Are marine n-3 fatty acids protective towards insulin resistance? From cell to human

Marine n-3 fatty acids improve most of the biochemical alterations associated with insulin resistance (IR). Experimental models of dietary-induced IR in rodents have shown their ability (often at a very high dose) to prevent IR, but with sometimes a tissue specific effect. However, in a high sucrose diet-induced IR rat model, they are unable to reverse IR once installed; in other rodent models (dexamethasone, Zucker rats), they are inefficacious perhaps because of the severity of IR. The very low incidence of type-2 diabetes (T2D) in Inuits in the 1960s, which largely increased over the following decades in parallel to the replacement of their traditional marine food for a western diet strongly suggests a protective effect of marine n-3 towards the risk of T2D; this was confirmed by reversal of its incidence in intervention studies reintroducing their traditional food. In healthy subjects and insulin-resistant non-diabetic patients, most trials and meta-analyses conclude to an insulin-sensitising effect and to a very probable preventive or alleviating effect towards IR. Concerning the risk of T2D, concordant data allow us to conclude the protective effect of marine n-3 in Asians while suspicion exists of an aggravation of risk in Westerners, but with the possibility that it could be explained by a high heterogeneity of studies performed in this population. Some longitudinal cohorts in US/European people showed no association or a decreased risk. Further studies using more homogeneous doses, sources of n-3 and assessment of insulin sensitivity methods are required to better delineate their effects in Westerners.