Vitamin D?

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Hunting Dog
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Vitamin D?

Post by Hunting Dog » Sat Sep 26, 2020 7:23 pm

So there's apparently a study or two saying that vitamin D levels are relevant to catching/surviving covid. See here.

research is by Michael Holick who appears to have a vested interest.

But, if that was actually a thing, would it provide an answer (apart from poverty/work situations) as to why BAME populations in northern hemisphere were more affected?

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Re: Vitamin D?

Post by sTeamTraen » Sat Sep 26, 2020 7:47 pm

My mother worked as a paediatrician in public health clinics in Birmingham in the 1960s and 1970s. She told me that she saw quite a few cases of rickets in Asian households where the fathers refused to let the mothers leave the house during the day. These were first-generation immigrants from the subcontinent for whom this was standard behaviour. You can make all the vitamin D you need hanging the washing out in the sun every day in Dhaka, not so much stringing it over radiators in Sparkbrook. But 50 years on I would not expect this to be a huge problem for BAME communities.

That said, I'm waiting to see COVID research that unconfounds vitamin D deficiency from all of the other general health variables that go to make someone a well person or not. As far as I know, vitamin D only has one function (calcium uptake) and is unlikely to fight viruses; nor would stronger bones normally be associated with that, other than (again) in a general overall health factor. Maybe people with more vitamin D have that because they spend more time out of doors.

In any case, for otherwise healthy people to rush out and start taking massive doses will cause problems. The body can't store vitamin D for a rainy day --- it's like oil in your car's engine, once you've got enough there's no point in adding more.
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Re: Vitamin D?

Post by Gfamily » Sat Sep 26, 2020 8:56 pm

The have been Medcram video explainers about the (possible) role of vitamin D for a couple of months at least.
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Re: Vitamin D?

Post by discovolante » Sat Sep 26, 2020 9:02 pm

sTeamTraen wrote:
Sat Sep 26, 2020 7:47 pm
My mother worked as a paediatrician in public health clinics in Birmingham in the 1960s and 1970s. She told me that she saw quite a few cases of rickets in Asian households where the fathers refused to let the mothers leave the house during the day. These were first-generation immigrants from the subcontinent for whom this was standard behaviour. You can make all the vitamin D you need hanging the washing out in the sun every day in Dhaka, not so much stringing it over radiators in Sparkbrook. But 50 years on I would not expect this to be a huge problem for BAME communities.

That said, I'm waiting to see COVID research that unconfounds vitamin D deficiency from all of the other general health variables that go to make someone a well person or not. As far as I know, vitamin D only has one function (calcium uptake) and is unlikely to fight viruses; nor would stronger bones normally be associated with that, other than (again) in a general overall health factor. Maybe people with more vitamin D have that because they spend more time out of doors.

In any case, for otherwise healthy people to rush out and start taking massive doses will cause problems. The body can't store vitamin D for a rainy day --- it's like oil in your car's engine, once you've got enough there's no point in adding more.
On the other hand, it is getting to the time of year where it's sort of woolily recommended that people take a vit D supplement anyway. And I am not sure if covid is going to encourage people to brave the cold of each other's gardens or just stay indoors a lot more anyway e.g. less waiting outside a the bus stop on the daily commute, online shopping etc. So if people are only taking a smallish dose then it probably might be a situation where it doesn't actually do any harm? As long as people don't go round thinking it makes them immune or some.
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Re: Vitamin D?

Post by Squeak » Sat Sep 26, 2020 9:34 pm

I thought it was fairly uncontroversial that low vitamin D levels are likely for people with dark skin and low access to light. A quick Google scrounged up this paper on D deficiency in pregnant women in Switzerland that seems typical of the genre.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372923/

I know that lots of the excitement over vitamin D as some sort of wonder supplement for all ailments seems to be waning as people start to control for other measures of well-being, but I don't think it's all been knocked over yet.

Certainly GPs at this end of the world (42S) are still very proactive about testing for and prescribing Vit D. (Including me. Anecdotally, the dramatic drop in the number and severity of colds I've had since the gp put me on D supplements means that Calliope is never going to let me do taking them, no matter what meta-analyses I stick under her nose.)

And, fire another anecdote, a Tamil friend of mine recently arrived home after a year in Bristol (Tassie winter - English year - Tassie winter) and was found to have alarmingly low rates of vitamin D. I promise that she's allowed to leave the house, though life as a post doc might mean she didn't leave the lab much....

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Re: Vitamin D?

Post by basementer » Sat Sep 26, 2020 11:28 pm

The BMJ wrote:Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data
https://www.bmj.com/content/356/bmj.i6583
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Re: Vitamin D?

