FATS OF LIFE NEWSLETTER. December 2008 Contents. Volume 3 Issue 4 FATS OF LIFE STAFF

Transcription

1 FATS OF LIFE NEWSLETTER Volume 3 Issue 4 Contents HEART DISEASE Atherosclerosis Arteries Have Less Atherosclerotic Change with Higher Intake of Omega-3s... Links Between Atherosclerotic Plaque, Carotid Arteries and High Intake of Omega-3s... Heart Failure Seafood Omega-3s May Benefit Patients with Heart Failure... High Fish Intake Linked to Lower Heart Disease and Heart Failure Mortality... MATERNAL AND INFANT HEALTH Mother s Fish Intake and Long Breastfeeding Time Favor Child s Development Scores... Arachidonic Acid Added to Omega-3s in Pregnancy Does Not Lower Omega-3s IMMUNE FUNCTION Eating Fish Before 9 Months of Age May Lower the Likelihood of Eczema... Consumers with Fish Allergies Not Sensitive to Two Fish Oil Supplements... VISUAL FUNCTION Age-Related Macular Degeneration Twice Weekly Fatty Fish Linked to Reduced Chance of Advanced Macular Degeneration... High Intake of Seafood Omega-3s Halves the Chance of Advanced Dry AMD... MENTAL HEALTH Bipolar Disorder People with Bipolar Disorder Have Shortfalls in Brain DHA and Other Fatty Acids... Dementia Low EPA and Depression Linked to Greater Risk of Dementia... Childhood Hyperactivity and Intelligence Children Whose Mothers Ate Fish in Pregnancy Are Less Hyperactive... FATS OF LIFE STAFF Editor Joyce A. Nettleton, DSc joyce@fatsoflife.com Communications Manager Angela Dansby angela@fatsoflife.com Sponsor DSM Nutritional Products, Inc., Kaiseraugst, Switzerland Letters and editorial comments should be submitted to Nettleton at joyce@fatsoflife.com and technical comments to Dansby at angela@fatsoflife.com. Subscribe to Fats of Life at 1

2 HEART DISEASE Atherosclerosis Arteries Have Less Atherosclerotic Change with Higher Intake of Omega-3s Associations between the consumption of long-chain omega-3 fatty acids (seafood omega-3s), found predominantly in fatty fish Intake of omega-3s from fish lowers the risk of death from heart disease in people with the disease. Can they also help prevent the disease in those who don t show any signs of it? This study suggests yes. and fish oil, and reduced risk of dying from heart disease or developing the disease are well-documented in scientific literature. For these reasons, people with heart disease and those at high risk for it are advised to eat more fatty fish or consume omega-3s to prevent the onset or progression of the disease. A recent study provides additional evidence that omega-3s may slow the development of atherosclerosis, a major cause of heart disease. Assessment of heart disease risk rests on the evaluation of a person s risk factors, including age, family history, lifestyle, etc. But nowadays, additional measurements of risk may include scanning the coronary (heart muscle) arteries for calcium and evaluating the thickness of the lining of the carotid arteries (leading from the heart to the brain) using ultrasound technology (CIMT). Using these measurements, a study among middleaged and older US adults examined to what extent fish or omega-3 consumption might be related to the development of atherosclerosis observed. Participants included 6,814 men and women aged 45 to 84 years of different ethnicities. They were recruited from 6 US communities and did not have any signs of heart disease. The investigators collected information about the participants social habits, diet, lifestyle and other heart disease risk factors. Particular attention was given to the frequency, type and preparation of seafood the participants consumed. Fish consumption was divided into fried fish and shellfish, non-fried fish (broiled, steamed, baked or raw) and non-fried fish plus shellfish. Nearly half of the participants reported eating no shellfish. Average omega-3 intakes ranged from 40 to 220 mg/day across the groups. Those eating the most omega-3s were more highly educated, affluent, physically active and less likely to smoke. Participants with the highest omega-3 consumption were 31% less likely to have thickening of the lining of the common carotid arteries compared with those in the lowest intake group. Those with higher intakes of non-fried fish were 20% more likely to have a lower CIMT score, but the inclusion of shellfish weakened this association. On the other hand, omega-3 consumption was not related to heart High consumption of omega-3s was associated with significantly less thickening of the lining of the carotid arteries. Study participants who ate non-fried fish compared to fried or no fish were more likely to have healthier arteries in the heart. calcium measurements. The highest level of omega-3, but not fish, consumption was associated with lower blood triglycerides and higher HDL ( good ) cholesterol concentrations. These findings confirm previous reports that eating fried fish does not protect the heart in any measurable way, and in fact, may be linked to greater risk of heart disease. But just the opposite was true with higher intakes of non-fried fish, specifically with increased intakes of omega-3s, which are concentrated in fatty fish. Higher intake of seafood omega-3s was associated with less atherosclerosis, as reflected in about a third less chance of having adverse thickening of the carotid arteries. This observation reinforces many reports that eating such omega-3-rich fish discourages atherosclerosis, and thus, protects the heart. An ounce of fish is worth the pound of the heart. Links Between Atherosclerotic Plaque, Carotid Arteries and High Intake of Omega-3s In the preceding study on atherosclerosis in older adults, individuals with higher intakes of the longchain omega-3 fatty acids (seafood omega-3s) found 2

