Neurons and Exercise

Neurons and Exercise

Saturday, November 9, 2019

Targeted Lead Detox with Thiamine, Zinc, and Selenomethionine

Targeted Lead Detox with Thiamine, Zinc, and Selenomethionine

“Lead has inflicted more deficits to human intelligence than any other pollutant.” P. Grandjean1
Lead is an element found in the earth’s crust. Because of its ductility and low cost it has been mined and processed into a variety of useful chemicals and products. More lead than ever before makes its way into our bodies primarily from our drinking water and the air we breathe. Since the amount of lead ingested and inhaled has increased, the amount of lead in our bones has also increased more than 10 fold1. Major sources of lead include:
·         Lead in drinking water – A 2016 American Water Works Association Study estimated that more than 6.1 million homes in the U.S. get drinking water through lead pipes called “service lines”2. Because of lead corrosion in these pipes, levels of lead exceeding the EPA’s action level (15mcg/L) persist in some cities. Recent examples include Flint, MI where 9,000 children were exposed to lead levels as high as 1500mcg/L and Newark, NJ where 10% of drinking water samples exceeded 66.9mcg/L.
·         Tetraethyl lead (TEL) as a gasoline additive – TEL was phased out as a road vehicle fuel additive in the U.S. by early 2000’s. However, TEL is still used in aviation gasoline (a.k.a. avgas) for planes with internal combustion engines and in gasoline for road vehicles of some developing countries3.
·         Lead from coal-fired power plants - In 2008 103 facilities in the U.S. were identified as emitting more than 1,000 pounds of lead per year into the atmosphere4.
·         Lead from paint - Lead paint is a major source of lead exposure in children5. It is estimated there were 38 million housing units in the U.S. that had lead paint in 20006.  Even a small paint chip can contain 10 to100 milligrams of lead7.  

