March 2007 HEART HEALTH. Marine Omega-3s Improve the Heart s Reflex Control Mechanisms

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1 HEART HEALTH Marine Omega-3s Improve the Heart s Reflex Control Mechanisms To fully understand the ways nutrients affect heart health, scientists try to determine how they act in the body and in various tissues. They must also consider how nutrients interact with each other, because nutrients almost never perform alone. In seeking to understand how the consumption of fish protects the heart, researchers have discovered many different effects. Most studies indicate that heart health benefits from eating fish are largely attributable to the unique longchain omega-3 polyunsaturated fatty acids* (marine omega-3s) found almost exclusively in fish. They have observed similar effects whether people consume fish or marine omega-3s. Although eating fish has other advantages, the research focus has been on how marine omega-3s work. A report from Milan, Italy, suggests that marine omega-3s may improve the sensitivity of receptors in the aorta called baroreceptors. These control the heart rate and the adaptability of the heart to changing conditions. We now know that marine omega-3s have anti-arrhythmic, antiblood clotting and anti-inflammatory effects. They also lower blood triglycerides (fats), improve heart rate, tend to slow the progress of atherosclerosis and have mild blood pressure-lowering effects. In patients with impaired heart function, as in heart failure, increased arterial blood pressure increases the risk of mortality. The regulation of arterial blood pressure is controlled by pressure-sensitive receptors called baroreceptors located in the main arch of the aorta. The baroreceptors provide reflex control of the heart rate (beats per minute) and heart rate variability, an indication of the adaptability of the heart to changing conditions. Aortic arch The higher the variability, the greater the heart s ability to respond to varying conditions. It is uncertain whether the heart s baroreceptors are affected by dietary fatty acids, particularly marine omega-3s. If so, this would suggest another way in which marine omega-3s might benefit heart health. A report from Milan, Italy, suggests that marine omega- 3s improve baroreceptor sensitivity. The researchers devised a way to stimulate the baroreceptors in patients with chronic heart failure who had consumed about 2 grams/day of marine omega-3s for 4 months. At the same time as they applied the mild stimulation, they measured the patients blood pressure, heart rate and electrocardiogram. The investigators repeated the evaluations in a group of patients who consumed a placebo for 4 months. When the measurements in the 2 groups were compared, the patients who consumed the marine omega-3s had significantly increased heart rate variability, whereas the placebo patients had no change. Blood pressure was unchanged in both groups. The investigators also reported evidence that the baroreceptor control of heart rate was improved in the marine omega-3 group, but not in the placebo group. Even though the study did not find changes in the clinical status of the patients, these findings suggest that improved baroreceptor sensitivity would reduce the risk of mortality in patients with chronic heart failure. Fish Oil and Dietary Guidance May Improve Atherosclerosis Progress of atherosclerosis can be monitored by ultrasound scans or pictures of the carotid artery. An important contributor to heart disease is atherosclerosis, the long slow deterioration of the body s main arteries. Atherosclerosis usually begins in childhood and progresses as we age. As the condition advances, the walls of the arteries lose their elasticity and become upholstered with deposits of fats, cholesterol and cells. These deposits or plaques impede blood flow, impair circulation and increase the chance of blood clot formation. A clogged artery that becomes blocked from a clot or from excessive plaque can result in a heart attack or stroke. The progress of atherosclerosis can be monitored using * Desribed in the glossary on page 12. 1

2 images of an artery, often the carotid artery in the neck, generated from ultrasound waves. These images reveal changes in arterial plaque and the thickness of the arterial wall (Figure). Other changes to the blood vessel walls, such as stiffening, are reflected in the time required for blood to return to the heart after each heartbeat. These techniques formed the basis of a Norwegian study on the progression of atherosclerosis in older men. The 563 men in the study, aged 65 to 75 years, were given dietary counseling or not, with or without fish oil supplements for 3 years. The amount of marine omega-3s in the fish oil supplements (2.4 grams marine omega-3s/day) was roughly equivalent to 2 servings of salmon per day. Dietary advice was similar to that of the American Heart Association. Participants receiving dietary counseling were advised to limit their intake of fat to no more than 30% of total energy and to substitute mono- and Figure. Ultrasound image of carotid plaque (red) and polyunsaturated fats narrowed artery. Courtesy of for saturated fats. Tristram Clinic, Hamilton, NZ. Dietary cholesterol was limited to a maximum of 300 mg/day. Participants given dietary counseling also received vegetable oils and soft margarines rich in monoand polyunsaturated fatty acids. At the beginning and end of the 3-year period, participants provided blood samples for fatty acid measurements, received an ultrasound scan of their carotid artery and had an