When we think of triggers for migraine episodes, we often consider dietary offenders like alcohol, nitrates, and monosodium glutamate. A new study suggests that we should also be considering heavy metal exposures, especially in patients who also have trace element deficiencies. 

Researchers at the University Medical Center Groningen, Netherlands, and Yozgat Bozok University, Yozgat, Turkey, measured serum levels of specific heavy metals and trace elements in 50 patients diagnosed with migraine, and compared them to 50 age- and sex-matched healthy controls.

The investigators, headed by Dr. Sevilay Vural collected blood samples from migraine patients during acute attacks prior to any treatment, and from control subjects during routine health evaluations. All the patients met International Classification of Headache Disorders criteria for migraine.

The researchers measured heavy metals and trace elements using atomic absorption spectrophotometry, a sensitive method for detecting metal concentrations in biological samples. The elements analyzed included lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), copper (Cu), zinc (Zn), iron (Fe), and selenium (Se).

Vural and colleagues found the following correlations and connections between heavy metals, trace elements, and migraine headaches:

• Lead (Pb): Compared with the control subjects, the migraine patients had significantly higher serum levels, suggesting a potential role in migraine pathogenesis.
• Cobalt (Co): The migraine patients also showed increased serum cobalt levels, which could be linked to oxidative stress mechanisms.
• Zinc (Zn):  Zinc was significantly lower in migraine patients versus controls
• Selenium (Se): Selenium was also significantly lower among the migraineurs.

The authors found that Arsenic (As) and Nickel (Ni) levels were slightly elevated in migraine patients. Likewise, there were no significant differences between the two groups on levels of Cadmium (Cd), Copper (Cu), Tin (Sn), Mercury (Hg), Antimony (Sb), Molybdenum (Mo) or Iron (Fe).

The findings indicate that imbalances in certain heavy metals and trace elements are associated with migraine attacks. Most significantly, elevated lead and cobalt levels may contribute to oxidative stress and neuroinflammation, key factors in migraine pathophysiology.

Conversely, reduced zinc and selenium levels could impair antioxidant defenses, making individuals more susceptible to migraines (Vural S, et al. Headache, 2024).

To better understand these phenomena, we need to take a closer look at how heavy metals and trace minerals independently affect migraine physiology, and how the exposures and deficiencies combine to create an especially painful situation.

Metals, Minerals & the Migraine Brain

Migraine is a prevalent neurological disorder characterized by intense, recurrent headaches often accompanied by nausea, vomiting, and sensitivity to light and sound. The pathophysiology is complex and multifaceted, involving genetic, environmental, and biochemical factors.

Oxidative balance is usually disrupted in migraine patients. Several studies have shown that episodic and chronic migraine are associated with worsening oxidative stress and free radical production.  The body relies on key nutrients and anti-oxidants to maintain oxidative balance.  Exposure to heavy metals and trace mineral deficiencies will impair the process of maintaining healthy oxidative balance.   

To better understand how this happens, let’s examine potential mechanisms by which heavy metals can impact migraine:

• Neurotoxicity: It is well known that heavy metal are neurotoxins.  Probably the best example if this is with excess mercury.  Headaches are the most common symptom of mercury exposure (Donma O, Donma MM. Biol Trace Elem Res. 2002). In those who already have migraines, even minute exposure can lead to worsening symptoms such as headache as well brain fog.
• Inflammation: Several heavy metals, especially lead, can lead to increases in pro-inflammatory cytokines which have been associated with migraine attacks.
• Hormonal Disruption:  Hormonal fluctuations are a common trigger for migraine, particularly in women.  Several heavy metals, especially cadmium and mercury, are known endocrine disruptors which can worsen hormone imbalances. 
• Impaired Detoxification Pathways: During and after a migraine, the body produces a significant number of inflammatory agents and neurochemicals which need to be processed, neutralized, or excreted in order to return to baseline.  Excessive lead and mercury can inhibit the enzymes involved in these detoxification pathways, potentially leading to prolonged symptoms.
• Oxidative Stress:  As noted above, oxidative stress is heightened during and after a migraine.  Several heavy metals such as arsenic, lead, and cadmium promote free radical formation, thereby increasing oxidative stress. This makes it more difficult to return to baseline. 
• Mitochondrial Dysfunction: Maintaining mitochondrial health is key in preventing migraines.  We know that several nutrients including Coenzyme q10 and riboflavin are essential in supporting mitochondrial energy production.  Unfortunately, these can become progressively depleted with each migraine episode.  To compound the situation, we know that heavy metals like mercury and arsenic impair mitochondrial function. That means reduced energy production, and increased brain susceptibility to migraine triggers. 

