by hereme888 | 2025-10-25 01:00:16+00:00
From OpenEvidence.com:

"After ingestion, bismuth is primarily found in trace amounts within organs such as the kidney, liver, spleen, and, in rare cases, the brain, where it accumulates intracellularly—especially in lysosomes and nuclear membranes—and extracellularly in basement membranes of blood vessels.[1-4] In normal therapeutic use, the amount of tissue-bound bismuth is extremely low and is not associated with adverse effects. Potential consequences of tissue-bound bismuth are generally negligible at standard doses, but chronic or excessive exposure can lead to toxicity, most notably neurotoxicity (bismuth encephalopathy).[1][4-6] In cases of bismuth intoxication, histochemical studies have shown accumulation in neurons and glial cells, particularly in the cerebellum, thalamus, and hippocampus, with clinical manifestations including confusion, myoclonus, and encephalopathy.[1][4-6] However, these effects are reversible upon discontinuation of bismuth exposure, and recovery is typically complete within weeks.[5-6] Animal studies confirm that bismuth binds to proteins such as ferritin and metallothionein, and is retained in lysosomes, nuclear membranes, and myelin-associated proteins.[2][4][7] The kidney is the primary site of accumulation and excretion, and tissue levels decline after cessation of exposure, with little evidence of permanent retention at therapeutic doses.[2-3] In summary, permanent tissue binding of bismuth is minimal and clinically insignificant with standard use, but chronic high-dose exposure can result in neurotoxicity and other organ effects, which are reversible after stopping bismuth.[5-6][8-9]"

1. Autometallographic Tracing of Bismuth in Human Brain Autopsies. Stoltenberg M, Hogenhuis JA, Hauw JJ, Danscher G.

Journal of Neuropathology and Experimental Neurology. 2001;60(7):705-10. doi:10.1093/jnen/60.7.705.

2. Metallobiochemistry of Ultratrace Levels of Bismuth in the Rat II. Interaction of Bi With Tissue, Intracellular and Molecular Components. Sabbioni E, Groppi F, Di Gioacchino M, Petrarca C, Manenti S.

Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS). 2021;68:126752. doi:10.1016/j.jtemb.2021.126752.

3. Distribution of Bismuth in the Rat After Oral Dosing With Ranitidine Bismuth Citrate and Bismuth Subcitrate. Canena J, Reis J, Pinto AS, et al.

The Journal of Pharmacy and Pharmacology. 1998;50(3):279-83. doi:10.1111/j.2042-7158.1998.tb06861.x.

4. In Vivo Distribution of Bismuth in the Mouse Brain: Influence of Long-Term Survival and Intracranial Placement on the Uptake and Transport of Bismuth in Neuronal Tissue. Larsen A, Stoltenberg M, Søndergaard C, Bruhn M, Danscher G.

Basic & Clinical Pharmacology & Toxicology. 2005;97(3):188-96. doi:10.1111/j.1742-7843.2005.pto_973132.x.

5. Bismuth Encephalopathy- A Rare Complication of Long-Standing Use of Bismuth Subsalicylate. Borbinha C, Serrazina F, Salavisa M, Viana-Baptista M.

BMC Neurology. 2019;19(1):212. doi:10.1186/s12883-019-1437-9.

6. Bismuth Subgallate Toxicity in the Age of Online Supplement Use. Sampognaro P, Vo KT, Richie M, Blanc PD, Keenan K.

The Neurologist. 2017;22(6):237-240. doi:10.1097/NRL.0000000000000144.

7. Bismuth Tracing in Organotypic Cultures of Rat Hippocampus. Locht LJ, Munkøe L, Stoltenberg M.

Journal of Neuroscience Methods. 2002;115(1):77-83. doi:10.1016/s0165-0270(02)00004-3.

8. Bioactive Bismuth Compounds: Is Their Toxicity a Barrier to Therapeutic Use?. Gonçalves Â, Matias M, Salvador JAR, Silvestre S.

International Journal of Molecular Sciences. 2024;25(3):1600. doi:10.3390/ijms25031600.

9. Review Article: Safety of Bismuth in the Treatment of Gastrointestinal Diseases. Tillman LA, Drake FM, Dixon JS, Wood JR.

Alimentary Pharmacology & Therapeutics. 1996;10(4):459-67. doi:10.1046/j.1365-2036.1996.22163000.x.