Low-Level Lead Exposure & Implications for Human Health

ceramic lead cup

A 2018 study published in The Lancet Public Health suggests that of the 2.3 million deaths every year in the US, about 400,000 are attributable to lead exposure, of which 250,000 are from cardiovascular disease.1 This estimate is about 10x larger than previous approximations.1 The Global Burden of Disease study estimated that 558,000 deaths were attributed to lead in 2015.2

Lead is one of many recognized risk factors for cardiovascular disease, and Lanphear et al were the first to test whether the relation with cardiovascular disease mortality was evident in a population with concentrations of lead in blood below 5 ?g/dL.1 Previously, amounts of lead in blood lower than 10 ?g/dL had been associated with cardiovascular disease mortality. Results from Lanphear et al suggest that low-level lead exposure is an important risk factor for death in the US, particularly for cardiovascular disease deaths.1

What Is Lead?

Lead is one of the most widely used metals in the world,3 and although it is toxic, it has been incorporated into many different products including paints, cosmetics, fuel, etc. for its unique properties like a low melting point and resistance to corrosion.4 However, lead persists in the environment and cannot be metabolized in the human body.3 It can enter the body via a variety of routes; particles from lead-based paint or housing renovation can adhere to food and be ingested, or industries that use lead in manufacturing can pollute the air and soil, exposing humans via the food chain.5

Lead can be absorbed by the intestines and through the skin, and almost 90% of it binds to erythrocyte proteins (albumin).4 Once inside the human body, lead may travel to different tissues and organs, including the liver and kidneys, where it can exhibit oxidative damage on cells and tissues, and on cellular organelles by uncoupling the respiratory chain in mitochondria.4 DNA damage is a significant consequence of oxidative stress.3

Learn more about Functional Medicine

How can exposure to lead, even at low levels, affect health outcomes? A 2018 study provided the first published evidence that lead exposure results in DNA damage via promoting oxidative stress and the promoter methylation of DNA repair genes in a human cell line. While the study was conducted in vitro, the results suggest that lead exposure decreases cell viability, induces oxidative stress–mediated DNA damage via the Nrf2-ARE signaling pathway, and decreases the expression of DNA repair genes.3

Lead has also been associated with peripheral arterial disease, electrocardiographic abnormalities, and left-ventricular hypertrophy.1 Due to the major route of excretion from the body, the kidneys are more vulnerable to lead; it promotes kidney damage via oxidative stress and lipid peroxidation.4 Lead has also been known to induce an inflammatory cascade in various tissues, causing respiratory, neurologic, digestive, cardiovascular, and urinary diseases.6

Exposures in Children

A population-based case-controlled study suggests that prenatal exposure to lead and cadmium, as reflected by their concentrations in placental tissues, may be associated with an increased risk for neonatal orofacial clefts.7 A number of studies suggest that lead exposure disproportionately affects children in lower-income neighborhoods, and even older children ages 5 to 12 years may be at risk of central nervous system effects.8 A 2018 study compared blood levels of older children from a historically contaminated urban neighborhood to those of demographically matched children from a nearby rural locale and predicted significantly higher blood lead levels in the urban children.8

In 1979, Needleman et al suggested that lead exposure in children, at doses below those producing symptoms severe enough to be diagnosed clinically, appears to be associated with neuropsychological deficits.9 In 2004, a study published in Environmental Health Perspectives reviewed recent developments across the globe on the subject of low-level lead exposure and children’s cognitive development and found that there is no safety margin at existing exposures.10 Despite seeing a reduction in lead exposure over time, Koller et al state, “it could be argued that current baseline blood levels continue to constitute a global public health risk.”10

Emerging Research

What other emerging research links lead to undesirable health outcomes? A recent study suggests that the regular consumption of beverages in glazed, ceramic cups increases the chances of lead-related health risks.11 The chronic daily intake of lead by children and adults consuming from new ceramic cups were 1.3–5× and 1.28–6× more, respectively, than that from old ceramic cups. In both cases, intake values far exceeded the WHO reference dose of 0.0006 mg Pb/kg bw/day in children (<11 years) and 0.0013 mg Pb/kg bw/day in adults. According to the study, these levels of lead consumption in children might be predicted to be associated with a decrement in IQ by at least one point and associated with adverse effects in adults, especially women of childbearing age.11

