Malnutrition, characterized by weight and muscle loss, is prevalent among older patients. Its etiology is multifactorial, often involving an imbalance between energy intake and requirements, primarily due to impaired food consumption. Disease-related inflammation significantly reduces appetite and food intake, acting as a crucial risk factor for malnutrition. The Global Leadership Initiative on Malnutrition (GLIM) proposed a new diagnostic framework requiring at least one phenotypic criterion (unintentional weight loss, low BMI, reduced muscle mass) and one etiologic criterion (reduced food intake, malabsorption, or inflammation). While thresholds for weight loss, BMI, and energy intake are defined, the classification of inflammation as an etiologic criterion remains unclear. C-reactive protein (CRP), a marker of systemic inflammation, is typically <0.5 mg/dl in healthy individuals, but elevated levels are associated with low food intake in hospitalized older patients. This study aimed to establish a CRP threshold indicating an increased risk of low food intake in acutely ill older hospitalized patients, to clarify the inflammation criterion within the GLIM framework. The study aimed to provide a more precise definition of inflammation as an etiological criterion within the GLIM framework for diagnosing malnutrition, particularly in older hospitalized patients.

Existing literature highlights the multifactorial nature of malnutrition in older adults, often stemming from an energy imbalance due to reduced food intake [1,2,3]. Studies have demonstrated a strong link between disease-related inflammation, diminished appetite, and reduced food intake [4,5,6,7], emphasizing inflammation as a significant risk factor for malnutrition. The lack of a standardized definition for malnutrition previously hindered its diagnosis and treatment. The GLIM criteria aim to address this by providing a global diagnostic framework, yet the specifics of classifying inflammation as an etiologic criterion remain ambiguous. Previous research has shown correlations between CRP levels and decreased food intake [4, 5, 6], but lacked a clear threshold for identifying increased risk of impaired food consumption in older adults. This study aimed to address this gap in the literature, specifically focusing on acutely ill, older hospitalized patients.

This cross-sectional study used a post-hoc analysis of data from two prior studies conducted in two German acute care geriatric hospital departments. 377 patients (aged 63-100) were included. Nutritional status was assessed using the Mini Nutritional Assessment Short Form (MNA-SF), categorizing patients into normal, at-risk, and malnourished groups. Nutritional intake was measured using the food intake item of the Nutritional Risk Screening (NRS-2002) and the plate diagram method, grouping patients into categories based on percentage of requirements (>75%, 50–75%, ≤50%). CRP levels were analyzed using standard procedures, categorized as no inflammation (0.0-0.49 mg/dl), mild inflammation (0.5-3.0 mg/dl), and moderate to severe inflammation (≥3.0 mg/dl). Geriatric assessments included the Barthel Index (self-care), Montreal Cognitive Assessment (MOCA) or Mini-Mental State Examination (MMSE) (cognitive function), and Depression in Old Age Scale (DIA-S) or Geriatric Depression Scale-15 (GDS-15) (depression). Data analysis was performed using SPSS software. Continuous variables were presented as means/SDs or medians/IQRs, and categorical variables as absolute numbers and percentages. Kruskal-Wallis test, pairwise comparisons, one-way ANOVA Tukey test, and Chi-square test were used as appropriate. Significance was set at P < 0.05.

The study population (mean age 82.2 ± 6.6 years; 241 females) comprised 27% with no inflammation, 40% with mild inflammation, and 33% with moderate to severe inflammation. 23% were malnourished, and 53% were at risk of malnutrition. 22% (82 patients) had food intake <50% of requirements, with 45% of this group showing moderate to severe inflammation. A significant difference in median CRP concentrations across food intake levels was observed. Patients with food intake <50% of requirements had a significantly higher median CRP level (2.3 mg/dl) than those with intake >75% (0.7 mg/dl, P < 0.001). No significant differences were found in median CRP levels across MNA-SF categories. The proportion of patients with food intake <50% of requirements increased progressively with CRP levels above 3.0 mg/dl (from 19% at 2.0-2.99 mg/dl to 28% at 3.0-4.99 mg/dl, P = 0.062).

This study confirms the association between inflammation, as measured by serum CRP, and low food intake in older hospitalized patients. A CRP level ≥3.0 mg/dl was identified as a potential threshold for acute inflammation leading to reduced food intake. This aligns with previous research showing that patients with CRP >3.0 mg/dl frequently had food intake <75% of requirements [5]. However, the study population consisted of very old and acutely ill patients with multiple comorbidities, making it difficult to isolate the effect of acute inflammation. Previous studies have applied different, sometimes lower, CRP cut-offs for identifying malnutrition, demonstrating the need for clearer guidelines regarding the inflammation criterion in the GLIM framework. This study highlights the clinical relevance of the CRP threshold in identifying patients at risk of malnutrition due to inflammation; however, other factors likely contribute to low food intake in this population.

A serum CRP of 3.0 mg/dl appears to be a useful threshold for acute inflammation associated with reduced food intake in acutely ill older patients. This finding offers guidance regarding the inflammation criterion in the GLIM malnutrition diagnosis. Further research is needed to define clinically relevant thresholds for acute and chronic inflammation in relation to acute and chronic malnutrition, considering the duration of inflammatory exposure and the often multifactorial etiology of malnutrition in older adults.

The study's limitations include its post-hoc design using two different methods for assessing food intake (plate diagram and NRS-2002), the absence of a gold standard for evaluating food intake in older adults, and the inclusion of a population of very old, acutely ill patients with multiple comorbidities. This makes it challenging to differentiate between the effects of acute and chronic inflammation. The multifactorial nature of malnutrition in older individuals suggests that other factors beyond acute inflammation contribute to low food intake, introducing potential residual confounding. Future prospective studies are needed to address these limitations.