Seven meta-analyses and systematic reviews (1,2,3,4,5,6,7) and three later clinical trials (1,2,3) argued that low vitamin D status increased susceptibility to COVID-19 and the risk of greater disease severity and mortality. Furthermore, there are five meta-analyses and systematic reviews of vitamin D supplementation for the prevention of acute respiratory infection (ARI) and COVID-19, as well as a later clinical trial, all showing that supplementation can protect against COVID-19 infection, disease severity and death. The evidence could not be much more conclusive than this.
Consequently, it was surprising to learn about Joliffe et al.’s recent randomised controlled trial of vitamin D to prevent ARIs and COVID-19, which concluded that: “Among people aged 16 years and older with suboptimal vitamin D status, implementation of a population level test-and-treat approach to vitamin D supplementation was not associated with a reduction in risk of all cause acute respiratory tract infection or COVID-19.”
Joliffe et al.’s U.K. study was a test-and-treat approach used to determine the effect of correcting suboptimal vitamin D status (25-hydroxyvitamin D (25(OH)D) < 75 nmol/L) on the risk of contracting ARIs and COVID-19. Those with 25(OH)D < 75 nmol/L (30 ng/mL) were randomised to six months of supplementary vitamin D at 3200 IU/day, 800 IU/day, or no supplements. The outcome was the percentage of subjects with confirmed ARI or COVID-19.
What was different about this trial that might have caused it to fail? Analysis of Joliffe et al.’s paper gives rise to a number of observations.
Of particular importance was the treatment of participants randomised to ‘No supplementation’. Instead of being given a placebo, as would be normal in a controlled study, they were given nothing and were informed that it was a vitamin D trial, thereby alerting them to the fact that vitamin D supplementation could be an important infection preventive in the middle of the COVID-19 pandemic. As a result, almost 50% reported taking their own vitamin D supplements. We do not know what level of supplementation these participants took and we can assume that if 50% reported supplementation, the actual number was probably higher. As Dr. David Grimes noted in a BMJ Rapid Response, this was therefore “a randomised uncontrolled study” [18]. Consequently, any comparison of the intervention arm with the ‘no supplementation’ arm was rendered meaningless. The authors sought to overcome this limitation by conducting sensitivity analysis, but this is no substitute for conducting a properly controlled trial.
Furthermore, the authors took the unusual step of retesting those who had baseline vitamin D levels of ≥75 nmol/L (≥30 ng/mL) after two months. If they now proved to have vitamin D levels of <75 nmol/L (<30 ng/mL), they were included in the study and supplemented for four months. These new participants amounted to 11% in the lower dose group and 20% in the higher dose group, which again risks distorting the results as they would have been less likely to benefit from vitamin D, as their second attempt at a baseline level would almost certainly have been only slightly below 75 nmol/L (30 ng/mL).
Following on from the first observation, most of the results depended upon all three groups actually telling the truth about the amount of supplemented vitamin D, whereas it is well known that participants respond to questionnaires in a manner designed to minimise criticism to themselves. For example, in the intervention arm, 90.9% reported that they took supplements at least six times a week. Based on the findings of other studies, this degree of adherence seems high. According to the authors, the fact that those retested showed a significantly higher vitamin D level compared with the ‘control group’ provides “objective evidence of a high level of adherence”. Though it indicates some adherence, it is not possible to make this kind of judgement merely from an increase from baseline levels. Elsewhere in sensitivity analysis, it appears that 94% claimed to have taken supplements “more than half the time”. How much more? If they only took the supplements for half the time, this would render a dose of 3200 IU/day an effective dose of 1600 IU/day.
The authors report that not even 60% were tested for vitamin D levels at the end of the trial, but there was no sub-group analysis to determine whether the supplements raised vitamin D levels to a level shown previously to be protective against ARIs and COVID-19. Interestingly, the ‘control’ group had a mean level of 66.6 nmol/L (26.6 ng/mL), suggesting that their supplementation was probably considerable; a recent large European study found that the U.K. had the second lowest mean vitamin D levels at 47 nmol/L (18.8 ng/mL). Given that the mean age of the participants in this Jolliffe et al. study was >60, this mean level of 66.6 nmol/L (26.6 ng/mL) was all the more remarkable since the elderly are known to have lower vitamin D levels.
