What is Manganese Toxicity?
Manganese (Mn) is a mineral that’s found naturally in the environment and plays a crucial role in many important body processes. This mineral is built into certain proteins and helps support the immune system, control how the body uses energy, regulate growth, assist in clotting and bleeding, and help rid the body of harmful products of stress. Without enough Mn, these functions may not work as they should.
The best way to get enough Mn is through foods, mainly plants. Some vitamins or health supplements might also contain Mn. Drinking water may contain small amounts of Mn, but these amounts are controlled to avoid harmful effects. Breast milk and baby formula also give infants the essential Mn they need during their early growth period.
Getting too much Mn, a condition known as manganism, is rare but can occur due to exposure in the workplace, accidental intake, or through medical treatments. Too much Mn can cause problems that resemble Parkinson’s disease. This happens because Mn deposits itself in areas of the brain responsible for movement control, and alters how brain cells that produce a chemical called dopamine work. Excessive Mn can also harm the heart and liver, and may increase the risk of death in infants.
The most common causes of manganism include receiving certain medical nutrition treatments in severely ill patients, drinking water from contaminated wells, and exposure through jobs like welding, smelting, and mining. Mn is easily absorbed in the gut, and how much is taken in can depend on the diet. The liver and pancreas help to get rid of excess Mn, but this may not happen if Mn is given by injection, which can potentially lead to manganism.
What Causes Manganese Toxicity?
There are a few key ways in which someone can be exposed to toxic levels of the metal manganese, which can lead to a condition known as “manganism”. This includes working in industries such as mining, welding, smelting and battery manufacturing.
Here are the three main methods of how manganese can enter your body:
1. Inhalation: Once inhaled, manganese particles can be transported to your brain by nerves in your nose and face.
2. Pulmonary absorption: Manganese can be absorbed directly into your bloodstream or lymphatic system, which in turn, spreads it throughout your body.
3. Swallowed secretions: Respiratory secretions carrying manganese can be swallowed and absorbed into your body.
The size of the particles also matters: medium-size particles that get deposited into your lower airways can play a key role in respiratory absorption.
If you consume manganese from plants, your liver usually filters out any excess to avoid toxicity. However, people with liver problems can face higher risk of manganese accumulation in the bloodstream, which can lead to toxicity.
Apart from work environment, another source of manganese exposure could be your drinking water. This can occur especially if you drink well-water, which can have high manganese levels due to adjacent rock beds, certain types of soil, agricultural fertilizers and human waste, among others. Regular consumption of such water can affect children’s IQ, memory and academic performance. The US guideline suggest your drinking water should have less than 400 micrograms of manganese per liter.
Breastfeeding infants get their necessary manganese requirements without the risk of toxicity. But infants who primarily consume baby formula could potentially be at risk, especially if the formula is mixed with water containing high manganese amounts.
Chronic use of Total Parenteral Nutrition (TPN), a method of feeding that bypasses the gastrointestinal tract, could potentially lead to manganism given that our bodies cannot readily remove intravenous manganese. In addition, exposure to the manganese compound MMT, commonly found in gasoline, can risk manganism with chronic and high exposures.
Risk Factors and Frequency for Manganese Toxicity
Manganism, a health condition caused by exposure to too much manganese, can affect certain groups of people more than others. These groups include children, the elderly, women, people with certain previous health conditions, and people exposed to manganese in their environment or work.
- Children, especially infants, are a high-risk group. This is due to their bodies’ higher propensity to take in the metal through their digestive system and transfer it to the brain. Their bodies also have a lower ability to naturally dispose of the metal.
- Older people are also at a higher risk. Excessive exposure to manganese can worsen the gradual decline in fine motor skills often associated with aging
- Women tend to have higher levels of manganese. This might be due to them having more capacity to absorb manganese from food, possibly because they tend to have lower iron levels in their blood. This is also the reason why pregnant women usually have higher manganese levels than those who aren’t pregnant.
- People living in countries with fewer restrictions on the amount of metals allowed in their water supply are often exposed to more manganese. Studies from Bangladesh, for example, show a clear link between consuming manganese-contaminated water and negative effects on learning and academic performance in children.
Signs and Symptoms of Manganese Toxicity
Manganese toxicity can cause symptoms similar to early stage Parkinson’s disease, along with psychiatric problems. However, it’s rare for all symptoms to appear together, making diagnosis a bit tricky. It’s important to take a careful patient history, noting any changes from normal behavior. If psychiatric problems and memory issues are a noted factor, this could suggest manganese toxicity.
Examinations should include neurological and cardiovascular assessments, along with cognitive function tests. It’s especially key to look at symptoms in patients of a certain age or with specific health conditions to differentiate it from Parkinson’s disease.
