Vitamin D levels and Covid-19

[jim mcnamara]

https://www.nutraingredients.com/Ar...d-Covid-19-open-letter-to-world-s-governments

[tl;dr[] : Change suggestions of Vitamin D supplementation in the UK - higher - the health officialdom just came down hard against Vitamin D supplementation increases of any kind.
[/tl;dr]

Interestingly, local governments in the NW US, where cloudy days dominate, suggest 2000 IU of Vitamin D daily during winter months. Portland is an example.

This open letter seems aimed more at the UK than elsewhere. At issue is the stuff we all encountered in med school 50 years ago: Hydroxy Vitamin $D_{3}$ supplementation is dangerous.

The dominant view is why Vitamin D RDA's are very low relative to what humans normally get from sunlight -- assuming you see the sun. The US RDA is 400 IU - 800 IU depending on age. One moderate exposure to full sunlight (April - September in the Northern Hemisphere ) for 30 minutes can produce ~20000 IU. Why? Your body makes its own Vitamin D from sunlight. And stores it in adipose tissue if you do not need it. Modern lifestyles limit outdoor exposure, so do climate and seasons.

The letter claims that previous supplementation ( especially in low sunlight populations , sounds like the UK to me) has positive outcomes on Covid-19 infection rates and disease progression.

 

[Evo]

sounds like the UK to me) has positive outcomes on Covid-19 infection rates and disease progression.

This doesn't sound like it.

COVID-19: UK Prime Minister Boris Johnson imposes tighter Coronavirus curbs on millions, 'cannot continue with Christmas as planned'

"UK Prime Minister Boris Johnson on Saturday (local time) imposed tighter Coronavirus controls on millions of people in England and drastically scaled back plans to ease restrictions over Christmas, seeking to curb a new more infectious strain of the virus.
The number of cases in England has soared in the last two weeks because of a variant of the virus that scientists said is up to 70 percent more transmissible. Johnson said the Government had to take urgent action.
"It is with a very heavy heart I must tell you we cannot continue with Christmas as planned," Johnson told a news conference. "I sincerely believe there is no alternative open to me."
London and southeast England - about a third of the English population - are currently in the highest level of a three-tier system of rules but will now be placed in a new Tier 4 level.
People in that tier will be required to stay at home except for essential reasons such as work, and non-essential retail will close, as will indoor leisure and entertainment. Social mixing will be limited to meeting one other person in an outdoor space."

https://www.newshub.co.nz/home/world/2020/12/covid-19-uk-prime-minister-boris-johnson-imposes-tighter-coronavirus-curbs-on-millions-cannot-continue-with-christmas-as-planned.html?fbclid=IwAR2NFGVakXMccmvh0vaj8YUEp3QqjhpgCR7ebvm84oejy939JRstt2cPI_U

 

[jim mcnamara]

@Evo Yup.

I thought the point was: UK climate->low Vitamin D levels ->UK says 'no' to supplementation->open letter
Maybe I was not clear. And yes, they have the same economic/social issues many countries face.

IMO it is getting too late in the pandemic anyway.

 

[OmCheeto]

Dr. Campbell has done at least 8 videos in the last 3 months that talked about vitamin D.
He finally convinced me to buy some. They arrived last week: 400 tablets for $8, at just the right dosage: 2000 IU/day.

Here's his latest:

Dec 17, 2020

 

[BillTre]

I live in Oregon.
Several years ago, my doctor recommended that I take 2000IU/day since my Vit. D was low.
He said it is preventative for a number of potential problems
Although I have other health issues, I remain Covid free.
I am also mindful of isolation measures.

 

[Ygggdrasil]

The US National Institutes of Health says "There are insufficient data to recommend either for or against the use of vitamin D for the prevention or treatment of COVID-19."
https://www.covid19treatmentguidelines.nih.gov/adjunctive-therapy/vitamin-d/

Most of the research suggesting a role for Vitamin D in COVID-19 are observational studies which are difficult to interpret because of confounding factors. In particular, Vit D deficiency correlates with other factors (such as race/ethnicity, age, obesity and hypertension, which are also risk factors for poor COVID-19 outcomes. Unless there is a good randomized trial, it's difficult for public health agencies to make recommendations for or against a certain treatment.

