Follow up - Two.one
Bimodal distribution - 2 cohorts would average into muddied results. If lack of VitA & excess Retinoic Acid cause the same symptoms then bimodal is expected.
The paper “A novel hypothesis for COVID-19 pathogenesis: Retinol depletion and retinoid signaling disorder.” (Sarohan et al, 2021) was very thorough and helpful, great work by the team. I added more excerpts to the last post:
Summary points about the paper -
They note that there have not been many clinical studies regarding vitamin A in Covid19 care comparable to studies on vitamin D.
They make the very important point that low vitamin A also effects vitamin D metabolism (noted in the schizophrenia series).
Their focus is on acute illness and low vitamin A levels are their expectation as a treatment need. They do caution against indiscriminate supplementation of vitamin A, recommending medical supervision.
They make the helpful suggestion that checking vitamin A blood levels prior to vaccinations and providing supplements if low would likely improve efficacy of the vaccine.
*Checking vitamin D and providing it in advance would help prevent autoimmune adverse reactions. **Providing vitamin C in advance and after a vaccination (traditional type or the bioweapon type) would help the body cope with the inflammatory response and be protective against cytokine storm.
They make it clear that vitamin A deficiency is a cause of immune deficiency, and it leads to the NF-kB hyperinflammation loop (but they don’t call it that ;-). Retinoid signaling dysregulation is their term for abnormal retinol and Retinoic Acid levels and the resulting increase in Th17 cells and drop in Treg cells.
What their paper and other papers I have read may be missing, and a possible benefit to not having much clinical trial research done yet, is the possibility of two phases of illness and two cohorts of patients which might have skewed results of a study that provided everyone with vitamin A supplements equally -
Acutely ill patients may have the expected typical response of the infection process leading to more Retinoic acid activation depleting vitamin A levels, leading to deficiency and then leading to the NF-kB inflammation and more Th17 cells instead of Treg cells.
LongCovid patients may have developed the gene change that leads to over-activation of Retinoic acid and may be experiencing Retinoid Toxicity. Others who already had ME/CFS after EBV/mononucleosis might also have the gene change and be at risk for worsening of their symptoms if given vitamin A supplements. LongCovid patients or others who get a CoV infection might benefit from adequate vitamin A during the acute infection but excess supplementation might worsen risk of the virus infecting endothelial cells and add a risk of Retinoid Toxicity symptoms - which coincidentally or causally include kidney and liver damage.
If a study had a mixed group of participants that included enough of the LongCovid ME/CFS type of patient, then a clinical trial that provides vitamin A supplementation would make them worse and that would skew the results of the study. The rest of the patients might have improved on average. I would look for a bimodal distribution in patient outcomes - or do a genetic or other screening first before providing vitamin A supplements to people who might get worse from excess.
I did eat carrots, kale, and sweet potatoes when I was sick with CoV. It was later after I had been recovered for months when I developed worsening Retinoid Toxicity symptoms. I had increased my usual carrot and kale intake even more with mango season. I had mononucleosis and then undiagnosed Chronic Fatigue Syndrome type symptoms off and on ever since.
Genetic differences in the endocannabinoid system may also be a factor in people with worse LongCovid or ME/CFS. *Addition - autoimmune antibodies against phospholipids has been seen in some LongCovid patients. So they might develop a need for an external source of cannabinoids in balance, not just CBD. Too much CBD alone or too much THC alone can have negative effects as they are needed in balance and are signalling chemicals.
I had a comment that my work is helpful, and thanks, very welcome, but it is hard to know what to do, especially with brain fog symptoms and ME/CFS.
What worked for me has happened in stages and took years, slow and gradual steady progress is the goal. The body has to clean up what it can as long as it takes. Prevention is nicer because you start out feeling okay.
At this point, I do suspect that reducing vitamin A would help (*ME/CFS & check if the list of Retinoid Toxicity symptoms sounds similar) and strictly reducing it is needed in order to help enough in my personal experience. One quarter of a peach left me feeling sicker for two days.
