ce4faac86532e1d2daa562d1ace6c305 nutrients-17-00226.pdf be72537a4c3e835ce7c4c266262cb9cca83a4575 nutrients-17-00226.pdf 3a99ef33592400a7a90eca48d228220de2792d407283b44b2e751eb81b1c6715 nutrients-17-00226.pdf Title: Vitamin D Supplementation Is Associated with Inflammation Amelioration and Cognitive Improvement in Decompensated Patients with Cirrhosis Subject: Background/Objectives: Decompensated cirrhosis is characterized by systemic inflammation and innate and adaptive immune dysfunction. Hepatic encephalopathy (HE) is a prevalent and debilitating condition characterized by cognitive disturbances in which ammonia and inflammation play a synergistic pathogenic role. Extraskeletal functions of vitamin D include immunomodulation, and its deficiency has been implicated in immune dysfunction and different forms of cognitive impairment. The aim was to assess changes in cognitive function and inflammation in decompensated patients with cirrhosis receiving vitamin D supplementation. Methods: Patients with cirrhosis discharged from decompensation in two tertiary hospitals in Spain (from September 2017 to January 2020) were assessed before, at 6 and 12 months after vitamin D supplementation. A comprehensive neuropsychological battery and neuroinflammatory markers were examined. In a subgroup of patients, peripheral immune blood cells were analyzed. Results: Thirty-nine patients were recruited. Of those, 27 completed the 6 months evaluation and were analyzed [age 62.4 11.3 years; 22 men; Model for End-Stage Liver Disease (MELD) 11.7 4.0; prior overt HE 33%; median 25-hydroxyvitamin D (25OHD) plasma level 12.7 gr/L] and 22 achieved 12 months assessment. At baseline, learning and memory (R = 0.382; p = 0.049) and working memory (R = 0.503; p = 0.047) subtests correlated with plasma 25OHD levels. In addition, processing speed (R = -0.42; p = 0.04), attention (R = -0.48; p = 0.04), Tinnetti balance (R = -0.656; p < 0.001) and Tinnetti score (R = -0.659; p < 0.001) were linked to neuroinflammation marker IL-1. Patients with lower 25OHD had a greater proportion of TH1cells at baseline and a larger amelioration of IL-1 and IL-6 following supplementation. An improvement in working memory was found after 25OHD replacement (46.7 13 to 50 11; p = 0.047). Conclusions: This study supports that vitamin D supplementation modulates low-grade inflammation in decompensated cirrhosis providing cognitive benefits, particularly in working memory. Keywords: vitamin D; cognitive function; liver cirrhosis; inflammation; human Author: Raquel Diaz-Ruiz, Maria Poca, Eva Roman, Rocio Panadero-Gomez, Berta Cuyàs, Irene Bañares, Angela Morales, Marta Puerto, Rocio Lopez-Esteban, Elena Blazquez, Marta Fernández-Castillo, Rafael Correa-Rocha, Marta Rapado-Castro, Irene Breton, Rafael Bañares, German Soriano and Rita Garcia-Martinez Creator: LaTeX with hyperref Producer: pdfTeX-1.40.24 CreationDate: Thu Jan 9 09:12:54 2025 CET ModDate: Thu Jan 9 09:15:13 2025 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 19 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2018001 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- LEVXPH+EURM10 Type 1 Builtin yes yes yes 10 0 AZUTVD+VnURWPalladioL-Bold Type 1 Custom yes yes yes 15 0 CFDXUA+URWPalladioL-Roma Type 1 Custom yes yes yes 21 0 LIVFZE+URWPalladioL-Bold Type 1 Custom yes yes yes 27 0 JRBMHZ+URWPalladioL-Ital Type 1 Custom yes yes yes 32 0 CZMDWU+CMSY10 Type 1 Builtin yes yes yes 37 0 QZBFWS+VnURWPalladioL Type 1 Custom yes yes yes 42 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 80 0 ECFCNL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 156 0 ECFCNM+PalatinoLinotype CID TrueType Identity-H yes yes yes 159 0 ECFCNN+PalatinoLinotype TrueType WinAnsi yes yes no 165 0 ECFCNP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 168 0 ECFDFO+PalatinoLinotype TrueType MacRoman yes yes no 171 0 ECFJCN+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 285 0 ECFCNL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 288 0 ECFCNM+PalatinoLinotype CID TrueType Identity-H yes yes yes 291 0 ECFCNN+PalatinoLinotype TrueType WinAnsi yes yes no 297 0 ECFCNP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 300 0 ECFDFO+PalatinoLinotype TrueType MacRoman yes yes no 303 0 ECFJCN+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 378 0 ECFCNL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 381 0 ECFCNM+PalatinoLinotype CID TrueType Identity-H yes yes yes 384 0 ECFCNN+PalatinoLinotype TrueType WinAnsi yes yes no 390 0 ECFCNP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 393 0 ECFDFO+PalatinoLinotype TrueType MacRoman yes yes no 396 0 CRUZTT+VnURWPalladioL-Italic Type 1 Custom yes yes yes 456 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-02-05 04:18:23 CET RepresentationInformation: nutrients-17-00226.