1. INTRODUCTION:

Docosahexaenoic acid (DHA) is one of the major building blocks of the brain, the omega-3 fatty acid, critical for optimal brain health and function at all ages of life. Researchers are now finding that DHA provides brain-boosting benefits in infants and aging adults. DHA is an omega-3 fatty acid that is a primary structural component of the human brain, cerebral cortex, skin, sperm, testicles and retina. It can be synthesized from alpha-linolenic acid or obtained directly from maternal milk or fish oil. It is found in cold water fatty fish, such as salmon. It is also found in fish oil supplements, along with eicosapentaenoic acid (EPA).

2. STRUCTURE:

DHA's structure is a carboxylic acid(~oic acid) with a 22-carbon chain (docosa- is Greek for 22) and six (Greek "hexa") cis double bonds (-en~);the first double bond is located at the third carbon from the omega end. Its trivial name is cervonic acid, its systematic name is all-cis-docosa-4,7,10,13,16,19-hexa-enoic acid, and its shorthand name is 22:6(n-3) in the nomenclature of fatty acids.

3. METABOLIC SYNTHESIS:

Cold-water oceanic fish oils are rich in DHA. Most of the DHA in fish and multi-cellular organisms with access to cold-water oceanic foods originates from photosynthetic and heterotrophic microalgae, and becomes increasingly concentrated in organisms. DHA is also commercially manufactured from microalgae; Crypthecodinium cohnii and another of the genus Schizochytrium. DHA manufactured using microalgae is vegetarian. Some animals with access to seafood make very little DHA through metabolism, but obtain it in the diet. However, in strict herbivores, and carnivores that do not eat seafood, DHA is manufactured internally from α-linolenic acid, a shorter omega-3 fatty acid manufactured by plants (and also occurring in animal products as obtained from plants).

Eicosapentaenoic and docosapentaenoic acids are the principal products of α-linolenic acid metabolism in young men and illustrates the importance of DHA production for the developing fetus and healthy breast milk.(Malone, 2011) Rates of conversion 15% higher for women, ( Giltay, Gooren, Toorians, and Katan 2004) and that those taking oral contraceptives demonstrated 10% higher DHA levels (Giltay, E.J., Gooren, L.J.G., Toorians, A.W.F.T., Katan, M.B., and Zock, P.L. 2004).

Administration of testosterone or the aromatase inhibitor anastrozole, which blocks conversion of testosterone to estradiol, reduces DHA conversion. DHA is a major fatty acid in sperm and brain phospholipids and in the retina. Dietary DHA may reduce the risk of heart disease by reducing the level of blood triglycerides in humans. Below-normal levels of DHA have been associated with Alzheimer's disease. A low level of DHA is also spotted in patients with retinitis pigmentosa.

4. DHA AND BRAIN DEVELOPMENT:

In the human infant, brain development undergoes its most rapid and complex growth during the last trimester of pregnancy and the first two years after birth. This means that during this period the child’s eventual neurological development is highly dependent on its dietary intake of essential nutrients, especially omega-3 oils.

Because the fetal and infant brain is unable to convert enough alpha-linolenic oil (an omega-3 oil found in some plant oils) into DHA, the baby almost totally depends on its mother for its supply. There is good evidence that the placenta selectively takes up DHA so as to ensure an adequate supply for the growing baby. Some 70% of energy supply during fetal development is devoted to brain development, and lipids make up 50 to 60% of the structure of the brain, with DHA making up 30% of the brain and 50% of the retina’s structure. In developing babies, higher levels of DHA levels are needed for the growth of neuronal cells than other brain structures. The composition of the membranes of neural cells is under constant reconstruction, and can change drastically with changes in diet. Infants with neurological abnormalities at birth had significantly lower levels of arachidonic acid and DHA and higher trans fatty acid levels. In contrast, infants with higher arachidonic acid, DHA, and essential fatty acid levels had more normal neurological function. the impact of DHA on visual development in 6-month-old infants found that retinal and visual cortex maturation was greatly improved in infants receiving DHA-enriched egg yolk . researchers found that maternal and fetal DHA levels measured at birth correlated with attention and distractibility at 12 and 18 months, with those having higher DHA levels fairing better than those with low levels. It is also interesting to note that DHA plays a major role in muscle function and coordination in developing infants. A recent study using newborn baboons revealed that the highest levels of DHA are found in the motor control areas of the brain, which also play a major role in memory, social development, and behavior.