electrocardiogram. After 3 years, thickening of the inner wall of the artery and accumulation of plaque increased in all groups and neither was affected by the consumption of fish oil. Thickening of the arterial wall was less in the men who received only dietary counseling. However, the measurement of arterial elasticity was significantly better in the men who consumed fish oil compared with the control group of men not receiving dietary advice. Another interesting finding in this study was the significant increase in high-density lipoprotein cholesterol (HDL), the so-called good cholesterol in the men who consumed marine omega-3s and received dietary counseling compared with the control group. Men with improved HDL cholesterol also had less increased thickening in their arterial blood vessel walls. These observations suggest that the consumption of marine omega-3s was linked to favorable arterial changes and improved HDL cholesterol. Dietary counseling was linked to slower progress in atherosclerosis, but the effect was not observed in men consuming marine omega-3s. Improved dietary habits and increased consumption of marine omega-3s can make a difference, even later in life. What is encouraging about this study, in spite of its modest achievements, is the demonstration that improved dietary habits and increased consumption of marine omega-3s can make a difference, even later in life. The novelist George Eliot knew this when more than 100 years ago she wrote, It s never too late to be who you might have been. She was probably not thinking of healthy eating though. MOTHERS & INFANTS Higher Intake of Fish in Pregnancy Improves a Child s Neurodevelopment Whether to eat fish during pregnancy, and if so, which ones, is a highly contentious issue, particularly in the United States. Fear of the potential harm from mercury in seafood, which in large amounts can damage the developing brain, has caused many women to ask, Why take the risk? To protect their developing baby, many women avoid eating any seafood or eat very little of it. Recent findings from the Fear of the potential harm from mercury in seafood, which in large amounts can damage the developing brain, has caused many women to ask, Why take the risk? United Kingdom suggest that mothers who avoid fish during their pregnancy actually jeopardize the neurodevelopment of their offspring. How can this be? The answer appears to lie in the critical nutrients in fish necessary for optimum 2

3 brain development. Results from a long-term study in the United Kingdom on the health of pregnant women and their children suggest that the children whose mothers ate the most fish during their pregnancy had the most favorable neurodevelopmental outcomes. In the Avon Longitudinal Study (ALSPAC), the investigators examined the relationship between the fish consumption habits of women during their pregnancy and the cognitive, behavioral and developmental outcomes of their children at different ages. The researchers used a questionnaire to assess the frequency of eating fish and the types and amounts of fish consumed in 8,800 pregnant women during their last trimester of pregnancy. Mothers also provided information periodically about the behavior and development of their children from 6 through 81 months of age. The children s intelligence quotient (IQ) was assessed when they were 8 years old. At that time, there were 5,449 children available for evaluation. To determine the relationship between the amount of fish consumed and the children s developmental outcomes, the investigators divided the findings according to three levels of fish consumption: none, 1 to 340 grams/week (up to 12 oz/week) and more than 340 grams (12 ounces) per week. Twelve ounces per week is the maximum amount of fish per week the U.S. Food and Drug Administration and the U.S. Environmental Protection Agency recommend for pregnant and nursing women. The agencies suggest this limit to avoid the possibility of consuming too much mercury. When the ALSPAC investigators compared the children of mothers who did not eat fish with children whose mothers ate 340 grams of fish or more/week, they observed significantly lower (i.e., suboptimal) scores for verbal IQ, fine motor development, positive social skills in the children whose mothers avoided eating fish. Higher scores were significantly more likely for children whose mothers ate 340 grams or more fish/week for verbal and full IQ scores at age 8 years, positive social behavior at age 7, and for various developmental measures such as fine motor skills, social development and communication at ages 18 to 42 months. The bottom line: children of mothers who ate the most fish had the most favorable developmental outcomes in a variety of measures. The investigators also calculated the marine omega-3 intake of the mothers based on the type and amount of fish they ate. When the children s developmental scores were evaluated in terms of the mother s intake of marine omega-3s, the data showed that as the mother s marine omega-3 intake increased, fewer children had suboptimal verbal IQ scores. Put another way, a child was more likely to have a lower (suboptimal) verbal IQ score as the mother s omega-3 intake fell. Mothers in the ALSPAC study consumed, on average, 3 times as much seafood as US women 34 grams/day compared with 11 grams/day in the U.S. As you would expect, their intake of mercury was also higher (0.05 vs 0.02 micrograms/kg bodyweight), yet their children apparently suffered no adverse effects from this level of mercury exposure. One possible explanation for this observation