HEART HEALTH Women with High Intakes of Seafood Omega-3s May Have Fewer Strokes... 2

Transcription

1 FATS OF LIFE NEWSLETTER Volume 7 Issue 1 April 2012 Contents HEART HEALTH Women with High Intakes of Seafood Omega-3s May Have Fewer Strokes... 2 MOTHERS AND INFANTS Learning and Behavior in Adolescents Whose Mothers Ate Fish During Pregnancy... 2 MENTAL HEALTH Perinatal Depression Depressive Symptoms in Early Pregnancy Linked to Lower Breast Milk DHA Levels... 4 Postpartum Depressive Symptoms Linked to High Omega-6 and Low Omega-3 Intakes... 5 Alzheimer s Disease Challenge: Assessing Brain Fatty Acid Changes During Cognitive Decline... 6 VISUAL FUNCTION Seafood Omega-3s and High-Dose Vitamin A Slow Visual Loss in Retinitis Pigmentosa... 7 DHA Restriction in Early Development Leads to Distortions in Visual Pathways... 8 Corneal Nerves Regenerate and Function After Injury and DHA Plus PEDF Treatment...10 BRAIN FUNCTION Peripheral Nerves with Higher Long-Chain Omega-3s Better Protected from Injury...11 CLINICAL CONDITIONS Muscle Strength: Build it Better with Fish Oil and Strength Training Fats of life Staff Editor Joyce A. Nettleton, DSc sciencevoice@q.com Communications Manager Angela Dansby angela@fatsoflife.com Sponsor DSM Nutritional Products, Inc., Columbia, MD, USA Letters and editorial comments should be submitted to Nettleton at sciencevoice@q.com and technical comments to Dansby at angela@fatsoflife.com. Subscribe to Fats of Life at Higher Long-Chain Omega-3s Linked to Lower Risk of Colorectal Polyps in Women

2 HEART HEALTH Higher intakes of fish or long-chain omega-3 fatty acids have been associated with reduced stroke risk in several studies, especially in women. Data from a large population of Swedish women suggest that higher intakes of seafood omega-3s may reduce the risk of total stroke in women by approximately 16%. Women with High Intakes of Seafood Omega-3s May Have Fewer Strokes There is considerable evidence that eating fish or the long-chain omega-3 polyunsaturated fatty acids (omega-3s) they contain is associated with a lower risk of stroke in women. Not all research studies agree, however, and some reports suggest that men who consume fatty fish regularly may also have a lower risk of stroke. Stroke is the third leading cause of death in the U.S. and is the most common cause of long-term disability. It occurs more frequently in people who smoke or have high blood pressure. The most common type of stroke in western populations is the thrombotic type, in which a blood clot or severe narrowing of a cerebral artery blocks the flow of blood and oxygen to a part of the brain. Previous evidence from a very large study in Swedish women suggested that women above the age of 49 who ate more than 3 servings of lean fish per week had a 33% lower chance of developing a stroke compared with women who ate little or no fish. In a new report from this study, the investigators wondered if the consumption of fatty fish or seafood omega-3s were linked to a lower risk of stroke. They compared the occurrence of stroke in women in the highest fifth of participants in terms of their fat, cholesterol and fatty acid intakes with participants in the lowest fifth. Women with the highest intakes of seafood omega-3s had a 16% lower risk of all types of stroke compared with women in the lowest fifth of intake. Women who ate the most fish consumed an average of 730 mg per day of seafood omega-3s, 5 times more than the 144 mg per day consumed by women in the lowest group. The risk of thrombotic stroke was also 17% lower among the highest fisheaters, but this estimate did not quite achieve statistical significance. High cholesterol intakes were linked to a 20% greater chance of stroke compared with low intakes. These findings confirm several previous reports that seafood and seafood omega-3s are associated with a lower risk of stroke, especially in women. Given the many other health advantages associated with eating fatty fish regularly, from cardiovascular to visual and perhaps cognitive benefits, making seafood meals a regular habit may pay healthy dividends. MOTHERS AND INFANTS Learning and Behavior in Adolescents Whose Mothers Ate Fish During Pregnancy Persistent worries about the potential dangers from consuming fish and the methylmercury they contain continue to frighten women away from eating fish during pregnancy, especially in the U.S. Mercury is A long-running study on the effects of maternal fish consumption and prenatal exposure to methylmercury reports findings on the development of the offspring who are now adolescents. The news is encouraging. Figure. Salmon tacos. Image courtesy of the Alaska Seafood Marketing Institute. present in nearly all seafood in the form of methylmercury. Seafood consumption is already very low in the U.S. and Canada, as shown in government surveys and research studies. Some estimates suggest that as many as 20% of women of child-bearing age eat no fish or shellfish. This poses a problem for 2