3 Alaska Inuit who have very high intakes of seafood omega-3s also have high levels of plaque in their arteries. This study reports that they are less likely to develop thickening in the lining of their carotid arteries. in seafoods were about a third less likely to develop unhealthy thickening in the lining of their carotid arteries. This observation suggests they had less atherosclerosis, a major cause of heart disease. In the study on atherosclerosis described here, investigators examined the presence and severity of atherosclerotic plaque in native Inuit populations in Alaska who consume very high levels of seafood omega-3s. The researchers also measured the thickening of the carotid artery lining as an additional assessment of atherosclerosis risk. The main question was whether this population might be protected from developing arterial plaque (Illustration) or adverse changes in their carotid arteries because of their high intake of seafood omega-3s. The occurrence of atherosclerotic plaque in the carotid arteries of these native Inuit was higher than reported in one study in the continental U.S., in spite of the Inuit s high consumption of seafood omega-3s. About half the Inuit adults had detectable plaque, whereas the figure for a mixed population in the continental U.S. was about 34%. However, about 60% of the Inuit adults smoked, and this habit undermines heart function and increases the risk of heart disease and atherosclerosis. On the benefit side, however, the Inuit who had the highest intakes of seafood omega-3s had less thickening of the lining of their carotid arteries compared with those having lower intakes. As in the preceding study, a higher intake of seafood omega-3s was associated with less harmful changes in the arteries. These observations suggest that a higher consumption of these fatty acids helps preserve healthy arterial function, but that once atherosclerotic plaque is established, these nutrients may be less protective of healthy artery function. High intakes of seafood omega-3s were associated with healthier carotid arteries, but did not protect against the development of arterial plaque, a hallmark of atherosclerosis. The investigators noted that the food habits and diet of the Alaskan Inuit have changed markedly in the last 20 to 30 years in ways that do not promote heart health. These changes include more processed foods, bacon and shortening at the expense of traditional foods. Type 2 diabetes and metabolic syndrome rates have increased markedly, further adding to the high risk of heart disease in this population. It seems a cruel irony that the traditional diet of Arctic natives, first associated with the heart healthy properties of seafood omega-3s, may have given way to lifestyle habits that promote the disease once unknown to these people. Heart Failure Seafood Omega-3s May Benefit Patients with Heart Failure The heart health benefits of regularly consuming fish or the long-chain omega-3 fatty acids (seafood omega- 3s) they contain extend across many different types of heart disease. Just as patients differ in the type and severity of their heart disease, so does the effectiveness of these nutrients in lowering the risk heart disease mortality. Patients who have had a heart attack (myocardial infarction) may experience a 50% lower chance of sudden cardiac death, but those with ventricular arrhythmias and implantable cardioverter defibrillators 3

4 The heart health benefits of consuming fish or longchain omega-3s extend across many different types of heart disease. This study explored their effects in patients with chronic heart failure. may get little benefit. Much less is known about the benefits of seafood omega-3s in people who have chronic or congestive heart failure. In congestive heart failure, the heart cannot pump sufficient blood to meet the body s need. As a result, patients with this type of heart disease experience shortness of breath with exertion, fatigue and weakness. The occurrence of chronic heart failure rises with age, reaching about 10% of Americans over the age of 70. In the study described here, investigators in Italy recruited patients with congestive heart failure and assigned them to groups receiving seafood omega-3s or a placebo. On average, participants were 67 years of age. Most participants were already taking statin medications to lower their LDL ( bad ) cholesterol levels and all were receiving appropriate medications to manage their health. The study was conducted over 3 years. Results from the study were evaluated in terms of total mortality, deaths from heart disease and hospital admissions, mainly for heart disease. Over the 3-year period, those patients who took the seafood omega-3s were slightly, but significantly, less likely to die or be hospitalized for heart disease compared with those who took the placebo. In relative terms, the omega-3 patients chances of dying were 9% lower. The investigators also observed that almost half the reductions in hospital admissions for heart disease were due to fewer ventricular arrhythmias, the main cause of sudden cardiac death. This study is noteworthy in showing that even among heart patients receiving the recommended care for their condition, adding seafood omega-3s to the treatment protocol was associated with additional benefits on mortality and fewer hospital admissions. Moreover, there were no adverse effects, other than mild gastrointestinal discomfort. The bottom line from this report is that increasing seafood omega-3 intake is without harm and might significantly help patients with chronic heart failure. High Fish Intake Linked to Lower Heart Disease and Heart Failure Mortality Asian populations have among the world s highest fish consumption and the lowest rates of heart disease mortality. Links between these observations have been reported in many studies, but establishing a causal relationship between fish or long-chain omega-3 fatty acid (seafood omega-3s) consumption and significantly less heart disease has been elusive. Observations