Heavy Metal Detoxification
In addition to the integrative interventions outlined in this protocol, readers are encouraged to review the Metabolic Detoxification protocol, as ensuring that the body’s general intrinsic detoxification pathways are functioning optimally may help avoid heavy metal accumulation and toxicity.
Several dietary constituents have been investigated for their ability to mitigate metal toxicity. They work by reducing or inhibiting metal absorption from the gut, binding up toxic metals in the blood and tissues to help draw them out of the body, or reducing free-radical damage (a significant contributor to the pathology caused by heavy metals). Most studies have been limited to animal and cell culture models, although the results of human studies have been encouraging.
For additional information on nutritional strategies to address iron toxicity, refer to Life Extension’s Hemochromatosis protocol.
Maintain Nutrient Sufficiency
Since many toxic metals mimic nutritionally essential metals, they compete for the same transport mechanisms for absorption from the intestines and uptake into cells. Therefore, adequate intake of essential trace minerals may reduce toxic metal uptake. For example, nutritional zinc or iron deficiency can increase cadmium absorption (Thévenod 2013), and lead absorption from the gut appears to be blocked by calcium, iron, and zinc (ATSDR 2007b; Patrick 2006). In animal models, selenium blocks the effects of lead when administered before exposure and reduces mercury toxicity (Patrick 2006). It also increases its excretion in humans (Li 2012; Zwolak 2012).
Choose Fish Oil Supplements over High-Mercury Fish
Most toxicology data support the recommendation, in non-pregnant adults, to limit consumption of high-mercury fish (shark, swordfish, king mackerel, tilefish) to no more than one serving (7 oz.) per week. The Environmental Protection Agency recommends that pregnant women, nursing mothers, and young children avoid eating high-mercury fish because the fetal brain is more sensitive to mercury toxicity than the adult brain (Defilippis 2010). High-quality fish oil supplements represent a good alternative source of omega-3 fatty acids (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) (Foran 2003).
The International Fish Oil Standards Program (IFOS) is an organization dedicated to differentiating high-quality fish oil products from those of lesser quality. In order to ensure your fish oil supplement does not contain dangerous concentrations of contaminants such as heavy metals, check the label to ensure your fish oil supplement achieves the rigorous IFOS 5-star rating (IFOS 2013).
In addition to its role as a possible competitive inhibitor of mercury and lead absorption, selenium also increases toxic metal excretion. Moderate (100 mcg/day) increases in dietary selenium increased urinary excretion of stored mercury in long-term mercury-exposed Chinese residents (Li 2012), and 100-200 mcg/day reduced blood and hair levels of arsenic in Chinese farmers with arsenic poisoning (Zwolak 2012). Selenium also appears to mitigate the toxicity of some heavy metals, such as cadmium, thallium, inorganic mercury, and methylmercury, by modulating their interaction with certain biomolecules (Whanger 1992). In another study, supplementation with 100 mcg of selenium (in the form of selenomethionine) daily for 4 months led to a 34% reduction in levels of mercury detected in body hair. The authors of the study concluded that “… mercury accumulation in [… body] hair can be reduced by dietary supplementation with small daily amounts of organic selenium in a short range of time” (Seppanen 2000).
Modified Citrus Pectin
Three studies have investigated the use of modified citrus pectin (MCP) on the mobilization of metals from body stores. In the first, 8 healthy individuals were given 15 g of MCP daily for 5 days and 20 g of MCP on day 6. Significant increases in urinary excretion of arsenic, mercury, cadmium, and lead occurred within 1 to 6 days of MCP treatment. There was a 150% increase in cadmium excretion and a 560% increase in lead excretion on day 6 (Eliaz 2006). Essential minerals such as calcium, zinc, and magnesium were not noted to increase in the urinary analysis. Second, in a series of case reports, 5 patients with different illnesses took MCP alone or in combination with alginate for up to 8 months. The patients showed a 74% average decrease in toxic heavy metals after treatment (Eliaz 2007). In a third trial, 7 children with blood lead levels >20 µg/dL received 15 g/day of MCP for 2 to 4 weeks. Blood lead levels dropped an average of 161%, and urinary lead excretion increased by an average of 132% (Zhao 2008).
Data from preliminary human studies reveal that naturally-occurring dissolved silicon from mineral waters appears to antagonize the metabolism of aluminum, potentially reduce Alzheimer's risk, and support cognitive function (Gillette Guyonnet 2007). In human subjects, soluble silicon (orthosilicic acid) decreases aluminum absorption from the digestive tract and decreases its accumulation in the brain (Jurkic 2013). In one study, Alzheimer’s patients drank up to 1 L of mineral water daily (containing up to 35 mg of silicon/L) for 12 weeks. Over the study period, urinary excretion of aluminum increased without affecting urinary excretion of the essential metals iron and copper. In addition, there was a clinically relevant improvement in cognitive performance in at least 3 out of 15 individuals (Davenward 2013).
