected against inflammation and cell death.

The study by Michael A. Collins, PhD, and colleagues was reported Sept. 8 at the 14th Congress of the European Society for Biomedical Research on Alcoholism in Warsaw.

An earlier analysis by Collins and Loyola colleague Edward J. Neafsey, PhD, which pooled the results of 143 studies, found that moderate social drinking may reduce the risk of dementia and cognitive impairment. (Moderate drinking is defined as a maximum of two drinks per day for men and 1 drink per day for women.)

It appears that small amounts of alcohol might, in effect, make brain cells more fit. Alcohol in moderate amounts stresses cells and thus toughens them up to cope with major stresses down the road that could cause dementia. But too much alcohol overwhelms the cells, leading to inflammation and cell death.

In the new study, Collins and colleagues exposed cultures of adult rat brain cells to amounts of alcohol equivalent to more than four times the legal limit for driving. These cell cultures were compared with cultures of brain cells exposed to the same high levels of alcohol, plus a compound found in fish oil called omega-3 docosahexaenoic acid (DHA).

Researchers found there was about 90 percent less neuroinflammation and neuronal death in the brain cells exposed to DHA and alcohol than in the cells exposed to alcohol alone.

Further studies are needed to confirm whether fish oil protects against alcohol-related dementia. "Fish oil has the potential of helping preserve brain integrity in abusers," Collins said. "At the very least, it wouldnt hurt them."

But Collins added that best way for an alcohol abuser to protect the brain is, if possible, to quit drinking or cut back to moderate amounts. "We dont want people to think its okay to take a few fish oil capsules and then continue to go on abusing alcohol."

Tel Aviv University research finds a 20-25 percent reduction in pressure ulcers with a fish oil enriched diet

Chock-full of Omega-3 fatty acids and antioxidants, fish oil can help lower blood pressure, reduce inflammation in the skin and joints, and promote healthy fetal development. Now a Tel Aviv University researcher has found that it has a positive effect on bedsores, too.

A common problem in critically ill patients, bedsores result from constant pressure on the skin and underlying tissue due to prolonged sitting or lying down. Painful and prone to infection, the pressure ulcers need to be healed, says Prof. Pierre Singer of the Sackler Faculty of Medicine. With Ph.D. candidate Miriam Theilla at the Rabin Medical Center, he designed a randomized experiment to determine the impact of dietary fish oil supplements on the bedsores of critically ill patients.

After a three week period of adding eight grams of fish oil to their patients daily diet, the researchers found not only a significant lessening of pain and discomfort from bedsores — a 20 to 25 percent improvement, according to the Pressure Ulcer Scale for Healing — but also a more efficient immune system and a reduction to inflammation throughout the body. The results were reported in the British Journal of Nutrition and the American Journal of Critical Care.

Boosting the immune system

Inspired by the results of a previous study showing that dietary fish oil supplements for critically ill patients raised oxygen levels in body tissues, Prof. Singer and his fellow researchers sought to determine whether the supplement could also help heal bedsores, which are also formed by a lack of oxygen, reduced blood flow, and skin wetness.

To test this theory, the researchers developed a randomized study with 40 critically ill patients. Half the patients were given standard hospital diets, and the rest had a daily addition of eight grams of fish oil added in their food. After a three-week period, the patients in the fish oil group had an average of 20 to 25 percent improvement in the healing of their bedsores compared to the control group.

Beyond the size of the bedsores, the researchers also measured different immune parameters and found that the patients in the fish oil group had experienced a boost in their immune system and a reduction in swelling. "We saw a modification in the expression of a group of molecules associated with directing leukocytes, or white blood cells, in the direction of the wound, which could explain the improved healing," explains Prof. Singer. In addition, researchers noted a significant decrease in the amount of C-reactive protein in the blood, which is associated with inflammation and linked to viral and bacterial infections, rheumatic diseases, tissue injury, and necrosis.

Natural pain management?

Next, Prof. Singer and his fellow researchers plan to explore the use of fish oil as a method of natural pain management. By measuring the intensity of pain experience in post-surgical patients who have undergone either knee or hip replacements and comparing it to the amount of fish oil the patient has received, they hope to determine whether the nutrient-rich oil can also reduce their patients suffering.

Human genetics have evolved by harnessing the power of a wide variety of nutrients which have been available in our food supply for countless generations. Over the past half century many of these natural nutrients which are so essential to our health have been slowly and systematically removed from the foods we eat.

Widely-used fish oil supplements modestly increase amounts of a hormone that is associated with lower risk of diabetes and heart disease, according to a study accepted for publication in The Endocrine Societys Journal of Clinical Endocrinology & Metabolism (JCEM).

Fish oil supplements, also called omega 3 fatty acid capsules, raise levels of adiponectin in the bloodstream. Adiponectin is an important hormone that has beneficial effects on metabolic processes like glucose regulation and the modulation of inflammation. In long-term human studies, higher levels of adiponectin are associated with lower risks of type 2 diabetes and coronary heart disease.

"While prior animal studies found fish oil increased circulating adiponectin, whether similar effects apply in humans is not established," said the studys lead author, Jason Wu, PhD, of the Harvard School of Public Health. "By reviewing evidence from existing randomized clinical trials, we found that fish oil supplementation caused modest increases in adiponectin in the blood of humans."

