As most of you may have already seen, there is a lot of observational evidence that people with low vitamin D have the worst C19 outcomes. Obviously, correlation by itself doesn't mean causation. But it is a hint.
On top of the hint, we already have dozens of RCTs that vitamin D supplements suppress respiratory infections.
https://www.bmj.com/content/356/bmj.i6583
And now we have this study. Every study and line of evidence has flaws, which is why you look at the totality of the evidence.
From the evidence I've seen, low vitamin D is a bigger problem in modern societies than vitamin D toxicity. Vitamin D is available OTC and many people use it apparently responsibly. I would expect that to continue with appropriate messaging.
It would be great if we could pursue a consensus on this while it can still make a difference, even in the absence of perfect data. It was a mistake in the early US messaging to downplay the importance of masks even though we didn't have perfect data on it.
https://news.ycombinator.com/user?id=devaboone
And she's done a series on it:
https://www.devaboone.com/post/vitamin-d-part-1-back-to-basi...
In absurdly high doses, sure. The Institute of Medicine certifies 4,000 IUs as the upper safe daily limit, although doctors will prescribe higher doses for people with a Vitamin D deficiency.
The Mayo clinic did a study of Vitamin D levels in 20,308 people across 10 years. The result was that 8% of people had Vitamin D levels higher than 50ng/ml (typically a sign of Vitamin D toxicity) but found no correlation between those levels of Vitamin D. They found one, one person out of 20k, who actually displayed symptoms of Vitamin D toxicity. Their blood levels of Vitamin D were over 350ng/ml. They had been taking 100k IUs (25x the suggested dose) as a routine daily supplement. I can only find one reported death from Vitamin D overdose, and it was a 10 year old boy who was mistakenly given 600,000 IUs of Vitamin D a day instead of growth hormone by a hospital in 2015.
Let's compare that to Tylenol (acetaminophen). Tylenol contains 500mg of acetaminophen. Maximum suggested daily dose is 8 tablets, so 4g. 25 times that is 100g. So someone abusing tylenol as hard as that person abused Vitamin D would be consuming 100g of tylenol a day. Medical literature suggests that you go to the ER immediately if you consume over 10g of acetaminophen. Of people who hit blood levels requiring treatment, 5% die and 58% have severe liver damage as a result. I can't find a good, easy correlation between the blood levels requiring treatment and amount taken, but I'm going to go out on a limb and guess that taking 200 Tylenols puts you there.
So if we compare the risk, relatively, Vitamin D requires you to take over 150 times your maximum daily dose for an extended period of time (dosing for children is lower than adults) to cause death. If you take 25x the amount of Tylenol once, there's a good chance you die or have severe long term outcomes.
Vitamin D is amazingly safe, provided you treat it like a medication and don't randomly swallow fist fulls of the capsules. Many people in the US (and some parts of Europe, especially in the north) should actually already be taking a supplement. Low Vitamin D levels are exceptionally common now. In the case of the US, obesity causes low Vitamin D levels, not going outside often enough causes low Vitamin D, and not eating foods containing vitamin D causes low Vitamin D. That's a disease practically tailored to our obese, couch-bound, junk-food inhaling residents. In northern Europe, I think they largely blame the seasonal changes in daylight patterns.
I'm all for calling out danger, I just don't see any here. I don't doubt that some people will manage to hurt themselves. I can already hear someone thinking "if 4,000 IUs keeps me a little safe, I can take 1,000,000 IUs and not wear a mask". If we're really that concerned that someone will harm themselves, we should be able to just add Vitamin D to the tracking system we use for Sudafed. Don't let anyone but more than 10k IUs per day. That's enough for 2 adults and a child at healthy doses, but low enough that taking that much every day is unlikely to harm you in the immediate future (and doesn't seem to be likely to harm you at all, but it is above the suggested dose).
"with appropriate messaging"
And, also, you're talking about one expert opinion, perhaps this person doesn't live at 41 degrees south where our both too cold and too dark for half the year or more to get enough sun exposure and peoples diets are often quire poor.
That's why we need to look at the data in aggregate, and have localities / states set their own guidelines and encourage / incentivise doctors to do more testing and symptom analysis.
