Low Vitamin D May Not Be Linked to Epstein-Barr Virus Status
Low 25(OH)D3 did not affect EBV load or anti-EBV nuclear antigen-1 titer in a young, healthy cohort
Low 25-hydroxyvitamin D3 [25(OH)D3] levels did not affect Epstein-Barr virus (EBV) load or anti-EBV nuclear antigen-1 (EBNA-1) titer in a young, healthy cohort, according to a recent report (Ramien et al., 2013).
“Mounting evidence implicates both late age at EBV infection and hypovitaminosis-D as key environmental risk factors in MS,” wrote Caren Ramien of the Department of Neuroscience and Trauma, Blizard Institute, Queen Mary University of London, U.K., and colleagues. “Supporting evidence for a potential physiological interaction between EBV and vitamin D comes from recent studies, which showed the blocking effect of Epstein-Barr Nuclear Antigen 3 (EBNA-3) on the transcription of [vitamin D receptor]-dependent genes. This led us to test for in-vivo interdependence between EBV- and vitamin D status.”
Of 98 healthy, young, first-year medical students at the University of Birmingham, U.K., who were seropositive for EBV, 44 gave plasma samples in October and 54 gave plasma samples in November. Vitamin D status should theoretically be higher in the autumn, after exposure to more sunlight during the summer months. The investigators measured EBV load using quantitative polymerase chain reaction, and they measured 25(OH)D3 levels using isotope-dilution liquid chromatography-tandem mass spectrometry.
Levels of 25(OH)D3 measured during the autumn were surprisingly low in this young, healthy cohort, with a mean value of 40.5 nmol/L ± 5.02. Levels below 50 nmol/L represent insufficiency, and 69% of the participants had levels that low or lower. The recommended level is 75 nmol/L or above, and only 2.8% of participants had recommended values.
Investigators found a positive correlation between EBV load and EBNA-1 titers. At low 25(OH)D3 levels, however, there was no interdependence between EBV load, anti-EBNA-1 titers, and 25(OH)D3 status. The investigators therefore suggest that insufficient levels of serum 25(OH)D3 do not affect EBV replication and anti-EBNA-1 titers.
“Interestingly, acute upper respiratory tract infections, which can also exacerbate MS, have been associated with serum vitamin-D levels of < 40 nmol/L in healthy individuals,” the study authors write. “It is, therefore, of great interest to test whether and how vitamin-D supplementation decreases microbial infection by switching on genes involved in anti-pathogen immunity.”
Limitations of this study include relatively small sample size, lack of longitudinal data, and failure to account for HLA type of the participants. The investigators suggest that higher 25(OH)D3 serum levels than those observed in this cohort may be needed to see effects on EBV status.
“We were surprised to find 69% of our UK autumn cohort with insufficient levels of 25(OH)D3,” the study authors conclude. “Even post-summer 25(OH)D3 levels, bearing in mind that 2007 was one of the wettest UK summers in recent years, were low in this UK cohort, which highlights the need for raising awareness of hypovitaminosis-D in MS patients and the general UK population and the introduction of adequate supplementation strategies. Our work, which focused on hypovitaminosis-D and EBV status as two potential culprits in MS, highlights the need for further studies to elucidate the conundrum of risk factors and disease triggers in MS.”
Key open questions
- How would these findings in a young, healthy cohort with relatively low vitamin D levels compare with those in cohorts of MS patients with hypovitaminosis-D and with sufficient vitamin-D levels?
- What effect, if any, would the HLA type of the study subjects have on any potential association between vitamin-D levels and EBV?
- Is there any temporal association between hypovitaminosis-D, viral dynamics, and antiviral immunity, as might be determined in longitudinal studies?
Disclosures
The Erasmus Programme, Aims2Cure, MRC, and Roan Charitable Trust supported this study. The study authors reported having no financial disclosures.