Hacker Newsnew | past | comments | ask | show | jobs | submitlogin
Early clinical trial shows anti-depressant prevents hospitalization from Covid (jamanetwork.com)
119 points by notknifescience on Jan 9, 2021 | hide | past | favorite | 109 comments



This presentation from the Covid-19 Early Treatment Fund (a non-profit funding over a dozen trials) summarizes the data so far on Fluvoxamine. https://docs.google.com/presentation/d/1u7resy2bGA1_HIgj6Nc7...

Executive Director Steve Kirsch wrote this post on the most promising early treatments and CETF feels Ivermectin and Fluvoximine are the two most promising which they are currently funding studies on. He's continuing to update this post almost daily. As of now, the data is still insufficient to be conclusive (which he highlights) but I appreciate they are sharing these kind of insights from the front lines, at least for those capable of understanding the nature of evolving research and the associated uncertainties. Of particular interest, he links to Washington University's large-population, remote trial of fluvoximine that's free and anyone can apply and participate from home.

https://www.quora.com/What-is-the-current-treatment-for-Covi...


Ivermectin? The animal dewormer? Did COVID suddenly grow glutamate-gated chloride channels?


Ivermectin has been known even before COVID-19 for having antiviral properties. And it's not an animal dewormer - it's been recognized as essential medicine for humans by the WHO and there's even a Nobel Prize for Medicine awarded for its application in eradicating parasites in humans. During the last 30 years, nearly 4 billion doses of it have been applied to humans.


To be clear, this isn't saying that any anti-depressant is effective for COVID. It appears to be a unique side-effect of Fluvoxamine.

There are several existing drugs which have been found to have modulatory effects on early COVID infections. The key word here is "early", as most of them only have a significant impact before the infection gets out of control.

Keep in mind that Hydroxychloroquine is one of the existing drugs discovered to have some effect on early infections, but it clearly failed to have much impact on late-stage infections.

The study authors were careful to exclude severe or late-stage infections from their trial to avoid similar failures:

> Participants were community-living, nonhospitalized adults with confirmed severe acute respiratory syndrome coronavirus 2 infection, with COVID-19 symptom onset within 7 days and oxygen saturation of 92% or greater.


“ Keep in mind that Hydroxychloroquine is one of the existing drugs discovered to have some effect on early infections, but it clearly failed to have much impact on late-stage infections”

Do you mind sharing your evidence that HCQ helps with early infections? Because I know many studies that showed no benefit, for example:

https://www.nejm.org/doi/full/10.1056/nejmoa2016638

That is one of many studies.


The proposed mechanism for HCQ (zinc affinity) implies that it would be most effective if taken before the onset of symptoms, perhaps even before viral load is high enough to test positive. Obviously this makes it challenging to do a study. Nearly all studies that I’m aware of are initiated on patients that are already showing symptoms, because the patients are enrolled at the hospital, and few have the necessary zinc supplication. The expectation is that these studies would show little benefit, and indeed that is the case.

There remains no studies with large sample sizes done as far as I know with HCQ+zinc given as a prophylactic measure immediately upon first exposure.

EDIT: It's also worth mentioning that this isn't some crank theory about COVID. It is well known that zinc inhibits replication of RNA virus, giving the immune system more time to respond. I used to get colds 5-6 times a year, and the flu almost every year. When I learned about this effect zinc has, I started taking mega doses of zinc upon exposure, whether I'm close to someone known to be sick, flying through airports, or just caught in cold weather. I have not had cold or flu symptoms since I started this regimen about 2 years ago. Of course that is just an anecdote. There are, IIRC, observational studies showing this effect across larger populations.


Sure and when you have results of a RCT of zinc plus HCQ in prophylactic patients and publish it I will read it with great interest and if the data looks good I will be giving it to all my patients.

If, however, you want to tell me that I should be using it now, because of a proposed mechanism and theoretical benefit, by using that logic why shouldn't I be giving my patients all other vitamins/supplements/medications that have been variously proposed and have their own believers?

Aside from HCQ+zinc, what other cheap, low risk interventions do you propose be given and studied?

