Manganese Toxicity Symptoms, Side Effects & Remedies

Required in trace amounts, this metal can wreak havoc in the body in excess. Too much manganese triggers oxidative stress, inflammation, as well as cognitive and reproductive issues. It can make infections more dangerous and lead to a Parkinson’s-like condition called manganism. Read on to find out more about manganese toxicity and ways to combat it.

What is Manganese?

Manganese (Mn) is a trace metal essential to all forms of life. As such, each person needs it for normal development, growth, and functioning [1, 2, 3].

Multiple enzymes require manganese as a cofactor. These enzymes play roles in:

• Energy (ATP) production in the mitochondria [4]
• Antioxidant defense (including superoxide dismutase) [5]
• Burning fats, proteins, and sugars [1, 2]
• Brain development and health [6]
• Immune response [2]
• Sex hormone production and reproductive health [2, 7]
• Digestion [4]
• Building bones and connective tissue [2, 7]

Traces of manganese are part of a healthy diet. However, exposure to excess levels can produce symptoms of toxicity [8].

Keeping manganese in balance can be tricky. Levels toxic to some processes are beneficial for others [9, 10].

Because it’s found pretty much everywhere, people are more likely to have excess manganese than to be deficient.

Absorption & Elimination

You get most manganese through your diet [5].

Of the manganese you consume in food, only 1 – 5% is absorbed into the blood. This level is tightly regulated based on the amount of Mn in your diet. You will absorb less if you’re eating a lot of manganese-rich food [6].

Excess manganese is transported to the liver and released into the bile, which is passed back into the gut and removed with the stool. About 80% of manganese is eliminated this way, while small amounts can also be removed with urine, sweat, and breast milk [8, 11].

Manganese is mostly stored in the bones (40%), liver, kidneys, pancreas, and adrenal and pituitary glands. Some are dispersed in your bloodstream and can readily travel across the blood-brain and placental barriers [11, 8].

Testing

Blood, urine, and saliva levels are poor indicators of Mn exposure and body burden [11, 12, 13].

RBC (red blood cell) manganese levels are a better measure of the actual content of manganese in tissues, but are only relevant for recent exposure, spanning a couple of months [14, 15].

For those with long-term, low-dose Mn exposure, hair, nail, and bone Mn content may give a more accurate exposure estimate [16, 11].

You can check your brain levels with an MRI. But it is only good for recent exposures, spanning a few months [11].

Symptoms of Manganese Toxicity

Symptoms of high manganese include [17, 18, 19]:

• Headaches
• Eye issues
• Sore throat
• Anxiety
• Irritability
• Insomnia
• Memory loss
• Hand tremors
• Exaggerated reflexes
• Muscle cramps

Aside from the above symptoms, too much manganese can cause a long list of side effects. These mainly depend on the amount and duration of exposure.

However, these symptoms are also common to many other health conditions. For an accurate diagnosis and appropriate treatment or management plan, talk to your doctor about any symptoms you are experiencing.

Side Effects of Too Much Manganese

1) Manganism (Manganese Toxicity)

Overexposure to Mn, usually in the workplace, causes manganism, a syndrome similar to Parkinson’s disease [20, 21].

The early phase — sometimes called “manganese mania” — affects mental health, leading to irritability, apathy, aggressiveness, hallucinations, and psychosis [22, 8].

Next, issues with short-term memory and computational ability follow [22].

Symptoms of early poisoning stages are reversible [12].

At a point, manganese toxicity becomes irreversible. It starts to damage the brain, and a horrifying sequence follows: the damage progresses, even without further exposure. Symptoms include a loss of balance, uncontrollable tremors (dystonia), slow and clumsy movements (bradykinesia), face muscle spasms, speech disturbance, rigidity, and gait abnormalities [22, 8, 23, 11].

Many symptoms of manganism resemble those of Parkinson’s disease. However, manganism targets different brain regions (globus pallidus and striatum as opposed to substantia nigra). It is also doesn’t improve with levodopa, unlike Parkinson’s [23, 5].

