Block 1. Multi-centre clinical trial on arrhythmia endpoints (SOFA)

A multi-centre clinical trial on arrhythmia endpoints (SOFA) will answer the question whether a mix of n-3 fatty acids as present in fish oil indeed prevents life-threatening cardiac arrhythmia. This trial is currently being executed in Western Europe and will be extended it to Eastern Europe to obtain a sufficient number of patients to answer the research question with sufficient power. This will be completed by May 2004. Data collection will be completed by June 2005 and the results will be reported by January 2006.

Block 2. Effect n-3 fatty acids on electrocardiographic risk markers in patients

In an on-going study the effects of fish n-3 fatty acids on premature ventricular contractions and other electrocardiographic risk markers in patients are measured. Results from this project will determine planning of later studies in Blocks 2, 3 and 4.

Block 3. The n-3 fatty acids and underlying electrophysiological mechanisms of heart diseases (months 0-24)

In this block the electrophysiological mechanisms underlying effects of n-3 fatty acids on heart disease will be addressed. Mechanistic insights will give leads for differential health effects of various n-3 fatty acids. An arrhythmia model in isolated pig hearts that is currently being developed will be applied. Effects of specific n-3 fatty acids on electrophysiological processes will be investigated both at the whole organ and at the cellular level. A first study to validate the model will be completed after 6 months. In a later stage the model will be used to investigate potential efficacy of specific n-3 fatty acids in fish and other foods, and to study the relation between the fatty acid composition of the heart and other muscles. Results will be used in Block 4. Block 3 will last 24 months.

Block 4. Conversion and metabolic control of different n-3 fatty acids in human body

In this part of the project the conversion and metabolic control of different n-3 fatty acids in the human body, including alpha-linolenic acid (ALA) from vegetable oil, the parent compound of longer chain n-3 fatty acids as present in seafood (EPA, DHA and minor others) will be studied. This will provide information on the potential efficacy of different dietary n-3 fatty acids, how the body controls n-3 fatty acid metabolism, and how tissue levels of different n-3 fatty acids can be modulated by other dietary factors. In a human study we will feed different dietary n-3 fatty acids to investigate if and how much ALA intake affects EPA and DHA levels in muscle tissue.