DHA

Synonym(s): docosahexaenoic acid, doconexent, Omega-3 fatty acids

Nutrient group: fatty acids

Sources and physiological effects

Dietary sources
Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid from the omega-3 family. In the diet, DHA is particularly abundant in fatty deep sea fish such as tuna, salmon, mackerel, herring and sardine. These contain enriched omega-3 fatty acids in the form of EPA, DHA and ALA in their cell membranes and fatty tissue due to their consumption of special microalgae and krill. Due to the high omega-3 content, the cellular membranes of these fish remain flexible at low temperatures.Plant sources of DHA include certain microalgae such as Ulkenia or Schizochytrium algae. In enriched form, as algae oil capsules, they are a suitable plant-based alternative for vegetarians, vegans and people with aversion to fish.
Physiological effects
Cell membranes	As a component of the cell membranes responsible for the permeability and elasticity of the cells
Blood vessels	Increase in NO-induced vasodilation, Reduction of inflammation markers Reduced release of platelet activating factor and reduction of platelet aggregation Systolic and diastolic blood pressure reduction Increase renal blood flow and improve microcirculation
Cardiovascular system	Cardioprotective effect through antiarrhythmic and antithrombotic effects
Nervous system	Participation in brain and nerve development Synthesis of serotonin and dopamine receptors Influence on eye function through involvement in retinal development Influence of retinal development
Fat metabolism	Reduction of triglyceride values Improvement of LDL values and increase of HDL values

EFSA Health Claims

Health Claims		EFSA Opinion
DHA	Contributes to the maintenance of normal brain function Contributes to vision maintenance Contributes to normal heart function Helps maintain normal blood cholesterol levels


Standard values	DHA contributes to maintaining normal brain and heart function; DHA contributes to maintaining normal vision. The claim may only be used for foods containing at least 40 mg DHA per 100 g and per 100 kcal. For the claim to be admissible, consumers should be informed that the positive effect of daily intake of 250 mg DHA is achieved.

Recommended intake

Nutrient requirements
Daily intake of DHA is expected to be between 100 and 200 mg (minimum intake) and 300 - 400 mg (desirable intake). Other recommendations are 8 g EPA/DHA per week for women and 10 g/DHA per week for men. This corresponds to 1140 mg or 1430 mg per day. For therapeutic use, doses of 3.5 g/day are recommended.
Increased demand	Pregnancy, lactation, growth, low fish consumption, inflammatory and chronic degenerative diseases
Special group at risk of deficiency	Allergies, Alzheimer's disease, multiple sclerosis, psoriasis, rheumatoid arthritis, macular degeneration, ADHD

Detailed information

DHA as an essential foodstuff

Docosahexaenoic acid (DHA) is a polyunsaturated, long-chain omega-3 fatty acid that the body can synthesize endogenously to a certain extent. Docosahexaenoic acid is produced in the human organism by desaturation and elongation process of alpha-linolenic acid and from the resulting eicosapentaenoic acid. This transformation process is inadequate due to the limited enzymatic capacity of humans. Only about 10 % of alpha-linolenic acid is ultimately converted into the higher unsaturated derivatives eicosapentaenoic acid and docosahexaenoic acid (1). The brain can only produce DHA to a limited extent (2), other organs such as the heart are not equipped for this at all (3). An exogenous supply of DHA is particularly necessary in times of increased demand. An additional supply of DHA is often considered necessary and is only possible throughthe intake of cold deep sea fish and special species of algea.

EPA and DHA - same family, different spectrum of action

Research results of recent years illustrate the different effects of the two omega-3 fatty acids EPA and DHA. While EPA is particularly involved in the formation of anti-inflammatory eicosanoids, the main effect of DHA is to increase the fluidity and permeability of membranes. Increasingly, differences in the organ presence of the individual omega-3 fatty acids are also becoming clear. The typical organs and tissues sites for EPA include the liver and for DHA, the retina and the brain (4).

Docosahexaenoic acid and cerebral functions

Regular and sufficient exogenous DHA supply is particularly important for cognitive development and performance. DHA is found in high concentrations in the brain, nerve tissue and rhodopsin of the eyes. It is necessary for maintaining the permeability and flexibility of the cell membranes and is required by the postsynaptic receptors for neurotransmission. Systemic undersupply of DHA is associated with neurodegenerative diseases, reduced cognitive performance and behavioral problems. New studies show that neuroprotectin D1 (NPD1), a DHA-dependent molecule, has essential functions in maintaining the integrity and lifespan of brain cells. These molecular genetic mechanisms regulate various neurobiologically active peptide compounds with a neuroprotective effect (6). In addition, DHA can increase neurotransmitter synthesis in the synaptic cleft (7), which can directly influence neuropsychiatric processes. A lack of DHA promotes neuronal dysfunctions, such as that which occur in Alzheimer's disease, and contributes to age-related neurological structural and process changes (8). Several studies have shown that regular DHA supplementation in older people (e.g. 900 mg/d for 6 months) can improve memory functions (9), increase speech, learning skills and mood parameters (10) and slow down cognitive decline (11). An increased intake of DHA could also significantly improve mood, impulse control and affect regulation in healthy individuals (12). In school children, higher DHA values correlated with better reading comprehension and faster learning of vocabulary (13).