Also there's some Joe Rogan-esque "just take the 5000 IU bro" even though 4000 is the recommended supplement upper bound. And devaboone warns against even using that much.
For breastfed babies, France recommend an intake of 25µg to 30µg but it's half of that in the UK (8.5 to 10µg).
It is basically wasteful, only in extreme cases you could 'overdose' vitamins.
This is not true. Vitamin D is fat-soluble, not water-soluble. Your kidneys can only filter out water-soluble vitamins. B vitamins are water-soluble; that's why there's practically no upper limit to how much you can take. Your kidneys will filter out the extra (assuming you aren't eating buckets full of the stuff).
Vitamin D toxicity occurs specifically because your body can't remove the excess vitamin D stored in your fat.
That's also why severe overdose happens over time, as opposed to instantly. You have to take a huge amount of Vitamin D at once to overdose (like millions of IUs) but you can cause toxicity using smaller doses over longer periods of time. If your body could flush it out, that wouldn't be true. Any excess would be removed and you would start each day "fresh".
Many over-the-counter vitamin D supplements appear dosed for people with problems absorbing the chemical.
Not really. It depends on the person obviously but the recommended values are too low due to statistical errors.
Up to 4000 iu per day likely ok.
Both are very far below the 4000 that's often cited here. So I think that 4000 is not a recommended intake but a limit before it becomes risky. For normal people it doesn't make sense to then aim for that maximum dosage.
One thing to consider is biological inefficiency. A 4,000 IU capsule contains 4,000 IUs, but that doesn't mean your body can't actually extract all 4,000 IUs.
That said, I think 1k IUs is considered a standard dose for people without a deficiency. 4k IUs are generally used by people who are currently deficient, or have other issues that cause the deficiency. Doctors will sometimes prescribe doses up to 10k IUs for deficient people.
200 iu sounds very low.
Note, the Endocrine Society currently suggests a minimum 25(OH)D level of 30 ng/ml (75 nmol/liter) and suggests much higher levels of supplementation if you need to raise it: "to raise the blood level of 25(OH)D above 30 ng/ml may require at least 1500 –2000 IU/d of supplemental vitamin D."
Holick, Michael F., Neil C. Binkley, Heike A. Bischoff-Ferrari, Catherine M. Gordon, David A. Hanley, Robert P. Heaney, M. Hassan Murad, and Connie M. Weaver. “Evaluation, Treatment, and Prevention of Vitamin D Deficiency: An Endocrine Society Clinical Practice Guideline.” The Journal of Clinical Endocrinology & Metabolism 96, no. 7 (July 1, 2011): 1911–30. https://doi.org/10.1210/jc.2011-0385.
It's also worth noting that studies have shown that without sun exposure, people may require even higher levels of supplementation to maintain their 25(OH)D levels:
Heaney, Robert P., K. Michael Davies, Tai C. Chen, Michael F. Holick, and M. Janet Barger-Lux. “Human Serum 25-Hydroxycholecalciferol Response to Extended Oral Dosing with Cholecalciferol.” The American Journal of Clinical Nutrition 77, no. 1 (January 2003): 204–10. https://doi.org/10.1093/ajcn/77.1.204.
"CONCLUSIONS: Healthy men seem to use 3000-5000 IU cholecalciferol/d, apparently meeting > 80% of their winter cholecalciferol need with cutaneously synthesized accumulations from solar sources during the preceding summer months. Current recommended vitamin D inputs are inadequate to maintain serum 25-hydroxycholecalciferol concentration in the absence of substantial cutaneous production of vitamin D."
I think this winter I will run an experiment on myself.
It's a pretty useless one in this case. Old people are much more likely to have vitamin D deficiency. They are also more likely to die of COVID. The low vitamin D is a marker of frailty, not a cause.
This was not simply observational. There will be no correlation between being given higher dose vitamin D and age in this trial, the results appear at first blush to be showing Vitamin D is working independant of age.
By the by this /exactly/ why a randomised trial has been the gold standard for medical treatment for so long. False correlations, confounding factors etc are all vastly less likely to skew the results. 2 groups chosen at random, nobody in the groups or treating them knows which is which. 1 group given treatment, 1 given a placebo. How much difference do we see in the 2 groups as a result of treatment.