What target blood level should have been attempted in this supplementation trial? While it is clear from a meta-analysis that baseline vitamin D levels of <75 nmol/L (<30 ng/mL) were associated with increased COVID-19 infection, hospitalisation, ICU admission, and mortality, few studies actually assess a minimum effective blood level to avoid these outcomes. Seal et al. show that the risk of hospitalisation or mortality continues to decrease up to at least a blood level of 150 nmol/L (60 ng/mL). This was considerably higher than the level achieved in Joliffe et al.’s higher dose supplementation group (102.9 nmol/L or 41.16 ng/mL). Another study by Borsche et al. conducted regression analysis to determine that zero COVID-19 mortality could be achieved at a vitamin D blood level of 125 nmol/L (50 ng/mL), again considerably higher than levels achieved in Joliffe et al.’s study. The Borsche et al. authors recommend raising serum vitamin D to 125 nmol/L (50 ng/mL) in order to save the most lives, even in patients with comorbidities.
The dosage may also have contributed to the apparent failure of this trial. Even the higher group dosage of 3200 IU/day (supposing that all participants took it every day) was considerably lower than the dosage used in many successful trials. Bergman et al. showed that 4,000 IU/day given for one year was effective in preventing respiratory tract infections in those who suffered frequently, while 4,000 IU/day for one month also achieved a lower COVID-19 infection rate, the risk reducing with increasing vitamin D levels, and a dose of 5,000 IU/day versus 1,000 IU/day in mild-moderate COVID-19 patients for two weeks reduced the recovery time for cough and gustatory sensory loss. Supplementation to achieve a vitamin D blood level of 75 nmol/L (30 ng/mL) also decreased the risk of COVID-19 infection, severe disease and mortality. These trials suggest that either a dose of at least 4,000 IU/day would be appropriate or that participants supplement to achieve a blood level of at least 125 nmol/L (50 ng/mL), as per the Borsche et al. study, but preferably 150 nmol/L (60 ng/mL), as per the study by Seal et al. As previously mentioned, without testing all participants at the end of the study, it is impossible to determine the true adherence to the allocated doses. Because many of these trial subjects were elderly, it is worth bearing in mind that they will need a higher dose of vitamin D for it to be effective.
An analysis of outcomes based on baseline vitamin D levels is sadly lacking. In fact, the authors state that outright vitamin D deficiency (<25 nmol/L or 10 ng/mL) at baseline was rare, and the study therefore lacked power to detect an intervention effect in this group, who are more likely to derive clinical benefit from supplementation.
In fact, Grant et al. warn of the problems of designing clinical trials of vitamin D in a similar manner to randomised controlled trials (RCTs) of therapeutic drugs, through failure to recognise that vitamin D is a nutrient with a unique metabolism requiring specific consideration in trial design. They show that RCTs of vitamin D can fail for several reasons, all of which are relevant in Joliffe et al.’s study: few participants have low baseline 25(OH)D concentrations; relatively small vitamin D doses; participants ingesting other sources of vitamin D; results being analysed without consideration of 25(OH)D concentrations achieved. Grant et al. recommend designing an RCT using adjustable vitamin D supplementation based on serum 25(OH)D concentrations to achieve target 25(OH)D levels, as was successfully carried out by Gönen et al.
Finally, a point about vaccination. Unfortunately, the Joliffe et al. study was conducted during the vaccine rollout. Those who had received one or more doses of the vaccine at baseline were 2.5%, while over 89% had received one or more doses by the end of the study. There is no discussion of what the impact of this might have been on the results and the authors state that they did not carry out a sensitivity analysis. Nevertheless, they claim that sub-group analysis showed that there was “no effect of vitamin D on risk of COVID-19 either before or after COVID-19 vaccination”.
Nevertheless, increasing evidence shows that vaccination inhibits both a normal innate and adaptive immune response, impairs type 1 interferon signalling and increases inflammation, making individuals more susceptible to COVID-19. We can see the impact of this in two U.K. studies, one showing that participants with two doses of the vaccine were 44% more likely to be infected with COVID-19 more than 14 days after vaccination and the other showing that vaccine effectiveness against COVID-19 turned negative after 80 days. Elsewhere, a preprint paper showed that vaccination could increase risk of Omicron infection by up to 27% after five months, with negative effectiveness for three doses against four out of five Omicron subvariants, and showing that a greater number of vaccinations could give rise to a higher risk of infection. A Lancet preprint study also found negative vaccine effectiveness against Omicron infection with two doses after 15 weeks and negative vaccine effectiveness against hospitalisation and death after a year. Furthermore, in the elderly, another preprint study found that impaired vaccine responses contributed to their increased susceptibility to COVID-19 infection. These findings suggest that Jolliffe et al. were unwise to ignore vaccination as a confounding factor, since the higher risk of COVID-19 infection in the vaccinated may have rendered their relatively small vitamin D dose ineffective.
