Omega-3 Essentials: Health Benefits

Omega-3 fatty acids are a growing market, with global finished product sales of US$24.5 billion in 2011 and expected to hit US$34.5 billion by 2016, according to Packaged Facts. The growth is coming from many different angles, as formulators have been increasingly incorporating omega-3s into all different types of products, from dietary supplements and fortified foods/beverages to pet foods and infant nutrition. The driving force behind this omega-3 spread has been a rapidly expanding body of research and education on the numerous potential health benefits of increased omega-3 intake. Formulators have also confronted several challenges to including omega-3 ingredients into food, beverages and other new applications.

Omega-3s are active in the body's inflammatory cascade, where they can release chemical signals for anti-inflammation. As anti-inflammatory, omega-3s can be helpful in numerous health situations, including joints, blood vessels and various membranes. However, the bulk of influential research has been on benefits to various organs, including the heart and the brain.

Research analysis from Dariush Mozaffarian, M.D., Harvard University, Boston, found modest consumption of fish (one to two servings per week), especially species higher in the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduced the risk of coronary death by 36 percent and total mortality by 17 percent.¹ He noted intake of 250 mg/d of EPA and DHA appeared sufficient for primary prevention. For the various individual cardiovascular effectsanti-arrhythmia, anti-thrombosis, and lowering of triglycerides, heart rate and blood pressurethe positive effect seems to plateau at about 750 mg/d EPA/DHA intake. He noted the effects on arrhythmias and thrombosis take weeks to materialize, while the effects on triglycerides, heart rate and blood pressure take months to years to manifest.

Mozaffarian pointed out for consumers to reach the 250-mg/d EPA/DHA dose found to provide adequate heart health protection, they would have to consume 10 servings of catfish, 11 servings of cod, four servings of halibut, six servings of light tuna or almost six servings of shrimp per week. Salmon and anchovies are richer sources, requiring only one serving per week to meet the intake level, but Americans generally do not consume much seafood on such a regular basis, so many have turned to dietary supplements to boost their omega-3 intake.

One indicator of omega-3 heart health may be the Omega-3 Index, a measure of the amount of EPA and DHA in red blood cells (RBCs), expressed as a percent of total fatty acids. Clinical and laboratory research from William Harris, Ph.D., America Heart Institute of St. Luke's Hospital, Kansas City, MO, and his team demonstrated the Omega-3 Index was inversely associated with risk for coronary heart disease (CHD) mortality.² He noted an Omega-3 Index of 8 percent or greater was associated with the greatest cardioprotection, while and index of 4 percent or less was linked to the least protection. Harris noted the average index score in Japan, where CHD is rare, is 9 to 10 percent.³ Additional research has shown 8 percent or higher omega-3 index reduces probability for acute coronary syndrome,⁴ and on the low end, an index of 4 percent or lower is associated with accelerated brain aging.⁵ Overall, the Omega-3 Index is inversely associated with the rate of cellular aging and mortality.⁶

On the opposite end of the aging continuum, brain development in babies is dependent on DHA. Babies breastfed by mothers supplementing with DHA showed improved brain and eye development.⁷ Further, plasma DHA levels in pregnant women may play a role in the development of the central nervous system in the fetus.⁸ Bruce Holub, Ph.D., University of Guelph, Ontario, noted DHA levels in the brain increase about 30-fold from about 24 weeks gestation to about 2 years of age. DHA concentrates in the phospholipid-rich brain and retina, he explained.

Not getting enough DHA in the womb can have negative consequences in the first few years after birth. Lack of adequate DHA intake (340 g/d seafood threshold) during pregnancy (data assessed at 32 weeks) increased the risk of the children having suboptimum cognitive outcomes, such as prosocial behavior, fine motor, communication and social development scores.⁹

DHA doesn't favor the just the young and old. Middle-aged adults with high serum levels of DHA may perform better on cognitive function tests.¹⁰ EPA and ALA (alpha linolenic acid, a precursor to EPA and DHA) do not appear to confer the same benefit. Healthy adults may also improve visual acuity with DHA supplementation.