3 women during pregnancy and lactation. Women who eat no fish or very little seafood and do not take fish oil supplements have almost no dietary source of the long-chain omega-3 fatty acids found in seafood. These fatty acids are critical for the healthy development of the brain and retina of the fetus. It also means these mothers have smaller body stores of these omega-3s for the fetus to draw upon and to provide sufficient amounts in their breast milk. With very few exceptions shark, king mackerel, tilefish and swordfish most fish in the seafood marketplace has very low levels of contaminants, including methylmercury. Many studies have reported that women who eat plenty of commercially available fish during pregnancy have offspring with significantly lower chances of having suboptimal developmental scores on a variety of test measures. In other words, their children perform better and do not have any signs of harm from low-level exposure to mercury. One of the strongest reasons for asserting that eating fish during pregnancy benefits, not harms, the offspring comes from the long-term research study conducted in the Seychelles Islands. People there consume 10 times as much fish and shellfish as eaten in the U.S. and their children show no clinically meaningful detriments from such a diet at all stages of development. Yet mothers in the Seychelles have higher hair mercury levels and dietary intakes than women in the U.S. The most recent study from the Seychelle Islands reports the cog nitive and behavioral test results in the adolescent offspring of mothers who have been monitored since pregnancy. These offspring were 17 years of age, on average. They underwent a series of learning tests and behavioral assessments to evaluate their learning abilities and social behaviors. These included such aspects as mental health, antisocial behavior, substance abuse and referrals to a school counselor. The test findings were then analyzed for their relationship to prenatal methylmercury exposure and adjusted for confounding (interfering) factors such as maternal intelligence and sex. Adolescents whose mothers ate fish daily and had high exposure to methylmercury during pregnancy had higher learning and behavioral scores compared with those having less exposure. These results are presumably due to the nutrients in the fish. The investigators found that higher exposure to prenatal methylmercury was associated with better performance on the achievement scores, suggesting that the students had enhanced problem-solving ability. Similarly, the adolescents with the highest methylmercury exposure had improved scores on several behavioral assessments. For example, there were fewer substance abuse reports, especially for females with the highest scores. Overall, learning and behavior scores were either higher in the students exposed to greater methyl mercury levels, or there was no link between scores and prenatal mercury exposure. Of the 27 evaluations given, only one adverse association was observed and that was for the lowest category of referrals to a school counselor. There was no association between methylmercury exposure and the more troublesome category of frequent referrals. There is no reason to think that methy lmercury itself was contributing to the improved performance of these students. In all likelihood, methylmercury exposure reflects greater fish consumption and higher nutrient intakes, especially of seafood omega-3s, selenium, iron, iodine and others especially advan tageous in the brain development. This long-running study on the outcomes in mothers and their offspring according to their environmental exposures to fish and contaminants has reported over 70 different endpoints for learning, achievement and 3

4 problem behaviors. To date there has been no consistent pattern of adverse or undesirable associations between prenatal methylmercury exposure and developmental outcomes. These findings provide substantial reassurance that eating plenty of fish during pregnancy and the exposure to methylmercury that goes along with it is not linked to harmful effects in the offspring. Eating fish and shellfish during pregnancy is one of the easiest ways to obtain critical nutrients that promote healthy fetal and infant development. MENTAL HEALTH Perinatal Depression Depressive Symptoms in Early Pregnancy Linked to Lower Breast Milk DHA Levels Some women develop depressive symptoms during or after childbirth, but it is unclear why some women do and others do not. A history of depressive illness and difficult socioeconomic conditions increase Pregnant women with low long-chain omega-3 status may face a higher risk of developing depressive illness. A new report describes an association between low breast milk DHA levels and depressive symptoms in early pregnancy. the risk of developing this condition, but other factors, including nutrition may contribute as well. Several studies have examined whether a woman s long-chain fatty acid status is associated with the odds of developing perinatal depressive symptoms. There is good reason to think that having too little of the long-chain omega-3s found in fish and shellfish in tissues may contribute to the risk. These fatty acids are necessary components of the brain and contribute to its structure and function. Low omega-3 status has often been associated with a higher risk of depressive illness unrelated to pregnancy. In Western countries, fish intake is generally low, especially among women. Unless a woman takes fish oil or omega-3 fatty acid supplements, she is likely to have low concentrations of these fatty acids in her blood and tissues. Having a low seafood omega-3 status may limit the amount of these fatty acids, especially DHA, she has available to pass on to the developing fetus and supply in her breast milk. Because no one had actually measured the breast milk omega-3 content from women with depressive symptoms, researchers at the University of North Carolina, U.S., examined this question. The researchers recruited pregnant women at less than 20 weeks gestation and followed them through their pregnancy and the first 4 months after delivery. They assessed the women twice during pregnancy for symptoms of depressive illness and measured the fatty acids in their breast milk in the 4th month after delivery. The assessment of dietary omega-3 consumption indicated that these women consumed less than one-third of the recommended intake of omega-3s during pregnancy. At less than 20 weeks gestation, 12% of the women had symptoms of depressive illness and this proportion increased to 16% by weeks 24 to 29. These estimates are at the higher end of some, but not all, estimates of the prevalence of depressive symptoms during pregnancy. Women with fewer years of education, lower income, younger age and who smoked were more likely to have symptoms of depressive illness. The low consumption of omega-3s was also reflected in the low concentrations of DHA in breast milk. Women with more than 16 years of education had higher breast milk DHA, but the level was still 25% below the worldwide average. For less educated mothers, the breast milk DHA level was less than half the worldwide average. The investigators also observed a significant association between the depressive symptoms in women at less than 20 weeks ges tation and low breast milk DHA content. 4

