Omega-3 fatty acids

Synonym(s): Alpha-linolenic acid, DHA, docosahexaenoic acid, doconexent, eicosapentaenoic acid, EPA, fish oil, fish oil concentrate

Nutrient group: fatty acids

Sources and physiological effects

Dietary sources
In the diet, omega-3 fatty acids are particularly abundant in fatty, cold-water fish such as tuna, salmon, mackerel, herring and sardine. By consuming special microalgae and small crustaceans, they accumulate omega-3 fatty acids in the form of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and alpha-linolenic acid (ALA) in their cell membranes and fatty tissue. Due to the high omega-3 content, the animals' cellular membranes remain flexible at low temperatures. The advantage of high-quality fish oil capsules over fish is that the quantities of omega-3 fatty acids they contain are standardized and the fish oil has been freed of harmful substances. Vegetable sources of omega-3 fatty acids are available as an alternative for vegetarians, vegans and people with fish aversion. Certain DHA-rich microalgae such as Ulkenia or Schizochytrium algae can be taken in enriched form as algae oil capsules. In addition, vegetable oils such as linseed oil are rich in alpha linolenic acid and rapeseed, nut, sesame and soybean oils are also valuable omega-3 fatty acid suppliers. There are also foods on the market that are enriched with omega-3 fatty acids. These include, bread, margarine and eggs with an increased omega-3 content.
Physiological effects
Cell membranes	As a component of the cell membranes omgega 3s are responsible for the permeability 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
Fat metabolism	Alpha-linolenic acid is the precursor of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) Positive influence on cholesterol levels by lowering LDL values and increasing HDL values

EFSA Health Claims

Health Claims		EFSA Opinion
Omega-3 fatty acids	Support normal blood pressure Have a positive effect on arterial function Contribute to normal heart function Help maintain normal cholesterol levels at The positive effect is achieved with a daily intake of 250 mg

Recommended intake

Nutrient requirements

A daily requirement of EPA and DHA is assumed to be between 100 - 200 mg (minimum intake) and 300 - 400 mg (desirable intake). Other recommendations were 8 g EPA/DHA per week for women and 10 g EPA/DHA per week for men. This corresponds to 1140 mg or 1430 mg per day. For therapeutic use, dosages 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 deficieny	Allergies, Alzheimer's disease, multiple sclerosis, psoriasis, rheumatoid arthritis, macular degeneration, ADHD

Nutrient safety
EFSA- Opinion: Up to 5 g omega-3 fatty acids per day has no negative effects.

Detailed information

Omega-3 fatty acids are essential bioactive substances

Omega-3 fatty acids are characterized by double bonds on the third C atom. Alpha-linolenic acid is the base component for all unsaturated fatty acids in the omega-3 line. In the human body, the more unsaturated fatty acid eicosapentaenoic acid (EPA) can be produced from this fatty acid through the introduction of further double bonds and subsequent chain extension. Trough further extension and desaturation docosahexaenoic acid (DHA) is formed. These two forms of fatty acids are the most important omega-3 fatty acid for many endogenous processes. Studies show that the conversion processes of alpha-linolenic acid into EPA and further into DHA are far more complicated than previously assumed. The human organism is only able to produce EPA and DHA to a limited extent due to enzymatic limitations, which is why these two fatty acids are now regarded as essential nutrients.¹

Improvement of omega-3 index

The omega-3 fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) have proven beneficial effects on lipid metabolism. The omega-3 index, which represents the percentage of the two omega-3 fatty acids in the total fatty acid content of the serum, is suitable as a laboratory diagnostic parameter. If the omega-3 index is <4 %, the risk of sudden cardiac death is ten times more likely than with an index > 8 %.¹

