Mercury Interactions with Selenium and Sulfur and the Relevance of the Se:Hg Molar Ratio to Fish Consumption Advice

Eating fish is often recommended as part of a healthful diet. However, fish, particularly large predatory fish, can contain significant levels of the highly toxic methylmercury (MeHg). Ocean fish in general also contain high levels of selenium (Se), which is reported to confer protection against toxicity of various metals including mercury (Hg). Se and Hg have a high mutual binding affinity, and each can reduce the toxicity of the other. This is an evolving area of extensive research and controversy with variable results in the animal and epidemiologic literature. MeHg is toxic to many organ systems through high affinity for -SH (thiol) ligands on enzymes and microtubules. Hg toxicity also causes oxidative damage particularly to neurons in the brain. Hg is a potent and apparently irreversible inhibitor of the selenoenzymes, glutathione peroxidases (GPX), and thioredoxin reductases (TXNRD) that are important antioxidants, each with a selenocysteine (SeCys) at the active site. Hg binding to the SeCys inhibits these enzymes, accounting in part for the oxidative damage that is an important manifestation of Hg toxicity, particularly if there is not a pool of excess Se to synthesize new enzymes. A molar excess of Se reflected in an Se:Hg molar ratio > 1 is often invoked as evidence that the Hg content can be discounted. Some recent papers now suggest that if the Se:Hg molar ratio exceeds 1:1, the fish is safe and the mercury concentration can be ignored. Such papers suggested that the molar ratio rather than the Hg concentration should be emphasized in fish advisories. This paper examines some of the limitations of current understanding of the Se:Hg molar ratio in guiding fish consumption advice; Se is certainly an important part of the Hg toxicity story, but it is not the whole story. We examine how Hg toxicity relates also to thiol binding. We suggest that a 1:1 molar ratio cannot be relied on because not all of the Se in fish or in the fish eater is available to interact with Hg. Moreover, in some fish, Se levels are sufficiently high to warrant concern about Se toxicity.