 

[OmCheeto]

The US National Institutes of Health says "There are insufficient data to recommend either for or against the use of vitamin D for the prevention or treatment of COVID-19."
https://www.covid19treatmentguidelines.nih.gov/adjunctive-therapy/vitamin-d/

Most of the research suggesting a role for Vitamin D in COVID-19 are observational studies which are difficult to interpret because of confounding factors. In particular, Vit D deficiency correlates with other factors (such as race/ethnicity, age, obesity and hypertension, which are also risk factors for poor COVID-19 outcomes. Unless there is a good randomized trial, it's difficult for public health agencies to make recommendations for or against a certain treatment.

At 2¢ a day, I'll take my chances.

 

[jim mcnamara]

Actually there are several RCT's going now:
https://clinicaltrials.gov/ct2/results?cond=Covid19&term=cholecalciferol&cntry=&state=&city=&dist=

Gives --
31 mostly early stage studies on COVID and cholecalciferol ( Vitamin $D_3$ )

Try the link and see the studies if one interests you.

I would assume some of them will clarify things - one way or the other.

There are RCT's on cholecalciferol that are not COVID specific. The point in my post above is that other scientists do appear to me to have concern. I'm not positing certainty or true causation.

What @Ygggdrasil is talking about is called standard of care, usually published by organizations like the CDC, FDA, or WHO.

Just to be clear, medical procedures and therapies are not all defined in/by standard of care. For example, consider off label prescriptions as a simple example. Or @BillTre 's example of off label above.

 

[Jarvis323]

This is one of the studies people have been citing lately.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456194/

 

[Ygggdrasil]

This is one of the studies people have been citing lately.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456194/

From the paper you cite:

Wow, those numbers are almost too good to be true! If that holds up in larger sample sizes and in other RCTs, then it looks like vitamin D is some sort of miracle drug that outperforms drugs like remdesivir or monoclonal antibodies.

 

[russ_watters]

Dr. Campbell has done at least 8 videos in the last 3 months that talked about vitamin D.
He finally convinced me to buy some. They arrived last week: 400 tablets for $8, at just the right dosage: 2000 IU/day.

Me too!

Note: this message has not been scanned for sarcasm.

One moderate exposure to full sunlight (April - September in the Northern Hemisphere ) for 30 minutes can produce ~20000 IU.

 

[russ_watters]

Sunlight ≅ ventilation

 

[OmCheeto]

Me too!

Note: this message has not been scanned for sarcasm.

jim mcnamara said:
One moderate exposure to full sunlight (April - September in the Northern Hemisphere ) for 30 minutes can produce ~20000 IU.

"Except during the summer months, the skin makes little if any vitamin D from the sun at latitudes above 37 degrees north (in the United States, the shaded region in the map) or below 37 degrees south of the equator. People who live in these areas are at relatively greater risk for vitamin D deficiency."​

reference: https://www.health.harvard.edu/staying-healthy/time-for-more-vitamin-d

Dated 2008, so this is not a promotion of vitamin D as a cure for Covid, but simply a reminder that vitamin D is a necessary component for a healthy immune system, of which I'm sure there are lots of things.

I live in Oregon.
Several years ago, my doctor recommended that I take 2000IU/day since my Vit. D was low.
He said it is preventative for a number of potential problems
Although I have other health issues, I remain Covid free.
I am also mindful of isolation measures.

Same here. Though in my case, I had been ill for 6 months , and the only thing wrong with my bloodwork was a vitamin D deficiency. EVERYTHING else was in the normal range. It was the middle of January, and they prescribed 50,000 IU/day, which had no effect on my symptoms. So even at super high doses, it doesn't cure everything.

 

[Astronuc]

Your body makes its own Vitamin D from sunlight. And stores it in adipose tissue if you do not need it. Modern lifestyles limit outdoor exposure, so do climate and seasons.

A growing number of studies point to vitamin D deficiency as a risk factor for heart attacks, congestive heart failure, peripheral arterial disease (PAD), strokes, and the conditions associated with cardiovascular disease, such as high blood pressure and diabetes.

https://www.hopkinsmedicine.org/health/wellness-and-prevention/vitamin-d-and-the-heart
and https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.107.706127

The above symptoms would increase the risk if one were to develop Covid-19, i.e., contract SARS-Cov2. There is also a correlation of increased mortality during the winter months, particularly late December and early January, around the winter solstice in the N. Hemisphere. I would expect a similar trend during late June and early July in the S. Hemisphere.

