Evaluating the impact of inflammation caused by Norovirus on vitamin A biomarker concentrations Público
Victor, Courtney (Spring 2019)
Abstract
Background: As of 2018, there are still millions of individuals who are vitamin A deficient worldwide, which causes adverse health outcomes such as ocular manifestations and impaired immune system function. While it is known that inflammation has an impact on measurements of vitamin A biomarkers, there is no standardized approach to adjust assessments for inflammation.
Goal: The goal of this research was to evaluate the impact of inflammation caused by norovirus infection on vitamin A biomarkers, retinol and retinol binding protein.
Methods: Using longitudinal data collected from 52 individuals in two separate norovirus challenge studies, we assessed the molar relationship between retinol and retinol binding protein, compared the methodology and utility in the Thurnham and Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) inflammation-adjustment approaches on longitudinal data, and assessed the kinetics of serum retinol over the course of an infection using linear-mixed methods.
Results: The average ratio between retinol and RBP was 0.69 (IQR=0.12), which violates popular assumptions but corroborates findings from other studies. While both the BRINDA and Thurnham-adjustment approaches were appropriate using longitudinal data, the mild inflammatory response resulted in 0 or 1 individual in the early convalescence or late period in 7 of the time points. Thus, we were unable to compare the results of the Thurnham correction factor approach. Although the BRINDA-adjustment initially was successful in correcting retinol towards baseline on days 2, 3, and 4 post-exposure, retinol was significantly different (1.02-1.12 µmol/L) from baseline on days 4 (p=0.03), 7 (p<0.001), 14 (p<0.001), and 35 (p=0.01). Lastly, we were able to demonstrate a 0.01 µmol/L reduction in retinol as a result of inflammation by day post-exposure (p=0.03).
Conclusions: The results of this study demonstrate (1) the presumed molar 1:1 ratio is not upheld even in healthy populations subjected to a norovirus challenge, (2) the BRINDA approach was more appropriate than Thurnham in the face of low-levels of inflammation, and (3) modeling indicated an overall effect of inflammation by day post-exposure on changes in retinol concentration.
Public Health Implications: Because we found that the ratio between retinol and RBP was not equimolar, future assessments that use RBP as a proxy to measure vitamin A levels should consider adjusting the cutoff values for VAD. While both correction methods are appropriate for longitudinal analysis, adjustment for inflammation in populations with low-levels of inflammation should be conducted using the BRINDA approach. Finally, we demonstrated that consideration for inflammation is needed even in populations with low-levels of inflammation as it can still alter serum retinol levels.
Table of Contents
LITERATURE REVIEW……………………………………………………………..…1
METHODS……………………………………………………………………………...17
RESULTS………………………………………………………………………...……..22
DISCUSSION…………………………………………………………………………...27
PUBLIC HEALTH IMPLICATIONS…………………………………………………..33
REFERENCES…………………………………………………………………………..34
TABLES AND FIGURES……………………………………………………………….37
APPENDIX A: IRB EXEMPTION LETTER.…………………………………………..40
APPENDIX B: SUPPLEMENTAL TABLES…………………………………………...41
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