Covid 19: adjuvant approaches etc,

[Arik]

Study of interest:

WEST LAFAYETTE, Ind. — Scientists recently gained insights into how vitamin D functions to reduce inflammation caused by immune cells that might be relevant to the responses during severe COVID-19. In a study jointly published by Purdue University and the National Institutes of Health, scientists do just that.

https://www.purdue.edu/newsroom/rele...lammation.html

Study:

Autocrine vitamin D signaling switches off pro-inflammatory programs of TH1 cells
Nature Immunology (2021)

Abstract

The molecular mechanisms governing orderly shutdown and retraction of CD4+ type 1 helper T (TH1) cell responses remain poorly understood. Here we show that complement triggers contraction of TH1 responses by inducing intrinsic expression of the vitamin D (VitD) receptor and the VitD-activating enzyme CYP27B1, permitting T cells to both activate and respond to VitD. VitD then initiated the transition from pro-inflammatory interferon-γ+ TH1 cells to suppressive interleukin-10+ cells. This process was primed by dynamic changes in the epigenetic landscape of CD4+ T cells, generating super-enhancers and recruiting several transcription factors, notably c-JUN, STAT3 and BACH2, which together with VitD receptor shaped the transcriptional response to VitD. Accordingly, VitD did not induce interleukin-10 expression in cells with dysfunctional BACH2 or STAT3. Bronchoalveolar lavage fluid CD4+ T cells of patients with COVID-19 were TH1-skewed and showed de-repression of genes downregulated by VitD, from either lack of substrate (VitD deficiency) and/or abnormal regulation of this system.

https://www.nature.com/articles/s41590-021-01080-3

So the first link says it's not the Vitamin D supplements

Sent from my moto z4 using Tapatalk

[WillBrink]

So the first link says it's not the Vitamin D supplements

Sent from my moto z4 using Tapatalk

It's a downstream metabolite of D3, and if you read between the lines of their irrational fear of taking high dose D (which data does not support BTW...) for covid, explains that, and abstracts below more so.

Would ingestion of the active metabolite be more effective and or efficient? Very possible, but needs data and far as I know, not avialiable yet, so D3 supps are the current option, and that metabolite may explain some of the anti inflammatory benefits of D3, specfucu to covid.

FYI, It's essential to get adequate Mg for production of active metabolites of D3:

https://brinkzone.com/is-magnesium-t...-to-the-big-d/

[Arik]

I was diagnosed with low vitamin D a few years before COVID. Maybe 2016 - 17 or so. It was like 13ng/mL. Since then I've been talking supplements and they've varied been 500IU to 2000IU. My last blood work in June showed 45.6 ng/mL

Since new year I've been cranking it up to 8-10k IU but I started noticing what I think are side effects so lately I've gone down to 6000IU and will occasionally skip a day. Seems to be working and the side effects are less and less frequent.

I do eat everything with the exception of carbs. Every day meat, (whole) vegetables and (whole) fruits but I've never tested for magnesium

Sent from my moto z4 using Tapatalk

[Disciple]

Since new year I've been cranking it up to 8-10k IU but I started noticing what I think are side effects so lately I've gone down to 6000IU and will occasionally skip a day.

If it is not too private what were those possible side effects?

[Arik]

If it is not too private what were those possible side effects?

I started getting occasional heart palpitations. Which became almost daily which became multiple times per day. Not all the time, not every day but very very often. To the point that if I didn't have one a day I'd notice. Never lasting more than a split second. Happened to look it up and one of the side effects of too much vitamin D is heart palpitations. I stopped taking them for a few weeks just to see and the symptoms decreased to the point of almost going away. I started taking 4k IU then 6k now with just a rare occurrence that's becoming less intense and more rare

Sent from my moto z4 using Tapatalk

[WillBrink]

I started getting occasional heart palpitations. Which became almost daily which became multiple times per day. Not all the time, not every day but very very often. To the point that if I didn't have one a day I'd notice. Never lasting more than a split second. Happened to look it up and one of the side effects of too much vitamin D is heart palpitations. I stopped taking them for a few weeks just to see and the symptoms decreased to the point of almost going away. I started taking 4k IU then 6k now with just a rare occurrence that's becoming less intense and more rare

Sent from my moto z4 using Tapatalk

May be due to increased rec for Mag, so adding in some Mg and getting 25OHD levels checked again would be warranted. I find for most, 5k IU seems to be the dose that gets the optimal levels.