Perhaps it's not so much the amount of vitamin D, but rather a consequence of the process.

Vitamin D is not one chemical but many. The natural type is produced in the skin from a universally present form of cholesterol, 7-dehydrocholesterol. Sunlight is the key: Its ultraviolet B (UVB) energy converts the precursor to vitamin D₃. In contrast, most dietary supplements are manufactured by exposing a plant sterol to ultraviolet energy, thus producing vitamin D₂. Because their function is almost identical, D₂ and D₃ are lumped together under the name vitamin D — but neither will function until the body works its magic (see figure).

https://www.health.harvard.edu/stay...r-health-breaking-old-rules-raising-new-hopes

So the type of Vitamin is apparently important, but could the fact that sunlight converts 7-dehydrocholesterol be an, if not the, important factor?

 

[Ygggdrasil]

This is one of the studies people have been citing lately.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456194/

Here's the non-peer reviewed results from a larger randomized clinical trial in Brazil (n = 240 patients vs n = 76 for the smaller study cited above) looking at whether treatment of hospitalized COVID-19 patients with vitamin D affects the length of hospital stay:

Importance Patients with COVID-19 may exhibit 25-hydroxyvitamin D deficiency, but the beneficial effects of vitamin D3 supplementation in this disease remain to be proven by randomized controlled trials.

Objective To investigate the efficacy and safety of vitamin D3 supplementation in patients with severe COVID-19.

Design, Setting, and Participants This is a multicenter, double-blind, randomized, placebo-controlled trial conducted in two centers (a quaternary hospital and a field hospital) in Sao Paulo, Brazil. The trial included 240 hospitalized patients with severe COVID-19. The study was conducted from June 2, 2020 to October 7, 2020.

Interventions Patients were randomly allocated (1:1 ratio) to receive either a single oral dose of 200,000 IU of vitamin D3 or placebo.

Main Outcomes and Measures The primary outcome was hospital length of stay, defined as hospital discharge from the date of randomization or death. Secondary outcomes were mortality, admission to ICU, mechanical ventilation requirement, and serum levels of 25-hydroxyvitamin D, creatinine, calcium, C-reactive protein, and D-dimer.

Results Of 240 randomized patients (mean age, 56 years; 56% men), 232 (96.7%) were included in the primary analysis. Log-rank test showed that hospital length of stay was comparable between the vitamin D3 supplementation and placebo groups (7.0 days [95% CI, 6.1 to 7.9] and 7.0 days [95% CI, 6.2 to 7.8 days]; hazard ratio, 1.12 [95% CI, 0.9 to 1.5]; P = .379; respectively). The rate of mortality (7.0% vs 5.1%; P = .590), admission to ICU (15.8% vs 21.2%; P = .314), and mechanical ventilation requirement (7.0% vs 14.4%; P = .090) did not significantly differ between groups. Vitamin D3 supplementation significantly increased serum 25-hydroxyvitamin D levels compared to placebo (difference, 24.0 ng/mL [95% CI, 21.0% to 26.9%]; P = .001). No adverse events were observed.

Conclusions and Relevance Among hospitalized patients with severe COVID-19, vitamin D3 supplementation was safe and increased 25-hydroxyvitamin D levels, but did not reduce hospital length of stay or any other relevant outcomes vs placebo. This trial does not support the use of vitamin D3 supplementation as an adjuvant treatment of patients with COVID-19.

https://www.medrxiv.org/content/10.1101/2020.11.16.20232397v1

 

[Jarvis323]

Here's the non-peer reviewed results from a larger randomized clinical trial in Brazil (n = 240 patients vs n = 76 for the smaller study cited above) looking at whether treatment of hospitalized COVID-19 patients with vitamin D affects the length of hospital stay:
https://www.medrxiv.org/content/10.1101/2020.11.16.20232397v1

There's a lot of comments that seem insightful. Maybe we can hypothesize that you should account for the delay in achieving optimum levels, so if you've just contracted Covid-19 and your levels are low, then the active form Calcifediol should be taken. Maybe over the counter supplementation after severe illness is ineffective?