from large population samples have been the mainstay of these associations. High intakes of seafood omega-3s were linked to significantly lower chances of mortality from heart disease and heart failure in Japanese adults aged 40 to 79 years. One of the most important studies from Japan in recent years reported that those with the highest fish or omega-3 intakes had significantly less ischemic heart disease (insufficient blood supply to the heart) compared with those whose intakes were lowest. This was one of only a handful of studies to report significantly less heart disease with higher fish consumption rather than lower mortality from heart disease. That said, establishing that deaths from heart disease are significantly lower with higher fish or seafood omega-3 intakes remains important. Even with the advances in medical care for heart disease, it remains the leading cause of death in developed countries. In this latest report from Japan based on nearly 111,000 adults 40 years of age or more, epidemiologists in Japan and the U.S. examined whether fish or seafood omega-3 consumption was related to the likelihood 4

5 of dying from heart disease. The investigators looked at total heart disease deaths and those from specific causes, such as stroke, heart failure and cardiac arrest. As expected, with increased consumption of fish or seafood omega-3s, the likelihood of dying from any type of heart disease fell significantly by 18%. Specific types of heart disease mortality, including stroke and cardiac arrest, were not significantly linked to fish or seafood omega-3 intakes, but there was a trend toward lower mortality from heart failure. After many confounding variables were taken into account, there was a 42% lower chance of mortality from heart failure as seafood omega-3 intakes increased. Study participants with the highest intake of seafood omega-3s consumed more than two grams of these fatty acids daily about 20 times more than the average American. In terms of the amount of fish eaten, the highest daily intakes were about 86 g (3 ounces). This study provides additional evidence that the regular consumption of fish or seafood omega-3s is linked to a significantly lower likelihood of death from heart disease and heart failure. Individuals wanting to be proactive about heart health should consume fish at least twice a week or seafood omega-3 supplements regularly. MATERNAL AND INFANT HEALTH Mother s Fish Intake and Long Breastfeeding Time Favor Child s Development Scores Mothers who consume fish regularly during their pregnancy have better pregnancy outcomes than mothers who do not eat fish. Studies in different parts of the world have reported a lower chance of preterm delivery, better infant visual acuity, and improved cognition and problem-solving among other advantages in the offspring of mothers who consumed fish or long-chain omega-3s during their pregnancy. The growing evidence that favors having sufficient dietary intake of long-chain or seafood omega-3s during pregnancy led to international recommendations that pregnant and nursing women consume at least 200 mg/day of docosahexaenoic acid (DHA). Unfortunately, most women in western countries consume much less than that. In the study described here, researchers examined a large database of pregnant women and their offspring from the Danish National Birth Cohort. This registry obtains health and demographic information about women during pregnancy and monitors the health and development of their offspring. About 86% of the participants ate fish once or twice a week with only about 3% of them never eating fish. The most frequently consumed species were lean fish such as cod. In addition to the developmental milestones of the offspring, the investigators examined the effects of length of breastfeeding related to the children s development. They noted that mothers who consumed the most fish were also most likely to breastfeed their infants the longest. In this population, women breastfed for an average of 8 months, with or without adding other foods. In contrast to these Danish women, the breastfeeding times of American mothers peak at 3 months. When comparing the results of the children s motor, social or cognitive and total development scores at 18 months of age according to the mothers fish intake, all three scores showed significant trends toward better performance as the mothers fish consumption increased. When the length of breastfeeding was taken into consideration, maternal fish intake remained associated with higher developmental scores at 18 months. Duration of breastfeeding was also linked to a greater number of developmental milestones achieved by the children at 18 months, after accounting for parental and child characteristics and the mother s fish consumption. 5

6 These investigators also Mothers who breastfed assessed the children s longer and ate more developmental attainment relative to the than 340 g (12 oz) of fish/week during mothers fish intake pregnancy had according to the recommendations of the U.S. children with better government. The current US fish consump- developmental scores at 18 months of age. tion advisory for pregnant women suggests that women consume no more than 340 g (12 oz) of fish/week. However, Danish women who ate more fish than this had children with better developmental outcomes and no adverse effects. These findings support the previous observations from the Avon Longitudinal Study in which the children of mothers who ate more than 340 g of fish/week had better developmental outcomes than children whose mothers did not eat fish or ate it less often. Thus, these studies question the soundness of advice that limits fish consumption during pregnancy to no more than 340 g/week. The implication of these findings is that mothers who eat at least 340 g (12 oz) of fish/week have children with