Lead Toxicity ACAM April 21, 2010

Dorothy Merritt, MDThis lecture is dedicated to Clair Patterson, whose inadvertant discovery of severe lead contamination in the US while trying to date the age of the Earth, lead to the Clean Air Act of 1970 and the removal of lead from gasoline for sale in the US in 1986 despite attempts of the ETHYL Corporation to get him fired from his position at Cal Tech. His persistance paid off for the betterment of society.

This lecture also recognizes Thomas Midgley, an engineer whose dabbling in chemistry resulted in lead being introduced into gasoline, CFCS (chlorofluorocarbons) being unleashed on the atmosphere. His untimely death was from being strangled in a bed of pulleys he had himself invented for turning polio victims, which he himself contracted after his construction of his device. He may deserve the 20th century’s top “Darwin Award” for removing his DNA from the pool in a most unusual way caused by his own invention.

Lead –Who Is Affected The MostLead –Who Is Affected The Most

Blood-brain barrier is not complete Blood-brain barrier is not complete until 6 months of age so lead can until 6 months of age so lead can be absorbed by CNS of fetus and be absorbed by CNS of fetus and young childyoung child

((lead crosses placenta).lead crosses placenta).

Absorption of lead is estimated to be as much as Absorption of lead is estimated to be as much as FIVE FIVE TO TEN TIMES GREATERTO TEN TIMES GREATER in infants and young children in infants and young children than in adults.than in adults.

Needleman H. Ann Rev Med 2004;55:209-222Needleman H. Ann Rev Med 2004;55:209-222

Lead: Where does it come from?Lead: Where does it come from?

Soft vinyl lunchboxes- found to contain more Soft vinyl lunchboxes- found to contain more than 90 times legal limitthan 90 times legal limit

Candy imported from MexicoCandy imported from Mexico Imported children’s jewelryImported children’s jewelry Leaded gasoline- currently used in farm Leaded gasoline- currently used in farm

machinery, boats, racing carsmachinery, boats, racing cars

Lead: Where does it come from?Lead: Where does it come from?

AirAir-- indoor dust exposure greater than soil or indoor dust exposure greater than soil or paint chipspaint chips

WaterWater- 20% of total daily exposure (“lead-free” - 20% of total daily exposure (“lead-free” brass fixtures 5-7% lead)brass fixtures 5-7% lead)

ImportsImports- lead-glazed dishware, leaded crystal. - lead-glazed dishware, leaded crystal. Lead solder in imported canned food,foods from Lead solder in imported canned food,foods from Mexico, China, Spices, WineMexico, China, Spices, Wine

MedicineMedicine-- Ayurvedic and foreign medicines Ayurvedic and foreign medicines Vinyl mini-blindsVinyl mini-blinds imported before 1996 imported before 1996 Cosmetics Cosmetics

Lead in WineLead in Wine

For 432 wines tested in the bottle, the lead For 432 wines tested in the bottle, the lead in domestic wines ranged from 1 to 521 in domestic wines ranged from 1 to 521 parts per billion, with an average of 41. parts per billion, with an average of 41. The level in imported wines ranged from 4 The level in imported wines ranged from 4 to 673 parts per billion with an average of to 673 parts per billion with an average of 94.94.

Lead in WineLead in Wine

. . When the wine was poured, the level in domestic When the wine was poured, the level in domestic wines ranged from 3 to 720 parts per billion, with an wines ranged from 3 to 720 parts per billion, with an average of 58, and imports from 13 to 1,980, with average of 58, and imports from 13 to 1,980, with an average of 195an average of 195

The EPA limit for lead in drinking water is 50 parts The EPA limit for lead in drinking water is 50 parts per billion.per billion.

