Tuesday, 26 November 2013

Is EBV-infection under the control of Vitamin-D?

Ramien C, Pachnio A, Sisay S, Begum J, Leese A, Disanto G, Kuhle J, Giovannoni G, Rickinson A, Ramagopalan SV, Moss P, Meier UC.Hypovitaminosis-D and EBV: no interdependence between two MS risk factors in a healthy young UK autumn cohort. Mult Scler. 2013 Nov 5. [Epub ahead of print]

Late Epstein-Barr virus infection and hypovitaminosis-D as environmental risk factors in the pathogenesis of multiple sclerosis are gaining great interest. We, therefore, tested for in-vivo interdependence between Epstein-Barr-virus (EBV)-status and 25-hydroxyvitamin D3 (25(OH)D3) -level in healthy young individuals from a United Kingdom (UK) autumn cohort. EBV-load was measured by quantitative polymerase chain reaction and 25(OH)D3 levels by isotope-dilution liquid chromatography-tandem mass spectrometry. This young, healthy UK autumn cohort showed surprisingly low levels of 25(OH)D3 (mean value: 40.5 nmol/L ± 5.02). Furthermore, we found that low 25(OH)D3 levels did not impact on EBV load and anti-EBV nuclear antigen-1 (EBNA-1) titers. However, we observed a correlation between EBV load and EBNA-1 titers. These observations should be of value in the study of the potential relationship between hypovitaminosis-D and EBV-status in the pathophysiology of multiple sclerosis
“As EBV-status and suboptimal Vitamin-D levels are potential risk factors for MS, we wanted to test whether they acted in concert or independently. In collaboration with Birmingham’s CMV/EBV teams, we measured EBV-status and Vitamin-D levels in young, healthy medical students.

What did we find? To our surprise, the majority of students had insufficient Vitamin-D levels. Interestingly, the samples were obtained in 2007 after one of the wettest UK summers. We did not see an effect on the control of EBV-infection at these suboptimal vitamin-D levels.

There are now two potential scenarios: vitamin-D and EBV-status act independently as risk factors in MS or optimal vitamin-D levels may be needed to exert an effect on EBV-infection.”

Several studies have monitored anti-EBV responses and vitamin-D levels in MSers:

Epstein-Barr virus antibodies and vitamin D in prospective multiple sclerosis biobank samples. Salzer J, Nyström M, Hallmans G, Stenlund H, Wadell G, Sundström P. Mult Scler. 2013 Oct;19(12):1587-91. 2013 Apr 2.

Vitamin D supplementation and antibodies against the Epstein-Barr virus in multiple sclerosis patients. Disanto G, Handel AE, Damoiseaux J, Hupperts R, Giovannoni G, Smolders J, Ramagopalan SV. Mult Scler. 2013 Oct;19(12):1679-80.

Review on EBV and VitD: Vitamin D: a link between Epstein-Barr virus and multiple sclerosis development? Disanto G, Meier U, Giovannoni G, Ramagopalan SV.  Expert Rev Neurother. 2011 Sep;11(9):1221-4.

“Furthermore, given my past area of work, I am very interested in the literature on Hepatitis-C/ Hepatitis-B/HIV-infection. They are testing similar ideas on persistent virus infections and Vitamin-D at the moment to see whether vitamin-D supplementation has an effect on anti-viral immune responses, immunopathology and the response to treatment.”

Low vitamin D serum concentration is associated with high levels of hepatitis B virus replication in chronically infected patients. Farnik H, Bojunga J, Berger A, Allwinn R, Waidmann O, Kronenberger B, Keppler OT, Zeuzem S, Sarrazin C, Lange CM. Hepatology. 2013 Oct;58(4):1270-6. doi: 10.1002/hep.26488. Epub 2013 Aug 7.

Vitamin D deficiency is associated with severity of liver disease in HIV/HCV coinfected patients. Guzmán-Fulgencio M, García-Álvarez M, Berenguer J, Jiménez-Sousa MA, Cosín J, Pineda-Tenor D, Carrero A, Aldámiz T, Alvarez E, López JC, Resino S. J Infect. 2013 Nov 1. S0163-4453(13)00326-5. 10.1016/j.jinf.2013.10.011. [Epub ahead of print]

“So far we conclude that rainy UK summers may impact on your health and you may want to consider vitamin-D supplementation in the UK or spending your summer holidays somewhere sunny.”

CI: Ute-Christiane Meier reports no conflict of interest


  1. Can anyone please tell me if the summer of 1978 was a good one?

    1. Not a great summer in the UK.

  2. Thanks Ute,

    Couldn't you repeat your measurements in the blood described in this paper ?
    The summer level of 25(OH)D in August was almost 50% higher than the winter level in February.

    Lower serum vitamin D levels are associated with a higher relapse risk in multiple sclerosis.

    Runia TF, Hop WC, de Rijke YB, Buljevac D, Hintzen RQ.

    Neurology. 2012 Jul 17;79(3):261-6.

  3. These vitamin d levels were measured in October/November so they are not even near there lowest level for the year and the actual range rather than average was 20–78 nmol/L (I can be on average comfortable with my head in the cooker and my feet in the freezer). It says that vitamin d deficiency in this country is serious and supplementation is needed if only to protect bone health.

    It would have been interesting to have followed their levels through the winter and seen what happened rather than a single snap shot. EBV may react to a rise or fall in vitamin d the way cold sores react to sun shine.

  4. @Barbara&Anonymous: I agree, our study gives only a snapshot and does not account for potential lag effects as VitD and EBV were measured at the same time. However, that was the best we could do with our existing cohort, budget and ethics.
    There is also a very interesting editorial in the October issue of Multiple sclerosis:
    Understanding the joint effects of EBV and VitD in MS (A. Ascherio/K. Munger) http://msj.sagepub.com/content/19/12/1554.long.
    I am sure more labs will be looking into this and the picture will be more complete in the not so distant future.


  5. "EBV may react to a rise or fall in vitamin d the way cold sores react to sun shine."

    Maybe even cold sores i.e. Herpes Simplex also should be further investigated. Not to leave any stone unturned.

    This blog has earlier referred to a study that showed that Aclyclovir - a common herpes simplex-treatment reduced MS-attacks with over 30 per cent.

    1. EBV is a member of the herpes virus family. Severe EBV infection is treated with Acyclovir so the reduction of relapses MS may well be due to its action on EBV rather than herpes simplex.

    2. It could be that herpes simplex reacts to sunlight because, to the virus, it is an indicator that the vitamin d levels are about to rise and the person is at their most vulnerable state.


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