I have published my third book. There is more information about Mercury and the additional benefits of selenium in the book.
Mercury can be inhaled as mercury vapor, absorbed in the gut from
ingested food and water, or injected in the body by vaccinations. Common
sources of mercury include amalgam fillings, fish, and vaccines containing
Thimerosal. Mercury’s toxicity primarily
stems from its ability to tightly bind with the essential element selenium and
thereby lower available selenium levels in the body creating a selenium
deficiency1.
Selenium is used in some enzymes to protect us from oxidative
effects of toxic metals commonly found in the body such as aluminum, manganese,
nickel, lead, cadmium, and mercury. Selenoenzymes are involved in reducing the
oxidative effects of these metals by reducing the amount of reactive oxygen
species (ROS) induced by these metals in the body. ROS causes damage to our bodies by weakening
and killing mitochondria and the cells powered by these mitochondria.
Mercury is particularly toxic because it creates selenium
deficiency, inhibits selenoenzymes, and induces ROS formation. The resulting ROS kills mitochondria because
mercury prevents selenoenzymes from providing protection from ROS. Selenium
supplementation provides four levels of protection from mercury:
1) Prevents
mercury induced selenium deficiency in the brain2,3
2) Prevents
mercury induced mitochondrial death and neurotoxicity in the brain due to ROS2,3,4
3) Facilitates
mercury detoxification by urinary excretion of mercury5
4) Facilitates
mercury detoxification by formation of inert mercury selenide (HgSe)1
Targeted Detox during Chronic Mercury Exposure
It has been demonstrated that targeted detox of humans being
chronically exposed to mercury is possible by taking 100mcg of selenomethionine
daily for twelve weeks. The group being supplemented with selenomethionine had
significantly enhanced urinary excretion of mercury5. In those with
mercury induced selenium deficiency it may take on average 2 - 4 weeks to first
restore the body’s selenium reserves before enhanced mercury excretion is
observed (Figure 1)
Figure
1. Mercury concentrations in
urine samples on different days, where the supplementation group took
100mcg/day selenium-enriched yeast (SelenoPrecise, Pharma Nord, Denmark) and
the placebo group did not take a selenium supplement. The supplementation group was 53 volunteers
(27 men and 26 women) and the placebo group was 50 volunteers (25 men and 25
women). The results were statistical significance, as indicated with ++ p <
0.01 and +++ p < 0.001, compared with the placebo group5.
Selenomethionine supplementation for 4 months has been shown to
lower mercury level in hair samples. This study involved 23 people randomly
divided into two groups all with serum selenium less than 90mcg/L. Thirteen
people were given selenomethionine (100mcg/day of selenium enriched yeast) and
10 people were given a placebo. In only those given the selenomethionine
supplement, mercury level in pubic hair was lowered 34%, serum selenium rose by
73%, and blood selenium rose by 59%, on average6.
Therefore supplementation with selenomethionine produced by
selenium-enriched yeast (100mcg/day) has been proven to provide targeted detox during
chronic mercury exposure. Selenomethionine supplementation enhances urinary mercury
excretion in humans and lowers accumulated mercury in three to four months as
measured in human pubic hair samples5,6. This selenium method of
mercury detox is targeted because it does not remove essential trace metals
from the body as does non-targeted chelation treatments with thiols and
dithiols.
Essentiality
of Selenium
In mammals the amount of selenium in the brain is actively
maintained at the expense of selenium in other tissues. Mice fed a selenium deficient diet had only
13% of their normal whole-body selenium, but still had 56% of their normal
brain-selenium and 100% of their normal hippocampal-selenium7,8. Therefore,
there is a selenium hierarchy among the lobes of the brain and all the organs, with
the hippocampus at the apex and the whole brain just below. The hippocampus is
responsible for spatial memory creation and storage.
It is not an evolutionary accident that the brain is at the top of
the selenium hierarchy with the hippocampus at the apex. Homo sapiens evolved
to be the top predator on the food chain by using their hippocampus to remember
locations where in the past they had optimal hunting and gathering. The
hippocampus allows humans to create and store maps in their brains in order to
again find these optimal locations. Selenium protects the hippocampus from a
variety of neurotoxic metals, such as aluminum, lead, and mercury, allowing
maps and dreams to chart the course of human survival9.