Bureau of Alcohol, Tobacco, and Firearms 1991Bureau of Alcohol, Tobacco, and Firearms 1991

Lead glaze used on plate imported from Lead glaze used on plate imported from Portugal and sold at American Home Portugal and sold at American Home

FurnishingsFurnishings

Fatal Case of Lead Poisoning Fatal Case of Lead Poisoning from Injestion of Jewelryfrom Injestion of Jewelry

A 4-year old male died of acute encephalopathy 3 days after A 4-year old male died of acute encephalopathy 3 days after being admitted for intractable vomiting, stomach pain, and being admitted for intractable vomiting, stomach pain, and listlessness.listlessness.

A metal charm, seen in his stomach on radiograph and was A metal charm, seen in his stomach on radiograph and was later found to contain 99.1% lead.later found to contain 99.1% lead.

Reebok later recalled 500,000 of these charms, which they had Reebok later recalled 500,000 of these charms, which they had given away free with pairs of girl’s shoes. given away free with pairs of girl’s shoes.

MMWR. March 23, 2006 / 55(Dispatch);1-2MMWR. March 23, 2006 / 55(Dispatch);1-2

Is There A Safe Level Of Lead?Is There A Safe Level Of Lead?

In Oct. 2007, the Campaign for Safe Cosmetics reported In Oct. 2007, the Campaign for Safe Cosmetics reported that 61% of lipsticks it tested contained lead in levels up that 61% of lipsticks it tested contained lead in levels up to .65 ppm. The FDA has determined levels above to .65 ppm. The FDA has determined levels above

.1 ppm in toys are hazardous to children’s health..1 ppm in toys are hazardous to children’s health. In Nov. 2007, Sens. John Kerry, Barbara Boxer and In Nov. 2007, Sens. John Kerry, Barbara Boxer and

Dianne Feinstein urged FDA to test a range of lipsticks Dianne Feinstein urged FDA to test a range of lipsticks for lead, publicly report the results, and take immediate for lead, publicly report the results, and take immediate action to reduce consumers’ exposure to lead from action to reduce consumers’ exposure to lead from cosmetic products.cosmetic products.

Fourteen months later, FDA has made no public Fourteen months later, FDA has made no public statements, issued no reports, and taken no action to statements, issued no reports, and taken no action to reduce consumers’ exposure. reduce consumers’ exposure.

Occupations at risk for lead Occupations at risk for lead toxicitytoxicity

Electricians, plumbers, painters, Electricians, plumbers, painters, ceramicists,ceramicists, Munitions specialists, paint and ink Munitions specialists, paint and ink

manufacturing, etc.manufacturing, etc. Electrical tower and generating station Electrical tower and generating station

maintainancemaintainance..

http://www.haz-map.com/lead.htmhttp://www.haz-map.com/lead.htm

Distribution of workers with BLLs greater than or equal to 25 µg/dL, by industry, 2003-2004

Services (3.3%)

Mining (7.6%)

Construction (17.1%)

Manufacturing (70.5%)

Other (1.5%)

Total = 12,712

Section 44 of The Construction Chart Book, Fourth Edition, December 2007 -

Number of workers with BLLs greater than or equal to 25 or 40 µg/dL, by detailed construction sector, 2003-2004

Other heavy & civil engineering

Building equipment

Nonresidential

Residential

Foundation, structure, & building

Utility

Highway, street, & bridge

Other specialty trade

Building finishing

Blood lead levels (BLLs)

25 µg/dL

40 µg/dL

1,051

406

412

92

70

41

41

39

14 Section 44 of The Construction Chart Book, Fourth Edition, December 2007

Lead ToxicologyLead Toxicology

Approximately 30-40% of inhaled lead is Approximately 30-40% of inhaled lead is absorbed into the bloodstream. absorbed into the bloodstream.

Infants can absorb up to 50% of lead Infants can absorb up to 50% of lead ingested from food, water, contaminated ingested from food, water, contaminated dust, or soil.dust, or soil.

Adults absorb only 10-15% of ingested lead.Adults absorb only 10-15% of ingested lead.

