ReviewThe ratio of energy expenditure to nitrogen loss in diverse patient groups – A systematic review
Introduction
In 1816, François Magendie reported to the French Academy of science that animals could not use atmospheric nitrogen to “animalize” ingested food and that a dog on a nitrogen-free diet would die after one month. From his studies, he drew two conclusions: (a) none of the nitrogen-free diets were “preeminently nutritive”, and (b) nutritional nitrogen was the source of the majority of the nitrogen in a dog’s body.1 With the discovery of amino acids in the late 19th century, nitrogen was linked directly to protein. Since then, the nitrogen molecule – despite its potential toxicity – has played an important role in nutritional science and is frequently used as a surrogate marker for protein synthesis, degradation, and mass.
The measurement of body nitrogen losses using urinary nitrogen excretion measurements represents an important window for the evaluation of protein catabolism. Currently, there are no direct measurements of protein breakdown that are readily available to clinicians. Urinary nitrogen excretion and the excretion of methylhistidine are the only readily available techniques that clinicians can rely upon to estimate protein catabolism in the clinical setting. However, compensation for “nitrogen losses” and the achievement of a “positive nitrogen balance” for the preservation of lean body mass are amid the main goals of nutritional support.
The energy to nitrogen (E/N) ratio plays an important role in the provision of nutrition support, either by enteral nutrition or parenteral nutrition (PN). To achieve maintenance and/or improvement of lean body mass, one needs to prevent most administered amino acids from being burned for energy. To achieve optimally this goal, dietary nitrogen should be administered with a certain amount of non-protein energy.2 Thus, the levels of energy intake determine the change in nitrogen balance that can be achieved with specific nitrogen intakes. For active young men, it has been shown that 8.5 g of nitrogen per day are sufficient to promote nitrogen balance provided the caloric requirements are fully met with 3250 kcal/day.3 This is equivalent to an E/N ratio of 382:1. Military and civilian survival ration kits were created with units of food containing 500 kcal of which 7–8% were derived from protein; this is equivalent to an E/N ratio of 313:1–357:1.3
Most current commercial formulations developed for enteral nutrition have an E/N ratio of approximately 70:1 to 300:1, with the higher ratios representing formulations for use in patients with renal and hepatic disease. In contrast to enteral nutrition, when prescribing PN therapy as the nutritional intervention, the availability of hospital or pharmacy-based compounding allows the amount of nitrogen and non-protein calories to be varied independent of each other. This process allows for multiple variations of the E/N ratio. The more recent development of a ready-to-use, triple chamber bag for PN has created a need for better understanding of the protein needs and the E/N ratio amongst various groups of patients receiving PN therapy.
There are numerous nutritional guidelines published that recommend a specific intake or narrow range on intakes of calories and protein for various patient groups. It is still unclear whether the recommended intakes are adequate to meet energy expenditures and nitrogen losses of patients. In addition, most nutritional studies fail to consider the relationship between energy and protein intakes when evaluating various nutritional regimens. A knowledge of the range of energy expenditures and nitrogen losses in different patient populations is important for the design of clinical trials designed to test the clinical consequences of matching energy and protein intakes to expenditures.
The goal of our review was to assess energy expenditures and nitrogen losses in various groups of patients that require nutritional support and to correlate the nitrogen losses with total energy expenditure (TEE). To accomplish this goal, we performed a literature search for all papers which reported nitrogen loss and measured energy expenditure in the same patient groups. To our knowledge, this is the first systematic review of energy expenditure, nitrogen (protein) loss, and E/N ratio in hospitalized patients and healthy controls.
Section snippets
Methods
A Medline literature search was performed for all papers reporting energy expenditure and nitrogen or protein metabolism in the same patient population, regardless of publication date or publication language. We identified 53 papers4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56 that matched these criteria. One study49 included the same
Results
Fifty three papers4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56 reported the energy expenditure and nitrogen excretion of 1107 subjects (one paper54 did not report the number of patients) in 91 different cohorts with an average age (mean ± SD) of 45.7 ± 14.5 years. Details of the studies are given in the appendix table, available as
Discussion
This systematic review of energy expenditure and nitrogen (protein) loss in healthy and hospitalized subjects is the first such review published in the medical literature and presents data on measured energy expenditure and nitrogen excretion in 881 patients and 226 healthy subjects. The huge majority of the studies were published prior to 2000, only six of them– reporting on 172 patients and 16 healthy women – were published in 2000 or later; although treatment modalities might have changed,
Conflict of interest
All authors are employees of Baxter Healthcare.
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