Introduction to Bismuth and Its Uses
Bismuth is a brittle, silvery-white heavy metal used in cosmetics, electronics, and notably, over-the-counter pharmaceuticals [1.2.1]. Its low toxicity profile makes it a common ingredient in medications designed to treat gastrointestinal issues like diarrhea, heartburn, and upset stomach [1.2.1, 1.7.1]. The most well-known of these is bismuth subsalicylate (BSS), the active ingredient in Pepto-Bismol and Kaopectate [1.7.1]. Bismuth compounds are also a key component in quadruple therapy for eradicating Helicobacter pylori infections, a common cause of peptic ulcers [1.2.1]. Historically, various bismuth salts were used to treat syphilis before the advent of modern antibiotics [1.2.1]. Despite its proximity to toxic metals like lead and arsenic on the periodic table, bismuth and its compounds are considered relatively safe, largely due to their poor solubility in bodily fluids [1.5.5].
The General Toxicology of Bismuth
Bismuth toxicity is rare but can be severe when it occurs [1.3.2]. Most cases of toxicity are associated with chronic, high-dose ingestion of bismuth-containing compounds over months or even years [1.3.2]. When used as directed for short periods, such as for traveler's diarrhea, the risk is minimal [1.2.6].
The primary targets for bismuth toxicity are the central nervous system and the kidneys [1.6.2].
- Neurotoxicity: This is the most well-documented form of severe bismuth toxicity, often presenting as a progressive encephalopathy [1.2.4]. Symptoms have an insidious onset, beginning with mild changes like apathy, irritability, poor concentration, and sleep disturbances [1.2.3, 1.2.4]. This prodromal phase can last for weeks or months as bismuth levels rise in the body [1.2.3]. It can then escalate rapidly over 24-48 hours into a more severe state characterized by confusion, myoclonus (involuntary muscle twitching), ataxia (loss of coordination), and difficulty speaking [1.2.3, 1.3.5]. In severe cases, seizures and coma can occur [1.2.4].
- Nephrotoxicity (Kidney Damage): Acute bismuth poisoning, often from a large single overdose, is more likely to cause kidney damage than neurotoxicity [1.6.2]. This can manifest as acute tubular necrosis, where the small tubules of the kidney are damaged, leading to renal failure [1.6.1, 1.2.4]. Signs include decreased urine output (oliguria) and abnormal kidney function tests [1.6.1]. The kidneys are a primary site for bismuth accumulation [1.4.4].
Other reported, though less common, effects of chronic toxicity include pigmentation of the skin and gums (a blue-black line), and bone and joint problems [1.2.4, 1.2.6]. The most common and harmless side effects of oral bismuth are temporary and include a black tongue and dark stools [1.2.2].
Pharmacokinetics: How the Body Processes Bismuth
Understanding bismuth's journey through the body is key to understanding its toxicity profile. The vast majority of orally ingested bismuth (about 99%) is not absorbed and is eliminated in the feces [1.2.3]. However, a small fraction (less than 1%) is absorbed into the bloodstream [1.2.3, 1.4.5].
- Absorption: Different bismuth compounds have slightly different absorption rates. Colloidal bismuth subcitrate (CBS) and bismuth subgallate are absorbed slightly more than bismuth subsalicylate [1.4.5].
- Distribution: Once absorbed, bismuth is distributed throughout the body's tissues, with the highest concentrations found in the kidneys and liver [1.2.3, 1.4.4]. It can cross the blood-brain barrier, which is how it can lead to neurotoxicity [1.6.5].
- Metabolism: Absorbed bismuth is not metabolized in the body [1.2.3].
- Elimination: Bismuth is eliminated from the body very slowly through both urine and feces [1.4.3, 1.4.4]. Its elimination has multiple phases, with a long terminal half-life that can be over 20 days [1.4.1]. This slow elimination means that with continuous use, bismuth can accumulate in tissues, leading to a steady rise in blood concentrations and increasing the risk of toxicity [1.4.1, 1.6.2]. Blood bismuth levels typically need to exceed 50 µg/L to be associated with toxicity, with normal levels being under 5 µg/L [1.9.1].
Comparison of Bismuth Compounds
Different bismuth salts have been associated with varying levels of risk, primarily due to historical usage patterns and solubility.
| Feature | Bismuth Subsalicylate (BSS) | Colloidal Bismuth Subcitrate (CBS) | Bismuth Subgallate/Subnitrate |
|---|---|---|---|
| Common Use | Over-the-counter for diarrhea, indigestion (e.g., Pepto-Bismol) [1.7.1] | Prescription for H. pylori eradication and ulcers [1.2.1, 1.5.6] | Previously used for gastrointestinal issues; linked to historical toxicity cases [1.5.1] |
| Toxicity Risk | Neurotoxicity is rare; main overdose concern is often from the salicylate component [1.5.1, 1.7.1] | Extremely safe at prescribed doses; neurotoxicity is rare [1.5.1, 1.5.6] | Historically associated with an epidemic of neurotoxicity in the 1970s due to prolonged, high-dose use [1.5.1] |
| Absorption | Bismuth is minimally absorbed; salicylate is readily absorbed [1.5.3] | Slightly higher absorption compared to BSS [1.4.5] | Associated with significant bismuth absorption and accumulation in historical cases [1.5.2] |
Diagnosis and Treatment
Diagnosing bismuth toxicity requires a high index of suspicion, especially in a patient with progressive neurological decline and a history of using bismuth-containing products [1.9.2].
- Diagnosis: The diagnosis is confirmed by measuring elevated bismuth levels in the blood or urine [1.9.2]. Blood levels over 50-100 μg/L are considered toxic [1.6.4, 1.9.1]. Other diagnostic tools include a patient history, evaluation of symptoms (myoclonus, ataxia), an EEG to show non-specific brain wave slowing, and a CT scan of the head, which may show hyperdensities in the brain cortex due to bismuth accumulation [1.9.2, 1.9.5]. It's also important to measure salicylate levels if BSS overdose is suspected [1.9.2].
- Treatment: The cornerstone of treatment is immediate discontinuation of the bismuth-containing product [1.2.3, 1.9.4]. In most cases, symptoms gradually improve over weeks to months with only supportive care as the body slowly eliminates the metal [1.2.3]. The role of chelation therapy, which uses agents to bind heavy metals and enhance their excretion, is unclear and debated [1.9.4]. Some case reports show improvement with chelators like DMPS, while others report no benefit or even worsening of symptoms [1.2.3]. Chelation is typically reserved for life-threatening cases [1.2.6].
Conclusion
So, how toxic is bismuth to humans? The answer is that it is generally considered to have low toxicity, especially when used in over-the-counter medications according to directions for short-term relief [1.2.1, 1.8.3]. Harmless side effects like black tongue and stool are common, but severe poisoning is rare [1.2.2]. The real danger lies in chronic, excessive use, which allows the heavy metal to accumulate in the body, leading to a distinct and potentially debilitating, though usually reversible, neurotoxic syndrome [1.3.2]. Acute overdose is more likely to harm the kidneys [1.6.2]. Awareness of the risks associated with long-term use is the most critical factor in preventing bismuth toxicity.