better developmental outcomes without harmful effects, while those who eat little or no fish have children with lower developmental scores. Fear of environmental contaminants, which drives pregnant women away from eating fish, fails to protect child development and may be detrimental to it. Arachidonic Acid Added to Omega-3s in Pregnancy Does Not Lower Omega-3s The high demand for long-chain polyunsaturated fatty acids in pregnancy, especially in the third trimester, makes it imperative that Experts recommend that pregnant and nursing women consume at least 200 mg of DHA, a longchain omega-3, daily. They saw no need for increased consumption of arachidonic acid, a longchain omega-6 fatty acid. pregnant and nursing women have adequate dietary sources of these nutrients. The need is greatest for docosahexaenoic acid (DHA) one of the two main long-chain omega-3s (seafood omega-3s) found mostly in fish and shellfish. The availability of DHA depends almost entirely on the mother s diet, whereas concentrations of arachidonic acid, the main long-chain omega-6 polyunsaturated fatty acid, are relatively stable. Experts now recommend that pregnant and nursing women consume at least 200 mg of DHA/day, and agree that sufficient arachidonic acid is available from the diet and additional amounts are unnecessary. As fish, fish oil or seafood omega-3 supplements are the main sources of DHA, women who do not eat fish or take fish oil supplements are highly likely to have low intakes and stores of DHA. In fact, several studies have reported very low DHA levels in the breast milk of US women who eat little fish, a reflection of low DHA intakes. Because arachidonic acid is generally regarded as sufficient, little attention has been given to providing additional amounts of this fatty acid to pregnant and nursing women. This assumption has been re-examined in a recent study from the Netherlands. The question is whether large amounts of seafood omega-3s might lower arachidonic acid levels. Several recent studies in which pregnant women consumed cod liver oil or omega-3 supplements reported that no effects of the omega-3 supplements on arachidonic acid levels. Most studies have observed no correlation between arachidonic acid and seafood omega-3s. The Dutch investigators explored the effect on the mothers breast milk fatty acids of adding two different amounts of arachidonic acid to the seafood omega-3 supplement given to a sample of nursing women. They included a group of women who received only the omega-3s and another group given a placebo without fatty acids. All mothers were given vitamins and minerals. The arachidonic acid concentration in the breast milk of mothers who consumed the placebo declined over the 8-week study, but DHA concentrations did not. When seafood omega-3s were included in the diet, DHA concentrations rose significantly within 2 weeks, but changes in arachidonic acid were not significant. Similarly, the addition of arachidonic acid to the omega-3 supplementation significantly increased its concentration in breast milk without affecting the concentration of DHA. 6

7 The investigators also examined the effects of seafood omega-3 and arachidonic acid supplementation on the mothers red blood cell fatty acid concentrations. This measurement reflects what is available to the mother for transfer to her breast milk. As might be expected, the unsupplemented mothers experienced a strong decline in their red cell DHA that was restored with seafood omega-3 supplementation. Red cell arachidonic acid levels were unaffected by the omega-3 supplementation. Adding arachidonic acid to the supplementation increased the red cell concentration of this fatty acid, but at the higher level, reduced the amount of DHA gained by the red cells. Providing additional arachidonic acid to nursing mothers along with seafood omega-3s increased the breast milk and red blood cell content of arachidonic acid, but provided no evidence that these mothers needed more of it. What does this supplementation study mean? First, it shows clearly that providing seafood omega- 3s to nursing women increases their breast milk and red blood cell levels of DHA. As a result, more DHA will be available to the nursing infant and the mother s own supplies will not be greatly diminished. Providing additional arachidonic acid with the omega-3s also increased the amount of arachidonic acid in breast milk and red blood cells, without affecting DHA or total omega-3 concentrations. However, the highest level of arachidonic acid supplementation reduced the red cell DHA. That observation cautions that unnecessary or excessive supplementation with arachidonic acid might potentially interfere with DHA. This study is consistent with the conclusion of the international expert group on dietary fatty acids in pregnancy that pregnant and nursing women do not need additional arachidonic acid. IMMUNE FUNCTION Eating Fish Before 9 Months of Age May Lower the Likelihood of Eczema Childhood allergies have become more common throughout the world with no comprehensive explanation why. Parental history of allergies, tobacco smoke and environmental allergens all contribute to allergic conditions, Childhood allergies have become more common throughout the world with no good explanation why. The mother s diet during pregnancy and her child s consumption of fish may be linked to a lower chance of childhood eczema. as might diet. A mother s food habits during pregnancy as well as her child s diet, especially in the first year, have been examined for possible relationships to the development of eczema, rhinitis and asthma. Maternal intake of longchain omega-3 fatty acids (omega-3s) found mainly in fish and shellfish has received attention because these nutrients are often in short supply unless a mother eats fish regularly. Omega-3s modify immune function usually tempering