5 Pregnant women with less than 12 years education had breast milk DHA concentrations less than half the worldwide average. They were also more likely to have depressive symptoms in early pregnancy. While this association does not establish that low DHA causes depressive illness, it suggests a link. It also raises a red flag about the mother s and her infant s nutrition. With these low intakes and low breast milk DHA concentrations, both mother and infant have suboptimal nutrition. This situation can be readily improved if the mothers include fish in their diet regularly. Greater fish or fish oil consumption by these mothers may not improve the mothers symptoms of depressive illness, but the fatty acids they contain will help build better brains for both mother and child. Postpartum depressive symptoms occur more frequently in developing countries than in rich ones. Poor nutrition and difficult socioeconomic conditions may increase the risk of this condition. Postpartum Depressive Symptoms Linked to High Omega-6 and Low Omega-3 Intakes Depressive illness during and after pregnancy affects from 10% to 40% of women worldwide, according to the World Health Organization. The occurrence of this burdensome condition is higher in less developed countries where treatment may be limited and difficult living conditions complicate the situation. Having previously had depressive illness and low nutrient intakes increase the risk for developing this trouble some condition. Improving the nutrient intakes of pregnant and nursing women may be one of the more feasible approaches to reducing the occurrence of depressive symptoms. Dietary fat, particularly the type of fatty acids in foods, is an important component of good maternal and infant nutrition. Increasingly, foods and diets contain large amounts of vegetable oils that are rich in omega-6 fatty acids. While these fatty acids are essential, their greater abundance in the food supply has crowded out the less widely distributed omega-3 fatty acids. Moreover, optimum maternal and infant health requires the long-chain omega-3s found mainly in fish and shellfish (omega-3s). Women who do not eat seafood have few other ways of obtaining these omega-3s from foods. Mothers whose diets contained mainly vegetable oils high in omega-6 fatty acids and very few foods with omega-3s were 2½ times more likely to develop depressive symptoms one month postpartum than mothers whose diets had more omega-3s. In the study described here, researchers in Brazil examined the food and fatty acid intakes of women in the first trimester of pregnancy and the presence of depressive symptoms in the mothers 30 days after delivery. They wondered if the fatty acid intakes of these mothers might be related to the occurrence of postpartum depressive symptoms. Because of the difficulty in estimating small intakes of nutrients consumed infrequently from food intake information, the investigators obtained estimates only for the most abundant omega-6 and omega-3 fatty acids. These are linoleic and alpha-linolenic acids, respectively. The investigators calculated the ratio of these dietary fatty acids then looked at the occurrence of depressive symptoms in the different categories of fatty acid consumption. The investigators observed that mothers with high dietary ratios of omega-6 to omega-3 fatty acids were more likely to develop postpartum depressive symptoms compared with women having lower ratios. Mothers with intake ratios greater than 9.1 were 2½ times more likely to develop postpartum depressive symptoms compared with mothers whose intake ratios were below 9.1. For comparison, this ratio in US diets is about 10. The investigators also noted that the prevalence of depressive symptoms 30 days after delivery in these 5