Another source of orthosilicic acid studied for their metal reducing properties are compounds called zeolites. Zeolites are aluminum/silicon oxide-based crystalline compounds with adsorbent properties that have broad industrial applications and are finding applications in medicine (Montinaro 2013; Beltcheva 2012). Inclusion of zeolite (as the zeolite clinoptilolite) in high-lead diets of laboratory mice reduced tissue lead concentration by 77-91%, increased the percentage of healthy red blood cells, and reduced chromosomal damage (Topashka-Ancheva 2012; Beltcheva 2012). A clinical study on 33 men evaluated the ability of the zeolite clinoptilolite to increase heavy metal urinary excretion (Flowers 2009). To be included in the trial the men had to test positive, above a predetermined threshold, for at least four of the nine metals in a urinary test panel (ie, aluminum, antimony, arsenic, bismuth, cadmium, lead, mercury, nickel, and tin). The men were given either 15 drops of a clinoptilolite water suspension or placebo suspension twice daily for a maximum of 30 days. Significant increases in the urinary excretion of all 9 metals were observed in the men taking clinoptilolite as compared to placebo without a negative impact on electrolyte profiles. It has been hypothesized that the biological activity of some zeolites may be attributed to their orthosilicic acid releasing properties (ie, they are a source of orthosilicic acid) (Jurkic 2013).
Vitamin C is a free-radical scavenger that can protect against oxidative damage caused by lead (Patrick 2006), mercury (Xu 2007), and cadmium (Ji 2012); it may prevent the absorption of lead as well as inhibit its cellular uptake and decrease its cellular toxicity (Patrick 2006). Observational data suggest an inverse relationship between serum levels of ascorbic acid and blood levels of lead; in other words, the higher the blood levels of vitamin C the lower those of lead (Simon 1999). Vitamin C supplementation (500 mg/day) in 12 silver refiners with high blood lead levels (mean of 32.8 µg/dL) demonstrated a 34% reduction in lead levels after 1 month (Tandon 2001). In a small study of 75 male smokers, vitamin C (1000 mg/day) reduced blood lead levels by 81% after one week of supplementation. Lower dose vitamin C (200 mg/day) had no effect (Dawson 1999).
Through its antioxidant action, vitamin E mitigates some of the toxic damage caused by heavy metals, which are strong inducers of oxidative stress in tissues. In one study, rats were fed a diet containing lead acetate and subsequently developed sings of toxicity such as oxidative damage to lipids and alterations in blood chemistry parameters. When either vitamin E or garlic oil were administered in conjunction with the lead, the toxic effects were ameliorated. The researchers who conducted the study noted that the protective effect of vitamin E was probably due to its ability to support detoxification and scavenge tissue-damaging free radicals (Sajitha 2010). In another animal study, one group of mice were given toxic heavy metals (lead, mercury, cadmium, and copper) in their drinking water for 7 weeks, while another group underwent the same treatment but, in addition, received vitamin E five times weekly. The scientists found that the mice not receiving vitamin E exhibited evidence of oxidative injury to their kidneys and testis, whereas those organs appeared normal in mice receiving vitamin E. Also, the mice not receiving vitamin E showed changes in plasma levels of creatinine, urea, and uric acid while these blood parameters did not change significantly in the vitamin E group (Al-Attar 2011). Vitamin E has also been shown to counter the deleterious effects of heavy metals in humans. In several groups of workers regularly exposed to airborne heavy metal toxicity due to the nature of their work, daily supplementation with 800 mg vitamin E and 500 mg vitamin C for 6 months led to improved markers of intrinsic antioxidant defenses and decreased markers of oxidative damage. In fact, following the period of supplementation, the activity of certain intrinsic antioxidant systems reached levels comparable to those observed in control subjects not exposed to the toxicants (Wilhelm Filho 2010).
Folic acid is a cofactor in sulfur-containing amino acid metabolism. Sulfur-containing amino acids (cysteine and methionine) are precursors to known heavy metal chelators (alpha-lipoic acid and glutathione). In a study of 1105 pregnant women, 841 of which were followed through late pregnancy or delivery, higher blood folate levels were associated with lower blood mercury levels during mid- and late-pregnancy (Kim 2013). A similar study in Australia on 173 pregnant non-smokers demonstrated that the failure to use folic acid or iron supplements during pregnancy was associated with higher blood cadmium levels (Hinwood 2013).