Omega-3 fatty acids and the inflammatory process

The most important function of EPA and DHA is the formation of eicosanoids, which act as local mediators. Depending on where they are synthesized, they are divided into prostaglandins (synthesized in all tissues), prostacyclins (produced in the endothelial cells of vessels), thrombboxane (produced in platelets), and leukotrienes that produce leukocytes. Eicosanoids are formed from both omega-3 and omega-6 fatty acids, but with different physiological effects. Omega-6 fatty acids form eicosanoids of the 2 and 4 series via arachidonic acid, which cause vasoconstrictive, proaggregatory and inflammation-promoting effects, while omega-3 fatty acids form eicosanoids of the 3 and 5 series, which have the opposite effect. For this reason, the latter are simply referred to as “good eicosanoids“.¹ A targeted intake of omega-3 fatty acids inhibits omega-6 metabolism by using the conversion enzymes to build up good eicosanoids. This reduces the formation of undesirable eicosanoids from arachidonic acid, which explains the therapeutic effect of omega-3 fatty acids in inflammatory diseases and cardiovascular prophylaxis.² According to studies, patients with chronic fatigue syndrome (CFS), or myalgic encephalomyelitis (ME), often have low levels of omega-3 fatty acids. However, they can play a decisive role in the inflammatory process by having positive effects on blood coagulation disorders and can lead to a mitigation of the so-called cytokine storm.

Inflammatory diseases: rheumatic forms, Crohn's disease, psoriasis

In rheumatic diseases, the clinical status and symptoms can be significantly improved by an additional intake of EPA/DHA.³ Omega-3 fatty acids also have good therapeutic benefits in inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. In particular, a reduction of clinical symptoms, maintenance of syndrom-free intervals and the reduction of medication for ulcerative colitis is notable.¹ In inflammatory skin diseases such as psoriasis, which are attributed to a disorder of arachidonic acid metabolism, supplementation can significantly improve symptoms such as itching, erythema and dandruff.⁴

Omega-3 fatty acids in cardiovascular diseases

Epidemiological studies and meta-analyses have shown that omega-3 fatty acids play an important role in maintaining cardiovascular function. Large-scale clinical studies show a significant reduction in overall mortality, cardiovascular mortality and sudden death.⁵ Alpha-linolenic acid helps to control total cholesterol and LDL levels.^6,7 and reduce atherogenic plaque formation and vascular inflammation.^8,9 This reduces the risk of cardiovascular disease by 40 – 60 %.¹ Further studies support the antihypertensive effects of EPA and DHA. Both fatty acids can prevent an increase in blood pressure as a preventive measure and but can also reduce existing high blood pressure.¹⁰ EPA and DHA have an anti-aggregatory and vasodilating effect on the endothelial cells of the vessels and can lower the triglyceride level. Thus, they contribute significantly to the protection against cardiovascular diseases.^11,12 In this context, omega-3 fatty acids also seem to be important as an accompanying measure in metabolic syndrome. Due to their lipid-lowering and endothelprotective properties and influence on glucose homeostasis, omega-3 fatty acids are seen as an important part of overall therapy.¹³ Omega-3 fatty acids are used in type 2 diabetes to reduce the risk of arteriosclerotic and thrombogenic secondary diseases.¹⁴

Prevention of neurodegenerative and depressive diseases

In addition to cardiovascular prophylaxis, omega-3 fatty acids are neuroprotective¹⁵ and are an effective measure to reduce the risk of dementia. Several meta-analyses indicate an improvement in cognitive parameters in patients and a reduction in disease indices.¹⁶ An inhibition of proline endopeptidase in the brain of Alzheimer's patients is a possible mechanism of action, which can prevent memory loss.¹⁷
Omega-3 fatty acids can also positively influence the behavior and cognitive abilities of healthy people. Omega-3 supplementation is associated with increased attention and learning ability and with a generally improved mood profile due to increased vitality and reduced states of anger, anxiety and depression.¹⁸ Meta analysis increasingly confirm a significant antidepressant effect of omega-3 fatty acids, which indicates, supplementation may also be suitable as a therapeutic measure for depression and depressive moods.^19,20,21

Pregnancy and lactation: Omega-3 for infantile cerebral development

Omega-3 fatty acids are particularly important for the development of the fetus and the infant. It is assumed that the fetus accumulates about 30 mg omega-3 fatty acids per week in the brain. This influences both brain and vision development. From the beginning of the 3rd trimester, the supply of omega-3 fatty acids is particularly important, as the development of the central nervous system progresses strongly during this time. Since cerebral development extends into the first months of birth, breast milk contains a high concentration of omega-3 fatty acids, which is ultimately determined by the mother's intake levels. A lack of DHA in these critical phases in particular is associated with mental and psychomotor damage and visual function disorders in the child.¹ New epidemiological studies have shown that a high intake of omega-3 fatty acids in the form of fish during pregnancy can increase children's intelligence quotients in later life and improve social behavior.²²