(edit: additional thoughts) If you don't have any others, than I suggest you reevaluate why you think HCQ+zinc is unique (it's not). If you do, then you'll have a list of them and probably a list of reasons for each and a ranking of which are the most promising and which are the least. When you do this, it forces you to critically think about how best to rank these and how that ranking might change with evidence. Then it forces you to study the evidence.

In an above post I mentioned that I did give HCQ to patients in the hospital back in March when it was the only thing that had ANY evidence (and the evidence was poor, but it was all they had). It made no difference, and it may have caused some deaths due to QTc prolongation (personally I believe it is very safe and I've taken it for malarial prophylaxis before).

edit: (I removed a snarky line, apologies)


You are reading way, way too much into what I actually said. This is obviously a political issue for you and I have no desire to engage any further. Good day, sir.


Apologies if I did. There are a large number of people who believe that the reason we don't use HCQ is due to a conspiracy. You may have just wanted to point out that the combination has never been used.


That’s it. Cheers.


(pre-covid) I had an older co-worker that told me he doesn't regularly supplement w. vitamins, but as soon as he feels himself coming down with something, he takes some zinc, and said he could usually kick most colds before they really got a hold. I'd never heard of that before, and would always try vitamin C or whatever. I've tried zinc once, (again, pre covid days), and I guess I kicked whatever I was about to get. Would it have made a difference, who knows?


It would. At least with colds, both the theory is pretty clear and there’s mounting experimental evidence. Zinc is pretty much a common cold cure, if you take it early enough and have a decent immune system to start with.


Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies: https://www.jstage.jst.go.jp/article/bst/advpub/0/advpub_202...


That appears (there is no date) to be a brief paper from February or March. I’m interested in what you think that paper says?

Read what the title says and read the short paper. It has zero references to results of use in patients other than referring to a news release. There is link that it is being used in clinical trials, but no results.

We know HCQ does not do anything for Covid after hundreds of studies. It is time to move on. Focus on other potential treatments.


There's a bunch of very professional-looking websites claiming the effectiveness of HCQ, especially early on :

https://hcqtrial.com/

https://hcqmeta.com/

(And now https://c19study.com/ ?)

Sadly, I only have been able to find this as criticism :

https://sciencebasedmedicine.org/hcqtrial-com-astroturf-and-...


EDIT: Also note that those links are all the run by the same group, the FAQs are the same.

Consider reading the IDSA (Infectious Disease Society of America) guidelines. They get updated fairly regularly and are composed of the boots on the ground infectious disease specialist physicians who are trying to help people.

https://www.idsociety.org/practice-guideline/covid-19-guidel...

Unfortunately, HCQ became politicized which added a bunch of noise. There are a lot of people who are invested in being right for various reasons rather than trying to find the truth, and many of these websites are biased.

For what it's worth, I am a physician who prescribed HCQ to patients in March (with appropriate informed consent from pts/families) when he had no other idea of treatment options based on the original study which purported to show decreased viral load. It became obvious that it didn't matter whether patients got it or not in my experience (some got better and some died whether or not they got it), numerous studies then confirmed this. Most if not all hospitals were trying it with the first wave back in Jan-March and then we stopped using it when data came out that it didn't change anything. Then, things got crazy because it became promoted by certain politicians (this happened when any physician with experience had already realized it was a placebo) AND then there was a big scandal where a paper was published showing increased mortality that based on falsified data and later retracted.


A certain politician and a certain very high-profile doctor.

There's also this point of view :

https://freerepublic.com/focus/f-news/3858145/posts

A later, more polished and detailed version in French :

https://www.agoravox.fr/tribune-libre/article/traitements-a-...

However, while I had found these arguments compelling, the issue was that they took the effectiveness of HCQ as a starting point. Which just seems to go against the available evidence at this point.


What sucks most is that there are several medicines that have found to have a positive effect that got drowned in the HCQ noise.


There are a lot of potential medications that are being studied and it's good to remember that we have to do good science to know what we are doing. So far, only steroids (specifically dexamethasone) has shown a mortality reduction. Remdesivir maybe decreases length of stay in the hospital.