inflammatory responses. They are thought to influence the maturation of a child s immune system even before birth. There is evidence suggesting that maternal consumption of fish or omega-3s during pregnancy reduces or delays the development of childhood eczema and that its symptoms may be less severe. However, the research to date is inconsistent and several studies reported no relationship between a mother s omega-3 intake during pregnancy and allergic conditions in her offspring. Likewise, there have been reports that the early introduction of potentially allergenic foods, such as fish, in the child s first year is associated with a lower chance of allergic disease by age 4. Many parents avoid or delay giving such foods to their children thinking that they will promote allergic responses. In the study described here, the prevalence of eczema in one-year-old Swedish children was examined in relation to family history of allergic diseases, environmental factors and a child s consumption of fish. In Sweden, both fish consumption and eczema are common, with 60% of families eating fish 1 to 3 times/week by the time a child is one year old. 7

8 The Swedish investigators obtained dietary and health information from nearly 5,000 families living in the western region of the country. Participating parents provided information about the household environment, family history of allergies, the child s food consumption, presence of eczema and doctor-diagnosed food allergies. At the age of one year, 21% of the children had eczema, with half developing the condition by 4 months of age. Children who ate fish before the age of 9 months were 25% less likely to develop eczema by the age of one year than children who did not eat fish. fish before they were 9 months old. Of all the likely factors affecting the development of eczema, the greatest likelihood occurred in children with allergy to cow s milk. The next most predictive factors were having a sibling or mother with eczema. A 25% lower chance of having eczema was observed in children at one year of age who ate Interestingly, the main types of fish consumed were lean white species, the ones usually lower in omega-3s. For that reason, this association with eating fish early in life may not be linked to dietary omega-3s, but this study cannot establish that point. Other studies have reported that childhood fish consumption helps reduce the likelihood of allergies, and in one report, eating fish before the age of one was associated with a lower risk. Although it may seem counter-intuitive, introducing fish to a child s diet early may be a successful strategy to lessen the chance of eczema. Consumers with Fish Allergies Not Sensitive to Two Fish Oil Supplements Individuals who have allergic reactions to eating fish or shellfish often wonder whether it is safe to take fish oil supplements. Might they provoke an allergic response? In general, the answer to this question is no, because fish oil supplements are rigorously refined and purified. These processes remove non-lipid substances, such as proteins, which are the usual cause of allergic responses. The cleanup also removes environmental contaminants and other impurities. What remains is pure oil containing long-chain omega-3 fatty acids (omega-3s). A small study among individuals with documented fish allergies found that consuming oral fish oil supplements did not provoke any allergic response. Among the foods most likely to provoke an allergic response, fish ranks fairly low, but fish allergies are well-known. In contrast, shellfish allergies are about 5 times more common. A recent small study reported its findings on the responses of 6 individuals with documented fish allergies to the consumption of 2 different fish oil supplements. Each participant exhibited a positive skin prick test to at least 3 of 6 different fish allergens. When they took one fish oil capsule orally, none of the allergic participants experienced any allergic response to the fish oil. Although this is a very small study with only two commercially available products, it offers encouragement to those who, because of food sensitivities or allergies, fear they might respond adversely to taking a fish oil supplement. It is difficult to find individuals with fish allergies for this kind of study, so these results are reassuring. Many large clinical trials using fish oil supplements or purified omega-3 fatty acids from fish oil have reported few side effects from taking them. Those that have been noted include mild gastrointestinal discomfort, fishy aftertaste and difficulty swallowing a large capsule. In this more rigorous assessment, it is welcome news that no adverse reactions occurred among individuals with established fish allergies. VISUAL FUNCTION Age-Related Macular Degeneration Twice Weekly Fatty Fish Linked to Reduced Chance of Advanced Macular Degeneration One of the most compelling advances in understanding what long-chain omega-3 fatty acids do has come from studies on age-related macular degeneration (AMD). This degenerative eye condition affects the retina and is the leading cause of blindness in older adults. The advanced wet form of the condition (Illustration), while less common than the dry form, accounts for about 85% of severe loss of vision. 8

