Vitamin D and COVID 19- hope or hype?

Introduction

In a word, hype. It would be so nice to have a simple and cheap way to alleviate the ravages of COVID19, or other infections, readily available to all. Hydroxychloroquine, Ivermectin, Vitamin C, Zinc and a host of other have come and gone, but Vitamin D for many makes more sense – we really do need this and its lack causes big problems.

Now, a recent study has claimed giving people Vit D when admitted with COVID19 halved the risk of death and reduced ITU admissions by 75%. Staggeringly impressive findings which have woozled their way around cyberspace. Worth a look!

Latitude Vitamin D and MS!

Yet let me start by saying I take Vitamin D every day and have done since my diagnosis of MS ten years ago. The evidence behind this is for me quite compelling, if not totally conclusive.

This is compounded by our modern indoor lives and our destruction of the habitats of oily fish which in the past provided the bulk of Vitamin D intake in many northern latitudes. There, fish were the staple up till this millennia and provided enough Vitamin D in an environment where sunlight is insufficient to catalyse the step required for its synthesis in the skin.

I could go on at length about Vitamin D and MS, it’s a fascinating subject, an amazing substance, strictly speaking more of a hormone that a vitamin, and less controversial in a way because advising people with MS to take Vitamin D is now standard practice.

However, it’s not a magic bullet. MS is not caused by the lack of Vitamin D: its primary cause is infection with the EBV virus which causes glandular fever in teenagers in concert with the presence of certain genes. Vitamin D deficiency increases the risk. Indeed, taking Vitamin D can reduce the risk of developing auto-immune conditions, and so is particularly worthy for the families of anyone with these conditions.

Vitamin D and COVID

As its immune effects are well known, reasonable questions have been asked about the role of Vitamin D in COVID19. In those early pandemic days I certainly thought taking it was a good idea. Precautionary principle and all that. Low levels of the ‘sunshine Vitamin’ are certainly associated with poor outcomes, so the common sense notion to take supplements to boost those levels and hey presto reduce your risk took off.

Sadly, initial hopes that it might make a big difference faded in the face of evidence. This doesn’t stop online pundits, in particular, the increasingly popular and erratic Dr John Campbell claim “definitive evidence” that Vitamin D prevents severe illness. He plays to his audience with the accompanied emotive ’why oh why oh why’ type appeal to the 77,000 people who liked (and presumably shared) the post and its 1.3 million views. He concludes by suggesting the authorities are being negligent in not treating everyone with infection with Vitamin D. His mission statement is to ‘follow the evidence wherever it leads‘ so lets do precisely that and see where we go.

Definitive “Evidence”?

His ‘definitive evidence’ relates to a paper published on MDPI publishing platform. This is known for lack of selectivity and occasional publishers of nonsense, so it needs healthy skepticism, let’s have a look at its claims:

The title claims “definitive evidence” of benefit – not mincing their words, so Yippee! Incredible news!! At last something cheap and effective for COVID19!! Or does it?? Even reading the introductory comments makes me wonder:

“The TSA of the protective role of vitamin D in mortality risk showed that the z-curve was inside the alpha boundaries, indicating that the positive results need further studies. Discussion: The results of the meta-analyses and respective TSAs suggest a definitive association between the protective role of vitamin D and ICU hospitalization”

TSA analysis? Z curve? Alpha boundaries??  Hummm, now Im clever enough to tie my shoelaces in the morning, I understand p values and standard deviation, but these authors have clearly used some very obscure statistical tools to come to the conclusion of their meta-analysis. Also a “Definitive Association” in the abstract is a little more nuanced than the”Definitive Evidence” in the title. (There is a definitive association between ice cream sales and sunburn, but I’m pretty sure eating ice cream does not cause sunburn) Given that their hypothesis is relatively simple I find this suspicious. So, lets have a close look at what they have actually done:

First they select 5 out of 78 studies relating to Vitamin D which were good enough to be included, which as an aside, says something about how awful much Vitamin D research is. Their statistical tool, Trial Sequential Analysis is a method of eliminating errors from randomised controlled trials, so it seems a glaring error that one of the trials they include is an observational cohort study, skewing their conclusions. If this study is removed then their findings show less benefit. This is rather like a horse falling at the first fence, but let’s go on….

Bias matters

To be fair they go on to consider the risk of bias (ROB) of the five studies they included and illustrate the problem in a nice graphic. Now it starts to get really interesting:

(Legend: R—bias arising from the randomisation process; D—bias due to deviations from intended interventions; Mi—bias due to missing outcome data; Me—bias in measurement of the outcome; S—bias in selection of the reported results; O—overall risk of bias.)