Currently beside fluvoxamine, there is research being done on colchicine (usually used for gout), ivermectin (controversial because the main people promoting it believe so strongly in it that they flat out say on their website it is unethical to perform randomized control trials to study it at this point, which is bonkers), various vitamins have been proposed.


There is this new study which was being publicised earlier in the week: https://www.google.com/amp/s/www.nytimes.com/2021/01/08/heal...

The study claims they do reduce mortality. It is, however, a non-reviewed preprint.


The addresses of those websites do not make them look very professional, in my judgement.


It makes me wonder - or seems to insinuate to - that Fluvoxamine may directly impact the immune system. The only other alternative is that some molecular structure of Fluvoxamine kills off the virus?


It would probably be any SSRI though?


No, it's strictly Fluvoxamine as far as we know.

SSRIs aren't all interchangeable, especially when it comes to side effects. Fluvoxamine is very different than other SSRIs because it has significant effects at the sigma-1 receptor. The only other SSRI with significant sigma-1 activity is Sertraline, but it has the opposite effect at sigma-1.

However, it's possible that the anti-COVID properties are unrelated to Fluvoxamine's actions at the serotonin transporter or the sigma-1 receptor. We just don't know.


The similarly named Fluoxetine has lesser (but still significant) effects at Sigma-1. Since Fluoxetine is so widely distributed (because it's Prozac), there is quite a bit of observational data that Fluoxetine is also correlated with reduced clinical severity. Obviously, even a strong correlation is not causation but it is certainly grounds for prioritizing investigation, especially since Fluoxetine/Prozac is very well-tolerated, inexpensive and widely available in mass quantity.


Fluvoxamine has the highest sigma-1 affinity by far. Fluoxetine's affinity is about an order of magnitude lower.

We don't even know if sigma-1 is responsible for the effects observed, but it wouldn't make sense to give someone Fluoxetine instead of Fluvoxamine (which is also widely available), especially when it would require overdose levels of Fluoxetine to achieve similar sigma-1 effects.

More numbers available in the full text here: https://pubmed.ncbi.nlm.nih.gov/24508523/


Generally speaking, "SSRI" is an ideal goal which isn't perfectly realized; all drugs in that class bind "off-target" to proteins other than SERT.

In this case, fluvoxamine pharmacology is pretty clean and there is experimental evidence only for binding to sigma-1 receptor in addition to SERT (also to a whole bunch of CYP enzymes).

Unfortunately the function of sigma-1 is not well understood but it affects calcium signalling in intracellular compartments where covid-19 replicates


It's suspected to be a specific side effect, not a part of the reuptake inhibition.


Note that "antidepressant" is largely a marketing term. The drug in particular is fluvoxamine, a potent selective serotonin reuptake inhibitor (SSRI). This doesn't mean that other antidepressants will work (if fluvoxamine really does work in larger trials).

Believe it or not, fluvoxamine isn't even approved by the FDA for depression. It probably works, but it's only labeled for OCD (https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/02...). Usually, we'll preserve it for more refractory cases of OCD since it tends to have more side effects and interactions than other SSRIs.


Tiny study, just like chloroquine that is somehow still being talked about...

>Findings In this randomized trial that included 152 adult outpatients with confirmed COVID-19 and symptom onset within 7 days, clinical deterioration occurred in 0 patients treated with fluvoxamine vs 6 (8.3%) patients treated with placebo over 15 days, a difference that was statistically significant.

It honestly worries me how quick people are to jump on these band wagons. Call me when you've at least got 100 cases to review.


As unfortunate as this is, 152 isn't such a small study compared to what's common.

Not saying this is a result that should be taken as definite, but it's strong enough to warrant further looking into this (which was never really true for hydroxychloroquine).


You're correct, only 24 (no placebo group so I guess that's the equivalent of 48?). I thought it was bigger...

https://www.connexionfrance.com/French-news/French-researche...


It also wasn't a randomized trial and had numerous methodological errors.


For all relevant studies with 10,000 or more patients and the correct treatment protocols. See: http://www.hcqlost.com


Respectfully, that's just a counter. It links to another hcq*.com site. That seems to cherry pick results.

Don't get me wrong, this whole thing is a fucking mess.

