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A theory on enhancing Vitamin A excretion by enhancing glucuronidation
How Vitamin A is eliminated:
Retinol is conjugated with glucuronic acid; the β-glucuronide undergoes enterohepatic circulation and oxidation to retinal and retinoic acid. Retinoic acid undergoes decarboxylation and further conjugation with glucuronic acid.
Hypothesis:
It seems the availability of glucuronic acid in the body is pivitol for the elimination of multiple substances including Vitamin A, xenobiotics, and other toxic substances. Perhaps this is a rate limiting factor to Vitamin A detox considering the body can only produce a limited quantity, and with the onslaught of environmental stressors it is speculated in research that availability of glucuronic acid could be scarce in certain scenarios.
“Retinyl beta-glucuronide is a natural human metabolite of retinoic acid generated in the liver by UDP glucuonyltransferase. Glucuronidation is used to assist in the excretion of toxic substances, drugs or other substances that cannot be used as an energy source. Glucuronic acid is attached via a glycosidic bond to the substance, and the resulting glucuronide, which has a much higher water solubility than the original substance, is eventually excreted by the kidneys.” https://pubchem.ncbi.nlm.nih.gov/compound/Retinyl-beta-glucuronide”
“D-Glucurono-γ-lactone (DGL) that regulates the formation of glucuronic acid has been offered as a glucuronic acid source as well. The fact that the two compounds, DGL and glucuronic acid, are physiologically interchangeable opens a new perspective - a number of studies have revealed that even at high dosages the compound is relatively safe. DGL can be found in minimal amounts naturally, with wine being the richest source with 20 mg/l. The DGL is safe at supplemental dosages (e.g. 500-3000 mg/day) and is short-lived in the humans; it is quickly absorbed via oral administration, metabolized and excreted in the urine. DGL hepatoprotective and detoxifying properties are reported.”
Purchasing isolated glucuronic acid seems very hard to get unless you are ordering from a lab. It is available in Kombucha in large amounts. However, there is a supplement you can buy online. Glucuronolactone converts to glucuronic acid in the body. This conversion occurs back and forth; there are equal amounts of each molecule in the body [2]. Upon glucuronolactone ingestion, glucuronic acid levels (in both blood and urine) will rapidly increase [4].
Another product of glucuronolactone breakdown is called D-glucaro-1,4-lactone. About 25% of glucuronolactone is quickly converted to it. This compound is a potent inhibitor of beta-glucuronidase, an enzyme dominantly produced by your gut bacteria. (This is theoretically a good thing for Vitamin A excretion).
Glucuronolactone is commonly used in energy drinks (not as common anymore). What is absolutely mind blowing is how little information is available online regarding this substance. Additionally, Reddit hardly fails me, but there are not many personal anecdotes from people other than the fact that energy drinks with glucuronolactone provide them with a better experience than those that don’t have it. I was also surprised to see this hasn’t really been discussed in the forum.
Has anyone tried glucuronolactone? Did I miss something in my logical progression that makes this idea seem unreasonable? Tonight, I drank a large amount of Kombucha that had over 2,000mg glucuronic acid. It could be an absolute placebo, but I do feel that it gave me energy and a better mood (although this could have been the small amount of caffeine).
Looking forward to hearing other’s thoughts and ideas.
There is a nice amount in an apple. ‘An apple a day keeps the doctor away’ 🍏
I looked into this a while back. I think it’s important to include plenty of foods containing glucuronic acid. One of the reasons I don’t do a very limited diet.
There are many bottlenecks in the process of removing vA from the body. I suspect that different ones are more/less of a problem for different people. Too much glyphosate exposure, for example, traps retinoic acid in its most damaging form. The one I’ve been focused on recently is bile flow into the gut. This is stage 3 liver detoxification and if it’s not flowing well into the gut then it can recycle in the blood (‘leaky’ liver or cholestasis to call it it’s proper name). Excess vA seems to cause cholestasis. Other things cause this too and can predispose people to vA toxicity I believe (chicken or egg). Garrett Smith has a ‘love your liver’ programme. However, I not agreeing with the way it’s going at the moment. I’m in favour of a holistic style approach. Low vA and other toxin lifestyle, lower stress, sunshine, moderate exercise, sleep, laughter etc.
I also read somewhere that oleic acid (olive oil) enhances it, but now I can't find the source.
I ordered some glucoronolactone and will see how that goes. Pretty cheap
It's probably insignificant, but kombucha should contain carotenoids from the tea. A cause for concern?
Is there a source for the claim that apples contain glucuronic acid? I was unable to confirm.
@jeremy Stephanie Seneff has written a lot about glyphosate causing vitamin A toxicity by blocking/slowing the CYP enzymes (I think it’s CYP26) that breaks down retinoic acid to it’s less toxic forms. Just google seneff & retinoic acid and you get her papers and an interview. She used to talk about this a lot. Now she doesn’t.
https://www.sciencedirect.com/science/article/abs/pii/0271531796000450
I saw this quote on the Weston A Price site, so take it with a grain of salt, but if it is right eating a high protein diet could deplete vitamin A faster:
"...mainstream men’s health writers are advocating diets very high in protein, which deplete vitamin A reserves..."
Was the quote from an article by Chris Masterjohn? If so, we could pay him to explain what he means, although he is not a fan of Grant or Dr Smith, especially the latter.