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News - Is DHA harmful? EPA and DHA - the natural balance

By Nutri People

A lot has been written in product leaflets in recent years suggesting that EPA (eicosapentaenoic acid) is more beneficial than DHA (docosahexaenoic acid) and that DHA may inhibit EPA activity or might even be harmful.

It has also been claimed that DHA is an unwanted substance or impurity and that DHA supplements are unnecessary because DHA can be naturally produced from EPA in the body.  EPA supplements are available, which boldly claim to have “NO DHA”.  Where does this “EPA is good, DHA is bad” message come from and why?

EPA and DHA are long-chain polyunsaturated fatty acids (PUFAs) belonging to the omega 3 series of fatty acids. They are formed in the body from alpha-linolenic acid (ALA), an omega 3 essential fatty acid(1), which is obtained from oily fish and fish oils, flax seed oil and a limited number of other vegetable oils; ALA is not manufactured in the body. The conversion of ALA to DHA is thought to be 1% in infants and even lower in adults(2), pointing to a requirement for DHA in the diet.

DHA and EPA are both preferentially incorporated into all cell membranes and increase membrane fluidity.

EPA converts to DHA, albeit slowly and inefficiently, in humans. DHA can also convert back to EPA. This sluggish conversion suggests the need for preformed DHA in the diet to adequately supply the brain, cardiovascular system and other organs(3).

Modern man (homosapiens) developed a large brain as a consequence of eating a high-fish diet in his early ancestry. In fact, 60% of the brain’s dry weight is composed of fat, of which PUFAs form the largest part(4). DHA and AA (arachidonic acid) are the main PUFAs in the brain(5) and nervous system(6) AA is formed in the body from omega 6 linoleic acid (LA), found in seed oils such as sunflower, flax and borage. It is also present in fish and meat(1).  

Oily fish naturally supply both EPA and DHA. A 100g portion of cooked, wild Atlantic salmon, for example, provides 2.218g of omega 3 fatty acids, of which 0.411g is EPA, 1.429g is DHA and 0.378g is ALA(7).

If DHA is unwanted or harmful, perhaps we should stop eating fish altogether?

All the evidence would suggest not. In Western diets, membranes contain higher ratios of omega 6 PUFAs to omega 3 PUFAs including large quantities of AA(8). AA can play a significant and potentially harmful role in inflammatory processes in cells and organs.

According to Professor Crawford from the Institute of Brain Chemistry and Human Nutrition at the London Metropolitan University(9), the brain uses only DHA and not EPA. EPA does not have the same relevance for brain function and composition as DHA. All animals and humans use DHA to create synaptic structures, neurons and photoreceptors in their eyes and have done so for millions of years. A recent article in the Journal of Neurochemistry supports this view(10).

DHA is also required for development of sensory, perceptual, cognitive and motor neural systems during the period of rapid growth seen in the brain during foetal development and the first two years of life (11,12). The placenta is also known to selectively transfer DHA to the human foetus in preference to other Omega 3s(13,14).

The role of EPA in inter-utero development is less clear, but it is present in small amounts in both colostrum and breast milk (15,16). 

It has now been established that the brain is reliant on both DHA and EPA in adulthood and that the adult brain cortex undergoes synaptic turnover throughout life. The central role that DHA plays in foetal brain development appears to continue in adult life (17,18). 

Health benefits

There are many studies demonstrating a positive effect of fish-source DHA and omega 3 fatty acids. For example, a three month, Japanese double-blind, placebo-controlled study assessed the effect of daily supplementation with high potency DHA capsules on the negative behaviour of final year medical students. At the end of the study (exam time), students taking high DHA supplements remained calm, whereas those on placebo displayed increased aggression and hostility(19).

A double-blind, placebo-controlled, four month study in 30 people with bipolar disorder assessed the effect of either 9.6g per day of omega 3 fatty acids (EPA and DHA) or olive oil, in addition to their usual treatment. Results showed that people taking omega 3 demonstrated a significantly longer remission period that those on olive oil(20).

In 1999, the Lancet published the GISSI-Prevenzione study, which involved over 11,000 patients with heart attacks.

Researchers found that those who supplemented with Omega 3s, but not vitamin E, significantly reduced their risk of cardiovascular (CV) death, non-fatal heart attack or stroke. In the first year of the study, there was a 40% reduction in CV death(21).

There is now mounting evidence from both epidemiological studies and dietary intervention trials to support cardio-protective role of DHA/EPA-rich fish oil. Beneficial effects reported include regulation of eicosanoid production, plasma triacylglycerol and blood pressure lowering effects, regulation of ion flux in cardiac cell plus modification of serum markers for cardiovascular disease(22).