Lead Toxicology-BLL vs BoneLead Toxicology-BLL vs BoneBlood Lead LevelsBlood Lead Levels Reflects last 30-60 days of exposureReflects last 30-60 days of exposure Doesn’t show previous toxic levels that predict future toxicityDoesn’t show previous toxic levels that predict future toxicity Approximately 40-70% comes from bone storage (isotope studies)Approximately 40-70% comes from bone storage (isotope studies) In pregnancy, 80% of the BLL can be from bone storageIn pregnancy, 80% of the BLL can be from bone storage NHANES studies use BLL in their analysisNHANES studies use BLL in their analysis

Bone Lead LevelsBone Lead Levels Predict long term health outcomes-vascular, renal, neurological, Predict long term health outcomes-vascular, renal, neurological,

cataracts, hypertensioncataracts, hypertension NIH Normative Aging Studies use Bone Lead by K shell fluoroscopy NIH Normative Aging Studies use Bone Lead by K shell fluoroscopy

in their analysisin their analysis Currently you must mobilize Lead from Bone with EDTA challenge to Currently you must mobilize Lead from Bone with EDTA challenge to

predict bone stores clinicallypredict bone stores clinically

Deposition in Soft TissueDeposition in Soft Tissue

Autopsy studies show the liver to be Autopsy studies show the liver to be the largest repository of soft tissue the largest repository of soft tissue lead (33%), followed by kidney cortex lead (33%), followed by kidney cortex and medulla, pancreas, ovary, spleen, and medulla, pancreas, ovary, spleen, prostate, adrenal gland, brain, fat, prostate, adrenal gland, brain, fat, testis, heart, and skeletal muscle. testis, heart, and skeletal muscle.

Routes of ExcretionRoutes of Excretion

Approximately one-third of total excretion of Approximately one-third of total excretion of absorbed lead occurs via bile, gastric fluid, absorbed lead occurs via bile, gastric fluid, and saliva. and saliva.

The remainder occurs via renal excretion. The remainder occurs via renal excretion.

Lead can also be excreted in significant Lead can also be excreted in significant amounts via sweat. amounts via sweat.

NOEL NOEL NNo o OObservable bservable EEffect ffect LLevel evel

Lead is unique as a toxicant in that there is agreement Lead is unique as a toxicant in that there is agreement among these governmental agencies as to its among these governmental agencies as to its toxicitytoxicity

CDC CDC Centers for Disease Control Centers for Disease Control ATSDRATSDR Agency for Toxic Substances and Disease Agency for Toxic Substances and Disease

RegistryRegistry EPAEPA Environmental Protection Agency: Environmental Protection Agency:

““There is no toxic threshold for lead. This means There is no toxic threshold for lead. This means there is no measurable level of lead in the body there is no measurable level of lead in the body below which no harm occurs.” below which no harm occurs.”

Lead and ChildrenLead and Children

““The developing nervous system of a child The developing nervous system of a child can be affected adversely at BLLs of less can be affected adversely at BLLs of less than 10 µg/dL. than 10 µg/dL.

““For children, there may be no threshold for For children, there may be no threshold for developmental effects.”developmental effects.”

ATSDR. Case Studies in Environmental Medicine. ATSDR. Case Studies in Environmental Medicine. Lead Toxicity.Lead Toxicity.

www.atsdr.cdc.gov/HEC/CSEM/lead/physiologic_effects.html

Galveston, Texas-Pre IKEGalveston, Texas-Pre IKE

20% of all Galveston children have lead 20% of all Galveston children have lead levels above CDC poisoning levels-14ug/dllevels above CDC poisoning levels-14ug/dl

12 block area mostly affected12 block area mostly affected

Dr. Dr. WinifredWinifred J. J. HamiltonHamilton PhD, SM. PhD, SM. ...... " "Childhood Lead Childhood Lead Poisoning in Galveston, TexasPoisoning in Galveston, Texas," ,"

Evidence of PediatricToxicityEvidence of PediatricToxicity Below 10 Below 10 µg/dLµg/dL

A significant inverse relationship was observed A significant inverse relationship was observed between blood lead levels and reading and math test between blood lead levels and reading and math test scores and comprehension testing.scores and comprehension testing.