is the selenium content of fish. Selenium is a mineral that counteracts mercury, minimizing its toxic effects. The authors boldly stated that these findings, based a large sample of mothers and children, provide no evidence that pregnant women should restrict their seafood consumption. Limiting fish consumption does not protect the child from potential harm and may interfere with the child s optimum development. Further, there was no evidence of benefit to the children if their mothers ate less Findings from the ALSPAC study provide no evidence that pregnant women should restrict their seafood consumption. Limiting fish consumption does not protect the child from potential harm and may jeopardize the child s development. than 340 grams of seafood/week. In an editorial accompanying this report, Dr. Gary Meyers, who has for years studied maternal fish consumption and children s development in the Seychelles Islands, noted, there has never been even one child with prenatal 3

4 mercury poisoning from consuming fish, outside of Japan, where there was massive industrial pollution in Minamata Bay in the 1950s and 1960s. It s time for pregnant women to put fish consumption in a healthier perspective, at least for the sake of their children. Fish Oil Supplementation in Pregnancy Linked to Better Toddler Eye-Hand Coordination Consumption of fish during pregnancy, which provides marine omega-3s, the long-chain omega-3 polyunsaturated fatty acids found almost exclusively in fish, has been associated with improved developmental assessments in young infants. The best-known effects are better scores in visual acuity and general developmental tests. Although some studies have reported improvements in children as long as one year after birth, most reports have described short-term effects. For this reason, it is unclear whether the early benefits observed with higher marine omega-3 intakes during pregnancy have long-lasting effects. Researchers at the Maternal consumption of fish or marine omega-3s University of Western Australia, led by Dr. Jan during pregnancy has been Dunstan, have been studying the developmental outcomes of associated with improved developmental assessments children whose mothers consumed fish oil in young infants. Whether the early benefits are longlasting is unclear. their pregnancy. In a during the last half of recent report, they described the test results for mental development, language and behavior in children aged years whose mothers consumed relatively large amounts of fish oil (3.3 grams of marine omega-3s per day) during pregnancy. This amount would be roughly equivalent to 3 servings of salmon/day. They compared the results with outcomes in children whose mothers consumed a placebo supplement. The study included 83 mothers and 72 children who completed the study after years. Children from both groups of mothers did not differ in height, weight or other growth indicators. In the assessment of mental development, 5 of the 6 features evaluated did not differ between the groups, but for eye and hand coordination the groups differed. Children whose mothers consumed fish oil had significantly better scores than the control children. Moreover, the eye and hand coordination scores were directly related to the content of marine omega-3s in the children s red blood cells. This suggests that these fatty acids were important in the development of eye and hand coordination. When the investigators took into consideration other possible confounding factors, such as the mother s education, this difference remained significant. Proper eye and hand coordination depends on good visual function, which is related to higher levels of marine omega-3s. Some other studies have reported improved motor skills and coordination of movements with higher levels of marine omega-3s in the mothers and such findings would be consistent with those in this study. Readers should note that this study used high levels of marine omega-3s, so it is not known whether similar results would be observed with amounts that are more practical. The high dose was not linked to any undesirable outcomes. The study increases the evidence that children s development benefits when their mothers consume plenty of marine omega-3s during pregnancy. Is Problem Childhood Behavior Linked to Marine Omega-3s? A child s behavior is affected by many influences, so the idea that the levels of particular fatty acids a child has at birth could affect his behavior years later may seem farfetched. But such a possibility has a reasonable basis, considering how the brain works. For example, we know that the communication of signals between brain cells and between the brain and the rest of the body is sensitive to the types of fatty acids in brain cell membranes. The types of fatty acids found in fish, marine omega-3s, facilitate brain cell communication. Marine omega-3s have also been linked to memory, learning skills, aggressive behavior, hostility, depression and other aspects of brain function. 4