Absorption
and Translocation of Oral Selenium
Oral treatment of rats with selenomethionine containing radioactive
selenium-75 (Se-75) revealed the highest concentration of Se-75 in the
cerebellum followed by identical levels in the cerebral hemisphere and spinal cord.
Retention of Se-75 in all parts of the central nervous system (CNS) was longer
after oral administration of radioactive selenomethionine than radioactive
sodium selenide10. This work proves that the selenium in orally
administered selenomethionine does cross the BBB and is retained longer in the
CNS than sodium selenide.
The active maintenance of selenium in the brain involves a selenium
carrying protein named Sepp1 (a.k.a. selenoprotein P) and its receptor
(apolipoproteinE receptor 2) interacting on the blood-brain-barrier (BBB) to
translocate selenium from the blood to the brain8. Each human Sepp1
protein carries 10 selenocysteines across the BBB. Selenomethionine is
converted to selenocysteine by the transsulfuration pathway in the liver, where
Sepp 1 is biosynthesized and released into the blood11,12. In mice,
unable to make Sepp1, the amounts of selenium in the cortex, midbrain,
brainstem, cerebellum, and hippocampus are all significantly lower than normal7.
Sepp 1 is required for both protection against oxidative injury and for
transport of selenium from the liver to peripheral tissues and organs including
the brain13.
Selenocysteine biosynthesized from selenomethionine and transported
to the brain by Sepp 1 has an affinity for methylmercury many orders of
magnitude greater than cysteine’s binding affinity for methylmercury14.
This is due to mercury having a million times greater binding force with
selenium than sulfur15. Selenocysteine is enzymatically metabolized
to L-alanine and selenide in the body12. Selenide and inorganic mercury
react by a non-biological process in the body to form mercury selenide16.
Mercury and selenium in mercury selenide are so tightly bonded that the mercury
is metabolically inert and therefore non-toxic17,18.
Supplementation for mercury detox with forms of cysteine not containing selenium, such as
N-acetylcysteine (a.k.a. NAC), is not recommended. The sulfur in both cysteine
and NAC has much lower affinity for mercury than selenocysteine14. This lower affinity may account for why the
selenium in sodium selenite (Na2SeO3) is more effective
than NAC at lowering mercury levels in the brain, liver, and kidney of rats19.
There are currently no studies showing NAC facilitates elimination of mercury
in humans and on the safety of long-term supplementation with NAC.
Sources
of Dietary Selenium
Plants growing on selenium rich soil take up the inorganic salts
selenite and selenate. Plants incorporate this inorganic selenium into organic
compounds, such as the amino acids selenomethionine and selenocystiene20.
These selenium containing amino acids are significantly less toxic to humans
than are selenite and selenate salts21.
When humans consume vegetables, grain, and nuts grown on selenium
rich soil they ingest selenium primarily as selenomethionine and
seleneocysteine. There are selenium deficient areas where crops do not contain
sufficient selenium for routine human consumption. Also because selenium is not usually added to
soil as fertilizer, many farming areas in the world that were in the past producing
selenium rich crops are now producing crops with declining selenium content. In
these areas of the world selenium supplementation is recommended.
Selenomethionine
Supplementation
The selenium method of mercury detox requires taking orally a
selenomethionine supplement, daily for at least 12 weeks:
·
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
Supplements for human use are not regulated by the U.S. FDA.
Because of this some supplement manufacturers have incorrectly labeled product
on the market that contains no selenomethionine or less than the amount stated
on the label22-24. Therefore products with third party certification
are recommended. Certifying agencies
include: Consumerlab.com, 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 gram25.
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 intake26, however only about 34% may actually be free
selenomethionine after gastrointestinal digestion27. Pharma Nord packages tablets of
Bio-SelenoPrecise® as 50, 100, and 200mcg of selenomethionine. 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/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 yeast25.
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 selenomethionine28.
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 129.
