Heavy Metals and Cardiovascular Disease Risk

Hypertension and family history are well-known risk factors for cardiovascular disease. But did you know heavy metal exposure could also be contributing to CVD risk? Read on to learn about the associations between heavy metal exposure and cardiovascular disease, the benefits and risks of chelation therapy, and what other treatments might help.

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Heavy Metal Exposure

Humans are exposed to various heavy metals from food, water, and the environment (1, 2):

• Mercury from seafood, high-fructose corn syrup, rice, and beauty products
• Arsenic from soil, crops, water, fertilizer, and tobacco
• Cadmium from batteries, plastic stabilizers, vegetables, chocolate, and cigarettes
• Lead from soil, house paint, smoking, and batteries
• Antimony from food, water, coal, and medicine
• Tungsten from industrial sources, water, and food

Heavy metals are distributed to almost all tissues. Once in our bodies, xenobiotic metals displace essential minerals such as calcium and magnesium, increase inflammation, and disrupt normal cellular processes. Eventually, toxins should be excreted by the liver via bile or filtered by the kidneys and expelled in the urine. However, metals can hang around for a long time, depending on the type and the individual’s detox capabilities. For example, most arsenic is cleared from the blood in a few hours, but the half-life of lead in bone approaches 30 years (1).

Heavy Metals Are Associated with Cardiovascular Disease

Epidemiological studies indicate clear links between heavy metal exposure and CVD-related risks and outcomes. The National Health and Nutrition Examination Studies (NHANES) are recurring, massive surveys that have been conducted since 1959 to track health, nutrition, environmental exposures, and infectious disease among populations. Repeatedly in these large studies, heavy metal levels were related to cardiovascular health (3, 4, 5, 6, 7, 8). Additional prospective studies have confirmed that cadmium (9, 10, 11), lead (12, 13, 14), arsenic (15, 16), antimony (17), and tungsten (18) levels are associated with hypertension, peripheral artery disease, and CVD risks and events. It’s worth mentioning that these adverse effects don’t occur only after high levels of exposure; many negative cardiovascular outcomes have been linked to exposure levels below current “safe” standards (19, 14, 15). Chronic, low-dose toxin exposure is a huge concern that I have written about previously.

Epidemiological studies indicate clear links between heavy metal exposure and CVD-related risks and outcomes.

The relationship between hypertension, a key risk factor for CVD, and mercury is well established in the literature (20). However, the story behind mercury and CVD risk may be confounded by the fact that fish consumption, often accredited to omega-3 fatty acids DHA and EPA, lowers CVD risk while simultaneously raising a population’s mercury exposure. Selenium, vitamin C, and vitamin E may also mitigate mercury’s toxic effects (1). What’s more, organic mercury found in seafood acts differently than inorganic mercury found in dental amalgams, and the two are not always measured and analyzed separately. Therefore, studies have yielded mixed results (21, 22, 23, 24, 25).

Heavy Metals Mediate CVD through Oxidative Stress Mechanisms

Atherosclerosis begins when lipids are able to pass through the damaged endothelium into the blood vessel wall, a process initiated and mediated by oxidative stress (26). At any given time, cells can withstand a certain amount of reactive oxidative species (ROS), but oxidative stress occurs when the delicate balance between creation and degradation of ROS is destabilized. Antioxidants such as glutathione, ascorbic acid, carotenoids, and antioxidant enzymes like paraoxonase and superoxide dismutase protect against elevated ROS.

Because of their electron-sharing properties, heavy metals can bind to sulfhydryl groups of antioxidants and enzymes, modifying their function and activity. Cadmium, arsenic, and lead can bind to glutathione, depleting its levels and eventually leading to oxidative stress (27, 28, 29, 30). Lead, mercury, and other metals can deactivate paraoxonase and other antioxidant enzymes, also contributing to increased free radicals and oxidative stress (1, 31, 32).

Another source of oxidative stress is through disruption of metal ion homeostasis (33). By competing with and displacing necessary metals like calcium, zinc, iron, and copper, heavy metals disturb metal homeostasis and further contribute to excess ROS (1). Under these unstable conditions, even physiologically necessary metals can become toxic.

Heavy metal-induced oxidative stress promotes LDL peroxidation, one of the early events in atherosclerosis. Mercury, lead, and likely other heavy metals can catalyze LDL peroxidation (22, 34).

