Testosterone and estrogen are connected to sulfur metabolism in ways that involve molybdenum, zinc, copper, mercury, your intake of sulfur-rich amino acids, your gut microbiome, and your genes.
If you are male, your ears probably perk up anytime you hear information about influences on testosterone, sperm, and fertility. But don't forget about estrogen. Men need estrogen, but too much estrogenic signaling is antagonistic to testosterone signaling. So be sure to also read the section of this article about estrogen.
If you are female, your attention is probably more readily drawn to information about estrogen than testosterone. But also pay attention to the section below about testosterone because not only do you need testosterone, your whole body needs the antioxidant functions discussed in the first section below. In fact, the antioxidant functions impacted by sulfite affect most aspects of health and disease for all of us.
Sulfite, Molybdenum, and Testosterone
Sulfite is a sulfur compound that is well-known as a neurotoxin. Based on studies in mice, sulfite also appears to be toxic to male fertility by destroying testosterone-producing Leydig cells and shrinking the epididymis, the tubular structure around the testicles where sperm mature. Sulfite also destroys thiamine (B1), B6, folate, and perhaps other B vitamins.
Other evidence in studies on mice suggests that sulfite probably has its effects on the male anatomy by poisoning the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. Damage to these enzymes would lead to oxidative stress and cell death. This has broad implications for the health and function of all tissues in both sexes, not just the male anatomy.
In mice, molybdenum restored male fertility, normalized superoxide dismutase, and raised testosterone above the level of healthy control mice. This was almost certainly due to the fact that molybdenum is required for the conversion of harmful sulfite to helpful sulfate because it is the cofactor for the enzyme sulfite oxidase (SUOX).
However, the dose of molybdendum must be just right because too much molybdenum can harm antioxidant status and sperm number and quality. It's not certain how this occurs, but it is likely due to an indirect effect on zinc and copper status (which you need for healthy antioxidant function) when mercury is present.
Molybdenum substantially increases the degree to which mercury increases the production of metallotheionein, a mineral transport protein that binds to a variety of metals and minerals, including copper and zinc. When metallotheionein is elevated, it can lead to excretion of copper and zinc, potentially creating deficiencies.
What this could mean is that the more mercury you have in your body, and/or the more deficient you are in zinc and/or copper, the more careful you must be to avoid overconsuming or over-supplementing with molybdenum.
Since sulfite is produced via the metabolism of sulfur-rich amino acids, which are high in animal proteins, a diet rich in animal proteins increases the requirement for molybdenum to support SUOX, the enzyme that converts sulfite to sulfate.
Hydrogen Sulfide and Estrogen
Hydrogen sulfide is a "gasotransmitter" that acts as a signaling molecule in the body, much like nitric oxide does. In fact, they are both vasodilators, meaning that they cause blood vessels to dilate.
Hydrogen sulfide also has estrogenic activities, and its production is increased by estrogen. Hydrogen sulfide also increases estrogen production. So there is a positive feedback loop between hydrogen sulfide and estrogen.
Hydrogen sulfide's estrogenic effects could explain the presence of symptoms of "estrogen dominance" in women who do not have high levels of estrogen. If this is the case, it opens up opportunities for better understanding conditions like premenstrual cramps, migraines, and estrogen-sensitive cancers, which could be related to abnormally high hydrogen sulfide.
Hydrogen Sulfide, Your Gut Microbiome, and Your Genes
Hydrogen sulfide is produced by certain bacterial species in the gut, sometimes in copious quantities. In the hydrogen sulfide form of small intestine bacterial overgrowth (SIBO), bacteria produce high quantities of hydrogen sulfide that cause diarrhea or loose stools, which can lead to nutrient malabsorption and deficiencies.
High quantities of hydrogen sulfide can also produce nausea and vomiting instead of diarrhea. In fact, hydrogen sulfide is likely to be the mediator of nausea and vomiting during pregnancy.
Gut bacteria that produce hydrogen sulfide include H. pylori, E. coli, Desulfovibrio, Bilophila wadsworthia, and some strains of Lactobacillus. But the body has enzymes involved in clearing hydrogen sulfide so that our level of hydrogen sulfide is generally not at the mercy of bacteria or what we are feeding them.
The first enzyme involved in the breakdown of hydrogen sulfide is sulfide quinone reductase (SQR enzyme, SQOR gene), which requires coenzyme Q10, glutathione, vitamin B2 (as flavin adenine dinucleotide, FAD, which serves as the enzyme's cofactor).
Another enzyme involved in the breakdown of hydrogen sulfide is iron-dependent persulfide dioxygenase (PDO enzyme, ETHE1 gene). Deficiency of PDO due to a variant in the gene (ETHE1) that codes for the enzyme can cause symptoms that include diarrhea, intellectual impairment, low muscle tone that evolves into high muscle tone and tension, white or gray coloring in response to standing (orthostatic acrocyanosis, usually in the hands or feet), loss of mobility, seizures, loss of speech or swallowing, loss of social interaction, and pinpoints of red, brown, or purple patches on the skin or mucus membranes (petichiae).
Because I have seen transient, mild versions of these symptoms as a symptom cluster in one of my clients, I'm tempted to wonder if a moderate deficiency of this enzyme (e.g. due to a heterozygous variant in the ETHE1 gene), combined with certain bacteria in the gut, could generate these symptoms in people who are heterozygous for ETHE1. Unfortunately, I do not have data on this gene for this person, so I cannot check to see if he has a heterozygous variant of ETHE1.
Optimizing Sulfur Metabolism
Sulfur metabolism involves minerals like molybdenum and iron, and these minerals have interactions with others like zinc and copper. Molybdenum's potential negative impact on zinc and copper status appears to be affected by the presence of mercury. And the body's requirement for molydbenum increases with higher intakes of sulfur-rich amino acids (e.g. from animal proteins).
So when there are symptoms of impaired sulfur metabolism, potentially including imbalanced testosterone and/or estrogen, gastrointestinal symptoms, and neurological symptoms, it makes sense to test the status of molybdenum, copper, zinc, and mercury.
Evaluating the gut microbiome via stool testing, identifying potentially hidden influences that could be influencing the microbiome, and promoting a healthy microbiome could also be important steps in normalizing testosterone, estrogen, and symptoms that could be caused by excess sulfite and/or hydrogen sulfide.
These are some of the steps included in the Bio-Individual Blueprint system, which you can learn about by downloading the Bio-Individual Blueprint Roadmap. If you have already done that and are interested in speaking about potentially working together, schedule a time here.