Written by Slawomir (“Swavak”) Gromadzki, MPH
Manganese is required for the normal development, growth, and function of human bodies. It serves as a cofactor for many important antioxidants and enzymes including superoxide dismutase (SOD), catalase, glutamine synthetase, or pyruvate decarboxylase. By being a cofactor for these vital enzymes manganese contributes to the following processes: Production of energy (ATP) in mitochondria, metabolism of fat, protein and carbohydrates, sex hormone production and normal reproduction, immune system function and responses, brain development and function, bone and connective tissue (joints, etc.) production, antioxidant protection, and normal digestion.
The highest concentrations of Manganese is found in bones (about 40% of the total body Manganese), liver, kidneys, pancreas as well as adrenal and pituitary glands.
Manganese can readily cross both the blood-brain and placental barriers.
Wheat germ, tofu, sweet potatoes, nuts, brown rice, lima beans, chickpeas, spinach, legumes, organic cooked soybean, brown rice, nuts, and whole grains are suggested to contain the highest levels of Manganese [>, >]. It is also found in seeds, leafy green vegetables, and some fruits such as pineapple, acai or blueberries [>, >, >].
Wherever manganese is found, iron is usually also present as these two work together preventing the excess and toxicity of each other.
Manganese deficiency may lead to the following possible signs: Decreased bone calcium, osteoporosis, bone deformities, increased susceptibility to seizures, feebleness, defective insulin production, birth defects, diminished reproduction, lower IQ, skin lesions, lower mental and psychomotor development scores, etc.
Manganese protects against oxidative stress and cell damage, as a part of important antioxidant enzymes [>].
A study conducted with 47 young women showed that oxidative stress was lower in women taking Manganese supplements [>].
A Manganese-containing enzyme, Manganese superoxide dismutase (MnSOD), is the principal antioxidant enzyme found in our body. It neutralizes toxic effects of dangerous free radicals such as the reactive oxygen species (ROS) in mitochondria [>, >]. MnSOD protects cells from various cancer-causing agents, such as radioactive and toxic chemicals, oxidative stress and inflammation [>]. Manganese deficiency reduces MnSOD activity, which leads to cell damage and dysfunction [>].
Another important enzyme that contains Manganese is catalase. This is an essential antioxidant enzyme that converts harmful hydrogen peroxide into beneficial oxygen and water, thereby reducing oxidative stress [>]. Hydrogen peroxide is made by immune cells to fight with pathogens but when the war is over this lethal weapon needs to be deactivated by antioxidants such as catalase as otherwise it will damage also healthy cells.
Several enzymes with vital roles in the brain, function only in the presence of Manganese [>].
Deficiency of Manganese is associated with lower IQ scores in children [>].
Girls that had higher prenatal exposure to Manganese performed better in cognitive function tests [>].
However, early-life high Manganese exposures can adversely affect children’s behaviour [>].
SEIZURES & EPILEPSY
Some studies suggest that the presence of neurological symptoms in epileptics may be linked to low brain Manganese [>].
Manganese-deficient diet produces seizures in rats indicating that Manganese is important for normal brain function [>].
Patients with epilepsy have low blood Manganese [>].
In rats, long-term dietary Manganese deficiency causes seizures [>].
BONE HEALTH & OSTEOPOROSIS
Manganese deficiency can cause developmental defects including malformation of bones [>] because Manganese is a component of various enzymes involved in cartilage and bone production [>]. It plays an essential role in incorporating calcium into the growing bones [>]. Manganese also supports normal balance of calcium helping fight calcium deficiency.
Manganese supplementation effectively reduced loss of bone mass in female rat models of postmenopausal osteoporosis [>].
DIABETES & METABOLIC SYNDROME
Manganese deficiency can impair insulin production [>].
Manganese supplementation improved insulin production and glucose tolerance in mice on a high-fat diet [>].
Diabetics had lower levels of Manganese in the blood and immune cells [>].
A study with 550 Chinese adults showed that those with higher Manganese intake had lower risk of metabolic syndrome [>].
Maternal Manganese deficiency increases the susceptibility of animal offspring to high-fat-diet-induced obesity, inflammation and high cholesterol [>].
Manganese supplementation can increase levels of adiponectin which reduces the susceptibility to metabolic syndrome and diabetes [>].
