n-3 Fatty Acids in the Treatment of Diabetic Patients
Biological rationale and clinical data
- Raffaele De Caterina, MD, PHD12,
- Rosalinda Madonna, MD, PHD1,
- Alessandra Bertolotto, MD3 and
- Erik Berg Schmidt, MD4
- 1Institute of Cardiology, “G. d'Annunzio” University, Chieti, Italy
- 2C.N.R. Institute of Clinical Physiology, Pisa, Italy
- 3Dipartimento di Endocrinologia e Malattie del Metabolismo, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy
- 4Department of Preventive Cardiology, Aalborg Sygehus, Århus University Hospitals, Århus, Denmark
- Address correspondence and reprint requests to Professor Raffaele De Caterina, Institute of Cardiology, “G. d'Annunzio” University, Chieti, C/o Ospedale S. Camillo de Lellis, Via Forlanini, 50, 66100 Chieti, Italy. E-mail: rdecater{at}unich.it
- apo, apolipoprotein
- CET, cholesteryl ester transfer
- CHD, coronary heart disease
- CVD, cardiovascular disease
- DHA, docosahexaenoic acid
- EPA, eicosapentaenoic acid
- ERK, extracellular signal–regulated kinase
- LA, linoleic acid
- α-LNA, α-linolenic acid
- LT, leukotrienes
- MCP-1, monocyte chemoattractant protein-1
- PUFA, polyunsaturated fatty acid
- TX, thromboxane
The current interest for the use of n-3 (polyunsaturated) fatty acids in vascular disease can be originally tracked to observations in Greenland Inuits (Eskimos), revealing a lower prevalence of coronary heart disease (CHD) in these populations compared with Scandinavian control subjects (1–4). In a series of pioneering studies, Dyerberg and Bang (5,6) originally showed that Inuits had an attenuated platelet reactivity and a prolonged bleeding time compared with Scandinavian control subjects. This was attributed to the Eskimo diet, with an extremely high content of fish or of fish-derived products (such as seal), abundant in n-3 fatty acids, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (7). In other populations with a high consumption of fish, such as the Japanese (8,9) and the Alaskans (10), a similar inverse correlation between fish consumption and mortality from CHD has been subsequently found. However, in Western populations with a generally low intake of n-3 fatty acids, both protective effects (11–16) and no effects (17–20) of n-3 fatty acids on CHD have been reported. There are good explanations for the lack of uniformity in the epidemiological data, including the difficulty in maintaining constant feeding habits in a population during long observational studies and the influence of other dietary principles, including the simultaneous ingestion of saturated or other unsaturated fatty acids. Overall, the bulk of epidemiological data suggests the existence of favorable associations between fish consumption and mortality from CHD (21–24), as reflected in a recent health statement from the American Heart Association (25). In addition, a host of in vitro and in vivo studies have provided possible biological explanations for the epidemiological observations. Such studies have demonstrated that 1) diets rich in n-3 fatty acids partially replace n-6 with n-3 fatty acids in …