Symptoms of Chronic Mercury Exposure
and Selenium Deficiency
The risk
of hypothyroidism is increased with exposure to mercury and/or selenium
deficiency because a selenoenzyme (e.g. T4 deiodinase) is required to make the thyroid bioactive hormone T3
(a.k.a. triiodothyronine ) from prohormone T4 (a.k.a. levothyroxine)30. Mercury both inhibits this enzyme and slows its
production by creating a selenium deficiency31. Symptoms of hypothyroidism, mercury toxicity
and selenium deficiency all include:
·
Memory Loss
·
Fatigue
·
Brain Fog
·
Muscle Weakness
·
High TSH (a.k.a. thyroid-stimulating hormone)
secretion
Mercury and/or selenium deficiency also causes a
number of additional symptoms not seen in hypothyroidism:
·
Physical Tremors32
·
Seizures33
·
Impaired Language
Skills34-37
·
Impaired
Psychomotor Functions34-37
·
IQ Loss in
Children37,38
·
Mild Cognitive
Impairment in Adults33,34
Outcomes associated with prenatal mercury exposure include the
loss of IQ points, and decreased performance on tests, including memory,
attention, language skills, visuospatial cognition and psychomotor fuctions34,35. Outcomes associated with prenatal selenium deficiency also include both impaired language
skills and psychomotor function36,37.
Non-Targeted
Detox after Acute Mercury Exposure
When acutely exposed to a large dose of mercury during a relatively
short time period you should seek
immediate medical assistance. Severe
acute elemental mercury exposure has been managed by a combination of selenium
and N-acetylcysteine (NAC)41,42.
There are also chelators available by
prescription that will remove some mercury after acute exposure. Unlike
selenium that binds and detoxifies mercury irreversibly, chelators reversibly
bind and redistribute mercury in the body without detoxification. Some of this chelated mercury is eliminated
in the urine and bile, while some mercury is redistributed to the brain. For
this reason chelators should only be
used cautiously under a doctor’s supervision.
Pharmaceutical
Chelators for Acute Mercury Exposure
There are 11 pharmaceuticals that chelate metals approved by the
U.S. FDA, although only one of them (e.g. BAL) has been approved for treating
acute mercury toxicity43.
Unlike selenomethionine, the natural form of selenium that humans ingest
primarily from plants, pharmaceutical chelators are non-natural manmade
chemicals. Because of safety concerns, pharmaceutical chelators can’t be
recommended for routine use. The pharmaceutical chelators are dithiols and do
not contain selenium. Since these dithiols reversibly bind to both essential
and toxic divalent cations they can both transport these ions to other organs and
facilitate their elimination44. For instance in some cases they have
been found to chelate selenium45. The following is a list of four pharmaceutical
chelators with the first two being FDA approved with the third being used
without approval:
·
Dimercaprol (a.k.a. British Anti-Lewisite, BAL)
used by injection for mercury toxicity
·
Dimercaptosuccinic acid (a.k.a. Succiner, DMSA)
used orally for lead toxicity
·
Dimercaptopropane sulfonate (a.k.a. DMPS) used
for mercury toxicity46.
·
N,N’,-bis(2-mercaptoethyl)isophthalamide (a.k.a.
BDET, BDTH2, OSR#1, NBMI)
The last compound on the list, also called “Boyd Haley’s compound”,
is not approved by the U.S. FDA for use as a pharmaceutical chelator and has
been taken off the market as a supplement because it is non-natural. The FDA
concluded in 2008 that this compound had inadequate safety testing and
therefore may “present a significant or unreasonable risk of illness or injury”47.
Alpha
Lipoic Acid for Acute Mercury Exposure
Alpha lipoic acid (a.k.a. ALA) is naturally found in the body and when
reduced in vivo to dithiol-ALA it can
protect the body from metal induced reactive oxygen species (ROS). ALA is
not approved by the U.S. FDA for treating acute mercury exposure even though
one dithiol (e.g. BAL) is approved by the U.S. FDA for such a purpose43. When ALA was compared with other
dithiols (e.g. DMPS and DMSA) it proved to be significantly less effective at
removing inorganic mercury from the kidneys of rabbits48. ALA
removed only 35% while DPMS removed 86% of the mercury48. There is
no human clinical trial showing that oral administration of ALA as a supplement
facilitates the excretion of mercury or lowers mercury in the body and brain49.
Injection of ALA in rats
after injection of mercury results in an increase in biliary excretion of
inorganic mercury but high doses of ALA results in a decreased biliary
excretion of methylmercury50.