The correlation was noted at levels as low as 2.5 The correlation was noted at levels as low as 2.5 µg/dL.µg/dL.

The effect of blood lead was stronger in those with The effect of blood lead was stronger in those with levels below 5.0 µg/dL than those with levels above levels below 5.0 µg/dL than those with levels above 5.0 µg/dL. 5.0 µg/dL.

Public Health RepPublic Health Rep 2000;115:521-529. 2000;115:521-529.

Lead Toxicity Adult ConditionsLead Toxicity Adult Conditions

Neurological/behavioralNeurological/behavioral CardiovascularCardiovascular RenalRenal Degenerative Degenerative Cataracts, Osteoporosis, AutoimmuneCataracts, Osteoporosis, Autoimmune

Major Studies : NHANES (blood levels)Major Studies : NHANES (blood levels) NIH (bone levels)NIH (bone levels) www.cdc.gov/nchs/nhanes.htmwww.cdc.gov/nchs/nhanes.htm www.ncbi.nlm.nih.govwww.ncbi.nlm.nih.gov

Recognition of Heavy Metal ExposureRecognition of Heavy Metal Exposure

““Much about metals toxicity, such as the genetic Much about metals toxicity, such as the genetic factors that may render some individuals especially factors that may render some individuals especially vulnerable to metals toxicity, remains a subject of vulnerable to metals toxicity, remains a subject of intense investigation.” intense investigation.”

““It is possible that low-level metals exposure It is possible that low-level metals exposure

contributes much more towards the causation of contributes much more towards the causation of chronic disease and impaired functioning than chronic disease and impaired functioning than previously thought.”previously thought.”

Howard Hu MD MPH (keynote speaker ACAM 2009)Howard Hu MD MPH (keynote speaker ACAM 2009) Harvard School of Environmental and Occupational Health (Now in Michigan)Harvard School of Environmental and Occupational Health (Now in Michigan)

CDC NHANES Blood LeadCDC NHANES Blood Lead

Circulation Circulation 2006;114;1347-13492006;114;1347-1349Tim S. Nawrot and Jan A. StaessenTim S. Nawrot and Jan A. Staessen

NHANES DATANHANES DATA

“ “ Low Level Environmental Low Level Environmental Exposure To Lead Unmasked Exposure To Lead Unmasked

As Silent Killer”As Silent Killer”Editorial in Circulation 2006 with Latest NHANES Study On Lead And

Vascular Disease

Lead Toxicity-Early SymptomsLead Toxicity-Early Symptoms

Diffuse muscle weaknessDiffuse muscle weakness General fatigue/lethargyGeneral fatigue/lethargy Attention deficit/ irritabilityAttention deficit/ irritability MyalgiaMyalgia Joint pain/arthritisJoint pain/arthritis Loss of appetiteLoss of appetite Unusual taste in mouth/change in taste Unusual taste in mouth/change in taste

of foodof food

Lead Toxicity SymptomsLead Toxicity Symptoms

HeadacheHeadache InsomniaInsomnia IrritabilityIrritability Diminished libidoDiminished libido Weight loss of 10 lbs or more without Weight loss of 10 lbs or more without

known causeknown cause TremulousnessTremulousness

Lead-Related SymptomsLead-Related Symptoms

Personality ChangesPersonality Changes Peripheral neuropathy in extensor Peripheral neuropathy in extensor

surfaces- most common neurological surfaces- most common neurological symptom in adultssymptom in adults

Abdominal pain/crampingAbdominal pain/cramping Nausea/vomitingNausea/vomiting Short-term memory lossShort-term memory loss DepressionDepression

Lead-Related SymptomsLead-Related Symptoms

IncoordinationIncoordination ParesthesiasParesthesias ConstipationConstipation Inability to concentrateInability to concentrate ImpotenceImpotence

Normative Aging NIH StudyNormative Aging NIH StudyLead in BonesLead in Bones

30 year study looking at “normal aging”30 year study looking at “normal aging”

Lead stored in the bones from earlier in life is Lead stored in the bones from earlier in life is released into the blood and soft tissues from released into the blood and soft tissues from increased turnover of bones associated with increased turnover of bones associated with normal agingnormal aging

Lead and Osteoporosis: Mobilization of lead from bone in Lead and Osteoporosis: Mobilization of lead from bone in postmenopausal women Sibergeld,E,Schwartz,J,et al…. postmenopausal women Sibergeld,E,Schwartz,J,et al….

