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Retinyl esters, the blood test that can show Poison/"Vitamin A" toxicity even when total blood levels of A are LOW

In addition to serum retinol, there is now the fraction/percent of retinyl esters that can potentially indicate Poison/”Vitamin A” toxicity…even when total serum retinol is LOW.  This can answer so many of the questions about diseases that “seem” to be low in blood levels of Poison/”Vitamin A”, yet respond very positively to a low-to-no Vitamin A diet.  Now I will have to work on finding out what can help keep this ratio/percent lower…

Toward a Theory of Childhood Learning Disorders, Hyperactivity, and Aggression

Vitamin A toxicity is generally associated with increased levels of retinyl esters (the storage form of the vitamin) circulating with plasma lipoproteins unbound to retinol-binding protein (RBP). Retinyl esters react more randomly with cell membranes than the physiologically sequestered RBP and hence are a major form of vitamin A toxicity. Fasting retinyl ester concentrations >10% of total circulating vitamin A (retinol plus esters) are considered a biomarker for toxicity [146, 147].
However, retinol concentrations can be low as a result of liver damage and impaired hepatic mobilization of the vitamin, whereas other retinoid compounds, which are seldom measured, may be found in high concentration due to spillage from the damaged liver. As noted, retinoid toxicity can occur when circulating retinyl esters, unbound to protein, exceed the carrying capacity of RBP, and an accepted indicator of toxicity is percent retinyl esters >10% [147]. On the present theory, while smoking in pregnancy is associated with reduced retinol concentrations due to liver damage, normally stored but potentially toxic retinyl esters and retinoic acids are spilled into the circulation in bile, causing growth restriction and well as later-appearing neurocognitive deficits, hyperactivity, and aggression. Support for this concept comes from a study of retinoid profiles in patients with cirrhosis [170]. Serum retinol concentration was low, but the percentage of serum retinyl esters as a fraction of total vitamin (retinol plus esters) was 20%, double that of the accepted indicator of vitamin A toxicity (>10%).
Liver damage, indicated by elevated liver enzymes, was accompanied by a significantly lower median plasma retinol (ROL) concentration, consistent with earlier studies. However, it was noted for the first time that the retinyl ester-to-ROL ratio, the percentage of retinyl ester to total vitamin A (median, 24% versus 11%; ), and the concentration of RA in the experimental animals were all significantly higher compared to those of the controls.
A central hypothesis of this paper is that the “fetal origins of disease” [181, 182] are importantly related to maternal liver dysfunction in pregnancy. On this hypothesis, liver damage-induced alterations in retinoid metabolism and exposure serve to “program” the fetus to develop later-onset conditions and diseases, depending on the timing and duration of exposure and on the concentration of circulating retinoid compounds (retinyl esters and retinoic acids). The resulting spectrum of adverse birth outcomes could range from stillbirth and birth defects to preterm birth and fetal growth restriction and their sequelae.
Hence, it is possible that SIB [self-injurious behavior] associated with the genetic defect in HPRT could be due to the accumulation RA or associated toxic vitamin A compounds in brain such as retinyl esters, as well as uric acid. If the retinoid toxicity hypothesis is correct, the ratio of serum retinoic acid to retinol and percent retinyl esters as a fraction of total vitamin A should be significantly higher in patients with LNS [Lesch-Nyhan Syndrome] than in controls.

More on the actual laboratory process of determining retinyl esters (the technology to do this has apparently been around since 1978!):

Retinyl ester (vitamin A ester) and carotenoid composition in human liver.

Surgical liver biopsy samples from seven diseased and five healthy human subjects, 3-33 years of age, were analyzed by reversed-phase high-pressure liquid chromatography for retinol (vitamin A alcohol), retinyl esters (vitamin A esters), and carotenoids. Total liver vitamin A values ranged from 7.8 to 2860 nmol/g liver (2.2 to 817 micrograms/g). As a percentage, liver retinol decreased with increasing liver reserves of vitamin A. Retinyl palmitate was the predominant vitamin A ester (57 to 83 mole%) in all samples, with retinyl stearate (5.5 to 11.4%), oleate (4.9 to 17.2%), and myristate plus palmitoleate (pair not resolved; 3.3 to 11.9%) next most common. Lesser amounts of retinyl linoleate, linolenate, and arachidonate were found. Normal livers had significant amounts of several carotenoids: lutein (0.2 to 16.2 nmol/g), lycopene (10.2 to 55.1 nmol/g), alpha-carotene (3.0 to 7.3 nmol/g), and beta carotene (5.8 to 25 nmol/g). Total carotenoid values ranged from 26.5 to 67 nmol/g in normal liver samples. There was no correlation between liver vitamin A and individual or total carotenoids in normal livers.

Determination of Retinyl Esters and Retinol in Serum or Plasma by Normal-Phase Liquid Chromatography: Method and Applications (also attached)

Simultaneous Determination of Retinol and Retinyl Esters in Serum or Plasma by Reversed-Phase High-Performance Liquid Chromatography (also attached)

CDC Laboratory Procedure Manual (retinyl esters testing discussed within, also attached)

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