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Vitamin D, part 3 – The Evidence

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Re: Vitamin D, part 3 – The Evidence

#161

What about the study in Spain from a few days ago (I'm in Spain atm and it's kinda big news over here), at the Reina Sofia University Hospital in Córdoba, where they just announced the results of the randomized blind controlled trial and the results are incredible: 1 person out of 50 who got huge doses of vitamin D for a few days after arriving at the hospital with Covid-19 symptoms ended up in the ICU, where 13 out…

There is a lot of excitement about this study, but the details in it matter. It was randomized - but when you look at the two groups (treatment vs. control), they had some key differences. The control group (who didn't receive Vitamin D) had more men (69% vs 54%), more people with hypertension (57% vs 24%) and diabetes (19% vs 6%). So the groups were not the same. If you just compare the numbers of those who went int…

I disagree with your interpretation of the statistics. There are going to be inter-group differences with any controlled study. This is sampling error and it's exactly what the p-value and confidence intervals are meant to account for.

It's unlikely that the strongly significant result we're seeing in the study is due to sampling error.

Re: Vitamin D, part 3 – The Evidence

#162
post #98

Earlier quoted context omitted.

Interesting! Can you quote the part of the study where they say the results are not statistically signifcant when you control for diabetes and hypertension?

Here is what the article states: "Therefore, a multivariate logistic regression analysis was performed to adjust the model by possible confounding variables such as hypertension and type 2 diabetes mellitus for the probability of the admission to the Intensive Care Unit in patients with Calcifediol treatment vs Without Calcifediol treatment (odds ratio: 0.03 (95%CI: 0.003-0.25) (Table 3). The dependent variable consi…

Unless I'm reading your comment wrong, this p-value (0.03) is actually significant for a 95% confidence test.

Re: Vitamin D, part 3 – The Evidence

#163

Earlier quoted context omitted.

"Deficient" is not the same as "lower end of the normal range." If you suspect you are deficient, go to a doctor.

I said "low" not "lower end of normal". What part of my suggestion is refuted by the article?

"Low" is ambiguous. We are clarifying it.

Re: Vitamin D, part 3 – The Evidence

#164

Earlier quoted context omitted.

RCTs are high quality, because they are done in a controlled setting, testing against a control group, testing the null hypothesis. RCTs are able to show causality. The problem with RCTs is that they are very expensive, since it involves keeping people in a clinic, so usually RCTs are short term and can only afford to look at surrogate markers. However most often than not, surrogate markers are enough. Also RCTs tend…

> RCTs are high quality, because they are done in a controlled setting I have a personal interest in Amyotrophic Lateral Sclerosis, so I am reading patients' Internet forums since two years. Several patients report participating in trials but they also tell that they take other drugs without telling doctors (they do not want to be expelled from the trial). Those drugs could be whatever they fancy, and they change oft…

Those are anecdotes, the question is how often does it happen? Sure, it's possible, which is why we have reviews aggregating the findings of multiple studies.

The results of one study could be an anomaly, which is why replication is important in science. But when those results get replicated in tens or hundreds of such studies, we can start trusting those findings (although when surrogate markers are involved, their interpretation can be up for debate).

Also when people say "high quality", it's important to understand what it refers to. It means the authors can show that the study was designed for the declared primary outcomes. It means that adherence was ensured, versus an observational study relying on questionnaires. And it means a control group was used for comparison, which was randomized, thus the study preferably showing a dose dependent response.

Having a control group BTW minimizes the impact of the subjects not adhering to the program in the way that you describe, since you'd have rebels in both camps.

Re: Vitamin D, part 3 – The Evidence

#165

Earlier quoted context omitted.

There is a lot of excitement about this study, but the details in it matter. It was randomized - but when you look at the two groups (treatment vs. control), they had some key differences. The control group (who didn't receive Vitamin D) had more men (69% vs 54%), more people with hypertension (57% vs 24%) and diabetes (19% vs 6%). So the groups were not the same. If you just compare the numbers of those who went int…

I disagree with your interpretation of the statistics. There are going to be inter-group differences with any controlled study. This is sampling error and it's exactly what the p-value and confidence intervals are meant to account for. It's unlikely that the strongly significant result we're seeing in the study is due to sampling error.

I don't think it is all due to sampling error. In my article I mention that one of the areas in which Vitamin D shows promise is with respiratory illness. I think there likely is an effect, just not as dramatic as the headlines are making it.

Re: Vitamin D, part 3 – The Evidence

#166
post #92

This seems like it might be a little selective. What about these [1] [2] randomised controlled trials that show vitamin D supplementation has an effect on IBS symptoms? Or this [3] double-blinded trial showing supplementation improved sleep quality in people with sleep disorders? Or this [4] one showing improvements in depressive symptoms in overweight and obese subjects? The study cited in TFA is large but only uses…

I wrote the blog post. Unfortunately I was not able to include every study on Vitamin D, and had to pare it back to the largest and/or most significant studies. Most of the studies you mention are small and published in obscure journals. As for my argument, I would never claim that Vitamin D is "a pretty useless vitamin". It is extremely useful, and is lifesaving for people with hypoparathyroidism. But that doesn't m…

> Many of the people supplementing are doing it because they believe it will keep them healthy - and this does not appear to be the case.

