Docosahexaenoic Acid (DHA)

Overview

Docosahexaenoic acid (DHA) is the longest and most unsaturated of the omega-3 fatty acids. DHA is one of the most abundant fatty acids in the brain. In the fetus and young infant, DHA is essential for proper growth and development of the brain, (1) , (2) nervous system, and for the retina of the eyes. Breast-feeding is extremely important because an infant receives DHA from its mother’s milk. Cow’s milk and infant formulas do not contain DHA. In Europe, law mandates that infant formulas must contain DHA.

Although DHA can be consumed directly by eating certain kinds of fish, it can also be produced in the body. This process first requires the conversion of alpha linolenic acid (ALA), which is also known as omega-3, to EPA. In the next step of the metabolic process, EPA is converted into DHA. The metabolic processes that convert omega-3 to EPA accomplish this with desaturase and elongase enzymes. Desaturase enzymes produce additional double bonds, while elongase enzymes add carbon atoms to make a longer fatty acid chain. The parent or precursor omega-3 molecule, alpha linolenic acid, is a long-chain fatty acid that contains 18 carbon atoms with three double bonds. Under the influence of the desaturase and elongase enzymes, ALA is converted to eicosapentaenoic acid, which is a fatty acid that is 20 carbons long and contains five double bonds. EPA is then converted into DHA, which is a fatty acid that is 22 carbons long and contains six double bonds.

Studies using omega-3 (ALA) labeled with radioisotopes indicate that many Americans, who normally ingest large quantities of omega-6 oils, probably convert less than 2% of their dietary alpha linolenic acid into (ALA) into docosahexaenoic acid (DHA). (3) Although fish are the best dietary source of DHA, monitoring by the Environmental Protection Agency reveals that commercially available fish may have unacceptably high levels of mercury. (4) Because this problem is of such concern, the EPA warns that pregnant or nursing women and small children should limit their intake of fish. (5) The above issues underscore the importance of taking DHA as a nutritional supplement. Individuals taking DHA supplementation must be warned about the importance of also taking adequate levels of antioxidants.

Dosage Info

Dosage Range

250-1,000mg daily.

Most Common Dosage

500mg daily.

Dosage Forms

Capsules and tablets.

Adult RDI

None established

Adult ODA

None established

Active Forms

Docosahexaenoic acid

Absorption

DHA is absorbed from the intestinal tract, but since it is a fat, absorption is dependent on the amount of fat being consumed at that particular meal. One study reported that the absorption of EPA and DHA fish oils was increased three-fold when consumed with a high-fat meal. (6)

Toxicities & Precautions

General

Individuals who ingest supplemental DHA are advised to take additional antioxidants, especially vitamin E, to protect against free radical oxidation in the body.

Side Effects

Some people who take supplemental DHA in the form of fish oil complain of gastrointestinal burping and belching, which causes a “fishy" odor. (7)

Functions in the Body

Clinical Applications

Elevated Triglycerides

Patients who were given DHA (1.25 or 2.5 gm/day) for six weeks experienced approximately a 20 percent reduction in serum triglycerides. (8) Fish oil supplementation containing 1.0 g DHA and 1.5 g EPA significantly reduced plasma triacylglycerol levels. (9)

Premature Infants

It has been reported that DHA is important for early development of the brain, nervous system, and retina of the eyes. Pre-term infants need to be supplemented with DHA since these infants are often incubated and not breast-fed. (10) In one study, pre-term infants supplemented with DHA developed higher visual acuity. (11)

Schizophrenia

Studies indicate that patients with schizophrenia have lower levels of the long-chain omega-3 fatty acids. (12) Supplementation led to a significant improvement in 20 schizophrenic symptoms. (13) , (14)

ADHD

Researchers report that children with ADHD have low plasma levels of DHA and exhibit symptoms indicative of essential fatty acid deficiency. (15) However, the results of a short 4-month trial reported that children who received 345 mg/day of DHA did not exhibit a decrease in the symptoms of ADHD. (16)

Breast Cancer

There is an inverse relationship between the incidence of breast cancer and fish consumption, which suggests a role for DHA and EPA in the prevention of breast cancer. This may be due to the fact that the omega-3 fats competitively inhibit omega-6 fats, which are considered to promote breast cancer tumorigenesis and tumor cell proliferation. (17)

Cancer

In an animal model, the addition of DHA/EPA to the diet resulted in a 35 to 46% reduction in tumor growth. Also, in cell culture studies, DHA resulted in a 46% decrease in cancer cell growth. (18)

Depression

Studies indicate that people with major depression may have abnormal metabolism of the omega-3 polyunsaturated fatty acids. Thus, fatty acid analysis and appropriate supplementation may be an important aspect of treatment for patients suffering from major depression. (19)

Breast feeding (lactation)

DHA is essential for the development of the brain and eyes in infants. Consequently, nursing mothers should be educated about the importance of obtaining optimal intakes of DHA. Infants receiving adequate DHA, either from supplementation or from well nourished mothers, exhibit increased cognitive function (20) and visual acuity (21) compared to controls.

