The weight we carry: are heavy metals tipping the scales in ALS?

Richard Moore
Jul 1
9 min read

If you're living with ALS/MND, or caring for someone who is, you've probably heard every theory by now: it's genetic, it's bad luck, it's "just one of those things." None of these fully satisfy, and for good reason, known ALS genes explain only a minority of cases, and even when a gene is involved, it rarely tells the whole story (Goutman et al., 2023).

So researchers keep looking elsewhere. And one place they're now looking is something that may already be moving through your bloodstream.

A large study from the University of Michigan found that people with ALS carry higher levels of several metals and trace elements, lead, cadmium, copper, selenium and zinc among them, in their blood and urine than people without the disease, and that the combination matters more than any one on its own (Jang et al., 2025). Unlike your genes, this is something that can, in principle, be measured and understood.

This blog looks at what that study actually found, why metals might affect motor neurones in the first place, and why some people seem more affected than others.

What the researchers actually measured

The Michigan team, led by neurologist Stephen Goutman, collected blood plasma and urine from 454 people with ALS and 294 people without it, then measured the concentration of 23 different metals in each sample using a highly sensitive lab technique (Jang et al., 2025). It's less like a standard blood test and more like a full inventory check, not looking for one or two suspects, but cataloguing everything that's actually there.

Several stood out. In plasma, people with ALS had higher levels of lead, cadmium, copper, selenium and zinc than people without the disease. In urine, a similar pattern showed up for cadmium, copper, selenium and zinc, along with several other metals (Jang et al., 2025). None of this proves the metals caused the disease, but the difference between the two groups held up too consistently to dismiss.

It's worth pausing on what "metal" means here, because it covers two quite different things. Lead and cadmium are toxic at any meaningful level of exposure, there's no safe amount your body is supposed to have. Copper, zinc and selenium are different. They're essential nutrients your body needs in specific amounts, and the concern with these isn't that they're present, but that levels were higher than typical in people with ALS. The same nutrient can be protective at one level and harmful at another, which matters for how you read everything that follows.

When small weights add up: the "metal mixture" effect

When the researchers looked at single metals on their own, the risk linked to any one of them was real, but fairly modest. The picture changed once they combined exposures into a single score, weighting each metal by how strongly it related to ALS. People with the highest combined scores had close to three times the odds of having ALS compared with those at the lowest end (Jang et al., 2025).

Think of an old set of weighing scales. One coin on the tray barely moves the needle. Keep adding coins, a little lead, a touch of cadmium, some extra selenium and zinc, and at some point the scale tips, even though no single coin did the damage on its own. That's roughly what the researchers found: it's the combined weight of several metals together, not any one villain, that seems to matter most.

This combined score also predicted how fast the disease progressed. People with the heaviest load survived, on average, over a year less than those with the lightest (Jang et al., 2025), a difference that shows up not just in who develops ALS, but in how it behaves once it does.

Why would metals do this at all?

Metals aren't just inert pollutants that sit in the body doing nothing. Several of them interfere directly with processes that motor neurones rely on to survive. Lead and cadmium, for instance, are known to trigger oxidative stress: a kind of internal corrosion, not unlike rust forming on metal, but happening inside living cells (Cicero et al., 2017). Motor neurones are unusually long and energy-hungry, which makes them more exposed to this kind of wear than most other cells in the body.

Metals can also disrupt mitochondria, the structures inside cells that generate energy. A motor neurone works a bit like a power line running a long way from a power station to a muscle. Damage the power station and the line still carries some current, just less efficiently, with more waste produced along the way (Cicero et al., 2017).

One specific theme involves a protective enzyme called SOD1, whose job is to mop up the toxic by-products of ordinary cell activity. SOD1 depends on precise amounts of zinc and copper to fold into the right shape, a bit like a key that only turns the lock if it's cut to an exact size, and disturbed metal handling alongside SOD1 misfolding is a recognised theme in ALS biology (Jang et al., 2025). That doesn't mean a blood or urine metal reading proves this is happening in any one person. It's a plausible mechanism the field is still working through, not a diagnosis.

