Topic of the Month

Docosahexaenoic acid and brain health

August 1, 2012

Omega-3 fatty acids are considered essential fatty acids: They are necessary for health but the human body is not capable of producing them, hence they have to be consumed in the form of food. Also known as polyunsaturated fatty acids (PUFAs), omega-3 fatty acids play a crucial role in maintaining health as well as normal growth and development. They have become popular because of their potential benefits for the cardiovascular system. Research indicates that omega-3 fatty acids can reduce inflammation and may help lower risk of chronic diseases such as heart disease, cancer, and arthritis. Less well-known are the positive effects of omega-3 fatty acids – particularly of docosahexaenoic acid (DHA) – on the brain. As a key structural element, DHA is highly concentrated in the brain and appears to be important for its development as well as for cognitive (brain memory and performance) and behavioral function.

file

There is good evolutionary evidence suggesting that availability of DHA in the diet is the key limiting factor in determining brain size. In fact, the earliest evidence of DHA was found 3 billion years ago, when certain ocean-dwelling dinoflagellates, cyanobacteria and micro-algae evolved the ability to convert alpha linolenic acid (ALA) into DHA. These micro-algae and plankton remained the original source of DHA in the human diet. Small crustaceans (e.g., krill, shrimps) and fish eat the algae and plankton. Further up the food chain, carnivorous fish such as salmon and tuna eat those small fish, increasing the levels of DHA in their tissues – and poten-tially providing a DHA source for humans. The American Heart Association recom-mends eating fish (particularly fatty fish such as mackerel, lake trout, herring, sardines, albacore tuna and salmon) at least 2 times a week. Though it is clear that DHA is important for human brain health from con-ception to old age, much work remains to be done so that we fully understand its underlying mechanisms.

Fetus

The adult human brain accounts for around 23% of our energy needs while only making up 2% of our body weight. This high energy requirement largely arises from the biochemical processes required to enable electronic signal transmission. There are select nutrients that are responsible for the proper maintenance and development of the brain. These include vitamins A and D, iodine, iron, selenium, copper and zinc as well as the omega-3 fatty acid docosahexaenoic acid (DHA) and the omega-6 fatty acid arachidonic acid (ARA) – the latter relating to developing infants only. DHA accounts for some 10–15% of the nutrients in the adult brain. We process around 4 mg DHA per day, meaning that the half-life of the brain’s total DHA is around 2.5 years (1). Before a child is even conceived, the prospective mother should already be building up stores of DHA in her fat deposits by eating foods containing DHA (predominantly oily fish). 

The critical period of brain development is the rapid growth phase – from the last third of gestation up to two years of age – which is accompanied by a large increase in the cerebral content of ARA and DHA. Conse-quently, the developing brain is particularly vulnerable to an inadequate supply of nutrients because of the rapid trajectory of several neurologic processes, including synapse formation and myelination. Maternal PUFA status during pregnancy determines the supply of PUFA to the fetus, while new-born infants get their dietary supply from breast milk and/or formula (2). Infants who do not get enough omega-3 fatty acids from their mothers during pregnancy are at risk of developing vision and nerve problems.

The European Food Safety Authority (EFSA) carefully reviewed the evidence regarding DHA and brain and visual health and concluded that maternal DHA intake contributes to the normal development of the brain and the eye of fetuses and breastfed infants (3).

Infant

In the human frontal cortex, DHA rapidly accumulates between birth and 20 years of age, a period corres-ponding with rapid neuronal maturation, development of synapses and expansion of gray matter – a major component of the central nervous system containing neural cell bodies (4). There is mounting clinical evidence showing that the DHA status of human infants is positive correlation between the development of neural pathways or cortical networks in the brain, and thus cognitive functions, particularly on measures of attention and memory (5–7).

