DHA is an omega-3 fatty acid, so-called because it has a double-bond 3 carbon atoms away from the methyl end of the long carbon-chain carboxylic acid. All the fatty acids which are essential in the human diet are either omega-3 or omega-6. Although DHA can be synthesized in the body from alpha-lenolenic acid (a simpler omega-3 found in linseed oil and perilla oil), the capacity for synthesis declines with age. So the older you are (beyond infancy), the more you can benefit from DHA.

The omega-3 and omega-6 family of fatty acids are essential because they cannot be synthesized in the body, but must be obtained in the diet. Fatty acids are contained in the membranes of every cell in your body, but the essential fatty acids are particularly concentrated in the membranes of brain cells, heart cells and immune-system cells.

The most important long-chain fatty acid in the omega-6 family is arachidonic acid. Arachidonic acid has 20-carbons and 4 double-bonds. Arachidonic acid, gives rise to a whole group of 20-carbon, biologically-important substances known as the eicosanoids (eicosa- is Greek for "20"), including prostaglandins, thromboxanes, lipoxins and leukotrienes -- which affect immunity, inflammation and blood clotting (among other actions).

The primary source of omega-6 fatty acid in the diet is linoleic acid from the oils of seeds and grains. Sunflower, safflower and corn oil are particularly rich sources of linoleic acid, which is at the root of the omega-6 fatty-acid family. Evening primrose oil and borage oil are high not only in linoleic acid, but the omega-6 derivative gamma-linolenic acid (GLA).

Omega-3 fatty acids, on the other hand, are more frequently found in green leaves. The leaves and seeds of the perilla plant (widely eaten in Japan, Korea and India) are the richest plant source of alpha-linolenic acid, although linseed oil is also a rich source. Fish oil contains very little alpha-linolenic acid, but is rich in the omega-3 derivatives EPA and DHA.

Although most fish oils are high in EPA and DHA, there are some fish oils which are not. Flounder, swordfish and sole are particularly low in EPA and DHA. Fish oils with the highest levels of EPA and DHA include mackerel, herring and salmon. Some fish, such as cod and haddock, store most of their fat in the liver, therefore the liver oils of these fish should be taken rather than oil from the fillet.

Fish oil has achieved medical prominence primarily due to its ability to reduce heart disease in fish-eating populations such as Eskimos and Japanese. Even in Japan, fishermen have lower blood pressure and lower incidence of heart disease than do farmers. The omega-3 fatty acids EPA and DHA are the fish oil components held responsible for these benefits. EPA and DHA are elevated in blood plasma and in cell membranes at the expense of the omega-6 fat arachidonic acid in Eskimos and Japanese.

The most dramatic effects of fish oil on the heart, however, are in connection with cardiac arrhythmias (irregular heartbeats). In the United States, a quarter of a million people die annually within an hour of a heart attack as a result of arrhythmia. The protective effect of fish oil against cardiac arrhythmias has been strikingly illustrated by two similar experiments, one performed on rats [*5] and the other on marmoset monkeys [*6]. Middle-aged animals were fed sheep fat (saturated fat), sunflower seed oil (omega-6) or fish oil (omega-3) for 12 weeks (for rats) or for 24-30 months (for monkeys). With both rats and monkeys arrhythmia was produced in over 40% of the animals fed sheep fat, roughly 10% of the animals fed safflower oil and in none of the animals who were fed fish oil.

       DIETARY FAT                           RAT[*5]      MONKEY[*6]

       SHEEP FAT (Saturated)                44%          45%

     OLIVE OIL (Mono-saturated)          35%          not used

SUNFLOWER SEED OIL (Omega-6)    8%          13%

        FISH OIL (Omega-3)                      0%           0%

Phosphatidylethanolamine (an important phospholipid of the inner layer of cell membranes) from monkey heart tissue showed 5 times more (over 25% total) DHA in the fish-oil fed monkeys than in the other two groups. EPA accounted for over 6% of the fatty acid phosphatidylethanolamine of fish-oil fed monkeys, and was undetectable in the other two groups. A similar experiment on rats using purified DHA and purified EPA, rather than fish-oil, indicated that DHA is responsible for most of the anti-arrhythmic effect [*7]. DHA is more readily incorporated into heart cell membranes than EPA [*8]. It is the DHA in heart cell membranes, rather than DHA in the bloodstream, which is protective [*9].

