Neurological Effects

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There is evidence that alterations to n-3 fatty acid metabolism and the composition of the phospholipids in serum and membranes are involved in the pathogenesis of some neurological disorders (Ulbricht & Basch 2006). As a result, there has been much interest in understanding the effects of supplemental n-3 fatty acids in neurological development, cognitive function, depression, schizophrenia, and behavioural problems.

Cognitive function Low serum DHA level is considered a significant risk factor for the development of Alzheimer's dementia (Conquer et al 2000). Additionally, both

DHA and total n-3 fatty acid levels are significantly lower in cognitively impaired but non-demented people and people with other dementias. One of the first interventional studies was a small RCT of 4.3 g/day DHA in 20 elderly nursing home residents, assessing the efficacy of fish oil in the treatment of vascular dementia. DHA supplementation resulted in a small improvement in dementia rating scores within 3 months of treatment (Terano et al 1994).

The results from numerous animal studies, demonstrating neuroprotection from the n-3 EFAs and some slowing of neurodegeneration, appear promising (Hashimoto et al 2005, Mucke & Pitas 2004); however, more clinical trials are required to confirm these positive findings.

Alzheimer's dementia A 2003 prospective study conducted with a random sample of 81 5 older volunteers (aged 65-94 years) who initially were unaffected by Alzheimer's dementia (AD) 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, after adjustment for age and other risk factors (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 AD. Total n-3 EFA and DHA consumption correlated with this risk reduction; however, ALA and EPA did not (Maclean et al 2005). 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; however, further research is required before firm conclusions can be made (Lim et al 2006). Pregnancy, breast feeding and infants Despite numerous studies demonstrating a positive relationship in mothers and infants consuming greater amounts of EFAs on subsequent cognitive development and IQ of their offspring (Cohen et al 2005, Helland et al 2003, Williams et al 2001), the findings of the Evidence Report/Technology Assessment prepared for the Agency of Healthcare Research and Quality US Department of Health and Human Services concludes that based on the small number of current well-designed studies there is no conclusive evidence of any benefit Lauritzen et al 2001 (Moher 2005). It makes the observation that studies observing a positive relationship between omega-3 oils and cognition are those which assessed children under 1 year of age, whereas studies of older children did not maintain a significant statistical relationship.

According to the WHO and FAO the pregnant woman should take at least 2.6 g of n-3 EFAs, incorporating 100-300 mg of DHA, daily to look after the needs of the fetus (Bambrick & Kjellstrom 2004). Postnatal deficiencies have been associated with

reduced visual acuity, poor neurodevelopment and ill effects on behaviour. Breast-fed infants generally receive sufficient DHA if the maternal diet is adequate, but it is not known whether formula-fed infants receive adequate amounts if their formula does not contain PUFAs.

Depression The balance between n-6 and n-3 fatty acids influences the metabolism of biogenic amines, an interaction that may be relevant to changes in mood and behaviour (Bruinsma &Taren 2000). In several observational studies, low concentrations of n 3 PUFAs predicted impulsive behaviours and greater severity of depression. Additionally early research by Horrobin et al (1999) revealed that almost all studies on depression have found increased PG2 series or related thromboxanes and there is evidence that the older antidepressants (i.e. MAOIs and TCAs) either inhibit PFG synthesis or are powerful antagonists of their actions. Going one step further are the findings of a number of studies showing a correlation between low erythrocyte n-3 EFAs and suicide attempts; one of these demonstrated an eightfold difference in suicide attempt risk between the lowest and highest RBC EPA level quartiles (Huan et al 2004). Researchers from Belgium have also speculated about a seasonal variation in EFA status that correlates with seasonal patterns of suicide (De Vriese et al 2004); however, studies on larger populations of depressed people are required to confirm this link.

In spite of a plethora of epidemiological data correlating n-3 status with a range of depressive disorders, including major depression, postpartum depression and seasonal affective disorder, there are very few interventional studies. One conducted in 2005 involved 77 patients with depression who were randomly assigned to receive either 8 g/day of DHA-enriched (1.23%) fish oil or olive oil, in addition to existing medication, over 12 weeks. Interestingly, the fish oil group did not show significant improvement over the olive oil group, but both groups improved in mood over baseline. This was significant at 2 weeks and remained so throughout the study (Silvers etal 2005).

In response to a lack of demonstrated benefit, the authors of this trial note that previous successful interventions have predominantly used purified fish oil preparations, particularly ethyl-EPA, and therefore variable make-up of standard fish oil preparations may explain the inconsistency of results. Adding to the riddle is a question over optimal dosage and whether olive oil was in fact an inert placebo devoid of activity (2002).

A randomised study was conducted of 28 children aged between 6 and 12 years who were diagnosed as having depression according to the Children's Depression Fish oils 436

Rating Scale (CDRS), Children's Depression Inventory (CDI), and Clinical Global

Impression (CGI) (Nemets et al 2006). After 1 month of treatment, omega-3 fatty acid supplementation was shown to have highly significant effects on symptoms using the above three scales.

Aggressive behaviour The DHA component of fish oils has been used to reduce aggressive behaviour 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 at times of mental stress (Hamazaki et al 1996); however, another placebo-controlled trial found that DHA supplementation had no effect on aggressive behaviour under non-stressful conditions (Hamazaki et al 1998). Attention-deficit hyperactivity disorder It has been reported that many children with ADHD have EFA deficiency (mainly n-3 FA) 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. Several studies have investigated the effects of supplemental fatty acids to children with ADHD with mixed results; however, interpretation of findings is difficult because of the use of different treatments, measurements and subject selection (Richardson & Puri 2000).

Schizophrenia According to a 2003 review, four out of five placebo-controlled double-blind trials of EPA in the treatment of schizophrenia have produced positive results (Peet 2003).

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