Lead (Pb) is a metal which has been associated with human activities for the last 6000 years. Lead has no known beneficial function in human metabolism. It is one of the oldest known and most widely studied occupational and environmental toxins.
In ancient civilizations, uses of lead included the manufacture of kitchen utensils, trays, and other decorative articles. However, Pb is quite toxic to humans, with the most deleterious effects on the hemopoietic, nervous, reproductive systems and the urinary tract. In the last century, Pb toxicity has been extensively studied. The greatest risk for harm, even with only minute or short-term exposure, is to infants, young children, and pregnant women. In recent years, the focus in Pb toxicity has shifted away from adults exposed to high doses in industrial settings to the larger population of asymptomatic children with lesser exposures.
The early victims of lead toxicity were mainly lead workers and wine drinkers. Lead’s sweet flavor made it useful in winemaking, to counteract the astringent flavor of tannic acid in grapes. Lead-sweetened wine, containing as much as 20 mg of lead per liter, was an important part of the diet of upper-class Romans. The synchronous decrease in fertility and increase in psychosis among the Roman aristocracy has raised speculation implicating lead poisoning in the fall of Rome.
Atomic mass: 207.2
Sources of Exposure
The main sources of Pb exposure are paints, water, food stored in lead can liners, food stored in ceramic jars, dust, soil, kitchen utensils, and leaded gasoline (although banned in the United States in 1995 for automobiles, previous usage has widely dispersed it in the environment). Other potential sources are contaminated water (pipes cast in lead or soldered using lead solder), ammunition (shot and bullets), bathtubs (cast iron, porcelain, steel), batteries, ceramics, chemical fertilizers, leaded glass, newsprint and colored advertisements, and tobacco smoke. Children absorb lead up to 8x more efficiently than adults. Ingestion of deteriorating lead-based paint chips or dust is the primary source of lead exposure in children. Also, toys and other children’s products may contain lead or be painted with lead-based paint; imported children’s products pose a greater risk. Animal models also suggest that lead can be absorbed through the skin. Lead acetate can be found in some cosmetic products, hair dyes and rinses. Safe cosmetics are listed on the Environmental Working Group website.
In 1989, the U.S. Environmental Protection Agency reported that more than one million elementary schools, high schools, and colleges are still using lead-lined water storage tanks or lead-containing components in their drinking fountains. The EPA estimates that drinking water accounts for approximately 20% of young children's lead exposure. Other common sources are lead paint residue in older buildings (as in inner cities) and living in proximity to industrial areas or other sources of toxic chemical exposure, such as commercial agricultural land.
Lead deposits in the bone, teeth, kidney tubules, brain, thyroid, adrenals, liver, pancreas, heart and aorta. Lead in bone is of interest for two reasons. Bone is the largest repository of the body burden of lead, and, secondly, it is now recognized that lead may, in fact, influence bone metabolism. Lead may affect the ability of bone cells to respond to hormone regulation. A calcium-binding protein, osteocalcin, synthesized by osteoblasts, is inhibited at low levels of lead exposure, which may impair new bone formation as well as the functional coupling of osteoblasts and osteoclasts. Lead may also impair synthesis of components of bone matrix such as collagen or bone sialoproteins. A common molecular basis for the cellular effects may be altered or impaired calcium and cAMP messenger systems in cells.
In most individuals there is a "lead balance", that is one excretes as much as they take in, and the tissue levels are below the concentrations which result in pathological changes. However, an increase in the rate of intake will result in accumulation or a "positive lead balance". Since lead is chemically very similar to calcium, the body transports it as if it were calcium. Thus, the first place to which it is transported is to the plasma and the membrane sites in soft tissues. It is then distributed to the other sites mentioned above, where calcium plays an important role.
Lead is a divalent cation, and it binds strongly to sulfhydryl groups on proteins. Much of lead’s toxicity can be attributed to distortion of enzymes and structural proteins, but this versatile toxicant has many other targets. Lead binds to hemoglobin and prevents heme synthesis and this depresses mitochondrial respiration and the electron transport chain. Lead also blocks the impulse transmission and release of acetylcholine that leads to neurological defects.