Overall, this study by Joliffe et al., represents a wasted opportunity and proposes conclusions which are not warranted by the study methodology. We consider that raising vitamin D status in those with sub-optimal levels remains a valid means of protection against ARIs and COVID-19.
Rachel Nicoll and Michael Y. Henein and researchers in the Department of Public Health and Clinical Medicine and Heart Centre, Umea University, Sweden. This article was first published as an editorial in the Journal of Clinical Medicine.
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Why does anybody do trials like this, open label (unblinded) or without placebo? They are such a waste of time, but they are very common.
They get paid for conducting trials, irrespective of the quality.
And bogus trials like these are handy for strengthening the narrative that Covid jabs and The Cartel’s eye wateringly lucrative antivirals are the only effective treatment for Covid.
And it goes on their CV – whether or not it’s rubbish doesn’t matter because nobody interviewing them for a job will check the reference and actually read the paper.
Why is such a study necessary, when we now know that Norway, where the population has exceptionally high vitamin D levels due to a diet of mackerel and salmon, had the second lowest all-cause excess mortality in the world (second to Sweden) from 2020 to 2022?
Indeed. All five Nordic countries I think have good Vitamin D levels, as does Canada, thanks to both lots of fish and food fortification. The rest or the world, not so much. And it shows in their death rates, with a strong inverse correlation.
Why? Because controlled, comparative, blind studies are designed to show whether the hypothesis is true or false.
Epidemiological and uncontrolled trials are designed to ‘prove’ your hypothesis is true.
They are therefore meaningless but underpin nearly all ‘medical research’ as paid for and assisted by the pharmaceutical industry.
More stab poison propaganda. 80% of those who died from not with Rona, were fat. Ergo, we the healthy conclude the following: 1. Exercise 2. Drink Water 3. Ingest vitamins every day and plenty of them. 4. Proper dieting and keep the waistline within reasonable limits.
So the $cience will conclude the opposite. 1. Exercise is a waste of time 2. Ingest only Soft Drinks. 3. Vitamins are unhealthy. 4. Proper dieting means fast, fatty, sugar laced foods. $cience say. Teacher say. BBC say.
And right on cue, the BBC has a headline implying that drinking 2 litres of water a day is “too much”!
I swear, you can’t make this stuff up!
Now that is complete Boll ox.
They also seem to have chosen an inappropriate study population, they say deficiency (<25nmol/L) was “rare” but in the UK adult population the prevalence is around 20-25%, page 272 of the report linked on this page https://www.gov.uk/government/publications/sacn-vitamin-d-and-health-report
Maybe they are using the same definition of “rare” as the vaccine pushers use to describe serious adverse reactions.
Indeed, their definitions are quite elastic it seems.
Indeed. I know in NYC, doctors are surprised when they actually find anyone in the normal range of Vitamin D levels.
Isn’t COVID-19 an ARI? Or is it a special subject? There are better sources of info about the Vitamin D topic, such as this Ivor Cummins one from a few years ago: https://www.youtube.com/watch?v=v3pK0dccQ38
Incidentally, in the image, the salmon steak is easily the top of the list, followed by the eggs, and not much in the rest of it.
There’s a fundamental problem in this study in that there’s no measure of the participant engagement in the study — ie, there was very little reporting in the paper on whether people were actually filling in the surveys, and nothing in the statistical analysis.
The paper reports that “Availability of questionnaire and linkage data was also good, with 5979/6200 (96.4%) randomised participants contributing data to the intention-to-treat analysis“, but that doesn’t inform on whether the participants reported every month during the study period, and also doesn’t report on whether reporting rates in the vitamin D groups were similar to the no-supplement group.
All we know is that 5979 people bothered to return at least one month’s questionnaire. The authors could have reported the numbers that returned every questionnaire, but they decided that this aspect wasn’t important — I disagree, and suggest that in fact they should have disregarded any trial participant that didn’t return every questionnaire. It is also likely that participants would have become less engaged with time, with the ‘less enthusiastic ones’ more likely to have ‘given up’ by the end of the trial — this would introduce a calendar-time bias to the study, with uncertain impact.
