Low Blood Manganese Research Articles

Micronutrients in tinnitus: A National Health and Nutrition Examination Survey analysis

PurposeMicronutrients and their supplementation have been investigated in the development, severity, and treatment of tinnitus. This study aimed to evaluate associations between tinnitus parameters and levels of zinc, manganese, and vitamin B12. Materials and methodsThis retrospective study analyzed National Health and Nutrition Examination Survey 2011–2012 and 2015–2016 participants aged 20–69 who answered whether they had symptoms of tinnitus in the past year. Persons with tinnitus symptoms further reported how regularly they had symptoms and how disruptive symptoms were. Multivariable regressions accounting for age, gender, and race/ethnicity were used to evaluate the influence of low serum/blood levels of zinc, manganese, and vitamin B12 on tinnitus presence, regularity, and disruptiveness. ResultsThis study included 9439 participants, with 16.2% of the sample reporting tinnitus symptoms. In multivariable regression models, low blood manganese was associated with tinnitus regularity (proportional OR: 1.47 [95% CI: 1.06, 2.05], p = 0.0213) and tinnitus disruptiveness (proportional OR: 1.78 [95% CI: 1.08, 2.96], p = 0.0250), but not tinnitus presence (p = 0.4813). Low serum zinc and low serum vitamin B12 did not have statistically significant associations with analyzed tinnitus parameters. ConclusionsA nationally representative analysis found that low blood manganese was significantly associated with tinnitus regularity and disruptiveness, but found that serum zinc and vitamin B12 had no association with tinnitus parameters. These findings suggest that low micronutrient levels are unlikely to be contributors to tinnitus; however, the results suggest further research on manganese supplementation in patients with tinnitus may be merited.

Maternal Blood Manganese and Early Neurodevelopment: The Mothers and Children's Environmental Health (MOCEH) Study.

BackgroundManganese is an essential trace element and common component of water, soil, and air. Prenatal manganese exposure may affect fetal and infantile neurodevelopment, but reports on in utero manganese exposure and infant neurodevelopment are rare.ObjectiveThis study was conducted to investigate a relationship between maternal blood manganese level and neurodevelopment of infants at 6 months of age.MethodsData were obtained from the Mothers and Children’s Environmental Health (MOCEH) birth cohort study. The study population included 232 pairs of pregnant women and their infants at 6 months of age. Maternal blood manganese was measured at term, just before delivery. Mental and psychomotor development in infancy was assessed at 6 months of age using the Bayley Scales of Infant Development. The relationship between maternal blood manganese level and the mental and psychomotor development indexes (MDI and PDI) was estimated for manganese modeled as a linear and as a categorical variable and using penalized splines for nonlinear modeling.ResultsMean ± SD maternal blood manganese concentration was 22.5 ± 6.5 μg/L. After adjustment for potential confounders, blood manganese was used as a continuous variable in a linear and nonlinear model. Associations between maternal blood manganese and MDI and PDI scores followed an inverted U-shape dose–response curve after adjustment for potential confounders, with lower scores associated with both low and high blood concentrations [MDI: likelihood-ratio test (LRT) p = 0.075, PDI: LRT p = 0.038]. Associations of both outcomes with increasing blood manganese shifted from positive to negative at concentrations of 24–28 μg/L in this cohort of term, normal birth weight children.ConclusionAlthough no cut-off point has been established to define manganese toxicity, both high and low blood manganese levels may be associated with neurobehavioral function in infants.CitationChung SE, Cheong HK, Ha EH, Kim BN, Ha M, Kim Y, Hong YC, Park H, Oh SY. 2015. Maternal blood manganese and early neurodevelopment: the Mothers and Children’s Environmental Health (MOCEH) study. Environ Health Perspect 123:717–722; http://dx.doi.org/10.1289/ehp.1307865

Association of blood manganese level with diabetes and renal dysfunction: a cross-sectional study of the Korean general population

