Editorial [Hot topic: Polyunsaturated Fatty Acids and Human Health: A Critical Appraisal of the Evidence (Executive Editor: Antonio Cherubini)]

Polyunsaturated fatty acids (PUFA) are a family of lipids with more than one double bond in their molecule, that are identified by the position of the last double bond in their structure. The main groups are ω-3 PUFA, including alpha linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), and ω-6 PUFA including linoleic acid (LA) and arachidonic acid (AA). Few other nutritional substances have attracted in recent years more attention than pufa. Starting from the pioneer studies performed in Eskimos on the influence of fish on cardiovascular disease risk more than 30 years ago [1], the interest for the health benefits of these compounds has rapidly increased, as shown by the presence of more than 3500 papers on this topics reported in the pubmed since the year 2000 [2]. In this issue of the Journal the evidence concerning the benefits of PUFA in several diseases and conditions is critically discussed. Cardiovascular disease is the first area in which ω-3 PUFA have been investigated and where their benefits have been more clearly demonstrated not only in epidemiological studies but also in randomized controlled trials. Supplementation with ω-3 PUFA is effective in the treatment of hypertriglyceridemia [3] and in the reduction of mortality after myocardial infarction as well as in heart failure patients [4]. Several biological mechanisms can explain these beneficial effects: ω-3 PUFA have anti-arrhythmic, anti-thrombotic, anti-atherosclerotic properties. Moreover, PUFA are also involved in different mitochondrial processes, including mitochondrial calcium homeostasis, gene expression, respiratory function, ROS production and mitochondrial apoptosis [5]. Experimental studies have shown a beneficial effect of PUFA, both ω-3 and ω-6, on body composition, with a reduction of fat mass [6]. Since obesity is becoming a world wide epidemics, this activity deserves further investigation in humans. According to several reports, a higher dietary intake of PUFA seems to reduce the risk of developing type 2 diabetes and it might also improve metabolic control in patients with type 2 diabetes [7]. The anti-inflammatory effects of PUFA [8] suggest that they might represent an important treatment for inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease, although current evidence cannot be considered conclusive [9]. Kidney diseases leading to chronic renal insufficiency are increasing in the population: recent data from animal as well as human studies raise the hope that a higher dietary intake of PUFA may be protective against the progression to chronic kidney disease [10]. Also osteoporosis is a common condition, particularly in older subjects, with a high impact on health care expenditure. Although PUFA have been proposed as possible agents to treat this condition, more evidence is needed before they can be recommended in clinical practice [11]. Depression will become the second more important cause of disability in the population and therefore the availability of new therapies to reduce its burden is a major aim in this area. Although epidemiological findings increasingly suggest an inverse association between ω-3 PUFA and depression, with supportive biological plausibility, current evidence is not conclusive, due to methodological limitations of intervention trials [12]. Last but not least PUFA might offer a promising intervention in the prevention of dementia, an hypothesis that is currently being tested in ongoing trials [13]. In conclusion, except in the area of cardiovascular disease, the available evidence is not sufficiently strong to recommend the use of PUFA for the prevention or treatment of several diseases. Given the large potential benefits of PUFA on human health, new properly designed randomized clinical trials are required to clarify the role of PUFA. Furthermore, it would be important to investigate whether in each specific condition a diet enriched in PUFA, e.g. by increasing the intake of fish and several oils, would provide an adequate amount of them or a supplementation should always be recommended [14].