5 There is keen interest in finding out whether an infant s fatty acid status at birth affects learning and behavior in later childhood. The fatty acid composition of the developing brain is determined in large part by the transfer of fatty acids from the mother to the fetus during pregnancy. The mother obtains most of these fatty acids from the foods she eats. Children whose mothers who do not eat fish have less marine omega-3s in their brains than children of fish-eating mothers. Infants who are provided marine omega-3s in early life, from breast milk or fatty acidsupplemented infant formula, have more of these fatty acids in their tissues than children who do not receive these nutrients in early life. There is keen interest in finding out whether an infant s fatty acid status at birth affects learning and behavior in later childhood. To see if there was a connection between an infant s marine omega-3 fatty acid status at birth and his behavior at 7 years of age, researchers at Maastrict University in the Netherlands evaluated the behavior of children who had previously participated in a long-term study on essential fatty acids. Of the original 750 children, 292 were available for assessment 7 years later. Blood samples taken at birth and at age 7 were analyzed for their fatty acid composition. The investigators assessed the children s behavior using a commonly used test, the Child Behavior Checklist. This test provided scores for internalized behavior, such as anxiety and withdrawal, and for external behaviors, such as aggression and breaking the rules. The researchers reported that externalized behavior (e.g., aggression) was not related to any fatty acids levels in the infants at birth, but certain internalized problem behaviors (e.g., anxiety, withdrawal) were more likely in the 7-year olds who had low docosahexaenoic acid (DHA), a marine omega-3, at birth. Infants who were fed infant formula, which at that time did not contain long-chain polyunsaturated fatty acids* or marine omega-3s, were more likely to have problematic internalized behavior than breast-fed infants who obtained marine omega-3s. When the investigators grouped the children according to whether their blood DHA content at birth was above or below the middle value for the group, they observed that internalized problem behaviors were more common in the low DHA group. These findings do not prove that low DHA at birth causes behavior problems, but they suggest that the two could be connected. The observations imply, but do not prove, that mothers of infants with lower DHA values may have consumed too little marine omega-3s during their pregnancy. Additional support for a link between DHA status and behavior comes from studies in children with developmental and behavioral disorders whose behavior improved after they were given marine omega-3s. This study supports the notion that marine omega-3s may affect some aspects of childhood behavior. Long-Lasting Improvement in Visual Acuity with Higher DHA in Infancy The retina of the eye is one of the body s most powerful magnets for docosahexaenoic acid (DHA), one of the two principal long-chain omega-3 fatty acids found almost exclusively in fish and shellfish. These fatty acids, also known as called marine omega-3s, are critical components of the brain and eyes. They accumulate in these tissues during fetal life and for at least the first 2 years after birth. Because DHA is vital for the normal development and function of the retina, it is not surprising that infants born with low levels of DHA have lower scores on certain visual tests. Infants who receive DHA, a marine omega-3 fatty acid, after birth have higher scores on tests of visual acuity than infants who do not obtain DHA. Visual acuity is the ability to distinguish fine spatial details. This capacity develops quickly in the first 6 months of life, but continues to develop gradually after that until 4 to 6 years of age. Infants who receive DHA after birth, from breast milk or DHA-supplemented infant formula, have higher scores * Desribed in the glossary on page 12. 5

6 on tests of visual acuity than infants who do not obtain DHA. These differences have been reported in the first 6 months of life, and in one study, up to the age of 1 year. Researchers at the Retina Foundation in Texas, USA, have recently reported that the suboptimal visual acuity they observed in the first few months of life, when DHA was lacking in infant formula, persists until 4 years of age. In their study, the investigators compared the visual acuity scores of 4-year-old children, who, as healthy infants, were fed one of several options: breast milk, infant formula without DHA, infant formula with DHA, and infant formula with DHA and arachidonic acid (ARA), a long-chain omega-6 polyunsaturated fatty acid* that is also important in the brain. The scientists also measured the children s intelligence (IQ). Children who had been fed the unsupplemented formula as infants had significantly poorer visual acuity scores in their right eye compared with children who were breastfed or given DHA-supplemented formula. They also had significantly lower verbal IQ scores. Scores for left eye visual acuity did not differ significantly among any groups of children. The investigators pointed out that the differences in visual acuity they observed were subtle less than one line on an eye chart. Moreover, all children had acuity and intelligence scores in the normal range. But the study suggests that having too little DHA in infancy may have persistent effects detectable in childhood. Such observations raise the question of whether children with low DHA in early life can make up the difference later on. We do not know. We are learning that DHA is important for visual function throughout life, possibly reducing the chance of developing age-related macular degeneration. As the evidence accumulates, the bottom line is easier to read: DHA is an important part of healthy vision right from the beginning. MENTAL HEALTH Marine Omega-3s Linked to Reading Scores in Adults With or Without Dyslexia People with dyslexia have problems processing language and this can affect