5. DHA AND ADULT BRAIN:

It also plays a vital role in the ongoing structure and function of the adult brain. Structurally, DHA comprises carbons and six double bonds, making it the most unsaturated fatty acid in cell membranes and an important ingredient in increasing the fluidity of cell membranes. Changing the fluidity of cell membranes alters their physical properties, such as permeability and protein activity. This change can drastically alter cell signaling and plays a major role in increasing membrane permeability of cancer cells, making them more susceptible to immunologic and chemotherapeutic killing. Although many view the brain as a stable structure that changes little after adolescence, it is in fact always in a state of flux, not only by forming millions of new nerve connections, but also by replacing and altering its biochemical makeup, especially membrane lipids. Connected with this constant turnover of brain lipids are the phospholipase enzymes, which can release arachidonic acid and DHA from the cell membrane.39 Dietary changes can therefore drastically alter brain lipids, which can significantly alter brain function, even worsening neuropsychiatric disorders.

6. PREGNANCY AND LACTATION:

DHA has recently gained attention as a supplement for pregnant women, noting studies of improved attention and visual acuity. A working group from the International Society for the Study of Fatty Acids and Lipids recommended 300 mg/day of DHA for pregnant and lactating women, whereas the average consumption was between 45 mg and 115 mg per day of the women in the study. The March of Dimes recommends pregnant women consume at least 200 mg DHA per day.Other requirements are available from other sources.( Jennifer Denomme, Ken D. Stark, and Bruce J. Holub 2004) Docosahexaenoic acid single-cell oil (DHASCO) does not make infant formulas more like human milk than "conventional" formula containing alpha-linolenic acid and linoleic acid, which are precursors to DHA. A study found that preterm infants fed baby formulas fortified with DHASCO provided better developmental outcomes than formulas not containing the supplement. (Clandinin M, Van Aerde J, Merkel K, Harris C, Springer M, Hansen J, Diersen-Schade D ,2005). A study suggests that women who take DHA supplements during pregnancy give their babies some degree of added protection against getting common colds (Ramakrishnan, Usha; et al. 2011)

7. PROTECTION AGAINST ILLNESS:

7.1. Attention-Deficit Hyperactivity Disorder (ADHD):

Research on DHA supplementation and attention deficit hyperactivity disorder (ADHD) have shown mixed results. One study of pure DHA supplementation on children with ADHD found no behavioral improvements, (Voigt RG, Llorente AM, Jensen CL, Fraley JK, Berretta MC, Heird WC. 2001) while another study found fish oil containing both EPA and DHA did improve behavior, (Sinn N, Bryan J 2007 ) though these studies and most others regarding the influence of DHA on behavior are confounded by not controlling for gender differences(Malone J P, 2011).

7.2. Depression:

Although some studies have shown that fish oil reduces symptoms of depression, it isn't clear whether DHA alone has the same effect. Other studies suggest it may be EPA which has the positive effect on depression.

7.3. Heart Disease:

Fish oil appears to have positive effects on existing heart disease. It also may lower the risk for developing heart disease. Omega-3 fatty acids found in fish oil help lower triglycerides (fats in the blood), lower blood pressure, reduce the risk of blood clots, improve the health of arteries, and reduce the amount of arterial plaque, which narrows arteries and causes heart disease.

7.4. Raynaud Syndrome:

Several studies show that high doses (12 g) of fish oil can reduce sensitivity to cold in the fingers and toes of people with Raynaud syndrome. Doses should be taken only under a doctor's supervision.

7.5. Other Benefits:

Some people use DHA is for improving vision, preventing an eye disease called age-related macular degeneration (AMD), preventing and treating depression, dementia and reducing aggressive behavior in people in stressful situations.

DHA is used in combination with eicosapentaenoic acid (EPA) for a variety of conditions, including the prevention and reversal of heart disease, stabilizing heartrhythm, asthma, cancer, painful menstrual periods, hayfever, lung diseases, systemic lupus erythematosus (SLE), and certain kidney diseases. EPA and DHA are also used in combination for high cholesterol, high blood pressure, psoriasis, Raynaud’s syndrome, rheumatoid arthritis, bipolar disorder, certain inflammations of the digestive system (ulcerative colitis) and preventing migraine headaches in teenagers. DHA deficiencies are associated with foetal alcohol syndrome, attention deficit hyperactivity disorder, cystic fibrosis, phenylketonuria, unipolar depression, aggressive hostility, and adrenolekodystrophy. It is also used in combination with evening primrose oil, thyme oil, and vitamin E (Efalex) to improve movement disorders in children called dyspraxia.