I haven't seen a reliable study that shows HCQ is effective. I'd be happy to see one of you have one? Given the attention paid to this molecule, there should be some nice, randomised control trials with large n numbers.


Is there something specific that's wrong with their math?


They're lacking sufficient data to draw any real conclusions. Trend spotting like this requires very large data sets.

It would be more interesting to look at (say) NHS data. That's the quick way to avoid this sort of guessing...


They describe their significance calculation.


The efficacy of the vaccines currently being administered to millions were based on decisions made with data from ~200 confirmed cases.


Pfizers stage 3 vaccine trial have 41,000 participants. I'm not sure how you got 200, have I misunderstood you?

https://www.pfizer.com/news/press-release/press-release-deta....


Yes, you have. The efficacy estimate was based on roughly ~200 confirmed cases, which your link confirms for the Pfizer vaccine.


The relevant passage is below. Basically it's a funnel, so It takes testing a large amount of people to tease out just a handful of infections. 162 cases for placebo vs. 8 in the vaccine group.

Analysis of the data indicates a vaccine efficacy rate of 95% (p<0.0001) in participants without prior SARS-CoV-2 infection (first primary objective) and also in participants with and without prior SARS-CoV-2 infection (second primary objective), in each case measured from 7 days after the second dose. The first primary objective analysis is based on 170 cases of COVID-19, as specified in the study protocol, of which 162 cases of COVID-19 were observed in the placebo group versus 8 cases in the BNT162b2 group. Efficacy was consistent across age, gender, race and ethnicity demographics. The observed efficacy in adults over 65 years of age was over 94%.


To be clear, I am using the example of the current vaccines to prove the point that N=200 allows statistical inferences to be drawn.


The 200 you mention are comparable to the 6 in the comment above, not the 152.


The problem is the confirmed cases are the primary part of determining efficacy. The people who do not get the virus have a smaller impact on that statistic at higher numbers. EDIT: User runamok explains it well.

[1] https://www.cdc.gov/chickenpox/outbreaks/downloads/appx-f-in...


That would make sense because how many of these 41000 people would have been infected without the vaccine? 200 sounds quite reasonable.


Several months ago there was a post about vitamin D supposedly being effective in preventing hospitalization. What happened to that idea?


Vitamin D has been shown to reduce severity in several different studies. Everyone should consider taking it.

https://www.reddit.com/r/COVID19/search?q=vitamin+D&restrict...

https://www.youtube.com/watch?v=vN30emwcNS4


Its also been shown not to have an effect in at least one RCT, but the problem is social media skews against spreading that information (its kind of a downer so it won't get shared so much)

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

(Yes, the RCT uses cholecalciferol instead of calcifediol, so the reason why the intervention did not work may be that its a bit late. Yes, the Spanish trial had extremely good results, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456194/ but it looked unusual (100% adherence / no dropouts). Ultimately we still don't know, which is appalling. We need better ways to conduct RCTs cheaply and efficiently!)


So even just looking at these two studies, and the relatively safety and low cost of Vitamin D, why wouldn't you take it?


I would totally take it, but I wouldn't be very surprised if I still got a severe disease.

My point is that its important for people to have an accurate picture of what is the probability of it working, to have a good "feel" of what the likelihood of a good outcome is. Unfortunately social media is providing a skewed picture.

I'm not sure what mechanism would ensure that people get an accurate picture.


It has shown to be correlated with better outcomes. It is also correlated with being healthier, being active, and eating better. As far as I understand there is no strong evidence for a causal relationship.

To be clear, if you live in the northern hemisphere, you should be taking vitamin D. It's cheap and at worst harmless. But that's not the same as saying it will improve the outcome of covid patients.


Not just that there is a clinical trial done in spain where giving vitamin D as metabolized clearly improved covid19 patient outcomes.


IV calcifediol (Vitamin D) in early-stage COVID has improved outcomes in small randomized controlled trials.

Oral vitamin D has been shown to be ineffective at this point, but this isn't surprising: it takes a long time of sustained oral supplementation to raise levels.

Then there's a whole lot of evidence showing correlation, but as you point out, low vitamin D is an indicator of frailty. This is much weaker evidence.

