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Low-Level Lead Exposure & Implications for Human Health

ceramic lead cup
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Lead is one of the most widely used metals in the world, and although it is toxic, it has been incorporated into many different products, including paints, cosmetics, fuels, etc., for its unique properties, such as a low melting point and resistance to corrosion. However, lead persists in the environment and cannot be metabolized in the human body.1 It can enter the body via a variety of routes; e.g., 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.2

In 2017, lead exposure accounted for 1.06 million deaths and 24.4 million years of healthy life lost worldwide, with the highest burden in low- and middle-income countries.3 In addition, the Institute for Health Metrics and Evaluation estimates that as of 2016, lead exposure accounted for 63.2% of the global burden of idiopathic developmental intellectual disability, 10.3% of the global burden of hypertensive heart disease, 5.6% of the global burden of ischemic heart disease, and 6.2% of the global burden of stroke.3

Lead can be absorbed by the intestine and through the skin, and almost 90% of it binds to erythrocyte proteins.4 Once inside the human body, lead may travel to different tissues and organs, including the liver and kidneys, where it can cause oxidative damage to cells and tissues, including uncoupling the respiratory chain in mitochondria.4

A 2018 study provided the first published evidence that lead exposure results in DNA damage via promoting oxidative stress and promoter methylation of DNA repair genes in human lymphoblastoid TK6 cells.1 While this study was carried out in a human cell line, the study results suggest that lead exposure may decrease cell viability, induce oxidative stress–mediated DNA damage via the Nrf2-ARE signaling pathway, and decrease the expression of DNA repair genes.1

Lead Exposure and Cardiovascular Disease

A 2018 study published in The Lancet Public Health suggests that of the 2.3 million deaths every year in the United States, about 400,000 are attributable to lead exposure, of which 250,000 are from cardiovascular disease.5 This estimate is about 10x larger than previous approximations.5 A 2019 US cross-sectional study showed that lead exposure affects cardiovascular markers in young and middle-aged adults (18-65 years), with higher exposure increasing with age and generally resulting in worse health outcomes.6 The study suggests that increasing levels of lead exposure may contribute to people being propelled toward various cardiovascular pathologies.6

While blood lead levels (BLLs) above 5 µg/d in adults is considered elevated, sufficient evidence suggests that even BLLs <5 µg/d are associated with decreased renal function and that BLLs <10 µg/d are associated with increased blood pressure and hypertension.7 The mechanism by which lead induces hypertension may be related to oxidative stress, inflammation, alterations in the renin-angiotensin-aldosterone system, alteration of vasoactive and volume regulatory hormones, and nitric oxide dysregulation, among other mechanisms.6,8 Other conditions associated with lead exposure include:

  • Cardiovascular disease due to telomere shortening and lipid disturbance.9
  • Peripheral arterial disease, electrocardiographic abnormalities, and left-ventricular hypertrophy.5
  • Kidney damage via oxidative stress and lipid peroxidation4 and chronic kidney disease reflected by decreased estimated glomerular filtration rate and increased proteinuria.10
  • Respiratory, neurologic, digestive, and urinary diseases.11

Lead Exposure in Children

In children, there is no identified threshold or “safe” blood lead level below which no risk of poor developmental or intellectual function is expected.7 Young children are particularly vulnerable to lead poisoning because they absorb four to five times as much ingested lead as adults from a given source.3 Four million US households with children are exposed to high lead levels, and approximately 500,000 US children aged one to five years have BLLs higher than 5 µg/dL, the level at which public health action is recommended.12

A 2019 cohort study was one of the longest and largest psychiatric follow-up studies involving children tested for lead exposure and followed 579 New Zealand children for more than 30 years.13 Researchers reported BLLs above the level for clinical and environmental responses in 94% of the children, and childhood BLL was significantly associated with higher general psychopathology as well as internalizing and thought disorder symptoms into adulthood.13 Childhood BLL was also significantly associated with lower conscientiousness and agreeableness and higher neuroticism in adulthood.13

It is interesting to note that while thousands of children in the US have elevated blood lead concentrations, many of them are asymptomatic.14 The primary concern in this group is that multiple meta-analyses have demonstrated that, even at low blood lead concentrations, there is an inverse relationship between blood lead concentrations and intelligence quotient scores as well as markers of academic achievement. Furthermore, some research suggests that the dose-response curve is steeper at lower blood lead concentrations, meaning that the number of IQ points lost per unit increase in blood lead concentration is higher in the 1 to 10 mcg/dL lead range than in the 10 to 20 mcg/dL range.14