6 women was approximately 26%, much higher than the 11% prevalence previously reported for a sample of Brazilian women. These observations describe an association between high intakes of omega-6 fatty acids combined with low intakes of omega-3s and the risk of developing postpartum depressive symptoms. They do not demonstrate cause, but given what we know about the importance of longchain omega-3s in brain structure and function, the link is suggestive. It would be highly informative to learn whether increasing the fish (or fish oil) intakes of pregnant women in this community would affect the risk of postpartum depressive symptoms compared with similar women who did not eat fish. DHA has many protective functions in the brain, but how it functions in Alzheimer s disease is poorly understood. A new study shows how complex the situation is. Seafood and vegetable soup. Image courtesy of the Alaska Seafood Marketing Institute. Alzheimer s Disease Challenge: Assessing Brain Fatty Acid Changes During Cognitive Decline There is a growing literature about the links between the consumption of fish and shellfish, tissue levels of long-chain omega-3 fatty acids (omega-3s) found in seafood and the odds of developing age-related dementia. The most well known example of advanced mental loss is Alzheimer s disease, a condition prevalent in adults above the age of 65. About 13% of these adults have Alzheimer s disease, but nearly half (45%) of those 85 years of age or more have the condition, according to the Alzheimer s Association. Ultimately, the disease is fatal. Although much is known about the disease, little is understood about preventing or treating it. A promising area of research is understanding how DHA, one of the two major long-chain omega-3 fatty acids (omega-3s) found mainly in seafood and fish oil, might reduce the risk of developing Alzheimer s disease. For example, we know that DHA counteracts the inflammation that develops in the brain cells of individuals with the disease. It leads to the production of a potent substance NPD1 that protects cells and reduces the production of the abnormal protein that promotes the toxic effects of the disease. Further, we have learned that people who consume fish regularly and have higher tissue levels of DHA are less likely to develop Alzheimer s disease than people who do not eat fish. You might think that treating people who show the early symptoms of Alzheimer s disease memory loss, inability to speak coherently or understand language and other functional disabilities with DHA might slow the course of the condition. To date, DHA supplementation studies have been disappointing as symptoms progressed in spite of the intervention. There is some uncertainty whether the brain loses DHA with aging and whether the brain and blood fatty acids change with the onset of dementia. A few studies reported that the brains of individuals who died with Alzheimer s disease had less DHA compared with similar individuals who did not have the disease. Certain regions of the brain may lose more DHA than others, which may affect brain function. Some researchers observed an increase in the omega-3 content of red blood cells with age, but we are unsure about what happens in brain. Investigators in Quebec, Canada, tackled these questions in a study of older adults with different degrees of cognitive impairment 6

7 Omega-6 fatty acids in the brains of Alzheimer s patients were markedly reduced compared with cognitively unimpaired individuals. DHA levels, however, were not reduced. who were studied until their deaths. Participants were 85 years old when they entered the study. Participants with normal mental and cognitive function, mildly impaired cognition or Alzheimer s disease were randomly selected before they died and then had the fatty acids in three different regions of the brain analyzed. The blood fatty acids were determined approximately one year prior to death. The investigators found that brain linoleic acid (the major omega-6 fatty acid in the diet) and all omega-6 fatty acids were significantly and markedly reduced in the participants with mild cognitive impairment or Alzheimer s disease compared with the levels in cognitively normal participants. However, DHA and total omega-3 fatty acids were not significantly reduced in the Alzheimer s patients. Fatty acids in the blood and brains of Alzheimer s patients differ from those in unimpaired individuals, but changes in the blood do not reflect what happens in the brain during cognitive decline. In contrast, the blood levels of DHA were 30% to 50% lower in the Alzheimer s patients, but the amount of alphalinolenic acid, the plant-based omega-3, was 8 times higher compared with unimpaired individuals. Blood omega-6 levels did not differ among the groups of participants. When dietary fatty acid intakes were similar, what caused these changes? When the investigators looked at whether the levels of fatty acids in blood were correlated with those in the three regions of the brain selected, the blood and brain fatty acid levels were unrelated. This observation suggests that examining blood fatty acids does not reflect what happens to these fatty acids in the three brain regions examined. The researchers suggested that in Alzheimer s disease, DHA transport from the blood to brain may be altered, perhaps to maintain the levels of DHA in the brain. It is also unclear what the high levels of alpha-linolenic acid in the blood of Alzheimer s patients might signify. Further, we lack an effective way to assess the changes in fatty acid metabolism in the brain during cognitive decline. Unraveling the functions of DHA as cognition changes continues to be a daunting task. VISUAL FUNCTION Seafood Omega-3s and High-Dose Vitamin A Slow Visual Loss in Retinitis Pigmentosa The retina is a lightsensitive tissue lining Retinitis pigmentosa is a progressive, genetic eye disease that responds favorably to high-dose vitamin A supplementation. It also appears to respond better when long-chain omega-3 intakes are 200 mg per day or more. That s excellent news for patients with this condition. the inner surface of the eye. Its specialized photoreceptor cells respond to incoming light by initiating a chain of reactions that trigger nerve impulses to the brain. The photoreceptors consist of two types of cells, rods and cones. The rods are responsible for night vision and when these cells are impaired, night vision dims. Individuals with the gene-based disease retinitis pigmentosa (Illustration) develop poor night vision that progresses to impaired peripheral vision (tunnel vision) and then loss of central vision. Some drug treatments are available to assist patients with this condition, but the most widely used therapies now include nutrients: vitamin A in high doses and longchain omega-3 fatty acids (omega-3s) found in fish and shellfish. Vitamin A in large amounts used to be a worry because of its potential for liver damage, but its use in patients with retinitis pigmentosa has helped slow the loss in peripheral vision without detrimental effects and is now recommended. 7