This is important, because if the no-supplement group were less inclined to report each month then this would have had a material impact on the analysis and reported outcomes, with a bias towards having an artificially low estimate of infection risk in the no-supplement group. As the trial wasn’t placebo-controlled there is a real risk that this occurred — ie, we you two groups in the trial, half told that they were ‘special’ and given vitamin D, the other half told that they weren’t the special ones and that they’d not get the ‘free stuff’. This approach is almost certain to result in trial disengagement in the no-supplement group, and is exactly why you’d choose to use a placebo in this sort of trial (I’d suggest that impact on engagement is more important than the classical placebo effect).
They could have readily got around this limitation by doing analysis by the number of questionnaires returned in each of the study groups, but instead they appear to have ignored this and just did the analysis by the total number in the study group (ie, whether they were engaged in the trial or not). I also would have expected data on trial engagement in the paper (or at least the supplementary materials), which could have indicated whether it was problem in their trial or not.
A good indication of the ‘engagement’ of the participants is given in the willingness to take part in the post-trial vitamin D analysis (see last row of table 2) — while 92% (1483/1600) of the supplement group agreed to do this extra bit of the trial, only 76% (306/400) of the no-supplement group accepted the offer. I’d note that it is likely that this understates the trial disengagement in the no-supplement group, as they were actually offering ‘free stuff’ (a vitamin D test) at this point, which would usually be associated with a higher positive response rate.
I’m waiting for the randomised control study which shows that recurrent doses of cask-strength single malt whisky has a huge benefit against SARS-COV-2, and indeed all respiratory infections.
I would have thought we were beyond the time where we needed studies to ascertain whether fresh air and sunlight, with the associated vit. D, are beneficial for respiratory viruses and health in general. My grandmother knew that, and she had little formal education but the inherited wisdom of generations of Cornish ancestors.
And I’ve got some more news for our public health geniuses: respiratory viruses don’t like sea air. My grandmother knew that too.
Some studies are on the face of it absurd – this one being pretty high up on that list. What’s next.. a study to determine if food is essential for survival? The Vit D thing hasn’t become such a mainstay and staple of good health and nutrition for no reason. Why they’re intent on destroying decades of good advice & living is a good question.
As far as the Rona thing, there were indicators of Vit D being beneficial with the high counts of infection in African-Americans and those with darker skin – given their reduced ability to convert natural Vit D at this latitude.
As we’ve since learnt with the whole FTX scandal (and their funding & involvement of the Together trial to “determine the efficacy” of that which must not be named – IVM. Yeah right, we know what you’re trying to do with your seedy crooked enterprises), but news flash– there are clear and obvious motives to muddy the waters when so much money and compromising ethics is on the line yet this caution and sentiment goes flying out the window when it’s convenient? I’m so tired of this blatant use of power for power’s sake and those who should know better, falling for it. ABSOLUTE power does seem to corrupt absolutely.
And my grandmother also knew that crowded living conditions predisposed to conditions such as pneumonia and other illnesses.
So she would have known straightaway that the 2020- lockdowns were bollocks.
And our public health geniuses apparently didn’t know this. As I say, by rights jail time beckons.
I thought you’d been conducting your own study on the whisky already? with sample size of n=1.
I’m not sure it’s working, to be honest. You seem to get quite a few colds. Though have you had the rona yet?
Yeah, got another fluey thing now. This one I feel generally rough and can’t bear the feel of my own skin, sore all over. First one since August, which is a long time for me right now. Truth is, it’s the children (early primary school) – they’re just germ factories.
Going to try a whisky in a bit. Mum’s back now so I definitely don’t have to go anywhere, just wallow. I have no problem with drinking spirits during the day.
Generally speaking, if I’m spending a fair bit of time commenting on here I’m down with something.
Not sure if I’ve had the rona – in this household we’ve never done a single test (let alone jab, mask, or anything like that). We must have been in contact with it, at least the children have, as half the school was off last winter with the dreaded O.
But in December-January 2019-20 we all came down, within hours of each other, with miserable bug that, as we where to find out, were the classic symptoms of covid. Loads of people around us had it, and it’s notable that the area around us was scarcely affected by covid that spring.
Lukashenko said the same thing about vodka, lol.
Many years ago when in the wilds of Highland Bonny Scotland I was told about the single malts (cask-strength that is) that if you drink the right amount you’ll live for ever – it’s just finding that right amount.
Most people are unaware of the many, often highly dubious, ASSUMPTIONS that scientists make in so called ‘scientific’ studies, and then some people quote these studies as if they are the unerring word of God.
