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DHA omega-3 at the heart of cardiovascular health.

For some time, cardiovascular disease has been responsible for more deaths worldwide than any other condition, particularly in high-income countries. Awareness of the major risk factors--poor diet, insufficient exercise and smoking--is often fairly high; yet, it remains the cause of around 30% of all deaths. With an enormous global market seeking to improve heart health, manufacturers are presented with an exciting opportunity. Rob Winwood, European Director of Scientific Affairs at Martek Biosciences, reviews the latest international studies demonstrating the cardiovascular benefits of omega-3 fatty acids and the positive impact of today's more favourable regulatory environment.


In today's cluttered market, consumers are being bombarded with countless "healthy" messages in relation to numerous foods, drinks and supplements. With labelling still unclear in many areas, a lack of consistency across countries and/or industries, and the validity of some claims being questioned or even rejected altogether, it is small wonder that scepticism--and confusion--are rife. So, in the hunt for ingredients that will truly add value to products and hold long-term consumer appeal, robust scientific backing and clear direction from regulatory and/or legislative bodies are now more important than ever.

Making the Science More Specific

More than 4500 international studies have looked into the role of omega-3 fatty acids in the maintenance of cardiovascular health. Many researchers, especially early on, used fish or fish oils as the source of the omega-3s. Because fish contain two specific types of omega-3s, EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), the benefits identified were attributed to both. More recently, however, scientists have attempted to identify whether both EPA and DHA are actually responsible for heart health benefits, or if they could be attributable to DHA alone. The results of these newer studies confirm that DHA in isolation is indeed advantageous in various aspects of heart health. This means that manufacturers and brand owners can offer these valued benefits without the need to include fish products, which can limit the appeal or acceptability of their products. Recent studies into the role of DHA in heart health have explored a number of areas.

Reduction of Triglyceride Levels

High levels of triglycerides have been linked to atherosclerosis and the risk of heart disease. A 2007 study by Kelley et al. showed that supplementation for just 45 days with microalgal DHA resulted in a 24% decrease in triglyceride levels in male hypertriglyceridemic patients. (1) In the same year, research by Meyer et al. found that within 3 months, DHA-rich fish oil supplementation (2.16 g DHA/day) can improve plasma lipids in a dose-dependent manner in patients taking statins. (2) Interestingly for food and beverage manufacturers, Schwellenbach et al. found no significant differences in triglyceride-lowering benefits between DHA-only and DHA/EPA combination products when dosing is based on DHA. (3) This means that they are able to offer the benefits of DHA without the need to use fish oils, which may be unsuitable or undesirable for their products.

A subsequent paper published in the American Journal of Therapeutics reviewed 16 clinical trials relating to DHA and heart health. (4) It highlighted that doses of 1-2 g/day of algal DHA significantly lowered plasma triglyceride levels (by up to 26%) when administered alone or in combination with statins. The reduction in triglyceride levels was markedly greater in hypertriglyceridemic subjects than in normal ones. Furthermore, regression analysis showed a linear relationship between baseline triglyceride levels and the magnitude of their reduction, which could suggest people with very high triglyceride levels (>500 mg/dL) could benefit the most from DHA supplementation.

Lowering Blood Pressure

Keilson et al. found the DHA lowers diastolic blood pressure and reduced pulse rate in a statin-treated population that was at risk of cardiac disease. (5) Another 2007 study published in the Journal of Nutrition found that even low doses of algal DHA lowered diastolic blood pressure by 3.3 mmHg in middle-aged subjects. (6) This finding backed up previous studies that had included higher doses of DHA. Blood pressure in children is also reduced with DHA consumption, according to research published in the British Medical Journal. (7) It is not yet clear how DHA elicits this antihypertensive effect, but ongoing and future studies will help to provide further evidence and clarification of its ability to reduce blood pressure.


Optimizing Heart Rate

An accelerated and/or irregular heartbeat is a key risk factor in cardiovascular disease. As a result, achieving and maintaining a normal heart rate is highly desirable. Both the Keilson and Theobald papers mentioned above found that DHA, in the absence of EPA, helps to maintain a normal heart rate. Other research has shown that DHA can also reduce heart rate. (8) DHA's antiarrhythmic effects have been demonstrated in various studies, most recently by Harris et al. (9) A Finnish study just published by the American Heart Association showed that DHA, but not EPA or DPA, reduced the risk of atrial fibrillation in men. (10) The authors stated that "the preferential accumulation of DHA compared with EPA in myocardial cell membranes, together with the results from these studies, suggests that DHA may be the principal long-chain n-3 PUFA responsible for the cardioprotective effects." Scientists are still looking into the antiarrhythmic effects of omega-3 fatty acids, including Incalzi et al., who are focusing on elderly patients.

Lowering Arterial Plaque

Excessive arterial plaque levels can restrict blood flow and increase the risk of blood clots--and therefore stroke or myocardial infarction (heart attack). In a study published in November 2009, Bazan et al. found that diminished omega-3 fatty acids are associated with carotid plaques from neurologically symptomatic patients. (11) This was the latest in a number of papers published during the past decade demonstrating how the risk of atherosclerosis is reduced with DHA or DHA/EPA supplementation.


