expert opinion

What is the potential importance of dietary supplements with omega-3 fatty acids?

February 1, 2015


Prof. Dr. Clemens von Schacky, Preventive Cardiology, Medical Clinic and Poli-Clinic I, Ludwig Maximilian University, Munich, Germany

“The two marine fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) cannot be synthesized by the human body; not even in sufficient quantities from the plant-source omega-3 fatty acid alpha-linolenic acid, under current conditions. Although human beings are dependent on ingesting EPA and DHA, sources of these fatty acids are slowly disappearing from our daily diet. Previously, hens were fed fish meal, and as a result their eggs contained EPA and DHA. Farmed fish, which make up at least 50% of the fish consumed in most of the industrialized countries, contain ever decreasing amounts of EPA and DHA because farmers are feeding less and less fish oil and fish meal, for financial reasons (1).

EPA and DHA are components of the phospholipids of every cell membrane. The fatty acid composition of the membranes of different cells is closely regulated both qualitatively and quantitatively, as is incorporation and redistribution of the different fatty acids. Proportions of DHA in brain fat can reach 70%, while in other organs, like the heart, DHA and EPA can constitute 5% of fat. The proportion of EPA and DHA in the cell membrane not only influences its physical properties (e.g., flexibility), it also modulates other cell functions, including those of the ion channels, signal transduction and gene expression (2). Moreover, EPA and DHA are precursors of biological reaction modulators such as eicosanoids and neuroprotectin, to which antiatherogenic, antiarrhythmic and anti-inflammatory activities have been attributed.

The proportion of EPA and DHA in internal organs correlates with amounts in the erythrocyte membrane. Measuring blood levels reveals EPA and DHA deficits; most extensively scientifically substantiated method of fatty acid measurement being the standardized measurement of fatty acid composition of the erythrocytes (HS-Omega-3 Index). If the omega-3 fatty acids are ingested with a low-fat meal (breakfast, for example, is commonly low in fat), their bioavailability can be up to 13 times poorer than after a high-fat meal. In many large intervention studies, EPA and DHA were given at breakfast in the form of an ethyl ester without emulsion, which represents the poorest bioavailability. This explains the sometimes neutral results from previous clinical studies. Moreover, the level of the HS-Omega-3 Index depends on genetic factors, distribution area, catabolism and other factors. It is therefore not surprising that the response of the HS-Omega-3 Index to increased intakes of EPA and DHA varies widely from person to person. Consumption and blood levels of EPA and DHA are therefore only loosely linked. Cell functions have a considerably stronger correlation with the HS-Omega-3 Index than consumption does.

Numerous epidemiological studies are based on determination of EPA and DHA intakes, while more recent studies have measured blood levels of the two fatty acids. An HS-Omega- 3 Index with a target range of 8–11% has been suggested for the prevention and treatment of cardiovascular diseases. In the studies, an HS-Omega- 3 Index below this target range was associated with an increased risk of total mortality, sudden cardiac death and fatal or non-fatal myocardial infarction (1). Studies also indicated a link between an inadequate HS-Omega- 3 Index and an increase in the probability of suboptimal brain structure and function, which expressed itself as restricted complex brain performance including executive function, memory capacity, attention span and the development of depression (2). However, the results of many clinical studies with targeted ingestion of EPA and DHA were inconsistent. Possible reasons for this, besides the use of dietary supplements containing EPA and DHA with poor bioavailability, were participants whose baseline blood levels were already in the target range, or similar participant blood levels in the intervention and control groups due to the great individual variability of response of the HS-Omega- 3 Index to the dietary supplement. Future intervention studies that recruit participants with a low baseline HS-Omega- 3 Index and achieve the suggested target range of 8–11% with variable dosages offer the prospect of clearer results. As yet there is no direct evidence that determination of the HS-Omega-3 Index must lead to therapeutic consequences, because as yet no large clinical study has been conducted based on the HS-Omega- 3 Index. However, several cardiological guidelines already recommend higher intakes of EPA and DHA in cardiovascular prevention.

The health problems mentioned have been increasing globally for years now: coronary heart disease, depression and cerebrovascular diseases, including dementia, will fill three of the top four places on the list of most common diseases in Western countries by 2020. In contrast, in Japan and Korea these diseases are rare and the HS-Omega-3 Index is substantially higher than in Western nations (1). The costs to the health systems of the latter are set to explode in consequence. Conversely, the percentage of people with an HS-Omega-3 Index below the recommended range appears to be increasing, since EPA and DHA seem to be disappearing from our diets. Many fish stocks are considered to be under threat and for years the amounts of fish caught have remained stagnant, as has the production of fish oil. Currently, new sources of EPA and DHA are being developed, like algae and krill. One way to utilize available resources more effectively would be to shorten the food chain, for instance by delivering fish oil directly to human beings – in the form dietary supplementation – instead of taking a fairly inefficient detour via fish farming. Previous large intervention studies have shown tolerance of EPA and DHA to be similar to placebo (2). No tendency to bleeding, which would be theoretically conceivable, was observed. Neither is there any justification for the suggestion by methodologically inadequate epidemiological studies that EPA and DHA could possibly increase the incidence of prostate carcinoma (1, 2). In contrast to long-living carnivorous fish, dietary supplements which commonly serve as sources of EPA and DHA are not contaminated with heavy metals or other toxins. The US FDA considers a daily dose of 3 g EPA+DHA as safe, whilst the European Food Safety Authority regards 5 g per day to be safe. Against this backdrop it is questionable whether the contention by some that dietary supplementation with EPA and DHA is unnecessary or even harmful is tenable.”

Based on: von Schacky C. Nahrungsergänzung mit Omega-3 Fettsäuren? herzmedizin. 3/2014.


  1.  von Schacky C. Omega-3 index and cardiovascular health. Nutrients. 2014; 6:799–814.
  2.  von Schacky C. Hirnstruktur und Hirnfunktion: Die Rolle der Omega-3-Fettsäuren. Z. Orthomolekulare Medizin. 12/2014.