Who's the alpha among omegas?

Fish oils. Flax. Krill. Chia. Algae. So many sources — which omega-3 source is best for your product for cardiovascular health? Michael A Schmidt, PhD, assesses the state of the research

In 2008, more than 1,000 papers and 140 randomised, controlled trials were published on omega-3 fatty acids and human health. Within this growing body of evidence, the literature on omega-3 fatty acids specific to cardiovascular health is among the most robust.

With respect to specific molecular forms, the literature on the cardiovascular effects of EPA and DHA is extensive, while the literature on the effects of ALA is less developed. A meta-analysis of alpha-linolenic acid (ALA) was recently conducted to assess whether ALA could modify 32 established parameters of cardiovascular risk.1 From this analysis of 14 studies, only fibrinogen, HDL cholesterol and fasting blood glucose were found to be modified. Another meta-analysis that evaluated five prospective studies and three clinical trials concluded ALA intake might also reduce the risk of fatal coronary heart disease.2 Moreover, a recent study showed that ALA intake was associated with lower risk of nonfatal acute myocardial infarction; those who survived MI had higher levels of adipose tissue ALA.3

In the human body, ALA is converted to EPA at rates of roughly 5-8 per cent in men and up to 20 per cent in women. Only 4 -9 per cent of dietary ALA is converted to DHA.4 This suggests that ALA is likely not sufficient to provide the molecular benefits attributed to EPA and DHA. Coupled with the more robust literature on EPA and DHA, it has led researchers to conclude that evidence currently supports EPA and DHA as the predominant cardioprotective nutrient among the fatty acids, with associated benefits ascribed to ALA.

One exception may be ALA in the presence of other flax constituents, such as lignans. For instance, numerous intervention trials report that consuming flaxseed daily can modestly reduce circulating total cholesterol (TC) by 6-11 per cent and low-density lipoprotein (LDL) cholesterol by 9-18 per cent in normolipemic humans, and by 5-17 per cent for TC and 4-10 per cent for LDL cholesterol in hypercholesterolemic patients.5

To date, the strongest evidence showing a cardiovascular benefit from EPA and DHA intake comes from three large controlled trials comprising a total of 32,000 people. In these trials, the supplemented group had a 19-45 per cent reduction in cardiovascular events vs the control group. Included were two major clinical trials on secondary cardiovascular-disease prevention. These were the GISSI and the Japan EPA Lipid Intervention Study (JELIS), which showed significantly reduced death rates and cardiovascular events in people taking 850mg and 1800mg/day DHA and EPA. In the GISSI study, only four months of EPA and DHA supplementation reduced sudden cardiac death by 45 per cent.

Smaller studies suggest that omega-3 fatty acids may decrease sudden cardiac death incidence by influencing atrial fibrillation, with a recent study finding greater effects for DHA over EPA.6 DHA is also rapidly incorporated into blood platelets, which can reduce their tendency to excessively aggregate. Commenting on results from a recent study, the authors concluded, "Consumption of DHA could be an effective and nonpharmacological way to protect healthy men from platelet-related cardiovascular events."7

In an interesting recent development, investigators measured telomere length at baseline and then measured it again after five years in people with coronary heart disease. Telomeres are the protective structures at the end of chromosomes. Telomere shortening is a sign of accelerated chromosome ageing, and it may be among the mechanisms by which omega-3 fatty acids confer cardiac protection. Researchers compared telomere length with blood levels of EPA and DHA. Subjects in the lowest quartile of blood EPA+DHA had the highest rate of telomere shortening, compared with those in the highest quartile of blood EPA+DHA, who had the lowest rate of telomere shortening. Each one standard deviation increase in DHA+EPA levels in blood was associated with a 32 per cent reduction in the odds of telomere shortening.8

EPA and DHA have widespread effects on vascular and cardiac cell architecture and function. Moreover, DHA is central to forming the architecture of peripheral nerves, which regulate heart rhythm. Omega-3 effects on heart function include, but are not limited to, improving arrhythmic thresholds as well as improving platelet, endothelial and arterial function. Various other effects are noted in Figure 1.

Supplemental forms
Fish oil supplements have undergone extensive study in cardiovascular disease and are the most common supplemental forms available. These supplements typically provide EPA and DHA in triglyceride or ethyl ester form. Omega-3 supplements from algae oil provide DHA as the principal fatty acid, which up to now has typically been bound to triglycerides. Now, however, algal EPA and DHA are expected to enter the marketplace with the fatty acids bound to phospholipids.