Chronic, low-level lead exposure (blood levels <10 µg/dL) is associated with increases in hypertension risk and reduction in kidney function. Higher levels of lead exposure affect the endocrine glands (changing the levels of thyroid hormones [at serum lead levels over 40-60 µg/dL] and reproductive hormones [at serum lead levels over 30-40 µg/dL] and lowering vitamin D levels).
Many of lead’s toxic properties are due to its ability to mimic or compete with calcium. At picomolar concentrations, lead competes successfully with calcium for binding sites on cerebellar phosphokinase C and thereby affects neuronal signaling. It inhibits calcium entry into cells.
Delta aminolevulinic acid dehydratase is extremely sensitive to lead. Inhibition of this enzyme results in increased circulating aminolevulinic acid (ALA). ALA is a weak gamma-aminobutyric acid (GABA) agonist that decreases GABA release by presynaptic inhibition. Increased circulating ALA may account for some of the behavioral disorders seen in patients with porphyria and perhaps in lead toxicity.
Of the many organs affected by lead, the most important is the central nervous system (CNS). Lead has diverse impacts on the CNS. Immature astrocytes are sensitive to lead, and lead interferes with myelin formation and the integrity of the blood-brain barrier. Lead interferes with the synthesis of collagen and affects vascular permeability. At high enough doses, this results in brain edema and hemorrhage as well as brain lesions, cognitive deficits, and behavioral changes. Lead can leave the body through feces or urine.
One of the earliest diagnostic signs present is the appearance of "lead lines" at the gingival border in the mouth. This occurs because the lead following calcium pathways is secreted with the saliva. It then is involved in a reaction with oral bacteria that produce sulfides. The lead reacts with these compounds to form a purplish, or black lead sulfide deposit which precipitates in the region of highest concentration, the "protected area" at the gingival border. Other metals also produce this phenomenon, but with differing colors for the deposit.
Following acute ingestion of a large amount of lead, there will be direct tissue interaction. This includes tissue mucosal tissue damage in the GI tract, and convulsion possibly resulting in death. The most sensitive system is the hematopoietic (blood forming) system, with hypochromic microcytic anemia common. The biosynthesis of hemes in general is deranged by the presence of lead. All actively dividing cells are especially susceptible; hence acute intoxication has major potential for GI and renal mucosal damage. In addition, there is a high risk of neurological damage. Over long-term exposure with a gradual build-up of a positive lead balance, there is no sudden onset of symptoms as seen with acute poisoning. The initial symptoms include clumsiness, ataxia, vertigo, irritability and insomnia. In affected children, they are often considered “slow" - the real basis for the difficulty is not recognized. As the lead levels rise, hyper-excitability is seen. Confusion, delirium and convulsions may occur in some cases, while in others there is progressive lethargy leading to a comatose state. Studies have shown a slowing of sensory motor reaction time in male lead workers and some disturbance of cognitive function in workers with blood lead levels >40 µg/100 ml.
Exposure to high Pb levels can produce renal tubular damage with glycosuria and aminoaciduria (saturnine gout). There are several experimental studies in rats and mice in which long-term administration of a lead compound in food or drinking water produced renal tumors. Further studies show that renal carcinogenicity occurs on a background of proximal tubular cell hyperplasia, cytomegaly and cellular dysplasia. Renal adenocarcinoma occurs in a high percentage of exposed animals, and incidence is dependent on length and severity of Pb exposure.
At very high blood Pb levels, lead is a powerful abortifacient. At lower levels, it has been associated with miscarriages and low birth weights of infants. Predominantly to protect the developing fetus, legislation for Pb workers often includes lower exposure criteria for women of “reproductive capacity".
Additional symptoms of chronic lead toxicity include: anemia, anorexia, anxiety, bone pain, brain damage, confusion, constipation, convulsions, dizziness, drowsiness, fatigue, headaches, hypertension, inability to concentrate, indigestion, irritability, loss of appetite, loss of muscle coordination, memory difficulties, muscle pain, pallor, tremors, vomiting, and weakness.