Omega-3 fatty acids from fish oil must meet the highest purity requirements

When supplementing omega-3 fatty acids, it is essential to pay attention to the quality of the raw material. Only fish from clean waters with a seal of quality should be used as raw material. Special multi-stage molecular distillation processes enable the removal of foreign and harmful substances (oxidized foreign substances, dioxins and furans, polychlorinated biphenyls, heavy metals, polyaromatic hydrocarbons, etc.) and standardization of the EPA and DHA content. A concentration process guarantees a high EPA and DHA content of 33 % EPA and 22 % DHA. According to the study by the University of Innsbruck, most fish oil concentrates on the Austrian market cannot meet the pharmacological requirements for standardization and purity. Therefore, the use of standardized and purified omega-3 preparations is expressly recommended in prevention and therapy.¹

Linseed oil –the vegetable Omega-3 fatty acids

Linseed oil is obtained from the mature seeds of flax (Linum usitatissimum). It used to be a popular household remedy for cough, burns and stomach complaints, but today it is used preventively and therapeutically in naturopathy and in supportive micronutrient therapy due to its high proportion of the essential omega-3 fatty acid “alpha-linolenic acid“. While EPA and DHA are mainly used in prevention of inflammatory processes, alpha-linolenic acid is used to prevent cardiovascular diseases. Linseed oil can reduce the production of inflammation-promoting cytokines,²³ help to control total cholesterol and LDL levels,^6,7 reduce atherogenic plaque formation and vascular inflammation.^8,9 Linseed oil supplements also show a significant improvement in immune competence.²⁴ Studies suggest that the fatty acid ratio could also influence a person's psychosocial behavior. People with low omega-3 and high omega-6 ratio demonstrate different behaviors to people with high omega-3 and low omega-6 values.²⁵

Omega-3 fatty acids and their effects on muscles

Taking omega-3-rich krill oil may have a positive effect on muscle function and size in healthy people over 65. In a randomized, double-blind, controlled study conducted by the University of Glasgow, the administration of 4 g of krill oil to 102 relatively inactive men and women over 65 years of age showed an increase in thigh muscle strength of 9.3%, grip strength of 10.9% and thigh muscle thickness of 3.5% after 6 months, compared to the placebo group. Furthermore, it could also be observed that there was an increase in the fatty acid profile of red blood cells by 214% in EPA, 36% in DHA and 61% in the omega-3 index compared to the control group.²⁶

Reference values

Parameter	Substrate	Reference value	Description
Fatty acids (total)	Serum	1600 - 2900 mg/l	Fatty acid profile
Omega - 3 - fatty acids	EDTA	50 - 250 mg/l	Fatty acid profile, Omega - 3 - Index
Omega - 3 - Index (EPA and DHA)	EDTA	> 8,0 % FS	Omega - 3 - Index
EPA (20 : 5)	EDTA	11 - 33 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
Accelerated risk for	Arteriosclerosis, ADHD, depression, Alzheimer's disease

Indications

Effect	Indication	Dosage
Physiological effects at a low intake	For general health and prevention	1 - 1.5 g/d
	Therapeutic support for allergies, asthma bronchiale, allergic rhinitis, COPD, thyreoditis	1.5 - 4g/d
	For support of ADHS & hyperactivity	1 - 5 g/d
	Therapeutic support for depressions, dementia, Alzheimer's disease	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 a heart attack, arrhythmias and hypertension	1.5 - 6 g/d

Administration

General mode of administration
When	Omega-3 fatty acids should be taken with meals. Hint: The intake should be regular and long-term. The combination with antioxidants is recommended as undesirable lipid peroxidation can limit the biological effectiveness. Use in persons taking anticoagulants should be under medical supervision.
Side effects
Omega-3 fatty acids 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 requiring dose adjustment.
Contraindications
Acute pancreatitis, cirrhosis, gall bladder inflammation, coagulation disorders

Interactions

Drug interactions
Anticoagluants (e.g. Phenprocoumon, ASS)	Can prolong bleeding time and reduce platelet aggregation in high doses with vitamin K–antagonists or ASA (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 (methylphenidate)	Omega-3 fatty acids can improve the effectiveness of methylphenidate
Cholesterol-lowering drugs (statins)	Support of statin therapy by cardioprotective and lipid modulating effects of omega-3 fatty acids
Nutrient interactions
Glucosamine	Omega-3 fatty acids 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

Multiple unsaturated omega-3 type fatty acids

Related Substances

Fish oil concentrates:

Here EPA and DHA are bound as triglycerides.
The also available ester form is not approved in the EU.