Three posts on Peaches: 1. (brief intro) 2. (My day didn’t get better) 3. (My “everything” hurt - nociceptive pain evaluation) . It felt like fibromyalgia, another diagnosis that I didn’t get. I could tell some of the foods that made me worse, so I didn’t get worse enough to meet insurance criteria for a diagnosis. Which makes me wonder if fibromyalgia is also Retinoid Toxicity by another name.
Therefore restricting vitamin A rich foods a lot, may mean giving up vitamin A fortified dairy products or fortified dairy equivalents, or meal bars, one-a-day supplements, and liver and meats, and tomatoes, carrots, kale, sweet potatoes, cantaloupe, watermelon, peaches, mangos, apricots, and other deep green veggies or orange or red fruits and vegetables.
Histamine excess is part of Retinoid Toxicity so restricting histamine containing foods or trigger foods is also a need. That gets into some long lists also. Anything fermented, aged, simply older leftovers, canned goods, may contain more histamine from the food being more pre-digested, metabolized partially from the fermentation or aging. This includes alcohol, kombucha, soy sauce, Worcestershire sauce, olives, pickles, yogurt, Kefir, cheese. Mold is a problem and that can make peanut butter a problem. Citrus fruit can be a histamine trigger food within the gut. Avoiding all of those strictly - totally may be needed to start feeling better.
Seriously, not just smaller portions, stop using them as ingredients or main dishes, or at all. Keeping a food and symptom diary for a while can help to see patterns because the pain happens the next day after a big vitamin A intake.
I have handouts that I can try to simplify, but in the meantime, they are available as is:
Histamine foods - downloadable pdf.
Alkalizing foods are beneficial for reducing inflammation, this handout includes sections on other food categories that can be inflammatory or cause other GI symptoms. - downloadable pdf.
The high dose niacin protocol also seems to be very important for my health. I started it around the time that I learned about Retinoid Toxicity and cut down on carotenoid intake, so I made both changes at once - harder to know if one would have worked as well without doing the other change also.
This morning I was concentrating on the previous post and forgot to drink my niacin powder/water. This afternoon I had the sad/bad mood of serotonin deficiency. I had been sticking with niacin after breakfast, lunch and dinner and had been steadier of mood. It seems really important and helps with clearer thinking as well as not being sad and moody - thinking more negatively about everything. The high dose niacin also makes me feel more energetic and helps clear congestion.
Longer ago I took high dose iodine which I think was a need to reduce my fibromyalgia symptoms even more and restore thyroid function and my energy level.
CoV wise - forgetting my pomegranate peel tea led to worsening of some of my endothelial symptoms - see this post, which was Round one - the first in this mini series.
The Retinol paper is very thorough and reminded us of why SARS-CoV-2 like endothelial cells - they have a lot of ACE2 and TMPRSS2 receptors which spike can enter a cell at. Pomegranate peel helps protect/block access to the ACE2 receptors. It helps fight CoV in many ways. It also prevents the fusion cleavage site from opening which would prevent the S1 subunit from being able to freely enter nAChR receptors or expose the prion like sections within the cleavage site.
Bonus - it is now pomegranate season in the Northern Hemisphere again! The outer peel can air dry readily if the white layer is removed and it isn’t too humid. I use the inner pith fresh or frozen or dehydrated with an air/warmth dehydrating unit. If it discolors too much during drying the medicinal benefit seems to be gone too. Overheating an extract/tea also will destroy the medicinal benefits.
Addition - FAS, ADHD, vaccine injured, and drug injured/akathisia patients may also have had a liver gene change leading to overactivating Retinoic Acid, but that is part of my theory or in a reference I will have to add later. I wanted to add the point that an unknown number of people may be not well because of their food and just changing the food can make a huge difference - normalize function, but not a cure to the underlying gene change, no peaches for me. Because the symptoms are that bad, not worth it.
Disclaimer: This information is being shared within the guidelines of Fair Use for educational purposes and is not intended to provide individual health care guidance. Please seek a functional health care practitioner for individualized health guidance.
(Sarohan et al, 2021) Sarohan AR, Kizil M, Inkaya AC, et al., (2021). A novel hypothesis for COVID-19 pathogenesis: Retinol depletion and retinoid signaling disorder. Cellular Signalling 87 (2021) https://www.sciencedirect.com/science/article/pii/S0898656821002102?via%3Dihub
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