Dietary selenium and mercury intakes from fish consumption during pregnancy: Seychelles Child Development Study Nutrition Cohort 2.

Some health agencies have issued precautionary principle fish advisories to pregnant women based on the presence of methylmercury (MeHg) in fish that could possibly be harmful to the developing fetus. Fish, however, is a rich source of selenium (Se) and other nutrients essential for normal brain development. Selenium is also thought to have a key role in alleviating MeHg toxicity. We estimated the dietary Se and MeHg intakes and dietary Se:Hg molar ratios from the fish consumed in a high fish-eating pregnant cohort where no adverse associations of fish consumption and outcomes has been reported. We used dietary data collected as part of the Seychelles Child Development Study Nutrition Cohort 2 (n = 1419). In this cohort 98% of participants consumed fish, with an average intake of 106.2 g per day. Daily Se intakes from fish consumption were 61.6 µg/ d, within the range recommended during pregnancy. The mean dietary Se:Hg molar ratios was 6. These findings demonstrate that fish consumption exposes pregnant Seychellois women to Se in excess of MeHg. Based on these findings, fish consumption, especially fish with Se:Hg ratios above 1, may help pregnant women achieve optimum dietary Se intakes, which may protect against MeHg toxicity.

Anticholinergic medication: Related dry mouth and effects on the salivary glands.

OBJECTIVE: Salivary glands are among the most sensitive target organs of medications with anticholinergic (AC) properties, interrupting the neural stimulation of saliva secretion and reducing saliva flow. Hyposalivation results in dry mouth, leading to dental caries, intraoral infection, orofacial pain, problems with speaking and swallowing, and diminished oral health--related quality of life. Current understanding of the pharmacokinetics of AC medications and their effect on muscarinic receptors in the salivary glands were reviewed to assist clinicians in predicting salivary damage in patients with AC medication-induced dry mouth. STUDY DESIGN: We summarized the literature related to the mechanisms and properties of AC medications, anticholinergic adverse effects, and their effect on salivary function and management strategies to prevent oral health damage. RESULTS: Although a large number of studies reported on the frequencies of medication-induced dry mouth, we found very limited data on predicting individual susceptibility to AC medication--caused hyposalivation and no prospective clinical studies addressing this issue. CONCLUSION: Dry mouth is most frequently caused by medications with AC properties, which interrupt the neural stimulation of saliva secretion. Interdisciplinary care should guide pharmacotherapeutics and dental interventions should aim in preventing AC salivary adverse effects and reducing the oral health burden from AC medication-induced dry mouth.

Duration of effect of Biotène spray in patients with symptomatic dry mouth: A pilot study.

OBJECTIVES: The objective of this study was to assess the duration of effect of a single dose of Biotène Moisturizing Spray on xerostomia compared to water spray. STUDY DESIGN: This double-blind randomized controlled crossover trial compared the duration of effect of 2 agents on relieving xerostomia in adult patients recruited through convenience sampling. Following a xerostomia questionnaire, qualifying patients with an unstimulated whole saliva flow rate of ≤0.20 mL/min rated their baseline level of discomfort from oral dryness and received a single dose (3 sprays) of Biotène Moisturizing Spray or water (active control). Patients indicated their level of oral discomfort every 15 min and the precise time when relief ceased. After a minimum 48-h washout, patients repeated the exercise with the alternative product. RESULTS: The baseline severity of discomfort from oral dryness among qualifying patients was significantly related to their level of hyposalivation (P = .001). The mean duration of effect of Biotène Moisturizing Spray was 27 ± 25 min, which was not significantly different from that for water (26 ± 25 min; P = .88; n = 25). CONCLUSION: Biotène Moisturizing Spray and water spray had variable durations of effect averaging approximately 30 min. The results of this pilot study provide guidance regarding anticipated usage and dispensing needs for patients with objective xerostomia. ClinicalTrials.gov NCT03663231.

Maternal polymorphisms in glutathione-related genes are associated with maternal mercury concentrations and early child neurodevelopment in a population with a fish-rich diet.

INTRODUCTION: Glutathione (GSH) pathways play a key role the metabolism and elimination of the neurotoxicant methylmercury (MeHg). We hypothesized that maternal genetic variation linked to GSH pathways could influence MeHg concentrations in pregnant mothers and children and thereby also affect early life development. METHODS: The GCLM (rs41303970, C/T), GCLC (rs761142, T/G) and GSTP1 (rs1695, A/G) polymorphisms were genotyped in 1449 mothers in a prospective study of the Seychellois population with a diet rich in fish. Genotypes were analyzed in association with maternal hair and blood Hg, fetal blood Hg (cord blood Hg), as well as children's mental (MDI) and motor development (PDI; MDI and PDI assessed by Bayley Scales of Infant Development at 20 months). We also examined whether genotypes modified the association between Hg exposure and developmental outcomes. RESULTS: GCLC rs761142 TT homozygotes showed statistically higher mean maternal hair Hg (4.12 ppm) than G carriers (AG 3.73 and GG 3.52 ppm) (p = 0.037). For the combination of GCLC rs761142 and GCLM rs41303970, double homozygotes TT + CC showed higher hair Hg (4.40 ppm) than G + T carriers (3.44 ppm; p = 0.018). No associations were observed between GSTP1 rs1695 and maternal hair Hg or between any genotypes and maternal blood Hg or cord blood Hg. The maternal GSTP1 rs1695 rare allele (G) was associated with a lower MDI among children (ß = -1.48, p = 0.048). We also observed some interactions: increasing Hg in maternal and cord blood was associated with lower PDI among GCLC rs761142 TT carriers; and increasing Hg in hair was associated with lower MDI among GSTP1 rs1695 GG carriers. CONCLUSIONS: Maternal genetic variation in genes involved in GSH synthesis is statistically associated with Hg concentrations in maternal hair, but not in maternal or fetal blood. We observed interactions that suggest maternal GSH genetics may modify associations between MeHg exposure and neurodevelopmental outcomes.