If you suspect that you or someone you know has been exposed to toxic levels of manganese in their workplace or in the environment, seek medical attention as soon as possible.

2) Oxidative Stress

Trace amounts of manganese help your body fight oxidative stress, but too much of this metal actually makes it worse. In excess, manganese builds up in mitochondria and increases the production of reactive oxygen species (ROS). It also depletes the antioxidant glutathione, according to rat and monkey studies [20, 23, 4].

3) Inflammation

Excess manganese triggers the release of several inflammatory molecules (including TNF-α, IL-6, IL-1β, prostaglandins, and nitric oxide). It also activates the body’s key inflammatory signal, NF-κB. Altogether, this can cause inflammation in the brain and body [4, 24, 23].

In a study of 633 people, those eating high-manganese diets had raised inflammatory markers (about 50% higher IL-1b and IL-6, 32% higher IL-8, and a more active NF-κB) [25].

4) Impaired Cognition

Too much manganese can cause neurodevelopmental problems in children. Twelve studies linked higher early-life manganese exposure with a lower IQ [26, 27].

In addition, a review of 21 studies concluded manganese in drinking water worsens cognitive function in school-aged children [28].

Children who are exposed to higher Mn perform more poorly in school, measured by mastery of language, mathematics, and overall grade average:

• In 2 studies conducted in Canada with 630 children, higher Mn levels in drinking water were associated with lower IQ scores [29].
• In a study of 201 school children in Bangladesh, higher drinking water Mn was associated with lower achievement scores in mathematics [11].
• Among 172 children in Mexico, those exposed to more airborne Mn performed worse on cognitive function tests [30].
• In another group of 265 Mexican children, higher Mn hair levels were linked with decreased verbal memory and learning [31].
• Similarly, in another 2 studies of 83 Brazilian children and 106 US children, higher Mn hair levels were associated with poorer cognitive function and lower IQ [32, 33].

Long-term exposure to high levels of manganese has also been linked to mild cognitive impairment in adults [34].

In 95 workers, those exposed to more Mn-containing welding fume had poorer working memory [35].

Further, in a study of 60 Chinese workers, higher bone and fingernail but not blood manganese was linked to worse cognitive function [36].

5) ADHD

Studies in children and adolescents found that higher exposure to manganese is associated with inattention and hyperactive behavior [16, 26].

In a meta-analysis of 4 studies with 175 children with ADHD and 999 healthy children, those with ADHD had higher manganese levels [37].

In addition, in a study of 288 adults living in a mining district in Mexico, those exposed to higher air Mn levels were more likely to have attention problems [38].

6) Brain Damage

Mn in excess can be toxic to the brain. Researchers mostly observed it in people who accidentally ingest or inhale large quantities of this metal in their workplace [39, 12].

In a study of 66 people, welders chronically exposed to manganese had smaller brain areas (globus pallidus, cerebellum) compared to unexposed people. Those with larger reductions had more cognitive and behavioral symptoms [40].

Also, in 1112 workers, those exposed to high Mn had lower blood BDNF levels. BDNF helps give birth to new brain cells and supports overall brain health [41].

Manganese exposure was linked to impaired motor function in 154 and 100 children and adolescents living near a manganese plant in Italy and Mexico, respectively [42, 43].

Rat and monkey studies reveal manganese might lead to these unwanted effects by depleting dopamine in the brain [39].

7) Anxiety

15 studies describe mood disruption after overexposure to Mn, including anxiety, nervousness, irritability, and aggression [44].

In one study of 101 people, patients suffering from generalized anxiety had elevated Mn levels [45].

8) Parkinson’s

It is possible that the elderly have a propensity for Parkinson’s that could be “pushed over the edge” by increased doses of manganese [11].

Also, chronic exposure to high Mn levels may accelerate Parkinson’s disease by lowering dopamine and promoting protein clumping in the brain (alpha-synuclein protein misfolding) [4].

