You're Exposed to Arsenic. Your Genes Determine If It Accumulates.

Your GSTM1 gene encodes a glutathione S-transferase enzyme that catalyzes one of the most critical steps in arsenic elimination. The enzyme binds glutathione to arsenic molecules, making them water-soluble and excretable. Without this enzyme, arsenic stays lipid-soluble and accumulates in fatty tissues, bone, and organs.

Approximately 50% of people have a complete gene deletion called GSTM1 null, meaning they produce zero GSTM1 enzyme. These individuals have significantly reduced capacity to clear not only arsenic but also other heavy metals, benzene, and environmental carcinogens. If you’re GSTM1 null, your arsenic clearance is reduced by 50-70% compared to people who have a functioning gene.

You might feel this as a low-grade fatigue or brain fog that improves slightly when you reduce your exposure to contaminated foods and water. Over years, you may accumulate enough arsenic in your hair and nails that it becomes visible on mineral analysis. Some people with GSTM1 null report skin changes, neuropathy, or mood changes that are slow to develop but persistent.

Your GSTP1 gene encodes another glutathione S-transferase, this one specialized in clearing electrophilic compounds and the oxidative byproducts that arsenic generates. Arsenic is metabolized by oxidation, which creates reactive oxygen species; GSTP1 helps neutralize those species by conjugating them to glutathione.

The Ile105Val variant (Val allele) occurs in roughly 35-40% of the population and reduces GSTP1 enzyme activity by 30-50%. This is a functional impairment, not a deletion like GSTM1, but the effect is real. People with the Val variant have slower clearance of arsenic-induced oxidative stress and impaired phase II capacity for other electrophilic toxins.

You experience this as increased susceptibility to oxidative stress. Arsenic exposure triggers more free radicals in your cells, and your GSTP1 variant can’t neutralize them as efficiently. Over time, this accumulates as mitochondrial damage, accelerated aging, and potentially increased cancer risk.

Your MTHFR gene encodes the enzyme that converts folate into methylfolate, the active form needed for methylation reactions throughout your body. One of those reactions is critical for arsenic detoxification: methylation is how your body converts inorganic arsenic into monomethylarsonic acid, a form that’s easier to excrete.

The C677T variant, present in roughly 40% of the European ancestry population, reduces MTHFR enzyme activity by 40-70%. This slows your methylation cycle, which means you produce less glutathione and have reduced capacity to methylate arsenic for excretion. This is a compounding problem if you also carry GSTM1 or GSTP1 variants.

You might feel this as fatigue, brain fog, or mood changes that don’t improve with normal amounts of folate supplementation. When you’re exposed to arsenic, these symptoms intensify. Some people report that standard B vitamins don’t help, but methylated forms do, because the methylated versions bypass the MTHFR block.

Your SOD2 gene encodes superoxide dismutase 2, an antioxidant enzyme that sits inside your mitochondria and neutralizes free radicals generated by normal energy production. This is essential during arsenic exposure because arsenic generates massive oxidative stress inside mitochondria, and SOD2 is one of your cell’s primary defenses against that damage.

The Val16Ala variant is present in roughly 40% of the European ancestry population as homozygous, and the Ala variant is associated with reduced SOD2 enzyme activity and faster accumulation of mitochondrial oxidative damage. If you have the Ala/Ala or Ala/Val genotype and are exposed to arsenic, your mitochondria accumulate damage faster than someone with Val/Val.

You experience this as persistent fatigue, decreased exercise tolerance, or slow recovery from illness. Arsenic exposure makes this worse because it’s a direct mitochondrial toxin. Some people report that they felt fine until a period of arsenic exposure, at which point fatigue became debilitating.

Your NQO1 gene encodes an enzyme that reduces quinones and other electrophilic compounds, protecting your cells from oxidative damage. NQO1 is especially important in the liver, where it helps clear benzene metabolites and other industrial pollutants. During arsenic exposure, NQO1 also helps neutralize reactive oxygen species generated by arsenic metabolism.

The Pro187Ser variant is a null mutation present in 4-20% of the population depending on ancestry, and it eliminates NQO1 enzyme activity entirely. People with the Ser/Ser genotype (homozygous null) have essentially zero NQO1 function and significantly impaired phase II capacity. The heterozygous Ser carriers have about 50% activity.

You might not notice this during low-level arsenic exposure, but once exposure increases, the lack of NQO1 becomes a bottleneck. You develop symptoms of oxidative stress accumulation: brain fog, fatigue, or joint pain that standard antioxidants don’t fully resolve.

Your CYP1B1 gene encodes a phase I cytochrome P450 enzyme that metabolizes estrogens, environmental carcinogens, and heavy metals like arsenic. During arsenic metabolism, CYP1B1 catalyzes the first oxidation step that makes arsenic water-soluble and available for phase II conjugation. If this step is slow, arsenic stays in your body longer.

The Val432Leu variant, present in roughly 35-40% of the population, affects CYP1B1 enzyme activity and substrate specificity. This variant alters how efficiently your liver processes arsenic and environmental carcinogens, potentially increasing oxidative stress during the metabolic process itself. The metabolic byproducts can accumulate if downstream phase II enzymes (GSTM1, GSTP1) are also impaired.

You experience this as slow arsenic clearance that worsens if you’re exposed to multiple environmental toxins simultaneously. People with CYP1B1 variants often report that they react more strongly to pesticide exposure, air pollution, or other phase I substrates. Arsenic exposure symptoms persist longer in these individuals.