Prenatal exposure to methylmercury and LCPUFA in relation to birth weight.

BACKGROUND: Epidemiologic studies have been inconclusive regarding the impact of coexposure to long chain polyunsaturated fatty acids (LCPUFA) and methylmercury (MeHg) from fish consumption during pregnancy on measures of fetal development. OBJECTIVES: We evaluated the association between birth weight and prenatal maternal LCPUFA status and MeHg exposure in the Republic of Seychelles. METHODS: We measured LCPUFA in maternal whole blood collected at 28 weeks of gestation and following delivery and MeHg in maternal hair obtained at delivery. There were 230 births with complete data on birth weight and covariates. Multiple linear regression models controlled for infant sex, gestational age, maternal age, smoking during pregnancy, intrapartum weight gain, prepregnancy body mass index, maternal socioeconomic status, parity, gestational diabetes, and alcohol use during pregnancy. RESULTS: The average birth weight was 3252 g (range 1654-4450) and the average gestational age was 39 weeks (range 34-41). Prenatal MeHg exposure and maternal LCPUFA status were not associated with birth weight. Infant sex and length of gestation were the only predictors, with male sex and increased gestational age consistently associated with greater birth weight. CONCLUSIONS: These findings do not support a relationship between prenatal exposure to LCPUFA and/or MeHg from fish consumption and birth weight.

Choline status and neurodevelopmental outcomes at 5 years of age in the Seychelles Child Development Nutrition Study.

Choline is an essential nutrient that is found in many food sources and plays a critical role in the development of the central nervous system. Animal studies have shown that choline status pre- and postnatally can have long-lasting effects on attention and memory; however, effects in human subjects have not been well studied. The aim of the present study was to examine the association between plasma concentrations of free choline and its related metabolites in children and their neurodevelopment in the Seychelles Child Development Nutrition Study, an ongoing longitudinal study assessing the development of children born to mothers with high fish consumption during pregnancy. Plasma concentrations of free choline, betaine, dimethylglycine (DMG), methionine and homocysteine and specific measures of neurodevelopment were measured in 210 children aged 5 years. The children's plasma free choline concentration (9·17 (sd 2·09) µmol/l) was moderately, but significantly, correlated with betaine (r 0·24; P= 0·0006), DMG (r 0·15; P= 0·03), methionine (r 0·24; P= 0·0005) and homocysteine (r 0·19; P= 0·006) concentrations. Adjusted multiple linear regression revealed that betaine concentrations were positively associated with Preschool Language Scale ­ total language scores (ß = 0·066; P= 0·04), but no other associations were evident. We found no indication that free choline concentration or its metabolites, within the normal physiological range, are associated with neurodevelopmental outcomes in children at 5 years of age. As there is considerable animal evidence suggesting that choline status during development is associated with cognitive outcome, the issue deserves further study in other cohorts.

The chemical forms of mercury in human hair: a study using X-ray absorption spectroscopy.

Human hair is frequently used as a bioindicator of mercury exposure. We have used X-ray absorption spectroscopy to examine the chemical forms of mercury in human hair samples taken from individuals with high fish consumption and concomitant exposure to methylmercury. The mercury is found to be predominantly methylmercury-cysteine or closely related species, comprising approximately 80% of the total mercury, with the remainder an inorganic thiolate-coordinated mercuric species. No appreciable role was found for selenium in coordinating mercury in hair.

The chemical nature of mercury in human brain following poisoning or environmental exposure.

Methylmercury is among the most potentially toxic species to which human populations are exposed, both at high levels through poisonings and at lower levels through consumption of fish and other seafood. However, the molecular mechanisms of methylmercury toxicity in humans remain poorly understood. We used synchrotron X-ray absorption spectroscopy (XAS) to study mercury chemical forms in human brain tissue. Individuals poisoned with high levels of methylmercury species showed elevated cortical selenium with significant proportions of nanoparticulate mercuric selenide plus some inorganic mercury and methylmercury bound to organic sulfur. Individuals with a lifetime of high fish consumption showed much lower levels of mercuric selenide and methylmercury cysteineate. Mercury exposure did not perturb organic selenium levels. These results elucidate a key detoxification pathway in the central nervous system and provide new insights into the appropriate methods for biological monitoring.