8. DIETARY SOURCES:

The best sources of DHA are: seafood, algae, and especially coldwater fish. Salmon has the highest content of DHA of any fish source, ranging from 2000 to 3000 milligrams per 6 ounce serving. Additional top fish sources of DHA are: tuna, bluefish, mackerel, swordfish, anchovies, herring, sardines, and caviar. Besides fish oils, vegetable oils (primarily flaxseed, soy, and canola) are also rich sources of omega 3 fatty acids, with flaxseed oil being the best. For infants, breast milk from a mother who eats a healthy diet contains significant amounts of DHA. Infant formula may or may not have any DHA.

9. DHA IN INDIAN FOODS

Omega 3 Alpha Linolenic Acid (ALA):

It can be converted by human body to EPA and EPA into DHA.

Food Sources:

Flaxseed (The best source for LNA)

Hempseeds

Walnuts (The best nut)

Pistachios

Pumpkin seeds

Brazil Nuts

Sesame seeds

Avocado (The best fruit)

Dark green leafy vegetables (Spinach, Kale, Mustard greens, Collard)

Canola Oil (Best source for omega 3 for cooking)

Soybean oil

10. AVAILABLE FORMS

DHA is available as a supplement in two common forms:

· Fish oil capsules, which contain both DHA and EPA (eicosapentaenoic acid), another omega-3 fatty acid

· DHA from algae, which contains no EPA

It takes an average of 3-months to achieve omega-3 essentiality, a term used in the literature to reflect steady-state 7% to 8% Red Blood Cell Omega-3 levels, the omega-3 marker for establishing clinical sufficiency.

11. PRECAUTIONS:

Fish oil capsules contain both DHA and EPA. Supplements containing EPA may not be recommended for infants or small children because they upset the balance between DHA and EPA during early development. Pregnant women should talk to their doctor before taking fish oil supplements. Fish oil capsules may cause minor side effects, such as loose stools, stomach upset, and belching.

12. POSSIBLE DRUG INTERACTIONS

12.1. Antihypertensives:

DHA may lower blood pressure, so it could make the effects of antihypertensives stronger.

12.2. Anticoagulants:

EPA in fish oil supplements may increase bleeding time, so fish oil could make the effects of these drugs stronger. The same does not appear to be true of DHA alone.

12.3. Diabetes Medications:

Theoretically, fish oil supplements may lower blood sugar levels and could make effects of diabetes drugs stronger.

12.4. Aspirin:

Combined with aspirin, fish oil could help treat some forms of heart disease. However, this combination may also increase the risk of bleeding.

12.5. Cyclosporine:

Omega-3 fatty acids may reduce some of the side effects of cyclosporine, which is often used to stop rejection in transplant recipients.

13. REFERENCES:

1. Crawford MA, Hassam AG, Stevens PA. Essential fatty acid requirements in pregnancy and lactation with special reference to brain development. Prog Lipid Res. 1981;20:31-40.

2. Hoffman DR, Theuer RC, Castaneda YS, et al. Maturation of visual acuity is accelerated in breast-fed term infants fed baby food containing DHA-enriched egg yolk. J Nutr. 2004 Sep;134(9):2307-13.

3. Green P, Glozman S, Kamensky B, Yavin E. Developmental changes in rat brain membrane lipids and fatty acids .The preferential prenatal accumulation of docosahexaenoic acid. J Lipid Res. 1999 May;40(5):960-6.

4. Colombo J, Kannass KN, Shaddy DJ, et al. Maternal DHA and the development of attention in infancy and toddlerhood.Child Dev. 2004 Jul;75(4):1254-67.

5. Stillwell W, Ehringer W, Jenski LJ. Docosahexaenoic acid increases permeability of lipid vesicles and tumor cells. Lipids. 1993 Feb;28(2):103-8.

6. Horrobin DF, Bennett CN. New gene targets related to schizophrenia and other psychiatric disorders: enzymes, binding proteins and transport proteins involved in phospholipid and fatty acid metabolism. Prostaglandins Leukot Essent Fatty Acids. 1999 Mar;60(3):141-67.

7. Horrocks LA, Yeo YK . Health benefits of docosahexaenoic acid (DHA).Pharmacol Res. 1999 Sep;40(3):211-25.

8. University of Maryland. Docosahexanoic acid.[Internet] [cited 31,2013]. Available from: http://www.umm.edu/altmed/ articles/docosahexaenoic-acid-000300.htm#ixzz2KfUzyb3q

Received on 11.03.2015 Modified on 10.05.2015

Asian J. Nur. Edu. and Research 5(3): July- Sept.2015; Page 425-428

DOI: 10.5958/2349-2996.2015.00084.1

Docosahexaenoic Acid (Dha) – The Magic of Master Brain