It's a good question. It's always worth asking. It's always worth checking. The rabbit hole of stat analysis of treatments goes pretty deep from there. Ethical issues come in. Expense. But we all need to make the effort to understand it on some level or we're marks for snake-oil.
To put this in perspective: I take 800iu as a maintenance dose to keep my vitamin D levels up. (I'm doing this under a doctor's supervision: I've been sick with low levels and she does blood tests occasionally to be sure). 2 eggs is simply not enough.
> Randomization generated groups with comparable percentage of unfavorable risk factors as there was no significant difference in subjects with at least one risk factor, except for high blood pressure and diabetes mellitus, known risk factors for unfavorable disease progression [2], which were more frequent in patients not treated with calcifediol.
These are HUGE risk factors. Also:
> This pilot study has several limitations as it is not double-blind placebo controlled. On the other hand, in the first studies evaluating risk factors for severe disease and/or death from COVID-19, the possible role of obesity was not considered. Therefore, given the isolation characteristics of the patients, we did not collect the BMI, which would have allowed us to add obesity as a risk factor for severe evolution of COVID-19 [37] It is striking to consider that obesity shares with aging and black or asian ethnicity a surprising overlap as risk factors for severe COVID-19 and vitamin D deficiency.
Yeah, BMI would've been nice too.
Still, check out table 2. Even with these limitations, seems powerful.
"At least one prognostic bad risk factor(@)
Group receiving Calcifediol: 48%
Group without Calcifediol: 61.54%"
"@) Patients with at least one of the following risk factors (age >60, previous lung disease, chronic kidney disease, diabetes mellitus, hypertension, cardiovascular disease or Immunosuppressed and transplanted patients)."
That's what can be concluded from "at least one": (52% had no bad risk in D group, but only 38.46% had no bad risk in the other group). But it is also not clear where there were more patients with "multiple" factors! Or if they were those who had more problems at the end.
The whole paper contains neither raw data nor any graphs and only means and standard deviations, as far as I see? I would personally really like to see the graphs of distributions or to use raw data to check myself.
The critical question is how good the randomization was done.
Yes, we can see some things are a little unbalanced. But the effect is so massive: we might see 4/5 of the control's rate of ICU admissions if the "one prognostic bad risk factor" determined outcome entirely; instead, we see 1/50 of the rate.
But we still don't know if the persons with multiple bad risk factors were those who ended with bad outcomes? As far as I understand, if it was like that or not can't be seen from the paper at all, and I can imagine that it could have happened. I would really prefer the more raw data to the tables with the selected means and deviations given.
Indeed, checking that the two groups look similar after randomization is completely optional. This study does an OK job of doing so.
There's both known and unknown reasons why someone might be predisposed to have a bad outcome. The reason we randomize, rather than try and make "balanced" groups, is that it addresses both unknown and known factors.
Yes, you can, by chance, get more people who are going to have a bad outcome in one group; about 5% of the time you'll get a p<0.05 finding this way. :P
Given that Vitamin D deficiency can cause high blood pressure, their decision not to correct for this might be the better option.
But for most people, if you’re over 25 bmi you probably could lose some weight. And at a population levels the errors above average out, even in a smaller group.
People make a big deal over the exceptions to it while ignoring that it is broadly accurate and that exceptions are not as common.
https://newsroom.heart.org/news/chronic-anabolic-steroid-use...
I’ve been in these two modes:
1) genuinely overweight with too much fat and not enough muscle
2) nearly overweight according to BMI while very fit, with low fat and high muscle. got here from the other state by exercising a lot, losing fat and gaining muscle.
I think I would have to become totally sedentary again to get rid of my muscle mass and actually reach the lower end of “normal weight” according to BMI, while starving myself and feeling feeble.
Not knowing you personally, it seems statistically more likely to me that your idea of "fit, low fat, high muscle" is what's at fault here (as opposed to BMI). Sure, you could be an exception. But all things being equal, you probably aren't. (Also maybe I misunderstand - if you mean that BMI was saying you were at the high end of normal then ... isn't that just saying that you're fine?)
(Of course if a medical professional or academic specializing in such matters also thought BMI was inaccurate in your case then I would tend to view things differently.)
In his prime he was considered overweight. BMI is way too simplistic for taller athletes.
https://www.webmd.com/diet/features/how-accurate-body-mass-i...