9 The development and progression of AMD to severe visual impairment is related to heredity and environmental factors, especially smoking. Obesity, being Caucasian Illustration of neovascular or wet and having a family history of the AMD. Image reproduced courtesy of the Macula Foundation. condition increase a person s chance of developing AMD. However, protective factors have emerged, particularly several nutrients that concentrate or function in the retina. A large clinical trial by the US government reported that high-doses of the antioxidant vitamins C, E and beta-carotene (a substance that can be converted to vitamin A), and the minerals zinc and copper significantly slowed the progress of AMD to its advanced stages. This trial has been extended to include the evaluation of long-chain omega-3 fatty acids (omega-3s) and the antioxidants lutein and zeaxanthin in deterring this condition. These three substances are all concentrated in the retina and are critically involved in healthy visual function. Several studies on AMD have reported that fish consumption or higher intakes of omega-3s are associated with a lower chance of developing AMD or having the condition progress to more advanced stages. For example, the US government trial observed that people with early AMD who consumed the most fish, omega-3s or docosahexaenoic acid (DHA), a longchain omega-3, had a 40% lower chance of developing advanced AMD. A second large trial is currently underway to find out if providing these substances to individuals with early signs of AMD will halt or slow progression of the disease. Large studies on AMD and other eye diseases are also being conducted in Europe and Australia. Here, findings from a 7-country study in Europe involving nearly 5,000 people describe the prevalence of AMD in adults 65 years of age and older. This study examined the relationship between AMD, the consumption of various nutrients and a person s medical status. Eating fatty fish twice a week or consuming 300 mg/day of EPA + DHA was associated with a 60% to 70% lower chance of developing the advanced or wet type of AMD. The most striking observation from this study was a 50% reduction in the likelihood of developing advanced wet AMD in individuals who ate fatty fish (e.g., salmon, tuna, mackerel, sardines) at least once a week. People who ate fatty fish less often did not experience a lower risk of advanced AMD. Further, those who consumed 300 mg/day or more of long-chain omega-3s had an even lower risk of advanced AMD 70% less. This association strongly suggests that the long-chain omega-3s in fish are the key protective factors guarding against advanced AMD. This interpretation is plausible because the retina is known to concentrate docosahexaenoic acid (DHA), one of the two main omega-3s in fish oil. DHA is important for healthy visual function and the conversion of light energy to signals that trigger visual responses. The other main long-chain omega-3, eicosapentaenoic acid (EPA), has anti-inflammatory properties that help preserve retinal function. This large observational study expands the evidence favoring the regular consumption of fatty fish for healthy retinal function and a lower chance of AMD-related blindness, particularly in older adults. It seems insightful to ensure that fatty fish is on the menu at least twice a week. High Intake of Seafood Omega-3s Halves the Chance of Advanced Dry AMD As mentioned in the preceding article, a large US government trial with antioxidant nutrients in individuals with the early stages of age-related macular degeneration (AMD) found that high-doses of these nutrients slowed progression of the disease to its more destructive stages, particularly the wet form. This study, known as AREDS, has been extended to evaluate the effectiveness of adding the antioxidants lutein and zeaxanthin or long-chain omega-3 fatty acids (omega-3s) or all of these nutrients to the high-dose vitamin and mineral treatment. Participants in this second phase (AREDS2) include individuals with early to moderate stages of AMD. The aim of the trial is to learn whether either or both sets of additional nutrients might further 9

10 slow AMD if used with antioxidant vitamins and zinc. Because advanced AMD is the leading cause of blindness in older adults, the results of this study could have far-reaching preventive applications in people with or at risk of developing AMD. Illustration of geographic atrophy in AMD. Image reproduced courtesy of the Macula Foundation. In this report from the first AREDS study, the investigators monitored more than 2,000 participants for signs of disease progression from early stage drusen (yellow spots in the retina) to either type of advanced AMD. Neovascular AMD is the advanced form of wet AMD, whereas geographic atrophy, patches of degenerated retinal cells (Illustration) is an advanced form of dry AMD. Most of those enrolled in the study were 70 years of age or older. At least half the enrollees participated for 6 years. The investigators estimated the participants intake of omega-3s from the amount and frequency of their eating different types of fish and shellfish. Over the study period, 9% of participants developed neovascular or wet AMD and 5% developed geographic atrophy. The lower chance of developing geographic atrophy was related to higher omega-3 consumption. Individuals who consumed the highest amounts of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the two main omega-3s in fish oil, experienced a 60% lower Individuals with early AMD who consumed about 250 mg/day of long-chain omega-3s were half as likely to develop the dry form of advanced AMD as those with the lowest omega-3 intakes. likelihood of geographic atrophy compared with those consuming the least amount. A similarly lower risk was observed for EPA consumption alone, but not for DHA. When the odds of developing wet AMD were evaluated, no significant relationships with omega-3 intakes were observed. This finding contrasts with the study described in the preceding article. In spite of that, participants who had the highest intake of tuna, 1 to 2 servings/week, had only half the chance of developing wet AMD compared with those who ate tuna 1 to 3 times/month. These findings break new ground in several ways. First, the study separated the types of advanced AMD into its two main forms, wet and dry. The chances of developing the latter were significantly lower with higher intakes of