In a meta-analysis of 22 studies with over 2,000 patients with Parkinson’s and as many healthy controls, those with Parkison’s had higher Mn blood levels [46].

The evidence is still uncertain: several studies claim prolonged and chronic occupational exposure to Mn is predictive of Parkinson’s disease [2], but other studies disagree [47].

9) Alzheimer’s

High manganese may be involved in Alzheimer’s by increasing blood amyloid-beta levels. Amyloid beta creates plaques in the brain linked to cognitive impairment in Alzheimer’s. Chronic Mn treatment in monkeys increased these brain plaques. Additionally, advanced stages of manganese poisoning have been linked to dementia [48, 49, 50].

10) ALS

Mn smelters and miners are more likely to suffer from both manganism and amyotrophic lateral sclerosis (ALS) [49, 4].

One study found higher Mn levels in the spinal cord of 7 ASL patients compared to 6 controls [51].

In addition, ALS is common in patients with liver cirrhosis, a condition in which manganese builds up since bile flow is impaired [49].

11) Sex Hormones

Reproductive Health

An observational study conducted among factory workers in the ’80s showed that Mn-exposed male workers had significantly fewer children than those not exposed to Mn, suggesting this metal may decrease fertility [52].

More recently, in a study of 84 male workers exposed to Mn and 92 controls, those exposed to manganese had lower testosterone and higher gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) levels. They also had decreased sperm motility [53].

Several studies have found higher prolactin levels in Mn-exposed workers (251 and 179 welders) and children living in Mn-rich zones (77 and 225 children). High prolactin levels can cause reproductive problems in both men and women [54, 55, 56, 57].

Early Puberty

Manganese can trigger the early onset of puberty (by stimulating the hypothalamic-pituitary axis). Exposure to Mn induces early puberty in rats, raising sex hormones such as estradiol [58, 59, 60, 61].

12) May Impair Sleep

In a study of 15 people, chronic Mn intoxication decreased REM sleep [62].

Similar effects were also observed in rats, where manganese intoxication also caused circadian rhythm disturbances [63, 64, 65].

13) Bacterial Infection

Invading microbes can use Mn to resist host immune responses. In fact, Mn uptake is essential for the virulence or harmfulness of many bacteria [66, 67].

In mice, a high-Mn diet promotes S. aureus, a common cause of skin and respiratory infections, sinusitis, and food poisoning [68].

14) Prion Disease

Mn overload may trigger misfolding and aggregation of prion proteins [4, 50].

Animals and humans with prion disease have increased Mn levels in blood, brain, and liver [50].

However, to date, there is no evidence to say Mn overload causes prion disease [50].

15) Heart Damage

Too much manganese prevents the heart muscle from working and excessively expands blood vessels, leading to large blood pressure drops [11, 18].

16) Sense of Smell

In a study of 60 people, those exposed to airborne Mn had an impaired sense of smell [69].

17) Asthma

Mn belongs to the group of “transitional metals,” known inducers of occupational asthma. Nevertheless, only a single case of Mn-induced asthma has been well-documented so far [70].

18) Infant Mortality

High manganese levels in water have been linked to increased infant mortality [11].

Across North Carolina (population over 8 million), an increase in groundwater Mn was associated with a higher rate of county-level infant deaths [71].

In a study of over 26,000 babies in Bangladesh, infants exposed to higher water Mn were more likely to die during the first year of life [72].

19) Cancer and Liver Disease Mortality

In an observational study of 14 Chinese towns and 28 villages, the concentration of Mn in drinking water was associated with higher cancer rates and deaths [73].

Similarly, high drinking water but not airborne Mn levels were associated with higher cancer mortality in the state of North Carolina [74].

On the other hand, higher airborne levels of on-road Mn were linked with higher chronic liver disease deaths in North Carolina [75].

Who is More Likely to Develop Manganese Toxicity?

This is not an exhaustive list of people who may develop manganese toxicity; by the same token, not everyone on this list is in danger. If you suspect that you have been exposed to toxic levels of manganese, seek medical attention as soon as possible.