BackgroundThe purpose of this study was to evaluate the association between blood manganese levels and the prevalence of chronic diseases in the Korean population.MethodsThis was a cross-sectional study based on the Korean National Health and Nutrition Examination Survey (KNAHNES). The study included 3996 participants 20 years of age or older whose blood manganese levels had been measured. The participants were also evaluated for the presence of five chronic diseases: diabetes, renal dysfunction, hypertension, ischemic heart disease, and stroke.ResultsBlood manganese levels were significantly lower in the diabetes group compared with the non-diabetes group (1.26 ± 0.02 vs. 1.35 ± 0.01 μg/dL; p = 0.001) and the renal dysfunction group compared with those with normal renal function (1.28 ± 0.03 vs. 1.35 ± 0.01 μg/dL; p = 0.04). There was no significant association between blood manganese levels and the presence of ischemic heart disease or stroke. A multivariate logistic regression analysis adjusted for age, sex, and body mass index was performed; the odds ratio was 0.652 (95% CI: 0.46–0.92) for diabetes and 0.589 (95% CI: 0.39–0.88) for renal dysfunction when comparing the higher quartiles (Q2-4) with the lowest quartile (Q1) of blood manganese level. The prevalence of diabetes was 7.6% in Q1 and 5.3% in Q2-4 (p = 0.02). Similarly, the prevalence of renal dysfunction was 6.8% in Q1, compared with 4.6% in Q2-4 (p = 0.02).ConclusionThe prevalence of diabetes and renal dysfunction increased in participants with low blood manganese levels, suggesting that blood manganese may play a role in glucose homeostasis and renal function.

Anticonvulsant-induced changes in tissue manganese, zinc, copper, and iron concentrations in Wistar rats

Human epileptics have been reported to have low blood manganese (Mn) concentrations in comparison to nonepileptics, an observation that is important because Mn deficiency can increase seizure susceptibility in experimental animals. Factors that have been suggested to contribute to the low blood Mn levels in epileptics include anticonvulsant use, seizure-induced tissue redistribution of Mn, and genetics; in the present study, the first of these possibilities was tested. Wistar rats were fed semipurified diets containing diphenylhydantoin ([DPH] 3 g/kg diet), phenobarbital ([PB] 2 g/kg diet), or primidone ([PRIM] 3 g/kg diet) for 7 weeks, at which time they were killed and tissues collected and analyzed for Mn, zinc (Zn), copper (Cu), and iron (Fe) concentrations. In comparison to pair-fed rats, DPH- and PRIM-fed rats had significantly elevated liver Mn concentrations, while Mn concentrations in blood, brain, heart, and kidney were unaffected by anticonvulsant exposure. Changes in the concentrations of Zn, Cu, and Fe in specific tissues were also found. Overall, these findings suggest that the anticonvulsants tested do not lead to significant derangements in the metabolism of Mn.

Manganese and epilepsy: brain glutamine synthetase and liver arginase activities in genetically epilepsy prone and chronically seizured rats.

Low blood manganese (Mn2+) concentration is associated with epilepsy in humans and rats. The low Mn2+ concentration is attributed by some investigators to the seizure activity associated with the epilepsy, whereas others propose that the low Mn2+ concentration may be secondary to genetic mechanisms underlying the epilepsy. To begin to differentiate between these possibilities, Mn(2+)-binding enzymes of liver and brain (i.e., arginase and glutamine synthetase, respectively) were assayed in rats exposed to chronically induced seizures and in genetically epilepsy-prone rats (GEPRs). Chronic seizures caused a decrease in whole blood Mn2+ levels but did not affect brain Mn2+ concentrations. Arginase activity was increased in livers of rats with chronic seizure as compared with controls, but this difference was eliminated when Mn2+ was added to the assay. Brain glutamine synthetase activity was unaffected by chronic seizures, but the activity of this enzyme was significantly lower in GEPR brain than in control brain. Liver arginase activity tended to be lower in GEPRs, although the difference was not statistically significant. These data indicate that seizures affect liver arginase activity through changes in liver Mn2+ concentration, but GEPRs show abnormalities in Mn(2+)-dependent enzymes apparently independent of seizure activity.

Low blood manganese levels in Liverpool children with Perthes' disease.

The aetiology of Perthes' disease of the hip, avascular necrosis of the head of the femur, is unknown. Children with the disease have a generalised abnormality of growth. A similar disproportionate growth is found in chicks given a diet deficient in manganese. In Liverpool, which has the highest incidence of Perthes' disease reported anywhere in the world, children with the disease were shown to have lower blood manganese levels than controls. This is evidence that manganese deficiency around the time of birth may be a cause of Perthes' disease, but the results require confirmation.

Association of low blood manganese concentrations with epilepsy.

A comparison of hospitalized epileptic patients with matched normals showed that the mean whole blood manganese (Mn) concentration of the epileptic population was significantly lower than the mean of the normal population. The whole blood Mn concentration in the epileptics did not correlate either with seizure frequency or with anticonvulsant therapy. It was observed, however, that patients whose epilepsy was a result of trauma had significantly higher blood Mn concentrations than patients whose history was negative for trauma.