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How the 5 Big Heavy Metals Affect DNA Methylation

heavy metals and methylation

As discussed in previous blogs, there are many factors that can influence DNA methylation

We may be exposed to heavy metals through food, air, and water contamination. Shockingly, rice often contains high levels of arsenic, which is why rice milk and other rice derived foods are off limits for pregnant and nursing mothers. For more, see this public service announcement from the U.S. Food and Drug Administration. 

In addition to general concerns over how heavy metals in food and water affect our health, there is a growing concern over the ability of heavy metals to induce gene-specific DNA methylation.

Although most metals found in food products are beneficial in trace amounts (such as selenium, for example), high intakes due to food, air, and water contamination have been shown to be highly toxic.

Five metals are of particular concern: arsenic, cadmium, chromium, lead and mercury. These are the heavy metals that have been most extensively studied for their effects on health, with several mechanisms of action proposed.

How heavy metals affect human health

Similar to dietary factors, heavy metals may directly influence the activity of methylation and demethylation enzymes (DNMTs and TETs respectively). Additionally, heavy metals may change the availability of s-adenosylmethionine (SAMs), effectively blocking the methionine cycle.

Heavy metals can also directly influence the methylation of specific genes by binding to transcription factors. This has the effect of either allowing or denying DNMTs access to methylate these genes (See Figure 4).

Table 2 shows common sources of heavy metals and summarizes their impact on specific gene expression. One common source is a contaminated water supply. Heavy metals bioaccumulate, meaning that they are ingested by animals and are stored in the body because they are difficult to remove. As we go higher up the food chain, with one animal eating another, these contaminants become more concentrated, leading to highly contaminated food sources for larger predators.  This is why certain large species of fish, namely tuna and swordfish, tend to have higher levels of heavy metals – they are bigger and eat other small fish, absorbing all the toxic chemicals from their food along the way. 

Importantly, levels of exposure to these metals can vary widely based on location, and these contaminants are often very difficult to clear from the environment. This means that their effects can linger for long periods of time.

Potential mechanism of action of heavy metals on DNA methylation. Adapted from Martin EM and Fry RC, 2018

Figure 4. Potential mechanism of action of heavy metals on DNA methylation. Adapted

from Martin EM and Fry RC, 2018 1.

In figure 4a, a heavy metal inhibits DNMT from accessing cytosine residues in the promoter region of the gene, resulting in gene-specific hypomethylation.  In figure 4 b, a heavy metal inactivates the transcription factor, allowing DNMT access to the promoter region, resulting in gene-specific hypermethylation.

Heavy metals and their influence on DNA methylation

MetalSourceKey genes affectedMain studies
ArsenicFood products (shellfish, meat, poultry, dairy products, cereals), contaminated groundwaterKCNQ1, SQSTM1, sex-specific profilesAmeer et al. 2017 Toxicol. Appl. Pharmacol.
Argos et al. 2015, Environ. Health Perspect.
CadmiumFood products (shellfish, kidney meats, grain, cereals), emissions from fossil fuels and cigarettesDNMT1Hossain et al. 2012, Environ. Health Perspect., Virani et al. 2016.
ChromiumFood products (broccoli, liver, and brewer’s yeast), inhaled carcinogensTumor suppressor genesWang et al. 2012, J. Hazard. Mater,
Ali et al. 2011, Mol. Carcinog.
Lead Food products (fruit juices, root vegetables), inhaling paint dust, water supplied through old pipesCOLIA1, Alterations in imprinted genes, sex-specific responseLi et al. 2013, Clin. Toxicol.
Hanna et al. 2012, Hum. Reprod.
MercuryFood products (fish), dust, water supplyEMID2, sex-specific profilesCardenas et al. 2017, Sci. Rep.
Goodrich et al. 2013, Eviron. Mol. Mutagen.

Table 2 further shows potential sources of contamination and food products with high amounts of various heavy metals. The table further highlights specific genes influenced by altered methylation which may lead to several disease states. 

The takeaway

As we’ve seen, heavy metals can have multiple impacts on our health, some good, some bad. For the most part, normal dietary patterns easily provide the trace amounts of beneficial heavy metals like copper and selenium needed for good health. The problem then is avoiding exposure to the heavy metals that play no known role in human health and that can be downright toxic even in small amounts. 

The best strategy is to be aware of heavy metals both in your environment and in the food you eat every day and to take appropriate steps to minimize your exposure. Water filters are a great way to reduce heavy metal exposure through drinking water, for example. You can also look at the household items you purchase, including furniture, paint, cleaning products, and even children’s toys and pet toys. These are all potential sources of heavy metals, such as from lead paint, with household dust a common route of heavy metal exposure. 

Fortunately, as more manufacturers respond to conscious consumer demand for safe, non-toxic products, the use of heavy metals and other potentially toxic chemicals decreases overall. This helps to reduce levels of these contaminants in the wider environment, supporting a healthier ecosystem. 

Dr. Aaron Gardner, BSc, MRes, PhD

Dr. Aaron Gardner, BSc, MRes, PhD is a life-scientist with a strong background in genetics and medical research, and the developing fields of personalized medicine and nutrition. Read his full bio here.

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