reading, recognizing words, math, music and processing certain types of information. The condition typically appears in childhood and often persists into adulthood. It is more common in boys than girls and tends to run in families. We now recognize that dyslexia has a neurological origin and that people with this disorder process information in a different area of the brain than those who are not dyslexic. More recently, we learned that deficiencies or imbalances in long-chain polyunsaturated fatty acids* (PUFAs) are involved in dyslexia, but it is not clear how. Children with Deficiencies or imbalances in dyslexia and closely related condi- long-chain polyunsaturated fatty acids (PUFAs) are tions involving impaired reading involved in dyslexia, but it skills have low is not clear how. blood levels of long-chain PUFAs and exhibit some of the symptoms of essential fatty acid deficiency. More recently, reports have emerged describing improved reading and language skills in dyslexic children supplemented with long-chain PUFAs. It has not always been clear whether all longchain PUFAs are involved, or mainly those from seafood, the marine omega-3s. The study described * Desribed in the glossary on page 12. 6

7 here adds new information to the emerging picture of fatty acids in dyslexia. Researchers at Oxford University and the University of Stirling in the United Kingdom examined the pattern of fatty acids, mainly long-chain PUFAs, in the red blood cells of adults with dyslexia and a group of healthy people similar in age who did not have reading difficulties. Both groups had similar fatty acid levels in their red blood cells, but differed significantly in their reading scores. The investigators then explored whether each group s reading scores was related to any individual PUFA level. They observed that higher reading scores in both groups were related to higher levels of total omega-3 PUFAs in the blood. In the non-dyslexic group, higher levels of docosahexaenoic acid (DHA), one of the two main marine omega-3s found almost exclusively in seafood, were strongly related to better reading scores. DHA was unrelated to reading scores in the dyslexics. Higher reading scores were related to higher levels of total omega-3s in dyslexic and nondyslexic adults. In people with dyslexia, DHA was unrelated to reading scores. These observations suggest that marine omega- 3s are involved in reading ability and that in people without dyslexia, DHA appears to be linked to improved reading skills. The study involved only a small number of participants, so it was not possible to better define the relationships between individual fatty acids and reading. It would be useful to confirm whether DHA affected reading ability in dyslexics, as it appeared unrelated in this study. There were hints that omega-6 PUFAs might also be involved in reading ability, but nothing conclusive could be determined. The authors noted that a larger randomized controlled trial- the most rigorous design is currently underway to better understand the involvement of PUFAs in dyslexia. We look forward to reading the results. Marine Omega-3s May Improve Outlook of Patients Tending to Harm Themselves Some people with certain mental disorders and behaviors, such as aggression and irritability, are more likely to inflict harm on themselves and attempt suicide. These characteristics are more common in women, smokers, those who drink excessively and in whites. People with these behaviors are usually treated with medications. Understanding these types of disorders is challenging, but evidence is emerging that, as in patients with depression, bipolar disorder and violent tendencies, patients with self-harm have disordered fatty acid patterns in their blood. Like patients with depression, bipolar disorder and violent tendencies, patients who intentionally harm themselves have disordered fatty acid patterns in their blood. A team of investigators in Ireland and the United States took a closer look at the fatty acid profiles of patients who were hospitalized for intentionally harming themselves. They compared them with patients selected from the medical ward, who were matched for age and sex. None of the patients had been diagnosed with psychiatric or psychotic disorders or were taking any psychotropic medicines. All study participants ranged in age from 15 to 65 years. The investigators found some striking differences in the polyunsaturated fatty acids (PUFAs) between the two groups. The self-harm patients had significantly lower levels of total omega-6 PUFAs, which are derived from plant foods, and lower levels of marine omega-3 PUFAs in their blood. The omega-6 fatty acid, linoleic acid, which is the predominant PUFA in the western diet, was significantly lower in the self-harm patients, but its long-chain derivative was not. Both of the major marine omega-3s, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were significantly lower in the self-harm patients compared with the control patients. As has been observed in earlier studies, the self-harm patients also had lower levels of blood cholesterol. These observations suggest that PUFAs participate in mechanisms linked to behavior and that having too little may be detrimental. Whether these low levels were related to dietary intake or metabolism could not be determined in this small study. However, the investigators extended their study to 7