Lead is a known neurotoxin and excessive blood lead levels in children have been linked to learning disabilities, attention deficit disorder (ADD), hyperactivity syndromes, and reduced intelligence and school achievement scores.
Signs & Symptoms
Lead Toxicity Evaluation
In adults, lead toxicity should be considered in the differential diagnosis of abdominal pain, arthralgia, hypertension, severe headache, increased intracranial pressure, CNS dysfunction, anemia, and renal dysfunction. An occupational history and an inventory of possible sources of exposure are useful. Measuring of blood lead concentration is the most effective and accepted diagnosis for lead exposure. The accepted toxic threshold for lead in infants, children and women of child bearing age is ≤ 10 µg/dL, approved by the American Pediatric Association. However, for adults there is no such threshold, as concentration of lead from 10 µg/dL and above in blood exhibits toxicity. Additionally, Pb blood levels are only indicative of exposure over the previous 90 days. Any child with growth failure, abdominal pain, behavior change, hyperactivity, language delay, or anemia should have a blood lead test to rule out lead toxicity.
Nutrients Known to be Protective Against Lead
Sulfur-containing amino acids, calcium, iron, zinc, vitamin C, vitamin E, certain algae (laminaria, fucus, chlorella) all are antagonistic for reuptake and retention of lead. EDTA has been clinically shown to be an effective IV chelating agent for lead and DMSA is an effective oral chelator of lead.
Toxicity from inorganic lead can be treated with EDTA chelation, but organic lead compounds such as tetra-ethyl lead produces a similar symptomology but cannot be treated with this agent because they have already formed strong ligands with their organic constituents. The alkyl lead is eventually converted to inorganic lead, which can be treated with EDTA.
In the United States, DMPS is not considered an appropriate drug against lead toxicity. DMPS, although known for its antidotal efficacy against mercury, has also been reported to have limited efficacy for treating lead and arsenic poisoning. The drug is registered in Germany for treatment of mercury intoxication, but it is not approved in the United States, so unless special permission is given by the U.S. Food and Drug Administration, it is unlawful for physicians to use it in the United States (though some do) - nor is it lawful for pharmacies to compound it.
Protocols for Lead Detoxification
As with all detoxification protocols, the type, dose and duration of detoxification agents should always be individually assessed. The following may serve as a basic guideline for detoxification of excess lead from chronic exposure. After 60 days, laboratory screening should be used to reassess protocol. Before initiating a detoxification program, a CBC with chemistry, including a thyroid panel with lipids, should be performed. In addition, whole blood elements to assess the mineral status and a urine creatinine clearance should be performed every 60 days when using synthetic detoxifying agents (EDTA). Administration of synthetic agents may cause a depletion of essential elements such as zinc, iron, calcium, magnesium, copper and other trace minerals. Of greatest concern is potential kidney toxicity that can occur when the body releases its lead stores for excretion through the kidneys. Those with underlying kidney disease may not be able to undergo aggressive lead detoxification therapy.
- The cornerstone of lead toxicity management is the termination of exposure. For children, this means inspection of the home, and if this does not reveal lead, a survey of other possible sources.
- Assess whole blood cell element analysis to determine mineral nutrient deficiency and supplement appropriately.
Supplement with calcium as MCHC 1000 mg daily.
Supplement with oral zinc 25 to 50 mg daily.
Supplement 200 mcg of selenium daily.
Assess vitamin D status (25-hydroxy vitamin D) and supplement vitamin D-3 accordingly.
Supplement buffered vitamin C (corn free source) at 500 mg up to 3000 mg daily adjusting to bowel tolerance. Vitamin C is a free-radical scavenger that can protect against oxidative damage caused by lead, mercury, and cadmium. It may prevent the absorption of lead as well as inhibit its cellular uptake and decrease its cellular toxicity. 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.
Supplement natural vitamin E (D-alpha tocopherol) at 400 IU daily.
Garlic has been shown to detoxify lead. 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. Add garlic to the diet and supplement with standardized garlic-allicin powder extract.