Bone StorageBone Storage

A study of lead-stable isotope signatures revealed A study of lead-stable isotope signatures revealed that approximately 40-70 percent of blood lead in that approximately 40-70 percent of blood lead in adults comes from bone lead.adults comes from bone lead.

10-88% of blood lead may come from bone due to 10-88% of blood lead may come from bone due to increased mobilization of bone during pregnancy. increased mobilization of bone during pregnancy. approximately 80 percent of cord blood may result approximately 80 percent of cord blood may result from liberated bone. from liberated bone.

Hernandez-Avila M. Arch Environ Health 2000;55:355.Hernandez-Avila M. Arch Environ Health 2000;55:355.

Populations at risk for lead toxicity Populations at risk for lead toxicity from increased bone turnoverfrom increased bone turnover

Menopausal womenMenopausal women

Hyperthyroidism in either sexHyperthyroidism in either sex

Cisplatin chemotherapyCisplatin chemotherapy

Patients with osteoporosis or osteopeniaPatients with osteoporosis or osteopenia

Vitamin D deficiency-50% of populationVitamin D deficiency-50% of population

Populations at Risk For Lead Populations at Risk For Lead ToxicityToxicity

Pregnant women with elevated BLLs Pregnant women with elevated BLLs may have an increased chance of may have an increased chance of miscarriage, spontaneous abortion or miscarriage, spontaneous abortion or stillbirth, and preterm labor, and stillbirth, and preterm labor, and newborns with low birth weight or newborns with low birth weight or neurologic problems. neurologic problems.

Populations at Risk For Lead Populations at Risk For Lead ToxicityToxicity

Pregnancy and lactation- young women in Pregnancy and lactation- young women in inner-city areas of the United States who may inner-city areas of the United States who may have had heavy exposure to lead during their have had heavy exposure to lead during their childhoodchildhood. .

Lead mobilization during pregnancy is Lead mobilization during pregnancy is potentially very hazardous to the fetus. Lead potentially very hazardous to the fetus. Lead passes across the placenta almost without passes across the placenta almost without hindrance. Blood lead levels in mother and hindrance. Blood lead levels in mother and fetus are usually identical.fetus are usually identical.

Environ Health Perspect 1996;104(Suppl 1)Environ Health Perspect 1996;104(Suppl 1)

Adult Lead Exposure: Time for ChangeAdult Lead Exposure: Time for Change We have assembled this mini-monograph on adult lead exposure We have assembled this mini-monograph on adult lead exposure

to provide guidance to clinicians and public health professionals, to provide guidance to clinicians and public health professionals, to summarize recent thinking on lead biomarkers and their to summarize recent thinking on lead biomarkers and their relevance to epidemiologic research, and to review two key lead-relevance to epidemiologic research, and to review two key lead-related outcomes, namely, related outcomes, namely, cardiovascular and cognitive. cardiovascular and cognitive.

