Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) are recommended for management of patients with wide-ranging chronic diseases, including coronary heart disease, rheumatoid arthritis, dementia, and depression. Increased consumption of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is recommended by many health authorities to prevent (up to 0.5 g/day) or treat chronic disease (1.0 g/day for coronary heart disease; 1.2–4 g/day for elevated triglyceride levels). Recommendations for dietary intake of LC n-3 PUFAs are often provided for α-linolenic acid, and for the combination of EPA and DHA. However, many studies have also reported differential effects of EPA, DHA and their metabolites in the clinic and at the laboratory bench. The aim of this article is to review studies that have identified divergent responses to EPA and DHA, and to explore reasons for these differences. In particular, we review potential contributing factors such as differential membrane incorporation, modulation of gene expression, activation of signaling pathways and metabolite formation. We suggest that there may be future opportunity to refine recommendations for intake of individual LC n-3 PUFAs (1).

Available evidence from  randomized controlledt rials indicates that provision of eicosapentaenoic and docosahexaenoic acids reduces systolic blood pressure, while provision of ≥2 grams reduces diastolic blood pressure (2).

Dietary n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with reduction of inflammation, although the mechanisms are poorly understood, especially how the spleen, as a secondary lymphoid organ, is involved. To investigate the effects of EPA and DHA on spleen gene expression, male C57BL/6J mice were fed high fat diets (HFD) differing in fatty acid composition, either based on corn oil (HFD-CO), or CO enriched with 2 g/100 g EPA and DHA (HFD-ED), for eight weeks. Spleen tissue was analyzed using transcriptomics and for fatty acids profiling. Biological processes (BPs) related to the immune response, including T-cell receptor signaling pathway, T-cell differentiation and co-stimulation, myeloid dendritic cell differentiation, antigen presentation and processing, and the toll like receptor pathway were downregulated by HFD-ED compared with control and HFD-CO. These findings were supported by the down-regulation of NF-κB in HFD-ED compared with HFD-CO fed mice. Lower phospholipid arachidonic acid levels in HFD-ED compared with HFD-CO, and control mice suggest attenuation of pathways via prostaglandins and leukotrienes. The HFD-ED also upregulated BPs related to erythropoiesis and hematopoiesis compared with control and HFD-CO fed mice. Our findings suggest that EPA and DHA down-regulate the splenic immune response induced by HFD-CO, supporting earlier work that the spleen is a target organ for the anti-inflammatory effects of these n-3 fatty acids (3).

References___________________________________

(1) Distinguishing Health Benefits of Eicosapentaenoic and Docosahexaenoic Acids
Fraser D. Russell, Corinna S. Bürgin-Maunder
Mar Drugs. 2012 Nov; 10(11): 2535–2559. Published online 2012 Nov 13. doi: 10.3390/md10112535

(2) Long-Chain Omega-3 Fatty Acids Eicosapentaenoic Acid and Docosahexaenoic Acid and Blood Pressure: A Meta-Analysis of Randomized Controlled Trials
Paige E. Miller, Mary Van Elswyk, Dominik D. Alexander
Am J Hypertens. 2014 Jul; 27(7): 885–896. Published online 2014 Mar 6. doi: 10.1093/ajh/hpu024

(3) Splenic Immune Response Is Down-Regulated in C57BL/6J Mice Fed Eicosapentaenoic Acid and Docosahexaenoic Acid Enriched High Fat Diet
Nikul K. Soni, Alastair B. Ross, Nathalie Scheers, Otto I. Savolainen, Intawat Nookaew, Britt G. Gabrielsson, Ann-Sofie Sandberg
Nutrients. 2017 Jan; 9(1): 50. Published online 2017 Jan 10. doi: 10.3390/nu9010050

The name describes the structure of the molecule:

• "Docosa-" is derived from the Greek word for 22, indicating that the molecule has 22 carbon atoms.
• "-hexaenoic" indicates that there are six double bonds in the molecule.
• "Acid" refers to the presence of a carboxylic acid group (-COOH) in the molecule.