It does not take a statistical genius to see that the Murai study is the only one of their 5 selected trials which is not significantly biased: indeed the authors themselves say “Only the study conducted by Murai had a low risk of bias” – so what did that study show? Brazilian researchers gave those admitted with COVID19 an intravenous dose of Vitamin D and looked at how they did compared to placebo. Disappointingly they found:

“Among hospitalized patients with COVID-19, a single high dose of vitamin D3, compared with placebo, did not significantly reduce hospital length of stay. The findings do not support the use of a high dose of vitamin D3 for treatment of moderate to severe COVID-19.”

For me, strange statistical manoeuvres hide what is clear from a detailed look at their work. Vitamin D doesn’t seem to work at preventing COVID19, and nor it seems, does it help reduce the severity of illness once you are admitted. I so wished it did.

Associations are clues, not causes

It’s all back to that word “Association” again. The word which seems absent from too many online pundits vocabulary. As I have blogged before, low Vitamin D levels are a consequence of many things: being housebound, stuck indoors, sedentary roles, eating a poor diet, polluted urban environments and being ill. Severe COVID19 is also associated with low levels of Vitamin D. Conversely high Vitamin D levels are a happy consequence of a diet rich in fresh oily fish and an active outdoor life.

Can a simple supplement really reverse all these multifactorial threats to health?

Even if it did, the inverse care law applies. Those taking supplements tend to be wealthier and more concerned with health which confounds many observational studies, including claims that if population levels of Vitamin D were normal COVID19 would not be a threat to anyone. Indeed! If we all were able or capable enough to lead active outdoor lives and were in good health we would be more resilient and the pandemic would not have been so severe.

The real world

But lets remember that people get old; genetic causes are behind a host of illnesses and vulnerabilities, the lived environment can be harmful, social and political policies can kill, work related problems exist, and the various genuine anxieties of the modern ailing world cause malaise which cannot be laid at the door of low Vitamin D levels despite the clear associations.

It’s rather like the notion that ability to balance on ones toes is a sure indicator of longevity. Of course it it – so is the ability to jump over a fence or run for a bus. This doesn’t mean that we should all spend time balancing on our tippy toes, or jumping over fences in order to live longer – those that can will, those that can’t are more frail, thats all it means.

Likewise, when it comes to autism, there a a multitude of claims of cause based on association with vaccine coverage, pesticides and organic food sales? What!! Organic food sales!!!

The paper certainly does not offer definitive evidence that Vitamin D reduces the risk of severe illness. It shows a definitive association, but that is very different from causation. I would not like to see people stop eating Ice cream to prevent sunburn, or avoid effective prevention and treatments in the hope that taking Vitamin D to prevent or ameliorate COVID19.

Big Punditry

Dr Campbell seems to have forgotten that correlation does not equal causation- which of course he hasn’t, but he doesn’t let that interfere with his videos which sadly misinform his multitude of fans. Others like Mercola milk the Vitamin D story even more – you can buy Vitamin D from his website for just 2.5 times that you pay on the high street.

Despite his lamentable appeal to those nasty public health officials, Vitamin D is in any case officially recommended for those at risk of its lack, and there are millions who are. To quote the NHS website: “Government advice is that everyone should consider taking a daily vitamin D supplement during the autumn and winter.”

However, it’s not a silver bullet when it comes to acute infections.

What to do?

For me I will continue to take Vitamin D as recommended by MS research and neurologists. Even better, I will continue to spend as much time outdoors as possible as long as I am able to do so. I do though, not expect it to have the benefit on infection or COVID19 claimed by Dr John Campbell and others who have jumped on this bandwagon to create, once again, poorly targeted sensation, outrage and anger.

Bad Medicine

Missing out on useful treatments that have been shown benefit in the hope that Vitamin D will do the job is potentially harmful. Taking Vitamin D continues to make sense for many, but it simply cannot match the benefits of simply being outside for as many hours a day as possible, as I have blogged before. There are effective ways of preventing and treating COVID19, Vitamin D is not one of them.

I suspect the paper will not pass peer review or get published in a decent journal, so it will disappear into the morass of pseudo-science. Yet it leaves in its wake in at least 77,000 people who liked the video and the 1.3 million who viewed it sadly misinformed, and thats not counting the Tweets, Tick-Tocks (if thats what they’re called) and other routes of dissemination of unedited nonsense. That is a lot of what I’m increasingly calling reverse-education.

Thanks for reading the blog. If you have any comments or feedback to leave it in the box below and I will get back to you as soon as I can. For now, I’m off outside!