Patients with manganese toxicity may show changes in their emotional and psychiatric state early on. This can include quick mood swings, personality changes, hallucinations, psychosis, memory issues and insomnia. There might be decreased libido, depression, anxiety, and a drop in IQ.
Physical symptoms may include tremor, difficulty in walking, headaches, speech difficulties, hyperreflexia, hypertonicity, and tremors. Severe symptoms can involve abnormal movements and “cock-walk”, characterized by walking on tiptoes with a forward tilt.
Manganese toxicity can also affect the cardiovascular and lung system. Some might develop a form of obstructive lung disease while others could experience hemodynamic changes including low blood pressure, slow heart rate.
- Checking the patient’s occupational history can be helpful in diagnosing manganese toxicity, particularly for those working in jobs with potential exposure to manganese such as welding, metal manufacturing, mining, smelting, battery manufacturing, or those exposed to gasoline combustion and steelworkers
- Assessing the patient’s personal protective equipment usage can also be significant as those without appropriate respiratory protection have a higher risk of developing symptoms
- Investigating the patient’s living conditions can give insights. For instance, if the patient recently moved from a country with poor public drinking water conditions or relies on a well for water, they might have been consuming water high in manganese
- Moreover, patients at risk can be flagged by querying about drug use or previous hospitalizations for chronic intravenous therapy, which potentially exposed them to high levels of manganese
- Also, it is crucial to take into account the patient’s past medical history specifically any known or presumed liver issues
This as these conditions increase the risk of developing manganese toxicity. And finally, for male patients having difficulty conceiving a child, despite an unremarkable female partner’s health, manganese toxicity could be a possible cause as it might result in decreased fertility.
Testing for Manganese Toxicity
Finding the best way to detect manganese toxicity in the body has been challenging. Because your body usually gets rid of manganese through the liver, tests of manganese levels in your urine often aren’t reliable, as they’re usually quite low and don’t always match up with harmful levels in your blood.[77] Tests of manganese levels in your blood are also hard to pin down because manganese doesn’t stay in the body very long. Plus, tests done over time don’t always give clear results that doctors can use.[65] Testing for manganese in your saliva also has its problems. Even among people exposed to the same level of manganese, the tests can vary a lot, which means they’re not a great tool for measuring toxicity.[78]
Tests of manganese levels in hair and nails have given mixed results, with some studies finding them reliable and others not.[79] Researchers led by Grashow suggested that tests of manganese in nails might help track exposure over several months, but aren’t really useful beyond that.[81] More recent research suggests that testing hair and nails might help to show how much manganese someone’s been exposed to, but also supports the idea that tests of saliva aren’t great for measuring this.[82]
But there may be promise in measuring the levels of both manganese and iron in the blood. A study led by Neil did just this, finding a reliable ratio of manganese to iron in blood plasma and red blood cells in people exposed to airborne manganese.[21]
Another team of researchers, led by Liu, came up with a new test for measuring manganese in bone, which is where a lot of body’s manganese ends up. This test, called neutron activation analysis, showed promise in a study where it was used to measure manganese in the bones of hands.[83]
MRI scans have also been useful, especially when looking at current or recent exposure to manganese. The scans can help show where manganese builds up in the brain. By looking at a specific part of the brain called the globus pallidus, and comparing it to another area, researchers can see how much manganese is present.[60][84]
Other tests, like PET scans, the use of a special type of MRI scan that can measure specific molecules in the brain, and tests of manganese and a protein called ferritin in the blood, have also been used to try to get a clearer picture of how much manganese is in the brain.[85][86][87]
To sum it up, diagnosing manganese toxicity requires doctors to be on high alert, especially when they’re treating patients who have a higher risk of exposure. The best approach involves a team of healthcare professionals, including a neurologist, who can help figure out whether the patient’s symptoms are due to manganese toxicity. A toxicologist may also be asked to weigh in. Tests like MRIs or blood tests may also be used, but these should be ordered by professionals who are familiar with this kind of toxicity and the latest research.
Treatment Options for Manganese Toxicity
The treatment for manganism toxicity, a condition caused by too much exposure to manganese, begins with addressing immediate issues and controlling ongoing exposure. The best way to address manganism is to remove the patient from the source of the manganese exposure. This could be related to their work environment, living conditions, or certain medical procedures.
One option for treating manganism involves chelation therapy, using substances like EDTA (Ethylenediaminetetraacetic acid) and Para-aminosalicylic Acid (PAS). Chelation therapy works by significantly reducing the quantity of manganese in the patient’s blood and increasing its release through urine. However, this doesn’t usually reduce the toxic effects of the disease since manganese’s impacts are long-term and often irreversible.
