Discussion
The overall results indicated that designing an enteral formula with a low DII score for critically ill patients is associated with a significantly greater reduction in serum hs-CRP, LDL-c, and FBS levels compared to the group receiving standard formula. On the other hand, the average change in GCS score was significantly higher, and changes in APACHE II, SAPS II, and NUTRIC scores were significantly lower in the intervention group compared to the control group. Moreover, the intervention group had a significantly shorter LOS compared to the control group.
Our results demonstrated that although hs-CRP levels did not differ significantly between the two groups on day 7, it was statistically significant on day 14. Additionally, the hs-CRP decrease trend was statistically significant in the intervention group, while no significant changes were observed in the control group. This is in line with previous findings, demonstrating a significant positive relationship between DII and several inflammatory biomarkers, including IL-6 (19, 20) and hs-CRP concentration(19). CRP is a non-specific biomarker reflecting any inflammatory condition that commonly increases 4-6 hours after trauma or surgery (21). The declining trend in hs-CRP levels indicate the patient’s entry into the anabolic phase; at this point, nutritional intervention can be effective (17). The hs-CRP test is widely used to accurately measure the low levels of CRP and diagnose vascular inflammation (22). In a Lothian Birth cohort study, Corley et al. investigated the association between the energy-adjusted DII score (derived from food-frequency questionnaires) with the serum level of hs-CRP. Their result indicated that DII/E-DII, as a valid index, has the ability to estimate inflammatory markers, and diet seems to play an important role in regulating the inflammatory conditions in the body (23). On closer inspection, inflammatory biomarkers such as TNF-a and IL-1 have several common pro-inflammatory properties, such as prostaglandin E2 (PGE2) production as well as the activation of collagenase (24), which in cases such as rheumatoid arthritis can cause joint damage. Vitamins and minerals can affect cyclooxygenase and lipoxygenase pathways, modulate the production of prostaglandins such as PGE2, and thereby alter the response to injuries and infections (25).
Recently, this effect has been studied especially in patients with malnutrition and it was observed that diets rich in n-3 fatty acids, arginine, glutamine, and vitamins C and E improve clinical outcomes including infections, inflammation, and complications occur in patients after surgery or trauma. (26, 27). In accordance with previous literature, our enriched low-DII formula with anti-inflammatory properties may affect this process in critically ill patients by increasing the intake of dietary antioxidants.
The present study also suggested that LDL-c levels in the group receiving low-DII-score formula decrease significantly compared to the group receiving standard formula. Previous studies have proposed the mechanisms underlying inflammation-related alterations in lipid metabolism, leading to increased levels of LDL-c, lipoprotein (a), and triglycerides and decreased HDL levels (28). A recent study conducted by Phillips et al. Found that diets with higher DII scores (more pro-inflammatory diet) caused unfavourable alterations in lipid profile, including elevated LDL-c levels (29). Moreover, Ridker et al. found that the higher levels of hs-CRP are significantly associated with items of metabolic syndrome including hypertriglyceridemia, Low HDL-level, obesity, hypertension and abnormal glucose metabolism (22). These findings are consistent with another study conducted by Vahid et al. on 400 patients using a food frequency questionnaire. In that study, they determined the inflammatory index of individuals’ diet and found that subjects in the third tertile of DII had significantly higher levels of FBS, HbA1C, LDL, TG, and body fat, but lower levels of HDL. Their results also showed that those who consumed a more pro-inflammatory diet were at higher risk for prediabetes (30). Decades ago, Scientists found that inflammation exacerbates insulin resistance, which can eventually lead to higher FBS levels (31). Hyperglycemia is probably a sign of an active inflammatory response that is accompanied by an increase in tumour necrosis factor (TNF) activated by nuclear factor kappa b (NF-β). Hyperglycemia can also increase the production of reactive oxygen or nitrogen species and counteracts insulin activity in the human body (32). This pathway explains the significant decrease in FBS levels in the intervention group compared to the control group in our study.
Regarding clinical parameters, the GCS score, as a scoring system for assessing the TBI severity, was significantly higher in the intervention group than in the control group. Previous studies have shown that the lower the score of GCS in TBI patients, the higher unfavourable outcomes following trauma and mortality tend to be (33, 34) Traumatic brain injury may cause severe brain inflammation, resulting in cerebral oedema and elevated intracranial pressure. This condition can worsen the GCS score (35); therefore, reducing inflammation can help to maintain GCS. Inflammation in critically ill patients is characterized by major alterations in energy, macronutrients and micronutrients requirements, as well as changes in metabolism and reduced nutrient absorption. These destructive processes ultimately increase the risk of malnutrition in critically ill patients admitted to the ICU (36). The NUTRIC score, a new screening tool assessing patients’ nutritional risk (37), was found to be significantly higher in the group received low DII formula than the control group on day 14. The three prognostic indices, APACHE II, SOFA, and SAPS II scores, are highly regarded in clinical assessments due to the use of multiple physiological variables (38). According to our results, the APACHE II score did not differ significantly between the intervention and control groups at baseline and day 7. On day 14, however, this score was significantly lower in the intervention group compared to the control group. On the other hand, the trend of the SAPS II scores in the intervention group was significantly downward throughout the long-term intervention period, while this trend was upward in the control group. Moreover, a significant difference was found between the two groups. In a retrospective cohort study, Basil et al. examined the prognostic indices (APACHE II, SOFA and SAPS 3) as well as biological markers (hs-CRP/Albumin and lactate) in 765 patients to predict the mortality rate of surgical patients admitted to the ICU. They found out that prognostic indices such as APACHE II, APACHE DP (APACHE death probability), SAPS 3, and SAPS 3 DP (SAPS 3 death probability) have greater predictability than biological markers such as lactate, albumin, CRP and CRP/albumin in patients’ mortality admitted to the ICU (39).
Mean hospital LOS in the intervention group was significantly lower than the control group. This is consistent with our other findings on reducing the level of inflammation and the severity of the disease in ICU. Similarly, a study of 193 patients who underwent colorectal surgery found that lower hs-CRP levels on the second postoperative day (POD2) were associated with a shorter hospital LOS (40).
In the present study, a homogeneous group of TBI patients was enrolled, which adjusted the impact of confounding variables in both study groups. Patients were carefully and regularly monitored by recording nutritional intake and clinical testing, a major advantage over more poorly controlled studies. In the present pilot study, although the sample size was calculated based on the study of Lee et al. (41), a larger sample size would have increased precision. In this study, the samples were obtained from a single hospital. With these encouraging results as background, future multi-centre studies should be planned to obtain more robust results. Moreover, it might be advisable to extend follow-up for longer periods of time.