This study by Gregus, et al., had a “large influence on determining the
ALA chelation protocol” as described by A.H. Cutler51. Cutler also said “I suggest people get the
actual paper and read it … if they are going to draw conclusions about what
they will or won’t do.”51 I will summarize the paper here in some
detail so you can draw your own conclusions:
The study by Gregus, et al., found that the amount of mercury
excreted in the bile depends upon both on the dosage of ALA and the time
between injections of inorganic mercury and ALA50. Using a medium
dose of ALA (150mcg/Kg) with one minute between these injections there is a 30
fold increase in biliary excretion of mercury. But when this dose of ALA is
administered 1 and 24 hours after mercury there is only 3.3 and 1.4 fold increases
in biliary excretion of mercury, respectively50. This indicates ALA is only
efficacious for acute, not chronic, mercury exposure as it significantly
increases biliary excretion of mercury only if taken within a few hours of
exposure. ALA does not significantly facilitate the excretion of mercury once
mercury is stored in tissues and organs.
This study also provides evidence that ALA redistributes mercury in
the body of rats. For instance, ALA administered
1 minute after inorganic mercury decreased mercury levels in the rat kidney by
half, but increased mercury in the rat brain 2.9 fold, lung 2.7 fold, heart 4.3
fold, and muscle 3.1 fold50. In addition, ALA at 300mcg/Kg decreases
biliary excretion of methylmercury and ALA at 150mcg/Kg increases methylmercury
levels in the rat brain 2.6 fold50. This indicates that ALA redistributes both inorganic and
methylmercury and significantly increases mercury in many tissues and organs of
the rat including the brain.
The fact that ALA provides non-targeted chelation is reinforced by a
study showing ALA redistributes selenium in the bodies of aged rats by lowering levels of selenium in the brain,
heart, muscle, and blood plasma52. For this reason it is recommended
that serum selenium levels should be monitored if taking ALA as a supplement52. If you have been taking ALA and seen
improvement it may be preventing metal toxicity (i.e. ROS) due to metals other
than mercury.
Because
ALA likely redistributes inorganic and methylmercury in the human body as well
as in rats and increases mercury in rat and human tissues and organs including
the brain, both I and the FDA do not recommend taking ALA as an oral supplement
or injection for either acute mercury exposure or detox from chronic mercury
exposure.
Conclusion
Selenium is an essential trace atom required by the body that is
normally supplied as selenomethionine in the vegetables and grains our
ancestors have eaten for thousands of years.
The selenium in selenomethionine is quickly converted in the liver to a selenium-carrier
that crosses the blood-brain-barrier enriching and protecting the brain with
selenium. Because there are selenium deficient areas
where crops do not contain sufficient selenium for routine human consumption, daily
selenomethionine supplementation is recommended and can provide four levels of
protection from mercury toxicity:
1) Prevents
mercury induced selenium deficiency in the brain2,3
2) Prevents
mercury induced mitochondrial death and neurotoxicity in the brain due to ROS2,3,4
3) Facilitates
mercury detoxification by urinary excretion of mercury5
4) Facilitates
mercury detoxification by formation of inert mercury selenide (HgSe)1
Daily selenomethionine
supplementation is proven to facilitate urinary mercury excretion and
decrease accumulation of mercury in human hair. Other methods of mercury
detoxification, such as NAC and ALA,
should be avoided due to a lack of such proven testing in humans.