EDTA may stop more manganese from entering the central nervous system, which could limit further harm, though it can’t completely eradicate all damage. Hence, in patients with advanced or prolonged manganism, chelation therapy might not completely stop all decline.
Another substance used for chelation therapy, Para-aminosalicylic acid (PAS), known to be used as an anti-tuberculosis medication, has shown clinical benefits regarding manganism treatment. It can reach the parts of the brain affected by manganism. PAS could chelate – or grab onto and remove – both forms of manganese causing toxicity. Based on research, it’s believed that the anti-inflammatory properties of PAS could be beneficial due to neuroprotective effects.
Another attempted treatment is the use of a supplement known as Levodopa (L-dopa). Initial studies pointed out potential benefits, but longer-term use did not seem to provide positive results. In fact, when L-dopa treatment was stopped, the symptoms of manganism advanced despite the initial therapy.
Doctors have found that several vitamins and supplements can help manage manganism. Alongside chelation therapy, they often recommend iron supplements, which have been shown to improve neurological symptoms. Vitamin E may prevent cell damage caused by manganism, and substances such as glutathione and N-acetylcysteine may decrease the harmful effects of manganism in cells. Certain plant extracts have also shown potential benefits.
Lastly, newer treatments are being researched, including the use of substances like taurine and Rasagiline. Taurine may reduce the harmful effects of manganese, mainly by preserving the function of energy-producing structures in the brain. It also seems to improve memory and learning impairments. Rasagiline, an inhibitor used in the treatment of Parkinson’s disease, also shows potential for protecting cells from damage caused by manganism.
What else can Manganese Toxicity be?
When certain symptoms arise in patients, particularly movement disorders and cognitive difficulties, there are several conditions that doctors need to consider before making a diagnosis.
One possible condition is Idiopathic Parkinson’s disease. This typically shows up as slow movements, a shuffling walk, difficulty maintaining balance, and a particular kind of tremor known as a “pill-rolling” tremor. It is quite similar to a condition called manganese toxicity, but a few key differences can help doctors tell them apart. For instance, manganese toxicity often triggers less severe tremors, affects a younger age group, and it can be linked to certain occupational exposures.
Another potential condition is Dementia with Lewy bodies, where patients can display symptoms similar to those of Parkinson’s disease along with cognitive difficulties, such as problems with short-term memory, multitasking, and understanding spatial relationships. These patients might also experience visual hallucinations.
In addition, Frontotemporal dementia might be considered. Patients with this condition may show disinhibition, apathy, compulsive behaviors, and a range of communication impairments.
Also, Essential tremor, a neurological disorder known for causing high-frequency tremors in different body regions could be a potential condition.
Multiple system atrophy is another complex disorder that can cause symptoms like difficulty maintaining blood pressure when standing, problems with movement and balance, and lack of responsiveness to a common Parkinson’s disease medication. Like others, Corticobasal degeneration affects the brain causing difficulties in coordinated movements and changes in behavior and emotions.
Another possible suspect is Progressive supranuclear palsy, which can cause difficulties with eye movement and display Parkinson’s-like symptoms.
It’s also important for doctors to consider the common condition known as drug-induced Parkinsonism, which usually arises due to certain medications.
Chronic use of the recreational stimulant known as Methcathinone has also been linked to symptoms similar to manganese toxicity.
Lastly, doctors might also consider other neurodegenerative disorders, chronic and repeated head injuries, certain infections like HIV or syphilis, structural brain disorders, and metabolic disorders that can negatively affect the brain.
What to expect with Manganese Toxicity
There is very little research on the long-term health effects of being exposed to manganese, along with whether patients can recover once they’re no longer in contact with it. According to the small amount of research that is available, it appears that recovery from some mental health symptoms may be possible after removing the source of exposure, while recovery from others might not be.
For instance, a study followed a group of workers who had been exposed to manganese for a decade and a half. Even though they showed signs of improvement about 14 years after their initial exposure, they still struggled with a few tasks, such as moving smoothly, drawing, and keeping their hands steady. This group of workers also experienced more feelings of anger, confusion, exhaustion, and hostility the more manganese they were exposed to, indicating a possible correlation between long-term exposure and these symptoms. Researchers also noted that the workers developed respiratory problems, possibly due to the inflammation caused by manganese exposure.
Interestingly, older adults exposed to manganese often experience these symptoms to a greater extent than younger individuals. Researchers think this could be because older people may have age-related neurological changes that make them more susceptible to the harmful effects of manganese. These age-related cognitive deficits seemed to persist even after people were no longer being exposed.