1) People with Occupational Mn Exposure

Unlike dietary exposure, inhaled manganese bypasses the bile, enters directly into the bloodstream, and can pass into the brain [5, 76].

Occupational exposure to manganese is a health hazard for miners, welders, ferroalloy workers, battery manufacturers, car mechanics, and people manufacturing glass and ceramics [49, 23].

Finally, Mn toxicity can occur in rural workers exposed to Mn-containing pesticides such as maneb [77].

2) Infants and Children

Younger children absorb proportionally more manganese. Newborns may absorb up to 40%, compared to roughly 3% in adults [11, 78].

Children also accumulate more manganese in the brain, since their blood-brain barrier is more permeable. In addition, their bile excretion capacity is lower [11].

Therefore, children may easily exceed the recommended dietary intake of manganese through a combination of sources [78].

The 2011-2012 National Health and Nutrition Examination Survey (NHANES) found higher Mn levels in children, the highest ones being in 1-year-olds [79].

Formula-Fed Babies

Cow’s milk-based and soy-based infant formulas are higher in Mn than human breast milk. Hence, formula-fed infants have higher Mn levels than in their breast milk-fed counterparts [39].

However, the body usually adapts by reducing gut absorption and increasing bile excretion. These mechanisms appear to work remarkably well, even in preterm infants [80].

3) Those on Parenteral Nutrition

Parenteral nutrition solutions (IV solutions) are routinely used in critically-ill and preterm infants who cannot tolerate oral feeding. These solutions can contribute to excessive Mn levels [80].

In newborns on total parenteral nutrition, Mn burden can be increased by 100-fold, compared to breastfed infants [5].

Mn toxicity has also been reported in adults receiving long-term parenteral nutrition. In such cases, manganese can build up in the brain and this can be detected before any symptoms arise. Stopping parenteral nutrition lowers Mn, allowing for it to be cleared from the brain [18, 78].

4) People with Liver Disease

Patients suffering from liver failure may be more likely to suffer from manganese toxicity since their main manganese removal system — the production and flow of bile — isn’t working [5].

Any existing liver damage may delay or decrease manganese elimination, in turn, increasing its blood levels [18].

People with liver cirrhosis have increased blood and brain manganese. One MRI imaging study also measured higher brain manganese in those with liver dysfunction and liver failure [81].

5) Iron-Deficient People

Iron has a strong influence on manganese balance. Both metals share transporters (transferrin and DMT1) [39]. Iron deficiency increases the production of these transporters and, inadvertently, the accumulation of Mn [5].

People with iron deficiency tend to have increased Mn body burden [5]. This is especially important for vegetarians, who already tend to have higher Mn levels [82].

Children breastfed for prolonged periods of time are more likely to have iron deficiency and may have higher blood Mn levels [83].

6) Women

According to the 2011 – 2012 NHANES study of US residents, women have significantly higher blood manganese levels than men [79].

Similar observations come from Canada, China, Korea, and Italy where women’s blood Mn levels are about 23 – 29% higher than men’s [84, 85, 86, 87].

Additionally, the 2011 – 2012 NHANES showed that pregnant women accumulate even higher Mn levels [79].

7) People with Neurological Diseases

Pre-existing neurological diseases have been associated with Mn toxicity, possibly because of the potential for combined effects [11].

8) Patients with Kidney Failure

Chronic kidney failure on dialysis may develop manganism even of their overall external exposure is low [88].

9) People with Rare Genetic Mutations

Rare mutations in SLC30A10 and SLC39A14 genes that cause inborn errors of manganese metabolism have only recently been discovered.

Mutations in these genes can cause high manganese blood levels (hypermanganesemia) and Mn buildup in the brain, resulting in movement disorders, liver disease, low iron, and high red blood cell mass (polycythemia) [89, 90].

Sources of Manganese

Food

People eating vegetarian and Western-type diets may have manganese intakes as high as 10.9 mg/day, which is the upper recommended limit from all sources [91].

