For most people, vitamin D supplements will do nothing to ward off COVID-19 or reduce its severity, a massive new study has found.
Scientists looked at DNA collected from nearly 1.3 million people in 11 countries, seeing if they could find a link between genetic markers associated with high vitamin D levels and the chance of catching it, and for those who did catch it, how sick they got.
They found no link whatsoever, despite some previous studies suggesting vitamin D might offer some protection.
"It's always been a very appealing prospect that vitamin supplementation might improve outcomes or might be a preventive therapy, and this study's found no evidence for that," said Prof Michael Baker, an epidemiologist at the University of Otago.
Vitamin D has been looked at closely through the course of the pandemic. A study last year found it could reduce ICU admissions by up to 80 percent - but was later withdrawn, after serious irregularities with its design emerged. Some others have found an association between vitamin D deficiency and worse outcomes.
"Most vitamin D studies are very difficult to interpret since they cannot adjust for the known risk factors for severe COVID-19 (eg. older age, institutionalisation, having chronic diseases) which are also predictors of low vitamin D," said Guillaume Butler-Laporte, an infectious diseases researcher at McGill University in Quebec, Canada.
"Therefore, the best way to answer the question of the effect of vitamin D would be through randomised trials, but these are complex and resource intensive, and take a long time during a pandemic."
Dr Baker said observational studies often can't separate the effects of one thing - in this case, vitamin D - from others.
"One of the problems is that often people taking vitamin D have different features from people who don't - that's called confounding. You really need good-quality trials normally to investigate whether vitamin D is protective."
The biggest randomised, controlled trial to date only had 240 people in it - and it found dosing COVID-19 patients with vitamin D did nothing.
This latest research analysed data from a number of previous studies using a statistical technique called Mendelian randomisation, which Dr Baker says "gets around the fact of confounding".
"It uses genetic markers of high vitamin D levels in the blood. They were able to look at over 4000 individuals with COVID-19 and 1.2 million people without the infection - so it's an enormously large study, and they found no protective effect whatsoever associated with genetic markers for high vitamin D."
People with high genetic disposition towards high levels of vitamin D weren't more or less likely to catch the virus, and their outcomes were no better than those with normal levels.
"At this stage you'd have to conclude there's very little support for vitamin D making a big difference to the pandemic," said Dr Baker.
But that doesn't mean supplements can't still play a role on an individual basis. The studies included in the latest research only looked at individuals with European ancestry, and Dr Baker says darker skin reduces the body's ability to make vitamin D.
The study also didn't include anyone with clinical vitamin D deficiency, "and it remains possible that truly deficient patients may benefit from supplementation for COVID-19 related protection and outcomes".
"Supplementation might be useful for that group, but it's not likely to be protective for people with typical levels," said Dr Baker.
Instead, both he and the study's authors say we'll have to rely on other ways to end the pandemic - such as vaccines, which we know actually work.
The latest study was published in journal PLOS Medicine.