The lead standards of the U.S. Occupational Safety and Health The lead standards of the U.S. Occupational Safety and Health Administration are woefully out of date given the growing Administration are woefully out of date given the growing evidence of the health effects of lead at levels of exposure evidence of the health effects of lead at levels of exposure previously thought to be safe…previously thought to be safe…

According to a Mini Monograph published in the same journal, According to a Mini Monograph published in the same journal, the authors recommend workers with BLL between 11-20 have the authors recommend workers with BLL between 11-20 have quarterly levels, and those under 10ug/dl have semiannual quarterly levels, and those under 10ug/dl have semiannual exams. Removal of high risk workers until <10. Pregnant women exams. Removal of high risk workers until <10. Pregnant women should avoid exposure >5ug/dlshould avoid exposure >5ug/dlEnviron Health Perspect 115:451–454 (2007) and 115: 463-471 Brian S. Schwartz and Howard Hu

Lead Exposure and Cardiovascular Lead Exposure and Cardiovascular Disease Disease

A Systematic ReviewA Systematic Review

Ana Navas-Acien, Eliseo Guallar, Ellen K. Silbergeld andAna Navas-Acien, Eliseo Guallar, Ellen K. Silbergeld andStephen J. RothenbergStephen J. Rothenberg

doi:10.1289/ehp.9785 (available at http://dx.doi.org/)doi:10.1289/ehp.9785 (available at http://dx.doi.org/)Online 22 December 2006Online 22 December 2006

Lead and Cardiovascular Lead and Cardiovascular Disease- “Silent Killer In US”Disease- “Silent Killer In US”

Blood lead concentrations as low as 2.07 Blood lead concentrations as low as 2.07 µg/dL likely represent a public health hazardµg/dL likely represent a public health hazard

In NHANES 1999 to 2000, In NHANES 1999 to 2000, 38%38% of US adults of US adults had a blood lead level above this threshold. had a blood lead level above this threshold.

In areas with historical contamination of the In areas with historical contamination of the soil by heavy metals, house dust remains a soil by heavy metals, house dust remains a persistent source of exposure even decades persistent source of exposure even decades after the cessation of the industrial activity.after the cessation of the industrial activity.

Circulation 2006;114:1347-1349Circulation 2006;114:1347-1349

Cardiovascular DiseaseCardiovascular Disease

Those in the highest tertile of blood lead:Those in the highest tertile of blood lead: ( 3.63-10.0 µg/dL ) vs (2ug)( 3.63-10.0 µg/dL ) vs (2ug)

- 2.52.5 times risk for stroke mortality vs 1.51 times risk for stroke mortality vs 1.51- 1.891.89 times risk for myocardial infarction times risk for myocardial infarction

mortality vs .81mortality vs .81- 1.701.70 times risk for cardiovascular disease times risk for cardiovascular disease mortality vs .55mortality vs .55

Circulation 2006;114:1347-1349Circulation 2006;114:1347-1349

Lead and Cardiovascular High Levels of Lead in Bone Associated

With Increased Risk of Death from Cardiovascular Disease in Men

6x increased CV Death*

"The findings with bone lead are dramatic. It is the first time we have had a biomarker of cumulative exposure to lead and the strong findings suggest that, even in an era when current exposures are low, past exposures to lead represent an important predictor of cardiovascular death, with important public health implications worldwide,“ Marc Weisskopf, assistant professor of environmental and occupational epidemiology at HSPH and lead author of the study.

Circulation 2000 Sept 8, online

Lead and HypertensionLead and Hypertension

““At blood levels 4.0-31.1 At blood levels 4.0-31.1 µg/dL there is a positive association between µg/dL there is a positive association between both systolic and diastolic blood pressure and risks of both systolic both systolic and diastolic blood pressure and risks of both systolic and diastolic hypertension among women aged 40-59.” NHANES III and diastolic hypertension among women aged 40-59.” NHANES III STUDY JAMA 2003;289:1523-32STUDY JAMA 2003;289:1523-32

Systolic blood pressure and hypertension risks were associated with Systolic blood pressure and hypertension risks were associated with elevated tibial bone lead in a metaanalysis of papers on bone lead and elevated tibial bone lead in a metaanalysis of papers on bone lead and hypertension Epidemiology 2008;19 496-504hypertension Epidemiology 2008;19 496-504

There is a positive correlation of increased stress and hypertension in There is a positive correlation of increased stress and hypertension in patients with increased bone lead levels EHP 115; 1154-1159patients with increased bone lead levels EHP 115; 1154-1159