The eye can be considered a structural extension of the brain. It also contains high levels of DHA, and thus the DHA status of infants is important in determining their visual acuity. In the DIAMOND study (8), where 244 infants were fed infant formula containing various levels of DHA and ARA, it was shown that a 0.32% level of DHA and a 0.64% level of ARA produced the most efficient improvement in visual acuity, as measured by visual evoked potential (the time lag from a visual image being shown to an infant to the time an electronic signal is received in its visual cortex). It seems likely that the cognitive and visual benefits of a supplementation will only be obtained for a developing child whose diet is deficient in DHA (9). This is supported by some large scale trials that have recently been carried out on populations with sufficient DHA in their diets, which, unsurprisingly, demonstrated no benefits on cognition or vision (10). These studies are often included in meta-analyses, which means they are also skewed to show no benefits (11,12).

The fact that the rate of DHA accretion is greatly enhanced in the brain of the fetus during the third semester of pregnancy means prematurely born infants (i.e., those earlier than 33 weeks) are particularly likely to suffer cognitive development delays due to the relatively low DHA levels in their brains at birth. A recent study provided evidence that this can be remedied ex utero by ensuring the premature infant is supplemented with a level of DHA that it would normally have received in the womb had it gone full term (13). Interestingly, it was also reported that boys and girls respond differently to such a supplementation.

Child

Functional magnetic resonance imaging (fMRI) is a useful way of measuring increased activity in specific parts of the brain by measuring blood flow. This technique offers considerable promise with regard to under-standing the physiological effects of DHA intake on the brain. A study on a group of 44 boys aged 8–10 years used fMRI to determine the effect of supplementation of daily doses of 400 mg and 1200 mg day algal DHA on brain activity(14). When the children were performing a sustained attention task, significantly in-creased activity in the brain areas responsible for motor planning, organization and regulation (dorsolateral prefrontal cortex) was observed in the group receiving DHA compared with the placebo group. The level of change was dependent on the dose of DHA received.

The cause of attention-deficit hyperactivity disorder (ADHD), which commonly emerges in childhood, is thought to be multifactorial: various studies suggest that genetic factors, neurotransmitter imbalances or food sensitivities may adversely affect behavior in some children with ADHD. A few studies have focused on metabolism of essential fatty acids, which play important structural roles as components of all cell mem-branes, affecting their biological properties. ADHD has been associated with low concentrations of DHA in the erythrocyte membrane and plasma in children and adults (15, 16).

Adult

The cognitive benefits of DHA have also been shown to apply to the normal adult population. A study of
280 healthy adults aged 30–54 years showed that increasing DHA (but not eicosapentaenoic acid or alpha-linolenic acid) serum phospholipids levels were related to better performance on tests of nonverbal reasoning and mental flexibility, working memory and vocabulary (17).

randomized controlled trial demonstrated that a daily supplementation of 900 mg DHA for 6 months can improve learning and memory function of healthy elderly participants (aged 55 and over) who had com-plained of mild memory impairment (18). The improvement in memory was equivalent to restoring the memory of the individual to the state it was in 3 years earlier.

The European Food Safety Authority (EFSA) concluded that DHA contributes to the maintenance of normal brain function and normal vision, with recommended intakes of 250 mg per day for the general population (19). Symptoms of omega-3 fatty acid deficiency include fatigue, poor memory, dry skin, heart problems, mood swings or depression and poor circulation.

Currently of great interest is whether omega-3 fatty acids can be used to delay the onset of, or even treat, cognitive disease in old age. Cognitive decline is accompanied by significant changes in fatty acid metabo-lism. In animal experiments, it has been demonstrated that the process of dementia is accompanied by loss of DHA. However, this has not proven to be the case in humans, though it remains possible that some minor brain structures do become deficient in DHA. There is good evidence from observational studies that high omega-3 fatty acid intake protects against the onset of dementia including Alzheimer’s disease (AD) in humans (20, 21). DHA intervention trials in AD patients have not shown any clear benefits, though there are indications that DHA may slow the rate of decline in individuals with a certain genotype of apolipoprotein E, helping to stabilize and solubolize lipoproteins as they circulate in the blood (22). As well as this genetic confounding, other metabolic changes in the dementia sufferer, such as changes in DHA homeostasis and reduced glucose uptake, appear to be masking the role of DHA as dementia progresses (23). In the absence of any pharmaceutical breakthrough in the treatment of AD, understanding the role of DHA is clearly worthy of more in-depth research.