Selenium tells a slightly different story. It's sometimes called a "Goldilocks" nutrient, because too little of it is a problem, and so is too much. The body needs selenium to build antioxidant enzymes that protect cells from damage, but in excess it becomes a problem in its own right. In 1977, doctors investigated a small cluster of ALS cases among farmers living within a few miles of each other in a remote part of South Dakota. The common thread turned out to be the region's naturally selenium-rich soil, already known at the time to poison livestock (Kilness & Hochberg, 1977). The cluster was one of the earliest clues that pointed researchers toward environmental selenium exposure as something worth investigating in ALS, though a handful of cases in one county is a hypothesis-generating finding, not proof of a wider pattern.

Lead, mercury and cadmium: the quieter culprits

Copper, selenium and zinc dominated the headlines from the Michigan study, but other research has focused specifically on lead, mercury and cadmium, metals people may encounter through older buildings, occupational exposure, pollution and diet.

A 2025 study from South Korea compared hair samples from ALS patients with healthy controls and found significantly higher concentrations of mercury, lead and cadmium in people with ALS. Forty percent of ALS patients had mercury levels above half the reference safety limit, compared with ten percent of the control group (Yoo et al., 2025). Hair testing can offer useful clues about longer-term exposure, though it's a less direct measure than blood or urine, and it can't tell us what's actually happening inside the nervous system.

Mercury has also been linked to ALS through an unusual biomarker: toenails. Because toenails grow slowly and steadily, they record months of chemical exposure rather like the growth rings of a tree. One U.S. study found that people with ALS had toenail mercury levels associated with around two and a half times the odds of the disease, an association partly explained by mercury building up through fish and shellfish consumption (Andrew et al., 2018).

The most striking finding, though, comes from a study of children's teeth. Researchers used teeth from people later diagnosed with ALS to measure metal exposure during early childhood, years, sometimes decades, before any symptoms appeared, and found measurable differences in early-life metal uptake between future ALS patients and controls (Figueroa-Romero et al., 2020). The weight we carry, it seems, can start accumulating long before anyone notices anything is wrong.

Is it in the genes? Why some people seem more affected than others

This is the question almost everyone asks eventually: if metals matter this much, why doesn't everyone exposed to them get ALS? We don't fully know yet, but the Michigan researchers tried to find out, and what they found was unexpected.

Known ALS-causing genes explain only around 70% of familial ALS (cases that run in families) and around 15% of sporadic ALS (cases with no family history), and sporadic cases make up most of the total. How much of a person's ALS risk comes down to genetics overall varies enormously between studies, anywhere from under a tenth to well over half (Goutman et al., 2023). For most people with ALS, genes are part of the picture, but nowhere near all of it.

To test whether genetics changes how much metals matter, the Michigan team built two polygenic risk scores: small genetic dials, built from hundreds of individual variations, that nudge a person's underlying risk up or down. One reflected general genetic risk for ALS; the other reflected genes involved specifically in how the body processes and clears metals. They then asked whether a person's position on either dial changed how dangerous their metal exposure was.

It didn't. Whether someone's genetic dial sat high or low, the relationship between metal mixtures and ALS risk stayed about the same (Jang et al., 2025). Many researchers had expected metals to be most harmful in people already genetically primed for ALS, the way two risk factors often compound each other. Here, that didn't hold. Metal exposure seemed to matter regardless of genetic background.

That doesn't mean genetics is irrelevant to ALS. It may simply mean the genes researchers currently know how to measure aren't the ones deciding who's most vulnerable to metals, and that other, unidentified genetic factors, or differences in lifestyle and exposure history, explain why some people seem to tolerate a heavier metal load than others (Jang et al., 2025). This fits a broader idea in ALS research called the exposome: the lifetime accumulation of environmental exposures layered on top of genetic susceptibility, rather than any single cause acting alone (Goutman et al., 2023).

Where this leaves us, for now

A near-tripling of risk linked to metal mixtures is a striking result from a large, carefully run study. It also comes from one research group, studying one population, at one point in time, and association isn't the same as proof of cause. For now: metals and trace elements in your body appear to be part of the ALS story, the combination matters more than any one of them, and genetics, at least as we can currently measure it, doesn't seem to be deciding who that affects most.