The meta-analysis reviewed and analyzed results from 14 randomized, placebo-controlled clinical trials. In total, 682 subjects were treated with fish oil, and 641 were given placebos – most commonly olive and sunflower oils. In those taking fish oil, adiponectin levels increased by 0.37 ug/mL. The results also suggested the effect of fish oil on adiponectin differed substantially across the trials, suggesting that fish oil supplementation may have stronger influence on adiponectin in some populations and weaker effects in others.

This is the first study to pool data from previous trials to suggest that fish oil consumption increases adiponectin in humans. The findings quantify the potential impact of fish oil on adiponectin level, and highlight the need to further investigate populations that may particularly benefit from fish oil supplementation.

"Although higher levels of adiponectin in the bloodstream have been linked to lower risk of diabetes and coronary heart disease, whether fish oil influences glucose metabolism and development of type 2 diabetes remains unclear," said Wu. "However, results from our study suggest that higher intake of fish oil may moderately increase blood level of adiponectin, and these results support potential benefits of fish oil consumption on glucose control and fat cell metabolism."

Despite the uncertainty about the effectiveness of fish oil on cardiovascular and metabolic diseases, about 37 percent of adults and 31 percent of children nationwide use omega-3 supplements, according to the 2007 National Health Interview Survey from the National Institutes of Healths National Center for Complementary and Alternative Medicine (NCCAM).

A large-scale National Eye Institute study has shown fish oil supplements containing omega-3 fatty acids do not alter the progression of age-related macular degeneration, says a national team of researchers including David M. Brown, M.D., an retina specialist at The Methodist Hospital who ran Houstons part of the study.

Another key finding of the Age-Related Eye Disease Study 2, or AREDS 2, is that lutein and zeaxanthin may be safer than beta-carotene in reducing risk of disease progression.

"If you look at all the analysis performed in the AREDS 2 study, it looks like lutein taken with zeaxanthin is at least as effective and may be better than beta-carotene," Brown said. "If you also consider that beta-carotene was associated with increased lung cancer rates in all former smokers, I no longer recommend any formulations containing beta-carotene."

Researchers saw a modest decrease in the development of age-related macular degeneration (AMD) among those who took high amounts of zinc, but that result was not statistically significant.

"Millions of older Americans take nutritional supplements to protect their sight without clear guidance regarding benefit and risk," said NEI director Paul A. Sieving, M.D., Ph.D. "This study clarifies the role of supplements in helping prevent advanced AMD, an incurable, common, and devastating disease that robs older people of their sight and independence."

Like beta-carotene, lutein and zeaxanthin can be converted to vitamin A in humans and can collect at the retina, where they probably limit chemical damage caused by light. Lutein is found in foods like egg yolk and animal fat deposits. Zeaxanthin is found in some berries, corn, and paprika.

AREDS 2s results agree with past studies that have shown an association between beta-carotene consumption and the development of lung cancer in current or former smokers. About half of AREDS 2 participants reported having been smokers at some point in their lives.

Macular degeneration is a disease in which retina damage causes a loss of visual acuity in the center of the eye, called the macula. AMD is a major cause of blindness in the elderly, and currently affects about 11 million Americans. National Eye Institute experts believe that number will double by 2050.

About 12 years ago, the National Eye Institute began funding studies to look at how diet and dietary supplements affect the progression of the disease. AREDS showed a 25 percent decreased risk of AMD when study participants took vitamin C, beta-carotene (a precursor to vitamin A), vitamin E, zinc, and copper (called the AREDS Formulation).

The five-year AREDS 2, which began in 2006, was a national study of more than 4,200 people. It suggests fish oil supplements probably do not need to be added to the formulation, and that lutein with zeaxanthin might replace beta-carotene in the AREDS Formulation, since lutein is not associated with increased risk for lung cancer.

"The first AREDS study showed us that vitamins really make a difference in decreasing the complications of AMD," Brown said. "Now with the AREDS 2, we have solid data on what to recommend to our patients. Based on the AREDS 2 data, I now recommend that my patients no longer take beta-carotene but look for a vitamin with 10 mg Lutein, 2 mg zeaxanthin, 80mg zinc, 2mg copper, 500mg vitamin C, and 400 IU vitamin E."

Contrary to earlier studies, new research suggests that omega-3 fatty acids may not benefit thinking skills. The study is published in the September 25, 2013, online issue of Neurology®, the medical journal of the American Academy of Neurology. Omega-3s are found in fatty fish such as salmon and in nuts.

"There has been a lot of interest in omega-3s as a way to prevent or delay cognitive decline, but unfortunately our study did not find a protective effect in older women. In addition, most randomized trials of omega-3 supplements have not found an effect," said study author Eric Ammann, MS, of the University of Iowa in Iowa City. "However, we do not recommend that people change their diet based on these results. Researchers continue to study the relationship between omega-3s and the health of the heart, blood vessels, and brain. We know that fish and nuts can be healthy alternatives to red meat and full-fat dairy products, which are high in saturated fats."

The study involved 2,157 women age 65 to 80 who were enrolled in the Womens Health Initiative clinical trials of hormone therapy. The women were given annual tests of thinking and memory skills for an average of six years. Blood tests were taken to measure the amount of omega-3s in the participants blood before the start of the study.

The researchers found no difference between the women with high and low levels of omega-3s in the blood at the time of the first memory tests. There was also no difference between the two groups in how fast their thinking skills declined over time.