I agree with much of your thinking - just not this particular conclusion.

1. As you mention, we know that low-to-moderate levels of vitamin D supplementation is safe.

2. We also know that a solid chunk of the population does not get enough sunlight / is vitamin D insufficient.

3. There are no large-scale trials yet for some items where vitamin D is suspected to have good effects. But there are a few nevertheless, which you share within the article itself - cancer, mortality, respiratory disease particularly stand out.

4. There are also a pile of smaller but promising, statistically significant, double-blinded, randomised controlled trials in a bunch of useful areas.

5. So this seems to be a Pascal's Wager type of situation, where supplementation is all upside and no downside, as long as people don't get crazy with it.

As you say it's not a panacea, and to cite an old comment, I am aware [1] that there are other benefits you get from sunlight. But even if it doesn't do as much as people think, I don't see why it is bad advice for most people to supplement vitamin D to keep themselves healthy!

[1] https://news.ycombinator.com/item?id=19247337

Re: Vitamin D, part 3 – The Evidence

#167
post #157
post #43

Earlier quoted context omitted.

> This is a departure from the discussion of supplementing vitamin D though, isn't it? I don't think so, no. If my hypothesis is correct, the problem is not that they didn't go outside and play sports. The problem is that they are sick , and sick people don't go outside as much. Forget Vitamin D for a moment. Imagine that every time you were outside for an hour, the Outside Fairy granted you one Outside Token. Over t…

That’s very true, but Outside Tokens are really cheap and are low risk so encouraging people to buy them seems like a reasonable hedge to make until the hypothesis can be proven.

So long as it doesn't supplant other real treatments, which it inevitably will within the framework of a recommendation to potentially very ill/desperate people.

Re: Vitamin D, part 3 – The Evidence

#168
post #52

Earlier quoted context omitted.

> What is a reasonable hypothesis then? The logical conclusion is that vitamin D, as we measure it, is proxying for another factor that we haven't yet detected. This X-factor is heavily influenced by sun exposure, but at most weakly influenced by vitamin D supplementation in its current form. Analogously imagine that we had no concept of the health benefits of exercise. We detected that people with gym memberships we…

You're still assuming that Vitamin D is involved in some interaction that itself is the cause of people being sick. Your reasoning is not allowing for the simpler possibility: sick people have less Vitamin D because sick people are too sick to go outside.

That's certainly a possibility, but we have two reasons to believe it's not true.

One, even careful attempts to control confounders, still shows a substantial health benefit associated with higher sun exposure.[1] In other words, even among people with no discernible health conditions, the most sun exposed are healthier.

Two, randomized control trials show improvements in biomarkers like blood pressure[2] and lipid profile[3]. In animal experiments, intense UV exposure is directly linked to a reduction in obesity and metabolic disease.[4]

[1] https://pubmed.ncbi.nlm.nih.gov/24697969/ [2] https://www.sciencedaily.com/releases/2014/01/140117090139.h... [3] https://pubmed.ncbi.nlm.nih.gov/28553593/ [4] https://diabetes.diabetesjournals.org/content/63/11/3759

Re: Vitamin D, part 3 – The Evidence

#169

Earlier quoted context omitted.

RCTs are high quality, because they are done in a controlled setting, testing against a control group, testing the null hypothesis. RCTs are able to show causality. The problem with RCTs is that they are very expensive, since it involves keeping people in a clinic, so usually RCTs are short term and can only afford to look at surrogate markers. However most often than not, surrogate markers are enough. Also RCTs tend…

> The problem with RCTs is that they are very expensive, since it involves keeping people in a clinic This may be a noob question, but why? For something like a vitamin supplement, can't you just give the study participants a box of their 50 possibly-placebo pills and require them to take one per day? If you're worried about compliance, can't you require them to write down the time each day when they take the pill—or…

There are "smart" pill bottles for that purpose, that record what time they are opened.

Re: Vitamin D, part 3 – The Evidence

#170
post #92

This seems like it might be a little selective. What about these [1] [2] randomised controlled trials that show vitamin D supplementation has an effect on IBS symptoms? Or this [3] double-blinded trial showing supplementation improved sleep quality in people with sleep disorders? Or this [4] one showing improvements in depressive symptoms in overweight and obese subjects? The study cited in TFA is large but only uses…

Did you read the article? > It is an essential hormone, definitely, but not a magical pill that will ward off disease. There are conditions that benefit from Vitamin D supplementation - for hypoparathyroidism, a condition that can cause dangerously low calcium levels, Vitamin D is lifesaving. For otherwise healthy adults, the benefit is less clear. Takeaways: it's not clear what preventative benefits it has. Even to…

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