Omega-3 Docosapentaenoic Acid (DPA): What is known?

Omega-3 Docosapentaenoic Acid (DPA): What is known?

Did EPA and DHA overshadow the health benefits of DPA?

An invited health news highlight written by Dr. Gunveen Kaur, PhD, and Prof. Andrew Sinclair, PhD, Metabolic Research Unit, School of Medicine, Deakin University, Waurn Ponds, VIC, 3217, Australia.

Nutrition Remarks Health News Highlights (January 23, 2012)

What is omega-3 DPA?

Docosapentaenoic acid (DPA) is a dietary omega-3 fatty acid mainly found in fish, fish oil, seal oil and red meat. Its biological properties have not been thoroughly studied. Unlike, the other popular omega-3 fatty acids (EPA and DHA), DPA has not been extensively subjected to research due to the limited availability of the pure compound. However, the available scientific literature suggests that DPA also have beneficial health effects.

There is another form (isomer) of DPA known as omega-6 DPA. Omega-6 DPA content is low in most mammalian tissues, except testes tissue. The omega-3 isomer of DPA is substantially higher in fish & fish oils, than the omega-6 isomer.

Metabolism of omega-3 DPA

The laboratory studies conducted using liver cells have shown that omega-3 DPA and EPA are inter-convertible in the liver cells; however, there was little evidence of conversion of EPA and omega-3 DPA into DHA. This means omega-3 DPA can act as a source of EPA. Similarly, in animals, omega-3 DPA can also form EPA. However it does not appear to be readily metabolised to DHA, except in liver tissue. In addition to EPA production (retro-conversion to EPA), omega-3 DPA is found in a number of different tissues. Its specifically higher accumulation in heart and skeletal muscle and in kidneys compared with EPA suggests that omega-3 DPA might have beneficial effects in these tissues.

Beneficial effects of omega-3 DPA

Inhibition of thrombosis/aggregation in platelets: Platelet aggregation is an early event in the development of thrombosis and is initiated by thromboxin A2 (TXA2). The results from a study conducted in rabbit platelets showed that omega-3 DPA was the most potent inhibitor of COX-1 activity (the enzyme involved in synthesis of TXA2), thus inhibiting platelet aggregation most effectively. In a human whole blood study, omega-3 DPA was equally effective as EPA and DHA in inhibiting platelet aggregation in female subjects, however, in male subjects only EPA inhibited platelet aggregation.

Greater wound-healing/ability: Endothelial cell migration and proliferation are important processes in the control of wound-healing response of blood vessels. Direct pretreatment of endothelial cells with omega-3 DPA resulted in a dose-dependent increase in migration. Moreover, maximum stimulation of endothelial cell migration by omega-3 DPA pretreatment was achieved at a concentration one-tenth of that required for maximal stimulation by EPA pretreatment. Also, omega-3 DPA may have a positive role in preventing angiogenesis (new blood vessel formation) as omega-3 DPA pretreatment suppresses the bovine aortic endothelial cell tube-forming activity induced by vascular endothelial growth factor.

Alters expression of various genes: Very few studies have looked at the effects of pure DPA on expression of genes. However, in liver cells, omega-3 DPA has been shown to induce PPARα, which is involved in fat oxidation, but EPA and DHA had a stronger and more consistent effects. Omega-3 DPA reduces the expression of lipogenic genes in mice and liver cells. These genes are involved in synthesis of fat in the body. The mice fed with omega-3 DPA have also shown a reduction in liver triglyceride levels.

Omega-3 DPA is involved in the reduction of the expression of inflammatory genes such as tumor necrosis factor (TNF-α) in cell culture models. Inflammation in walls of blood vessels is thought to play a role in the development of atherosclerotic plaques and thus lead to cardiovascular disease (CVD). The action of omega-3 DPA in reducing the expression of inflammatory genes suggests its beneficial role in CVD and many other inflammation associated complications conditions including nervous system disease.

What amount of DPA is considered to be beneficial?