Post by jdc » Sat Sep 26, 2020 11:34 pm

sTeamTraen wrote:
Sat Sep 26, 2020 7:47 pm
As far as I know, vitamin D only has one function (calcium uptake) and is unlikely to fight viruses; nor would stronger bones normally be associated with that, other than (again) in a general overall health factor.
https://www.ncbi.nlm.nih.gov/pmc/articl ... 0infection.
Vitamin D can modulate the innate and adaptive immune responses. Deficiency in vitamin D is associated with increased autoimmunity as well as an increased susceptibility to infection.
sTeamTraen wrote:
Sat Sep 26, 2020 7:47 pm
In any case, for otherwise healthy people to rush out and start taking massive doses will cause problems. The body can't store vitamin D for a rainy day --- it's like oil in your car's engine, once you've got enough there's no point in adding more.
Yes, massive doses will cause problems but afaict only because the body can store vitamin D for a rainy day. https://www.health.harvard.edu/staying- ... -new-hopes
Like the other fat-soluble vitamins, vitamin D is stored in the body's adipose (fat) tissue. That means your body can mobilize its own reserves if your daily intake falters temporarily — but it also means that excessive doses of vitamin D can build up to toxic levels. At those extremes, vitamin D can raise blood calcium to levels that can cause grogginess, constipation, and even death. But it takes massive overdosing to produce toxicity, and doses up to 2,000 IU a day are considered safe.

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Re: Vitamin D?

Post by bob sterman » Sun Sep 27, 2020 6:41 am

sTeamTraen wrote:
Sat Sep 26, 2020 7:47 pm
In any case, for otherwise healthy people to rush out and start taking massive doses will cause problems. The body can't store vitamin D for a rainy day --- it's like oil in your car's engine, once you've got enough there's no point in adding more.
For people who are truly deficient the standard treatment is a massive loading dose (e.g. 300,000 IU) in a matter of days / weeks before moving on to a daily maintenance supplement. But I guess using your analogy this would like pouring litres of oil into an empty engine???

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Re: Vitamin D?

Post by FredM » Sun Sep 27, 2020 7:41 am

At the molecular level there is evidence that Vitamin D may have a positive effect on immune function. 1,25-dihydroxycholecalciferol (bioactive form of D) binds to a receptor that regulates the expression of genes important for immune function and cytokine production. See Rachez C., Freedman L.P., Mechanisms of gene regulation by vitamin D(3) receptor: a network of coactivator interactions. Gene. 2000;246(1–2):9–21 and citations. Whether this translates into a protective effect is another matter.

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Re: Vitamin D?

Post by Woodchopper » Sun Sep 27, 2020 8:35 am

jdc wrote:
Sat Sep 26, 2020 11:34 pm
sTeamTraen wrote:
Sat Sep 26, 2020 7:47 pm
As far as I know, vitamin D only has one function (calcium uptake) and is unlikely to fight viruses; nor would stronger bones normally be associated with that, other than (again) in a general overall health factor.
https://www.ncbi.nlm.nih.gov/pmc/articl ... 0infection.
Vitamin D can modulate the innate and adaptive immune responses. Deficiency in vitamin D is associated with increased autoimmunity as well as an increased susceptibility to infection.
Yes, people may be affected by having insufficient Vitamin D even if it isn’t so bad they get tickets.

As you can see here: https://fastrt.nilu.no/VitD-ez_quartMEDandMED_v2.html people in Northern Europe won’t produce any Vitamin D from sunshine during some or all of the winter. Even on the north shore of the Mediterranean someone would need to spend about an hour in the sun at midday to get an adequate dose.

As Disco writes, in the northern hemisphere winter it’s a good idea to make sure you get enough from dietary sources. Most commonly oily fish, egg yolks or various products with added Vitamin D. I take cod liver oil supplements.

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Re: Vitamin D?

Post by shpalman » Sun Sep 27, 2020 9:15 am

sTeamTraen wrote:
Sat Sep 26, 2020 7:47 pm
In any case, for otherwise healthy people to rush out and start taking massive doses will cause problems. The body can't store vitamin D for a rainy day --- it's like oil in your car's engine, once you've got enough there's no point in adding more.
We'd all develop vitamin D deficiency on actual rainy days, unless we took a supplement that morning, if it were literally true that the body can't store it. But the car engine is storing oil, in the sump. That's why you don't need to keep putting more oil in all the time.

The half-life seems to be about two weeks so if you're going to be out of the sun for longer than that, supplementation ought to be helpful but not as helpful as a week in the sunshine, but this paper gives a confusing result which only seems to suggest that submarine crews are vitamin-D deficient even before they get in the boat especially if they are going to be in the control group...* they probably had too few subjects and when they split them into three groups (placebo vs. 1000 IU/day vs. 2000 IU/day) they ended up with slightly different average BMIs in the three groups (26 vs 27 vs 30) , and then noted that everyone lost a few kg.