Algal cells have a remarkable ability to take up and accumulate heavy metals from their external environment. The primary ones used for toxic metal excess are Chlorella vulgaris, a green microalga, and Laminaria japonica, a brown alga. Chlorella and Laminaria japonica are both chelators, moving toxic metals out of the body, and transporters, moving metals from deeper stores to more readily removable areas. Both work in unison with each other and can remove toxic metals from the body through urinary excretion. Administer 1000 to 2000 mg of Laminaria japonica concentrate (Modifilan) daily and 1000 to 2000 mg of chlorella. Adjust dosage to bowel tolerance; may be taken for long periods of time.
Cilantro works well with alga to chelate, or bind up toxic metals. The issue with cilantro taken alone is that although it chelates metals, it does not remove them in the urine. This means they can recirculate to deposit elsewhere in the body. Hence, taken with algas, metals are more effectively eliminated in the urine.
Shilajit is an ancient traditional medicine (Tibetan and Ayurvedic) and has been ascribed a number of pharmacological activities. It has been used for ages as a rejuvenator and for treating a number of disease conditions. It is an effective detoxifier of metals and contains over 60 minerals. Modern scientific research has systematically validated a number of properties of shilajit and has proven that shilajit is truly a panacea. It is important to purchase the highest grade of shilajit.
Instruct patient to drink adequate amounts of pure water (Adult’s urine volume should be about 2 liters per day).
More aggressive treatment involves the use of EDTA chelation (edetate calcium disodium) (CaNa2EDTA) (Calcium Disodium Edetate®) or oral dimercaptosuccinic acid (succimer DMSA). CaNa2EDTA was the preferred method until recently, when dimercaptosuccinic acid, an oral agent, was found to have equal efficacy. Both agents will reduce an elevated blood lead level to 40%–50% of its baseline. After treatment is concluded (5 days for EDTA; 19 days for DMSA), body pools tend to equilibrate, and blood lead levels begin to rise, often requiring repeated courses.
Check for renal clearance first. The protocol for IV EDTA chelation is available from the American College for the Advancement in Medicine (ACAM). If you are unfamiliar with EDTA or DMSA chelation therapy, you may wish to refer the patient to a physician who is board certified by the American Board of Chelation Therapy (ABCT).
Aga M, Iwaki K, Ueda Y, et al. Preventive effect of Coriandrum sativum (Chinese parsley) on localized lead deposition in ICR mice. J Ethnopharmacol 2001;77:203-208.
Antilla A, Keikkila P, Pukkala E, et al. Excess lung cancer among workers exposed to lead. Scand J Work Environ Health 1995; 21: 460-469.
Aposhian V. DMSA and DMPS - Water soluble antidotes for heavy metal poisoning. Ann Rev Pharmacol Toxicol 1983;23:193-215.
Aposhian HV, Maiorino RM, Gonzalez-Ramirez D, et al. Mobilization of heavy metals by newer, therapeutically useful chelating agents. Toxicology 1995;31;97(1-3):23-38.
ATSDR. ToxGuide for Lead. 2008a:1–2. Available online at http://www.atsdr.cdc.gov/toxguides/toxguide-13.pdf.
ATSDR. Toxicological Profile For Lead. 2007b:1-582. Available online at http://www.atsdr.cdc.gov/toxprofiles/tp13.pdf.
Bressler J, Goldstein G. 1991. Mechanisms of lead neurotoxicity. Biochem. Pharnacol. 41:479-84.
Cory-Slechta DA. 1997. Relationships between Pb-induced changes in neurotransmitter system function and behavioral toxicity. Neurotox. 18:673-88 18.
Cremer JE. The toxicity of tetraethyl lead and related alkylmetallic compounds. Ann Occup Hyg 1961; 3:226–230.
Cremer JE, Callaway S. Further studies on the toxicity of some tetra and trialkyl lead compounds. Br J Ind Med 1961;18:227-282.
Flora SJS, Bhattacharya R, Vijayaraghavan R. Combined therapeutic potential of meso 2,3-dimercaptosuccinic acid and calcium disodium edetate in the mobilization and distribution of lead in experimental lead intoxication in rats. Fund. Appl. Toxicol. 1995;25:233-240. [PubMed]
Fu H, Boffetta P. Cancer and occupational exposure to inorganic lead compounds: a meta-analysis of published data. Occup Environ Med 1995;52:73-81.
