Manganese (Mn) is the 12th most abundant element on the earth. Many are unaware that this metal is used in the production of fungicides, batteries, fuel additives, paint, a variety of important alloys, steel, drink cans and glass. It is among the country’s mineral reserves.
Manganese is essential to human health as it is a co-factor in human enzyme functions and is required for normal human development, the regulation of blood sugar and vitamins, and the maintenance of nerve and immune cell functions.
This article was inspired by the report of tests on samples collected from the water supply in the Kuala Koh area in Kelantan, which showed a manganese level of 2.53 milligramme per litre, which is 2,500% above the normal level.
This raised the issue of manganese poisoning as a possible contributing factor in the unexplained Bateq deaths in July 2019. Knowledge about manganese poisoning has increased markedly in the last two decades, compared to before when it was caused mainly by occupational exposure among welders and smelters.
It is now known that apart from environmental sources of manganese, human activities can expose individuals to additional sources of manganese, e.g. in fungicides, water purification agents and medical imaging contrast agents.
Manganese from these various sources ultimately end up in the water supply and makes its way into ground and surface waters. The highest concentration of manganese is found in groundwater and surface water near mining operations.
Manganese gets into the body through oral (eating) and inhalation (breathing) exposure. Intravenous injection of illegal narcotics containing manganese is another route of exposure. While the half-life of manganese in the blood is short, it has a long half-life in tissues.
Recent data suggest that there is significant manganese accumulation in human bone with a half-life of about eight to nine years, meaning that it will only be completely eliminated in 16 to 18 years after the initial exposure.
Manganese is eliminated through the liver and faeces, with limited urinary excretion. It can accumulate rapidly in some brain structures where its elimination rate is reported to be slower than from either the liver or kidney.
Manganese exposure and poisoning can occur in a variety of situations. The various factors that impact manganese poisoning include age, gender, ethnicity, genetics and pre-existing medical conditions. The consumption of water or food contaminated with high manganese levels has serious consequences.
High manganese levels in drinking water in Canada have been reported to be associated with high manganese levels in hair samples of school-age children with increased hyperactivity, impaired cognitive development and decreased intelligence quotients (IQs).
Drinking water contaminated with manganese levels four to five times the World Health Organisation (WHO) standard, has been reported to be inversely associated with achievements in mathematics in Bangladeshi students – the higher the level, the lower the maths score.
Italian school-age children living near an iron alloy factory, which exposed them to high soil levels of manganese, have been found to have impaired motor coordination, hand dexterity and smell identification. Babies who drink infant formulas may consume more manganese than recommended.
There are reports that the hair samples of babies who consume infant formulas have higher levels of manganese than breastfed babies; and suggestions that the higher dietary manganese intake is associated with the risk of developing attention deficit hyperactivity disorder (ADHD).
Illicit intravenous drug abusers in several countries have been reported to have high manganese levels in blood and urine, together with impaired speech, slowness of movement (bradykinesia) and lack of muscle control or co-ordination of voluntary movements (ataxia).
Some of these symptoms continued to worsen even after cessation of drug abuse.
The features of manganese poisoning may appear slowly over months and years.
There is much evidence that manganese exposure can lead to a permanent neurological disorder termed manganism, with features that include irritability, aggressiveness, hallucinations, tremors, difficulty walking and facial muscle spasms. Some studies report difficulty with concentration and memory problems.
Manganese exposure can cause an inflammatory response in the lungs, which can lead to impaired lung function and increased risk of infection, like bronchitis and pneumonia.
Liver function can also be affected by excess manganese exposure, which increases the risk of excessive accumulation of manganese in the brain, leading to neurodegeneration – a condition termed manganese hepatic encephalopathy.
Excess manganese exposure can also lead to decreased libido, impotence and sexual dysfunction, with an indirect impact on reproductive outcomes. There is suggestion that excess manganese has a significant effect on heart function with inhibition of heart contraction, low blood pressure and dilation of blood vessels.
The mechanism of cardiac toxicity is not known. Increased manganese levels in water sources have been reported to be associated with an increase in infant mortality in North Carolina in the United States and in Bangladesh.
The challenge in the management of manganese poisoning is the lack of an effective biomarker that is useful in diagnosis, especially in the early stages. Without such a biomarker, risk assessment is problematic.
Although current approaches, i.e. manganese/iron ratio and manganese levels in hair and toenails, appear promising, more needs to be done. The primary strategy in managing manganese poisoning is removal from the source of exposure.
If the poisoning is life-threatening, supportive treatment is necessary. The body’s manganese levels can be reduced by chelation therapies, and possibly, iron supplementation.
Chelation with ethylenediaminetetraacetic acid (EDTA) has been shown to increase urinary excretion of manganese and decrease manganese blood levels, but it does not improve symptoms significantly.
A study with iron supplementation, in addition to chelation, has shown improvement of neurological symptoms, suggesting that iron supplementation may help reduce blood manganese levels and lower the body’s manganese burden.
Para-aminosalicylic acid (PAS), which is used in the treatment of tuberculosis, has been reported to show promise in the treatment of severe manganese poisoning.
As manganese neurotoxicities are usually irreversible and will continue to progress despite removal from exposure, the answer has to lie in prevention. This means ensuring that human activities do not contaminate water, air and food with manganese.