DHA status in psychiatric disorders

Today there is increasing evidence that insufficient DHA status is associated with many psychiatric disorders such as depression, aggressiveness, manic disorders and bipolar disorders. The importance of omega-3 fatty acids in the development of psychiatric diseases is supported by epidemiological studies. For example, an inverse correlation between the intake of omega-3 fatty acids and the frequency of depression as well as omega-3 status and addictions has been documented. Basic research has also shown that in depressed patients DHA depletion is accompanied by a disturbed glucose metabolism in certain brain regions (14). Low omega-3 levels were also observed in manic diseases (15). In addicts, a low DHA level correlates with a higher relapse rate in withdrawal treatments (16). Targeted supplementation with omega-3 fatty acids can positively influence psychiatric symptoms such as increased aggression (17). In adolescents with bipolar disorders, DHA supplementation led to significant improvements in symptoms (18). A supply of 400 mg/d DHA for children and 700 mg/d DHA for adults is generally recommended (19).

DHA for the prenatal development of the child

An increased intake of DHA during pregnancy and lactation is now recommended by leading prenatalists (20). Adequate DHA supplementation of the mother during pregnancy and breastfeeding correlates positively with the development of visual acuity in the child, with psychomotor development and with the intelligence quotient (21).

Reference values

Parameter	Substrate	Reference value	Description
DHA (22 : 5)	EDTA	1.4 - 9.6 mg/l	Omega-3-Index
DHA (22 : 6)	EDTA	47 - 92 mg/l	Omega-3-Index

Deficiency symptoms

Impact on	Symptoms
Cell	Disturbed cell membrane flexibility and permeability
Skin	Dry, flaky skin Increased tendency to atopy and eczema
Immune system	Increased production of inflammation-promoting cytokines promotes susceptibility to infections and the appearance of atopias
Pregnancy	Deficient embryonic CNS development due to reduced DHA incorporation in synapses and resulting reduction in cognitive performance
Children	Concentration disorders, abnormalities in development and behavior
Increased risk for	Arteriosclerosis, ADHD, depression, Alzheimer's disease

Indications

Effect	Indication	Dosage
Physiological effects at a low intake	For general prevention	1 - 1.5 g/d
	Therapeutic support of allergies, asthma bronchiale, allergic rhinitis, COPD	1.5 - 4 g/d
	For support of ADHS	1 - 5 g/d
	Therapeutic support for depressions, dementia, morbus Alzheimer	1.5 - 4 g/d
	During pregnancy and lactation to support the child's cerebral development	1 - 3 g/d


Pharmacological effects at a high intake	Therapeutic support for cardiovascular diseases and as secondary prophylaxis after heart attack, arrhythmias and hypertension	1.5 - 6 g/d

Administration

General mode of administration
When	Docosahexaenoic acid (DHA) should be taken with meals. Note: Intake should be regular and long-term. The combination with antioxidants is recommended as unwanted lipid peroxidation can limit the biological effectiveness. Use in persons taking anticoagulants should be under medical supervision.
Side effects
Omega-3 fatty acids such as DHA reduce platelet aggregation, platelet aggregation promoting platelet formation and lower plasma factor VII and fibrinogen levels. This moderately prolongs blood coagulation, reducing the need for warfarin or phenprocoumon and requires dose adjustment.
Contraindications
Acute pancreatitis, cirrhosis, gall bladder inflammation, coagulation disorders

Interactions

Drug interactions
Anticoagulants(e.g. Phenprocoumon, ASA)	Can prolong bleeding time and reduce platelet aggregation in high doses with vitamin K–antagonists or ASA (control INR values).
NSAID's (e.g. Ibuprofen, ASA, Diclofenac)	The anti-inflammatory and immunomodulating effect of omega-3 fatty acids can reduce the need for NSAIDs.
Psychostimulants (methylphenidate)	DHA can improve the effectiveness of methylphenidate.
Cholesterol-lowering drugs (statins)	Support of statin therapy through cardioprotective and lipid modulating effects of DHA.
Nutrient interactions
Glucosamine	Omega-3 fatty acids (such as DHA) and glucosamine complement each others through their anti-inflammatory effect for therapy of inflammatory diseases of the locomotor system.