Krill oil has emerged as a novel omega-3 source, which also contains choline and astaxanthin. The EPA and DHA found in krill oil supplements occur bound in phospholipid form. The benefit of phospholipid- vs triglyceride-derived vs ethyl ester-derived forms of EPA and DHA is under investigation.

Supplements containing ALA are typically derived from flax, chia, hemp, walnut, pumpkin seed and other plant sources. According to the American Heart Association, patients with documented coronary heart disease should consume 1g of EPA plus DHA daily. For those who need to lower triglycerides, 2-4g of EPA plus DHA are recommended (under a physician's care). The National Academy of Sciences has recommended that daily ALA intake reach 1.6g/day in men and 1.1g/day in women. While ALA contributes to the total omega-3 intake, the current consensus argues that preformed EPA and DHA are necessary to achieve cardioprotective benefits.

All recommendations on omega-3 intake are evolving and are likely to change as more evidence becomes available.

Omega-3 status and risk
Higher blood levels of omega-3 fatty acids have been linked to lower risk of cardiovascular disease. Recent studies have demonstrated that when the EPA and DHA content of red blood cells (RBC) is greater than eight per cent of the total fatty acids, there is a 90 per cent reduced risk for sudden cardiac death. This is when compared to an RBC EPA/DHA content of less than four per cent.9 Measurement of red blood cell fatty acids may one day become a standard in assessing cardiovascular risk, much like our current use of total cholesterol, LDL, HDL and triglycerides. While such testing is currently not a standard part of medical practice, assessment of RBC omega-3 fatty acids is now widely available to physicians throughout the world.

Michael A Schmidt, PhD, did his PhD research in molecular medicine and biochemistry within the Life Sciences Division at NASA Ames Research Center and currently teaches in the Metabolomics Training Program at the University of Colorado. He is the author of Brain-Building Nutrition: How Dietary Fats and Oils Affect Mental, Physical, and Emotional Intelligence.

Figure 1. Omega-3 Effects

Omega-3s Increase these:

Omega-3s Decrease these:

HDL cholesterol levels

Triglyceride levels

Arrhythmia threshold

Platelet aggregation and adhesion

Arterial compliance

Adiponectin levels

Endothelium dependent vasodilation

Inflammation (IL-6, TNF alpha)

Atherosclerotic plaque stability

Blood pressure and heart rate






Small dense LDL



Blood pressure



Platelet activation



Immune response



Oxidative stress






Endothelial function









Adapted from: Vrablik, M, et al. Omega-3 fatty acids and cardiovascular disease risk: do we understand the relationship? Physiol Res 2009;58 Suppl 1:S19-26.

1. Wendland E, Farmer A, Glasziou P, Neil A: Effect of alpha linolenic acid on cardiovascular risk markers: a systematic review. Heart 2006, 92(2):166-169.
2. Brouwer IA, Katan MB, Zock PL: Dietary alpha-linolenic acid is associated with reduced risk of fatal coronary heart disease, but increased prostate cancer risk: a meta-analysis. J Nutr 2004, 134(4):919-922.
3. Campos H, et al. alpha-Linolenic acid and risk of nonfatal acute myocardial infarction. Circulation 2008;118.
4. Cur Opin Nutr Metab 2004;7:137-144.
5. Basset CM, et al. Experimental and clinical research findings on the cardiovascular benefits of consuming flaxseed. Appl Physiol Nutr Metab 2009;34(5):965-74.
6. Virtanen JK, et al. Serum long-chain n-3 polyunsaturated fatty acids and risk of hospital diagnosis of atrial fibrillation in men. Circulation 2009;120(23):2315-21.
7. Guillot N, et al. Increasing intakes of the long-chain omega-3 docosahexaenoic acid: effects on platelet functions and redox status in healthy men. 2009;23(9):2909-16.
8. Farzaneh-Far, R, et al. Association of marine omega-3 fatty acid levels with telomeric aging in patients with coronary heart disease. JAMA 2010;303(3):250-7.
9. von Schacky, C, Harris, WS. Cardiovascular benefits of omega-3 fatty acids. Cardiovasc Res 2007;73(2):310-315.

Hide comments


  • Allowed HTML tags: <em> <strong> <blockquote> <br> <p>

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.