Chemotherapy

The results of animal studies suggest that supplementation with DHA can make several types of chemotherapy both more effective and less toxic. In one study, mitomycin C was 10 times more effective in animals supplemented with DHA-containing menhaden oil. (22) In another study, after 2 months of treatment with cyclophosphamide, 50% of the animals on a 5% corn oil diet had died whereas none of the animals receiving the DHA/menhaden oil died. (23)

Infant Formulas

Compared to controls, at 18 months of age, infants receiving supplemental DHA in their infant formulas scored significantly higher in mental development, as gauged by memory, problem solving, discrimination, and other related skills, and also showed "significant developmental age advantage" in motor and cognitive skills. (24)

Bipolar disorder

Evidence suggests that long-chain omega-3 fatty acids contained in fish oils (EPA and DHA) exhibit mood-stabilizing properties in patients with bipolar disorder, which is also known as manic depressive illness. EPA and DHA seem to inhibit neuronal signal transduction pathways in a manner similar to lithium carbonate and valproate, which are medications frequently used to treat this disorder. In a four-month, double-blind, placebo-controlled trial, patients treated with the omega-3 fish oils exhibited a significantly longer period of remission, plus they scored better than the placebo group on virtually every outcome measure that was studied. (25) Researchers found that levels of DHA were lower in bipolar mood disorder patients than in controls and that supplementation of antioxidants and essential fatty acids may improve the patients’ symptoms. (26)

Dysmenorrhea

Providing DHA along with EPA for two months to adolescents with dysmenorrhea resulted in a marked reduction in menstrual symptoms. (27)

Heart Disease

Studies indicate that there is an inverse relationship between coronary heart disease risk and levels of docosahexaenoic acid. (28) , (29)

A study assessed the effect of omega-3 fatty acids on systemic arterial compliance (SAC). SAC is a measure of arterial elasticity and may serve as a marker for cardiovascular disease and related events. In this placebo controlled, randomized, double-blind trial, 38 individuals with dyslipidemias were randomly assigned to one of three groups: 3 g eicosapentaenoic acid (EPA) per day (n = 12), 3 g docosahexaenoic acid (DHA) per day (n = 12), or placebo (n = 14). Arterial functions, lipids and fatty acids were all measured prior to and following the treatment interventions. Compared to placebo the omega-3 fatty acids significantly increased the SAC. EPA increased SAC 36% and DHA increased SAC 27%. In addition, the omega-3 fatty acids significantly lowered the total and VLDL triacylgylcerol levels. (30)

Sickle cell disease

A group of patients suffering from sickle cell disease were administered menhaden fish oil (0.25 g/kg/d), which contained 12% EPA and 18% DHA. This treatment resulted in a substantial reduction of pain episodes requiring hospitalization from 7.8 hospitalizations the previous year down to 3.8 events/year. The authors suggest that the reduction in pain events requiring hospitalization were related to omega-3 fatty acid-dependent inhibition of thrombosis. (31)

X-linked retinitis pigmentosa

It has been discovered that individuals with this condition have a metabolic defect in the activity of their delta-5 desaturase enzyme activity, which inhibits their ability to biosynthesize DHA. (32) Another study provided evidence that DHA could be beneficial to patients with X-linked retinitis pigmentosa (XLRP). (33) There were not any identifiable safety risks associated with long-term docosahexaenoic acid supplementation to XLRP patients. Plasma antioxidant capacity, platelet aggregation, liver function enzyme activity, or plasma lipoprotein lipid content were not compromised by DHA supplementation. (34)

Zellweger syndrome

Individuals with this genetic peroxisomal disorder have low levels of DHA. (35) Patients treated with DHA exhibit improved vision and muscle as well as MRI-documented improvements in myelination. Treatment has been most successful when initiated before 6 months of age. (36)

Symptoms and Causes of Deficiency

A deficiency of DHA has become increasingly common for the following reasons:

    People do not regularly consume cold water fish, which is the primary dietary source of both DHA and EPA. Low-fat diets reduce the consumption of DHA and other important fatty acids. Omega-3 (alpha linolenic acid), which is the dietary precursor of DHA and EPA, is typically removed from food in order to increase product shelf life. In the last half century, there has been an increase in the use of processed oils from the omega-6 family such as corn, sunflower, and safflower oils, which competitively compete with and suppresses the conversion of omega-3 to EPA and DHA. Trans fatty acids from foods containing partially hydrogenated fats and oils inhibit enzyme delta-6-desaturase. This may reduce the conversion of omega-3 to EPA and DHA, and also omega-6 to its longer chain fatty acids. (37) The following nutrients are required for proper function of delta-6 desaturase enzyme activity, which converts omega-3 to EPA and DHA. They are niacin, pyridoxine, ascorbic acid, and zinc. Thus, a deficiency of any of these nutrients could impair the biosynthesis of EPA and DHA. (38)