In essence, the presence of heavy metals worsens the migraine state, and blocks the pathways necessary to both eliminate toxins and resolve migraine symptoms.

Normally, in this state, minerals and vitamins come to the rescue.  Several key elements such as magnesium and zinc help to dampen inflammation, reduce oxidative stress, and stabilize cell membranes, all of which help to mitigate the situation. 

Unfortunately, as the Vural study shows, that help is not always available because many people with migraines are vitamin- and mineral-deficient.  

Let’s review the roles played by Zinc and Selenium–the two trace elements identified as deficient in this study—in the context of migraine.

Zinc is important for migraine prevention due to its involvement in multiple physiological processes, including neurotransmitter regulation, oxidative stress reduction, and immune modulation:

• Antioxidant Defense: Zinc is a cofactor for superoxide dismutase (SOD), an important enzyme that neutralizes reactive oxygen species (ROS), and reduces oxidative stress
• Anti-Inflammatory Effects: Zinc modulates immune responses by regulating cytokines and reducing the production of pro-inflammatory molecules, such as tumor necrosis factor-alpha (TNF-α) and interleukins.
• Hormonal Regulation: Zinc is involved in hormone metabolism, including the regulation of estrogen. Adequate zinc levels may help stabilize hormonal changes and prevent hormonally-driven migraines.

In addition, zinc supports neuronal health by maintaining cell membranes, promoting DNA repair, and reducing neuro-excitotoxicity by lowering glutamate and enhancing GABA (gamma-aminobutyric acid). 

Seleniumplays a role in several of the same processes. It is a potent antioxidant and vascular stabilizer, and it also modulates inflammation and hormone balance.  It is a key component of selenoproteins, including glutathione peroxidase (GPx), which neutralizes reactive oxygen species (ROS) and protects cells from oxidative damage.  Selenium supports vascular health by modulating nitric oxide (NO) and improving endothelial function, which is strongly linked to migraine prevention.

In the context of migraine management, there’s some clinical evidence to support the use of both Selenium and Zinc.

Selenium

• People with migraine showed lower selenium status compared with control subjects, and this was associated with higher incidence of migraine.
• A 2023 Frontiers in Neuroscience article noted a relationship between selenium and migraine. Daily intake greater than 93 mcg was associated with reduced migraine prevalence.
• A randomized clinical trial published last Spring in Frontiers in Nutrition showed that supplementation with 200 μg/day of selenium versus placebo for 12 weeks resulted in a significant increase in total antioxidant capacity (TAC), as well as lower migraine frequency and severity. 

Zinc

• Similar to selenium, zinc deficiency is associated with an increased risk of migraines with replacement demonstrating benefit.
• A study published in the journal Headache found that zinc supplementation in deficient individuals was associated with reduced frequency and severity of migraine attacks. The researcher found that intake of 16 mg of zinc per day reduced the risk of migraine by 30% on average, compared with intake levels of 6 mg or less.

The Challenge of Toxins

The study by Vural and colleagues had several important limitations.  First, it is a small study involving just 50 subjects, so  it is important that we not overstate the significance of the findings. Secondly, it was done in Turkey, and toxin exposures there may be different than in other parts of the world, raising a question about generalizability.

That being said, we know that the prevalence of heavy metal exposures is increasing in communities all over the world. Tainted water supplies and air pollution are, unfortunately, all too common here in the US and in many other countries.

Vural and colleagues only looked at a small number of toxic metals. But we know that exposure to other toxins such as “forever chemicals” (per- and polyfluoroalkyl substances) is also increasing, and these may also disrupt oxidative balance, potentially contributing to migraine onset. Likewise, nutrient deficiencies are also on the rise, and many such deficiencies are associated with migraine.

The point is that when we’re working with migraine patients, we need to look more comprehensively at their overall health status, and include assessment of toxin exposures and nutrient protectors.

What to do with these findings?

Approaching this situation can be daunting.  Supplementation to raise levels of helpful nutrients is a good place to start.  In my practice I like to start with nutrient testing, focusing particularly on nutrients that are likely to be deficient. This includes riboflavin, folate, B12, Coenzyme q10, Vitamin C, D, B12, zinc, iron, selenium and omega -3’s.  These can be measured individually or more comprehensively using advanced labs such as Vibrant America, Genova or similar panels.  Based on the results, I will tailor my dietary or supplementation recommendations. 