* - there were fewer vit-D deficient individuals in the control group after three months underwater than there were before. Quoth the raven: wut?
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Re: Vitamin D?

Post by jdc » Sun Sep 27, 2020 5:34 pm

Woodchopper wrote:
Sun Sep 27, 2020 8:35 am
jdc wrote:
Sat Sep 26, 2020 11:34 pm
sTeamTraen wrote:
Sat Sep 26, 2020 7:47 pm
As far as I know, vitamin D only has one function (calcium uptake) and is unlikely to fight viruses; nor would stronger bones normally be associated with that, other than (again) in a general overall health factor.
https://www.ncbi.nlm.nih.gov/pmc/articl ... 0infection.
Vitamin D can modulate the innate and adaptive immune responses. Deficiency in vitamin D is associated with increased autoimmunity as well as an increased susceptibility to infection.
Yes, people may be affected by having insufficient Vitamin D even if it isn’t so bad they get tickets.

As you can see here: https://fastrt.nilu.no/VitD-ez_quartMEDandMED_v2.html people in Northern Europe won’t produce any Vitamin D from sunshine during some or all of the winter. Even on the north shore of the Mediterranean someone would need to spend about an hour in the sun at midday to get an adequate dose.

As Disco writes, in the northern hemisphere winter it’s a good idea to make sure you get enough from dietary sources. Most commonly oily fish, egg yolks or various products with added Vitamin D. I take cod liver oil supplements.
I take an occasional vitamin D supplement in winter as a top-up. I do eat oily fish twice a week but that only gives me ~50% of the RDA two days a week which is clearly insufficient. I don't really eat eggs but they only have 20% of the RDA in two large eggs (100g) anyway.

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Re: Vitamin D?

Post by bob sterman » Sun Sep 27, 2020 5:58 pm

sTeamTraen - if you have time on your hands perhaps you'd like to probe some of the unusual aspects of this Vitamin D paper...

Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection
https://journals.plos.org/plosone/artic ... ne.0239799

- If the age range of the patients in the sample was 20-90 why is the youngest dot on the scatterplot aged 29???
- Why do they take the unusual step of reporting mean 25(OH)D as a natural logarithm? i.e. as ln 25(OH)D? I don't think they used the natural log in any tests?
- Why don't they treat 25(OH)D as a continuous variable and test whether it predicts a binary outcome (e.g. survival vs death)? They have dichotomized vitamin D status. What's the betting they tried dichotomizing it in various ways before settling on this particular threshold.
- In any case, they state (for Figure 1) that "the number of red dots (inpatient mortality) above the solid line is significantly less compared to the dots below the line", the solid line being the 30 ng/mL 25(OH)D line. Well, counting the dots I can't get this result with a chi-square.

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Re: Vitamin D?

Post by basementer » Sun Sep 27, 2020 6:25 pm

bob sterman wrote:
Sun Sep 27, 2020 5:58 pm
- Why do they take the unusual step of reporting mean 25(OH)D as a natural logarithm? i.e. as ln 25(OH)D? I don't think they used the natural log in any tests?
The paper says
25(OH)D, CPK and LDH levels, did not have a normal distribution, a log transformation was applied to correct their normality distribution.
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Re: Vitamin D?

Post by bob sterman » Sun Sep 27, 2020 6:52 pm

basementer wrote:
Sun Sep 27, 2020 6:25 pm
bob sterman wrote:
Sun Sep 27, 2020 5:58 pm
- Why do they take the unusual step of reporting mean 25(OH)D as a natural logarithm? i.e. as ln 25(OH)D? I don't think they used the natural log in any tests?
The paper says
25(OH)D, CPK and LDH levels, did not have a normal distribution, a log transformation was applied to correct their normality distribution.
Yes - but they didn't use the transformed variable in the test - which was simply to compare people above vs below 30 ng/mL 25(OH)D. They only seem to have used 25(OH)D as a dichotomized variable.

Can you see anywhere they used the transformed variable for anything?

Not in the supplementary information which very usually is a video of the author talking about the results.
Last edited by bob sterman on Sun Sep 27, 2020 6:55 pm, edited 1 time in total.

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Re: Vitamin D?