Cellular Ageing

One of the most recent studies published in the area of cardiovascular health looked into telomeric ageing. Telomeres are regions of DNA at the end of chromosomes that protect them from ageing. White blood cell telomere length is an indicator of biological age, which predicts morbidity and mortality in patients with CVD; telomeric attrition (or wearing) has an ageing effect on the blood cell. (12) Farzaneh-Feh et al. observed more than 600 patients with stable coronary artery disease during a period of between 5 and 8 years and found there was an inverse relationship between baseline blood levels of omega-3 fatty acids and the rate of telomere shortening. Their observations led them to speculate that "omega-3 fatty acids might exert bidirectional effects on telomerase depending on cellular context: in health tissues, they may enhance telomerase activity while suppressing it in cancerous cells." A double-blind, randomized, placebo-controlled study would indicate whether omega-3 fatty acids inhibit cellular ageing, but this initial study is clearly positive.


The overwhelming majority of studies into omega-3s and cardiovascular health has traditionally used EPA/DHA combined products. However, with growing consumer demand for non-fish-derived omega-3s, the increasing research into the cardioprotective effects of DHA alone is being welcomed by manufacturers and brand owners. Research to date has shown that both EPA and DHA have benefits for heart health, but we are now seeing that DHA's benefits are more marked and/or more extensive. Significantly, DHA also offers benefits in other areas of health (brain and eye health, for example) that EPA does not. At the same time, progress is being made in the regulatory environment, with the European Food Safety Authority (EFSA) concluding last year that 250 mg should be the labelling reference intake value for long-chain omega-3 fatty acids. Subsequently, the European Commission approved statements on DHA's importance for infant brain and eye health--and it is hoped that similar statements will be finalized for cardiovascular health. These factors make for an exciting and lucrative opportunity. Although further independent and robust science is undoubtedly required and further legislative clarification would be valuable, DHA promises to be at the heart of cardiovascular health in the 21st century.


(1.) D.S. Kelley, et al., "Docosahexaenoic Acid Supplementation Improves Fasting and Postprandial Lipid Profiles in Hypertriglyceridemic Men," Am. J. Clin. Nutr. 86, 324-333 (2007).

(2.) B.J. Meyer, et al., "Dose-Dependent Effects of Docosahexaenoic Acid Supplementation on Blood Lipids in Statin-Treated Hyperlipidaemic Subjects," Lipids 42(2), 109-115 (2007).

(3.) L.J. Schwellenbach, et al., "The Triglyceride-Lowering Effects of a Modest Dose of Docosahexaenoic Acid Alone Versus in Combination with Low Dose Eicosapentaenoic Acid in Patients with Coronary Artery Disease and Elevated Triglycerides," J. Am. Coll. Nutr. 25, 480-485 (2006).

(4.) A.S. Ryan, et al., "Clinical Overview of Algal-Docosahexaenoic Acid: Effects on Triglyceride Levels and Other Cardiovascular Risk Factors," Am. J. Therapeut. 16(2), 183-192 (2009).

(5.) L.M. Keilson, et al., "Docosahexaenoic Acid Lowers Diastolic Blood Pressure and Reduces Pulse Rate in a Statin-Treated Cardiac Risk Population," J. Am. Coll. Cardio. 49(Suppl.), 350A (2007).

(6.) H.E. Theobald, et al., "Low-Dose Docosahexaenoic Acid Lowers Diastolic Blood Pressure in Middle-Aged Men and Women," J. Nutr. 137, 973-978 (2007).

(7.) J.S. Forsyth, et al., "Long Chain Polyunsaturated Fatty Acid Supplementation in Infant Formula and Blood Pressure in Later Childhood: Follow Up of a Randomised Controlled Trial," BMJ 326(7396), 953 (2003).

(8.) T.A. Mori and R.J. Woodman, "The Independent Effects of Eicosapentaenoic Acid and Docosahexaenoic Acid on Cardiovascular Risk Factors in Humans," Curr. Opin. Clin. Nutr. Metab. Care 9, 95-104 (2006) and K.D. Stark and B.J. Holub, "Differential Eicosapentaenoic Acid Elevations and Altered Cardiovascular Disease Risk Factor Responses After Supplementation with Docosahexaenoic Acid in Postmenopausal Women Receiving and Not Receiving Hormone Replacement Therapy," Am. J. Clin. Nutr. 79, 765-774 (2004).

(9.) W.S. Harris, et al., "Omega-3 Fatty Acids and Coronary Heart Disease Risk: Clinical and Mechanistic Perspectives," Atherosclerosis 197,12-24 (2008).

(10.) J. Virtanen, et al., "Serum Long-Chain n-3 Polyunsaturated Fatty Acids and Risk of Hospital Diagnosis of Atrial Fibrillation in Men," Circulation 120, 2315-2321 (2009).

(11.) H. Bazan, et al., "Diminished Omega-3 Fatty Acids are Associated with Carotid Plaques from Neurologically Symptomatic Patients: Implications for Carotid Interventions," Vasc. Pharmacol. 51(5-6), 331-336 (2009).

(12.) J.J. Fuster and V. Andres, "Telomere Biology and Cardiovascular Disease," Circ. Res. 99(11), 1167-1180 (2006).

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Title Annotation:health management; docosahexaenoic acid
Publication:Nutraceutical Business & Technology
Article Type:Report
Geographic Code:1USA
Date:May 1, 2010
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