Garlic contains many active sulfur compounds derived from cysteine with potential metal-chelating properties; these garlic constituents may also protect from metal-catalyzed oxidative damage. Rats fed garlic as 7% of their diet (either a week before, after, or during exposure to heavy metal toxins) for 6 weeks demonstrated significantly reduced lead, cadmium, or mercury accumulation in their livers (Nwokocha 2012). Garlic treatment also reduced the frequency of metal-related lesions in the livers of rats in the same study. Garlic may also increase the bioaccessibility of iron and zinc (both antagonists of cadmium and lead absorption) from dietary cereal grains (Gautam 2010). In a study of 117 car battery industry workers with occupational lead poisoning, garlic (1200 mg dried powder) daily for 4 weeks lowered blood lead as effectively as D-penicillamine (by approximately 18%). Additionally, treatment with garlic showed less adverse effects and more clinical improvement as compared to D-penicillamine (Kianoush 2012).
Cilantro (Coriandrum sativum) can bind and immobilize mercury and methylmercury from contaminated water (Karunasagar 2005). In mouse models, cilantro suspensions significantly reduced the deposition of lead into bones and reduced microscopic signs of lead-induced kidney and testicular damage (Aga 2001; Sharma 2010). In a case report, a patient exposed to mercury during amalgam-based dental filling removal developed adverse effects, including abnormal ECG readings, which reverted almost back to normal by the administration of 400 mg/day of cilantro extract prior to and after removal for 2-3 weeks. Mercury deposits were reported to be absent following treatment, although the details of the treatment and mercury analysis in this report are unclear (Omura 1996).
Alpha-Lipoic Acid and Glutathione
Sulfur-containing compounds can complex with heavy metals, and the sulfur antioxidants alpha-lipoic acid (ALA) and glutathione have been demonstrated to chelate a number of metals in cell culture (mercury for glutathione; cadmium, lead, zinc, cobalt, nickel, iron, and copper for ALA) (Patrick 2002). In a rat model, ALA and glutathione reduced some of the adverse changes in blood parameters, including drops in red blood cell number and size as well as reductions in hemoglobin concentration brought about by intoxication with lead, cadmium, or copper (Nikolic 2013). ALA and glutathione in a rat model both reduced cadmium-associated oxidative stress and improved the activity of the antioxidant enzyme catalase in kidney tissue (Veljkovic 2012).
N-acetyl cysteine (NAC) provides a source of sulfur for glutathione production and is effective at reducing oxidative stress due to heavy metal toxicity (Patrick 2006). As a sulfur-containing amino acid, it possesses two potential binding sites for metals and is capable of binding and sequestering divalent copper (II), trivalent iron (III), lead, mercury, and cadmium ions (Samuni 2013). Chronic exposure to toxic metals can decrease cysteine levels (Quig 1998). In animal models and cell culture experiments, NAC enhanced renal excretion of lead (Pb IV), lowered concentrations of mercury, and protected against cadmium-induced liver cell damage (Samuni 2013). Cysteine may also be useful as part of a complete protein (such as a whey protein), which provides additional essential amino acids that may block the entry of metals into nervous tissue (Quig 1998).
Glycine is a conditionally essential amino acid found in plant and animal proteins. Chemically, glycine is the simplest of all amino acids. It combines with many toxic substances and converts them to less harmful forms, which are then excreted from the body. Glycine is also involved in the body’s natural synthesis of glutathione (Ruiz-Ramirez 2014), which itself is an important detoxifier of heavy metals (Patrick 2002). In a study of “Stronger Neo-Minophagen C,” a Japanese drug containing glycine, glycyrrhizin, and cysteine, which is said to be protective against chronic cadmium toxicity, the authors concluded that the reported beneficial effects were due to glycine. Glycine appeared to reduce the oxidative stress of chronic cadmium toxicity (Shaikh 1999).
Among their myriad functions, certain strains of probiotic bacteria may minimize toxin exposure by trapping and metabolizing xenobiotics or heavy metals. The probiotic bacterial strains Lactobacillus rhamnosus (LC-705 and GG), Lactobacillus plantarum (CCFM8661 and CCFM8610), and Bifidobacterium breve Bbi 99/E8 were all shown to bind both cadmium and lead in laboratory studies (Ibrahim, Halttunen 2006; Halttunen 2008). Binding was observed for both live and heat-killed cultures of LC-705. However, the efficiency of heavy metal binding by probiotics may decrease when multiple strains are combined (Halttunen 2008). In mouse models, two different Lactobacillus plantarum strains reduced tissue accumulation of cadmium and lead and protected against oxidative stress (Zhai 2013; Tian 2012).
Chlorella, a unicellular green algae with the ability to bind cadmium (in animal models) and zinc, copper, and lead (in vitro), has been used to detoxify wastewater of metal contaminants (Almaguer Cantu 2008; Shim 2008; Uchikawa 2010). In preclinical studies, chlorella lowered the bioavailability and accelerated the excretion of methylmercury (Uchikawa 2010) as well as cadmium (Shim 2009) and reduced lead-induced bone marrow toxicity (Queiroz 2011).