Post by jdc » Sun Sep 27, 2020 6:55 pm

bob sterman wrote:
Sun Sep 27, 2020 5:58 pm
- Why don't they treat 25(OH)D as a continuous variable and test whether it predicts a binary outcome (e.g. survival vs death)? They have dichotomized vitamin D status. What's the betting they tried dichotomizing it in various ways before settling on this particular threshold.
I'll leave the other questions to steamtraen and basementer, but on the choice of this particular threshold, I have this: https://www.health.harvard.edu/blog/vit ... 6121910893
In 2010, the venerable Institute of Medicine (IOM) issued a report based on lengthy examination of data by a group of experts. To sum up, they estimated that a vitamin D level of 20 ng/mL or higher was adequate for good bone health, and subsequently a level below 20 was considered a vitamin D deficiency.
But in 2011, the respected Endocrine Society issued a report urging a much, much higher minimum blood level of vitamin D. At that time, their experts concluded: “Based on all the evidence, at a minimum, we recommend vitamin D levels of 30 ng/mL, and because of the vagaries of some of the assays, to guarantee sufficiency, we recommend between 40 and 60 ng/mL for both children and adults.”
A different opinion on the right target level of vitamin D is presented in an article titled “Vitamin D Deficiency: Is There Really a Pandemic?” published in the New England Journal of Medicine. In this piece, several of the leading epidemiologists and endocrinologists who were on the original IOM committee argue for a lowering of the currently accepted cutoff level of 20, stating that the level they estimated as acceptable was never intended to be used to define vitamin D deficiency. They feel that we are over-screening for vitamin D deficiency, and unnecessarily treating individuals who are perfectly fine.

Based on their analysis, a more appropriate cutoff for vitamin D deficiency would be much lower, 12.5 ng/mL.
Whether the authors of the PLoS One papers were persuaded by the weight of the endocrine soc's evidence or whether it was a convenient level that was just right for their results I couldn't say.

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Re: Vitamin D?

Post by jdc » Sun Sep 27, 2020 7:03 pm

btw, their other paper https://pubmed.ncbi.nlm.nih.gov/32941512/ splits into three groups and defines "adequate" as 30-34 ng/mL. While "deficient" is <20.

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Re: Vitamin D?

Post by shpalman » Sun Sep 27, 2020 7:52 pm

having that swing is a necessary but not sufficient condition for it meaning a thing
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Re: Vitamin D?

Post by shpalman » Sun Sep 27, 2020 8:09 pm

having that swing is a necessary but not sufficient condition for it meaning a thing
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Re: Vitamin D?

Post by sTeamTraen » Mon Sep 28, 2020 12:04 pm

The always-entertaing (although sometimes his own worst enemy) science blogger Leonid Schneider has some thoughts on this.
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Re: Vitamin D?

Post by sTeamTraen » Mon Sep 28, 2020 12:39 pm

bob sterman wrote:
Sun Sep 27, 2020 5:58 pm
- If the age range of the patients in the sample was 20-90 why is the youngest dot on the scatterplot aged 29???
I digitised the scatterplot by hand. I counted 193 alive and 35 dead, for a total of 228, versus 235 for the reported sample size. I may have missed a few if points closely overlapped on the Y-axis, but perhaps the X-axis was truncated on the left. Or "20-90" could have been a typo for "29-90", eitherby the authors or introduced later. (I've dealt myself with copy-editors who were clearly quite capable of looking at that and think "Hmmm, 29-90 doesn't look like a range, he must mean 20-90".)

More to follow as I read the paper and your points again.
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Re: Vitamin D?

Post by raven » Mon Sep 28, 2020 9:54 pm

Hunting Dog wrote:
Sat Sep 26, 2020 7:23 pm
So there's apparently a study or two saying that vitamin D levels are relevant to catching/surviving covid. See here.
Apparently everybody and his dog have heard about this. I take vitamin D over the winter, ever since I discovered it keeps my eczema/chapped hands at bay, and when I went to order some yesterday found that Boots* is sold out of the low dose ones I take.

Possibly because they're selling it in a special 'Immunity and Protection Bundle' with a packet of masks and an anti-viral hand sanitizer.

(MrRaven swears the local Boots doesn't even have shelf space for the ones I want anymore. He came home with some chewable monstrosities with calcium instead, but I can't take them 'cos they have sorbitol in. :roll: )

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Re: Vitamin D?

Post by jdc » Mon Sep 28, 2020 11:03 pm

sTeamTraen wrote:
Mon Sep 28, 2020 12:04 pm
The always-entertaing (although sometimes his own worst enemy) science blogger Leonid Schneider has some thoughts on this.
Heh, pretty liberal use of sarcasm in that piece. He's a bit more serious when he addresses Holick and his work though, I think "contempt" is the word I'm looking for here.

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Re: Vitamin D?

Post by sTeamTraen » Tue Sep 29, 2020 5:59 pm

An interesting exercise in that PLOS ONE paper posted above is to work out how many people died. That ought to be a pretty fundamental thing to report, right?

Spoiler:
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Re: Vitamin D?

Post by jimbob » Tue Sep 29, 2020 6:22 pm

sTeamTraen wrote:
Tue Sep 29, 2020 5:59 pm
An interesting exercise in that PLOS ONE paper posted above is to work out how many people died. That ought to be a pretty fundamental thing to report, right?

Spoiler:
Oh dear
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