Investigating Nutritional Therapy With EPA, GLA and Antioxidants Role in Sepsis Treatment-INTERSEPT STUDY

The effectiveness of nutritional support in modulating the chain of inflammatory response and in reducing demands of the respiratory system through use of nutritional intervention has received a growing attention, as a result of its capacity to interfere in a variety of biological processes [1]. Nutritional formulations that are low in carbohydrates and rich in lipids may reduce minute-ventilation and ventilatory demand, leading to a reduction of respiratory coefficient and CO2 production [2]. Gadek et al. [3] used a high lipid enteral diet enriched with eicosapentaenoic acid (EPA or fish oil), gamma-linolenic acid (GLA or borage oil) and enhanced levels of antioxidant vitamins in patients with ARDS, demonstrating a significant improvement, not only in the PaO2/FiO2 ratio, but also in several outcomes such as ventilator-free days, ICU-free days and reduced new organ dysfunctions. A recent clinical trial demonstrated that the use of this type of diet may produce better outcomes also in patients with acute lung injury (ALI) [4].

Recent pharmaceutical interventions proposed for sepsis have sought to focus on regulating the chain of pro and anti-inflammatory mediators [5,6], responsible for causing the systemic characteristics of the disease and, consequently, for leading to multiple organ failure. The inflammatory reaction is capable of activate synthesis of lipid mediators, such as prostaglandin E2, which are involved in the complex regulation of the inflammatory process [7].

Many of these inflammatory mediators are metabolites of omega-6 fatty acids, such as linoleic acid and the product of its elongation/desaturation, arachidonic acid [8]. Substitution of Omega-6 fatty acids by fatty acids rich in Omega-3, such as EPA, has proved to be beneficial in modulating the inflammatory processes both in animal models and in humans [9-17].

Interest has also grown around the potential metabolic effects of GLA. This oil is rapidly lengthened to dihomo-gamma-linolenic acid (DGLA) and is incorporated into tissue lipids. DGLA may, amongst other effects, suppress bio-synthesis of leukotrienes, being rapidly metabolized to monoenoic prostaglandins [18]. In addition, although EPA allows the elongation of GLA into DGLA, it tends to prevent its desaturation into arachidonic acid. This mechanism can produce an increase in 1 series prostanoids and a decrease in 2 series eicosanoids.

Research using animal models of sepsis-induced ARDS has shown that a diet low in carbohydrates and rich in EPA and GLA may modulate the production of inflammatory mediators, improving the functional capacity of the lungs. This type of diet is capable of rapidly reducing the phospholipid fatty acid content of arachidonic acid in inflammatory cell membranes [19], even if administered parenterally [20]. In animal models of sepsis, a diet enriched with omega-3 fatty acids has been associated with reduced mortality [21-24].