The ratio of energy expenditure to nitrogen loss respectively of energy to nitrogen provision (E/N) is considered a valuable tool in the creation of an enteral or parenteral formulation. Specific E/N ratios for parenteral nutrition (PN) have not yet been clearly defined. To determine the range of energy expenditure, nitrogen (protein) losses, and E/N ratios for various patient groups, we performed a systematic review of the literature.Medline 1950–2011 was searched for all studies on patients or healthy controls reporting energy expenditure and nitrogen loss at the same time.We identified 53 studies with 91 cohorts which comprised 1107 subjects. Mean TEE ± standard deviation (SD) was 31.2 ± 7.2 kcal/kg BW/day in patients (n = 881) and 35.6 ± 4.3 kcal/kg BW/day in healthy controls (n = 266). Mean total protein loss (TPL) was 1.50 ± 0.57 g/kg BW/day in patients and 0.94 ± 0.24 g/kg BW/day in healthy controls. A non-linear significant correlation was found between TPL and the E/N ratio.The E/N ratio is not a constant value but decreases continuously with increasing protein loss. These variations should be considered in the nutritional support of patients.