Transcript Selenium deficiency

- an essential
trace element
Basics
What is selenium?
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discoverer: Berzelius (1817)
occurrence in the earth‘s crust: 0.05 ppm
nonmetal (chalcogen)
close chemical relationship with sulphur
fields of application:
semi-conductor technology/photo technique, medicine
essential trace element for humans and animals,
possibly for plants as well
Close chemical relationship
Important inorganic selenium compounds
Sodium selenite = an inorganic salt of selenium
so-called sodium salt of selenous acid
(as pentahydrate)
Na2SeO3 • 5 H2O
Selenium intake
Selenium
Selenium
Selenium
Selenium
Selenium intake in Europe
SCF (2000):
Opinion of the scientific
committee on food on the
tolerable intake level of
selenium.
SCF/CS/NUT/UPPLEV/25 final
Selenium intake in Europe
Rayman MP (2000):
The importance of selenium to human
health. Lancet Vol 356, 233-241
Occurrence of selenium
inorganic
1. in traces in sulfides:
iron pyrites
FeS2
chalcopyrites
CuFeS2
zinc blende
ZnS
2. in rare minerals
3. technical:
lead chamber slurry
(1817 Berzelius)
4. drinking water (selenite, selenate;
e.g. < 2 µg/l)
organic
1. protein-bound:
vegetable:
animal:
predominantly as SeMet
predominantly as SeCys
Daily kidney?
(circa data on selenium in µg/100g)
Meat, fish
liver (beef)
filet (beef)
trout
herring
kidney (beef)
ca. (µg):
21
35
25
43
112
Milk, eggs, milk products
cow‘s milk
1
Camembert, 45% F.i.d.m. 3
Fruit
banana
grape
Vegetable
brussels sprouts
boletus
ca. (µg):
1
184
Bread, bakery products
rye bread
3
pasta (containing eggs) 20
Grain
rye
wheat bran
oat flakes
1
2
10
1
2
Elmadfa, Muskat, Fritzsche, (2004/05): Die große GU-Nährwertkalorientabelle, Neuausgabe
Selenium supply in Germany
Medium daily selenium intake:
30 µg/day
41 µg/day
 suboptimal supply: Ø 0.67 µg/kg body weight
VERA-study: Selenium serum concentrations
83 µg/l
82 µg/l
max. activity GPX: 95 µg/l
lowest cancer incidence: > 121 µg/l
 optimum intake: 1.5 µg/kg body weight
Source: DAZ Nr. 11, 2005
Recommendations of the DGE
(German Society for Nutrition)
Age
Selenium µg/day
infants
0 to 4 months
4 to 12 months
5 - 15
7 - 30
children
1 to 4 years
4 to 7 years
7 to 10 years
10 to 15 years
10 - 40
15 - 45
20 - 50
25 - 60
Source: Deutsche Gesellschaft für Ernährung e. V.:
"Selen - Schätzwerte für eine angemessene Zufuhr“ , 2000.
Recommendations of the DGE
(German Society for Nutrition)
Age
adolescents
+ adults
Selenium µg/day
15 to 65 years
pregnancy
lactation
Source: Deutsche Gesellschaft für Ernährung e. V.:
"Selen - Schätzwerte für eine angemessene Zufuhr“ , 2000.
30 - 70
30 - 70
30 - 70
Toxicology
1200 µg
selenium / day
“Lowest observed adverse effect level”
LOAEL
850 µg
selenium / day
“No observable adverse effect level”
NOAEL
300 µg
selenium / day
“Tolerable upper intake level”
UL
Source: SCF, (2000): Opinion of the scientific committee on food on the tolerable intake level of
selenium. SCF/CS/NUT/UPPLEV/25 Final
Safe total daily intake
Safe total daily intake according to age groups
“Tolerable upper
intake level”
Age group
1 - 3 years
4 - 6 years
7 - 12 years
13 - 14 years
15 - 17 years
adults
UL (Tolerable upper intake level)
60 µg selenium / day
90 µg selenium / day
130 µg selenium / day
200 µg selenium / day
250 µg selenium / day
300 µg selenium / day
Source: SCF, (2000): Opinion of the scientific committee on food on the tolerable
intake level of selenium. SCF/CS/NUT/UPPLEV/25 Final
Selenium metabolism
Modified according to:
Windisch, Gabler,
Kirchgeßner, (1997):
Umwelttoxikologie
(VO 910.305)
Systemkomponente “Tier”:
Selen WS (2004/05)
How does selenium reach the protein?
Modified according to:
Windisch, Gabler,
Kirchgeßner, (1997):
Umwelttoxikologie
(VO 910.305)
Systemkomponente “Tier”:
Selen WS (2004/05)
Distribution of selenium in the body
Selenium content of human organs and body fluids:
Source: Biesalski HK, Köhrle J, Schümann K, (2002): Vitamine, Spurenelemente und Mineralstoffe.
