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Clin Nutr. 2016 Jun;35(3):748-57. doi: 10.1016/j.clnu.2015.08.008. Epub 2015 Sep 5.

Meta-analysis is not enough: The critical role of pathophysiology in determining optimal care in clinical nutrition.

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Faculty of Medicine and Life Sciences, Maastricht University Medical Centre, Maastricht, The Netherlands. Electronic address:
Faculty of Medicine, University of Milan, 20100 Milan, Italy.
Service de Biochimie, Hopital Cochin, AP-HP, Hopitaux Universitaires Paris Centre, Paris, France.
Institute of Human Nutrition and Nutrition Biochemical Research Centre, University Hospital Southhampton, Southhampton, United Kingdom.
Department of Clinical Chemistry, University of Liverpool, Liverpool, United Kingdom.
Third Department of Medicine, Medical Faculty Hospital Hradec Kralove, Charles University, Prague, Czech Republic.


Evidence based medicine has preferably been based on prospective randomized controlled trials (PRCT's) and subsequent meta-analyses in many fields including nutrition and metabolism. These meta-analyses often yield convincing, contradictory or no proof of effectiveness. Consequently recommendations and guidelines of varying validity and quality have been published, often failing to convince the medical, insurance and government worlds to support nutritional care. Causes for lack of adequate proof of effectiveness are manifold. Many studies and meta-analyses lacked pathophysiological depth in design and interpretation. Study populations were not homogenous and endpoints not always clearly defined. Patients were included not at nutritional risk, unlikely to benefit from nutritional intervention. Others received nutrients in excess of requirements or tolerance due to organ failure. To include all available studies in a meta-analysis, study quality and homogeneity were only assessed on the basis of formal study design and outcome rather than on patient characteristics. Consequently, some studies showed benefit but included patients suffering harm, other studies were negative but contained patients that benefited. Recommendations did not always emphasize these shortcomings, confusing the medical and nutritional community and creating the impression that nutritional support is not beneficial. Strong reliance on meta-analyses and guidelines shifts the focus of education from studying clinical and nutritional physiology to memorizing guidelines. To prevent or improve malnutrition more physiological knowledge should be acquired to personalize nutritional practices and to more correctly value and evaluate the evidence. This also applies to the design and interpretation of PRCT's and meta-analyses.


Education; Guidelines; Meta-analysis; Nutritional support; Pathophysiology; Prospective randomized clinical trials

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