Foods with the highest manganese content include [21, 5]:

• Legumes
• Rice
• Whole grains
• Nuts

This metal is also found in seafood, seeds, chocolate, tea, leafy green vegetables, spices, soybean, and some fruits such as pineapple, blueberries, and acai. However, all these foods are generally healthy and avoiding them is not a good idea [21, 2, 81].

Supplements

Various supplements and multivitamins often contain manganese. Most people already have a more than adequate intake of Mn, and should be careful when supplementing this metal. In fact, we recommend against supplementing unless your doctor or nutritionist has specifically recommended it.

Around the web, Mn is discussed as a histamine-lowering and dopamine-increasing agent, although there is little research to support this. In fact, according to one study, manganese may actually decrease dopamine in the long run [18, 92].

Manganese supplements can cause a short-term boost in energy, but people often report side effects such as emotional instability, mood issues, racing pulse, nausea, and fatigue.

People with liver problems may not be able to clear manganese as effectively as others.

As a plant-rich diet provides more than enough manganese for most of us, you may want to skip on Mn and opt for other supplements that can provide the same benefits but without the toxic effects.

Water, Air, and Other Sources

Overexposure to Mn can occur through diverse sources, including drinking water, industrial pollution, and mining wastes [16].

Approximately 5.2 % of the 2,167 wells surveyed across the USA exceeded the health benchmark of 300 µg/L Mn [11].

In the industry, the majority of Mn is used to make alloys and steel. Mn is also used in the manufacturing of dry cell batteries, fuel additives (MMT), fungicides (e.g., maneb and mancozeb), paint, adhesives, ceramics, cosmetics, leather, glass, and textiles [2, 5, 93].

Mn poisoning has been reported in drug-addicts using ephedrone, “Russian Cocktail,” and “Bazooka” [39, 94, 18].

Additionally, Mn is used as a contrast agent for MRI. However, Mn in MRI is not toxic owing to the infrequent exposure and fast elimination [5, 18].

Ways to Combat Manganese Toxicity

Do not attempt to combat manganese toxicity on your own. If you suspect that you have been exposed to toxic levels of manganese, seek medical attention as soon as possible and follow your doctor’s instructions.

Substances that help with manganese toxicity include antioxidants, plant extracts, chelating agents, precursors of glutathione (GSH), and synthetic compounds [21].

The following substances have shown promise against manganese toxicity in limited, low-quality clinical studies; there is currently insufficient evidence to support their use in this context, and they should never replace what your doctor prescribes. Remember to talk to your doctor before starting any new supplement or making significant changes to your diet.

1. Among the best ways to keep your Mn levels in check is to make sure you take adequate amounts of iron. High-iron diets appear to suppress Mn absorption [8].
2. Calcium can also help decrease manganese absorption [95].
3. Taurine improved the impairment of learning and memory caused by excessive Mn in rats [96].
4. Magnesium [97, 98, 99, 100]

No clinical evidence supports the approaches listed below to combat manganese toxicity. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.

1. Vitamin E and Trolox (a water-soluble analog of vitamin E) protected animal brains from the toxic effects of Mn [21].
2. Glutathione (GSH) (in cell studies) [21]
3. N-Acetylcysteine (NAC), a precursor of GSH (in cell studies) [101, 102]
4. Melatonin (in mice and cells) [103, 104]
5. Quercetin (in rats) [105, 106, 107]
6. Acai – although acai (Euterpe oleracea) on its own is a source of Mn, its extract protected rat brain cells from Mn-induced oxidative stress. These protective effects are likely due to the antioxidant and anti-inflammatory effects components in the berries [108]
7. Lemon balm (Melissa officinalis) extract (in mice) [109]
8. Milk thistle (Silymarin) (in rats) [110]
9. Lycopene (in rats) [111]
10. Curcumin (in cells) [112]
11. Chelating agents, such as calcium disodium salt of the chelator EDTA (in humans and rats) [21]