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Sources and physiological effects

Dietary sources
Eicosapentaenoic acid, EPA for short, is a polyunsaturated fatty acid from the omega-3 family. In the diet, EPA is particularly abundant in fatty fish such as tuna, salmon, mackerel, herring and sardine. These fish accumulate omega-3 fatty acids in their cell membranes and fatty tissue, in the form of EPA, DHA and ALA, through the consumption of special microalgae and plankton. Due to the high omega-3 content, the cellular membranes of the fish remain flexible at low temperatures. Plant sources of EPA include certain microalgae such as ulkenia or schizuchytrium algae. In enriched form, as algae oil capsules, they are an alternative for vegetarians, vegans and people with fish aversion.
Physiological effects
Cell membranes	As a component of the cell membranes responsible for the permeability of the cells
Inflammations	Involved in the formation of anti-inflammatory eicosanoids by competitive displacement of arachidonic acid EPA has antithrombotic, anti-inflammatory and vasodilatory effects
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
Fat metabolism	Reduction of triglyceride values (reduction of LDL values and increase of HDL values)

EFSA Health Claims

Health Claims		EFSA Opinion
EPA	Contributes to normal heart function.
EPA	Helps maintain normal blood cholesterol levels.
Standard values	Positive effects are achieved with a daily intake of 250 mg.

Recommended intake

Nutrient requirements
It is assumed that the daily requirement for EPA is between 100 and 200 mg (minimum intake) and between 300 and 400 mg (desirable intake). Other recommendations include 8 g EPA per week for women and 10 g EPA per week for men. This corresponds to 1140 mg or 1430 mg per day. Dosages of 3.5 g/day are recommended for therapeutic use.
Increased demand	Pregnancy, lactation, growth, low fish consumption, inflammatory and chronic degenerative diseases
Special groups at risk of deficiency	Allergies, multiple sclerosis, psoriasis, rheumatoid arthritis

Detailed information

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 primarily involved in the formation of anti-inflammatory eicosanoids, the main effect of DHA is to increase the fluidity and permeability of membranes. Differences in the organ presence of the individual omega-3 fatty acids are also becoming increasingly apparent. Typical organs/tissues containing EPA include the liver and for DHA, retina and brain (1). Differences can also be seen in the retention of the two fatty acids in the cells. After the end of a course of fish oil supplementation the cells seem to retain the DHA content, while the EPA concentration in the mononuclear cells drops back to its initial value within 8 weeks (2). Practical recommendations are currently limited to information on the consumption of fatty fish or fish oil - because both products contain both EPA and DHA. However, for targeted micronutrient therapy, orthomolecular quality preparations with a high content of the therapeutically used fatty acid are recommended (1).

Inhibition of inflammatory mediators by EPA

Eicosapentaenoic acid serves as an intracellular base substance for series 3 eicosanoids and series 5 leukotrienes, which have antithrombotic, anti-inflammatory and vasodilatory effects in the body (3) (1). Acute inflammatory processes often have a high concentration of inflammatory and immunosuppressive eicosanoids of the 2 and 4 series, which are formed from arachidonic acid. An increased supply of eicosapentaenoic acid inhibits this conversion process - there is an increase in anti-inflammatory eicosanoids. Modulated fatty acid uptake has therapeutic potential in inflammatory diseases such as ulcerative colitis, rheumatism or arteriosclerosis (4) (3).

Cardioprotective effect of EPA

Epidemiological studies and meta-analyses have shown that omega-3 fatty acids play an important role in maintaining cardiovascular function – they significantly reduce the overall mortality rate, cardiovascular mortality and the number of sudden deaths (5). The Jelis study, involving 18,645 patients, investigated the effect of EPA on coronary heart disease in patients taking low-dose statins. Over 9000 of the study participants received 1800 mg per day. After an average follow-up period of 4.6 years, the rate of cardiac events in the group treated with statins only was 3.5% versus 2.8% in the EPA group - a significant difference of 19% (6). Another study showed the plaque-stabilizing and anti-inflammatory effect of EPA which contributes to its cardioprotective effects (7).

Reference values

Parameter	Substrate	Reference values	Description
EPA (20:5)	EDTA	11 - 33 mg/l	Omega-3-Index

Deficiency symptoms

Impact on	Symptoms
Cell	Disturbed flexibility and permeability of cell membranes
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
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
	Complementary therapy for allergies, asthma bronchiale, allergic rhinitis, COPD	1.5 - 4g/d





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

Administration

General mode administration
When	Eicosapentaenoic acid (EPA) should be taken with meals. Notes: It should be taken regularly and on a long-term basis. The combination with antioxidants is recommended, as unwanted lipid peroxidations can limit the biological effectiveness. The use in persons taking anticoagulants should be carried out under medical supervision.
Side effects
Omega-3 fatty acids (such as EPA) 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, ASS)	Can prolong bleeding time and reduce platelet aggregation in high doses with vitamin antagonist or ASA therapy (control INR values).
NSAIDs (e.g. ibuprofen, ASS, diclofenac)	The anti-inflammatory and immunomodulating effect of omega-3 fatty acids can reduce the need for NSAIDs.
Psychostimulants (methylphendiate)	EPA can improve the effectiveness of methylphenidate.
Cholesterol-lowering drugs (statins)	Support of statin therapy by cardioprotective and lipid modulating effects of EPA.
Nutrient interactions
Glucosamine	Omega-3 fatty acids (such as EPA) and glucosamine complement each other in their anti-inflammatory effect in the therapy of inflammatory diseases of the locomotor system.

Description and related substances

Description

Essential polyunsaturated omega-3 fatty acids

References

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

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

3) Gröber, U. 2008. Orthomolekulare Medizin. Ein Leitfaden für Apotheker und Ärzte.

4) Hahn, A. 2006. Ernährung. Physiologische Grundlagen, Prävention, Therapie.

5) Iglesias del Sol, A., Smulders, Y. M. 2006. Health effects of fish oil supplements: consumption advice sustained. Ned Tijdsch Geneeskd. 150(38):2069-71.

6) Ishikawa, Y. et al. 2010. Preventive effects of eicosapentaenoic acid on coronary artery disease in patients with peripheral artery disease. Circ J. 74(7):1451-7.

7) Cawood, A. L. et al. 2010. Eicosapentaenoic acid (EPA) from highly concentrated n-3 fatty acid ethyl esters is incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability. Atherosclerosis. 212(1):252-9.

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.