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Vitamin A Accutane Toxicity Notes
5 Aug 2018

VITAMIN A and ACCUTANE TOXICITY NOTES

Dr. PAUL S. ANDERSON

METABOLISM – ELIMINATION:  

Vitamin A: Cytochrome p450, and especially CYP3A4 oxidizing excess retinol, Vitamin D intake (a known CYP3A4-inducer), iron intake (CYP3A4 has an iron center), Copper and vitamin C.  Accutane (13-cisRA) cytochrome P450 enzymes (CYPs) including 2C8, 3A7, 4A11, 1B1, 2B6 and 2C9 responsible for the generation of 13-cisRA metabolites including 4-oxo-13-cisRA and is heavily converted via phase-2 glucuronidation.

Vitamin E may alleviate hypervitaminosis A.[1] And also appears to be an effective treatment (rabbits,[2] chickens[3]).

Taurine significantly reduces toxic effects in rats.[4] Retinoids can be conjugated by taurine and other substances. Significant amounts of retinotaurine are excreted in the bile,[5] and this retinol conjugate is thought to be an excretory form, as it has little biological activity.[6] Taurine, zinc, and vitamin E protect cells from retinol-induced injury.[9]

Vitamin K prevents hypoprothrombinemia in rats and can sometimes control the increase in plasma/cell ratios of vitamin A.[8]

LIPIDS:  

Cholestin in Red Rice Yeast significantly reduces toxicity (rats).[7]  Cholesterol prevents retinol-induced Golgi apparatus fragmentation. Consider phospholipid replacement (PTC…)[10]

Protocol Ideas (oral):  Mixed Tocopherols (100-300 IU-QD), Phosphatidylcholine 1-2 grams QD, Taurine 2-3 grams TID before meals, Vitamin K in mcg doses, Vit C 1-3 grams in divided doses per day, ALA 200-400 mg,  and a trace element formula with Mg, Cu, Zn etc (and Fe if anemic). Glutathione support. General B-Vitamin support.

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  1. McCuaig LW, Motzok I (July 1970). “Excessive dietary vitamin E: its alleviation of hypervitaminosis A and lack of toxicity”. Poultry Science 49 (4): 1050–1.doi:10.3382/ps.0491050. PMID 5485475.
  2. St Claire MB, Kennett MJ, Besch-Williford CL (July 2004). “Vitamin A toxicity and vitamin E deficiency in a rabbit colony”. Contemporary Topics in Laboratory Animal Science / American Association for Laboratory Animal Science 43 (4): 26–30.PMID 15264766.
  3.  Weiser H, Probst HP, Bachmann H (September 1992). “Vitamin E prevents side effects of high doses of vitamin A in chicks”. Annals of the New York Academy of Sciences669: 396–8. doi:10.1111/j.1749-6632.1992.tb17134.x. PMID 1444058.
  4. Yeh, Yen-Hung; Lee, Ya-Ting; Hsieh, Hung-Sheng; Hwang, Deng-Fwu (2008). “Effect of taurine on toxicity of vitamin a in rats”. Food Chemistry 106: 260.doi:10.1016/j.foodchem.2007.05.084.
  5. Skare, Kevin L.; Deluca, Hector F. (1983). “Biliary metabolites of all-trans-retinoic acid in the rat”. Archives of Biochemistry and Biophysics 224 (1): 13–8. doi:10.1016/0003-9861(83)90185-6. PMID 6870249.
  6.  Skare, KL; Sietsema, WK; Deluca, HF (1982). “The biological activity of retinotaurine”.The Journal of nutrition 112 (8): 1626–30. PMID 7097369.
  7. Yeh, Yen-Hung; Lee, Ya-Ting; Hsieh, You-Liang (2012). “Effect of cholestin on toxicity of vitamin a in rats”. Food Chemistry 132: 311. doi:10.1016/j.foodchem.2011.10.082.
  8.  Walker SE, Eylenburg E, Moore T (1947). “The action of vitamin K in hypervitaminosis A”. The Biochemical Journal 41 (4): 575–80. PMC 1258540. PMID 16748217.
  9.  Pasantes-Morales H, Wright CE, Gaull GE (December 1984). “Protective effect of taurine, zinc and tocopherol on retinol-induced damage in human lymphoblastoid cells”.The Journal of Nutrition 114 (12): 2256–61. PMID 6502269.
  10.  Sarkanen, Jertta-Riina; Nykky, Jonna; Siikanen, Jutta; Selinummi, Jyrki; Ylikomi, Timo; Jalonen, Tuula O. (2007). “Cholesterol supports the retinoic acid-induced synaptic vesicle formation in differentiating human SH-SY5Y neuroblastoma cells”. Journal of Neurochemistry 102 (6): 1941–52. doi:10.1111/j.1471-4159.2007.04676.x.PMID 17540009.