    Some of the major symptoms of a deficiency of DHA include the following: growth retardation in infants; weakness; impaired vision and learning ability; behavioral changes; dry skin; edema; increased inflammation; sticky platelets; elevated blood pressure; elevated triglycerides; altered metabolism; and weakened immune system.

Dietary Sources

The richest dietary sources of DHA are the oils from cold water fish such as salmon, mackerel, herring, sardines, and other marine animals.

References

  1. View Abstract: Helland IB, et al. Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children's IQ at 4 years of age. Pediatrics. Jan2003;111(1):e39-44.
  2. View Abstract: Colombo J, Kannass KN, Jill Shaddy D, et al. Maternal DHA and the Development of Attention in Infancy and Toddlerhood. Child Dev. Jul2004;75(4):1254-67.
  3. View Abstract: Gerster H. Can adults adequately convert alpha-linolenic acid (18:3n-3) to eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3)? Int J Vitam Nutr Res. 1998;68(3):159-73.
  4. EPA Fact Sheet. Mercury Update: Impact on Fish Advisories, EPA-823-F-01-011. Jun2001.
  5. EPA-Office of Water: Consumption Advisories. Available at: http://www.epa.gov/ost/fishadvice/advice.html. Accessed: Jul2001.
  6. View Abstract: Lawson LD, et al. Absorption of eicosapentaenoic acid and docosahexaenoic acid from fish oil triacylglycerols or fish oil ethyl esters co-ingested with a high-fat meal. Biochem Biophys Res Commun. Oct1988;156(2):960-3.
  7. View Abstract: Healy DA, et al. Effect of low-to-moderate amounts of dietary fish oil on neutrophil lipid composition and function. Lipids. Jul2000;35(7):763-8.
  8. View Abstract: Davidson M, et al. Effects of docosahexaenoic acid on serum lipoproteins in patients with combined hyperlipidaemia: a randomized, double-blind, placebo-controlled trial. J AM Coll Nutr. 1997;16:236-243.
  9. View Abstract: Lovegrove JA, Lovegrove SS, Lesauvage SV, et al. Moderate fish-oil supplementation reverses low-platelet, long-chain n-3 polyunsaturated fatty acid status and reduces plasma triacylglycerol concentrations in British Indo-Asians. Am J Clin Nutr. Jun2004;79(6):974-82.
  10. View Abstract: Uauy R, Mena P. Requirements for long-chain polyunsaturated fatty acids in the preterm infant. Curr Opin Pediatr. Apr1999;11(2):115-20.
  11. View Abstract: Werkman S, et al. A Randomized Trial of Visual Attention of Preterm Infants Fed Docosahexaenoic Acid Until Nine Months. Lipids. 1996;31(1):91-97.
  12. View Abstract: Ranjekar PK, Hinge A, Hegde MV, et al. Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients. Psychiatry Res. Dec2003;121(2):109-22.
  13. View Abstract: Laugharne J, et al. Fatty Acids and Schizophrenia. Lipids. 1996(Suppl.);31-S-163 - S-165.
  14. View Abstract: Peet M, Laugharne JD, Mellor J, Ramchand CN. Essential fatty acid deficiency in erythrocyte membranes from chronic schizophrenic patients, and the clinical effects of dietary supplementation. Prostaglandins Leukot Essent Fatty Acids. Aug1996;55(1-2):71-5.
  15. View Abstract: Burgess JR, et al. Long-chain polyunsaturated fatty acids in children with attention-deficit hyperactivity disorder. Am J Clin Nutr. Jan2000;71(1 Suppl):327S-30S.
  16. View Abstract: Voigt RG, Llorente AM, Jensen CL, et al. A randomized, double-blind, placebo-controlled trial of docosahexaenoic acid supplementation in children with attention-deficit/hyperactivity disorder. J Pediatr. Aug2001;139(2):189-96.
  17. View Abstract: Noguchi M. The Role of Fatty Acids and Eicosanoid Synthesis Inhibitors in Breast Cancer. Oncology. 1995;52:265- 271.
  18. View Abstract: Colquhoun A, Ramos KL, Schumacher RI. Eicosapentaenoic acid and docosahexaenoic acid effects on tumour mitochondrial metabolism, acyl CoA metabolism and cell proliferation. Cell Biochem Funct. Jun2001;19(2):97-105.
  19. Edwards R, Peet M, Shay J. Depletion of docosahexanoic acid in red blood cell membranes of depressive patients. Biochem Soc Trans. May1998;26(2):S142.