8 determine whether providing marine omega-3s to such patients might affect their behavior. They recruited a second set of self-harm patients, most of whom had personality disorders, who had been hospitalized for repeatedly injuring themselves intentionally. Patients were selected randomly to receive either marine omega-3s (3 grams/day) or corn oil supplements daily. Corn oil contains mainly the omega-6 PUFA linoleic acid. Patients consumed the supplements for 12 weeks. At the beginning and end of the study, a clinician assessed the patients using standardized tests for depression, aggression, memory, stress and daily ups-and-downs. IMMUNE FUNCTION Marine Omega-3 Derivative Saves Bone in Advanced Dental Disease Severe periodontitis increases the risk of heart disease, heart attack and hypertension, especially in younger men. Omega-3 polyunsaturated fatty acids* derived from seafood, marine omega-3s, are known for their anti-inflammatory properties in various conditions, particularly asthma and rheumatoid arthritis. They help reduce the production of inflammatory products associated with excessive immune responses. About the year 2000, it was found that marine omega-3s are used to make highly potent anti-inflammatory substances called resolvins, named for their ability to resolve or stop acute inflammation. The resolvin derived from eicosapentaenoic acid (EPA), one of the two main marine omega-3s, is called resolvin E1, and it triggers a halt to inflammatory processes outside the brain. Resolvin E1 is highly potent, but short-lived. At the end of the study, patients who consumed marine omega-3s had significantly improved scores for depression, perceived stress and daily ups-and-downs compared with patients consuming the corn oil supplements. There were no differences between the two groups in the assessments of aggression, irritability and memory. The investigators noted that at the end of 3 months, the scores had not leveled off, perhaps suggesting that over a longer period of time, the changes might have been even greater. Taken together, these studies confirm earlier reports that patients with similar behavioral difficulties have below normal levels of PUFAs, especially of marine omega-3s. Further, providing supplementary sources of these fatty acids makes a measurable and meaningful difference in these patients behavior. These types of psychosocial disorders are highly complex and it would be simple-minded to think the solution rests only with dietary PUFAs. However, the evidence continues to accumulate that these fatty acids, particularly the marine omega-3s, may reduce the danger and distress associated with these illnesses. Figure. Healthy tooth and gum structure (left) and erosion of gum and bone from periodontal disease (right). Reproduced courtesy of the American Academy of Periodontology. The team of scientists who first reported the production of resolvins turned their attention to the potential for resolvin E1 to control tissue damage caused by severe dental disease. When such disease becomes severe, a condition * Desribed in the glossary on page 12. 8

9 known as periodontitis, the gums and bone supporting the teeth deteriorate, causing extensive tissue damage (Figure). The danger does not end in the mouth. Severe periodontitis increases the risk of heart disease, heart attack and hypertension, especially in younger men. A heavy oral bacterial load increases the risk of atherosclerosis and the burden of underlying inflammation that accompanies heart disease. In fact, periodontal bacteria have been found in atherosclerotic plaque. In the study described here, researchers compared the responses of neutrophils white blood cells that fight bacterial infection to two anti-inflammatory agents, lipoxin and resolvin E1. Lipoxin is similar to resolvin E1 and is produced when aspirin is taken. Neutrophils from healthy people suppressed their inflammatory responses to both lipoxin and resolvin E1. In contrast, neutrophils from patients with periodontitis did not respond to lipoxin, but responded to resolvin E1. Thus, both healthy and infected people responded to resolvin E1, but only uninfected people responded to aspirintriggered lipoxin. In the second part of their study, the investigators examined how infected gum tissue would respond to the topical application of resolvin E1. They induced gum disease in experimental animals using a major microorganism found in periodontitis and then evaluated three different treatments. One group was given an anti-bacterial agent to suppress infection, another had resolvin E1 applied topically, and a third group was given a placebo treatment (ethanol). The most striking observation was a 95% inhibition of tissue and bone damage in the animals treated with resolvin E1. Treated animals showed no signs of osteoclast activity-cells that destroy bone. The most striking observation was a 95% inhibition of tissue and bone damage in the animals treated with resolvin E1. Neutrophils were not present in the tissue, even though the bacterial infection was active. Resolvin E1- treated animals showed no signs of bone-destroying cell activity. In contrast, animals treated with the bacterial inhibitor had their infection suppressed, but were not spared tissue and bone damage. These animals had large numbers of bone-destroying cells in their gum tissues. Similarly, the placebo treated animals developed infection and extensive tissue and bone loss. These remarkable findings indicate that resolvin E1 is strongly effective in stopping neutrophil and bonedestroying cell activity in periodontitis, even though it does not abolish bacterial activity. This suggests that the inflammatory activity associated with dental disease is more damaging than the infection itself, although a person doesn t