Prävention und Therapie mit Mikronährstoffen. Georg Thieme Verlag, Stuttgart
Selenium deficiency situations
Possible reasons of an absolute or relative
selenium deficiency
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reduced selenium supply
disturbed selenium intake
increased selenium losses
increased selenium demand
increased endogenous strain with radicals and
peroxides
increased exogenous strain with noxa
Reduced selenium supply
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nutritional conditions and habits
- extremely unbalanced nutrition
- vegetarians
- vegans
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parenteral nutrition
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diets
Disturbed selenium intake
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gastro-intestinal diseases
maldigestion, malabsorption,
celiac disease
Increased selenium demand
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pregnancy
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lactation
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high physical strain or stress
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elder persons
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immune deficiency
Increased selenium demand
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chronical destructive diseases,
above all tumour diseases
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rheumatism-related diseases
(arthritis, arthroses)
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cardiovascular diseases
(coronary heart disease,
cardiomyopathy, atherosclerosis)
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inflammatory diseases of the gastro-intestinal tract
(pancreatitis, Crohn‘s disease, ulcerative colitis)
Increased exogenous strain with noxa
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workplace
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heavy metals (e.g. amalgam)
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chemotherapy
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radiotherapy
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alcohol, nicotine
Diagnosis of the selenium status
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The determination from the whole blood
has been proven for the measurement
of the selenium level.
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Hair isn‘t that suitable as examination
material as it‘s not actively involved in
the metabolism.
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Special laboratories measure the
selenium content as a matter of
routine and relatively low-priced.
Selenium status
Recommendations for laboratory analysis (Germany)
Serum: Short-term parameter
deficient
< 65 μg/l =
< 0.81 μmol/l
normal
50 - 120 μg/l = 0.81 - 1.25 μmol/l
optimal
101 - 135 μg/l = 1.26 - 1.71 μmol/l
Whole blood: Long-term parameter
deficient
< 85 μg/l =
< 1.06 μmol/l
normal
60 - 120 μg/l = 1.06 - 1.50 μmol/l
optimal
121 - 162 μg/l = 1.51 - 2.05 μmol/l
Source: Gröber U, (2003): Selen. OM. Z. f. Orthomolekulare Medizin 4, 25-26
State of selenoprotein research
1973 - 2002
Selenoproteins with known
enzymatic function:
glutathione peroxidase
thioredoxin reductase
deiodase
2003
Selenogenome:
human:
rodent:
drosophila:
C. elegans:
2005
25 genes
24 genes
4 genes
1 gene
Selenoproteome: 30 - 70 forms
Modified according to: Schomburg L, Schweizer U, Köhrle J, (2005): Selen und
Selenoproteine. Humboldt Spektrum 3, 12-18
Selenium-containing proteins in humans
Selenoproteins:
Proteins, specifically containing selenocysteine
Enzymes
glutathione peroxidase
thioredoxin reductase
deiodase
selenophosphate synthetase 2
Selenium-binding
protein
selenoprotein P
Proteins with still
unexplained function
selenoprotein W
several other selenoproteins
Selenium-containing proteins in humans
Proteins, containing non-specifically
integrated selenium
muscle proteins
globin
other tissue proteins
Glutathione peroxidase
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1973 identified as selenoprotein
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contains 4 Se-atoms, bound as selenocysteine
in the active centre
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can be found everywhere in the organism
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catalytic activity: reduction of peroxides
Origin and effect of radicals
UVradiation
X-rays
elimination of
foreign substances
metabolic
processes
damage of cell membrane
DNA damage
inflammations (phagocytosis, PG-synthesis)
O2-transport
(Hb)
protein cross-linking
cell destruction
reperfusion
Glutathione peroxidase
Peroxide detoxification by glutathione peroxidase
GSH = reduced glutathione
GSSG = oxidised glutathione
E = enzyme
Glutathione peroxidases
Function
protect the organism from the
toxicity of endogenous and
exogenous peroxides
Glutathione peroxidases
Selenium deficiency  decrease in enzyme activity
oxidative destruction of biomolecules,
cells and tissues
involved in numerous human diseases and
disorders where radicals have either a
primary or secondary role, such as e.g.
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atherosclerosis
cardiomyopathy
amyotrophic lateral sclerosis
rheumatism
infertility
cancer
Deiodases
Function
activation (T4 to T3) and
deactivation (T4 to rT3) of the
thyroid hormones
provide appropriate levels of thyroid hormones
essential for growth, differentiation and metabolism
Deiodases
Selenium deficiency  decrease in enzyme activity
suboptimal (type-I and type-II-5’-deiodases)
or supraoptimal levels of active T3 (type-III-5-deiodase)
plays a role in various diseases, such as e.g.