It appears to me that the 8 patients on the treatment group who did not make it where exactly the ones who failed to reach adequate levels of 25OHD (above 30 ng/mL). The chart indicates that 5 patients from the treatment group failed even to reach 20 ng/ml. Unfortunately, the study gives no clue about this possible correlation, but that's my best guess.
I noticed that ventilation machine requirement was reduced by more than 50% in treatment group, but all 8 patients from treatment group who required it didn't survive. There is an indication that their outcome was predictable. IMHO, their specific data should be analyzed.

This trial appears to have been a wasted opportunity.
It is unclear why Vitamin D3 was orally administered to severely ill C-19 patients. It can take a fortnight to be metabolised into Calcifediol, the active, metabolised form required to trigger an immune response. A most unhelpful delay to the effective treatment of severely ill COVID-19 patients.
The RCT conducted at the teaching hospital in Cordoba used Calcifediol, with dramatic results. Compared to the untreated ‘control group’ there was a 96% reduction in the need for Intensive Care Unit admission, and a commensurate reduction in deaths.
One has to ask, therefore, why, in Sao Paulo, it was decided to administer un-metabolised Vitamin D3 rather than Calcifediol to severely ill C-19 patients for whom every day of non-treatment reduces the chance of a good outcome if not survival? Indeed, an experienced physician could have forecast the results obtained without the need for a trial.

The description of the amount of vitamin D used doesn't account for the mistake made in calculating vitamin D needs, nor is that mistake discussed in the article. In addition, making active forms of VitD from what is ingested is not an instant magic process. A body under attack may lack the energy to carry it out. Maybe it's just giving something by a pill is ineffective right now. What if you did transdermal? That would avoid the stomach/gut which is a place we know the virus attacks. Also vitamin D doesn't act alone. A person in ICU may not get a lot of vitK and may even be on anti-K blood thinners if they are a stroke risk. How many patients were on Lovenox vs something that thins blood via the vitamin K route? A daily exposure to a UV lamp may be more efficient for providing Vitamin D.
Anyway, the point is, I am not convinced that this test was properly done with reference to vitamin D. It takes weeks to normalize vitamin D in tissues where it is needed. Just testing the blood level after you gave a bolus pill is lying to yourself. It's like adding dye to water and saying, look, the sand at the bottom of the river turned all blue, we can assume it goes deep. What's the vitamin D status of hepatocytes after the one pill you gave? How much enzyme activity was there in the kidney to activate the D you gave?
Giving someone a vitamin is not like giving them a drug. The vitamin has to go to the tissues and do its work. You're thinking far too simplistically. VitaD affects thousands of reactions in the body and is not actively excreted as if it were an invader. That's nothing like a drug. Vitamins aren't drugs, that goes double for the fat soluble ones.

Thank you for this publication. Given that we already have two successful vitamin D RCTs and dozens of retrospective studies, I believe the null hypothesis is that vitamin D is effective in reducing COVID-19 severity. Therefore the failure of this study is not enough to accept a new hypothesis.

Digging into the details, the main problem is that the study was extremely underpowered. For example, the probability that it would have found a reduction of 50% in mortality with p<0.05 is only 25%. ICU admission and mechanical ventilation were a bit better with 61%, and 44%, and they indeed showed some effect (despite 1 treatment arm patient admitted to ICU before receiving treatment), although still not significant (as expected).

Sample size was calculated assuming vitamin D would reduce hospital stay from a mean of 7 to 3.5 days. That is extremely unlikely, especially given that bolus vitamin D takes a day or two to be mostly converted to 25(OH)D (and I assume more for 1,25(OH)d. anyone knows how long?).
In essence, the study had a low probability of achieving any of its endpoints..

Patients were recruited 10 days after symptoms, and 90% were already on oxygen. It is possible that improving innate immunity is not very relevant at that point. Whatever effect it may have had, was further reduced due to 62% of patients receiving steroids.

While the study does not show vitamin D is not effective, it does suggest that at a late stage, alongside steroids, it is not *immensely* effective, i.e. does not reduce odds of severe outcomes by 5x or more. Our analysis at Rootclaim suggests that a 5x reduction is a reasonable outcome when vitamin D is administered correctly.