Recommended dietary intakes (RDI) are most commonly expressed for total long chain omega-3 fatty acids of which omega-3 DPA is a member. There is no recommendation for DPA alone. We need more scientific investigations to decide the exact amounts of omega-3 DPA that we need to eat through our or to take as supplements.

References –

1. Tam PS, Sawada R, Cui Y, Matsumoto A, Fujiwara Y. The metabolism and distribution of docosapentaenoic acid (n-6) in the liver and testis of growing rats. Biosci Biotechnol Biochem. 2008 Oct;72(10):2548-54.

2. Tam PS, Umeda-Sawada R, Yaguchi T, Akimoto K, Kiso Y, Igarashi O. The metabolism and distribution of docosapentaenoic acid (n-6) in rats and rat hepatocytes. Lipids. 2000 Jan;35(1):71-5.

3. Gundstone FD, Harwood JL, Padley FB. The Lipid Handbook. London: Chapman & Hall,; 1994.

4. Kaur G, Sinclair AJ, Cameron-Smith D, Barr DP, Molero-Navajas JC, Konstantopoulos N. Docosapentaenoic acid (22:5n-3) down-regulates the expression of genes involved in fat synthesis in liver cells. Prostaglandins, leukotrienes, and essential fatty acids. [Research Support, Non-U.S. Gov’t]. 2011 Sep-Oct;85(3-4):155-61.

5. Kaur G, Begg DP, Barr D, Garg M, Cameron-Smith D, Sinclair AJ. Short-term docosapentaenoic acid (22:5 n-3) supplementation increases tissue docosapentaenoic acid, DHA and EPA concentrations in rats. The British journal of nutrition. [Research Support, Non-U.S. Gov’t]. 2010 Jan;103(1):32-7.

6. Holub BJ, Swidinsky P, Park E. Oral docosapentaenoic acid (22:5n-3) is differentially incorporated into phospholipid pools and differentially metabolized to eicosapentaenoic acid in tissues from young rats. Lipids. 2011 May;46(5):399-407.

7. Akiba S, Murata T, Kitatani K, Sato T. Involvement of lipoxygenase pathway in docosapentaenoic acid-induced inhibition of platelet aggregation. Biol Pharm Bull. 2000 Nov;23(11):1293-7.

8. Phang M, Garg ML, Sinclair AJ. Inhibition of platelet aggregation by omega-3 polyunsaturated fatty acids is gender specific-Redefining platelet response to fish oils. Prostaglandins Leukot Essent Fatty Acids. 2009 Jul;81(1):35-40.

9. Kanayasu-Toyoda T, Morita I, Murota S. Docosapentaenoic acid (22:5, n-3), an elongation metabolite of eicosapentaenoic acid (20:5, n-3), is a potent stimulator of endothelial cell migration on pretreatment in vitro. Prostaglandins Leukot Essent Fatty Acids. 1996 May;54(5):319-25.

10. Tsuji M, Murota SI, Morita I. Docosapentaenoic acid (22:5, n-3) suppressed tube-forming activity in endothelial cells induced by vascular endothelial growth factor. Prostaglandins Leukot Essent Fatty Acids. 2003 May;68(5):337-42.

11. Pawar A, Jump DB. Unsaturated fatty acid regulation of peroxisome proliferator-activated receptor alpha activity in rat primary hepatocytes. J Biol Chem. 2003 Sep 19;278(38):35931-9.

12. Gotoh N, Nagao K, Onoda S, Shirouchi B, Furuya K, Nagai T, et al. Effects of three different highly purified n-3 series highly unsaturated fatty acids on lipid metabolism in C57BL/KsJ-db/db mice. J Agric Food Chem. 2009 Nov 25;57(22):11047-54.

13. Kishida E, Tajiri M, Masuzawa Y. Docosahexaenoic acid enrichment can reduce L929 cell necrosis induced by tumor necrosis factor. Biochim Biophys Acta. 2006 Apr;1761(4):454-62.

