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"Vitamin" A(as a hormone) directly upregulates ACE2 expression, leading to increased risks of SARS-CoV2 infection on initial exposure
Vitamin A in resistance to and recovery from infection: relevance to SARS-CoV2
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884725/
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The VA metabolite all-trans retinoic acid has also been shown to up-regulate the expression of ACE2(37,38), resulting in the reduction of blood pressure and the attenuation of myocardial damage in spontaneously hypertensive rats(37). Increased levels of ACE2 after VA supplementation could have two effects: 1) it could increase the risk of SARS-CoV2 infection at the time of virus exposure(39), particularly in individuals who have an adequate VA status; or 2) it could reduce the risk of sympathetic over-activation seen in severe SARS-CoV2 infection, obese and diabetic patients(40–42) through VA supplementation that activates the ACE2-Ang 1–7-Mas axis.
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In addition, earlier VA supplementation may have unpredictable effects for the following reasons: First, it is plausible that VA supplementation at the time of SARS-CoV2 exposure would increase the risk or severity of an infection since the cellular infection mechanism of SARS-CoV2 is mainly mediated by ACE2 which can be up-regulated by retinoic acid, as discussed above. Second, however, activation of ACE2 in infected patients could reduce the risk of sympathetic over-activation seen in severe SARS-CoV2 infection, and in particular in obese and diabetic COVID-19 patients.
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Hi @rockarolla,
Thanks for posting that info.
There’s been a lot of news lately about the beneficial role and effectiveness in the use of Ivermectin in treating COVID-19.
Knowing that there’s this connection between COVID and the ACE2 receptor activation or proliferation via retinoic acid, then there might be some related mechanism explaining Ivermectin’s benefit.
Important metabolism enzymes for retinol / RA are the cytochrome P450 enzymes, most notably CYP3A4.
There this study:
Identification of cytochrome P4503A4 as the major enzyme responsible for the metabolism of ivermectin by human liver microsomes
https://pubmed.ncbi.nlm.nih.gov/9574819/
Could it be that ivermectin is ramping up the liver’s production of CYP3A4, and the beneficial side-effect of that is also the increased catabolism of retinol and retinoic acid? And, that in turn down-regulates the ACE2 receptors.
Thoughts?
My first thought is : can this help with the unpleasantness of detox? If I take a look at the side effects of Ivermectin, they seem to fit exactly the side effects of the low vA diet. Not very surprising. Maybe they are less frequent or less violent? As for a scientific debate, I am afraid I am not qualified. Also these days I feel I am sliding into pain, depression, stupidity, blindness. Not a good time to bring out new ideas, even though I still hope this will end up alright.
I just realized that the Thai grapefruit I had been eating for breakfast (not since going low A) had been messing up the P4503A4 really bad.
Whinge whinge. This is the price for moving your post back to the first line, sorry.
Yes, it could help I guess, and as an immunomodulator too, but there are antibiotics with even better safety profile like azithromycin that appears to be as anti COVID as ivermectin, maybe even better - who knows. Currently all hype is spinning around ivermectin and this is mildly annoying.
Macrolides May Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Entry into Cells: A Quantitative Structure Activity Relationship Study and Experimental Validation
https://pubs.acs.org/doi/10.1021/acs.jcim.0c01394
The global pandemic caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is threatening the health and economic systems worldwide. Despite the enormous efforts of scientists and clinicians around the world, there is still no drug or vaccine available worldwide for the treatment and prevention of the infection. A rapid strategy for the identification of new treatments is based on repurposing existing clinically approved drugs that show antiviral activity against SARS-CoV-2 infection. In this study, after developing a quantitative structure activity relationship analysis based on molecular topology, several macrolide antibiotics are identified as promising SARS-CoV-2 spike protein inhibitors. To confirm the in silico results, the best candidates were tested against two human coronaviruses (i.e., 229E-GFP and SARS-CoV-2) in cell culture. Time-of-addition experiments and a surrogate model of viral cell entry were used to identify the steps in the virus life cycle inhibited by the compounds. Infection experiments demonstrated that azithromycin, clarithromycin, and lexithromycin reduce the intracellular accumulation of viral RNA and virus spread as well as prevent virus-induced cell death, by inhibiting the SARS-CoV-2 entry into cells. Even though the three macrolide antibiotics display a narrow antiviral activity window against SARS-CoV-2, it may be of interest to further investigate their effect on the viral spike protein and their potential in combination therapies for the coronavirus disease 19 early stage of infection.
[..]
This outcome is not totally unexpected as azithromycin and clarithromycin have been shown to effectively interfere with cellular endocytosis(26,27) and with influenza virus infection.(13) Clarithromycin(28) and azithromycin were found to be active at lower doses against HCV infection in cell culture (screen in ref.(29)). Thus, these compounds are not specific antivirals against SARS-CoV-2 infection. The efficacy of clarithromycin as an antiviral drug has also been tested in nonhuman primates challenged with influenza viruses of different pathogenicity.(30)
...