For many adults, the real benefit of increased omega-3 intake is in the protective effect demonstrated in research. Nicolas Bazan, M.D., Ph.D., Louisiana State University, documented DHA's neuroprotection of the brain, including protection from gene mutation in diseases such as Parkinson's and Huntington's.¹¹ Bazan explained DHA concentrates in photoreceptors and synapses (important signaling structures between neurons) more than in any other cell membrane in the body. While DHA in the brain and eye helps with memory formation, excitable membrane (e.g., neuron) function, photoreceptor cell biogenesis and function, and neuron signaling, the omega-3 also helps protect the brain by enhances synthesis of neuroprotectin D1 (NPD1), which inhibits oxidative stress-induced apoptosis (cell death).¹² Bazan said this mechanism may be key to DHA's protection in stroke, macular degeneration, glaucoma, Alzheimer's disease, epilepsy, dry eye and other diseases.

DHA administered after brain trauma can protect the organ from related damage.¹³ In fact, the researchers from West Virginia University, Morgantown, suggested a potential benefit in providing DHA to groups at high risk of traumatic brain injury, such as military personnel and athletes in contact sports. Adina Michael-Titus, Ph.D., Centre for Neuroscience and Trauma at Queen Mary University of London, researched the effects of DHA on spinal cord injuries, both hemisection and compression, and found administration of DHA immediately following the trauma can help limit the extent of the head and spinal cord injury, while continued DHA intake in the weeks and months following injury can help recovery.

While supplement companies are not allowed to market omega-3s for such acute benefits as in cases of serious trauma, including the sports head injuries currently in the sports medicine spotlightin the research by Michael-Titus, DHA was given intravenouslythe research provides good insight into how omega-3s, especially DHA, can protect the brain.

DHA has dominated omega-3 research, perhaps because it is the end result of the series of conversions in the body. ALA is a true essential fatty acid (EFA), in that it can not be synthesized in the body and must come from the diet. The body can convert ALA to EPA, but most omega-3 experts report the conversion rate is generally poor. The omega-6 linoleic acid (LNA) may compete for the same conversion enzymes; given the typical American diet is overloaded with omega-6 fats, ALA conversion to EPA might suffer from this competitiona greater synthesis of arachidonic acid (AA), which tends to be proinflammatory, from LNA may result. Genetic influence on the desaturase and elongation enzymes that convert fatty acids also may be a factor, as may be deficiencies of micronutrients cofactors to the conversion enzymes. Hormones may also impact conversion of ALA to EPA, as women tend to have higher conversion rates than do men, possibly due to estrogen. With such a reportedly poor conversion, EPA is practically essential, as are omega-3s further along the conversion pathway, including docosapentaenoic acid (DPA) and DHA.

As the end of the conversion pathway, DHA is bigger than DPA, and both are bigger than EPA. The size and characteristics of these omega-3s can dictate their activities in the body. For instance, EPA is more easily oxidized, which inhibits its concentrations in brain membranes, but it also means it can produce eicosanoids, oxygenated derivatives that mediate inflammation and thrombosis. On the other hand, DHA's larger size helps it concentrate in brain and eye membranes, helping to keep receptors and synapses fluid and healthy. Its size also enables DHA to increase the size of LDL particles, limiting their entry into the endothelial wall. DHA, via LOX enzymes, can produce resolvins and protectins, eicosanoid-like signaling molecules collectively called docosanoids. DPA and EPA make some docosanoids, but to a lesser degree than does DHA.

Resolvins help resolve inflammation, thereby preventing a chronic inflammatory state, which can lead to numerous health problems. Protectins, such as neuroprotectin D1, protect membranes from attack complexes that were activated by pathogens such as bacteria or viruses. Charles Serhan, Ph.D., Harvard Medical School, explained D series resolvins and protectins (derived from DHA) and E series resolvins (derived from EPA) can help resolve inflammatory situations in arthritis, bacteria infection (e.g., E. coli), colitis, asthma, periodontal disease and ocular inflammation.

Alone and in tandem with DHA, EPA has demonstrated protective effects against inflammation, including in the eyes and joints;^14,15 may help alleviate depression by reducing cortisol levels;¹⁶ and has a modest effect on symptoms of attention deficit/hyperactivity disorder (ADHD).¹⁷

EPA appears to inhibit COX and LOX enzymes from converting AA into eicosanoids, including prostaglandin H2 (PGH2, pro-inflammatory) and thromboxane A2 (TXA2, prothrombotic).¹⁸ Incidentally, aspirin inhibits PGH2 and, therefore, TXA2 as well. EPA's competitive advantage over AA and associated inflammatory mediators in the desaturase pathway makes it the primary omega-3 for inflammation management.