On October 10, 2019 the U.S. Environmental Protection Agency (EPA) announced a proposal to create a trigger level of 10mcg/L of lead in drinking water tested at water taps inside homes8. This proposal does not change the EPA’s current action level of 15mcg/L of lead in drinking water. The EPA’s trigger and action levels for lead in drinking water are not a threshold for public health so a lead reading below that level doesn’t mean the drinking water is safe9.
On November 12, 2008 the U.S. EPA substantially strengthened the national ambient air quality standard for lead (73 FR 66964).  The EPA revised the level of the primary (health-based) standard from 1.5mcg of lead per cubic meter to 0.15mcg of lead per cubic meter of air4.
Safe levels for lead exposure in air and drinking water have not been defined as health risks associated with lead have been shown at very low doses.  For example, over 99% of the lead present in blood accumulates in erythrocytes and of this over 80% is bound to an enzyme ALAD (delta-aminolevulinic acid dehydrogenase)10. A blood level of only 15mcg/L results in 50% inhibition of (ALAD) resulting the accumulation of aminolevulinc acid (ALA) that has neurotoxic activity contributing to lead-induced toxicity of the brain11,12.
Individuals with certain genetic characteristics may not be protected by current regulatory standards for lead. For example, the ALAD gene contains two co-dominate alleles that depending upon which allele is expressed by an individual person results in higher or lower amount of neurotoxic ALA in response to lead10-12. In addition, people with a recessive genetic disorder called ALAD porphyria have an almost complete lack of ALAD and for this reason have increased sensitivity to lead exposure13.  
Lead Exposure Causes IQ Loss in Children
Lead in the bodies of children causes developmental delays in their brains resulting in lower IQ1. Because of this children are more vulnerable to lead toxicity than are adults. In 1986 the World Health Organization (WHO) set a special lead exposure limit for children at 50% of the adult exposure limit. In 2008 the World governmental Committee on Toxicology (COT) estimated that infants and young children exposed to WHO’s special lead exposure limit would have approximately a 36 mcg/L increase in blood lead level. This increase in blood lead level would in turn cause a 0.36 – 1.8 point decline in children’s IQ1.
In 1991 the CDC lowered the definition of lead toxicity from blood lead levels of 600mcg/L to 100mcg/L14.  Currently the CDC recommends public health intervention when a child’s blood lead level is more than 50mcg/L15. But now there are three studies that show that lead can cause IQ deficits in children at levels well below 100mcg/L16-18. There is a greater change in IQ with respect to lead concentrations from 10 to 100mcg/L than the change in IQ from 100 to 200mcg/L of lead in blood17,18.  This surprising result indicates that most of the brain damage occurs at the lowest doses of lead14.
This loss of IQ due to lead is an example of what is called “chemical brain drain”.  There is no safe level of lead that avoids “chemical brain drain” in infants and children’s brains. Targeted detox aimed at removing lead from the body is the only way to prevent “chemical brain drain” due to lead.
In addition to IQ loss, other symptoms of lead at blood lead levels less than 100mcg/L in children include19:
·         Altered mood and behaviors that may contribute to learning deficits, including attention deficits, hyperactivity, autistic behaviors, conduct disorders, and delinquency.
·         Altered neuromotor and neurosensory function, including gross and fine motor skills, visual-motor integration, and hearing threshold.  
Lead Exposure Causes Mild Cognitive Impairment (MCI) in Adults
Impairments in cognitive function, typically memory loss at a greater rate than seen in normal aging, is called mild cognitive impairment (MCI). MCI is a transitional state between the cognition seen in normal aging and dementia20. If the primary symptom is memory impairment, this state is called amnestic MCI. Amnestic MCI may not only be the first observable stage in Alzheimer’s disease but MCI is also a deficit in its own right that can be prevented and treated by modifying risk factors21. Chronic accumulation of lead in the body is an example of a risk factor for MCI that can be modified by targeted lead detox.
The U.S. National Institute for Occupational Safety and Health (NIOSH) in 2015 indicated 50mcg/L as a reference blood lead level for adults.  In spite of this the U.S. Occupational Safety and Health Administration (OSHA) recommends removing workers from lead exposure if their blood lead level is above 600mcg/L, and readmit them to work when it is below 400mcg/L. The American Conference of Governmental Industrial Hygienists (ACGIH) has set a biological exposure index of 300mcg/L for workers22.    
In an ideal world in order to test for lead causing MCI in adults would require two groups of people: one with and one without lead in their blood. However, in our lead-polluted world it is impossible to find an adult population that does not have some lead in their blood.  In 2016 40 non-lead exposed adults as a control group were age-matched to 45 lead-exposed workers and both their blood lead levels and cognition were tested.  The non-lead exposed group had a mean blood lead level of 154mcg/L and the lead exposed group has a mean blood lead level of 564mcg/L22.
Even with the control group not being lead-free, neuropsychological testing revealed a significant difference between the exposed and control groups in the areas of executive functions, short term memory, and psycho-emotional variables: tension, anxiety, and depression22. The conclusion is that greater lead exposure in adults does cause greater MCI.
Since there is no such thing as a “non-exposed” adult, even non-occupationally exposed adults have some MCI due to lead accumulation. This was tested in a cohort totaling 1089 community-dwelling elderly retired men with a mean age of 68.7 + 7.4 years. Blood and bone lead concentrations were measured along with cognitive assessment during the period 1991 to 1999. Performance on all cognitive tests worsened over time as function of increasing bone-lead level. The largest effects due to lead were observed to be on performance and reaction time scores in the visuospatial/visuomotor domain. It was concluded that non-occupational lead accumulation in adults does result in MCI23.    