Also lactoferrin could be helpful:
Liposomal Lactoferrin as Potential Preventative and Cure for COVID-19:
https://www.fulltxt.org/article/1060
A prospective observational study was performed in 75 patients with typical symptoms of COVID-19 who tested positive to IgM/IgG rapid test. Patients were isolated and treated at home using remote systems, reviewed twice a day for 10 days, and followed up to 1 month. A liposomal bovine lactoferrin (LLF) nutritional syrup food supplement (32 mg of LF/10 ml plus 12 mg of vitamin C) was administered orally in 4 to 6 doses per day for 10 days. In addition, a zinc solution was administered at the dose of 10 mg/10 ml twice or three times a day. A control group of 12 patients who took only LLF was included. All family members in contact with patients (256 persons) were also treated with half of this dose. The treatment allowed a complete and fast recovery in all patients (100%) within the first 4-5 days. Same treatment at lower dose prevented the disease in healthy persons directly related with the affected patients. Weakness (95%) followed by a dysfunction in the perception of smelling and tasting (88%), cough (83%), muscular pain (67%) were the most frequent complains. LF possess antiviral, immunomodulatory and anti-inflammatory effects which might be important for the treatment of COVID-19 infection. We conclude that LLF potentially prevent and cure COVID 19 infection.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271924/
In COVID-19 infection, Lactoferrin may have a role to play in not only sequestering iron and inflammatory molecules that are severely increased during the cytokine burst, but also possibly in assisting in occupying receptors and HSPGs to prevent virus binding. Receptor occupancy is an important characteristic of Lactoferrin, when taken as supplement. Furthermore, it may assist in preventing thrombocytopenia, and hypercoagulation, both prominent features of COVID-19 infection.
Possible action of (1) lactoferrin by occupying binding sites of (2) SARS-CoV-2 that causes COVID-19. (3) Entry into host cells occur when SARS-CoV-2 first attaches to Heparan sulfate proteoglycans (HSPGs). This attachment initiates the first contact between the cell and the virus, concentrating the virus on the cell surface, (4) followed attaching of the virus to the host receptor (ACE2) and association and entering are then facilitated via clathrin-coated pits (5) Virus replication can then happen inside the cell. (6) One of the characteristics of Lactoferrin, is that it attaches to HSPGs. (7) Currently we do not know if ACE2 is also a receptor for lactoferrin. (8) Lactoferrin may block the entry of SARS-CoV-2 into the host cell, by occupying HPSGs, thereby preventing SARS-CoV-2 initial attachment and accumulation on the host cell membrane.
Lactoferrin can enhance antiviral immune response to COVID-19 infection, according to a newly published study in
cells.
Lactoferrin (LF) is a protein found naturally in milk from humans and cows as well as other bodily fluids, which has
shown potential in fighting viral and bacterial infections and to exert anti-inflammatory and immune-modulating
activity (1,2).
The LF antiviral effect occurs by preventing the entry of viral particles into the host cells, either by directly binding to
the viral particles or blocking the virus receptor or co-receptor present on the host cell. LF is able to prevent the
internalization of some viruses, such as SARS pseudovirus, by binding to cell-surface HSPGs, which have been
shown to act as a necessary co-factors for SARS-CoV-2. Moreover, LF was shown to inhibit the entry of murine
coronavirus, as well as human coronaviruses hCoV-NL63.
LF has been reported to selectively inhibit cathepsin L, a lysosomal peptidase critical for endocytosis, which is a cell
entry pathway used by SARS-CoV-2 and has previously been noted as a potential supplement to prevent infection
as well as an adjunct treatment for those who have developed COVID-19.
This article puts ivermctin on par with the discovery of aspririn and antibiotics. who knew.
I suppose that should both encourage and discourage us, as aspirin and antibiotics are dual-edged swords, LOL.
Quote from Ourania on May 30, 2021, 6:00 amMy first thought is : can this help with the unpleasantness of detox? If I take a look at the side effects of Ivermectin, they seem to fit exactly the side effects of the low vA diet. Not very surprising. Maybe they are less frequent or less violent? As for a scientific debate, I am afraid I am not qualified. Also these days I feel I am sliding into pain, depression, stupidity, blindness. Not a good time to bring out new ideas, even though I still hope this will end up alright.
@ourania I've been very low and detoxing hard too. Hopefully darkness before the dawn!
Since on our side we have changed nothing in our diet, and we both are detoxing hard, as well as you... Could this be linked to this huge full moon we had?
Hugs and good luck!
https://player.vimeo.com/video/557891970
CENSORED: Ivermectin Drastically Reduces COVID deaths in India and Africa
Quote from Ourania on May 30, 2021, 6:00 amMy first thought is : can this help with the unpleasantness of detox? If I take a look at the side effects of Ivermectin, they seem to fit exactly the side effects of the low vA diet. Not very surprising. Maybe they are less frequent or less violent? As for a scientific debate, I am afraid I am not qualified. Also these days I feel I am sliding into pain, depression, stupidity, blindness. Not a good time to bring out new ideas, even though I still hope this will end up alright.
I just realized that the Thai grapefruit I had been eating for breakfast (not since going low A) had been messing up the P4503A4 really bad.
Whinge whinge. This is the price for moving your post back to the first line, sorry.
Have you had any serum retinol tests? Also, what other diagnostics?
No serum retinol test. Diagnosed over and over again: nothing wrong with you.