  20. View Abstract: Willatts P, Forsyth JS, DiModugno MK, et al. Effect of long-chain polyunsaturated fatty acids in infant formula on problem solving at 10 months of age. Lancet. Aug1998;352(9129):688-91.
  21. View Abstract: Jorgensen MH, Hernell O, Hughes E, Michaelsen KF. Is there a relation between docosahexaenoic acid concentration in mothers' milk and visual development in term infants? J Pediatr Gastroenterol Nutr. Mar2001;32(3):293-6.
  22. View Abstract: Shao Y, Pardini L, Pardini RS. Dietary menhaden oil enhances mitomycin C antitumor activity toward human mammary carcinoma MX-1. Lipids. Nov1995;30(11):1035-45.
  23. View Abstract: Shao Y, Pardini L, Pardini RS. Intervention of transplantable human mammary carcinoma MX-1 chemotherapy with dietary menhaden oil in athymic mice: increased therapeutic effects and decreased toxicity of cyclophosphamide. Nutr Cancer. 1997;28(1):63-73.
  24. View Abstract: Birch EE, et al. A randomized controlled trial of early dietary supply of long-chain polyunsaturated fatty acids and mental development in term infants. Dev Med Child Neur. 2000;(42):174-181.
  25. View Abstract: Stoll AL, et al. Omega 3 fatty acids in bipolar disorder; A preliminary double-blind, placebo-controlled trial. Archives of General Psychiatry. May1999;66:407-412.
  26. View Abstract: Ranjekar PK, Hinge A, Hegde MV, et al. Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients. Psychiatry Res. Dec2003;121(2):109-22.
  27. View Abstract: Harel Z, et al. Supplementation With Omega-3 Polyunsaturated Fatty Acids in the Management of Dysmenorrhea in Adolescents. American Journal of Obstetrics and Gynecology. Apr1996;174(4):1335-8.
  28. View Abstract: Simon J, et al. Serum Fatty Acids and Risk of Coronary Heart Disease. American Journal of Epidemiology. 1995;142(5):469-476.
  29. View Abstract: Stark KD, Holub BJ. Differential eicosapentaenoic acid elevations and altered cardiovascular disease risk factor responses after supplementation with docosahexaenoic acid in postmenopausal women receiving and not receiving hormone replacement therapy. Am J Clin Nutr. May2004;79(5):765-73.
  30. View Abstract: Nestel P, Shige H, Pomeroy S, Cehun M, Abbey M, Raederstorff D. The n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid increase systemic arterial compliance in humans. American Journal of Clinical Nutrition. Aug2002;76(2):326-330.
  31. View Abstract: Tomer A, Kasey S, Connor WE, et al. Reduction of pain episodes and prothrombotic activity in sickle cell disease by dietary n-3 fatty acids. Thromb Haemost. Jun2001;85(6):966-74.
  32. View Abstract: Hoffman DR, DeMar JC, Heird WC, et al. Impaired synthesis of DHA in patients with X-linked retinitis pigmentosa. J Lipid Res. Sep2001;42(9):1395-401.
  33. View Abstract: Hoffman DR, Locke KG, Wheaton DH, Fish GE, Spencer R, Birch DG. A randomized, placebo-controlled clinical trial of docosahexaenoic acid supplementation for X-linked retinitis pigmentosa. Am J Ophthalmol. Apr2004;137(4):704-18.
  34. View Abstract: Wheaton DH, Hoffman DR, Locke KG, Watkins RB, Birch DG. Biological safety assessment of docosahexaenoic acid supplementation in a randomized clinical trial for X-linked retinitis pigmentosa. Arch Ophthalmol. Sep2003;121(9):1269-78.
  35. View Abstract: Takemoto Y, Suzuki Y, Horibe R, Shimozawa N, Wanders RJ, Kondo N. Gas chromatography/mass spectrometry analysis of very long chain fatty acids, docosahexaenoic acid, phytanic acid and plasmalogen for the screening of peroxisomal disorders. Brain Dev. Oct2003;25(7):481-7.
  36. View Abstract: Martinez M. Restoring the DHA levels in the brains of Zellweger patients. J Mol Neurosci. Apr2001;16(2-3):309-16.
  37. View Abstract: Booyens J, et al. The role of unnatural dietary trans and cis unsaturated fatty acids in the epidemiology of coronary artery disease. Med Hypotheses. Mar1988;25(3):175-82.
  38. View Abstract: Horrobin DF. Loss of delta-6-desaturase activity as a key factor in aging. Med Hypotheses. Sep1981;7(9):1211-20.