Cumulative lead exposure increases pulse pressure in aging Cumulative lead exposure increases pulse pressure in aging populations EHP 1696-2000; 2007populations EHP 1696-2000; 2007

Heart rate variability as defined as autonomic dysfunction is Heart rate variability as defined as autonomic dysfunction is more pronounced on high air pollution days in patients with more pronounced on high air pollution days in patients with increased bone lead increased bone lead

Epidemiology 2008; 19; 111-120Epidemiology 2008; 19; 111-120

More Lead Effects

Blood Lead Predicts Homocysteine Blood Lead Predicts Homocysteine LevelsLevels“ “

In 1140 older adults, blood lead, but NOT tibial lead, In 1140 older adults, blood lead, but NOT tibial lead, homocysteine levels increasedhomocysteine levels increased .035 µmol/L for every .035 µmol/L for every 1.0 µg/L of blood lead.1.0 µg/L of blood lead.

Mechanisms:Mechanisms:

Ø Homocysteine metabolism is dependent on transulfuration and Homocysteine metabolism is dependent on transulfuration and remethylation. remethylation.

Ø Enzymes necessary in the transulfuration process contain Enzymes necessary in the transulfuration process contain sulfhydryl groups that lead may bind to and inihibit sulfhydryl groups that lead may bind to and inihibit homocysteine breakdown.homocysteine breakdown.

Environ Health Perspect 2005;113(1):31-35. Environ Health Perspect 2005;113(1):31-35.

Methylation Pathways and Methylation Pathways and LeadLead

Heartfixer.com

Methylation PathwaysMethylation Pathways

60% of US has MTHFR gene mutation (folate)60% of US has MTHFR gene mutation (folate) 50% of US has MTRR gene mutation (B12)50% of US has MTRR gene mutation (B12) 25% of US has MTR gene mutation (Methionine)25% of US has MTR gene mutation (Methionine) 21% of US has CBS gene mutation 21% of US has CBS gene mutation

(transulferation)(transulferation)

HuGe Publications (Human Genome Study)HuGe Publications (Human Genome Study)

Methylation cycle Methylation cycle

The Association between Blood Lead Levels and The Association between Blood Lead Levels and Osteoporosis –Results from the Third National Health and Osteoporosis –Results from the Third National Health and

Nutrition Examination Survey (NHANES III)Nutrition Examination Survey (NHANES III)

They found a significant inverse association between lead exposure and BMD They found a significant inverse association between lead exposure and BMD lossloss

Is Lead Exposure a Risk Factor for Bone Loss?Is Lead Exposure a Risk Factor for Bone Loss?(CDC)(CDC)

YESYES

Journal of Women’s Health Vol 14:Number 6 2005.Journal of Women’s Health Vol 14:Number 6 2005.VIJAYALAKSHMI POTULA, Ph.D., and WENDY KAYE, Ph.D.VIJAYALAKSHMI POTULA, Ph.D., and WENDY KAYE, Ph.D.

•

Past Adult Lead Exposure Is Linked To Past Adult Lead Exposure Is Linked To Neurodegeneration Measured By Brain MRINeurodegeneration Measured By Brain MRI

The current report suggests strongly that organic lead exposure is associated with white matter lesions, brain atrophy, and progressive cognitive decline. Could environmental exposures such as mercury, inorganic lead, pesticides, or solvents also The current report suggests strongly that organic lead exposure is associated with white matter lesions, brain atrophy, and progressive cognitive decline. Could environmental exposures such as mercury, inorganic lead, pesticides, or solvents also

cause progressive, long-term damage to the brain that mimics the aging process? cause progressive, long-term damage to the brain that mimics the aging process? Neurology, Neurology, 2006;66: 1462-1463 2006;66: 1462-1463

Lead Exposure Predicts Survival in ALSHigher lead levels predict better survival ! EHP: 116;943-947

Chronic lead exposure is associated with brain metabolic Chronic lead exposure is associated with brain metabolic abnormalities of glial cells (MRS) abnormalities of glial cells (MRS)

