The role of EPA and DHA (FISH OIL) in Neurological Functioning.

Fish oils also known as marine oils, are fats found in fish, particularly cold-water fish and other marine life such as phytoplankton and krill. These oils are rich sources of long-chain polyunsaturated fatty acids, also called omega-3 fatty acids. The two most studied fish oils are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These oils are rapidly absorbed from the gastrointestinal tract and compete with arachidonic acid for incorporation into phospholipids, particularly of platelets, erythrocytes, neutrophils, monocytes and the liver cells (Simopoulos, 1999). When stimulated, the cell membranes release polyunsaturated fatty acids (PUFA), which are then converted into 20-carbon eicosanoids. The most active of these metabolites are prostaglandins, prastacyclins and thromboxanes, which affect blood chemistry, muscle contraction, immune function and inflammation. Generally, DHA is considered the major component of phospholipids in the retina, brain, male reproductive tissue and myocardium. (Pizzorno et al., 2004).

Dietary fish contains a large number of nutrients very important for health, such as the vitamins B group; vitamin E, magnesium, calcium and potassium. They also contain the two polyunsaturated fatty acids, namely EPA and DHA. EPA has 20 carbon atoms and 5 double bonds and DHA has 22 carbon atoms and 6 double bonds. Supplemental fish oils have shown to have many positive effects on the body. First of all, they lower triglyceride levels and have an anti-inflammatory, antiarrhythmic, immune-enhancing and nerve-cell stabilizing properties. In addition, they help to form clots. Specifically, DHA is vital for normal brain development for the fetus and infant and for the maintenance of normal brain function throughout life. DHA appears to be a major factor in the fluidity and flexibility of brain and membranes. It could play a major role in maintaining how we think and feel.

Fish oils appear to have mood-stabilizing properties when used in the treatment of bipolar disorder. A four-month double blind, placebo-controlled study of thirty subjects with bipolar disorder that has appeared in the 'Journal of Neuroscience Research' (1999.56:565 -570), compared the effects of fish oil supplements with a placebo. Fourteen subjects received 9.6 g daily of fish oil, consisting of 6.2 g of EPA and 3.4 g of DHA, and sixteen subjects received olive oil as a placebo. This study showed improvement in the short-term course of the disorder with fish oil supplementation. Among those taking fish oil, there were longer periods of remission and the results were statistically significant. Mild gastrointestinal side effects were reported in the fish oil group.

In a landmark study published in the journal 'Lancet' (Kinsella JE), researchers examined the effects of dietary fish oil and vitamin E supplementation on death and disease in more than eleven thousand subjects who had suffered a heart attack within three months of entering the trial. The trial lasted forty-two months. The most significant result was the reduction in risk for overall and sudden cardiac death, which it is believed was due to the antiarrythmic effect of the fish oil. The study suggest that up to twenty lives per thousand post-heart attack patients could be saved by consuming daily doses of less than 1 g of EPA and DHA.

Based on epidemiological studies, the low levels of n-3 polyunsaturated fatty acids are associated with:

• Fetal alcohol syndrome
• Attention deficit hyperactivity disorder
• Learning deficits
• Cystic fibrosis
• Phenylketonuria
• Inflammatory disorders
• Rheumatoid arthritis
• Unipolar depression
• Senile dementia
• Cardiovascular disease
• Breast cancer
• Prostate cancer
• Asthma
• Depression
• Schizophrenia

Fatty acids are the main components of the brain and are found in high concentrations in two structural components: the neuronal membrane and the myelin sheath. About 50% of the neuronal membrane is composed of fatty acids, while in the myelin sheath lipids constitute about 70% (Yehuda et al., 2005).

The essential fatty acids play an active role in the neuronal membrane function and fluidity and the control of neuronal growth factors. They also are involved in the synthesis of neurotransmitters, degradation, release, reuptake and binding (Bruisma & Taren, 2000). Studies have pointed out that dietary polyunsaturated fatty acids influence noradrenergic and serotenegic neurotransmission and receptors function in the nervous system and as a result, they have a direct effect on function, mood and behavior.

According to Horrocks and Yeo, 1999, DHA plays an important critical role in the growth and functional development of the brain during the third trimester and the early postnatal period when maximal growth takes place. Considering that 15% of the brain growth occurs during infancy, more research should be directed to the consequences of variable omega-3 levels during late pregnancy and early infancy.