8 Image of mid-stage retinitis pigmentosa showing characteristic black, spicule-shaped deposits in the retina. Image 2006, Christian Hamel. Reproduced from Wikimedia Commons. Eye specialists also wondered whether long-chain omega-3s would be advantageous in individuals with this disease. DHA, one of the main long-chain omega-3s, concentrates in the retina during fetal and infant develop ment and is essential for optimum visual performance. There is some evidence that DHA levels in red blood cells are lower in patients with retinitis pigmentosa. Patients who consume higher amounts of seafood omega-3s (mainly DHA) appear to have a slower rate of visual decline. Most of these studies have involved a limited number of patients, which makes it difficult to obtain statistically significant results. To address the numbers problem, an experienced research group analyzed the combined the data from three of its studies. The consumption of long-chain omega-3s was estimated from dietary questionnaires and all participants had been consuming high-dose vitamin A for at least 4 years. Patients were screened annually for distance and retinal visual acuity and the rate of visual decline was calculated on annual basis. The participants formed two groups according to whether their omega-3 intake was above or below 200 mg per day on average. Those consuming 200 mg per day or more were considered high omega-3 consumers. The data analysis In this report, patients revealed that those patients who with retinitis pigmentosa consumed 200 mg who consumed at least of omega-3s per 200 mg per day of longchain omega-3s plus vitamin A experi- day and high-dose high-dose vitamin A enced a 40% slower experienced a 40% slower decline in vision decline in vision per year per year compared compared with patients with those who ate consuming less than 200 less than 200 mg of mg of omega-3s per day. omega-3s per day. From a practical point of view, this slowing in visual loss has huge implications. As the authors described it, consuming high-dose vitamin A plus at least 200 mg per day of seafood omega-3s would make it possible for many patients with typical retinitis pigmentosa to retain both visual acuity and central visual field for most of their lives. That s foresight! Cartooon 2012 by Donna Barstow. Donna Barstow Cartoons. DHA Restriction in Early Development Leads to Distortions in Visual Pathways If you pause to think about it, the ability of the eye to coordinate its visual responses to different types of inputs is quite remarkable. Besides responding to light with visual images, the eye responds to sound signals by turning the eye and head toward the direction of the sound. It responds to touch to determine the nature of the object it feels and processes three-dimensional vision as well. These coordinated functions occur as a result of 8

9 Figure. Visual pathways showing the pathway of retinal nerves to the superior colliculus and lateral geniculate nucleus to the visual cortex. Image courtesy of neurons from the retina converging with other sensory neurons in two specialized brain structures. These are the superior colliculus and the lateral geniculate nucleus. The pathways between the retina, the superior colliculus and lateral geniculate nucleus and the visual cortex are illustrated in the Figure. For retinal neurons to work properly together, they must be arranged in specific patterns in these brain structures. Anything that interferes with the formation of these patterns may affect the complex function of these structures and the communication between the retinal neurons and the visual cortex in the brain. As it happens, nutrient deprivation in early development and inter ference with the metabolism of particular fatty acids can do just that. This article describes studies conducted in Brazil by researchers interested in the effects of nutritional deprivation in early life on the development of the visual system. Their work was carried out in laboratory animals, but is relevant to human nutrition because intakes of some fatty Proper development of the visual pathways in the brain requires precise neural connections from the retina to the superior colliculus and lateral geniculate nucleus. Disturbances in long-chain fatty acids may disrupt these neural patterns. acids are very low and visual function is similar to human vision. The investigators examined the effects of omega-3 fatty acid restriction in animals prior to mating, with the restriction con tinued through pregnancy and lactation, up to 6 weeks after delivery. Restricted animals were fed small but sufficient amounts of linoleic acid, an essential fatty acid that must be supplied in the diet. They had no source of long-chain omega-3s, the fatty acids found mainly in seafood. Control animals received a diet sufficient in all the fatty acids and nutrients needed for growth and development. One group of omega-3-restricted animals received omega-3s one week after delivery to see if the effects of prenatal restriction could be corrected after birth. When the infant animals were evaluated at one month of age, the omega-3-restricted animals had about half the amount of DHA in the superior colliculus as found in the control animals. The investigators also observed that the arrangement and distribution of the retinal neurons in the superior colliculus was disordered compared with the controls. Instead of their orderly pattern, the neurons were fused, spread over a wider area and extended beyond their usual zone. This disarray was observed as early as 13 days after birth. Similar disarray was observed in the lateral geniculate nucleus as well. In contrast to the disorder in the omega-3 restricted animals, those replenished with fish oil after birth had neuronal patterns similar to the controls. The provision of long-chain omega-3s restored the normal pattern of neurons in the superior colliculus. Using a different approach, the researchers also showed that the omega-3 restricted animals had a longer period to complete the formation of neuronal patterns in these structures. This might be an adaptation to the omega-3 restriction. 9