The importance of DHA in modulating inflammation is now well accepted. It is metabolised to form protective compounds: resolvins and neuroprotectins that inhibit the generation of pro-inflammatory prostaglandins, leukotrienes and thromboxanes. These increase during trauma, particularly in acute neural trauma and neurodegenerative disease. DHA and its lipid mediators can thus limit neuro-inflammation and the resultant damage of oxidative processes. This is caused by pro-inflammatory prostaglandins, that are the result of oxidation of AA in membranes.

Dietary intakes of DHA can, thus, counterbalance the potentially harmful effects of inflammatory processes in the brain and retina of the eye (23,24).

All the evidence strongly indicates that DHA is neither harmful nor an “impurity”. On the contrary, it is essential for normal development and health. 

EPA Benefits

Isolated EPA may be of benefit in mental health disorders, such as bipolar disorder(25), Huntington’s disease(26), anorexia nervosa(27), schizophrenia(28) and depression(29).

These studies involved the use of a semi-synthetic, highly purified derivative of EPA, called ethyl-EPA, which is not a natural component of fish oil. It is not known whether ethyl-EPA can be converted in the body to DHA. Ethyl-EPA has been synthesised by chemically adding an ethyl group to EPA and is a pharmaceutical, rather than a food supplement. Ethyl-EPA is not identical to the EPA in ordinary fish oils.

A pilot study, published in 2004, investigated the efficacy of ethyl-EPA in Alzheimer’s disease. Researchers concluded that during the 12-week study period, any clinically important effects of ethyl-EPA on cognition were unlikely and that a longer study period might be required to show ethyl-EPAs benefit in alzheimer’s(30).

A 12-month, double-blind, multi centre, randomised, placebo-controlled trial, published in 2005, investigated the effects of ethyl-EPA in Huntington’s disease. It concluded that ethyl-EPA showed no benefit for patients with Huntington’s. However, a significantly higher proportion of the other patients demonstrated stable or improved motor function. Further studies were warranted to investigate the potential efficacy of ethyl-EPA(31).

A placebo-controlled trial using ethyl-EPA in schizophrenia concluded that patients on ethyl-EPA showed no more improvement in either residual symptoms or cognitive impairment than patients on placebo(32).

A further study involved one patient with non-treatable depression, who responded positively to ethyl-EPA supplementation(33). However, the positive clinical observations involved only one patient and cannot automatically be applied to other patients with illness, or the general population.

In summary, both EPA and DHA are beneficial but with different functions, with DHA being widely recognised as a physiologically essential nutrient in the brain for normal function and in the retina for visual acuity.

Going back to basics, early humans evolved on a diet of fish, and not on modified EPA (ethyl-EPA) or DHA alone. Societies with traditional, non-Western, high fish diets report lower incidences of mental health problems, cardiovascular disorders, arthritis and skin problems.

Ethyl-EPA may have a future benefit as a pharmaceutical product to treat specific and severe neurological or mental health disorders where dietary levels of EPA would be insufficient.

At Higher Nature, we are concerned that while there may well be a benefit for ethyl-EPA as a treatment for these medical conditions, to apply these findings to the wider area of nutrition, and exclude DHA, is misleading and goes against the evidence.

We maintain that a balance of EPA and DHA, as provided by nature in the fish oils that helped us develop the large brains we now possess, is the correct form of supplementation. 

