https://openworks.mdanderson.org/sumexp23/1102/thumbnail.jp

Fedirko, Veronika

Lee, Sangji

English

OpenWorks @ MD Anderson

Introduction• Inflammation, a potential factor contributing to gut barrier disfunction, is significant in colon carcinogenesis.• On the other hand, a weakened gut barrier is more prone to the foreign antigens, causing endotoxemia and inflammation, which promotes colorectal cancer (CRC)• Lipopolysaccharide (LPS)-binding protein (LBP): A biomarker for activation of innate immune responses to microbial products and a marker of LPS.• Intestinal fatty-acid binding protein (IFABP): Elevated in conditions characterized by increased intestinal permeabilityEffects of Supplemental Calcium and Vitamin D on Circulating Biomarkers of Gut Barrier Function in Colorectal Adenoma Patients: A Randomized Controlled TrialEffects of Supplemental Calcium and Vitamin D on Circulating Biomarkers of Gut Barrier Function in Colorectal Adenoma Patients: A Randomized Controlled TrialDavid Lee1,2 , Veronika Fedirko1Research QuestionDoes vitamin D and calcium supplementation affect the circulating biomarker of gut barrier function among individuals at high risk of CRC? If so, is there a difference in the treatment effect by BMI or pro inflammatory cytokine level?Conclusion:  Overall, our study findings indicate decrease in LBP and IFABP concentrations with administration of vitamin D over 1 year. This effect was stronger among individuals with higher BMI for LBP and among individuals with lower IL-6 concentrations for IFABP. Our results suggest that vitamin D could potentially be used as a protective agent against gut barrier dysfunction and inflammation, which is associated with CRC risk. Final analyses are being prepared to be submitted to the AACR conference or to be published.MethodParent Study• 11-center, randomized, placebo-controlled, partial 2x2 factorial chemoprevention clinical trial, the Vitamin D/Calcium Polyp Prevention Study (NCT00153816).• Participants: ages 45-75 years with at least one colorectal adenoma removed within 120 days prior to enrollment and with scheduled 3-year or 5-year colonoscopic follow-up examinations (patients were from 2 centers; Georgia and South Carolina).• Treatment Assignment: “4-arm study”: elemental Ca 1.2 g/d, vitamin D3 1,000 IU/d, both, or placebo;  “2-arm study”: women who declined to forego Ca supplementation were randomized to vitamin D or placeboAdjunct Study• Participants: 118 participants• Blood was drawn at the baseline and 1-year follow-up• LBP and IFABP level was analyzed through electrochemiluminescent Human LBP Assay Kit and ELISAStatistical Analysis• X2  Test for categorical variables and ANOVA or T-test to compare baseline characteristics of participants across treatment arms.• Generalized linear model (PROC MIXED) to compare the difference in biomarker levels between treatment groups• Stratified analysis by median level of baseline serum 25-OH-vitamin D, total calcium intake, BMI and inflammatory biomarker (IL6) concentration.• All analysis was done on SAS version 9.4.Vitamin D & Ca (4-arm) Vitamin D Only (2-arm)Characteristic Placebo (n=21)Ca(n=17)Vit D (n=20)Ca + Vit D (n=19) PPlacebo (n=22)Vit D (n=19) PAge, yrs 60 59 59 58 0.82 58 59 0.65Men, % 86 71 65 84 0.36 - - -White, % 81 71 75 94 0.28 68 84 0.29Smoking status, %Never 52 77 60 47 0.30 64 53 0.21Former 33 18 40 47 36 32Current 14 6 0 5 0 16Family hx of CRC, % 10 6 17 5 0.63 5 11 0.58ASA or NSAID users, % 67 94 60 58 0.08 50 47 0.87BMI, kg/m2 29 33 29 30 0.09 29 27 0.29Advanced adenoma, % 38 12 20 26 0.28 9 16 0.51Total energy, kcal/d 1,363 1,780 1,406 1,626 0.07 1,332 1,434 0.57Total calcium, mg/d 639 976 649 692 0.01 1,076 1,227 0.40Total vitamin D, IU/d 356 482 307 427 0.28 562 634 0.5425-OH-D, ng/ml 23 24 24 23 0.91 25 26 0.70Table 1. Selected baseline characteristics of the study participantsaaData are shown as mean unless otherwise specifiedFunding: NCI R25 CA056452, R21 CA182752 Reference1. Ghosh, S. S., et al. (2020). PMCID: PMC70330381. Department of Epidemiology, MD Anderson Cancer center2. Department of Epidemiology and Biostatistics, Texas A&M UniversityResult• LBP decreased in vitamin D group relative to the no vitamin D group after 1 year of supplementation.• LBP did not change in calcium group relative to the no calcium group and in the vitamin D and calcium group relative to the calcium group after 1 year of supplementation. • IFABP decreased in vitamin D group relative to the no vitamin D group after 1 year of supplementation.• IFABP also decreased in vitamin D and calcium group relative to the calcium group while there was no change in the calcium group and no calcium group after 1 year of supplementation.• LBP decreased in vitamin D group relative to the no vitamin D group, in participants with greater than or equal to median BMI but not in participants with less than median BMI.• IFABP decreased in vitamin D group relative to the no vitamin D group and calcium and in the vitamin D group relative to the calcium group, in participants with less than median IL-6 concentration but not in participants with greater than or equal to median IL-6 concentration.

Effects of Supplemental Calcium and Vitamin D on Circulating Biomarkers of Gut Barrier Function in Colorectal Adenoma Patients: A Randomized Controlled Trial

https://openworks.mdanderson.org/cgi/viewcontent.cgi?article=1102&context=sumexp23

Effects of Supplemental Calcium and Vitamin D on Circulating Biomarkers of Gut Barrier Function in Colorectal Adenoma Patients: A Randomized Controlled Trial

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