develop the inflammatory response without the initial infection. The next step is to evaluate resolvin E1 in people with periodontitis. Perhaps the path to heart health passes by disease-free teeth. CLINICAL CONDITIONS Cancer Marine Omega-3s and Other Nutrients May Lower Risk of Non-Hodgkin s Lymphoma Various environmental conditions contribute to the development of cancer, but clear understanding of the effect of diet has been elusive. Typical western food habits of abundant red and processed meats, dairy products and saturated fats, with low consumption of fruits, vegetables and fish, have been associated with increased risk of several cancers, including non- Hodgkin s lymphoma, a cancer of the immune system. Seeking more details about particular dietary components that could affect the chance of developing this cancer, Dr. Ellen Chang of the Northern California Cancer Center and colleagues in Sweden examined data available in a large Swedish cancer registry. They compared the consumption of many dietary items in patients who developed one of 4 types of non- Hodgkin s lymphoma with the intakes of people living in the same counties who did not develop the disease. Perhaps surprisingly, dietary fat of any type or amount was unrelated to the chance of developing any type of non-hodgkin s lymphoma. Type of dietary fat has often been linked to cancer risk, but data remain controversial. High consumption of fish, fatty fish and marine omega-3s were significantly linked to a 40% to 50% 9

10 lower chance of all types of non-hodgkin s lymphoma. Fish and fatty fish High consumption of fish, fatty fish and marine omega-3s were significantly linked to a 40% to 50% lower chance of all types of non-hodgkin s lymphoma. intakes were also linked to lower risk of diffuse large B-cell lymphoma, chronic lymphocytic leukemia and follicular lymphoma, 3 of the 4 types of lymphoma studied. These associations confirm a previous report by these researchers of the protective effect of seafood consumption and lower risk of all lymph and blood cancers. The study also extends the list of protective nutrients for this disease to include dietary fiber, beta-carotene, vitamins C and E, folic acid and iron. These nutrients abound in fruits and vegetables, as Popeye the Sailor Man (a popular cartoon character) knew. It was his claim to be strong to the finach, cause I eats me spinach, which put spinach on the menu for a whole generation. It s anyone s guess whether Popeye ate fish with his spinach, but apparently he didn t develop non- Hodgkin s lymphoma. Eating Fatty Fish Linked to Lower Risk of Prostate Cancer Prostate cancer is the most commonly diagnosed cancer in men after middle age. It is estimated that about 30% of all men in western countries will develop some evidence of this cancer in their lifetime. Fortunately, the disease grows slowly and men have a very low (about 3%) chance of dying from the disease. Several reports have observed a lower chance of developing prostate cancer in men who eat fish regularly. There is also lively controversy about the effect, if any, of the plant-based omega-3 fatty acid, alpha-linolenic acid on this disease. Several reports have observed a lower likelihood of developing prostate cancer in men who eat fish regularly. Marine omega-3 polyunsaturated fatty acids* (PUFAs), found almost exclusively in seafood, have been linked to lower risk of advanced prostate cancer. There is also lively controversy about the effect, if any, of the plant-based omega-3 fatty acid, alpha-linolenic acid, on this disease. Some studies have reported increased risk with high levels of alphalinolenic acid, while others have found no link between the two. That question remains unresolved. One characteristic of prostate cancer is the over-production of a key inflammatory substance produced from long-chain PUFAs. This substance, prostaglandin E2, was first isolated from extracts of the prostate gland. It is particularly known for its ability to enhance inflammatory responses, although it has diverse properties throughout the body. Control of prostaglandin E2 production by anti-inflammatory agents reduces the risk of prostate cancer. Further, the consumption of marine omega-3s reduces the production of prostaglandin E2. In this study from the Karolinska Institute in Sweden, investigators examined in detail the frequency of fish consumption and the types and amounts of fish consumed by men diagnosed with prostate cancer and men without the disease. Men who did not have prostate cancer were selected to match those with the disease for age and geographic residence. Both groups of men had similar fish consumption habits. Men who ate salmon and salmon-type fish (including herring and mackerel) had a significantly lower risk of developing prostate cancer compared with men who never ate fish. Men who ate 5 or more servings of fatty fish/week had a 64% lower risk of developing prostate cancer compared with men who did not eat fish. When the frequency of eating fish and the types of fish were considered, a clear pattern appeared. Men who ate salmon and salmon-type fish (including herring and mackerel) had a significantly lower risk of developing prostate cancer compared with men who never ate fish. For men eating 5 or more servings of fatty fish/week, risk of prostate cancer was 64% lower than men who didn t eat any fish. The importance of the type of fish consumed (fatty fish) was strengthened by the observation that frequent consumption of cod and other lean fish or shellfish was associated with significantly greater risk of the * Desribed in the glossary on page