10 These complicated, but elegant, studies extend our understanding of how long-chain omega-3s, particularly DHA, contribute to optimum visual Severe restriction of long-chain omega-3s during the critical phase of visual development resulted in disturbed neuronal patterns in two key brain structures involved in vision. development and its integration with other sensory pathways. The authors suggested that DHA is likely involved in establishing the correct pattern and arrangement of retinal neurons in the superior colliculus and lateral geniculate nucleus. They showed that critical nutrients and timing are necessary for optimum visual development. Next time you turn your head to see where that songbird is sitting, think of how nutrition affects such a complex process. Corneal Nerves Regenerate and Function After Injury and DHA Plus PEDF Treatment Some nerve cells have the ability to grow and repair themselves after they have been injured. Encouraging nerves to regenerate and function after damage is a topic of vigorous research and progress. Nervous system and spinal cord injuries affect over 90,000 people in the U.S. every year and recovery from central nervous system (brain and spinal cord) injury is limited. Nerve regeneration happens more readily in the peripheral nerves than in the central nervous system, although emerging research suggests that some central nervous system repair may occur under the right circumstances. In this report, researchers at Louisiana State University, USA, studied the ability of the sensory nerves in the cornea to regenerate after injury. The cornea is the transparent covering of the eye and is rich in sensory nerve fibers (Illustration). These nerves are damaged in certain types of surgery, such as LASIK, performed to reshape the cornea and sharpen vision. Usually, these nerves do not regenerate after injury. Damage to the corneal nerves reduces sensitivity, blinking and tear secretion. These changes may lead Some nerves have the ability to grow and repair themselves after they have been injured. Recently, researchers showed that corneal nerves can regenerate after surgical injury if provided with DHA and a specific growth factor. to dry eye syndrome and reduced corneal sensitivity. Experimental studies in animals with corneal nerve damage have shown that when DHA, a long-chain omega-3 fatty acid found mainly in seafood, and a growth factor called PEDF are applied to the eye after surgery, corneal nerves regenerate almost fully. In this study, the investigators evaluated corneal nerve regeneration after injury and to what extent the regenerated nerves were functional. To do that, they assessed the treated eyes with a fine probe to elicit a blink response. If no blinking was observed, the cornea was considered insensitive. As in their previous work, the researchers observed extensive corneal nerve regeneration in the injured eyes treated with DHA and PEDF growth factor. Nerve regeneration was similar to that in the uninjured eyes. In the sensory evaluation, the investigators found that for the first 4 weeks after surgery, corneal sensitivity was low, about a quarter of the control eyes. However, by week 6, sensitivity was nearly 70% of the control eyes and at 8 weeks, sensitivity was similar to that in the control eyes. Additional evaluation of how well the regenerated nerves functioned showed that a topical injury to the surface of the cornea healed just as quickly in the corneas with regenerated nerves treated with DHA and PEDF as in the control corneas. After 72 hours, corneas from the treated regenerated group had healed virtually completely, similar to the control corneas. 10

11 These fascinating New studies showed that and insightful studies have nerves regenerated in demonstrated the the cornea after surgical powerful effect of injury are functional DHA and PEDF on and respond to stimuli. the regeneration Corneas with regenerated of corneal nerves nerves healed after injury after surgical just was well as control injury. Moreover, corneas. the regenerated nerves functioned as well as uninjured corneal nerves. These studies have clear and practical implications for eye care immediately following corneal surgical procedures, such as LASIK surgery. They have the potential to prevent the undesirable side effects of such surgery that occurs in untreated eyes, namely, dry eye syndrome and reduced corneal nerve sensitivity. Next, perhaps, corneal nerve regeneration will be demonstrated in humans. BRAIN FUNCTION Peripheral Nerves with Higher Long-Chain Omega-3s Better Protected from Injury Peripheral nerves those in the trunk and limbs connect the brain and spinal cord to all other parts of the body. They allow us to sense Patients with peripheral neuropathy may have impaired sensation in their hands and feet and reduced muscle strength. Clinicians need ways to hasten or improve nerve regeneration and ease patient symptoms. DHA might help. temperature, pressure, touch and so on. If disease or injury damages the peripheral nerves, communication b e t w e e n t h e affected area and the brain is disrupted and sensory information may not be appropriately relayed. Such circumstances make an individual more susceptible to injury, burns and falls. Damage to the peripheral nerves is called peripheral neuropathy and can be sensed by tingling, numbness, pricking sensations or muscle weakness (Illustration). Conditions that may result in peripheral neuropathy include diabetes mellitus, alcohol abuse, tumors, repetitive strain injuries, autoimmune diseases, infections and traumatic injury. Peripheral neuropathies can often be treated, sometimes cured and usually managed to prevent new damage. As long as the nerve cells have not been destroyed, peripheral nerves can regenerate. Illustration of the pricking sensation of peripheral neuropathy in the foot. One strategy for improving the neural sensitivity of patients with peripheral neuro pathy is to promote nerve regeneration. A promising approach for this is to increase the availability of long-chain omega-3 fatty acids (omega-3s), found mainly in fish and shellfish. Research attention has focused particularly on DHA, one of the two major seafood omega-3s. Several studies in animals have shown that dietary restriction of omega-3s leads to lower levels of DHA in the brain and retina. Animals fed supplemental DHA exhibit improved visual acuity, nerve growth and resistance to damage from injury or disease. Nerves require DHA to grow and concentrate this fatty acid in their endings where growth occurs. A clear demonstration of the effect of DHA on nerve regeneration is described in a study on corneal nerves in this issue. Other research has reported improved recovery and reduced damage after spinal cord injury in animals given DHA or omega-3s. In this article, investigators in London, UK, evaluated the effect of peripheral nerve injury and recovery in animals with higher levels of omega-3s and lower amounts of omega-6 fatty acids. They used mice specially bred to have more omega-3s and less omega-6s in their tissues and compared them with control animals. 11