[Arik]

How much would be good without overdoing it? 300mg/day + food? Less?

Sent from my moto z4 using Tapatalk

[WillBrink]

How much would be good without overdoing it? 300mg/day + food? Less?

Sent from my moto z4 using Tapatalk

That's a good number to shoot for.

[WillBrink]

A new paper on vite D and covid of interest:

Nutrients
. 2021 Nov 12;13(11):4047.

Rapid and Effective Vitamin D Supplementation May Present Better Clinical Outcomes in COVID-19 (SARS-CoV-2) Patients by Altering Serum INOS1, IL1B, IFNg, Cathelicidin-LL37, and ICAM1

Abstract
Background: We aimed to establish an acute treatment protocol to increase serum vitamin D, evaluate the effectiveness of vitamin D3 supplementation, and reveal the potential mechanisms in COVID-19.

Methods: We retrospectively analyzed the data of 867 COVID-19 cases. Then, a prospective study was conducted, including 23 healthy individuals and 210 cases. A total of 163 cases had vitamin D supplementation, and 95 were followed for 14 days. Clinical outcomes, routine blood biomarkers, serum levels of vitamin D metabolism, and action mechanism-related parameters were evaluated.

Results: Our treatment protocol increased the serum 25OHD levels significantly to above 30 ng/mL within two weeks. COVID-19 cases (no comorbidities, no vitamin D treatment, 25OHD <30 ng/mL) had 1.9-fold increased risk of having hospitalization longer than 8 days compared with the cases with comorbidities and vitamin D treatment. Having vitamin D treatment decreased the mortality rate by 2.14 times. The correlation analysis of specific serum biomarkers with 25OHD indicated that the vitamin D action in COVID-19 might involve regulation of INOS1, IL1B, IFNg, cathelicidin-LL37, and ICAM1.

Conclusions: Vitamin D treatment shortened hospital stay and decreased mortality in COVID-19 cases, even in the existence of comorbidities. Vitamin D supplementation is effective on various target parameters; therefore, it is essential for COVID-19 treatment.

https://pubmed.ncbi.nlm.nih.gov/34836309/

[WillBrink]

This may be the most important paper published since all this started. It supports my early model in my main article on the topic of adjuvant approaches, and I jave updated that article with this ground breaking paper:

Is Ferroptosis a Key Component of the Process Leading to Multiorgan Damage in COVID-19?

Antioxidants 2021, 10(11), 1677;
Abstract

Even though COVID-19 is mostly well-known for affecting respiratory pathology, it can also result in several extrapulmonary manifestations, leading to multiorgan damage. A recent reported case of SARS-CoV-2 myocarditis with cardiogenic shock showed a signature of myocardial and kidney ferroptosis, a novel, iron-dependent programmed cell death. The term ferroptosis was coined in the last decade to describe the form of cell death induced by the small molecule erastin.

As a specific inducer of ferroptosis, erastin inhibits cystine-glutamate antiporter system Xc-, blocking transportation into the cytoplasm of cystine, a precursor of glutathione (GSH) in exchange with glutamate and the consequent malfunction of GPX4. Ferroptosis is also promoted by intracellular iron overload and by the iron-dependent accumulation of polyunsaturated fatty acids (PUFA)-derived lipid peroxides. Since depletion of GSH, inactivation of GPX4, altered iron metabolism, and upregulation of PUFA peroxidation by reactive oxygen species are peculiar signs of COVID-19, there is the possibility that SARS-CoV-2 may trigger ferroptosis in the cells of multiple organs, thus contributing to multiorgan damage.

Here, we review the molecular mechanisms of ferroptosis and its possible relationship with SARS-CoV-2 infection and multiorgan damage. Finally, we analyze the potential interventions that may combat ferroptosis and, therefore, reduce multiorgan damage.

Full paper: https://www.mdpi.com/2076-3921/10/11/1677/htm