11 disease, compared with men who avoided fish. The researchers suggested that these observations may reflect the very low levels of marine omega-3s in these lean seafoods. Why the risk would be increased with eating lean fish compared with not eating any fish is not known. Other interesting links with the type of fatty acids in the diet emerged. For example, men with the highest intakes of total omega-6 PUFAs, the kind found in vegetable oils and seeds, had a 35% greater risk of prostate cancer. Risk was also significantly greater with the highest intakes of alpha-linolenic acid, the plant-based omega-3 fatty acid. As expected from the results with fish consumption, the highest intake of marine omega-3s, abundant in fatty fish, was linked to significantly lower prostate cancer risk. The researchers also screened the participants to identify variants in the gene responsible for prostaglandin E 2 production. They identified one genetic variant that, when present in men who ate the greatest amount of salmon-type fish, was associated with an even lower risk (72%) of prostate cancer, lower, than observed with fish consumption in the overall sample. This finding gives further weight to the evidence linking prostaglandin E 2 metabolism with risk of this disease. This study is important in several regards. It further documents the link between high intake of marine omega- 3s and lower risk of prostate cancer in a sample of over 1,300 men with the disease. It supports a link between a high consumption of omega-6 PUFAs, mainly linoleic acid, which predominates in vegetable oils and seeds, and increased risk of prostate cancer. Finally, it reports a strong link between the genes for reduced production of prostaglandin E2 and significantly lower risk of the disease. The large task remaining is to understand how these polyunsaturated fatty acids affect the development of prostate cancer. Prostate Cancer Recurrence Linked to Prostate Fatty Acids When prostate cancer is detected in its earliest stages and is confined to the prostate itself, nearly all treated men will be disease-free in 5 years. However, the disease does recur in a small percentage of cases. Having a healthy diet, active lifestyle and avoiding obesity decrease the chances of recurrence. Some studies have reported a lower risk of the disease in men who consume fatty fish regularly. A clearer picture of how particular types of dietary fats might affect risk of recurrence would have considerable practical application. A recent study tried to determine which fatty acids might be linked to the recurrence of prostate cancer. Investigators at the University of Illinois, Chicago, USA, examined the fatty acids in healthy prostate tissue of men who had prostate surgery. The patients did not receive any other treatment for the disease. Doctors monitored the men for 2 to 6 years, noting the number of cancer recurrences and the levels of PSA, a marker for the disease, every 3 months after surgery for 12 months and annually thereafter. There were 14 prostate cancer recurrences (about 8%). Men with recurrences had higher levels of PSA at the time of their original diagnosis and tended to be obese. The investigators also observed that the chance of having the cancer return was significantly lower in men who had higher levels of polyunsaturated fatty acids in their prostate tissue. Surprisingly, a high level of oleic acid, the main monounsaturated fatty acid in olive and 11

12 Recurrence of prostate cancer in men whose prostate had been removed was less likely in men with higher levels of polyunsaturated fatty acids in their prostate tissue. canola oils, was linked to greater risk of cancer recurrence. Levels of marine omega-3s or alpha-linolenic acid, the plantbased omega-3 fatty acid, were not related to risk of cancer recurrence. Neither was arachidonic acid, the long-chain omega-6 fatty acid that has been linked to advanced prostate cancer in other studies. What does a person do with this information? Right now, probably nothing. This was a relatively small study and its findings need to be confirmed in larger studies. A study with more cases of recurrence is needed to confirm the lack of association of disease recurrence with marine omega-3s. Right now, this observation does not fit with other reports. The good news remains: if caught early, prostate cancer does not make an easy comeback. GLOSSARY TERMS Long-chain: Refers to fatty acids having 20 or more carbon atoms. Monounsaturated: A fatty acid missing one pair of hydrogens so that it has one double bond. A common example is oleic acid. Omega-3: A fatty acid in which the first double bond or pair of missing hydrogens occurs 3 carbons away from the omega or non-acidic end of the fatty acid. Marine omega-3s refers mainly to EPA and DHA, also called long-chain omega-3 fatty acids because they have 20 or more carbons in their chain. Omega-6: A fatty acid in which the first double bond or pair of missing hydrogens occurs 6 carbons away from the omega or non-acidic end of the fatty acid. The most common omega-6 fatty acid in food is linoleic acid; in cell membranes, it is arachidonic acid. Polyunsaturated: A fatty acid with two or more double bonds. Common polyunsaturated fatty acids are linoleic, alpha-linolenic, arachidonic, eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids. Editor: Joyce A. Nettleton, DSc, joyce@fatsoflife.com Communications Consultant: Angela Dansby, angela@fatsoflife.com Sponsor: DSM Nutritional Products, Inc., Kaiseraugst, Switzerland, Subscribe to the Fats of Life Newsletter at 12