Low serum DHA level is considered a significant risk factor or the development of Alzheimer' dementia (Conquer et all., 2000). In a study presented at the annual meeting of the American Association for the Advancement of Science in Seattle, scientists with the US National Institute on Aging (NIA) have pointed out that alteration in fats - particularly cholesterol and ceramide - may contribute to a neurodegenerative cascade that destroys neurons in Alzheimer's disease. The researchers suggest that the oxidative stress brought on by the presence of the toxic beta amyloid peptide seems to trigger the accumulation of ceramide and cholesterol.

Another study reported by 'PubMed: Inflammation and Alzheimer disease', discusses the administration of 4.3 g/day DHA in 20 elderly nursing home residents and assesses the efficacy of fish oil in the treatment of vascular dementia rating. This study reports that DHA supplementation resulted in a remarkable improvement in dementia rating scores within three months of treatment.

A 2003 prospective study conducted with a random sample of 815 older volunteers aged between 65 and 94 years, who initially were unaffected by Alzheimer's dementia, found that consumption of fish once weekly was associated with a 60% reduced risk of developing the disease compared with those who rarely or never ate fish (Morris et al, 2003). A review of the evidence prepared for the US Department of health and Human Services in 2005 concluded that there is a significant correlation between fish consumption and reduced incidence of Alzheimer's. Although EFA and DHA consumption correlated with this risk reduction, ALA and EPA did not. A recent Cochrane review came to a similar conclusion and reported that there is a growing body of evidence from biological, observational and epidemiological studies to suggest a protective effect of omega-3 PUFAs against dementia. Finally, a recent new study by researchers from the University Medical Center Utrecht and the University of Maastricht and reported by 'PubMed: neurobiological Aging (62:275-280)', not only demonstrated the benefits of omega-3s but also the impact of high cholesterol. The researchers used data from a cross-sectional population-based study of 1,613 subjects ranging from 45 to 70 years old. Over a five-year period they tested for memory, psychomotor speed, cognitive flexibility (i.e. higher order information processing), and overall cognition. A self-administered food-frequency questionnaire was used to assess eating habits and risk was adjusted for age, sex, education, smoking, alcohol consumption, and energy intake. Marine omega-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid) were found to reduce the risk of impaired overall cognitive function by almost 20 per cent and speed by 28 per cent. Fatty fish consumption also had a similar benefit on cognition. Meanwhile higher dietary cholesterol intake was significantly associated with an increased risk (by 27 per cent) of impaired memory and flexibility.

All studies point to the fact that middle-aged adults who eat fatty fish regularly or take supplements of marine omega-3 polyunsaturated fatty acids are less likely to experience impaired cognitive function and speed. Researchers at Tufts University in Boston, US last year found that boosting levels of docosahexaenoic acid (DHA) in the blood and eating about three fish meals each week can almost halve the risk of Alzheimer's disease in elderly men and women.

Another study, published in the British Medical Journal, found that elderly people who eat fish or seafood even once a week, are at lower risk of developing dementia, including Alzheimer's disease.

The cause of Alzheimer's, a debilitating disease which affects an estimated 12 million around the world, is still not known and it is expected to increase along with the numbers of elderly. According to a study conducted by Bruinsma and Tauren, 2000, the balance between n-6 and n-3 fatty acids has large influence in the metabolism of biogenic amines, an interaction that may be relevant to changes in mood and behavior. Low concentration of n-3 PUFAs is closely linked to aggressive behavior and greater severity of depression. Additionally, early research by Bodnar LM  et al. in 1999, revealed that almost all studies of depression have found increased PG2 or related thromboxanes. There is also a clear correlation between low erythrocytes n-3 EFAs and suicide attempts: one study reported that there is an eightfold number in suicide attempt risk between lowest and highest RBC EPA level levels (Logan AC., 2003). Researched from Belgium have also speculated about a seasonal variation in EFA status that correlates with seasonal patterns of suicide (De Vriese et al., 2004)

Despite the clear correlation between the beneficial effects of n-3 on a vast range of neurological disorders such as depression, postpartum depression and seasonal affective disorder (SAD), there have been so far very few interventional studies. One particularly interesting study was conducted on 28 children aged between 6 and 12 years of age who were diagnosed as having depression according to the Children's Depression Rating Scale in United Kingdom (CDRS). After a month of treatment, omega-3 fatty acid supplementation has shown to have highly significant effects on symptoms of depression.