CARDIOVASCULAR HEALTH & CHOLESTEROL
Patients with hardening of the arteries (atherosclerosis) had lower levels of Manganese in the heart and blood vessels [>].
Men with a higher Manganese intake were less obese and had lower triglyceride (bad fat) levels [>].
Defective ovulation and testicular degeneration have been observed in Manganese-deficient animals [>].
Deficiency of Manganese can contribute to the development of depression [>].
Depressed patients were found to have low levels of the MnSOD, a Manganese-dependent SOD antioxidant enzyme [>].
Women with higher Manganese intake had a lower prevalence of depressive during pregnancy [>].
Autism is associated with increased glutamate in the brain [>]. Glutamine synthetase, an enzyme that converts glutamate into glutamine, requires and contains Manganese [>]. Therefore, deficiency of Manganese may lead to inability to convert glutamate to glutamine. As a result glutamate accumulates in the brain contributing to autism.
Adequate Manganese intake also helps prevent autism because MnSOD (Manganese superoxide dismutase) protects mitochondria in the brain from oxidative damage and dysfunction [>]. It is believed that mitochondrial dysfunction is another factor which contributes to autism.
Individuals with autism have low levels of Lactobacillus bacteria which depend on Manganese for antioxidant protection. In addition, Lactobacillus probiotic bacteria are known to increase levels of anti-anxiety hormones thus helping to treat anxiety, which is associated with autism [>].
A meta-analysis which reviewed 17 studies, showed that patients with Alzheimer’s disease tend to have significantly lower blood Manganese levels [>]. It is believed that Manganese deficiency may contribute to Alzheimer’s because it is required for proper mitochondrial function and prevention of glutamate accumulation in the brain and mitochondrial dysfunction. The increase of glutamate in the brain are associated with Alzheimer’s disease [>].
Administration of a Manganese peptide complex improved the appearance of several signs of skin photo-damage, such as hyperpigmentation [>].
PREMENSTRUAL SYNDROME (PMS)
Manganese deficiency was associated with increased mood swings and pain during PMS [>].
Women with PMS were found to have lower blood Manganese levels [>].
Manganese is required for the production and normal function of powerful antioxidant Manganese superoxide dismutase (MnSOD) which plays very important role in cancer prevention [>, >, >]. Many human cancers have low levels of MnSOD. A meta-analysis of 11 studies, found that patients with breast cancer have lower Manganese levels [>]. The level of MnSOD was reduced prior to the formation of cancer in mice [>].
NORMAL MANGANESE LEVELS
Normal ranges of Manganese for adults are believed to be the following: 4-15 μg/L in blood, 1-8 μg/L in urine and 0.4-0.85 μg/L in serum (the liquid component of blood) [>].
The estimated normal concentration of Manganese in the brain is set between 5.30 and 14 ng/mg protein [>].
The healthy concentration of Manganese is 1 mg/kg in the bone, 1.04 mg/kg in the pancreas, and 0.98 mg/kg in kidneys [>].
RECOMMANDED DAILY INTAKE
An adequate dietary intake is believed to be 2.3mg/day for men, and 1.8mg/day for women [>]. However, depending on the research and source, the values range from 2 to even 10mg of Manganese per day [>, >].
Infants up to 6 months: 3 mcg
7 to 12 months: 600 mcg
1 to 3 years: 1.2 mg
4 to 8 years: 1.5 mg
Boys 9 to 13 years: 2 mg
Boys 14 to 18 years: 2.2 mg
Girls 9 to 18 years: 1.6 mg
Men age 19 and older: 2.3 mg
Women 19 and older: 1.8 mg
Pregnant women age: 2 mg
Breastfeeding women: 2.6 mg
People on unrefined vegetarian diets may have higher Manganese intake of about 10mg per day, depending on the source of food and soil quality. Since 11mg per day seems to be the upper safe limit, it is probably better for vegans and vegetarians who are on a healthy unrefined diet to avoid long-term intake of additional sources of Manganese such as supplements containing more than 2mg of Manganese per daily dose.
On the other hand, it is rather the excess of an inhaled Manganese and not so much the excess of the ingested one that increases risk of toxicity. It is so because the Manganese we consume with food, water and supplements is under strict control. Only 3-5% of ingested Manganese is absorbed through the gut.