In a separate study, workers from a battery manufacturing factory were followed for eight years after they stopped being exposed to manganese. In this case, their hand steady and reaction time did not improve. However, the steadiness of their hand-forearm movements did, suggesting some recovery.
After people are no longer exposed to manganese, they mostly seem to recover, but they might still have lingering behavioral and neurological problems. To avoid further harm, the best advice is to stop activities that could result in additional exposure. Overall, these problems cause more health issues than deaths, and the prognosis is generally favorable once individuals are no longer exposed. More research will be needed to get a clearer picture of the expected course of recovery, especially with new treatments, such as nutritional supplements and chelation therapy.
Possible Complications When Diagnosed with Manganese Toxicity
Manganism, also known as manganese poisoning, is a condition caused by excessive exposure to manganese. Manganese is a naturally occurring element that is essential for human health in small amounts. However, when exposure to manganese is prolonged or at high levels, it can lead to serious health problems.
The history of manganism dates back to the early 19th century when it was first recognized as a health concern in workers exposed to manganese in mines and smelters. The symptoms were initially attributed to a form of Parkinson’s disease, as they shared similar characteristics. However, it was later discovered that manganism is a distinct condition caused by manganese toxicity.
The physical complications of manganism can be severe and debilitating. The central nervous system is particularly affected, leading to neurological symptoms similar to Parkinson’s disease. These symptoms include tremors, muscle rigidity, and difficulty with movement and coordination. Over time, these symptoms can worsen and lead to significant disability.
In addition to neurological symptoms, manganism can also affect other systems in the body. Respiratory problems, such as coughing and shortness of breath, can occur in individuals exposed to high levels of manganese dust or fumes. Gastrointestinal symptoms, such as nausea, vomiting, and diarrhea, may also be present.
Long-term exposure to manganese can also have detrimental effects on the liver and kidneys. Studies have shown that excessive manganese exposure can lead to liver damage and impaired kidney function. These complications can further contribute to the overall health decline in individuals with manganism.
It is important to note that manganism is a preventable condition. Occupational exposure to manganese can be minimized through proper safety measures, such as ventilation systems and personal protective equipment. Additionally, regular monitoring of manganese levels in the workplace can help identify and address potential hazards.
In conclusion, manganism is a condition caused by excessive exposure to manganese. It has a long history of affecting workers in industries where manganese is present. The physical complications of manganism primarily involve the central nervous system, leading to neurological symptoms similar to Parkinson’s disease. Other systems in the body, such as the respiratory, gastrointestinal, liver, and kidneys, can also be affected. Preventive measures should be taken to minimize exposure to manganese and prevent the development of manganism.
Preventing Manganese Toxicity
Understanding the risk of exposure to certain populations is crucial in reducing the risk of manganese (Mn) toxicity. The current safe level of manganese in drinking water is 400 micrograms per liter. Also, the amount of manganese from food sources should be less than 60 micrograms/kg. Knowing these safe levels can help individuals ensure the water in their homes is safe. This is particularly useful for healthcare providers in developing countries, to help treat children and adults showing signs of the disease.
If there’s a chance of exposure at work, workers should let the management know if their workplace isn’t meeting Occupational Safety and Health Administration (OSHA) standards. Individuals should adhere to current safety guidelines while welding or working in industrial manufacturing. They should also check their workplace’s standards against OSHA’s to ensure they’re not at risk of developing manganese poisoning or getting exposed to other harmful metals.
It’s important that families be aware of the risk of infant toxicity. Using water with high levels of manganese to prepare baby formula greatly increases the risk to infants. This is because young children are not mature enough to process and eliminate manganese efficiently. Women with a history of heavy bleeding or other conditions that may lead to iron deficiency should also be vigilant, as they are prone to develop manganese poisoning due to increased transferrin expression. Those using nutritional supplementation like Total Parenteral Nutrition (TPN) should also be careful, as this circumvents the usual regulatory functions in the gut that reduce absorption. The same applies to those with liver and pancreatic diseases.
If someone shows symptoms of manganese poisoning and has a history of exposure to manganese, it should be treated as a medical emergency. Early mental changes and worsening neurological symptoms that look similar to Parkinson’s disease are the main signs of toxicity. Avoiding further exposure, using substances that bind with manganese to help remove it from the body (‘systemic chelators’), and providing vitamins and nutritional supplements will form the mainstay of treatment. This should be done under guidance from neurologists and toxicologists.
Generally, individuals exposed to manganese have a good prognosis based on limited studies. Most patients show partial recovery of most symptoms, with some persistence of issues in those who were older at the time of onset or have motor and behavioral problems.
