Why focus on Retinoic acid?
Because too much Retinoic acid causes fibrotic damage and can lead to liver, kidney, and brain damage & testing for it or reducing vitamin A in the diet would not be tried currently.
Why focus on what the cause or causes of a problem are?
So that effective solution/s can be discovered and used.
Trying to treat a problem by treating symptoms is like trying to put out a fire while an arsonist is still setting more fires. You might put out a few flames, but the structure will still burn down - or develop fibrotic scarring and regions of cell death.
I like my liver, and my kidneys, and my brain - in fact I like all of my body parts to be functional and pain free. Pain is a signal that something is wrong - please find out what and repair the issue! Just taking pain killers doesn’t put out the smoldering fire, only the obvious flames.
“Liver toxicity of retinoid therapy Vitamin A metabolism involves storage in the liver. Hypervitaminosis A results in liver abnormalities, including fibrosis and cirrhosis. Ito cells are increased and promote fibrogenesis, which results in cirrhosis.” (1)
The effective solution for Retinoid Toxicity in standard literature is to stop use of retinoid medications.
The idea that some people may be over-converting retinoids to active Retinoic acid on an ongoing, long-term basis, as a result of infection or vaccine immune challenge, is new. The theory is not really being studied yet except by a few scientists outside of the mainstream - let alone clinically testing low vitamin A diets for patients with symptoms that might suggest it would help.
As a Registered Dietitian with chronic health concerns with vague symptoms of pain and fatigue I found that there is not much help and too often nocebo type of harm, either there is no problem besides imagining a problem - hypochondria; or the problem is psychosomatic - emotionally caused pain and fatigue. While it is true we can worry ourselves sick, I really felt something had changed and was physically wrong.
I was correct. I had a number of metabolic gene differences that cause chronic nutrient deficiencies which can cause chronic hormone imbalance. It took me a while but I modified my self care strategies with the more specific information about my metabolic issues and I got better.
Sharing how I got better is in the hope that it might help others get real answers instead of ~ You must be a hypochondriac or a psychosomatic person that should go see a talk therapist to complain to instead of me - your esteemed medical professional who is too important for you and your lab results.
It has been estimated that 80% of the diagnostic process in current times is based on lab test results. Unfortunately, lab results are based on ranges of “normal” that are based on the lab result values of people being seen at labs - patients largely rather than a healthy population chosen to be a standard for “healthy lab values”. Current lab values may be based on sick people’s labs - making anyone who is borderline seem “healthy” and “normal”. Also many lab indicators may be suggestive but need to be considered within a larger set of labs and physical or mental symptoms.
Nutrient research or medical research on topics that are to be discredited tend to use inappropriate doses or placebos that will give similar side effects so the experimental product" seems as safe and effective as the non-inert “placebo” or a helpful product seems ineffective or dangerous at the wrong dose. A recent example (2) is being published widely, suggesting that intravenous vitamin C therapy doesn’t help sepsis - maybe not at a third of the dose that has already been shown to be safe and effective for sepsis type issues.
Modern life provides many flame throwers, nature provides many fire extinguishers.
Protocol Collation & Therapy Goals (document)
The problem with Retinoic acid and/or histamine excess is that foods that would normally be thought beneficial are in fact causing harm. Eat more carrots, kale, broccoli, mango! and add to liver or kidney damage from a chronic fatigue syndrome type of issue that is causing more than tiredness and achy muscles.
So figuring out what those healthy but individually harmful foods are for each individual and stopping use of them is the treatment largely - stop being an arsonist in your own body. Moderation can help for some types of issues, but if autoimmune antibodies similar to food proteins is part of an individual issue, then 100% avoidance of that antigen is the ideal.
We tend to recognize that the beer or doughnuts or brownie dessert are not good for us but who would think that trendy probiotics or quinoa (a good betaine source, bad for me individually with a BHMT double gene allele) might be adding to digestive upset or other odd symptoms? Probiotic, fermented foods like yogurt, kombucha, live culture pickles or Kefir, would all increase histamine excess symptoms if that was a problem.