References
1)
Spiller,
H.A.; Rethinking mercury: the role of selenium in the pathophysiology of
mercury toxicity; Clin. Toxicology; DOI: 10.1080/15563650.2017 . 1400555 (2017)
http://dx.doi.org/10.1080/15563650.2017.1400555
2)
Ralston, N.C.V., et al.; Dietary and tissue selenium in relation to
methylmercury toxicity; Neurotoxicology; 29:802-11 (2008)
3)
Ralston, N.C.V., et al.; Importance of molar ratios in selenium dependent
protection against methylmercury toxicity; Biol. Trace Elem. Res.; 119:225-268
(2007)
4)
Glaser, V., et al.; Diphenyl diselenide administration enhances
cortical mitochondrial number and activity by increasing hemeoxygenase type 1
content in a methylmercury-induced neurotoxicity mouse model; Mol. Cell
Biochem.; 390:1-9 (2014)
5)
Li, Y-F,
et al.; Organic selenium supplementation increases mercury excretion and
decreases oxidative damage in long-term mercury exposed residents from Wanshan,
China; Environ. Sci. Technol.; 46:11313-18 (2012)
6)
Seppanen,
K., et al.; Effect of supplementation with organic selenium on mercury status
as measured by mercury in pubic hair; J. Trace Elem. Med. Biol.; Jun.;
14(2):84-7 (2000)
7)
Nakayama,
A., et al,; All regions of mouse brain are dependent on selenoprotein P for
maintenance of selenium; J. Nutr.; Mar.; 137(3):690-3 (2007)
8)
Burk,
R.F., et al.; Selenoprotein P and apolipoprotein E receptor-2 interact at the
blood-brain-barrier and also within the brain to maintain and essential
selenium pool that protects against neurodegeneration; FASEB J.; Aug.;
28(8):3579-88 (2014)
9)
Brody,
H.; Maps and Dreams; Gardners Books (2002)
10) Gronbaek, H. and Thorlacius-Ussing, O.;
Selenium in the central nervous system of rats exposed to 75-Se
L-selenomethionine and sodium selenite; Biol. Trace Elem. Res.; Nov.;
35(2):119-27 (1992)
11) Hill, K.E., et al.; Production of selenoprotein
P (Sepp 1) by hepatocytes is central to selenium homeostasis; J. Biol. Chem.;
Nov.; 287(48):40414-24 (2012)
12) Seale, L.A.; Selenocysteine -lyase: Biochemistry,
regulation, and physiological role in the selenocysteine decomposition enzyme;
Antioxidants; 8(357):1-15 (2019)
13) Burk, R.F.; et al.; Selenoprotein metabolism
and function: Evidence for more than one function for selenoprotein P; J.
Nutr.; May; 133(5 Suppl 1):1517S-20S (2003)
14) Sugiura, Y., et al.; Selenium protection
against mercury toxicity: high binding affinity of methylmercury by
selenium-containing ligands in comparison with sulfur-containing ligands;
Bioinorg. Chem.; Aug,; 9(2):167-80 (1978)
15) Zhang, H.; Impacts of selenium on the
biogeochemical cycles of mercury in terrestrial ecosystems in mercury mining
areas; Section 2.3 Mechanisms of selenium and mercury interactions; Springer
(2014)
16) Yang, D-T, et al.; Selenium and mercury in
organisms: Interactions and mechanisms; Environ. Rev.; 16:71-92 (2008)
17) Raymond, L.J., and Ralston, N.V.C.; Mercury:
selenium interactions and health implications; SMDJ Seychelles Med. Dental J.;
Special Issue; Nov. 7(1):72-7 (2004)
18) Nutall, K.I.; A model for metal selenide formation
under biological conditions; Med. Hypoth.; 24:217-21 (1087)
19) Joshi, D., et al.; Methylmercury toxicity:
amelioration by selenium and water-soluble chelators as N-acetyl cysteine and
dithiothreitol; Cell Biochem. Funct.; 32:351-60 (2014)
20) Meyer, C.A.C.; Dietary selenium
supplementation: Effects on neurodegeneration following traumatic brain and
spinal cord injury; Theses and Dissertations, Univ. Kentucky (2015)
21) Salbe, A.D., and Levander, O.A.; Comparative
toxicity and tissue retention of selenium in methionine-deficient rats fed
sodium selenate or L-selenomethionine; J. Nutr.; 120:207-12 (1990)
22) 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)
23) Gosetti,
F., et al.; Speciation of selenium in diet supplements by HPLC – MS/MS methods;
Food Chem.; 105:1738-47 (2007)
24) Kubachka,
K.M., et al.; Evaluation of selenium in dietary supplements using elemental
speciation; Food Chem.; March; 218:313-20 (2017)
25) 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)
26) 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)
27) 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)
28) 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)
29) 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)
30) Peeters, R.P. and Visser, T.J.; Metabolism of
thyroid hormone; NCBI Bookshelf (2017) https://www.ncbi.nlm.nih.gov/books/NBK285545/
31) Pantaleao, T.U., et al.; Effect of thimerosal
on thyroid hormones metabolism in rats; Endocr. Connect; Nov.; 6(8):741-7
(2017)
32) Lucchini, R.G. and Hashim, D.; Tremor secondary
to neurotoxic exposure: mercury, lead, solvents, pesticides; Handb. Clin.