DPA is an elongated version of EPA and has some similar effects. Compared to EPA and DHA, DPA was more potent at inhibiting both AA-associated platelet aggregation and TXA2 formation in the platelets.¹⁹ Higher plasma concentrations of DPA and EPA were associated with a lower risk of heart attacks in women, according to Harvard research.²⁰ DPA may also improve wound healing by encouraging blood vessel repair via stimulation of endothelial cell migration;²¹ this effect is similar to that of EPA.

Find more omega-3 insights in:

References Listed on the next page.

References:

1. Mozaffarian D and Rimm EB. "Fish intake, contaminants, and human health: evaluating the risks and the benefits." JAMA. 2006;296(15):1885-99.

2. Harris WS and Schacky CV. "The omega-3 index: a new risk factor for death from coronary heart disease?" Prev Med. 2004;39:212-220.

3. Itomura M et al. "Factors influencing EPA+DHA levels in red blood cells in Japan." In Vivo. 2008 Jan-Feb;22(1):131-5.

4. Block RC et al. "EPA and DHA in blood cell membranes from acute coronary syndrome patients and controls." Atherosclerosis. 2008 Apr;197(2):821-8.

5. Tan ZS et al. "Red blood cell ω-3 fatty acid levels and markers of accelerated brain aging." Neurology. 2012 Feb 28;78(9):658-64.

6. Pottala JV et al. "Blood eicosapentaenoic and docosahexaenoic acids predict all-cause mortality in patients with stable coronary heart disease: the Heart and Soul study." Circ Cardiovasc Qual Outcomes. 2010 Jul;3(4):406-12.

7. Jensen CL et al. " Effects of maternal docosahexaenoic acid intake on visual function and neurodevelopment in breastfed term infants." Am J Clin Nutr. 2005;82, 1:125-132.

8. Cheruku SR et al. " Higher maternal plasma docosahexaenoic acid during pregnancy is associated with more mature neonatal sleep-state patterning." Am J Clin Nutr. 2002; 76, 3:608-13.

9. Hibbeln J et al. Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): an observational cohort study." Lancet. 2007; 379:578-584.

10. Muldoon MF et al. " Serum Phospholipid Docosahexaenonic Acid Is Associated with Cognitive Functioning during Middle Adulthood." J Nutrition. 2010;140(4):848-53.

11. Bazan NG et al. " Docosahexaenoic acid signalolipidomics in nutrition: significance in aging, neuroinflammation, macular degeneration, Alzheimer's, and other neurodegenerative diseases." Annu Rev Nutr. 2011;31:321-51.

12. Bazan NG et al. "Neuroprotectin D1 (NPD1): a DHA-derived mediator that protects brain and retina against cell injury-induced oxidative stress." Brain Pathol. 2005 Apr;15(2):159-66.

13. Mills JD et al. "Dietary Supplementation With the Omega-3 Fatty Acid Docosahexaenoic Acid in Traumatic Brain Injury." Neurosurgery. 2011;68(2):474-481.

14. Stough C et al. " The effects of 90-day supplementation with the Omega-3 essential fatty acid docosahexaenoic acid (DHA) on cognitive function and visual acuity in a healthy aging population." Neurobiol Aging. 2012;33(4):824e1-824e3.

15. Miles EA and Calder PC. " Influence of marine n-3 polyunsaturated fatty acids on immune function and a systematic review of their effects on clinical outcomes in rheumatoid arthritis." Br J Nutr. 2012 Jun;107 Suppl 2:S171-84.

16. Jazayeri, S et al. " Effects of eicosapentaenoic acid and fluoxetine on plasma cortisol, serum interleukin-1beta and interleukin-6 concentrations in patients with major depressive disorder." Psychiatry Res. 2010; 178(1):112115.

17. Bloch MH and Qawasmi A. " Omega-3 Fatty Acid Supplementation for the Treatment of Children With Attention-Deficit/Hyperactivity Disorder Symptomatology: Systematic Review and Meta-Analysis." J Amer Acad Child Adolesc Psychiatry. 2011;50(10): 991-1000.

18. Needleman, P. et al. "Triene prostaglandins: prostacyclin and thromboxane biosynthesis and unique biological properties". Proc. Natl. Acad. Sci. U.S.A. 76:944-948.

19. Akiba S et al. "Involvement of lipoxygenase pathway in docosapentaenoic acid-induced inhibition of platelet aggregation." Biol Pharm Bull. 2000 Nov;23(11):1293-7.

20. Sun Q et al. "Blood concentrations of individual long-chain n-3 fatty acids and risk of nonfatal myocardial infarction." Am J Clin Nutr. 2008 Jul;88(1):216-23.

21. Kanayasu-Toyoda T et al. "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.