The synthesis of DHA in nature typically involves the elongation and desaturation of alpha-linolenic acid (ALA), a shorter-chain omega-3 fatty acid. Here is a simplified version of the process:

• ALA is first desaturated by the enzyme delta-6-desaturase to produce stearidonic acid.
• Stearidonic acid is then elongated to produce eicosatetraenoic acid.
• Eicosatetraenoic acid is desaturated again to produce eicosapentaenoic acid (EPA).
• EPA is elongated to produce docosapentaenoic acid.
• Finally, docosapentaenoic acid is desaturated to produce DHA.

It appears as a yellow liquid.

What it is for and where

• neurotransmission
• neurogenesis
• myelination
• synaptic plasticity
• neuroinflammation
• membrane integrity
• membrane organization

DHA is rapidly accumulated in the brain during gestation and early childhood. The consumption of DHA leads to many positive physiological and behavioral effects, including those on cognition. Cognitive changes throughout the life span correspond to the development, maturation and aging of the brain. The brain is an organ rich in lipids that consumes 20% of the body's energy, but includes only 2% of the body's mass. Quantitatively, docosahexaenoic acid (DHA; 22: 6 n -3) is the most significant n -3 PUFA in the brain while both eicosapentaenoic acid (EPA; 20: 5 n -3) and alpha-linolenic acid ( ALA; 18: 3 n -3) are present only in very small quantities (1).

Docosahexaenoic acid (DHA) is maintained and concentrated solely in the nervous system, particularly in photoreceptors and in synaptic membranes. DHA plays a key role in vision, neuroprotection, aging, memory and other functions (2).

Medical

• Neurology. DHA is crucial for brain health. It is one of the main structural components of neurons in our brain and is important for both the development and functioning of the brain throughout life.
• Psychiatry. DHA has proven useful in the treatment of major depressive disorder. It has the potential to improve the brain's responses to emotional stimuli.
• Ophthalmology. DHA is an important structural component of the retina of the eye. It is needed to maintain normal retinal function.
• Cardiovascular system. DHA helps reduce inflammation and improve cardiovascular function.
• Spinal cord. Research has shown that DHA can contribute to neuroprotection and promote neuroplasticity after spinal cord injury.
• Oncology. DHA is being studied for its potential use in the treatment of cancer. It has been used in combination with other drugs to improve the efficacy of cancer therapies.

Cosmetics

Antistatic agent. Static electricity build-up has a direct influence on products and causes electrostatic adsorption. The antistatic ingredient reduces static build-up and surface resistivity on the surface of the skin and hair.

Skin conditioning agent. It is the mainstay of topical skin treatment as it has the function of restoring, increasing or improving skin tolerance to external factors, including melanocyte tolerance. The most important function of the conditioning agent is to prevent skin dehydration, but the subject is rather complex and involves emollients and humectants that can be added in the formulation.

Skin health. DHA is often used in skin care products due to its anti-inflammatory properties. It can help reduce skin inflammation and the effects of ageing.

Tanning products. DHA is the active ingredient in most sunless tanning products. It interacts with the dead surface cells of the epidermis to darken skin colour and simulate a tan.

Docosahexaenoic acid studies

Molecular Formula  C₂₂H₃₂O₂

Molecular Weight   328.5 g/mol

CAS   25167-62-8

References______________________________________________________________________

(1) Michael J. Weiser, Christopher M. Butt, M. Hasan Mohajeri  Docosahexaenoic Acid and Cognition throughout the Lifespan  Michael J. Weiser, Christopher M. Butt, M. Hasan Mohajeri
Nutrients. 2016 Feb; 8(2): 99. Published online 2016 Feb 17. doi: 10.3390/nu8020099

(2) Nicolas G. Bazan, Miguel F. Molina, William C. Gordon Docosahexaenoic Acid Signalolipidomics in Nutrition: Significance in Aging, Neuroinflammation, Macular Degeneration, Alzheimer’s, and Other Neurodegenerative Diseases  Annu Rev Nutr. Author manuscript; available in PMC 2012 Jul 27.  Published in final edited form as: Annu Rev Nutr. 2011 Aug 21; 31: 321–351. doi: 10.1146/annurev.nutr.012809.104635