In addition to MCI, other symptoms of lead at blood lead levels less than 100mcg/L in adults include19:
·         Altered mood and behaviors including risk of various psychiatric symptoms including anxiety, depression, and schizophrenia.
·         Altered neuromotor and neurosensory function including decreased reaction time and walking speed, tremor, and increased risk of amyotrophic lateral sclerosis (ALS).  
Thiamine (Vitamin B1) for Targeted Lead Detox
Thiamine (a.k.a. vitamin B1) facilitates the elimination of lead in the bile and urine and lowers both tissue and blood lead levels.  When the diet of sheep was supplemented with thiamine (75mg/kg of body weight) there was a 72% increase in biliary and urinary excretion of lead24.  Calves treated for 20 days with both lead (5mg/day/kg) and thiamine (100mg/day) have 2 to 10 times less lead in their tissues as compared with calves treated with only lead25. Just two doses of thiamine (25mg/dose/kg of body weight) in the same day lowered the blood lead level 53% from 518mcg/L to 243 mcg/L in sheep treated with lead acetate (25mg/kg) for five days. In addition there was a significant reduction in serum zinc concentration in thiamine-treated animals26.  
In human studies with 13 men between 22-44 years of age who were being chronically and occupationally exposed to lead fumes for 10-15 years prior to and during the study period.  Their blood lead level at the start of the study averaged 441mcg/L and ranged from 319 to 501mcg/L. They took orally twice a day 50mg tablets of thiamine during the first 3 months and then took 100mg tablets twice a day for 30 days. Blood tests for lead revealed 14% lower blood lead levels after 4 months of treatment with 50-100mg of thiamine twice a day27. This is impressive in light of their past and continued occupational exposure to lead fumes.
Note that retention of oral thiamine in the human body is not more than 15mg even with mega doses of thiamine from 50 to 200mg27. After oral administration to humans thiamine’s elimination half-life is 154 minutes with only 2.5% recovered in the urine28.
Spectroscopic studies have revealed that lead interacts with the aminopyrimidine ring of thiamine leading to lead solubilization at physiological pH29. Lead also interacts with the sulfur atom in the thiazolium ring of thiamine. When this sulfur is blocked by acylation, such as in Benfotiamine, the modified thiamine can’t provide protection from lead30. Thiamine reduces lead levels in the blood, kidney, and bone during both simultaneous and post-exposure lead treatment29. The likely mechanism for targeted lead detox by thiamine involves facilitating both biliary and urinary excretion of lead when complexed with thiamine29,31.
Thiamine (Vitamin B1) Supplements
Thiamine (a.k.a. vitamin B1, B-1) can be taken as a supplement in pure form or in a B vitamin complex.  For instance a B50 complex tablet contains 50mg of thiamine and a B100 complex tablet contains 100mg of thiamine. Time-release B50 or B100 complexes are available from CVS and Puritan Pride. Non-time released tablets of just B-1 are available from Now Foods Company as 100mg tablets of B-1 (thiamine hydrochloride HCl) and Seeking Health as 50mg vegetarian capsules of B-1 (thiamine hydrochloride HCl).   
Zinc for Targeted Lead Detox
In rats fed a dietary supplement of lead acetate (50mg/kg of body weight) for 3 months there was higher than normal levels of lead in bone, kidney, prostate, testis, liver, epididymis, spleen, seminal vesicles, and blood. If these rats were co-administered a dietary supplement of zinc sulfate (1mg/kg of body weight) there was as much as a 30% decrease in the amount of lead accumulated in these organs32.
Zinc Supplements
The most bioavailable source of zinc is an amino acid or acid chelate of zinc such as zinc bisglycinate of zinc gluconate. Vendors of zinc supplements include Nature’s Way 30mg capsules of zinc bisglycinate and Carlson Labs 15mg tablets of zinc gluconate.         
Thiamine and Zinc for Targeted Lead Detox
In order to decrease the accumulation of lead in rats ingesting lead, it was found that a combination of thiamine and zinc as a dietary supplement is more effective than either thiamine or zinc alone33. Simultaneous dietary supplementation thiamine and zinc to rats that had been exposed to lead, decreased lead accumulation in the blood, liver, and kidney to a greater extent than either thiamine or zinc supplementation. Rats that were exposed to lead after having been given previously simultaneous thiamine and zinc supplementation had even a larger decrease of lead in the blood, liver, and kidneys. Therefore prevention is more effective than post-lead supplementation for decreasing lead accumulation33.
Selenomethionine for Targeted Lead Detox
Selenium can’t be solely recommended for lead detox. This is because, even though selenium has been shown to detoxify lead, it has not been shown to facilitate the excretion of lead.
In children, as whole blood and plasma selenium levels increase, serum lead levels decrease34.   In adults exposed to lead the levels of lead in the blood are 6% lower in those with higher blood selenium levels as compared with those with lower blood selenium levels35. Therefore in both children and adults higher blood plasma levels of selenium result in lower blood lead levels and less loss of IQ and cognition.
In the erythrocyte as concentration of lead increases so does the concentration selenium36. This is likely due to lead and selenium reacting together in the erythrocytes to form non-toxic lead selenide complex37. Therefore, lead toxicity increases the selenium and lead concentration in the erythrocytes while depleting selenium from the plasma. A selenium supplement would increase the selenium concentration in the plasma and increase the amount of lead detoxified in the erythrocytes, while decreasing lead in the blood plasma and decreasing IQ and cognition loss.