Studies suggest that lead is a carcinogenic factor in animal models, and epidemiological studies have suggested the association of blood lead concentration and death rate due to cancer in a number of populations, including in the US,12 South Korea,13 and Australia.14 In June 2018, the first study to demonstrate urinary lead concentration as an independent predictor of cancer mortality in the general population was published in Frontiers in Oncology.5 Using National Health and Nutrition Examination Survey 1999-2010 data and its Mortality Follow-Up study, Li et al found that “despite the marked decrease in environmental lead levels over the past three decades, lead exposure is still the significant determinant of cancer mortality in general population in US, and quantification of urinary lead may serve as a non-invasive approach to facilitate biomarker discovery and clinical translational research.”5

What steps can clinicians take to recognize toxicity in their patients? Learn more in the following articles.

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  1. Lanphear BP, Rauch S, Auinger P, Allen RW, Hornung RW. Low-level lead exposure and mortality in US adults: a population-based cohort study. Lancet Public Health. 2018;(3)4:e177-e184. doi:10.1016/S2468-2667(18)30025-2
  2. GBD 2015 Risk Factors Collaborators. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388(10053):1659-1724. doi:10.1016/S0140-6736(16)31679-8
  3. Liu X, Wu J, Shi W, Shi W, Liu H, Wu X. Lead induces genotoxicity via oxidative stress and promoter methylation of DNA repair genes in human lymphoblastoid TK6 cells. Med Sci Monit. 2018;24:4295-4304. doi:10.12659/MSM.908425
  4. Rana MN, Tangpong J, Rahman MM. Toxicodynamics of lead, cadmium, mercury and arsenic-induced kidney toxicity and treatment strategy: a mini review. Toxicol Rep. 2018;5:704-713. doi:10.1016/j.toxrep.2018.05.012
  5. Li S, Wang J, Zhang B, et al. Urinary lead concentration is an independent predictor of cancer mortality in the U.S. general population. Front Oncol. 2018;8:242. doi:10.3389/fonc.2018.00242
  6. Boskabady M, Marefati N, Farkhondeh T, Shakeri F, Farshbaf A, Boskabady MH. The effect of environmental lead exposure on human health and the contribution of inflammatory mechanisms, a review. Environ Int. 2018;120:404-420. doi:10.1016/j.envint.2018.08.013
  7. Pi X, Qiao Y, Wei Y, et al. Concentrations of selected heavy metals in placental tissues and risk for neonatal orofacial clefts. Environ Pollut. 2018;242(Pt B):1652-1658. doi:10.1016/j.envpol.2018.07.112
  8. Alvarez J, Del Rio M, Mayorga T, Dominguez S, Flores-Montoya MG, Sobin C. A comparison of child blood lead levels in urban and rural children ages 5-12 years living in the border region of El Paso, Texas. Arch Environ Contam Toxicol. 2018;75(4):503-511. doi:10.1007/s00244-018-0549-3
  9. Needleman HL, Gunnoe C, Leviton A, et al. Deficits in psychologic and classroom performance of children with elevated dentine lead levels. N Engl J Med. 1979;300(13):689-695. doi:10.1056/NEJM197903293001301
  10. Koller K, Brown T, Spurgeon A, Levy L. Recent developments in low-level lead exposure and intellectual impairment in children. Environ Health Perspect. 2004;112(9):987-994. doi:10.1289/ehp.6941
  11. Mandal PR, Das S. Leachable lead and cadmium in microwave-heated ceramic cups: possible health hazard to human. Environ Sci Pollut Res Int. 2018;25(29):28954-28960. doi:10.1007/s11356-018-2944-8
  12. Cheung MR. Blood lead concentration correlates with all cause, all cancer and lung cancer mortality in adults: a population based study. Asian Pac J Cancer Prev. 2013;14(5):3105-3108. doi:10.7314/APJCP.2013.14.5.3105
  13. Kim MG, Ryoo JH, Chang SJ, et al. Blood lead levels and cause-specific mortality of inorganic lead-exposed workers in South Korea. PLoS One. 2015;10(10):e0140360. doi:10.1371/journal.pone.0140360
  14. Gwini S, MacFarlane E, Del Monaco A, et al. Cancer incidence, mortality, and blood lead levels among workers exposed to inorganic lead. Ann Epidemiol. 2012;22(4):270-276. doi:10.1016/j.annepidem.2012.01.003

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