Prolactinia

On poison/”vitamin” A excretion [1]EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA). “Scientific opinion on dietary reference values for vitamin A.” EFSA Journal 13.3 (2015): 4028. https://doi.org/10.2903/j.efsa.2015.4028:

The majority of retinol metabolites are excreted in the urine, but they are also excreted in faeces and breath. The percentage of a radioactive dose of 14C‐labelled retinyl acetate recovered in breath, faeces and urine ranged from 18 to 30 %, from 18 to 37 % and from 38 to 60 %, respectively, after 400 days on a vitamin A-deficient diet (Sauberlich et al., 1974 [2]Sauberlich, H. E., et al. “Vitamin A metabolism and requirements in the human studied with the use of labeled retinol.” Vitamins & Hormones 32 (1975): 251-275. https://doi.org/10.1016/S0083-6729(08)60015-1). Retinol is metabolised in the liver to numerous products, some of which are conjugated with glucuronic acid or taurine for excretion in bile (Zile et al., 1982; Skare and DeLuca, 1983), and the amount of retinol metabolites excreted in bile increases as the liver retinol exceeds a critical concentration. Excretion of labelled retinol metabolites in bile of rats fed increasing amounts of retinol traced by [3H]-retinyl acetate was constant when hepatic retinol concentrations were low (≤ 32 μg/g (112 nmol/g) and increased rapidly (by eight-fold) as liver retinol concentration increased, up to a plateau at hepatic retinol concentration ≥ 140 μg/g (490 nmol/g) (Hicks et al., 1984 [3]Hicks, Veronica A., Desiree B. Gunning, and James Allen Olson. “Metabolism, plasma transport and biliary excretion of radioactive vitamin A and its metabolites as a function of liver reserves of vitamin A in the rat.” The Journal of nutrition 114.7 (1984): 1327-1333. https://doi.org/10.1093/jn/114.7.1327). This increased biliary excretion may serve as a protective mechanism for reducing the risk of excess storage of vitamin A.

We have the following graph from Hicks and friends:

So, in rats, it plateaued at ~2.5 mcg retinol equivalents/mL bile. The graph gives an impression that it is undesirable to have more than about 30 mcg retinol/g liver, but 200 mcg retinol/g liver is a common concentration in humans [4]Smith, Barbara M., and Eileen M. Malthus. “Vitamin A content of human liver from autopsies in New Zealand.” British Journal of Nutrition 16.1 (1962): 213-218. https://doi.org/10.1079/BJN19620022[5]Saha, N., et al. “Vitamin A reserve of liver in health and coronary heart disease among ethnic groups in Singapore.” British journal of nutrition 60.3 (1988): 407-412. https://doi.org/10.1079/bjn19880112 and a reasonable content range is 30-200 mcg retinol/g liver [6]Tanumihardjo, Sherry A. “Biological evidence to define a vitamin A deficiency cutoff using total liver vitamin A reserves.” Experimental Biology and Medicine 246.9 (2021): 1045-1053. https://doi.org/10.1177%2F1535370221992731, likely applying to humans as well.

There can be wide variations in bile flow between persons, for simplification, we can assume 600 mL/d [7]Esteller, Alejandro. “Physiology of bile secretion.” World journal of gastroenterology: WJG 14.37 (2008): 5641. http://dx.doi.org/10.3748/wjg.14.5641. It’s mostly water, not to be confused with the bile acids/salts in it [8]Boyer, James L. “Bile formation and secretion.” Comprehensive physiology 3.3 (2013): 1035. http://dx.doi.org/10.1002/cphy.c120027. If the saturation level of retinoids in bile can be extrapolated from rats to humans, we could discharge about 1,500 mcg of retinol equivalents in a day. Yet, poisons may be recovered from the intestine similarly to bile acids. We can count on a partial recirculation, although it’s supposed to decrease when the body is overloaded with retinoids. Some of these modified metabolites can be just as potent in activity as the native forms, but not necessarily [9]Barua, Arun B., and Neil Sidell. “Retinoyl β-glucuronide: a biologically active interesting retinoid.” The Journal of nutrition 134.1 (2004): 286S-289S. https://doi.org/10.1093/jn/134.1.286S:

[..]the rate of formation of RA from RAG was also dependant on the vitamin A status of the host. To this end, it was subsequently shown in human studies that when RAG was given orally to healthy adult American males, with apparently normal vitamin A status, neither RAG nor RA could be detected in the plasma of these volunteers (Reida, A., Barua, A. B. & Olson, J. A., unpublished observations). Taken together, these animal and human studies suggested that there was no appreciable intestinal absorption of orally dosed RAG to go into circulation in the blood when the vitamin A status is normal.

Retinoyl is for retinoic acid/retinoate, to a certain degree, the same can occur to retinol as retinyl glucuronide.

Rats are better metabolizers of retinoids and there are differences such as their bile being rich in taurine that might put them in advantage for excretion, conjugation with taurine makes metabolites more inert than when with glucuronic acid.

We don’t know about Diokine, but recycling of bile acids occurs in the following pattern in humans [10]Peters, A. Michael, and Julian RF Walters. “Recycling rate of bile acids in the enterohepatic recirculation as a major determinant of whole body 75SeHCAT retention.” European journal of nuclear medicine and molecular imaging 40.10 (2013): 1618-1621. https://doi.org/10.1007/s00259-013-2466-z:

I found in a textbook a claim that 30% of intestinal retinoids are usually recovered, I’m going by it until there’s something more concrete. It suggests that the loss of poisons and bile acids isn’t proportional. When we discount this fraction, we’re left with about 1,000 mcg of retinol equivalents per day, which is way higher than what’s usually detected in faeces, example [11]Ahmed, F., et al. “Excessive faecal losses of vitamin A (retinol) in cystic fibrosis.” Archives of Disease in Childhood 65.6 (1990): 589-593. http://dx.doi.org/10.1136/adc.65.6.589:

To explain why the toxin isn’t accumulating to an extreme degree, there are the oxidized metabolites (usually more water-soluble) that were not accounted for and it remains possible that a large portion of retinoids continues to be eliminated through the alternative routes, as pointed out in the first quote. Acute infectious episodes can result in marked urinary losses of poisons [12]Mitra, Amal K., and Jose O. Alvarez. “Increased urinary retinol loss in children with severe infections.” The Lancet 351.9108 (1998): 1033-1034. https://doi.org/10.1016/S0140-6736(05)79000-0, but normal regulatory processes tend to be disrupted. In typical conditions, if the level of retinoids in bile inevitably saturates after a given liver reserve, to enhance excretion, the body also has to option to increase the rate of activities in compensation.