In most cases of longstanding migraine, a combination supplement can be helpful to consistently ensure key nutrient adequacy.  Whenever possible, I like to identify healthy food sources of minerals, keeping in mind that it is equally important for these patients to avoid foods that could be migraine triggers or those to which they have sensitivities. This is tricky, and often requires careful analysis and planning.  I often work with a dietitian to review current dietary intake and provide meal suggestions for preventing migraine episodes.

Looking specifically at selenium, I recommend in the range of 50 -100 mcg per day, typically not exceeding 200 mcg/day. For zinc, 15 mg/day is a good target. Remember not to overdo it with zinc, as excess (>40 mg/day) can cause nausea, gastrointestinal upset, and copper deficiency with prolonged use. Chelated forms of zinc, such as zinc bisglycinate, are usually better-tolerated than non-chelated forms.   

Managing Toxin Overload

It is important to recognize that toxin exposure is often not a singular entity. It is usually multifaceted and quite pervasive.  If you are going to be testing, it is important to look at heavy metals as well as “forever chemicals” and environmental pollutants.  Again, the reference laboratories mentioned above can be helpful in providing comprehensive testing panels. 

There is much debate about testing methods for environmental toxins, so it is best to check with your laboratory as well as colleagues with expertise in toxicology and environmental health to determine the most appropriate panels for your patients.

While testing and focused treatment for severe toxin exposures is essential, there are also a number of general diet and lifestyle approaches that can be helpful in mitigating the cumulative burden of toxin exposure. These include:

• Increasing intake of high fiber foods which have been shown to prevent heavy metal disruption of the human gut microbiota.
• Increasing daily intake of detoxifying foods such as garlic, cilantro, chlorella, leafy greens, nuts, seeds, berries, tea, and whole grains.  Not only do these foods enhance natural detoxification, they are also rich in essential elements like magnesium, selenium, and zinc.
• Supplement with Broccoli-derived Sulforaphane. This phytochemical is a strong inducer of glutathione S-transferases (GST), which has been shown to detoxify pollutants, including airborne pollutants.
• Increase water intake to enhance detoxification, especially if hydration is suboptimal

• Exercise and Sauna. There is evidence that exercise that brings on a sweat promotes detoxification.  Preliminary evidence  suggests that sauna could be a good detox option, especially for people who find it difficult or impossible to exercise.

As practitioners, we need to stay Informed about environmental toxins, and the impact they have on our health. So do our patients. Familiarize yourself with resources that will help you stay on top of this topic. I find the following to be very helpful:

• The Environmental Working Group (EWG)does a great job identifying which foods, cosmetics and self-care products are most likely to contain high pesticide levels. EWG also has an app you can use when at the store to help make more informed choices. 
• Toxic-Free Futureis another excellent resource for identifying products that need better regulation, communities that may be at risk, as well as sensible steps to take to mitigate toxin exposure.
• Safe Seafood: The Monterey Bay Aquarium’s Seafood Watch website is a wealth of practical information and recommendations that can help people obtain the health benefits of fish and seafood with the minimum amount of environmental damage. 
• Safe Supplements: NSF https://www.nsf.org and www.Consumerlab.com  are good resources for assessing dietary supplements. They identify which brands test supplements for heavy metals and contaminants.
• Non-Toxic: Guide to Living Healthy in a Chemical World by Aly Cohen, MD and Frederick vom Saal, PhD, is an excellent book packed with useful and easily-implemented tips for minimizing toxin exposure, as well as recommendations and recipes for healthful, toxin-free meals.

Migraine is complex condition which is highly linked to oxidative stress, and promoted by multiple triggers.  The Vural study showing the connections between migraines, lead levels, and deficiencies of zinc and selenium eye-opening, as these factors are seldom under consideration when we talk about how we can help our migraine patients. We are just beginning to appreciate the contributory role of heavy metal toxicity which is heightened when there is co-existing trace element deficiency. 

We need to be increasingly aware of this connection, and the ways in which we can mitigate it through diet and lifestyle changes, to improve migraine status and quality of life. 

Robert Bonakdar MD ABOIM FACN is the director of the Scripps Center for Integrative Medicine.  He is also the co-director of the upcoming UC Irvine Samueli Center Nutrition and Supplementation in Clinical Care (NSCC) Conference Jannuary 30 – February 2, 2025:

Dr. Bonakdar blogs on integrative migraine management at Migrawell.com

For a 15% discount on the Nutrition & Supplementation in Clinical Care conference, use the discount code ABC15 when you register.