DHA + EPA. Second, the intake of EPA was associated with a reduced likelihood of dry AMD a new observation. Third, the chance of developing wet AMD was related to frequent tuna consumption, but not omega-3 intake. This observation is difficult to explain in light of several previous reports of lower risk of this form of AMD with higher omega-3 intakes. What is noteworthy is the large reduction in the odds of AMD progression to the advanced dry form at least 50% less with the highest intakes of EPA + DHA and with EPA alone. These amounts were about 250 mg of omega-3s/day, close to what is available in many overthe-counter fish oil supplements or from twice-weekly fatty fish consumption. This report from the AREDS study and the European eye study described in the preceding article increase one s confidence that long-chain omega-3s can significantly and safely reduce the likelihood of advanced AMD, once its early signs have appeared. Eating fatty fish regularly might provide visual clarity throughout life. MENTAL HEALTH Bipolar Disorder People with Bipolar Disorder Have Shortfalls in Brain DHA and Other Fatty Acids Various mental disorders and behavioral problems have been linked to low tissue content of long-chain omega-3 fatty acids (seafood omega-3s), found mainly in fish and shellfish. Some examples include depression, declining cognitive function in Alzheimer disease, attention deficit hyperactivity disorder, aggressive and hostile behavior, and schizophrenia. In these conditions, there have been efforts to determine whether increasing the consumption of seafood omega-3s eases the symptoms. While many results have been encouraging, 10

11 The long-chain omega-3s found in seafood are important contributors to brain structure and function. Deficits in one of them, DHA, have been observed in several mental disorders. This study adds bipolar disorder to that list. the findings have often been inconsistent. These conditions are more complicated than simply correcting possible fatty acid imbalances. Further indication that seafood omega-3s are involved in these disorders has come from examining the fatty acid content of key regions of the brain in individuals who died with various mental disorders. Scientists at the University of Cincinnati have reported that the docosahexaenoic acid (DHA) content of the orbitofrontal cortex (Illustration) of patients with major depression is significantly lower than in individuals who do not suffer from depression. DHA is one of the two main omega-3s found in seafoods and is a key structural component of neurons. Other research has reported reduced DHA content in certain brain regions of Alzheimer patients compared with those not having Alzheimer disease. These observations provide physical evidence of structural abnormalities in the brains of individuals with various mental disorders. In a new European study of the orbitofrontal cortex of patients who died with bipolar disorder, researchers compared cortex fatty acids of the patients with those in individuals not having bipolar or other mental disorders. They observed significant deficits in DHA, arachidonic acid and all long-chain polyunsaturated fatty acids, which are concentrated in the brain. The deficit in DHA was larger than for any other fatty acid. This region of the brain is involved in the control of mood, drive and responsibility, memory and many complex behaviors. Thus, it is not surprising that abnormalities in this region might affect diverse behaviors including psychiatric conditions. The investigators compared the results according to death by suicide in the patients and controls. Suicides were more common among the patients with bipolar disorder and these individuals had greater DHA deficits compared with the control patients who took their own lives. DHA was the only fatty acid that differed between the two groups. Cross-section of the human brain showing the orbitofrontal cortex in pale yellow. Samples were taken from area 10. Image reproduced courtesy of Professor Mark Dubin, University of Colorado. Patients with bipolar disorder had significant deficits in DHA, arachidonic acid and total polyunsaturated fatty acids in their frontal cortex. It is plausible that these deficits affect brain structure and function in this disorder. These intriguing observations add bipolar disorder to the brain conditions in which fatty acid abnormalities have been observed. How one interprets these findings is open to discussion. Reductions in both DHA and arachidonic acid suggest the involvement of various fatty acids in brain structure and function. For example, both fatty acids affect inflammation, but usually in opposite ways. DHA is the precursor of substances that preserve the integrity and function of neurons. These observations suggest that having sufficient DHA available for brain structure and function is likely important for optimal brain function and mental health. 11

12 Dementia Low EPA and Depression Linked to Greater Risk of Dementia The most common cause of cognitive loss in aging is Alzheimer disease, although dementia can result from other degenerative processes as well. Some conditions that increase the likelihood of dementia include family history and having the ε4 variant of the apolipoprotein E gene, a genetic variation linked to greater deposits of the abnormal proteins characteristic of Alzheimer disease. Although we have learned much about the abnormalities of this disease, no one knows what causes it. A study from France confirms that genetic factors and depression increase the odds of dementia and reports protective associations with higher levels of EPA, a long-chain omega-3 fatty acid. On the encouraging side, one condition associated with a substantially lower chance of developing Alzheimer disease is the frequent consumption of fish or having higher blood levels of docosahexaenoic