12 First, the researchers analyzed the fatty acids in spinal cord neurons (Figure) and confirmed that the specially bred animals had significantly more DHA. These neurons also had higher levels of another long-chain omega-3 (DPA). Next, they stretched isolated nerve cells from these animals and assessed their ability to withstand strain. This mechanical injury resulted in a 2½-fold loss of cells compared with uninjured cells. However, cells from the high-omega-3 animals lost only 13% of their cells. Peripheral nerve cells enriched in long-chain omega-3s were more resistant to destruction from mechanical injury or low oxygen conditions compared with unenriched cells. Figure. Spinal ganglion nerve cells. Image 2012 Photo Researchers, Inc. The researchers also explored the ability of the nerve cells to withstand an atmosphere of reduced oxygen. Those conditions were designed to mimic what happens when blood flow is reduced, which reduces the supply of oxygen. When the cells from control animals were kept in a low-oxygen atmosphere for a time, 8% to 21% of the cells perished. In contrast, cells from the high omega-3 animals resisted damage from the low oxygen environment and were comparable to cells not exposed to low oxygen. Working with the whole animal, the investigators examined peripheral nerve recovery in the control and high omega-3 animals. As early as one day after sciatic nerve injury, the high omega-3 animals were more responsive to touch than the control animals. This difference was observed with the amount of force needed to provoke the injured limb to withdraw. After 4 and 7 days, both groups had improved, but the high omega-3 animals were significantly more sensitive than the control animals by day 7. In a separate evaluation, the inves tigators observed significantly improved recovery in the high omega-3 animals compared with the controls, although recovery was not complete. Animals with sciatic nerve damage lost fewer nerve cells and achieved greater functional recovery when their nerve cells were enriched with long-chain omega-3s compared with unenriched animals. In summary, these studies showed that peripheral nerve fibers and cells enriched in long-chain omega-3s are more resistant to injurious conditions, regenerate better and lose less functional ability compared with conventional nerve fibers. These observations suggest that higher levels of omega-3s in perip heral nerves may have protective effects and may confer greater resistance to adverse conditions. In these demon stration studies, nerve enrichment was accomplished using animals specially bred to have higher tissue levels of omega-3s. A big question is whether increasing the consumption of omega-3s would have the same effect. These findings may spark more studies aimed at improving nerve regeneration with omega-3s in individuals with peripheral neuropathy or nerve injury. CLINICAL CONDITIONS Muscle Strength: Build it Better with Fish Oil and Strength Training With aging and reduced physical activity, skeletal muscles lose some of their strength, functional capacity and mass. With greater muscle weakness, an individual may be less able to get around and care for him/herself and usually face a greater risk of bone fracture and mortality. Many of these changes can be substantially slowed and muscle performance improved with appropriate physical activity and exercise, strength training and healthy nutrition. There are now many studies in older adults 12

