Title: The place of n-3 PUFA enteral nutrition in clinical management


Key words: enteral, parenteral, n-3 PUFA, n-6 PUFA, polyunsaturated fatty acids, cell membranes, eicosanoids, inflammatory markers, leukocyte, macrophages, surgery, trauma, sepsis, enteral nutrition, parenteral nutrition, Th1, Th2, glutamine, arginine, immunonutrition, nucleotides, gastrointestinal surgery, immunomodulating, malnourished, nutritional support,  


Date: Oct 2006




Nutrimed Module:


Type: Article


Author: Morgan, G


The place of n-3 PUFA enteral nutrition in clinical management

Both enteral and parenteral nutrition have a place in the management of the seriously ill. This review will look at the place of enteral nutrition and assess whether the introduction of the n-3 PUFA-based emulsions has improved clinical outcome. Earlier work using the n-6 PUFAs in parenteral nutrition indicated these types of emulsions to be immunosuppressive (Battistella 1997). By contrast, n-3 PUFAs have been shown to lead to changes in the n-3 to n-6 fatty acid composition of cell membranes with the production of a less pro-inflammatory eicosanoid profile. Inflammatory markers such a PGE2, TNF-alpha and the leukotriene B4 to B5 ratio are favourably modulated by the n-3 PUFAs (Chapkin 1991, Wachtler 1997, Wallace 2000). As well as moderating the inflammatory reaction, the n-3 PUFAs also favourably effect leukocyte and macrophage activity (Mayer 1998, Grimm 2002). Surgery and trauma, the main indication for enteral nutrition, can lead to the initiation of a state of hyper-inflammation with an acute phase reaction and suppression of the immune system leading to sepsis in some patients (O’Flaherty 1999). Impaired polymorph function is a prerequisite for sepsis and is impaired following surgery (Stephan 2002), along with poor Th1-mediated cell-mediated immunity (Ferguson 1999). It is now thought that the inflammatory and anti-inflammatory arms of the healing response to trauma or surgery are not biphasic, as originally thought, but are synchronous (Tschaichowsky 2002). Both are necessary in the fight against sepsis. Modulation of Th1-mediated cytokines, such as TNF- alpha, through the use of agents such as the n-3 PUFAs, helps to rebalance the inflammatory and anti-inflammatory arms of this system, thus inhibiting a hyper-inflammatory response. They also activate polymorph and lymphocyte activity. Glutamine, which activates white cells and increases the production of the Th1-mediated cytokines, has also been shown to reduce the early hyper-inflammatory response, reducing levels of sepsis in the critically ill (Calder 1999, Andrews 2002). It is effective parenterally but has also produced results when added to n-3 PUFA-containing enteral feeds (Houdijk 1998).


In clinical practice few studies have been conducted looking at the effect of the n-3 PUFAs alone in modulating inflammation via enteral feeding. Of the four studies (Kenler 1996,Swails 1997, Wachtler 1997, Weiss 2002), three reported a reduction in pro-inflammatory and an increase in anti-inflammatory markers, with a reduced incidence of sepsis and shorter hospital stay. Many more studies have been carried out looking at the use of n-3 PUFAs combined with glutamine, arginine and nucleotides, all possessing promotory effects on lymphocyte and immune function. Some 15 studies have now been published analysing the efficacy of the n-3 PUFA-containing immunonutrition agent Impact, for example. A meta- analysis of the results has been carried out (Marik 2001). From this it is clear that, in the groups of upper gastrointestinal surgery analysed, the use of Impact led to a more favourable immunological profile and significant reductions in sepsis, complications, and hospital stay. Overall mortality, however, appeared to be unchanged. Certain conclusions can be drawn from this work.


Firstly, immunotherapy appears to be most effective when given in the preoperative or early post- operative period (Braga 2002). Second, that the effect is dose dependent (Senkal 1995, Braga 1999) and, thirdly, that the reduction in the inflammatory markers and the sepsis rate only become apparent after the 5th day (Senkal 2000). The effectiveness also appears to be more pronounced in the malnourished (Suchner 2000, Braga 2002) and less effective in severe sepsis (Suchner 2000, Galban 2000). Its efficacy has been most well documented in upper abdominal cancer surgery (Marik 2001). Its use in medical ICU cases is less well defined (Griffiths 2003).


Sepsis remains the leading determinant of a favourable outcome following surgery and severe trauma. The early use of enteral nutrition with n-3 PUFA-containing formulae reduces the incidence of this complication in such groups. Early use of the bowel is feasible and helps to prevent mucosal atrophy, impaired gut immune function, increased gut permeability, and bacterial translocation, all related to postoperative sepsis (Jolliet 1999).


In summary, the enteral use n-3 PUFA-containing formulae provides an energy-dense, cost effective, source of nutrition with beneficial immunomodulating properties. These formulae help to support gut function and have been shown to reduce the incidence of sepsis and other complications in selected perioperative abdominal surgery and trauma patients, particularly in the malnourished. Though still requiring judicious use, in these patients requiring nutritional support during the acute phase of their illness, they help to improve clinical outcome.


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