SAFE UPPER DAILY INTAKE
11mg/day is suggested as the safe upper limit for Manganese with no observed adverse side effects.
Officially in EU no SUL is set, but it is safer to not take more than 4mg of Manganese from supplements as often about 5-10mg can be obtained from food. Fore this reason various sources suggest that SUL for Manganese from all sources (including food, water and supplements) should be 11mg per day.
INTERACTIONS WITH OTHER MINERALS & VITAMINS
– Excess Manganese affects (reduces) iron absorption as intestines cannot differentiate between manganese and iron. For instance, high manganese intake from black and green tea often causes iron deficiency. While high Manganese can contribute to iron deficiency and anaemia, the same Manganese also helps the body use and store iron to some degree, which can help prevent anaemia (caused by low iron).
– On the other hand, too much iron will reduce Manganese absorption and levels. At the same time, iron helps prevent excess Manganese and toxicity.
– Manganese and calcium compete also for absorption.
Since it is believed that most people may already have more than an adequate intake of Manganese, we should be careful with how much of this mineral we take with supplements such as multivitamins and minerals, unless we are deficient.
Manganese-containing supplements may have 1 – 20 mg of Manganese per daily dose. Therefore, taking into consideration that the safe daily intake is 11mg and that most of us probably already have enough of this minerals, I would rather chose a supplement that have no or small amount of Manganese (1-2mg per daily dose). Supplements containing higher doses of 5-10mg should also be safe but only for shorter period of time.
People with liver problems (described below) should avoid Manganese supplementation and environmental exposures to avoid its accumulation and toxicity.
SIDE EFFECTS OF EXCESSIVE MANGANESE INTAKE
Manganese “toxicity” is possible, although it is rare. Most people are safe consuming and taking up to 11 milligrams of Manganese per day. However, certain individuals, especially those with liver problems, aren’t able to flush excess Manganese from the body properly leading to its accumulation and toxicity.
Manganese can readily cross both the blood-brain barrier [>] and when in balance, it helps our body to fight oxidative stress and give other numerous benefits, but when we have too much Manganese it accumulates itself in mitochondria and increases the production of reactive oxygen species [>, >].
Excess Manganese also tends to deplete levels of glutathione, body’s strongest antioxidant. It also increases the release of several inflammatory molecules including prostaglandins. These can cause brain inflammation and neuron loss [>].
Excessive exposure to Manganese has many negative effects, especially on the brain, fertility, and development [>]. In animal studies, Manganese-containing compounds increase lung inflammation and cause lung damage [>]. Patients suffering from generalized anxiety have elevated Manganese levels [>].
Manganese in excess can be toxic to the brain. Its toxicity has been predominantly observed in occupational settings, following the accidental ingestion of large quantities of this metal, or more often after inhalation of high levels, where this metal can enter the brain directly through the nose [>, >]. Welders chronically exposed to Manganese had measurable brain volume reductions correlated with cognitive and motor deficits [>]. Manganese administration can lead to anxiety-like or compulsive-like behaviours [>], nervousness, irritability, and aggression [>]. Excess Manganese depletes dopamine and may lead to motor syndrome similar to symptoms of Parkinson’s disease [>].
Manganese in excess can cause neuro-developmental problems in children [>]. Children who ingested high Manganese in the drinking water for three years or more, performed more poorly in school [>]. Studies in children and adolescents show that higher exposure to Manganese is associated with inattention and hyperactive behaviour [>, >]. Increased symptoms of ADHD may be associated with increased blood Manganese levels [>].
FACTORS ASSOCIATED WITH EXCESSIVE MANGANESE LEVELS
EXCESSIVE DIETARY INTAKE
Overexposure to Manganese can occur through supplements, drinking water and infant milk formulas. However, Manganese ingested with food, water or supplements is under strict control as only 3-5% of it is absorbed through the intestines [>]. Cow milk-based and soy-based infant formulas have higher Manganese concentration than human milk [>], but if there is too much Manganese the body usually reduces its absorption and increases bile excretion of this metal. These mechanisms are known to be effective also in infants [>].
What seems to pose higher risk of toxicity than food and supplements is the inhaled Manganese as it can bypass bile excretion and enter the brain directly across the blood-brain barrier [>]. Exposure to Manganese is a health hazard for miners, welders, ferro-alloy workers, mechanics [>, >], or manufactures of batteries, glass and ceramics [>]. Manganese poisoning has been also reported in individuals addicted to ephedrone and ‘Bazooka’.
