While daily supplementation increased circulating vitamin D concentrations in study participants, elevated levels did not translate into improved immune responses, contrary to the results from other studies, the research team wrote.
“The null findings contrast with the results of our previous intervention study, in which we showed that vitamin D replacement in older adults with baseline 25(OH)D levels below 75 nmol/L boosted antigen-specific immunity and reduced inflammatory responses to a cutaneous VZV antigen challenge.”
They acknowledge that different study methods and analyses may explain divergent results but, notwithstanding, the current study rescinds the use of vitamin D supplements as an adjunct to SARS-CoV-2 vaccination.
“The fact that our results were consistent across a broad range of outcomes strengthens the interpretation that our null results are valid,” they write.
Conflicting results
Low vitamin D status is common in adults and linked to systemic inflammation. Given the vitamin’s known anti-inflammatory activity and proven role in regulating human immune functions, experts advocate supplementation to improve virus outcomes.
“An experimental study has demonstrated that vitamin D supplementation significantly increased the response to the cutaneous varicella zoster virus (VZV) antigen challenge in older adults with circulating 25(OH)D concentrations less than 75 nmol/L,” the authors explain.
“This enhancement was associated with a reduction in early inflammatory monocyte infiltration with a concomitant enhancement of T cell recruitment to the site the antigen challenge.”
However, other studies have produced conflicting results and challenge positive findings. This inspired researchers to question the validity of supplementation in the context of SARS-CoV-2 vaccination and subsequent immune responses.
Sub-study methodology
Researchers investigated the effect of vitamin D on immune responses to COVID-19 vaccines on adults with sub-optimal circulating vitamin D (25(OH)D) concentrations below 75nmol/L at baseline.
Participants were aged 16 or over and registered blood 25(OH)D concentrations of 75nmol/L or less. They consumed a daily dose of either 800 IU or 3200 IU of D-Pearls vitamin D3 capsules, supplied by Pharma Nord, or vegan alternative, Pro D3 (from Synergy Biologics), for six months.
The protocol involved three sub-studies as part of a randomised trial examining the role of vitamin D supplements in the prevention of acute respiratory infection in UK adults (CORONAVIT).
The first sub-study analysed the effects of supplementation on vaccine efficacy after two doses, the second examined antibody responses to the virus Spike (S) protein and the third evaluated antibody and cellular neutralising responses.
Only double vaccinated volunteers were invited to provide postal dried blood spot samples to determine antibody responses to S proteins and a subset of 101 provided venous blood samples for neutralising antibody and cellular immune responses to SARS-CoV-2.
Analysis results
Measurements of vitamin D status revealed significantly elevated average follow-up concentrations in both the low and high dose groups, compared to the control group, with mean differences of 28.8 nmol/L and 51.7 nmol/L respectively.
Similar breakthrough infections were reported among participants in both intervention groups. Five cases of COVID-19 (three in the 3200 vitamin D group and two controls) required hospital treatment, but none were fatal.
There were no discernible inter-arm differences in post-vaccination anti-Spike antibodies (IgGAM); in mean neutralising antibodies in the venous blood sample analysis, or antigen-specific cellular responses.
The authors’ commented: “Neither dose influenced SARS-CoV-2 vaccine efficacy or immunogenicity. Improvements in vitamin D status were not associated with inter-arm differences in the risk of breakthrough SARS-CoV-2 infection, post-vaccination titres of anti-S or neutralising antibodies or any cellular immune response investigated.”
Source: Nutrients
Published online, September 16, 2022: http://doi.org/10.3390/nu14183821
‘Vitamin D Supplementation Does Not Influence SARS-CoV-2 Vaccine Efficacy or Immunogenicity: Sub-Studies Nested within the CORONAVIT Randomised Controlled Trial’
Authors: David A. Jolliffe, Giulia Vivaldi, Emma S. Chambers, Weigang Cai, Wenhao Li, Sian E. Faustini, Joseph M. Gibbons 2, Corinna Pade, Anna K. Coussens, Alex G. Richter, Áine McKnight and Adrian R. Martineau