Fulton M, Raab G, Thomson G, et al. 1987. Influence of blood lead on the ability and attainment of children in Edinburgh. Lancet 1:1221-26.
Gennart JP, Bernard A, Lauwerys R. Assessment of thyroid, testis, kidney and autonomic nervous system function in lead-exposed workers. Int Arch Occup Environ Health 1992;64:49-57.
Gersl V, Hrdina R, Vavrova J, Holeckova M, Palicka V, Vogkova J, Mazurova Y, Bajgar J. Effects of repeated administration of dithiol chelating agent- sodium 2,3-dimercapto 1-propanesulphonate (DMPS) - on biochemical and hematological parameters in rabbits. Acta. Medica. 1997;40:3-8. [PubMed]
Gilfillan SC. 1965. Lead poisoning and the fall of Rome. J. Occup. Med. 7:53-60 2.
Hanninen H, Aitio A, Kovala T, et al. Occupational exposure to lead and neuropsychological dysfunction. Occup Environ Med 1998;55:202-209.
International Agency for Research on Cancer. Monographs on the evaluation of the carcinogenic risk of chemicals to humans. 1980;23:149-150.
Kaplan, Drora, Daniel Christiaen, and Shoshana Malis Arad. Chelating properties of extracellular polysaccharides from Chlorella spp. Applied and environmental microbiology 53.12 (1987): 2953-2956.
Koller LD. Immunological effects of lead. In: Mahaffey KR, ed. Dietary and Environmental Lead: Human Health Effects. Amsterdam: Elsevier Science Publishers, 1985; 339-354.
Kotok D. 1972. Development of children with elevated blood lead levels: a controlled study. J. Pediatr. 80:57-61.
Landrigan PJ, Boffetta P, Apostoli P. 2000. The reproductive toxicity and carcinogenicity of lead: a critical review. Am. J. Ind. Med. 38:231-43 24.
Lyngbye T, Hansen ON, Trillingsgaard A, et al. 1990. Learning disabilities in children: significance of low level lead exposure and confounding factors. Acta Pedriatr. Scand. 79:352-60.
Mao, P., and Molnar, J. J. The fine structure and histochemistry of lead-induced renal tumors in rats. Am. J. Pathol. 50: 571-603 (1967).
Moore, M. R., and Meredith, P. A. The carcinogenicity of lead. Arch. Toxicol. 42: 87-94 (1979).
Olszewer, E., and Carter, J. EDTA chelation therapy: a retrospective study of 2,870 patients. Journal of Advancement in Medicine Special Issue 2:1-2 (1989), 197-211.
Pocock SJ, Smith M, Baghurst P. 1994. Environmental lead and children’s intelligence: a systematic review of the epidemiological evidence. BMJ 309:11889-97.
Rabinowitz MB, Wetherill GW, Kopple JD. Kinetic analysis of lead metabolism in healthy humans. J Clin Invest 1976;58:260-270.
Schwartz BS, Stewart W, Hu H. Neurobehavioural testing in workers occupationally exposed to lead. Occup Environ Med 2002; 59: 648-649.
Sharma V, Kansai L, Sharma A. Prophylactic efficacy of Coriandrum sativum (coriander) on testis of lead-exposed mice. Biol Trace Elem Res 2010;136: 337-354.
Simons T. 1993. Lead-calcium interactions in cellular lead toxicity. Neurotoxicology 14:77-85 9.
Van Esch, G. J., and Kroes, R. The induction of renal tumors by feeding basic lead acetate to mice and hamsters. Br. J. Cancer 23: 765-771 (1969).
Wong O, Harris F. Cancer mortality study of employees at lead battery plants and lead smelters, 1947–1995. Am J Ind Med 2000;38:255-270.
Xue H.B., W.Stumm, L.Sigg: The binding of Heavy Metals to Algal Surfaces, Water Res 1988;22, 917.