Methods for Individualized Determination of Methylmercury Elimination Rate and De-Methylation Status in Humans Following Fish Consumption

Abstract

Methylmercury (MeHg) exposure via fish in the diet remains a priority public health concern. Individual variation in response to a given MeHg exposure and the biotransformation of MeHg that follows complicate our understanding of this issue. MeHg elimination from the human body occurs slowly (elimination rate (kel) approximately 0.01 day(-1) or approximately 70 days half-life [t1/2]) and is a major determinant of the Hg body burden resulting from fish consumption. The underlying mechanisms that control MeHg elimination from the human body remain poorly understood. We describe here improved methods to obtain a MeHg elimination rate via longitudinal Hg analysis in hair using laser ablation-inductively coupled plasma-mass spectrometry. We measured MeHg elimination rates in eight individuals following the consumption of 3 fish meals in two 75-day trials separated by a 4-month washout period. In addition, since MeHg biotransformation to inorganic Hg (I-Hg) is associated with Hg excretion, we speciated Hg in feces samples to estimate individual MeHg de-methylation status. We observed a wide range of MeHg elimination rates between individuals and within individuals over time (kel = 0.0163-0.0054 day(-1); estimated t1/2 = 42.5-128.3 days). The ratio of MeHg and I-Hg in feces also varied widely among individuals. While the %I-Hg in feces was likely influenced by dental amalgams, findings with subjects who lacked amalgams suggest that faster MeHg elimination is associated with a higher %I-Hg in feces indicating more complete de-methylation. We anticipate these methods will contribute to future investigations of genetic and dietary factors that influence MeHg disposition in people.

Current progress on understanding the impact of mercury on human health

“…However, the half-life was estimated to be 64 ± 22 days when hair concentrations were used. Rand et al (2015) measured MeHg elimination rates in eight individuals following the consumption of 3 fish meals in two 75-day trials separated by a 4-month washout period in the United States and estimated that the half-life ranged from 42.5 to 128.3 days. They also found that the ratio of MeHg and inorganic g (I-Hg) in feces varied widely among individuals suggesting that faster MeHg elimination is associated with a higher %I-Hg in feces indicating a more complete de-methylation.…”

Monomethylmercury degradation by the human gut microbiota is stimulated by protein amendments

“…The authors suggested that other factors such as diet or the activity of the gut microbiota might explain the remaining variance. Rand et al (2016) reported a high degree of inter-individual variability in the MMHg biotransforma-tion kinetics during a feeding experiment and proposed that the gut microbiome can be a significant modulating factor for MMHg absorption. Later, Caito et al (2018) showed that individuals who received antibiotic therapy had lower MMHg elimination rates than untreated individuals, highlighting the importance of gut microbiota in the elimination of MMHg.…”

What Is Your Gut Telling You? Exploring the Role of the Microbiome in Gut–Brain Signaling

“…showed that people with more demethylated mercury in the stool also eliminated mercury faster from the body. 49 The study suggests a role for gut bacteria in mercury metabolism but does not prove a direct link between the microbiome and how quickly mercury is cleared from the body.…”

“…Rand found that two participants who were taking antibiotics eliminated methylmercury more slowly than the rest of the small cohort. 49 , 50 Next, he plans to investigate how the gut microbiome affects methylmercury metabolism in young children and pregnant women.…”