 

Written by Dr. Gunveen Kaur, PhD, and Prof. Andrew Sinclair, PhD

 

More about Prof. Andrew Sinclair, PhD

 

Copyright © 2011 Nutrition Remarks. All rights reserved


Omega 3 DHA, a good fat for a healthy nervous system

Omega 3 DHA, a good fat for a healthy nervous system

DHA acts against Alzheimer’s, stroke, epilepsy, and other brain and retinal diseases

Frontier Voice of Nutrition Remarks (January 04, 2012)

Nalin Siriwardhana, PhD, interviewed Boyd Professor Nicolas G. Bazan, M.D., Ph.D., the Director of the Louisiana State University Health Sciences Center (LSUHSC) Neuroscience Center of Excellence, New Orleans

Docosahexaenoic acid (DHA) is an omega-3 fatty acid that offers promising benefits against several brain and eye (retinal and corneal) diseases, including Alzheimer’s, Parkinson’s, and age-related macular degeneration (a disease associated with aging that gradually impairs sharp central vision). DHA is necessary for healthy vision, memory, brain development, and successful aging. Those benefits are in addition to the well-known cardioprotection effects of this essential fatty acid called DHA.

Recent scientific studies provide clear evidence to encourage the intake of DHA. The major dietary sources of DHA are cold water, fatty fish such as salmon, tuna, sardines, and shellfish. Fish oil capsules contain both Eicosapentaenoic acid (EPA) and DHA, while vegetarian capsules from algae contain DHA but no EPA.

The nervous system protection effects of DHA are closely associated with a molecule produced from DHA called neuroprotectin D1 (NPD1). Nutrition Remarks interviewed Prof. Bazan G. Nicolas, the discoverer of NPD1. His prolific research began over 40 years ago with the discovery in 1970 that the brain rapidly releases essential fatty acids when confronted with stroke -like conditions as well as in seizures, as in epilepsy. This finding became a Citation Classic and the process is known as the “Bazan effect”. A simplified version of the conversation between Nutrition Remarks and Dr. Basan is as follows.

Question from Nutrition Remarks: Why do we need DHA or omega-3 fats?

Answer from Dr. Bazan: Omega-3 fatty acids are required to maintain different aspects of our health. Omega-3 fats are essential because our bodies cannot produce them due to lack of the required enzymes. Therefore, we need to take omega-3 from dietary sources such as fish and fish oil supplements. Specifically, DHA is necessary for our vision, brain development, memory, nervous system function and protection, homeostasis (sustaining internal stability or balance of functions), and successful aging, etc.

Question: What makes our nervous system become vulnerable to disease?

Answer: Several factors contribute to nervous system diseases, including genetic factors, nutrition deficiencies of omega-3 fatty acids and antioxidants, and unhealthy behaviors that include excessive alcohol consumption and drug addictions. Also, chronic inflammation and oxidative stress play a significant role in nervous system diseases.

Question: Why is DHA important for a healthy nervous system?

Answer: DHA is required for the development, maintenance, and proper functioning of a healthy nervous system. Low levels or deficiency of DHA has been reported in several nervous system diseases including Alzheimer’s disease.

Question: According to published technical explanations including yours, excessive and unhealthy oxidative stress and inflammation in the nervous system can cause detrimental health consequences. What are the common short-term and long-term mechanisms?

Answer: Over-activation of the brain’s immune cells (primarily the microglial cells) or the arrival of white cells (polymorphonuclear leukocytes) enhances oxidative stress to an unhealthy level, setting in motion an inflammatory response that causes damage and eventually nerve cell death. Thus, inflammatory mediators and harmful reactive oxygen and nitrogen radicals become abundant and cause damage to the nervous system over a long period of time. This also includes imbalances in calcium homeostasis and impairments in the cell mitochondria, and the effects can even be extended to unfavorable cardiovascular conditions. Oxidative stress and inflammation in the nervous can lead to

  1. Short-term effects such as poor communication between neurons making them less sensitive and responsive to changes and stimulus. Also, this may lead to memory impairment.
  2. Long-term effects include the onset of neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease, age-related macular degeneration, glaucoma, epilepsy, multiple sclerosis, Huntington’s disease, amyotrophic lateral sclerosis, and tauopathies.