Nutrigenomics could help far more people but the focus of genetic research has been more on changing genes or targeting a gene somehow, rather than identifying individual quirks and educating the individual that maybe the quinoa is causing you digestive upset because you can’t digest it without functional BHMT enzyme. More common would be methylation differences which would identify who really needs the methyl folate and methyl cobalamin (B12) forms and to avoid the fortified folic acid and cyanocobalamin sources. Having a lack of methyl donors increases risk for epigenetic gene problems (like POTS) and would reduce the breakdown of histamine.
Individual counseling helps people sort through their symptoms and daily routine to see where changes might help. It is our daily routine that is our life. Enjoying self care can help us enjoy more quality of life overall. It is an investment in your own fire department and lots of fire extinguishers.
Always track your own symptoms in a daily log when unsure what is going on, or when trying something new. Writing it down is boring but looking back over a few weeks can then show patterns of what you did one day or week, and how it left you feeling over the next few days. It is too easy to forget what you ate or whether you had insomnia unless you really do eat the same thing every single day (which isn’t healthy either - variety!).
Related post: Two favorites - all purpose.
Addition - kidney disease and retinoic acid toxicity involves increase signals for apoptosis of podocytes. Retinoic acid has a protective role in the kidneys in normal function and could have treatment value but the risk of excess needs to be addressed, suggestions for certain enzyme blockers are in the reference. (3)
Retinoic acid has roles in the brain cell growth and function. Deficiency is a negative in the brain also as it can reduce misfolded protein build up. The question is individual - does this specific person have overactivation of Retinoic acid? or a histamine excess problem? or other unknowns causing inflammation such as over expression of TRP channels leading to migraines? The following review article covers the roles of retinoic acid in normal function, in normal or deficient amounts and is considering it as a treatment for Alzheimer’s dementia. (4)
Retinoic acid in the Central Nervous System & amyloid removal.
“Retinoic acid signaling is extremely important in the central nervous system. Impairment of retinoic acid signaling pathways causes severe pathological processes in the central nervous system, especially in the adult brain. Retinoids have major roles in neural patterning, differentiation, axon outgrowth in normal development, and function of the brain.”
“Impaired retinoic acid signaling results in neuroinflammation, oxidative stress, mitochondrial malfunction, and neurodegeneration leading to progressive Alzheimer's disease, which is pathologically characterized by extra-neuronal accumulation of amyloid plaques (aggregated amyloid-beta) and intra-neurofibrillary tangles (hyperphosphorylated tau protein) in the temporal lobe of the brain.”
“Retinoids inhibit expression of chemokines and neuroinflammatory cytokines in microglia and astrocytes, which are activated in Alzheimer's disease. Stimulation of retinoic acid receptors and retinoid X receptors slows down accumulation of amyloids, reduces neurodegeneration, and thereby prevents pathogenesis of Alzheimer's disease in mice.” (4)
First do no harm. Individualized health care means not following a standard protocol that has a hope of helping slightly more than a placebo percentage of people slightly more than a placebo would help. Instead find out the specifics that may make that person one of the ones who won’t be helped, might even be harmed by the proposed standard or experimental treatment.
Disclaimer: This information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.
Roenigk HH Jr. Liver toxicity of retinoid therapy. J Am Acad Dermatol. 1988 Jul;19(1 Pt 2):199-208. doi: 10.1016/s0190-9622(88)70165-6. PMID: 3045164. https://pubmed.ncbi.nlm.nih.gov/3045164/
James Lopilato, Vitamin C and Sepsis: Data Turn Sour, Suggesting Harm
— Surprising results from the LOVIT trial. June 15, 2022, medpagetoday.com, https://www.medpagetoday.com/criticalcare/sepsis/99248
Chen A, Liu Y, Lu Y, Lee K, He JC. Disparate roles of retinoid acid signaling molecules in kidney disease. Am J Physiol Renal Physiol. 2021 May 1;320(5):F683-F692. doi: 10.1152/ajprenal.00045.2021. Epub 2021 Mar 1. PMID: 33645319; PMCID: PMC8174805. https://pubmed.ncbi.nlm.nih.gov/33645319/
Das BC, Dasgupta S, Ray SK. Potential therapeutic roles of retinoids for prevention of neuroinflammation and neurodegeneration in Alzheimer's disease. Neural Regen Res. 2019 Nov;14(11):1880-1892. doi: 10.4103/1673-5374.259604. PMID: 31290437; PMCID: PMC6676868.