References

  1. Umhau J. C. et al. Imaging incorporation of circulating docosahexaenoic acid  into the human brain using positron emission tomography. J Lipid Res. 2009; 50:1259–1268.
  2. Mohajeri M. H. and Winwood R. J. The role of DHA in cognitive performance of children. AgroFOOD industry hi-tech. 2012; 23(2):22–25.
  3. Official Journal of the European Union. Commission Regulation (EU) No 440/2011. 6th May 2011.
  4. Giedd J. N. et al. Brain development during childhood and adolescence: a longitudinal MRI study. Nat Neurosci. 1999; 2(10):861–863.
  5. Agostoni C. et al. Neurodevelopmental quotient of healthy term infants at 4 months and feeding practice: the role of long-chain polyunsaturated fatty acids. Pediatr Res. 1995; 38:262–266.
  6. Colombo J. et al. Maternal DHA and the development of attention in infancy and toddlerhood. Child Dev. 2004; 75:1254–1267.
  7. Lauritzen L. et al. The essentiality of long chain n−3 fatty acids in relation to development and function of the brain and retina. Prog Lipid Res. 2001; 40:1–94.
  8. Birch E. B. et al. The DIAMOND (DHA Intake And Measurement Of Neural Development) Study: a double-masked, randomized controlled clinical trial of the maturation of infant visual acuity as a function of the dietary level of docosahexaenoic acid. Am J Clin Nutr. 2010; 91(4):848–859.
  9. Forsyth S. Why are we undertaking DHA supplementation studies in infants who are not DHA-deficient? British Journal of Nutrition. Published online June 2012.
  10. Meldrum S. J. et al. Effects of high-dose fish oil supplementation during early infancy on neurodevelop-ment and language: a randomised controlled trial. Br J Nutr. 2012; 21:1–12.
  11. Simmer K. and Patole S. K. Longchain polyunsaturated fatty acid supplementation in infants born at term. The Cochrane Database Systematic Reviews. 2008; Issue 1.
  12. Hoffman D. R. et al. Toward optimizing vision and cognition in term infants by dietary docosahexaenoic and arachidonic acid supplementation: a review of randomized controlled trials. Prostaglandins Leukot Essent Fatty Acids. 2009; 81:151–158.
  13. Makrides M. DHA supplementation during the perinatal period and neurodevelopment: Do some babies benefit more than others. PLEFA. Published online June 2012.
  14. McNamara R. et al. Docosahexaenoic acid supplementation increases prefrontal cortex activation during sustained attention in healthy boys: a placebo-controlled, dose-ranging, functional magnetic resonance imaging study. Am J Clin Nutr. 2010; 91:1060–1067.
  15. Stevens L. J. et al. Omega-3 Fatty Acids in Boys with Behavior, Learning, and Health Problems. Physiol. Behav. 1996; 59:915–920.
  16. Young G. S. et al. Blood phospholipid fatty acid analysis of adults with and without attention deficit/ hyperactivity disorder. Lipids. 2004; 39(2):117–123.
  17. Muldoon J. N. et al. Serum phospholipid docosahexaenonic acid is associated with cognitive functioning during middle adulthood. Journal of Nutrition. 2010; 140:848–853.
  18. Yurko-Mauro K. et al. Beneficial effects of docosahexaenoic acid on cognition in age related cognitive decline. Alzheimer’s & Dementia. 2010; 6(6):456–464.
  19. Official Journal of the European Union. Commission Regulation (EU) 432/2012. 16th May 2012.
  20. Morris M. C. et al. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol. 2003; 60(7):940–946.
  21. Fotuhi M. et al. Fish consumption, long-chain omega-3 fatty acids and risk of cognitive decline or Alzheimer disease: a complex association. Nat Clin Pract Neurol. 2009; 5(3):140–152.
  22. Quinn J. F. et al. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer’s Disease: a randomized trial. J.Am. Med. Assoc. 2010; 304:1903–1911.
  23. Cunnane S. C. et al. Docosahexaenoic acid homeostasis, brain aging and Alzheimer’s disease: can we reconcile the evidence? PLEFA. Published online May 2012.