I think it's likely that taking oral vitamin D before infection probably improves outcomes somewhat.


I haven’t heard vitamin d administration is associated with better outcomes, but I’ve heard that vitamin d levels are inversely correlated with outcomes - i.e., people should take a blood test and determine if they are vitamin d deficient, and supplement as needed.


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

> 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.

Strengths: Randomized, very strong effect, strongly statistically significant.

Weaknesses: single trial, single center, relatively small sample, not blinded.

https://pmj.bmj.com/content/early/2020/11/12/postgradmedj-20...

> Greater proportion of vitamin D-deficient individuals with SARS-CoV-2 infection turned SARS-CoV-2 RNA negative with a significant decrease in fibrinogen on high-dose cholecalciferol supplementation.

Strengths: Randomized, blinded trial

Weaknesses: single trial, single center, relatively small sample, secondary outcome measure


I will say, I've been regularly taking Vitamin D for a while and recently started having some low back pain. Talked to the doctor and was told to take some magnesium. Apparently it is used along with Vitamin D. So if you find yourself in my situation, talk to your doctor.


> and at worst harmless.

Half true, you can take too much [0], it's just that it either has to build up over a long time or be from dosages far larger than you can buy without a prescription.

[0] https://www.healthline.com/nutrition/vitamin-d-side-effects


Vitamin D is key to T-cell function. T-cell immunity is involved in mild / asymptomatic covid cases (vs antibody immunity).


Yes, but are governments recommending it? Are doctors recommending it? Is WHO recommending it? I didn't hear anything about it except from that one post on HN, which I think is quite strange. If this works, then shouldn't there be a nation-wide plan to introduce more vitamin D in the diets of people?



The UK's health services are struggling at the moment.

So can the conclusion be that vitamin D does not work as expected? Or is the conclusion that still not enough people are taking vitamin D, and its usefulness should be better communicated?


The reasons for UK health services failing have little or no connection to vitamin D.

Vitamin D has shown signs that it slows down / makes covid less deadly.

Because we don't understand: who is taking it, in what amounts, local weather, what the numbers would be without it we can't assume anything from them struggling.


The amount recommended is insufficient for most people to get to the level where (correlation) has shown significantly reduced risk - that is >30 ng/ml (>75 nmol/l)

Another thing that is tricky is that it really depends how much you need to take on what your levels are personally. We know that the amounts they recommend are completely long term safe for everyone and long term good enough to avoid severe deficiency. But for most people there will still be insuficiency - the necessary average is actually around 2000 IU (for some people it should be up to 4000 IU, others less)


Please see Vitamin D public health campaign petition https://petition.parliament.uk/petitions/564133


> The UK's health services are struggling at the moment.

Are you saying the NHS is struggling with their doctors publishing dangerous recommendations? I’m not sure what you’re implying.


For what it's worth, many government authorities already recommend vitamin D supplementation under varying criteria simply for general health. Because a lot of people in temperate-latitude countries really do have a mild to moderate deficiency:

> Just over two-thirds of Canadians (68%) had blood concentrations of vitamin D over 50 nmol/L -- a level that is sufficient for healthy bones for most people. About 32% of Canadians were below the cut-off. About 10% of Canadians were below the cut-off of 30 nmol/L -- a level that is considered a deficiency.

In Canada, everyone is advised to discuss it with their doctors in relation to the winter season. My doctor tests it with my routine blood work. Many people take a supplement over the winter, especially those with darker skin. And people over 50 have a blanket recommendation to take a 400 IU dose daily year-round.


It was part of the regimen that Trump took when he got Covid.


Are you unconvinced? You know basically vitamin D is a kind of "master regulator" of metabolism / immune system.

Deficiency of vitamin D is immune system dysfunction.


I believe the studies, but my question is why do we let the health system suffer if there is such a simple solution? Why isn't "take vitamin D" in the same list as "wash your hands often" and "keep distance"?


Are you sure the government cares about your health?


I'm sure they at least care about getting the economy back on track.


Even small businesses?


I've seen it recommended by some authorities, but very timidly.