13 participants consumed fish oil providing 700 mg daily of EPA and DHA, the two main long-chain omega-3s in seafood; another group consumed no supplement; and the third group consumed fish oil for 2 months before as well as during the exercise program. Supervised resistance exercises were begun at a low level of intensity and gradually increased weekly until the last week of training. showing the health benefits of physical activities from alpine skiing to strength or resistance training and daily walking. Improvements associated with regular exercise include retention of muscle mass, greater strength and coordination, and better quality of life. A study of older women enrolled in a strength training program examined whether supplementation with fish oil would enhance the effects of exercise training. Good nutrition contributes to better health in older adults by improving bone density and strength, increasing heart and circulatory fitness and reducing the risk of some chronic diseases. Although we have a good understanding of how dietary fatty acids contribute to heart health, there is much less information about how fatty acids might affect skeletal muscle mass and function. Might they enhance the benefits of exercise on muscle metabolism, mass or strength? An interesting study by Brazilian researchers addressed this question in a study of healthy, white women 64 years of age who were sedentary. The investigators designed a 3-month, targeted exercise program aimed at strengthening the lower limbs. One group of Muscle performance was assessed before supplementation and training and at the end of the 3-month exercise period. In addition, the participants performed four exercises to assess their overall muscle function before and after training. These Sit and reach exercise. included getting up from a chair without using the arms, foot up-and-go, sit and reach, and a 6-minute walk test. Fish oil supplementation enhanced the improvements in strength and function observed with 3 months of moderate, graduated strength training in older women. At the end of the resistance training, muscle function improved in all groups, but the improvements were significantly greater in those who consumed the fish oil. Consuming fish oil prior to strength training did not confer any advantage. Muscle activation and the time lag for a mechanical response improved in the groups consuming fish oil, but were unchanged in the unsupplemented group. Strength training improved all measures of functional capacity in all groups, but fish oil was associated with an even better performance only in the chair-raising test. These findings confirm other reports of improved neuromuscular performance with moderate, graduated 13

14 strength training and its effects on muscle functionality in older women. However, this is the first report suggesting that omega-3s enhance the effects of strength training in older adults. These observations need to be confirmed by others, but they build on the known benefits of physical exercise and strength training and suggest an additional advantage from increased omega-3 consumption. If confirmed by others, these observations could have healthful implications for the mobility and quality of life in older adults whose lives may be sedentary. Higher Long-Chain Omega-3s Linked to Lower Risk of Colorectal Polyps in Women The most effective preventive strategy for colorectal cancer, which is the third most common cancer in the U.S., is finding and removing its earliest abnorm alities. These appear as polyps or small sacs in the colon or rectum (Illustration) and are detected during a colonoscopy exam. They are considered precancerous. A 1-cm polyp in the colon as revealed by colonoscopy. Image courtesy of Wikipedia. Because colorectal cancer usually does not reveal itself until the disease is advanced, looking for its earliest warning signs offers the greatest protection. A recent study reported that adults 50 years of age or older who had had a colonoscopy in the preceding 10 years had a 77% lower risk of developing colon cancer. Those findings say clearly that early screening works. Several aspects of diet and particularly fish consumption have been linked to the development of colorectal cancer for years, but the data have been inconsistent. Although several studies have suggested that individuals with high intakes of fish or the long-chain omega-3 fatty acids (omega-3s) they contain have a lower risk of the disease, there are enough studies reporting no association or even a higher risk of the condition, so that the evidence remains inconclusive. Now, a fresh approach Colorectal cancer is to this question has appeared. the third most common Investigators at cancer in the US Vanderbilt University, New research suggests U.S., focused on that higher intakes of whether the consumption of omega-3s was long-chain omega-3s in women may be linked to the odds of associated with a lower developing colorectal risk of developing polyps. One study suggested that supple- precancerous polyps in the colon. mentation with EPA, one of the two main omega-3s in seafood, was associated with the development of about 20% fewer polyps in patients with a genetically higher risk of developing these abnormalities. The Vanderbilt scientists studied the results of colonoscopies in adults who underwent routine screening. Participants with inflammatory bowel disease, cancer or a family history of colorectal cancer were excluded. The researchers collected information about the participants medical history, diet and socioeconomic factors. Women, but not men, with the highest intakes of omega-3s from seafood had a 33% lower risk of developing colorectal polyps, a forerunner of colorectal cancer. Men with the highest intakes of alpha-linolenic acid, the plant-based omega-3, had a significantly greater risk of developing polyps. The most striking observation was that women with the highest intakes of omega-3s had a 33% lower risk of developing polyps compared with women in the lowest intake category. These women also had the lowest excretion of a substance linked to the development of colorectal cancer. The investigators suggested that the 14

15 omega-3s were suppressing the production of this cancer-linked substance in the colon. Other evidence supports this interpretation. In men, high intakes of omega-3s were not associated with a lower frequency of polyps. However, men with the highest consumption of alpha-linolenic acid, the plant-based omega-3, were 50% more likely to develop polyps compared with men having the lowest intakes. There is no good explanation for this observation. Alphalinolenic acid has been associated with the development of other cancers in some, but not all studies, indicating that these data are inconclusive. The most encouraging aspect of this study is the implication that higher intakes of omega-3s in women may substantially reduce the chance of developing the precancerous lesions that could progress to colorectal cancer. The study needs additional confirmation by others, but the important health consequences of these observations might hasten such research. We have too few interventions that might reduce the risk of colorectal cancer, so each one warrants careful investigation. Exploring why the response occurred only in women, not men, is another priority. The questions always seem to outnumber the answers. 15