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-02-04 15:56:42 CET Size: 2018001 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 710 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Design Destination: subsection.2.1 Item: Title: Patients Destination: subsection.2.2 Item: Title: Treatment Destination: subsection.2.3 Item: Title: Neuropsychological Assessment Destination: subsection.2.4 Item: Title: Falls Assessment Destination: subsection.2.5 Item: Title: Fractures Assessment Destination: subsection.2.6 Item: Title: Infections Assessment Destination: subsection.2.7 Item: Title: Inflammatory Markers Destination: subsection.2.8 Item: Title: Statistical Analysis Destination: subsection.2.9 Item: Title: Results Destination: section.3 Children: Item: Title: Baseline Evaluation Destination: subsection.3.1 Children: Item: Title: Cognitive Function Destination: subsubsection.3.1.1 Item: Title: Assessment of Risk Falls and Fracture Risks Destination: subsubsection.3.1.2 Item: Title: Infections Destination: subsubsection.3.1.3 Item: Title: Inflammation Destination: subsubsection.3.1.4 Item: Title: Follow-Up Evaluation Destination: subsection.3.2 Children: Item: Title: Cognitive Function Destination: subsubsection.3.2.1 Item: Title: Assessment of Falls and Fracture Risks Destination: subsubsection.3.2.2 Item: Title: Infections Destination: subsubsection.3.2.3 Item: Title: Inflammation Destination: subsubsection.3.2.4 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: Vitamin D Supplementation Is Associated with Inflammation Amelioration and Cognitive Improvement in Decompensated Patients with Cirrhosis Author: Raquel Diaz-Ruiz, Maria Poca, Eva Roman, Rocio Panadero-Gomez, Berta Cuyàs, Irene Bañares, Angela Morales, Marta Puerto, Rocio Lopez-Esteban, Elena Blazquez, Marta Fernández-Castillo, Rafael Correa-Rocha, Marta Rapado-Castro, Irene Breton, Rafael Bañares, German Soriano and Rita Garcia-Martinez Subject: Background/Objectives: Decompensated cirrhosis is characterized by systemic inflammation and innate and adaptive immune dysfunction. Hepatic encephalopathy (HE) is a prevalent and debilitating condition characterized by cognitive disturbances in which ammonia and inflammation play a synergistic pathogenic role. Extraskeletal functions of vitamin D include immunomodulation, and its deficiency has been implicated in immune dysfunction and different forms of cognitive impairment. The aim was to assess changes in cognitive function and inflammation in decompensated patients with cirrhosis receiving vitamin D supplementation. Methods: Patients with cirrhosis discharged from decompensation in two tertiary hospitals in Spain (from September 2017 to January 2020) were assessed before, at 6 and 12 months after vitamin D supplementation. A comprehensive neuropsychological battery and neuroinflammatory markers were examined. In a subgroup of patients, peripheral immune blood cells were analyzed. Results: Thirty-nine patients were recruited. Of those, 27 completed the 6 months evaluation and were analyzed [age 62.4 11.3 years; 22 men; Model for End-Stage Liver Disease (MELD) 11.7 4.0; prior overt HE 33%; median 25-hydroxyvitamin D (25OHD) plasma level 12.7 gr/L] and 22 achieved 12 months assessment. At baseline, learning and memory (R = 0.382; p = 0.049) and working memory (R = 0.503; p = 0.047) subtests correlated with plasma 25OHD levels. In addition, processing speed (R = -0.42; p = 0.04), attention (R = -0.48; p = 0.04), Tinnetti balance (R = -0.656; p < 0.001) and Tinnetti score (R = -0.659; p < 0.001) were linked to neuroinflammation marker IL-1. Patients with lower 25OHD had a greater proportion of TH1cells at baseline and a larger amelioration of IL-1 and IL-6 following supplementation. An improvement in working memory was found after 25OHD replacement (46.7 13 to 50 11; p = 0.047). Conclusions: This study supports that vitamin D supplementation modulates low-grade inflammation in decompensated cirrhosis providing cognitive benefits, particularly in working memory. 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