Omega-3 vegetable fatty acids

Linseed oil (alpha-linolenic acid)
DHA-rich microalgae (Ulkenia sp., Schizochytrium sp.)

References

¹ Hahn, A. et al. 2006. Ernährung. Physiologische Grundlagen, Prävention, Therapie.
² Nannicini, F. et al. 2006. Alpha-linolenic acid and cardiovascular diseases, omega-3 fatty acids beyond eicosapentaenoic acid and docosahexaenoic acid. Minerva Cardioangiol. 54(4):431-42.
³ Volker, D. et al. 2000. Efficacy of fish oil concentrate in the treatment of rheumatoid arthritis. J Rheumatol. 27(10):2305-7.
⁴ Simopoulos, A. P. 2002. Omega-3 fatty acids in inflammation and autoimmune disease. J Am Coll Nutr. 21(6):495-505.
⁵ Holub, B. J. 2009. Docosahexaenoic acid (DHA) and cardiovascular disease risk factors. Prostaglandins Leukot Essent Fatty Acids.
⁶ Bloedon, L. T., Szapary, P. O. 2004. Flaxseed and cardiovascular risk. Nutr Rev. 62(1):18-27.
⁷ Luca, E. A. et al. 2004. Flaxseed reduces plasma cholesterol and atherosclerotic lesion formation in ovariectomized Golden Syrian hamsters. Atheriosclerosis. 173(2):223-9.
⁸Michael, H. 2006. Davidson, Mechanisms for the Hypotriglyceridemic Effect of Marine Omega-3 Fatty Acids. Am J Cardiol. 98(4A):27i-33i.
⁹ Kelley, D. S. et al. 1991. Dietary alpha-linolenic acid and immunocompetence in humans. Am J Nutr. 53(1):40-6.
¹⁰ Lukiw, W. J., Bazan, N. G. 2008. Docosahexaenoic acid and the aging brain. J Nutr. 138(12):2510-4.
¹¹ 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):153-68.
¹² Bowen, K. J. et al. 2016. Omega-3 Fatty Acids and Cardiovascular Disease: Are There Benefits? Current Treatment Options in Cardiovascular Medicine. 18(11).
¹³ Mukherjee PK, Chawla A, 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).
¹⁴ 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.
¹⁵ Cutuli, D. 2016. Functional and structural benefits induced by omega-3 polyunsaturated fatty acids during aging. Current Neuropharmacology CN. 14(999):1-1.
¹⁶ Issa, A. M. et al. 2006. The efficacy of omega-3 fatty acids on cogni tive function in aging and dementia: a systematic review. Dement Geriatr Cogn Disord. 21(2):88-96.
¹⁷ Park, Y. S. et al. 2006. Propyl endopeptidase inhibitory activity of unsaturated fatty acids. J Agric Food Chem. 54(4):1238-42.
¹⁸ Fontani, G. et al. 2005. Cognitive and physiological effects of omega-3 polyunsaturated fatty acid supplementation in healthy subjects. Eur J Clin Invest. 35(11):691-9.
¹⁹ Montgomery, P., Richardson, A. 2008. Omega-3 fatty acids for bipolar disorder. Cochrane Database Syst Rev. (2):CD005169.
²⁰ Lin, P. Y, Su, K. P. 2007. A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. J Clin Psychiatry. 68(7):1056-61.
²¹ Saunders, E. F. et al. 2016. Reconsidering Dietary Polyunsaturated Fatty Acids in Bipolar Disorder: A Translational Picture. The Journal of Clinical Psychiatry.
²² 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):39-44.
²³ James, M. J. et al. 2000. Dietary polyunsaturated fatty acids and inflammatory mediator production. Am J Clin Nutr. 71 (1 Suppl):343S-8S.
²⁴ Zhao, G. et al. 2004. Dietary alpha-linolenic acid reduces inflammatory and lipid cardiovascular risk factors in hypercholesterolemic men and women. J Nutr. 134(11):2991-7.
²⁵ Emanuele, E. et al. 2008. Serum omega-3 fatty acids are associated with ultimatum bargaining behaviour. Physiol Behav.
²⁶ Alkhedhairi, S. A. et al. 2022. The effect of krill oil supplementation on skeletal muscle function and size in older adults: A randomised controlled trial. Clin. Nutr. 41(6):1228-1235.

References Interactions
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