There's no single answer. Vitamin D is basically a panacea, but for some reason most medical professionals don't know. Modern western medicine is on the whole ignorant of the role of vitamin deficiencies in disease.


Doctors (and basically any degreed professional) aren't interested in recommending anything that doesn't involve them.


The pandemic concerns the work and lives of just about any doctor at the moment.


Doctors want things to get better as much as anyone. The timelag between new science and what a doctor recommends can take a generation.


This site has a fairly complete index of all the studies about vitamin D and COVID-19. The total weight of evidence is now quite strong.

https://vitamin-d-covid.shotwell.ca/


Vitamin D is still being discussed quite a lot on HN. My understanding is that it boils down to "It helps those who are deficient but doesn't do much, if anything, if you aren't deficient."

Now, a lot of people are deficient -- probably more now than usual due to the lock down because people aren't getting out much, so people are getting less sun exposure. So I tend to get downvoted when I say things like "If you are deficient, you should redress that. If you are not, extra Vitamin D seems to do nothing and is potentially bad for you (because it is fat soluble and you can hit toxic levels in your system if you overconsume)."

I think there may somewhat less excitement about it because it helps if you are deficient but not if you are not, so it fails to serve as a drug substitute. People tend to not get excited about the idea that treating nutritional deficiencies helps shore up your body's ability to fight disease, even in cases where that deficiency is fairly widespread and the disease in question is fairly deadly.

Hoomans: Not the most logical species.


One possible candidate drug I’ve read quite a bit about but have not seen anything on HN about is high-dose melatonin, and even typical melatonin use is associated with a lower chance of testing positive. There’s a bunch of papers discussing how it _could_ be useful, there are several studies underway but none have been completed yet.


I'm not at my best today. I've been trying to lay low and not crab at people online.

But zinc is another thing that looks promising from what I gather.


The trouble with that approach is that we don't really know the optimal vitamin D level for human health. There are clear symptoms of severe deficiency. But is 20 or 30 ng/ml really enough? Maybe we should target a level closer to 80?

The issue is further complicated by the interaction with other micronutrients such as calcium and vitamin K. Vitamin D intake has to be adjusted based on those as well. So it's tough to make a blanket recommendation for everyone.


There's always some excuse.

In this situation, I would say that anyone who is high risk and has no affirmative reason to believe Vitamin D is contra indicated should consider trying to take a small supplement and/or get some sunlight regularly.

For optimal absorption, you need to take Vitamin D, Vitamin K and Calcium together. Some Calcium supplements include those two vitamins.

For optimal results, do not consume calcium and iron together. This means if you are trying to improve your nutritional status via diet, do not eat high iron foods (like beef, broccoli) with high calcium foods (like cheese, milk). They interfere with each other in terms of absorption.

If you are in a really fragile state of health, all these details and more (such as bioavailability) matter a helluva lot. If you are not in a really fragile state of health, you may find that you don't need to care so much all these pesky details.

Anyone who is really interested in their own welfare can and should start a food and symptom journal and read, read, read about health stuff (and learn how to sort the wheat from the chaff). If you do that, you can get to a point of noticing symptoms of deficiency at an early stage.

I do this regularly and adjust my diet accordingly.

But these are not answers people want to hear. They want a pill, a shot, a surgery, a solution with a really big and obvious and immediate change so they can look at it and go "I did a thing and got a result." They don't want to hear "You need to track it over time and see how you feel in a week or a month to have any real idea what helps."

It's also inherently hard to isolate nutritional stuff. If you make any change at all to your diet, you have probably made multiple different changes.

The way to isolate it is to start with supplements, stick to your normal diet, make no more than one change per week and keep a journal so you can track it and see what happens.

Anything that has any health benefit will have side effects. Antibiotics routinely cause diarrhea and that's one of the more common side effects of alternative remedies, yet if I tell people that many of them will use that as an excuse to say "Oh, it has side effects. Nope. That's a big fat nope for me. I'm not doing that." even though it's the same side effect that antibiotics have and they wouldn't hesitate to take those.