acid (DHA), a long-chain omega-3 fatty acid. For example, in the Framingham heart study, older adults in the top fourth of blood DHA levels were 40% less likely to develop any type of dementia. Eating fish at least once a week was associated with a 60% lower chance of Alzheimer disease in a study of Chicago adults 65 years old or more. These impressive reductions in the odds of developing dementia inspired research on DHA and other seafood omega-3s in connection to cognitive function. A multi-year study in France has been examining the conditions linked to the development of dementia in community-living individuals 65 years old or more. In this report from one of the participating cities, the investigators confirmed a higher risk of dementia in individuals having the apolipoprotein E variant. They also found that participants with type 2 diabetes, depression or high blood triglyceride (fat) levels were at greater risk of dementia. The only factor linked to a lower chance of becoming demented was a person s blood concentration of eicosapentaenoic acid (EPA), one of the two main seafood omega-3s. The effect of EPA was observed only in participants who did not have depression. In depressed individuals, those with low blood DHA and high arachidonic acid levels had twice the risk of developing dementia. However, in the absence of depression, this fatty acid pattern was linked to only a modestly greater risk of dementia. Like other studies Having depression and reporting increased low blood levels of EPA health risks in greatly increased the odds of developing dementia. depressed individuals, particularly for heart High EPA levels were disease, this study linked to 30% lower observed substantially odds of dementia in higher odds of older adults without dementia in depressed individuals. Altered depression. omega-3 fatty acid patterns have been reported separately in depression and dementia and this study links the two observations. The finding that higher blood EPA levels were associated with lower odds of dementia raises the possibility that EPA might affect brain function through its anti-inflammatory properties or its effects on energy metabolism. This study is another reminder of the importance of seafood omega-3s in maintaining healthy brain function. It suggests that both EPA and DHA may have separate, but complementary, functions in keeping one s wits. Childhood Hyperactivity and Intelligence Children Whose Mothers Ate Fish in Pregnancy Are Less Hyperactive Many studies have reported a variety of desirable outcomes in children whose mothers ate fish during their pregnancy compared with children whose mothers did not eat fish. More recently, studies have noted better childhood performance scores when their mothers ate more fish than is recommended by the US government, 12

13 i.e., more than 340 g (12 oz)/week. Benefits have been observed in cognitive test scores, mental processing, behavior and motor function among others. Thus, it is becoming more difficult to defend recommendations that pregnant and nursing women should limit their fish consumption, provided they are not eating fish with high levels of contaminants such as mercury. The more worrying problem is that most women in developed countries eat too little fish. A new report from researchers at the University of Southampton, U.K., describes the relationship between a mother s fish consumption during pregnancy and the intelligence and behavioral scores of their children at age 9. The investigators noted that mothers who ate fish, especially fatty fish (e.g., salmon, tuna, rainbow trout, sardines), while pregnant tended to be more educated, older, and have higher intelligence scores and socioeconomic status compared with mothers who did not eat fish. They were less likely to smoke and more likely to breastfeed longer as well. At 9 years old, children whose mothers ate fish less than once/week were less likely to exhibit hyperactivity compared with children whose mothers did not eat fish. Social, emotional and total intelligence scores did not differ between the two groups. However, the children whose mothers ate fish once or twice a week or less had significantly higher verbal intelligence scores compared with children whose mothers did not eat fish. Verbal intelligence scores increased as the mother s fish intake rose. This observation supports a previous report from another UK study that linked children s intelligence scores with greater maternal fish consumption in pregnancy. In both studies, no adverse effects were observed in any of the children s performance assessments as the mother s fish consumption increased. This observation suggests that the fears associated with exposure to contaminants from maternal fish consumption are exaggerated. Children whose mothers ate fatty fish in pregnancy were less likely to exhibit hyperactivity and more likely to have higher verbal IQ scores compared with children whose mothers did not eat fish. Although the relationships between maternal fish consumption and less hyperactivity and higher verbal intelligence scores in their 9-year old children were significant, the possibility that these findings might relate to the children s own fish consumption cannot be ruled out. The assumptions for a credible link between a mother s diet and her child s development rest mainly on the importance of the transfer of long-chain polyunsaturated fatty acids to the fetus, especially of the seafood omega- 3 docosahexaenoic acid (DHA). These fatty acids are critical for the structure and function of the brain, which undergoes rapid development in the third trimester and early years of life. Lower brain DHA has been reported in the children of mothers who do not eat fish during pregnancy. Still, it is remarkable yet plausible that the mother s diet in pregnancy has long-lasting effects on child development. 13