Emerging Research

A recent study suggests that the regular consumption of beverages in glazed, ceramic cups increases the chances of lead-related health risks.15 The chronic daily intake of lead by children and adults, respectively, consuming from new ceramic cups were 1.3–5× and 1.28–6× more 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 in women of childbearing age.15

Studies suggest that lead is a carcinogenic factor in animal models, and epidemiological studies have suggested an association between blood lead concentration and death rate due to cancer in a number of populations, including in the US,16 South Korea,17 and Australia.18 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.2 Using National Health and Nutrition Examination Survey 1999-2010 data and its Mortality Follow-Up study, Li et al found that lead exposure continues to be a significant determinant of cancer mortality in the US, despite decreased amounts of environmental lead levels, and that monitoring urinary lead levels is a non-invasive approach that may support biomarker discovery and clinical research.2

Conclusion

While the concept that toxic chemicals accumulate in the body and are the cause of various health problems has long been a fundamental tenet of traditional healthcare systems around the world, researchers have learned a great deal in recent years about how toxins and toxicants affect us, where they originate, and how to improve our ability to detoxify in a toxic world. Understanding toxicity and taking practical steps to improve biotransformation are essential parts of any integrative approach to your patients’ health and well-being.

The most important aspect of management in a patient with an elevated blood lead concentration is identifying the source of lead and removing it from the patient’s environment.14 Optimizing the patient’s nutritional status is also paramount, with particular attention to ensuring adequate iron, calcium, and zinc intake.14 What other steps can clinicians take to recognize toxicity in their patients? Learn more at IFM’s Environmental Health Advanced Practice Module (APM).

Learn More About Biotransformation Pathways and Toxic Exposures

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References

  1. 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.
  2. Li S, Wang J, Zhang B, et al. Urinary lead concentration is an independent predictor of cancer mortality in the US general population. Front Oncol. 2018;8:242. doi:10.3389/fonc.2018.00242.
  3. Lead poisoning and health. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/lead-poisoning-and-health . Published August 23, 2019. Accessed August 30, 2021.
  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. 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.
  6. Obeng-Gyasi E. Lead exposure and cardiovascular disease among young and middle-aged adults. Med Sci (Basel). 2019;7(11):E103. doi:10.3390/medsci7110103.
  7. Lead toxicity: what are possible health effects from lead exposure? Agency for Toxic Substances and Disease Registry. https://www.atsdr.cdc.gov/csem/leadtoxicity/physiological_effects.html . Published July 2, 2019. Accessed August 31, 2021.
  8. Vaziri ND. Mechanisms of lead-induced hypertension and cardiovascular disease. Am J Physiol Cell Physiol. 2008;295(2):H454-H465. doi:10.1152/ajpheart.00158.2008.
  9. He L, Chen Z, Dai B, Li G, Zhu G. Low-level lead exposure and cardiovascular disease: the roles of telomere shortening and lipid disturbance. J Toxicol Sci. 2018;43(11):623-630. doi:10.2131/jts.43.623.
  10.  Jalili C, Kazemi M, Cheng H, et al. Associations between exposure to heavy metals and the risk of chronic kidney disease: a systematic review and meta-analysis. Crit Rev Toxicol. 2021;51(2):165-182. doi:10.1080/10408444.2021.1891196.
  11.  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.
  12.  Sancar F. Childhood lead exposure may affect personality, mental health in adulthood. JAMA. 2019;321(15):1445-1446. doi:10.1001/jama.2019.1116.
  13.  Reuben A, Schaefer JD, Moffitt TE, et al. Association of childhood lead exposure with adult personality traits and lifelong mental health. JAMA Psychiatry. 2019;76(4):418-425. doi:10.1001/jamapsychiatry.2018.4192.
  14.  Halmo L, Nappe TM. Lead toxicity. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK541097/. Published July 10, 2021. Accessed August 31, 2021.
  15.  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.
  16.  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.
  17.  Kim M-G, Ryoo J-H, Chang S-J, et al. Blood lead levels and cause-specific mortality of inorganic lead-exposed workers in South Korea. PLoS One. 2015;10(10):E140360. doi:10.1371/journal.pone.0140360.
  18.  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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