3 ms·

Vitamin D is great for the immune system. Should help with all infections. Including Covid. Always good to do the research ofc. But I'm not exactly surprised.

notafraudster 5y ago
Given that a lot of the COVID morbidity and mortality is the cytokine storm rather than the infection itself, I wouldn't consider it a priori clear that Vitamin D helps, is neutral, or harms patients who get COVID. The result isn't sufficient to answer the question. It establishes, generally, that Vitamin D deficient people are more likely to get COVID. It is not able to establish whether these suffer a common cause which affects both Vitamin D levels and COVID (even simple geography or SES would matter -- poor people are more likely to be vitamin deficient, and also more likely to work and live in a manner that exposes them to COVID). The included studies in the meta-analysis seem inconsistent about whether they attempt to adjust (in a "selection on observables" sense) for confounders, but only a few even mention confounders. For that reason I am not sure the use of the causal language "impact of... on" in the title is justified. I would consider this a lead that is worth investigating, but haven't really adjusted my very diffuse priors on the basis of this MA.
- AndrewBissell 5y ago
  > Given that a lot of the COVID morbidity and mortality is the cytokine storm rather than the infection itself, I wouldn't consider it a priori clear that Vitamin D helps, is neutral, or harms patients who get COVID. Autocrine vitamin D signaling switches off pro-inflammatory programs of cells: https://www.nature.com/articles/s41590-021-01080-3 https://www.nature.com/articles/s41590-021-01080-3
- tremon 5y ago
  You're identifying the right threat with Covid but you're misrepresenting the role of vitamin D: it is exactly through cytokine regulation that increased Vitamin D concentration is beneficial. See for example this study, from 2014: https://pubmed.ncbi.nlm.nih.gov/25331710/ https://pubmed.ncbi.nlm.nih.gov/25331710/ In conclusion, severe vitamin D deficiency is associated with elevated inflammatory cytokine concentrations in diabetic patients
  - AnthonBerg 5y ago
    Interesting. Thank you. Vitamin D is also correlated with exposure to ultraviolet light, i.e. sunlight. In that case, exposure to sunlight is a direct cause of vitamin D synthesis. Exposure to sunlight causes other things to happen. One of those things is that trans-urocanic acid—a substance synthesized by the body and found on the skin—is converted to the cis isomer, so into cis-urocanic acid, which induces immune suppression by activating serotonin receptor 5-HT2A. Sunlight reduces inflammation through the end result of activating a serotonin receptor! (This is wild!) Source: • Cis-urocanic acid, a sunlight-induced immunosuppressive factor, activates immune suppression via the 5-HT2A receptor, Proceedings of the National Academy of Sciences, 2006 — https://doi.org/10.1073/pnas.0603119103 https://doi.org/10.1073/pnas.0603119103 It's all very interesting. I'm super curious. (As far as I know, the 5-HT2A receptor is unusual among serotonin receptors in that it causes immune suppression; As I understand it, most of the other serotonin receptors cause immune system activation in the context of the immune system. And afaik serotonin receptors are widely purposed in the immune system.) Now. COVID-19 is a disease of inflammation and clotting. As far as I know, plasma serotonin is greatly elevated in COVID illness. Platelets have both serotonin transporters and serotonin receptors – type 5-HT2A. (In platelets, that receptor happens to induce clotting, not immunomodulation.) There is a strong correlation between SSRI use—serotonin reuptake inhibitors—and people faring much better with a COVID-19 infection. Randomized clinical trials have shown this: • Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial – The Lancet, October 17, 2021: https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00448-4/fulltext https://www.thelancet.com/journals/langlo/article/PIIS2214-1... Observational studies have shown a correlation. Here's a recent, large one: • Mortality Risk Among Patients With COVID-19 Prescribed Selective Serotonin Reuptake Inhibitor Antidepressants – Journal of the American Medical Association, November 15 2021: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2786136 https://jamanetwork.com/journals/jamanetworkopen/fullarticle... And there are plausible mechanisms of action: • Fluvoxamine: A Review of Its Mechanism of Action and Its Role in COVID-19 – Frontier in Pharmacology, April 2021: https://www.frontiersin.org/articles/10.3389/fphar.2021.652688/full https://www.frontiersin.org/articles/10.3389/fphar.2021.6526... The following preprint on the proposed mechanism of action is super interesting. It's a preprint but as far as I know the mechanisms have shown to hold true. • COVID-19 Pathophysiology: Are Platelets and Serotonin Hiding in Plain Sight?, preprint dated February 5, 2021: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3800402 https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3800402 Frankly, I'd be willing to bet real money that at least part of the correlation between having little vitamin D and faring poorly with COVID-19 is a reflection of a causative relationship: Little exposure to sunlight causing less than usual 5-HT2A-receptor immunomodulation causing more severe disease. How? Not exactly sure. But the papers try to present the case (and do so much better than a HN rando). I'm thinking receptor up/downregulation might have something to do with it maybe. And what seems to be the role of the 5-HT2A receptor as a negative feedback point in general in the immune system.
f6v 5y ago
> Vitamin D is great for the immune system. > Always good to do the research ofc. But I'm not exactly surprised. How can you say whether it’s good or not without doing the research in the first place?
- deleted 5y ago
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deleted 5y ago
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mcguire 5y ago
If you are vitamin D deficient. If not, taking supplements is a waste of time and may cause other long-term problems.