There's a lot of ignorance and prejudice and inherent resistance to resolving medical things nutritionally. In spite of study after study after study saying "Nutrition and exercise mitigate every known deadly medical condition ever in the history of human kind" when the rubber hits the road, people hand wave off nutrition as not important and "not something that will cure cancer, you dumbass!" and stuff like that.


Is it not any different than suggesting obese people get in shape to reduce their risk?

Low-hanging, non-risky fruit first.


Lots of people who are obese have tried like hell to "get in shape" and failed. It's not actually a slam dunk solved problem to say "Just lose the weight."

It pretty much is a slam dunk solved problem to say "If you are deficient in X, redress that." We know how to redress a vitamin D deficiency pretty confidently, simply and in a straight forward fashion.

I lost several dress sizes without trying by redressing other things, primarily nutrient deficiencies. I focused on eating an aggressively nutritious diet to redress a long list of deficiencies rooted in a genetic disorder that causes gut dysfunction.

So my experience fits with the general idea that "Solving obesity is harder than it looks and the solution may be something non obvious in any given case." Maybe our mental models of what is going on there will evolve and what I am saying will be "the obvious answer" to future generations, but it's not what is currently believed to be what works to solve obesity.

The current mantra is "Calories in. Calories out." and leads to metrics like "Eat less and exercise more" and some people find that wholly unworkable or unsustainable for various reasons.


Sorry, didn't mean to imply it's easy to lose weight, although I see that I did. Just meant that things to be encouraged (to reduce ones covid risk) don't necessarily need to be drugs that are proven to treat the disease.

Including taking your vitamins, even if you don't normally.


Yes, I agree, people should be doing the "easy, obvious, low risk" stuff first (if they can -- lots of people don't have the money, can't exercise adequately because of lock down, etc).

One of the problems is that is an inherently hard sell. People are terrible at measuring the disasters that should have happened but didn't.

If you convinced everyone to take their Vitamin D supplements, you would have an extremely hard time measuring the deaths that didn't happen but should have and an even harder time convincing the general public you weren't making up BS as click bait.

This is the bane of my existence. I have a serious medical condition and I know what the path not taken is supposed to look like and I've been getting better for nearly two decades when the condition is supposed to involve a steady and irreversible decline and I get told all the time that I am full of baloney and I can't possibly know that what I'm doing is effective and "X number of years of steady forward progress is just a wild coincidence -- stranger things have happened" and on and on.

Even people who believed me and took my advice have told me "I gave x, y and z nutritional things to my child and they are in the ER less but they aren't on less medication." by which this person meant the child's maintenance drugs were the same. But they implicitly failed to count the fewer antibiotics, steroids and other emergency treatment drugs as "less medication."

If you normally are in the ER every couple of months and need antibiotics for a month afterwards, being in the ER less constitutes a very significant reduction in use of medication. So this person was seeing results and going "But my child still needs just as much maintenance drugs, so the drug use is the same as before" when it absolutely wasn't the same as before.

So what you will see here is that the general public is much happier if you can tell them "X number of people were saved by a vaccine/antibiotic/ventilator/hospitalization" than if you tell them "We convinced the entire nation to take its vitamins and saw a dramatic reduction in incidence of disease."

If you tell them the second thing, the entire world will rise up and go "You are so full of shit. That's just a coincidence man. We didn't even need to take our vitamins. It just fucking died out for no apparent reason and you made me waste all this money on vitamins, you shit head, you."

So I've mostly quit trying to talk about "Things you -- yes, you as an individual -- can do to try to cope with this global pandemic." because I'm tired of being attacked with bullshit accusations of "practicing medicine without a license" and other crapola of that ilk.

I'm pretty damn sure I will survive this -- unless I stupidly try to be helpful, in which case an angry mob may decide I am somehow to blame for something. So: Whatever. "You fools do whatever the fuck makes sense to you and leave me the hell alone."



Yes, dosage should be 10k IU / day for starters with 5mg vitamin K2. Fat-soluble so take with a meal.

Vitamin D depletes Vitamin A and magnesium, get the former from foods and supplement the latter as magnesium glycinate and/or chloride.

Other common & relevant deficiencies are boron and zinc, especially zinc.