Chronic inflammation is a hallmark of atherosclerosis and is intimately linked with oxidative stress. Heavy metals including arsenic, cadmium, and lead increase markers of inflammation such as IL-6, TNF-alpha, C-reactive protein, and VCAM-1 (35, 36, 37).

Heavy metals have also been linked to CVD through mechanisms involving apoptosis (38, 39, 40), endothelial dysfunction (41), and epigenetic effects (1, 42).

Although many mechanisms by which heavy metals contribute to CVD have been identified, research in all these areas continues to enhance our understanding.

Can Chelation Therapy Treat CVD?

Chelators bind and mobilize metal ions from tissues to be filtered by the kidneys into urine or excreted by the liver via bile. In the 1950s, 17 of 20 patients with angina showed improvement with chelation therapy (43). Since then, medical practitioners, usually in alternative medicine practices, have treated CVD with chelation. But chelation’s efficacy for CVD has been questioned for just as long.

In the literature, very few randomized controlled trials (RCTs) have demonstrated benefits of chelation therapy on cardiovascular outcomes. One recent review reported benefits in 16 of 20 case reviews and only three of seven RCTs (44). Several of the RCTs may have been too small to detect statistical differences between therapy and placebo groups.

The Trial to Assess Chelation Therapy (TACT), published in 2012, was supposed to “prove” once and for all that chelation therapy offered no benefit for atherosclerosis, but instead, chelation yielded significant positive results (45, 46). The study divided 1,708 patients who were post-myocardial infarction (MI) into four groups: chelation or placebo chelation and with or without oral multivitamins and minerals. Edetate disodium (EDTA) chelation therapy reduced the primary composite endpoint (combination of all-cause mortality, MI, stroke, coronary revascularization, hospitalization for angina) by 18 percent. In patients with diabetes, the reduced relative risk was even greater, at 41 percent.

Despite these promising results, the TACT publication was met with skepticism and even outrage. The conventional medical community questioned the trial’s double blindness and validity of treatment centers. Furthermore, they claimed the results were dangerous because the mechanisms by which chelation therapy could help CVD were unknown. Others rebutted that just because the mechanism is unknown, it doesn’t negate the therapy outright. For example, antibiotics were discovered by accident, not through a suspected and then tested mechanism. Chelation for CVD remains a controversial issue.

Risks of Chelation Therapy

Chelation therapy carries serious risk and should only be done under the care of a knowledgeable practitioner. EDTA, the chelation agent used in the TACT trial, along with DMSA and DMPS, are harsh treatments often used for acute severe toxicity.

EDTA, as with any chelation agent, binds to essential metals and toxic metals alike. Urinary output of lead and cadmium, but also zinc and calcium, were increased after EDTA infusion therapy (19). Therefore, the status of calcium and zinc needs to be closely monitored. In the TACT trial, hypocalcemia was reported more in chelation patients than in placebo patients, although with no serious adverse effects. The FDA has only found four cases of hypocalcemia-induced mortality following EDTA chelation therapy out of “perhaps millions” of treatments, but the risk cannot be ignored (47).

In patients who have compromised detox ability, mobilizing heavy metals back into the bloodstream can back up the liver. The metals recirculate and are free to do more damage. This is one reason why some patients start to feel WORSE after they begin chelation therapy. These patients require intensive detoxification support.

Renal shutdown has also been reported but usually only occurs after large, frequent doses of harsh chelators (19).

Testing for Heavy Metal Burden Is Not Always Straightforward

Before starting a chelation regimen, the patient’s heavy metal burden first needs to be determined, which is not always an easy task. Hair, urine, and blood can each be tested for heavy metal contents, but the levels do not always accurately reflect body burden.

One option is to use the Mercury TriTest from Quicksilver Scientific. Inorganic and organic mercury are separately measured from hair, urine, and blood. Comparing inorganic mercury in the blood to that in urine tells us how well the kidneys are excreting dental mercury. Comparing organic mercury content in the blood to that in hair tells us how well the body is excreting organic mercury from fish. Different results require different supporting treatment.

If I find chelation treatment is necessary, I generally use gentler chelation agents, such as curcumin, N-acetylcysteine, citrus pectin, alginate, and chlorella. The patient could also require individualized detox support, which may include some or all of the following:

• Antioxidants, specifically glutathione
• Liver support; I recommend the DIM Detox product
• Methylation support
• Sauna
• Other key nutrients, including vitamin D, thiamin and other B vitamins, and lactoferrin

For more resources, check out my articles on how to reduce toxin exposure, how to lower blood pressure naturally, and other ways to prevent heart disease.