Neurol.; 131:241-9 (2015)
33) Wirth, E.K., et al.; Neuronal selenoprotein
expression is required for interneuron development and prevents seizures and
neurodegeneration; The FASEB J.; Nov.; 844-52 (2009)
34) Bose-O’Reilly, et al.; Mercury exposure and
children’s health; Curr. Probl. Rediatr. Adolesc. Health Care; Sept.;
40(8):186-215 (2010)
35) Grandjean, P., et al.; Cognitive defict in
7-year-old children with prenatal exposure to methylmercury; Neurotoxicology
and Teratology; 19(6):417-28 (1997)
36) Polanska, K., et al.; Selenium status during
pregnancy and child psychomotor development – Polish mother and child cohort
study; Pediatric Res.; 79(6):863-69 (2016)
37) Skroder, H.M., et al.; Selenium status in
pregnancy influences children’s cognitive function at 1.5 years of age; Clin.
Nutr.; Oct.; 34(5):923-30 (2015)
38) Ralston, N.V. and Raymond, L.J.; Dietary
selenium’s protective effects against methylmercury toxicity; Toxicology; Nov.; 278(1):112-23 (2010)
39) Cardoso, B.R., et al.; Effects of Brazil nut
consumption on selenium status and cognitive performance in older adults with
mild cognitive impairment: a randomized controlled trial; European J. Nutr,;
Feb.; 55(1):107-16 (2016)
40) Weil, M., et al.; Blood mercury levels and
neurobehavioral function; JAMA; Apr.; 293(15):1875-82 (2005)
41) Spiller, H.A., et al.; Severe elemental mercury
poisoning managed with selenium and N-acetylcysteine administration; Tox.
Comm.; 1(1):24-28 (2017)
42) Joshi, D., et al.; Methylmercury toxicity:
Amelioration by selenium and water-soluble chelators as N-acetyl cysteine and
dithiothreitol; Cell Biochem. Funct.; June; 32:351-60 (2014)
43) Wax, P.M.; Current use of chelation in American
Health Care; J. Med. Toxicol.; 9:303-7 (2013)
44) Sears, M.; Chelation: Harnessing and enhancing
heavy metal detoxification – A review; Sci. World J.; Article ID 219840; 1-13
(2013)
45) Blue, L.Y., et al.; Aqueous mercury
precipitation with the synthetic dithiolate, BDTH2; Fuel; June;
89(6):1326-30 (2010)
46) Rafati-Rahimzadeh, M., et al.; Current approaches
of the management of mercury poisoning: need of the hour; J. Pharmaceutical
Sci.; 22(46):1-10 (2014)
47) Pellicore, L.S.; Department of Health and Human
Services; July 8, 2008 Letter to Boyd E. Haley of CTI Science, Inc.; Regarding
N,N’-bis(2-mercaptoethyl)isophthalamide (2008)
48) Kieth, R.L., et al.; Utilization of renal
slices to evaluate the efficacy of chelating agents for removing mercury from
the kidney; Toxicol.; 116:67-75 (1997)
49) Patrick, L.; Mercury toxicity and antioxidants:
Part I: Role of glutathione and alpha-lipoic acid in the treatment of mercury
toxicity; Alternative Medicine Rev.; 7(6):456-71 (2002)
50) Gregus, Z., et al.; Effect of lipoic acid and
biliary excretion of glutathione and metals; Toxicology Appl. Pharm.; 114:88-96
(1992)
51) Cutler, A.H.; Comments by Andrew H. Cutler on
the study by Gregus are found in Cutler’s bibliography of papers on ALA: “This
is an excellent and useful paper. I suggest people get the actual paper and
read it rather than relying on the abstract if they are going to draw conclusions
about what they will or won’t do. This paper actually did have a large
influence on determining the LA chelation protocol…”
52) Cakatay, U., et al.; Postmitotic tissue
selenium and manganese levels in alpha-lipoic acid-supplemented rats; Chem.
Biol. Interact.; Feb.; 171(3):306-11 (2008)