The DHA component of fish oil has been widely used to reduce aggressive behavior in children and adolescents. One placebo-controlled study of 42 college students showed that DHA supplementation (1.5 1.8 g/day) prevented an increase in aggression toward others in time of mental stress (Hamazakie t al., 1996); however, another placebo-controlled trial found that DHA supplementation had no effect on aggressive behavior under non-stressful conditions (Hamazaki et al., 1998).

It has been reported that many children with ADHD have EFA deficiencies with a high correlation between severity of symptoms and severity of deficiency (Yehuda et al.,2005). Deficiency may be due to insufficient dietary intake or inefficient conversion of EFA to longer chain fatty acids. Theory and experimental evidence support a role for omega-3 in ADHD, dyslexia, developmental coordination disorder (DCD) and autism. Results from controlled treatment trials are mixed, but the few studies in this area have involved different populations and treatment formulations. Dietary supplementation with fish oils (providing EPA and DHA) appears to alleviate ADHD-related symptoms in most children. (Logan, 2003).

One of the most prominent areas of research in schizophrenia is brain fats. Schizophrenia affects approximately 1 in 100 individuals; over 45 million people are affected worldwide. Some studies have shown that sufferers have low levels of certain essential fatty acids in their neural cell membranes. It has been hypothesized that boosting the level of these essential fatty acids in the body helps reduce the symptoms of schizophrenia.

Dr. Iain Geln from the mental health of Aberdeen University found that 80 per cent of schizophrenics are EFA deficient. He gave 50 patients EFA supplements and reported a dramatic response. A larger placebo-controlled, crossover, ten- month study of the effects of EFA supplementation in schizophrenics, including supplements of zinc, B6, B3 and vitamin C with omega-6 fats, also produces significant improvements in schizophrenic symptoms. To date the evidence strongly suggests that some people diagnosed with schizophrenia do need and respond well to increased amounts of both omega-6 fats (evening primrose oil or starflower oil) and omega-3 fats, together with the 'co-factor' nutrients (zinc, B6, B3 and vitamin C) that help convert them into vital brain fats.

Manuela Boyle

References:

Simopolous AP: "Essential fatty acids in health and chronic disease" American Journal of Clinical Nutrition 21.6 (2000): 513-518

Pizzorno J., Murray M. "Textbook of Natural Medicine" St. Louis: Elsevier, 2006 Journal of Neuroscience Research (1999.56:565 -570)

Kinsella JE: "Effects of polyunsaturated fatty acids on factors related to cardiovascular disease" American Journal of Cardiology 60.12 (1987): 23-32G

Yehuda S, Rabinovitz, S., Mostofsky, D. : "Essential Fatty Acids are Mediators of Brain Biochemistry and Cognitive functions" Journal of Neuroscience Research. 1999. 56:565-570

Bruisma KA, Taren DL: "Dieting, essential fatty acid intake and depression" Nutritional Review 58.4 (2000): 98-108

Bodnar LM, Wisner KL: "Nutrition and depression: implications for improving mental health among child bearing-aged women" Biology Psychiatry. 2005. 58 (9): 679-85

Horrocks LA, Yeo YK: "Health benefits of docosahexaenoic acid (DHA)" Pharmacol Res 40.3 (1999): 211-25

Conquer JA et al. "Fatty Acid analysis of blood plasma in patients with Alzheimer's disease, other types of dementia and cognitive impairment" Lipids 35.12 (2000) 721-4

Morris MC et al " Does fish oil lower blood pressure? A meta-analysis of controlled trials" Circulation 88.2 (1993) 523-533

PubMed: neurobiological Aging (62:275-280)

Logan, AC: "Neurobehavioral aspects of Omega-3 Fatty Acids: Possible Mechanism and Therapeutic Value in Major Depression". Alternative Medicine Review. 2003. 8(4)  410-425

De Vriese SR: "In humans, the seasonal variation in polyunsaturated fatty acids is related to the seasonal variation in violent suicide and serotogenic markers of violent suicide. Prostaglandins, Essential Fatty Acids 71.1 (2204): 13-18

Hamazakie T et al. : "The effects of DHA on aggression in young adults: a placebo-controlled double blind study". American Journal of Clinical Nutrition 97.4 (1996): 1129-33