Description and related substances

Description

Essential polyunsaturated omega-3 fatty acids

References

1) Hahn, A. et al. Ernährung. Physiologische Grundlagen, Prävention, Therapie. 2006

2) Igarashi, M. et al. 2007. Rate of synthesis of docosah exaenoic acid from alpha-linolenic acid by rat brain is not altered by dietary N-3 polyunsaturated fatty acid deprivation. J Lipid Res.

3) Igarashi, M. et al. 2008. Rat heart cannot synthesize docosahexaenoic acid from circulating alphalinolenic acid because it lacks elongase-2. J Lipid Res. 49(8):1735-45

4) Singer, P. 2010 Praktische Aspekte bei der Zufuhr von Omega-3-Fettsäuren. E & M - Ernährung und Medizin. 25(Suppl. 1):3 – 18.

5) Calder, P. C. 2009. Omega-3-Fettsäuren. Ars Medici Dossier V.

6) Lukiw, W. J. et al. 2008. Docosahexaenoic acid and the aging brain. J Nutr. 138(12):2510-4

7) Cansev, M. et al. 2008. Oral administration of circulating precursors for membrane phosphatides can promote the synthesis of new brain synapses. Alzheimers Dement. 4(1 Suppl 1):S153-68

8) Mukherjee, P. K. et al. 2007. Docosanoids are multifunctional regulators of neural cell integrity and fate: significance in aging and disease. Prostaglandins Leukot Essent Fatty Acids. 77(5-6)

9) Yurko-Mauro, K. et al. 2009. Results of the MIDAS Trial: Effects of Docosahexaenoic Acid on Physiological and Safety Parameters in Age related Cognitve Decline. International Conderence; Alzheimer’s Association, Vienna.

10) Johnson, E. J. et al. 2008. Cognitive findings of an exploratory trial of docosahexaenoic acid and lutein supplementation in older women. Nutr Neurosci. 11(2):75-83

11) van Gelder, B. M. et al. 2007. Fish consumption, n-3 fatty acids, and subsequent 5-y

cognitive decline in elderly men: the Zutphen Elderly Study. Am J Clin Nutr. 85(4):1142-7

12) Conklin, S. M. et al. 2007. Serum omega-3 fatty acids are associated with variation in mood, personality and behavior in hypercholesterolemic community volunteers. Psychiatry Res. 152(1):1-10

13) Ryan, A. S., Nelson, E. B. 2008. Assessing the effect of docosahexaenoic acid on cognitive functions in healthy, preschool children: a randomized, placebo-controlled, double-blind study. Clin Pediatr (Phila). 47(4):355-62

14) Elizabeth Sublette, M. et al. 2009. Plasma polyunsaturated fatty acids and regional cerebral glucose metabolism in major depression. Prostaglandins Leukot Essent Fatty Acids. 80(1):57-64

15) Sublette, M. E. et al. 2007. Plasma free polyunsaturated fatty acid levels are associated with symptom severity in acute mania. Bipolar Disord. 9(7):759-65

16) Buydens-Branchey, L. et al. 2009. Low plasma levels of docosahexaenoic acid are associated with an increased relapse vulnerability in substance abusers. Am J Addict. 18(1):73-80

17) Buydens-Branchey, L., Branchey, M. 2008. Long-chain n-3 polyunsaturated fatty acids decrease feelings of anger in substance abusers. Psychiatry Res. 157(1-3):95-104

18) Clayton, E. H. et al. 2009. Reduced mania and depression in juvenile bipolar disorder associated with long-chain omega-3 polyunsaturated fatty acid supplementation. Eur J Clin Nutr.

19) McNamara, R. K. 2009. Evaluation of docosahexaenoic acid deficiency as a preventable risk factor for recurrent affective disorders: Current status, future directions, and dietary recommendations. Prostaglandins Leukot Essent Fatty Acids.

20) Koletzko, B. et al. 2001. Long chain polyunsaturated fatty acids and perinatal development. Acta Paediatr. 90(4):460-4

21) Helland, I. B. et al. 2003. Maternal supplementation with very long-chain n-3 fatty acids during pregnancy and lactation augments children’s IQ at 4 years of age. Pediatrics. 111(1):e39-44

References Interactions:
Stargrove, M. B. et al. Herb, Nutrient and Drug Interactions: Clinical Implications and Therapeutic Strategies, 1. Auflage. St. Louis, Missouri: Elsevier Health Sciences, 2008.

Gröber, U. Mikronährstoffe: Metabolic Tuning –Prävention –Therapie, 3. Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2011.

Gröber, U. Arzneimittel und Mikronährstoffe: Medikationsorientierte Supplementierung, 3. aktualisierte und erweiterte Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2014.