notafraudster 5y ago

Given that a lot of the COVID morbidity and mortality is the cytokine storm rather than the infection itself, I wouldn't consider it a priori clear that Vitamin D helps, is neutral, or harms patients who get COVID. The result isn't sufficient to answer the question. It establishes, generally, that Vitamin D deficient people are more likely to get COVID. It is not able to establish whether these suffer a common cause which affects both Vitamin D levels and COVID (even simple geography or SES would matter -- poor people are more likely to be vitamin deficient, and also more likely to work and live in a manner that exposes them to COVID). The included studies in the meta-analysis seem inconsistent about whether they attempt to adjust (in a "selection on observables" sense) for confounders, but only a few even mention confounders. For that reason I am not sure the use of the causal language "impact of... on" in the title is justified. I would consider this a lead that is worth investigating, but haven't really adjusted my very diffuse priors on the basis of this MA.

AndrewBissell 5y ago
> Given that a lot of the COVID morbidity and mortality is the cytokine storm rather than the infection itself, I wouldn't consider it a priori clear that Vitamin D helps, is neutral, or harms patients who get COVID. Autocrine vitamin D signaling switches off pro-inflammatory programs of cells: https://www.nature.com/articles/s41590-021-01080-3 https://www.nature.com/articles/s41590-021-01080-3
tremon 5y ago
You're identifying the right threat with Covid but you're misrepresenting the role of vitamin D: it is exactly through cytokine regulation that increased Vitamin D concentration is beneficial. See for example this study, from 2014: https://pubmed.ncbi.nlm.nih.gov/25331710/ https://pubmed.ncbi.nlm.nih.gov/25331710/ In conclusion, severe vitamin D deficiency is associated with elevated inflammatory cytokine concentrations in diabetic patients
- AnthonBerg 5y ago
  Interesting. Thank you. Vitamin D is also correlated with exposure to ultraviolet light, i.e. sunlight. In that case, exposure to sunlight is a direct cause of vitamin D synthesis. Exposure to sunlight causes other things to happen. One of those things is that trans-urocanic acid—a substance synthesized by the body and found on the skin—is converted to the cis isomer, so into cis-urocanic acid, which induces immune suppression by activating serotonin receptor 5-HT2A. Sunlight reduces inflammation through the end result of activating a serotonin receptor! (This is wild!) Source: • Cis-urocanic acid, a sunlight-induced immunosuppressive factor, activates immune suppression via the 5-HT2A receptor, Proceedings of the National Academy of Sciences, 2006 — https://doi.org/10.1073/pnas.0603119103 https://doi.org/10.1073/pnas.0603119103 It's all very interesting. I'm super curious. (As far as I know, the 5-HT2A receptor is unusual among serotonin receptors in that it causes immune suppression; As I understand it, most of the other serotonin receptors cause immune system activation in the context of the immune system. And afaik serotonin receptors are widely purposed in the immune system.) Now. COVID-19 is a disease of inflammation and clotting. As far as I know, plasma serotonin is greatly elevated in COVID illness. Platelets have both serotonin transporters and serotonin receptors – type 5-HT2A. (In platelets, that receptor happens to induce clotting, not immunomodulation.) There is a strong correlation between SSRI use—serotonin reuptake inhibitors—and people faring much better with a COVID-19 infection. Randomized clinical trials have shown this: • Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial – The Lancet, October 17, 2021: https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00448-4/fulltext https://www.thelancet.com/journals/langlo/article/PIIS2214-1... Observational studies have shown a correlation. Here's a recent, large one: • Mortality Risk Among Patients With COVID-19 Prescribed Selective Serotonin Reuptake Inhibitor Antidepressants – Journal of the American Medical Association, November 15 2021: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2786136 https://jamanetwork.com/journals/jamanetworkopen/fullarticle... And there are plausible mechanisms of action: • Fluvoxamine: A Review of Its Mechanism of Action and Its Role in COVID-19 – Frontier in Pharmacology, April 2021: https://www.frontiersin.org/articles/10.3389/fphar.2021.652688/full https://www.frontiersin.org/articles/10.3389/fphar.2021.6526... The following preprint on the proposed mechanism of action is super interesting. It's a preprint but as far as I know the mechanisms have shown to hold true. • COVID-19 Pathophysiology: Are Platelets and Serotonin Hiding in Plain Sight?, preprint dated February 5, 2021: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3800402 https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3800402 Frankly, I'd be willing to bet real money that at least part of the correlation between having little vitamin D and faring poorly with COVID-19 is a reflection of a causative relationship: Little exposure to sunlight causing less than usual 5-HT2A-receptor immunomodulation causing more severe disease. How? Not exactly sure. But the papers try to present the case (and do so much better than a HN rando). I'm thinking receptor up/downregulation might have something to do with it maybe. And what seems to be the role of the 5-HT2A receptor as a negative feedback point in general in the immune system.

f6v 5y ago

> Vitamin D is great for the immune system. > Always good to do the research ofc. But I'm not exactly surprised. How can you say whether it’s good or not without doing the research in the first place?

deleted 5y ago
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deleted 5y ago

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mcguire 5y ago

If you are vitamin D deficient. If not, taking supplements is a waste of time and may cause other long-term problems.