“The case against science is straightforward: much of the scientific literature, perhaps half, may simply be untrue.”
– Richard Horton, editor-in-chief of The Lancet
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60696-1/fulltext
“Why Most Published Research Findings Are False”
– John P. A. Ioannidis
“There is increasing concern that most current published research findings are false.”
https://www.researchgate.net/publication/7686290_Why_Most_Published_Research_Findings_Are_False
“Time to assume that health research is fraudulent until proved otherwise?”
Richard Smith, former British Medical Journal editor
https://richardswsmith.wordpress.com/2021/07/02/time-to-assume-that-health-research-is-fraudulent-until-proved-otherwise/
According to a BBC News article in 2017:
“Most scientists ‘can’t replicate studies by their peers'”
“Science is facing a ‘reproducibility crisis’ where more than two-thirds of researchers have tried and failed to reproduce another scientist’s experiments, research suggests.”
https://www.bbc.co.uk/news/science-environment-39054778
and then just a few years later, the BBC wasn’t allowing anyone to even question Big Pharma’s claims with their highly obvious massive conflicts of interest!
Dr. John Ioannidis is a real man of genius. And integrity as well. He went from being the most popular scientist in the world (by number of citations) to being vilified as a social pariah by the mainstream almost overnight because he refused to toe the company line. And now he is vindicated.
Still no word on how many people die within 28 days of eating a cheese sandwich..?
And what’s the betting if Marmite was involved it’d be “death *from* Marmite” on the cert, not “with” Marmite. Everybody favours the cheese and vilifies the Marmite..Check your confirmation bias at the door.. Personally, my money’s on the gluten.
I would expect a comparative study between Marmite, Bovril and Vegemite to follow.
Marmite and Vegemite are one thing. Bovril is a different animal.!
Matt Hancock’s lie in the HOC that his department had carried out a study into the effectiveness of vitamin D against the virus and found no benefit, as well as the guidance – believed by many people I spoke to to be law – to minimise time outdoors told me it WAS beneficial.
After all, if you correct your vitamin D deficiency by exercising in the sunshine and fresh air the absolute worst that can happen is that it has no effect on the virus but leaves you better protected against other health problems which deficiency either causes or worsens, and you benefit from the exercise, especially if you have a dog and chat to other dogwalkers while bums are sniffed..
I agree with the commenter -sorry, can’t remember who it was- who said everything the government has done since March 2020 has had, as one of its aims, damaging our physical, psychological or moral health.
The commenter was probably me. I have certainly stated countless times that every intervention, NPI’s in particular had as their sole aim damage to our physical and mental health. Just as I keep banging on about the depopulation agenda.
Mogwai has posted a video of Dr Mike Yeadon in the N R. in which he outlines his conviction that depopulation is the aim. Well worth a watch.
Yep, every single piece of advice, guidance, or mandated behaviour has served to damage health, with no apparent benefits.
Thick, dumb, stupid?
Or psychopathically criminal?
I will go with your last statement TJN.
Yeadon was quickly silenced by the mainstream early on. And yet he was right about so many things. He may have gotten some things wrong (for example, there was more than one wave of the virus after all), but most things he got right.
Well the answer to that is that the ‘waves’ were due to introducing a pathogen into relatively isolated populations, reduced mixing after the first lockdown could explain that.
But yes, Mike Yeadon is a good bloke, he cares about human beings while many of his detractors appear not to care at all.
Wow, talk about a rigged study! I really wonder who funded this study? Big Pharma? Or their shills and sycophantic lackeys in government?
Well, if you don’t pay tax in the UK, it wasn’t you!
I was wondering the same thing. Any trail can be designed to fail if that’s what the paymasters want. Same with failed Ivermectin trails. Plenty of countries around the world have used it with great success.
It seems that there are a lot of vested interests with an axe to grind against Vitamin D…..
Vitamin D is racist, that’s why.
UV B radiation from sunlight stimulates Vit D production in the body.
High skin melanin content blocks UV B radiation, so individuals with high melanin levels are more likely to be Vit D deficient.
Need I go on?
And of course if it was white people in Rhodesia, skin cancer might be racist.
I always thought though that the rigged vitamin D trials were part of the efforts to ensure that “vaccines” could be used as the only option under emergency legislation.
With such low quality study design was this paper published in The Beano?
The dumbing down of science is bad enough, let alone the motives of some of the people facilitating