10k IU/day exceeds the Tolerable Upper Intake as determined by the US's National Academy of Medicine, the European Food Safety Authority, and similar organizations. Medical doctor Deva Boone posted a report of toxicity at half that dose:

https://www.devaboone.com/post/vitamin-d-part-2-shannon-s-st...

This post and related posts about vitamin D were discussed on HN. See:

https://news.ycombinator.com/from?site=devaboone.com


I know, but that's in error:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541280/#:~:tex....

Doctors correcting vitamin D levels are finding 10k IU is a good starter dose and that is often insufficient to arrive at optimal levels.


Here's another report of toxicity at a similar dose:

https://jeffchen.dev/posts/Vitamin-D-And-Heart-Palpitations/

Dr Boone posted on HN, and claimed that vitamin K2 would not counteract high dose vitamin D:

https://news.ycombinator.com/item?id=24262492

I am not aware of any randomized controlled trial of vitamin K2 for protection against vitamin D toxicity.


Really the only way to know the correct dose for any individual is to conduct occasional blood tests and dynamically adjust up or down. There as so many factors including diet, body composition, sunlight exposure, genetics, etc. One individual might need a daily dose several times higher than another.


In your article the person was taking this dose for 5 years, and probably without vitamin k2 and developed hypercalcemia.


It's been confirmed and supported by other studies.


What’s the proposed mechanism of action?


From the article:

A potential mechanism for immune modulation is σ-1 receptor (S1R) agonism. The S1R is an endoplasmic reticulum chaperone protein with various cellular functions, including regulation of cytokine production through its interaction with the endoplasmic reticulum stress sensor inositol-requiring enzyme 1α (IRE). Previous studies have shown that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) with high affinity for the S1R reduced damaging aspects of the inflammatory response during sepsis through the S1R-IRE1 pathway, and decreased shock in murine sepsis models.


The sample size is small but the effect is strong, stronger than you almost ever see for this kind of thing.

(e.g. i suspect a tiny dose of antiviral or synthetic antibody would be effective for prophylaxis or early treatment. By the time somebody is seriously ill they are sick from the cytokine storm and possibly clearing the virus doesnt change the course of the disease.)


With so many studies being done on covid (by basically every lab in the world capable of doing so), the self selection biases are especially strong. That is, every study that confirms some statistically significant effect (often with a small sample size) will be published, and all of the corresponding studies which confirm the null hypothesis are buried. So you get a flood of seemingly compelling early evidence for covid effects or treatments, most of which will turn out to be false


Indeed. Presumably if it is effective, you could study people who are using Fluvoxamine for its anti-depressive properties, and you'd find that (other things equal, using something like propensity score matching), they have less serious cases of COVID.


I believe that is exactly how it was discovered as a potential treatment for Covid-19.


yup.

If you flip a coin 10 times, there is less than a 5% chance you will get 3 or fewer tails -- so if you do, that looks "statistically significant" that you have a weighted coin (which still doesn't guarantee it).

But if 500 people in different places flip a coin 10 times, what are the chances at least one of them will get 3 or fewer tails? Oops. It doesn't mean your chances of having a weighted coin went up.


It doesn't prevent the hospitalization, it prevents the symptoms that lead to hospitalization.


From a lay perspective, That seems a bit pedantic


The very first thing that popped into my head when I read the title was "Is there some sort of legal agreement when taking the one drug that clashes with some sort of covid related law?"

It's just sloppily written title that ends up asserting something that is baseless, misleading, and untrue.


Former homemaker here: Not to me it doesn't.


So, the capture of Afghanistan's production can help us against covid. ;-)


jamanetwork really needs to work on the accessibility of it's web design. Like most large online publishers of academic papers it recently made massive changes to it's journal sites so they're all javascript and CSS. Unlikely most large online publishers it hasn't realized what a mistake that was and implemented a fallback for content display in the absence of javascript execution. As is the page displays everything except the article in question (until you disable CSS).


I agree it's terrible web design, but like many such cases, it can be fixed by enabling Firefox's Reader View.




Consider applying for YC's Fall 2025 batch! Applications are open till Aug 4

Guidelines | FAQ | Lists | API | Security | Legal | Apply to YC | Contact

Search: