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High oral exposure and biological vulnerabilities may put formula-fed infants at risk for manganese-induced neurotoxicity.We sought to characterize manganese concentrations in public drinking water and prepared infant formulas commonly purchased in the United States, integrate information from these sources into a health risk assessment specific to formula-fed infants, and examine whether households that receive water with elevated manganese concentrations avoid or treat the water, which has implications for formula preparation.Manganese was measured in 27 infant formulas and nearly all Minnesota community public water systems (CPWS). The risk assessment produced central tendency and upper-end exposure estimates that were compared to a neonatal animal-based health reference dose (RfD) and considered possible differences in bioavailability. A survey study assessed esthetic concerns, treatment, and use of water in a Twin Cities community with various levels of manganese in drinking water.Ten percent of CPWSs were estimated to exceed the EPA health advisory level ofExcessive exposure to manganese early in life can have long-lasting neurological impacts. This assessment underscores the potential for manganese overexposure in formula-fed infants. U.S. agencies that regulate formula and drinking water must work collaboratively to assess and mitigate potential risks. https://doi.org/10.1289/EHP7901.

As a newly identified manganese transport protein, ZIP14 is highly expressed in the small intestine and liver, which are the two principal organs involved in regulating systemic manganese homeostasis. Loss of ZIP14 function leads to manganese overload in both humans and mice. Excess manganese in the body primarily affects the central nervous system, resulting in irreversible neurological disorders. Therefore, to prevent the onset of brain manganese accumulation becomes critical. In this study, we used Zip14−/− mice as a model for ZIP14 deficiency and discovered that these mice were born without manganese loading in the brain, but started to hyper-accumulate manganese within 3 weeks after birth. We demonstrated that decreasing manganese intake in Zip14−/− mice was effective in preventing manganese overload that typically occurs in these animals. Our results provide important insight into future studies that are targeted to reduce the onset of manganese accumulation associated with ZIP14 dysfunction in humans.

About 10 heavy elements were determined in 90 samples of baby food collected from Spanish and Serbian market. The results indicated that iron, manganese and copper were most frequently detected. Tin was the predominant toxic element in both Spanish and Serbian samples, with occurrence frequencies of 12.5% and 10.0%, respectively. Element intake for Spanish and Serbian infants were estimated and compared with the recommended reference values, for the majority of elements being lower than one. However, iron and manganese intake through consumption of infant/follow-on formulas were assessed to be higher than the respective daily intakes. Particular attention should be paid to the exposure of infants who consume porridges made of vegetables and fish or chicken, because they may ingest certain elements, particularly arsenic and lead, at levels that exceed the reference toxicological values. Principal component analysis (PCA) was applied to classify and distinguish the different types of baby food.

The purpose of this study was to estimate the daily manganese (Mn) intake of Korean children. This study was done using a three-day dietary intake survey of 257 Korean children (boys 123; girls 134). The Mn intake values were calculated based on a database that provides the Mn content of the frequently consumed Korean foods, alongside the food composition table provided by the Korean National Rural Living Science Institute. The average age, height, weight and body mass index of our subjects were 11.9 years, 155.4 cm, 48.9 kg and 20.2 kg/m2 in boys and 11.9 years, 154.1 cm, 43.5 kg and 18.3 kg/m2 in girls. The average daily energy intakes were 2,249.2 kcal in boys and 2,044.5 kcal in girls. Boys consumed significantly more Mn than girls, based on intake estimates of 4,585.3 µg (117.6% of adequate intake) and 4,029.3 µg (117.1% of adequate intake), respectively (P < 0.001). Boys had a Mn intake of 2,041.1 µg per 1,000 kcal of energy consumption, whereas for girls this was at 1,983.9 µg per 1,000 kcal. Neither group exceeded the tolerable upper intake level for Mn. The major food groups which contributed to Mn intake in our subjects were cereals (50.8%), vegetables (21.0%), seasonings (8.9%), and pulses (7.7%). Notably, boys derived a higher Mn intake through cereals and vegetable than did girls (P < 0.001, P < 0.05). The key food sources of Mn, in descending order, were rice, soybean curd, kimchi, black rice and cereals. We propose that the results of our study may be used as a basis for follow-up studies that examine the Mn intake of children.

This study was peformed to estimate manganese intake and the major food source of manganese in Korean adults. The 354 subjects aged over 20 years were measured anthropometrics and dietary intake using 24-hour recall method. Daily intake and the major food sources of manganese were calculated using manganese database of food composition tables in Korea, USA and Japan. The average age, height, weight and BMI were 54.6years, 165.7cm, 67.2kg and for men and 53.8 years, 153.7cm, 59.1kg and for women, respectively. The daily energy and manganese intake of men were significantly higher than those of women (1740.9 kcal vs. 1432.6 kcal; p

Daily intakes of iron (Fe), copper (Cu), zinc (Zn) and manganese (Mn) from whole-day food rations composed by dieticians and collected in hospital canteens in Krakow, Lodz, Olsztyn and Poznan, Poland, in the winters of 1993/94, 1995 and 1996, were determined by atomic absorption spectrometry. The average intake of Fe, 14 mg x day(-1), was satisfactory for both women and men; 13 mg Zn fulfilled the safe level for women (taken as the recommended minimum level to meet the needs of 97.5% of the population) but it was too low for men, and 1.3 mg Cu corresponded to 65-72% of the safe level set for this microelement in Poland. There is no recommended level set in Poland for Mn, but compared with recommended levels in Germany and the USA, the determined daily Mn intake equal to 3.7 mg should be sufficient. Statistical analysis confirmed higher amounts of Zn and Mn in diets collected in Krakow, higher Cu content in diets from 1996, and lower Mn content in food collected in 1995.

The estimation of the daily oral intake of manganese (Mn) can vary significantly with the method used. This study aims to compare two different approaches: the use of dietary records along with tables of the Mn contents of different foods and the parallel collection of identical aliquots which are analyzed for Mn. Dietary samples and information were collected during a 3-day dietary assessment with five participants. The average daily oral intake of Mn estimated from the dietary records and tables of Mn contents was 3.52 mg/day (S.D. = 1.9), which corresponds to an exposure dose (ED) of 50.27 microg/kg body wt./day (S.D. = 26.2). With a parallel collection of identical aliquots and chemical analysis, the average intake was 2.88 mg/day (S.D. = 0.64) for an ED of 41.18 microg/kg body wt./day (S.D. = 8.9). Thus, the use of tables gives an estimated oral dose 22% higher than the more accurate direct chemical analysis.

Manganese is classified as an essential trace element. It is present in significant amounts in tea. Tea accounts for about 40% of fluid intake in the United Kingdom, and world wide is the second most commonly consumed beverage. There has been a lot of work done looking at the mineral and trace element content of teas in view of this large population intake. Manganese has the potential for toxicity if taken in excess by routes that avoid its normal homeostatic mechanisms. As regards oral intake of manganese, there have been two case reports of potential manganese toxicity. These cases had disease states that may have affected the individuals manganese handling. This review looks at the potential impact of tea consumption on manganese intake and the difficulties around assessing manganese levels and status.

Five native hazelnut varieties from Turkey, namely, prime quality Tombul variety, and second grade quality Yassi Badem, Sivri, Karafindik, and Ham varieties were examined for their lipid characteristics (triacylglycerol. tocopherol, tocotrienol, phytosterol, and phytostanol composition) and 12 essential minerals. Among 12 triacylglycerols separated in all hazelnut varieties, 000 (61.0-77.5%) and OOL (10.5-22.8%) were the main components (where O = oleoyl and L = linoleoyl). Seven tocol isoforms (four tocopherols and three tocotrienols), seven phytosterols, as well as cholesterol, and one phytostanol were positively identified and quantified: among these, of alpha-tocopherol and beta-sitosterol were predominant in all hazelnut oils. Hazelnut varieties served as an excellent source of copper and manganese. Consumption of the recommended daily amount of 42.5 g of hazelnut from different varieties provides 44.4-83.6% of copper and 40.1-448% of recommended manganese intake for adults. These results Suggest that second grade quality hazelnut varieties were as good sources Of functional lipids and essential minerals as was prime quality Tombul hazelnut, With some exceptions (P < 0.05). (C) 2008 Elsevier Ltd. All rights reserved.

Although it has been proposed that trace minerals have anti-oxidative functions and are related to the control of blood pressure, only a limited number of studies directly address the issue. Thus, the purpose of our study was to assess the intake of copper and manganese, which are trace minerals, and to clarify their relation to blood pressure. In a cross-sectional study, the blood pressure of 640 normotensive adults, from 19 to 69 year-old (320 males and 320 females), was measured, and its correlation with the intake of copper and manganese was assessed using a 24-hour dietary recall method. The average value of the blood pressure was 126.4/80.2 mmHg for the males and 117.8/75.8 mmHg for the females. The daily copper intake was 1.3 mg/day for the males and 1.2 mg/day for the females. For manganese, the daily intake was 4.2 mg/day for the males and 4.1 mg/day for the females. Although the copper intake of all subjects showed a positive correlation with the systolic and diastolic blood pressures, there was no significant correlation when the potential confounding factors were adjusted. The manganese intake of the male subjects had a significantly negative correlation with the systolic blood pressure after adjusting for gender, age, body mass index, and energy intake. In conclusion, the daily manganese intake of the normotensitve adults showed a significantly negative correlation with the systolic blood pressure indicating a possibility of a positive effect of manganese on blood pressure.

To identify important risk factors of motor neuron disease (MND) in a focus (Hohara) on the Kii peninsula of Japan, 24-h dietary duplicates, rice, drinking water, and soils were analysed for metals in Hohara and control areas. The manganese content in 24-h food in Hohara was significantly (P0.01) higher than that in the remote control areas. The incidence of MND in Hohara was well explained by the two parameters, manganese content in food and the magnesium concentration in drinking water (r2 = 0.99), suggesting that MND in this focus can be understood as a result of excess intake of manganese from food coupled with low intake of magnesium from drinking water. The reference to epidemiology and occupational medicine supports this conclusion. The crude annual MND incidence per 10(5) population in other foci may be predicted as MND = e alpha ln[beta(Mn in food)gamma/(Mg in water)], where alpha is 5.389-5.748, beta is 0.170-0.166, and gamma is 1.239-1.226.

Chen and Copes raise some interesting issues regarding our article (Bouchard et al. 2011). In our study we investigated the change in IQ scores with respect to different exposure metrics for manganese. One of these metrics was home tap water manganese concentration, which was strongly associated with IQ deficits. Chen and Copes indicate that they consider it inappropriate to include in this analysis children who did not drink tap water at home. Second, they note that even for children in the highest quintile of water manganese concentration, the intake of manganese from water ingestion is below the recommended dietary manganese intake (Institute of Medicine 2001). In response to their first point, it is important to consider that children who do not drink tap water are still exposed through the consumption of many foods and drinks prepared with tap water. In addition, and perhaps most important, children might be exposed by inhalation of aerosols containing manganese when showering (Elsner and Spangler 2005). If this represents a significant source of exposure, which is unclear (Aschner 2006; Spangler and Elsner 2006), inhalation of aerosols could be responsible for inducing neurotoxic effects. Indeed, inhaled manganese is delivered to the brain much more efficiently than ingested manganese, because it bypasses normal homeostatic mechanisms. Third, Chen and Copes make the point that because dietary intake of manganese intake is much higher than the amount ingested from water, the decrease in IQ is more likely due to intake of manganese from water and food sources collectively, rather than from water alone. The intake of manganese from water consumption was indeed very small compared with dietary intake (medians, 8 and 2,335 μg/kg/month, respectively), but we found no evidence that dietary manganese is related to cognitive abilities. As we reported in our article (Bouchard et al. 2011), dietary manganese intake, assessed with a food frequency questionnaire, was not associated with IQ and did change the point estimates for water manganese concentration when included in the regression model. We believe that the interpretations that assimilate manganese present in water to dietary manganese have had the effect of dismissing the potential risks of this source of exposure, thus slowing research into this question. Little is known about the absorption and retention of manganese from food versus water, or about inhalation of aerosols in showers. Although more research is necessary to understand the mechanisms by which manganese present in water might be neurotoxic for children, we believe that our findings offer strong support for this hypothesis. Because manganese levels associated with significant cognitive deficits in our study are common in groundwater, this problem could have a great public health importance. For instance, 11% of domestic wells have manganese concentrations > 140 μg/L in the United States (U.S. Geological Survey 2009). We agree that additional studies, ideally with a prospective design, are necessary. Finally, a valid biomarker of manganese exposure would greatly advance our understanding of this metal’s toxic effects. We used hair, notably because its collection is much less invasive than blood sampling. Chen and Copes rightly point out the limitations of hair as a biomarker, and research should explore new biomarkers. For instance, in a small study, saliva manganese levels were significantly higher in welders than in nonexposed subjects, and levels increased in welders with the more years of exposure (Wang et al. 2008). Also in that study, saliva manganese concentrations correlated with serum concentrations. Saliva is less invasive to collect than blood and less prone to external contamination than hair; thus, it might be a useful biomarker.

The purpose of this study was to estimate daily intake of manganese in Korean adults. Manganese intake was estimated through the use of the database of manganese content in frequently consumed Korean foods after first conducting anthropometric measurement and a survey on dietary intake with 354 Korean adults. Average age, height, weight and body mass index were 54.6 years, 165.7 cm, 67.2 kg and 24.5 kg/m(2) in males and 53.8 years, 153.7 cm, 59.1 kg and 24.9 kg/m(2) in females. The daily energy intakes of subjects were 1740.1 kcal in males and 1432.6 kcal in females. Male and female subjects recorded, respectively, 5.2 mg and 4.1 mg in manganese intake indicating that the male subjects consume more manganese (p0.001). And they posted, respectively, 3.0 mg and 2.9 mg in manganese intake per 1000 kcal of energy consumption; it turned out that there was no significant difference. Daily manganese intake of both males and females posted, respectively, 148.8% and 135.2% of the adequate intake, and 8 males and 3 females surpassed the tolerable upper intake level. It is suggested that the study for accurate determination of manganese consumption needs to be more diversified based on the database of manganese content in Korean foods.

Two groups of adult male Sprague-Dawley rats were treated with manganese added to the drinking water in concentrations of 0.1 and 5.0 mg Mn 2+ /ml. Age-matched controls received distilled demineralized water. Spontaneous motor activity, measured in 60-min weekly sessions during 8 months, showed a significant increase during the 1 st month. Further exposure did not affect the motor activity to 6 months. But, on months 7 and 8 a significant reduction was observed compared with controls. Both hyper- and hypoactivity were not dose-dependent as the results obtained in both groups of manganese-exposed rats were similar. These findings should make health authorities aware of the potential involvement of low doses of manganese in the development of early behavioral problems long before the irreversible neurologic damage is established.

Twenty-eight adult men and women participated in a year-long study designed to determine accurately the nutrient intake of adults who lived at home and consumed self-selected diets. During four metabolic balance periods, 7 days each, corresponding to the seasons (spring, summer, fall, winter), duplicates of the diet, and all urine and feces were collected. Daily mean intakes for zinc and copper were 9.9 and 1.2 mg, respectively. These levels were less than the recommended daily intakes of 15 mg for zinc and 2 to 3 mg for copper. In contrast, the mean dietary intake of manganese was 3.0 mg/day which is within the suggested safe and adequate range of 2.5 to 5.0 mg. Metabolic balances were negative for all three elements possibly due to a reduction in food intake during the collection periods compared to the noncollection intervals. The collection of the duplicate diets apparently influenced the food intake during the collection weeks.

Metallic ions in the blood and the urine of the patient suffered from so-called “Minamata Disease” which is an encephalopathia of unknown cause were examined.Quantitative analysis of the manganese was investigated in patients as well as in cats which showed similar symptoms to the human. Furthermore, fish and shellfish obtained from the bay in the district of Minamata were also exmined.It was found that the amount of manganese was increased in the blood and urine of patients and cats, in liver of cats, in fish and in shellfish as compared to the control group s. It might be considered from the above results that the pathogenesis of “Minamata Disease” may be related to manganese intake by human and animals through fish and shellfish taken from the sea along this particular parts of the sea-coast.

The relationship between manganese superoxide dismutase (MnSOD) activity and manganese intake appears to be both tissue and species specific. In manganese deficient mice and chickens the activity of MnSOD in the liver is reduced (De Rosa et al., 1980). In manganese deficient rats the activity of MnSOD decreases in the heart and kidney (Paynter, 1980a) but may only change in the liver after prolonged deficiency throughout gestation and the early post-natal period (Zidenberg-Cherr et al., 1983). Post-natal changes in the activity of MnSOD in sheep have been related to an increased susceptibility to peroxidation in some tissues (Paynter and Caple, 1984). The aim of this study was to determine the effects of both low and high intakes of manganese on the activity of MnSOD in tissues of sheep.

Manganese (Mn) status was determined in 24 infants exclusively fed either human milk (n = 8) or formula (n = 16) from birth to 3 months. Mn intakes were estimated from test weighings , dietary records, and direct analyses of human milk and formula via graphite furnace atomic absorption spectrophotometry. Mean human milk Mn concentrations significantly decreased (p less than 0.05) with the progression of lactation, from 6.6 micrograms/L during the 1st month of lactation, to 3.5 micrograms/L by the 3rd month of lactation. Infant formulas were observed to contain considerably higher levels of Mn (70.0 to 1289.0 micrograms/L) than either human milk (means = 4.9 micrograms/L) or cows' milk (means 25.2 micrograms/L). At 3 months, human milk-fed infants consumed a smaller volume of milk (689.0 ml) than formula-fed infants (894.0 ml), and also received significantly less Mn (0.42 micrograms/kg/day) than formula-fed infants (183.22 micrograms/kg/day). Mean sera Mn concentrations of infants receiving human milk or formula were similar, with mean values of 4.4 and 4.7 micrograms/L, respectively. Manganese intakes of human milk-fed infants were found to be linearly correlated (r = 0.78) with the respective serum Mn concentration at 3 months of age.