Thank you for this study. The serum level aimed for of 30ng/ml is sufficient for bone health but the immune system needs higher levels, at least 40 if not 60ng/mL. More importantly, as the dose was late in the illness, in addition to being quite low. Single bolus doses of vitamin D3 are rarely effective as an intervention particularly when administered without the cofactors: (Mag, zinc, boron, vitamin B + K2 complex and Omega-3). Bolus doses of vitamin D3 start becoming effective up around 500,000 IU and there must be followup with a maintenance dose of at least 10,000 IU/day vitamin D3. The D3 group was disadvantaged by means of many values and risk factors, the three main ones known to us - hypertension, Diabetes II and COPD - by a factor of more than 4:3 vs the Placebo group.

 

[BillTre]

I thought the proposed use of Vit. D was as a prophylactic, not to prevent infection but to prevent the over stimulation of the immune system, which might prevent the more severe cases.
IIRC, it puts the immune system into a less excitable state, which ight not be an immediate response to
This, to me, this sounds like the Vit. D should be taken before getting infected, so that your immune system is well tuned up to deal with the infection, when it happens.

This study is looking at treatment after infection, which by that logic might be too late.

 

[jim mcnamara]

FWIW - I was wrong. There are several completed RCT's. This 1 hour video does a pretty complete review of relevant papers on Vitamin D - biochem, population studies, clinical, and randomized trial as well. It starts back in time and goes forward, presenting papers for each subtopic.

It is beyond what we should try to do here on PF, even as an insight.

If you are interested enough to comment on where we are in understanding this topic, then this review with a large bibliography is a great start. It has a medical point of view.

 

[pinball1970]

FWIW - I was wrong. There are several completed RCT's. This 1 hour video does a pretty complete review of relevant papers on Vitamin D - biochem, population studies, clinical, and randomized trial as well. It starts back in time and goes forward, presenting papers for each subtopic.

It is beyond what we should try to do here on PF, even as an insight.

If you are interested enough to comment on where we are in understanding this topic, then this review with a large bibliography is a great start. It has a medical point of view.

Anymore on this?

I can only get abstracts from Cochrane
https://www.cochranelibrary.com/cen...N-02270369/full?highlightAbstract=vit|covid|d

 

[sysprog]

If you're going to take vitamin D supplements, you should probably consider the co-factors --
e.g. magnesium: https://pubmed.ncbi.nlm.nih.gov/29480918/

 

[jim mcnamara]

https://clinicaltrials.gov/
NB: It has a separate Covid search portal.
This is the main entrance to the rabbit hole from hell. Aren't you glad you asked

It lists 308000+ RCT's. Search on Vitamin D, D3, D2, calcitriol, UVB. There are results links. NB: Human research has an extra, separate set of ethical protocols from other research areas.

This portal is how researchers might start a metadata (multiple results on the same topic) analysis. They then ask the original researchers in each of the relevant projects for copies of datasets - note the human issue complicates things again, e.g., HIPAA in the US.

Research areas may have special repositories, especially for genomes and protein data (proteomics) , ex:
https://www.nature.com/subjects/proteomic-analysis

So actual data access probably requires software. @Ygggdrasil would know more about this.
Posters - consider references on magnesium like these when you want to refer a question to a resource on human nutrient requirements:
https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/ (Good bibliography)
Details:
'Nutrient Metabolism Structures Functions and Genes 2Ed'. M Kohlmeier 2015
This gives links to primary indexes for genes involved in nutrient metabolism- Ex: OMIM
https://www.ncbi.nlm.nih.gov/omim

 

[russ_watters]

Dr. Campbell has done at least 8 videos in the last 3 months that talked about vitamin D.
He finally convinced me to buy some. They arrived last week: 400 tablets for $8, at just the right dosage: 2000 IU/day.

Me too!

Note: this message has not been scanned for sarcasm.

If I were a fan of self-deprecating irony I'd report that I developed an odd rash on my face this spring and after a variety of tests was found to have a vitamin D deficiency. I'm now taking a supplement. But no COVID, so... ¯\_(ツ)_/¯

https://clinicaltrials.gov/
NB: It has a separate Covid search portal.
This is the main entrance to the rabbit hole from hell. Aren't you glad you asked

Better than a rabbit hole to hell, I'd think.