People with liver failure have higher risk of manganese toxicity because excess Manganese is excreted from the body largely through the bile. Because bile production is impaired in those with certain liver problems too much Manganese may accumulate in the body [>]. That is why people with cirrhosis, liver dysfunction and liver failure have increased blood and brain Manganese levels [>].
Iron has a strong influence on Manganese levels because both minerals share the same transporters. Iron deficiency increases the number of these transporters leading to the accumulation of Manganese [>]. It is believed that vegetarians are at higher risk of this problem as they are often lower in iron and consume foods higher in Manganese [>].
WOMEN HAVE MORE MANGANESE THAN MEN
Blood Manganese levels of Chinese women are about 30% higher than in men [>]. Korean and Italian women have 25% higher and Canadian women have about 23% higher levels than men [>]. In US women were found to have significantly higher blood Manganese levels than men [>]. Pregnant women seem to accumulate higher levels of Manganese [>].
Patients subjected to micro-dialysis due to chronic kidney failure may develop manganism in the absence of external exposure [>].
HOW TO PREVENT MANGANESE TOXICITY
The following help prevent Manganese toxicity:
– If your water is contaminated with too much of Manganese, buy a water distiller (it removes all heavy metals and toxins and inorganic calcium from water) and drink only distilled water with added pinch of a sea or pink salt (read more >).
– Iron: The most effective way to keep Manganese levels in check is to make sure your dietary of iron is adequate as iron suppress Manganese absorption [>, >]. However, you must be careful to not have too much iron (especially from meat products and supplements) as in excess it is known to cause oxidative damage. The best and safe sources of iron are chlorella, spirulina, black molasses, moringa, wheat grass and other super foods. Occasionally you may also have supplemental iron such as iron bisglycinate, especially when you are deficient. Alpha lipoic acid helps prevent oxidative damage caused by excess iron intake.
– Magnesium reduced manganese toxicity in rats [>] while magnesium deficiency increased levels of Manganese [>, >]. On the other hand, the increased Manganese intake reduced the levels of magnesium [>].
– Vitamin E protected brains of rodents from the toxic effects of Manganese [>].
– Taurine improved the impairment of learning and memory caused by excessive Manganese levels in rats [>].
– Quercetin prevented Manganese-induced motor deficits and brain damage [>] and reversed Manganese-induced decrease in reproductive hormones (luteinizing hormone, follicle-stimulating hormone, and testosterone) while increasing sperm quality and quantity in rats [>].
– Lemon Balm (Melissa officinalis) extract reduced Manganese-induced brain oxidative damage in mice [>].
– Silymarin found in Milk Thistle (Silybum marianum) protected brain cells and prevented Manganese-induced oxidative damage in brains, livers, and kidneys of rats [>].
– Lycopene (high especially in tomatoes) reduced the neurotoxicity of Manganese in rats [>].
– Glutathione and N-Acetyl cysteine (NAC), a precursor of Glutathione, can decrease the toxicity of Manganese [>].
– Melatonin (made in the body from serotonin) significantly alleviates Manganese-induced neuronal loss and motor dysfunction in mice [>].
TESTING MANGANESE LEVELS
Studies do not recommend using Manganese levels in blood to test for Manganese exposure [>, >] because the half-life of Manganese in the blood is too short (only about 2 hours) [>]. Also urine or saliva tests are not regarded as reliable. Studies of Manganese toxicity often use hair Manganese content [>, >]. A relatively long half-life (about 8 – 9 years in humans) of Manganese in the bones, makes bone Manganese an ideal indicator to assess the body burden of Manganese [>].
Of the ingested Manganese, only 1 – 5% is absorbed into the blood. This level is strictly controlled based on the concentration of this metal in the diet. It means that our body absorbs less Manganese into the blood when more of it has been ingested [>].
Excess Manganese is normally transported to the liver where it is incorporated into the bile and then passed through the intestines to be excreted. Bile excretion accounts for about 80% of excess Manganese elimination [>]. Therefore, for proper elimination of excess Manganese, make sure your liver is healthy and functions normally. Small amounts of Manganese can also be removed from the body with urine and sweat.
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