Selenomethionine Supplements
Supplements for human use are not regulated by the U.S. FDA. Because of this lack of regulation some selenomethionine supplements contain no selenomethionine or less than the amount stated on the label38-40. Therefore products with third party certification are recommended.  Certifying agencies include:, NSF International, U.S. Pharmacopeia (USP), and UL.  There are commercial test laboratories that also perform third party testing for purity and percent of selenium as selenomethionine.   
The European Food Safety Authority (EFSA) has published a scientific opinion on acceptable selenium-enriched yeasts produced as selenomethionine supplements for human use. The source of selenium must be sodium selenite and the resulting product should contain 60 to 85% selenomethionine with less the 10% additional organic selenium and less than 1% inorganic selenium, such as residual sodium selenite. The dried product should contain no more than 2.5mg of selenium per gram41.
I am aware of only one selenium-enriched yeast supplement that has been tested by third parties. This is Bio-SelenoPrecise® tablets manufactured in Denmark by Pharma Nord under patent no. 1 478 732 B1. This type of L-selenomethionine supplement is 88.7% absorbed in Danish men with high habitual selenium intake42, however only about 34% may actually be free selenomethionine after gastrointestinal digestion43.  Pharma Nord packages tablets of Bio-SelenoPrecise® as 50, 100, and 200mcg of selenomethionine that can be cut in half with a pill-cutter.
Pharma Nord selenomethionine has been checked by two laboratories and it has 69-83% L-selenomethionine, 5% or less additional organic selenium, including selenocysteine, less than 1% inorganic selenium, and less than 2.2mg per gram of selenium. These results are summarized as product 3a, 3b, and 4 in EFSA’s Table 1 and they meet EFSA specifications for selenium-enriched yeast41.
Some selenomethionine supplements are made with higher purity than supplements made from selenium-enhanced yeast. However, it has been reported that plasma selenium is significantly higher when taking Pharma Nord Bio-SelenoPrecise® than seen in a comparable population of human subjects taking the same dose of higher purity selenomethionine44.
Manufactures of high purity yeast-free selenomethionine who have their product third party certified and/or tested include Sabinsa Corporation. Their Selenium SeLECT® product contains a minimum of 1.25% of L-selenomethionine, measured by HPLC, and 98.75% of dicalcium phosphate, measured by titration. Therefore it is 100% selenium as selenomethionine. Sabinsa Corp. has both UPC and NSF International product certification. Selenium SeLECT® is packaged and sold by Swanson (100mcg capsules) and Vitacost (200mcg capsules). Make sure the Supplement Facts on the bottles state: “Selenium from (as) Selenium SeLECT® L-selenomethionine”. 
The Food and Nutrition Board (FNB) of the U.S. Institute of Medicine has set the tolerable upper intake levels (UL) for selenium based upon age, including both selenium obtained from food and selenium obtained from supplements, as indicated in Table 145.

Recommendations for Targeted Lead Detox
Since we may be chronically exposed to lead from the air, drinking water, and lead paint, it is recommended to make a life-style choice of taking the following three supplements for the rest of your life:
·         Thiamine (a.k.a. vitamin B1, thiamin) -  50mg for children and 50-100mg for adults twice a day (morning and evening) or a time-released B50 or B100 complex once a day.
·         Zinc - 15mg for children and 30mg for adults per day (do not exceed 40mg per day)
·         Selenomethionine - The following amounts are recommended for targeted detox of not only lead but also mercury and arsenic:

·         Children 0 to 3 years of age: 25mcg/day
·         Children 4 to 8 years of age: 50mcg/day
·         Children 9 to 13 years of age: 100mcg/day
·         Adolescents 14 to 18 years of age and adults: 100-200mcg/day
Note that too much selenium will give you garlic-breath. So cut back on the amount of selenium per day if you are accused of having garlic-breath without eating garlic. 
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2.      GAO-18-620 Drinking Water – Approaches for identifying lead service lines should be shared with all states; U.S. Government Accountability Office; Report to Congressional Committees; Sept. (2018)
3.       Wikipedia – Tetraethyllead
4.       Technical Note – Estimating lead (Pb) emissions from coal combustion sources; U.S. EPA Office of Air Quality Planning and Standards; Revised (2011)
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19.  ATSDR Toxic Profile for Lead 2019
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21.  Crouse, D.N.; Preventing Alzheimer’s autism and stroke with 7 supplements, 7 lifestyle choices, and a dissolved mineral; Etiological Publishing (2016).
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23.  Weisskopf, M.G., et al.; Cumulative lead exposure and cognitive performance among elderly men; Epidemiology; 18(1):59-66 (2007)
24.   Olkowski, A.A., et al.; The effects of thiamine and EDTA on biliary and urinary lead excretion in sheep; Toxicol. Lett.; Dec.; 59(1-3):153-9 (1991)
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26.   Najarnezhad, V., et al.; The therapeutic potential of thiamine for treatment of induced subacute lead poisoning in sheep; Comp. Clin. Pathol.; 19:69-73 (2010)
27.  Kumar, B.D., et al.; Therapeutic potential of thiamine in lead toxicity – A clinical study; Indian J. Pharmacol. 26:277-81 (1994)
28.  Tallaksen, C.M., et al.; Kinetics of thiamin and thiamin phosphate esters in human blood, plasma, and urine after 50 mg intravenously or orally; Eur. J. Clin. Pharmacol.; 44(1):73-8 (1993)
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30.  Lonsdale, D., A review of the biochemistry, metabolism, and clinical benefits of thiamin(e) and its derivatives; Adv. Access Publication; eCAM; Feb.; 3(1):49-59 see pp55-56 (2006)    
31.  Flora, S.J., and Sharma, R.P.; Influence of dietary supplementation with thiamine on lead intoxication in rats; Biol. Trace Elem. Res.; Aug.; 10(2):137-44 (1986)
32.  Batra, N., et al.; The effect of zinc supplementation of the effects of lead on the rat testis; Reprod. Toxicol.; Sep.-Oct.; 12(5):523-40 (1998)
33.  Flora, S.J.S., et al.; Thiamine and zinc in prevention or therapy of lead intoxication; J. Int. Med. Res.; 17(1):68-75 (1989)
34.  Osman K., et al.; Interactions between essential and toxic elements in lead exposed children in Katowice, Poland; Clin. Biochem.; Nov.; 31(8):657-65 (1998)
35.  Pawles, N., et al.; The level of selenium and oxidative stress in workers chronically exposed to lead; Biol. Trace Elem. Res.; 170:1-8 (2016)
36.  Chiba, M., et al.; Indices of lead-exposure in blood and urine of lead-exposed workers and concentrations of major and trace elements and activities of SOD, GSH-Px and catalase in their blood; Tohoku J. Exp. Med.; 178:49-62 (1996)
37.  Flora, S.J.; et al.; Role of selenium in protection against lead intoxication; Acta Pharmacol. Toxicol. (Copenh.); Jul.; 53(1):28-32 (1983)
38.  Bakidere, S., et al.; Speciation of selenium in supplements by high performance liquid chromatography  - inductively coupled plasma  - mass spectrometry; Anal. Lett.; 48(9):1511-23 (2015)

39.  Gosetti, F., et al.; Speciation of selenium in diet supplements by HPLC – MS/MS methods; Food Chem.; 105:1738-47 (2007)

40.  Kubachka, K.M., et al.; Evaluation of selenium in dietary supplements using elemental speciation; Food Chem.; March; 218:313-20 (2017)

41.  Aguilar, F., et al.; Selenium-enriched yeast as source for selenium added for nutritional purposes in foods for particular nutritional uses and foods (including food supplements) for the general population; Scientific Opinion of the Panel on Food Additives; The EFSA J.; 766:1-42 (2008)

42.  Bugel, S., et al.; Absorption, excretion, and retention of selenium from a high selenium yeast in men with a high intake of selenium; Food Nutr. Res.; (2008)  

43.  Reyes, L.H., et al.; Selenium bioaccessibility assessment in selenized yeast after “in vitro” gastrointestinal digestion using two-dimensional chromatography and mass spectrometry; J. Chromatogr. A.; 1110(1-2):108-116 (2006) 

44.  Larsen, E.H., et al.; Speciation and bioavailability of selenium in yeast-based intervention agents used in cancer chemoprevention studies; J AOAC Int.; Jan.-Feb.; 87(1):225-32 (2004) 

45.   Food and Nutrition Board, Institute of Medicine, Selenium. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington, D.C.: National Academy Press; 284-324 (2000)