From the Guidelines
The primary treatment for elevated manganese levels is chelation therapy, typically using agents such as calcium disodium EDTA or para-aminosalicylic acid (PAS), along with removal from manganese exposure and iron supplementation in case of iron deficiency. This approach is supported by the most recent and highest quality study, which emphasizes the importance of treating toxicity by removing manganese-containing additives and using chelation agents and iron delivery 1.
Key Considerations for Treatment
- Removal from manganese exposure is essential and should be the first intervention, whether it's changing work environments, implementing proper protective equipment, or securing alternative water sources 1.
- Chelation therapy works by binding to manganese ions in the bloodstream, forming complexes that can be excreted through urine, thereby reducing the body burden of manganese and preventing further tissue damage.
- Iron supplementation is crucial in cases of iron deficiency, as competing for similar transport proteins with decreased iron levels can lead to an accumulation of manganese to toxic levels over time 1.
- Supportive care for neurological symptoms may include levodopa to address parkinsonian features, though its effectiveness varies.
Monitoring and Follow-Up
- Regular monitoring of blood manganese levels is necessary during treatment, with follow-up testing recommended at 1,3, and 6 months.
- The treatment strategy should be tailored to the individual's specific needs and circumstances, taking into account factors such as the level of manganese exposure, the presence of underlying medical conditions, and the severity of symptoms.
Important Notes
- Dietary intake does not typically lead to manganese toxicity, as absorption is tightly regulated in the gut 1.
- Manganese toxicity can have serious consequences, including neurological damage, which may be irreversible, emphasizing the need for prompt and effective treatment 1.
From the Research
Interpreting Manganese Levels
- Manganese levels can be interpreted based on whole-blood concentrations, with normal levels ranging from 73-219 nmol/L 2.
- Elevated levels of manganese (>219 nmol/L) can be a concern, even in patients receiving "manganese-free" parenteral nutrition 2.
Treatment for Elevated Manganese Levels
- Sodium para-aminosalicylic acid (PAS-Na) has been shown to be an effective treatment for serious chronic manganese poisoning, with one study reporting clinical cure in one patient and significant improvement in another 3.
- Chelation therapy, such as dimercaptosuccinate (DMSA) and D-penicillamine (PSH), may also be effective in enhancing the urinary excretion of manganese, although more research is needed to explore the benefits of chelator combinations 4.
- The use of CaEDTA, PSH, and DFOA has been shown to promote the excretion of manganese, iron, and copper, respectively, from the central nervous system 4.
Regulation of Brain Manganese
- Both hepatic and intestinal manganese excretion are required to regulate brain manganese during elevated manganese exposure 5.
- The intestines play a compensatory role in clearing brain manganese accumulated by early life manganese exposure, and hepatic and intestinal manganese excretion play important roles in functionally modulating manganese neurotoxicity 5.
Pharmacokinetic Modeling of Manganese
- Pharmacokinetic modeling of manganese has shown that uptake and elimination of manganese are dose-dependent, with increased elimination rate constants at higher dietary manganese concentrations 6.
- The models also indicate differential control of absorption in single gavage oral dose studies versus continuous high oral doses in the feed 6.