In our next blog, Heavy metals and ALS: what the evidence does (and doesn't) mean for you, we'll look more closely at what this kind of evidence can and can't responsibly support.

A practical note while we're here: none of this means anyone with ALS should start chelation or "detox" protocols, or stop, reduce or increase supplements containing zinc, copper or selenium without guidance from a health professional. These are essential nutrients, and both deficiency and excess can cause harm. Any testing or change to mineral intake should be guided by a qualified practitioner.

How You Nutrition Clinic can help

You can't undo a lifetime of metal exposure, and no nutrition plan rewrites that history. But your body's ability to manage everyday oxidative stress, and to keep minerals like zinc, copper and selenium in proper balance rather than excess or deficiency, is something nutrition can support. At You Nutrition Clinic, we work alongside your medical team to build a personalised, evidence-informed nutrition plan that supports your body's natural antioxidant defences, reviews mineral balance, and helps identify avoidable exposure risks where relevant, not a replacement for medical care, but a considered addition to it. If you, or someone you're caring for, would like to talk this through, we'd be glad to help.

If you, or someone you're caring for, would like to talk this through, we'd be glad to help. Our team is lead by Dr Kirstie Lawton and we work with people at any stage of thier journey , from symptom onset to advanced stage.

You can read more about our dedicated MND/ALS support programme, 'No Stone Unturned', at https://www.younutritionclinic.com/mnd or contact the clinic at admin@younutritionclinic.com.

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Disclaimer: This article is for informational and educational purposes only and does not constitute medical advice. Always consult with a qualified, registered medical doctor (MD) for diagnosis and treatment decisions.

References

Andrew, A. S., Chen, C. Y., Caller, T. A., Tandan, R., Henegan, P. L., Jackson, B. P., Hall, B. P., Bradley, W. G., & Stommel, E. W. (2018). Toenail mercury levels are associated with amyotrophic lateral sclerosis risk. Muscle & Nerve, 58(1), 36–41. https://doi.org/10.1002/mus.26055

Cicero, C. E., Mostile, G., Vasta, R., Rapisarda, V., Signorelli, S. S., Ferrante, M., Zappia, M., & Nicoletti, A. (2017). Metals and neurodegenerative diseases: A systematic review. Environmental Research, 159, 82–94. https://doi.org/10.1016/j.envres.2017.07.048

Figueroa-Romero, C., Mikhail, K. A., Gennings, C., Curtin, P., Bello, G. A., Botero, T. M., Goutman, S. A., Feldman, E. L., Arora, M., & Austin, C. (2020). Early life metal dysregulation in amyotrophic lateral sclerosis. Annals of Clinical and Translational Neurology, 7(6), 872–882. https://doi.org/10.1002/acn3.51006

Goutman, S. A., Savelieff, M. G., Jang, D. G., Hur, J., & Feldman, E. L. (2023). The amyotrophic lateral sclerosis exposome: Recent advances and future directions. Nature Reviews Neurology, 19(10), 617–634. https://doi.org/10.1038/s41582-023-00867-2

Jang, D. G., Dou, J. F., Koubek, E. J., Teener, S., Zhou, L., Bakulski, K. M., Mukherjee, B., Batterman, S. A., Feldman, E. L., & Goutman, S. A. (2025). Multiple metal exposures associate with higher amyotrophic lateral sclerosis risk and mortality independent of genetic risk and correlate to self-reported exposures: A case-control study. Journal of Neurology, Neurosurgery & Psychiatry, 96(4), 329–339. https://doi.org/10.1136/jnnp-2024-333978

Kilness, A. W., & Hochberg, F. H. (1977). Amyotrophic lateral sclerosis in a high selenium environment. JAMA, 237(26), 2843–2844. https://doi.org/10.1001/jama.1977.03270530051023

Yoo, J.-K., Kwon, S.-H., Yoon, S.-H., Lee, J.-E., Chun, J.-U., Chung, J.-H., Lee, S.-Y., Lee, J.-H., & Chae, Y.-R. (2025). Multi-metal exposure profiling in ALS patients in South Korea via hair analysis: A cross-sectional study. Biomedicines, 13(6), 1496. https://doi.org/10.3390/biomedicines13061496