EHP 115:519-25:Jan 2007 EHP 115:519-25:Jan 2007

Chronic lead exposure in women is associated with Chronic lead exposure in women is associated with reduction in cognitive measures reduction in cognitive measures

EHP on line Dec 11, 2008EHP on line Dec 11, 2008

Cumulative lead exposure and cognitive function in older Cumulative lead exposure and cognitive function in older men men

Epidemiology 2007:18: (59–66)Epidemiology 2007:18: (59–66)

Cognative decline in chronic lead exposure with concurrent Cognative decline in chronic lead exposure with concurrent HFE iron polymorphisms HFE iron polymorphisms

EHP;115: 1210-1215(2007)EHP;115: 1210-1215(2007)

Neurological Studies in Patients With Elevated Bone Lead

Progression to renal failureProgression to renal failure

Lead Chelation in Renal Lead Chelation in Renal InsufficiencyInsufficiency

The cost of this treatment for all 32 patients in The cost of this treatment for all 32 patients in the chelation group, including chelating agents, the chelation group, including chelating agents, measurements of lead, frequent hospital visits, measurements of lead, frequent hospital visits, and staff salaries, was approximately $120,000 and staff salaries, was approximately $120,000 ($3,750 per patient). ($3,750 per patient).

However, the cost of three years of However, the cost of three years of hemodialysis for this number of patients hemodialysis for this number of patients would would bebe approximately $1,950,000 ($61,000 per approximately $1,950,000 ($61,000 per patient) for those reaching end stage renal patient) for those reaching end stage renal failurefailure

Diabetes, Hypertension and Diabetes, Hypertension and Renal Failure –Normative Aging Renal Failure –Normative Aging

StudyStudy

Tibial bone lead and blood lead levels Tibial bone lead and blood lead levels predicted 17.6x worsening of serum predicted 17.6x worsening of serum creatinine over time in diabetic creatinine over time in diabetic hypertensives hypertensives

EPH: 112(11)l 1178-82 2004EPH: 112(11)l 1178-82 2004

Epigenetics and Lead

Prenatal lead exposure is inversely associated with genomic DNA methylation in cord blood. These data suggest that the epigenome of the developing fetus can be influenced by maternal cumulative lead burden, which may influence long-term epigenetic programming and disease susceptibility throughout the life course.

Pilsner JR, Hu H, Ettinger A, Sánchez BN, Wright RO, Cantonwine D, et al. 2009. Influence of Prenatal Lead Exposure on Genomic Methylation of Cord Blood DNA.Enviorn Health Perspect 117:1466-71.doi:10doi:10.1289/ehp.0800497.1289/ehp.0800497

Conclusion: NOW WHAT?Conclusion: NOW WHAT?

Genetic Methylation defects: Take NAC And Genetic Methylation defects: Take NAC And Methylated B vitamins-Metanx, Cerafolin Methylated B vitamins-Metanx, Cerafolin NAC or Deplin ? Avoid Iron Overload ?NAC or Deplin ? Avoid Iron Overload ?

Avoid exposure-anything made or grown Avoid exposure-anything made or grown overseas,old houses and historical districts, overseas,old houses and historical districts,

Test BLL yearly and prevent bone lossTest BLL yearly and prevent bone loss EDTA-gets bone and blood lead outEDTA-gets bone and blood lead out DMSA-gets blood lead outDMSA-gets blood lead out

Lead Evaluation in a Primary Care Lead Evaluation in a Primary Care PracticePractice

We measure everyone with disease/sx We measure everyone with disease/sx yearly and everyone over 50yearly and everyone over 50

Average lead levels in our population are Average lead levels in our population are 3-5. Highest 18, lowest <13-5. Highest 18, lowest <1

We do a lead H and P on most patients We do a lead H and P on most patients with disease interested in treating the leadwith disease interested in treating the lead

Check list for heavy metal symptoms used in our clinic

9,100 ug Pb/gm

Herbman/DMSA