The claim is that BMI does not differentiate between body lean mass and body fat mass. Things like hydrostatic testing are more accurate for determining body fat mass.
It’s well understood that BMI is totally wrong for athletes or anyone remotely muscular.
I assure you that's not my motivation at all. I'm not an expert in that field so I tend to trust the metrics used by the health professionals I encounter.
> BMI is widely regarded as totally obsolete
That is not my impression at all, but again I'm not a subject matter expert here. If you have reliable (ie academic or medical) sources I would be interested in learning more about any current preferred metrics.
What do you have in mind? With a bit of searching I haven't found much that's cheap. (Obviously you can take some tape or caliper measurements to improve your numbers but that's neither new nor particularly accurate.)
First, there is a fundamental constrain that it measures impedance only through legs and a little bit of belly, but no upper body (at least here in .cz, no consumer-grade scales have hand electrodes). I do road cycling as the only sport, and therefore get extremely skewed results as I have strong legs, but the rest of the body is much weaker.
Second, the measurements are almost non-repeatable. You get tens of percent difference across measurements, god forbid if you suddenly have moist feet etc. However, both scales used firmware cheating to mask this noise: once you set up a "profile", it will remember the initial value, and then change the following measurements only slightly. However, set up a second profile (preferably with a slightly modified age etc. to prevent advanced firmware cheating) and you get completely different results.
It's imperfect, but generally correct. More importantly, it's easy to measure. Accurate except for outliers isn't as much of an issue as you think it is, especially as these are generally already accounted for by its users.
https://en.m.wikipedia.org/wiki/Persistence_hunting
If that is the case then the body type would have been low mass overall, like marathoners.
As for best body type for quality of life today (at least from a health perspective), that seems relatively aligned.
This seems like the real question to me; I assume pre-agrarian humans were biologically optimizing to survive famine. Not being an expert on the subject, I wonder what sort of tradeoffs are associated with intense exercise regimes (and how the balance ultimately comes out with respect to modern society).
Infant and child mortality is much much lower.
I am your height and when I was in my 20s, I think I was in the 140s, later I was a little over 200, and now I am just about 185. So the range makes sense to me, but I've never been far from completely sedentary. I know a pro sports player at ~200 would be very skinny. I think Mariano Rivera was an example.
The data show that waist circumference is more reliable and more closely correlated with diseases associated with obesity.
https://www.webmd.com/diet/features/how-accurate-body-mass-i...
Management of this disease has improved over the last few months. More people hospitalized are surviving.[1]
[1] https://www.latimes.com/california/story/2020-08-09/covid-19...
However, for those who can get skin production it is probably better, as there may be other effects we don’t know of. Plus it self limits, whereas one can overdo supplements.
Quoting the article (which I hope all here will read),
"[typically] more than 40 % of patients hospitalized because of COVID‐19 pneumonia developed ARDS of which more than 50 % ultimately died."
That's a 20% fatality rate.
Of the 76 patients in this study - regardless of vitamin D treatment - only 2 died, and the rest were eventually discharged. This is an outstanding result.
None (!) of the hospitalized patients died in the vitamin D / HCQ / AZ group.
I will say that the average age - 58 - is rather young. Only 19 out of 76 were over 60.
"All hospitalized patients received as best available therapy the same standard care, (per hospital protocol), of a combination of hydroxychloroquine (400 mg every 12 hours on the first day, and 200 mg every 12 hours for the following 5 days), azithromycin (500 mg orally for 5 days) and for patients with pneumonia and NEWS score≥5, a broad spectrum antibiotic (ceftriaxone2 g intravenously every 24 hours for 5 days) was added to hydroxychloroquine and azithromycin."
They have since discontinued HCQ because they felt that studies had shown that it was ineffective. We shall see.
As with AIDS, it's the cocktail of drugs that appears to matter. What is effective pre-hospitalization (i.e. prophylactic) is different from the best protocol post-admission. And that, in turn, differs from the best course of treatment in the ICU. The improvement in outcomes over the last few months is a result of experience:
https://covid19criticalcare.com/wp-content/uploads/2020/07/F... (pdf)
“Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50%) p value X2 Fischer test p < 0.001.”
Which sounds like as strong a signal as a study of this scale could hope to show.