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Due to the proposed role of RQ and RER as a marker for substrate use, RQ and RER are often a popular clinical parameter to nutritionists to assess feeding adequacy (24). As a marker for substrate use, the RQ and RER can identify the metabolic consequences of under or overfeeding and the macronutrient distribution of the diet (55). Based on previous research the measured RQ of individuals after a typical Western diet or a mixed diet should be in the 0.85 to 0.90 range (55). Lipogenesis generally occurs when an individual is overfed and the RER measured is higher than 1.0. If an individual is underfed and endogenous fat stores are used to meet caloric requirements, the measured RER will be lower than 0.85 (56). The RER and RQ measurement plays a critical role in nutrition assessment and can be used to predict over or underfeeding in order to customize a patient’s energy needs (57). However, not all patients who are overfed show changes in RER (measured above one) (58). Only 64% (59 of 92) of patients who were overfed reported a rise in RER above 1.0 (58). Therefore, using RER > 1.0 to identify overfeeding resulted in 89% sensitivity but only 55% specificity (58). A more recent study reported increases in RQ above 1.0 were only observed in 28% (31 of 109) of individuals who were overfed (24).
Previous research suggests that high carbohydrate intake, especially when in excess of caloric needs, leads to lipogenesis, increased VCO2 and resulting in elevated RER values (58-61). Increases in VCO2 production affect respiratory status, increasing minute ventilation, alveolar ventilation, and VO2 (61). The most affected patients are nutritionally depleted, stressed, hypermetabolic, or have chronic obstructive pulmonary disease (COPD) with limited capability for eliminating CO2 (61). The most efficient way to reduce VCO2 production is fat oxidation (62). To lower the ventilatory demand for COPD patients, a high-fat diet intervention is often recommended (63).
Conflicting results from the clinical trials may be explained by the influence of unpredictable factors on measured values of RQ and RER. The proposed use of measured RQ and RER in nutrition studies assumes RQ and RER reflect only substrate utilization, especially under steady-state conditions (24). However, many factors that may impact the measured RQ and RER are difficult to identify. Individual’s variations in RQ and RER are regulated by differential expressions of specific genes (64). For example, serine peptidase has been reported to alter macronutrient fuel by promoting carbohydrate oxidation or impairing lipid oxidation, resulting in an increase in substrates oxidation (64). Meanwhile, genes involved in the protein phosphatase type 2A complex and unfolded protein binding was associated with reduced substrates oxidation values and favor fat for fuel metabolism (64). In summary, individuals have their own metabolic parameters resulting in a unique metabolic response to different metabolic states, e.g., stress or injury (24).
Previous research also shows that the use of respiratory quotient is not recommended for finely changing or rather adjusting the nutritional support regime. This is because the use of the RQ to determine under or over feeding is considered to be limited regarding its specificity and sensitivity. The RQ only shows a reflection of substrate utilization, and there are several factors that can alter the RQ measured in ways that clinically impossible to identify (26). Each patient has their unique metabolic machinery working in novel ways and the metabolism process becomes difficult to predict especially when contracts a disease or is injured. For example, the RQ value is usually affected or rather displaced by the patient with chronic illnesses such as diabetes mellitus or the ingestion of exogenous pharmacological substances such as alcohol which tend to lower the RQ value that is expected (25). In the case of diabetes mellitus, the activity of insulin is interfered with hence excess sugars are not incorporated into the cells to undergo lipogenesis hence the RQ, in this case, becomes of a lesser value and yet a patient may have overfed at that particular time. In this case, the RQ value does not include college to the expected RQ value after feeding or overfeeding.
Because RQ is influenced by several factors such as acid-base alterations, conditions in relation to metabolism, and body habitus, the ratio cannot be effectively used to determine energy provision. Based on a study conducted on PICU patients, the metabolic expectations were overestimated by the care providers where in this case the children who were below one year of age and were critically ill showed an unexpected overfeeding pattern because the majority were malnourished (398). In such cases, the use of targeted IC has shown promise in pointing out imbalances in energy brought about by overfeeding in individuals with underlying metabolic dysfunctions.
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