Editor’s Highlight: Variation in Methylmercury Metabolism and Elimination Status in Humans Following Fish Consumption

Abstract

Evaluating the potential for methylmercury (MeHg) toxicity relies on accurately predicting the mercury (Hg) body burden that results from eating fish. Hg body burden is directly determined by the slow elimination kinetics of MeHg in the human body (kel = 0.014 days-1 or t1/2 =50 days). Existing studies on MeHg half-life in humans demonstrate a wide range values (t1/2 = 30 to >150 days) and has lead to uncertainty in the derivation of a regulatory standard for acceptable daily oral intake. The causes of variation in MeHg toxicokinetics in humans remain little explored. Here we characterize variation in human MeHg metabolism and elimination rate (kel) in 37 adult volunteers who consumed 3 fish meals. We determined MeHg elimination rates via longitudinal Hg analysis in single hairs using laser ablation inductively coupled plasma mass spectrometry. We also measured MeHg metabolism (biotransformation) via speciation of fecal Hg. We find an average kel = 0.0157 days-1 (t1/2 = 44 days) amongst a more than 2-fold variation in kel across the cohort (0.0248-0.0112 days-1; t1/2 = 28-62 days). Although MeHg biotransformation varied widely between individuals, it showed a positive association with elimination rates across the cohort. A more than 2-fold change in kel over a period of 2 years was seen in some individuals. In 2 individuals, who received antibiotic for unrelated health issues, elimination rate was seen to slow significantly. Associations of kel with age, body mass index, gender, and fish eating habits were not observed. We establish that a measure of methylmercury metabolism and eliminaiton status (MerMES) can reduce uncertainty in determining an individual's MeHg toxicokinetics subsequent to eating fish.

Fecal Methylmercury Correlates With Gut Microbiota Taxa in Pacific Walruses (Odobenus rosmarus divergens)

“…Adult male Pacific walruses weigh up to 2,000 kg and eat approximately 2-3% of their body weight per day (Kastelein et al, 2000). Nevertheless, the range of fecal Hg species among walruses was comparable to values reported among Japanese men (n = 4;Ishihara, 2000) and adults in Rochester, NY (n = 33;Caito et al, 2018;n = 8, Rand et al, 2016) ( (Ishihara, 2000;Rand et al, 2016;Caito et al, 2018). Using an average wet/dry ratio for human fecal samples (4.18 unitless) (Rothenberg et al, 2019), the THg and MeHg concentrations were converted from wet weight to dry weight (see Supplementary Table 12 for THg and MeHg concentrations in wet weight).…”

Mercury exposure and its effects on fertility and pregnancy outcome

“…Methylmercury, derived from fish, and dimethylmercury are readily absorbed in the gastrointestinal tract. MeHg is slowly demethylated and oxidized to Hg 2+ . Once assimilated into the cell, Hg2+ and MeHg+ form covalent bonds with glutathione and cysteine residues of proteins .…”

“…MeHg is slowly demethylated and oxidized to Hg 2+ . 86 Once assimilated into the cell, Hg2+ and MeHg+ form covalent bonds with glutathione and cysteine residues of proteins. 87 Organic Hg is found as the most frequent and most hazardous form of exposure to Hg that is frequently identified as EtHg and MeHg.…”

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

“…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.…”