Question: How does DHA act against oxidative stress and inflammation in the nervous system?

Answer: An early nervous system response to oxidative stress, likely also in other organs, is the synthesis of protective molecules called docosanoids. Docosanoids are potent protective mediators derived from DHA available from cell phospholipids. The first identified docosanoid, NPD1, counteracts inflammation and oxidative stress, is anti-apoptotic (prevents cell death), and aims to restore homeostasis. Therefore it is important to maintain enough DHA in our body to fight against unhealthy inflammation and oxidative stress in the nervous system. Maintaining enough DHA not only protects us from nervous system disorders but also from other disease conditions including cardiovascular disease and some cancers.

Question: What would be the ideal level of DHA that we need to maintain in our body, and how often do we need to eat fish or take omega-3 supplements?

Answer: The American Heart Association recommends eating at least two servings/meals a week. Each serving is 3.5 ounces cooked, or about ¾ cup of flaked fish. However, we need more scientific investigation to decide the exact amounts that we need to eat or take as supplements to maintain a healthy nervous system. In general, we need to eat at least the recommended levels as most of us do not have enough DHA in our body.

At present, due to growing interest, there are several upcoming and ongoing clinical trials on omega 3-fats.

Boyd Professor Nicolas G. Bazan, M.D., Ph.D.,

Boyd Professor Nicolas G. Bazan, M.D., Ph.D.,

Original work: Bazan et. al., Docosahexaenoic Acid Signalolipidomics in Nutrition: Significance in Aging, Neuroinflammation, Macular Degeneration, Alzheimer’s, and Other Neurodegenerative Diseases, Annual Review of Nutrition Vol 31: 321-351(2012).

Nicolas G. Bazan, M.D., Ph.D., is a professor of ophthalmology, biochemistry and molecular biology, neurology and neuroscience at School of Medicine, Louisiana State University Health Sciences Center, and founding director of LSU’s Neuroscience Center of Excellence. He is the occupant of the Ernest C. and Ivette C. Villere Chair for Retinal Degeneration Research and the Chair of the LSUHSC Research Council/Translational Research Initiative. Other leadership responsibilities of Dr Bazan includes Senat Member of the German DZNE, a member of an NIH Study Section and the Chair of the Board of Governors of AFER (ARVO Foundation for Eye Research) He and his colleagues discover NPD1 and several other fundamental mechanisms through which essential fatty acids DHA and arachidonic acid regulate cell function and participate in the initiation and early progression of diseases. Through his research on synaptic signaling pathways he hopes to develop ways to reduce or prevent the irreversible brain damage caused by stroke, epilepsy, and neurodegenerative disease, as well as retinitis pigmentosa and age-related macular degeneration.

More about Dr. Bazan’s work and related links

http://www.medschool.lsuhsc.edu/neuroscience/faculty_detail.aspx?name=bazan_nicolas

http://www.fivestarpublications.com/unavida/

http://www.sciencedaily.com/releases/2011/09/110928185021.htm

http://www.eurekalert.org/pub_releases/2011-09/lsuh-lrd092811.php

http://www.medschool.lsuhsc.edu/neuroscience/NB%20weeks%20citation%20classic001.pdf

http://www.archive.org/details/LetsGetHealthyWithBillSwail122711Hour1

http://www.archive.org/details/GoodNewsHealthShow12-31-11hour2

The authors acknowledge the following:

Dr. Bazan acknowledges the support of NINDS, NEI, former NCRR, RPB, National Foundation Fighting Blindness, Arnold and Mabel Beckman Initiative for Macular Degeneration Research and the EENT Foundation.

Written by Nalin Siriwardhana, PhD

Copyright © 2011 Nutrition Remarks. All rights reserved.