Most of the dry weight of the brain is lipid (fat) because brain activity depends greatly upon the functions provided by lipid membranes. Compared to other body tissues, brain content of DHA and arachidonic acid is very high. DHA is particularly concentrated in membranes that are functionally active, namely in synapses and in the retina. There is a high correlation between sodium pump (Na⁺−K⁺−ATPase enzyme) activity and DHA content of membranes [NATURWISSENSCHAFTEN; Turner,N; 90(11):521-523 (2003)].

The ability of enzymes to produce the omega-6 and omega-3 family of products of linoleic and alpha-linolenic acid declines with age. One experiment showed that desaturase enzyme function in old rats was only 44% of the desaturase function in young rats [*26]. Because DHA synthesis declines with age, as we get older our need to acquire DHA directly from diet or supplements increases.

Because of the decline in DHA synthesis, it is not surprising that DHA content of brain cell membranes declines. DHA is also reduced when the brains of rats are experimentally exposed to high oxygen levels. Free-radical oxidation probably causes the depletion in both cases. Vitamin E treatment protected the rats from neuron damage from the oxygen. This suggests that Vitamin E may be important for prevention of neurodegeneration in humans [*25].

The greatest dependence on dietary DHA occurs in the foetus during the last third of pregnancy and (to a lesser extent) in the infant during the first 3 months after birth. It is during this period that brain synapses are forming most rapidly, and an infant's demand for DHA exceeds the capacity of the enzymes to synthesize it [*11]. The additional requirements are fulfilled by mechanisms believed to concentrate DHA absorption from the mother's placenta [*12].

After birth, the additional needed DHA comes from the nursing mother. Rapid brain growth in the human infant requires large amounts of omega-3 and omega-6 essential fatty acids. Human milk contains (in total fatty acids by weight) 12% linoleic acid, 0.5% alpha-linolenic acid, 0.6% arachidonic acid and 0.3% DHA [*13]. Infant formulas frequently have not contained arachidonic acid or DHA. One study showed that by (or just before) age 8, children who had been breast-fed as infants had an 8.3-point IQ advantage over children who had received formula [*14]. The study corrected for the education and social class of the mother.

Further support for the idea that DHA is critical for brain development came from an experiment which studied the effects of adding DHA (in the form of fish oil) to infant formula. At both 16 and 30 weeks of age the breast-fed and supplement-formula-fed infants showed significantly better visual acuity than the placebo-formula-fed infants [*15]. Arachidonic acid supplementation is also needed because DHA supplementation given alone lowers arachidonic acid levels [*16] and because arachidonic acid is essential for growth [*17,*18]. Deficiency of arachidonic acid during brain development is less reversible than deficiency of DHA [*19]. Recent reviews have firmly recommended the inclusion of both arachidonic acid and DHA in the formula of premature babies [*20].

Even in the best formulations the efficiency of DHA and arachidonic acid absorption by an infant is inferior to what is seen for breast milk. Therefore, the best way to ensure adequate DHA and arachidonic acid would be for a pregnant/nursing mother to take a DHA supplement. The content of DHA and EPA in human milk has been increased experimentally by giving fish oil supplements to lactating women [*21]. The diet of the mother may contain enough omega-6 fat to allow her to synthesize sufficient arachidonic acid. DHA supplementation would be particularly important for mothers who have consumed excessive alcohol, because alcohol inhibits the desaturase enzymes necessary for DHA synthesis [*22].

Arachidonic acid is similar to glutamate (glutamic acid) in that it can be harmful in conditions of restricted blood circulation (ischemia), but it is essential for normal brain function. It is the EPA (not DHA) in fish oil that can reduce arachidonic acid synthesis. Where pure DHA, rather than fish oil, has been used in infant formulas, inhibition of growth has been much less [*22]. The best infant formula should contain both DHA and arachidonic acid, however, because arachidonic acid improves growth.

An experiment studying maze-learning in rats demonstrated that, after training, the rats showed less cholesterol and more membrane fluidity in the hippocampal and cortical regions of the brain [*23]. Adult mice fed fish oil for 12 months showed more brain DHA, less brain arachidonic acid, more synaptic membrane fluidity and higher maze-learning ability [*24].

Fatty acid in phosphatidylethanolamine of human gray matter cell membrane is roughly 25% DHA, 25% stearic acid, 14% arachidonic and 12% oleic acid. In the outer segments of retina photo-receptors of the eye more than 50% of the fatty acid content is DHA. It is DHA's special properties of permeability and perhaps fluidity that probably accounts for this high concentration [*10].