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.