Article References

1. Mary G Enig PhD. Know your Fats. Bethesda Press, 2000. 2. Brenna JT, Salem N, Sinclair AJ, Cunnane SC. Alpha linolenic acid supplementation and conversion to n-3 long chain polyunsaturated fatty acids in humans. Prostagladins, Leukotrienes, and Essential Fatty Acids 2009,80 (2-3);85-91. 3. Arterburn LM, Hall EB, Oken H. Distribution, interconversion and dose response of n-3 fatty acids in humans. Am L Clin Nutr 2006;83:1467S-1476S. 4. Crawford MA, Cunnane S, Harbige LS. A New Theory of Evolution: Quantum Theory in Essential Fatty Acids and Eicosanoids. AOCS, 1992: p87-95. 5. www.fish-foundation.org.uk/references3.htm#Crawford. 6. Marszalek JR, Lodish HF. Docosahexaenoic acid, fatty acid-interacting proteins, and neuronal function: breastmilk and fish are good for you. Annual Review Cell Dev Biol. 2005;21:633-57. 7. www.numarkpharmacists.com/hn/Food_Guide/Salmon.htm. 8. Calder PC. Dietary modification of inflammation with lipids. Proc NutrSoc 2002, 61(3): 345-358. 9. Professor Crawford, Director, Institute of Brain Chemistry and Human Nutrition, London Metropolitan University, 31 Jewry Street, London, EC3N 2EY. 10. Cao D et al. Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function. J. Neurochem. 2009 Aug 13. E-published ahead of print. 11. McCann JC, Ames BN. Is docosahexaenoic acid, an n-3long chain polyunsaturated fatty acid, required for development of normal brain function? An overview of evidence from cognitive and behavioural tests in humans and animals. Am J Clin Nutr 2005; 82:281-95. 12. SanGiovanni JP, et al. Meta–analysis of dietary essential fatty acids and long chain polyunsaturated fatty acids as they relater to visual resolution acuity in healthy preterm infants. Paediatrics. 2000; 105:1292-1298. 13. Bazan NG. Lipid signaling in neural plasticity, brain repair, and neuroprotection. Mol Neurobiol. 2005 Aug;32(1):89-103. 14. Crawford MA, Hassam AG, Williams G. Essential fatty acids and fetal brain growth. Lancet. 1976 Feb 28;1(7957):452-3. 15. Morgan C, Davies L et al. Fatty acid balance studies in infants fed formula milk containing long chain polyunsaturated fatty acids. Acta Paediatrica 1998; 87: 136-142. 16. Young C, et al. Fatty acid compositions of colostrum, cord blood, maternal blood and major infant formulae in Japan. Acta Paediatrica Jpn. 1997;39:299-304. 17. Doidge N. The brain that changes itself. New York Viking Press 2007. 18. Bower B Grown up connections. Mice, monkeys remake brain links as adults. Sci News. 2006; 169:165. 19. Hamazaki T et al. The effect of docosahexaenoic acid on aggression in young adults. A placebo-controlled double-blind study. J Clin Invest, 1996, 97(4): 1129-33. 20. Stoll AL et al. Omega 3 fatty acids in bipolar disorder - A preliminary double-blind, placebo-controlled trial. Archives of General Psychiatry,1999:56(5);407-412. 21. No authors listed. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Lancet. 1999 Aug 7;354(9177):447-55. 22. Anderson BM, Ma DWL. Are all polyunsaturated fatty acids created equal? Lipids in Health 2009, 8:33 Epub ahead of print. 23. Bazan NG. Neuroprotectin D1 (NPD1): a DHA-derived mediator that protects brain and retina against cell injury-induced oxidative stress. Brain Pathol, 2005, 15(2):159-66. 24. Farooqui AA, Horrocks LA, Farooqui T. Modulation of inflammation in brain: a matter of fat. J. Neurochem,2007, 101(3):577-99. 25. Frangou S, Lewis M, McCrone P. Efficacy of ethyl-eicosapentaenoic acid in bipolar depression: randomised double-blind placebo-controlled study. Br J Psychiatry. 2006 Jan;188:46-50. 26. Puri BK, Bydder GM, Counsell SJ, Corridan BJ, Richardson AJ, Hajnal JV, Appel C, Mckee HM, Vaddadi KS, Horrobin DF. MRI and neuropsychological improvement in Huntington disease following ethyl-EPA treatment. Neuroreport. 2002 Jan 21;13(1):123-6. 27. Ayton K, Azaz A, Horrobin DF. A pilot open case series of ethyl-EPA supplementation in the treatment of anorexia nervosa. Prostaglandins Leukot Essent Fatty Acids. 2004 Oct;71(4):205-9. 28. Yao JK, Magan S, Sonel AF, Gurklis JA, Sanders R, Reddy RD. Effects of omega-3 fatty acid on platelet serotonin responsivity in patients with schizophrenia. Prostaglandins Leukot Essent Fatty Acids. 2004 Sep;71(3):171-6. 29. Peet M. Eicosapentaenoic acid in the treatment of schizophrenia and depression: rationale and preliminary double-blind clinical trial results. Prostaglandins Leukot Essent Fatty Acids. 2003 Dec;69(6):477-85. 30. Boston PF, Bennett A, Horrobin DF, Bennett CN. Ethyl-EPA in Alzheimer's disease-a pilot study. Prostaglandins Leukot Essent Fatty Acids. 2004 Nov;71(5):341-6. 31. Puri BK, Leavitt BR, Hayden MR, Ross CA, Rosenblatt A, Greenamyre JT, Hersch S, Vaddadi KS, Sword A, Horrobin DF, Manku M, Murck H. Ethyl-EPA in Huntington disease: a double-blind, randomized, placebo-controlled trial. Neurology. 2005 Jul 26;65(2):286-92. 32. Fenton WS, Dickerson F, Boronow J, Hibbeln JR, Knable M. A placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia. Am J Psychiatry. 2001 Dec;158(12):2071-4. 33. Puri BK, Counsell SJ, Hamilton G, Richardson AJ, Horrobin DF. Eicosapentaenoic acid in treatment-resistant depression associated with symptom remission, structural brain changes and reduced neuronal phospholipid turnover. Int J Clin Pract. 2001 Oct;55(8):560-3.

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