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Hashimoto‘s thyroiditis
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H2O2-dependent destruction of thyroid due to
continuous stimulation by TSH
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disorders in fetal brain development
Thioredoxin reductases
Function
play a decisive role in regulation of
transcription (transcription factors
NF-κB and AP-1)
are involved in DNA biosynthesis
regulate the cellular redox status, have a bearing on
the redox status of GSH (glutathione)
modulate folding (and consequently the function)
of proteins
have a large substrate range
(Trx, H2O2, dehydro-ascorbate, proteins)
Thioredoxin reductases
Selenium deficiency  decrease in enzyme activity
dysregulation of proliferation and
differentiation of cells:
is supposed to be part of the malignant
transformation of cells
total knockout of the enzyme
is considered to be a lethal factor in the
early embryonic stage
and cancer
Tumour prevention
Selenium is effective on two levels
1.
indirectly via incorporation into specific
selenoproteins e.g. GPx
2.
directly through built-up selenium
metabolites e.g. methylselenol
Chemopreventive effect of selenium
Fig. modified according to: Combs GF Jr, (1999): Chemopreventive mechanisms of selenium.
Medizinische Klinik (Munich) 94 (Suppl. III), 18-24
Selenium has a tumour-preventive property
Tumour-preventive effect verified in large studies
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Qidong-study: Primary hepatic cancer
(China 1985-1989, primary hepatic cancer, placebocontrolled, 20,847 probands)
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Linxian-study: Esophageal cancer
(China 1986-1991, esophageal cancer,
29,584 probands)
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Clark-study
Selenium has a tumour-preventive property
Clark-study
Effects of selenium supplementation for cancer prevention in patients
with carcinoma of the skin. A randomized controlled trial. Nutritional
Prevention of Cancer Study Group.
Clark LC, Combs GF Jr, et. al., (1996): JAMA 276 (24), 1957-1963
Design:
Probands:
Test centres:
Period of surveillance:
Medication:
multicentre, randomised,
double-blind, placebo-controlled
1,312
USA, low selenium regions
1983 - 1996
4.5 years
200 µg selenium/day
Selenium has a tumour-preventive property
Results of the Clark-study
Reduced incidence for secondary carcinoma in skin
cancer patients by selenium supplementation
and cancer
Kinds of cancer
Cancer figures in Germany
Estimated number of cancer incidences in Germany 2002
Man
48,650
prostate
4,350
testes
Woman
7,800
oral cavity and throat
2,600
32,550
lung
12,450
11,200
stomach
8,250
6,050
pancreas
6,600
35,600
large bowel and rectum
35,800
18,850
urinary bladder
7,100
900
Hodgkin‘s disease
850
5,850
Non-Hodgkin‘s lymphoma
6,250
5,500
leukemia
4,750
218,250*
total
206,000*
55,150
mammary
gland
11,350
uterine corpus
6,500
cervix
9,950
ovary
*Figures without non-melanotic skin cancer
Source: Gesellschaft der epidemiologischen Krebsregister e.V. in Zusammenarbeit mit dem Robert-KochInstitut. 5. überarbeitete, aktualisierte Ausgabe Saarbrücken, 2006
Prostate carcinoma
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important role as chemopreventive agent
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correlation between selenium deficiency and
increased incidence to contract prostate cancer
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inhibition of the growth in vitro by blocking the cell
cycle, the DNA synthesis and induction of
apoptosis
Reduction of prostate
carcinoma incidence by
preventive selenium
administration!
Mammary carcinoma
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tumour-protective characteristics in vivo
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low selenium concentrations in the blood in
case of mammary carcinoma patients
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secondary lymphedema:
- adjuvant therapy with selenium
- better transportation of the lymphs
- binding of radicals in the congested
tissue
- positive influence of immunocompetent cells
- avoidance of appearance of erysipelas
Ovarian carcinoma
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second most frequent malignant disease of the
female sexual organs
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increase with rising age
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9,950 incidences per year
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1.7% risk to contract ovarian carcinoma
in one‘s life
Bronchogenic carcinoma
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selenium supplementation protects
from lung carcinoma risk
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low plasma selenium levels
increase lung carcinoma risk
Colorectal carcinoma
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selenium deficiency correlates with the
risk to contract bowel cancer
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higher plasma selenium levels are
associated significantly with a lower risk
of bowel cancer
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induction of selenoprotein P and
thus, cell protection
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reduction of the risk of recurrence of
a colorectal adenoma
Dosage recommendations
and cancer
Chemotherapy
Selenium and chemotherapy
PRO selenium
+ reduction of side effects
+ resensitization of cells resistant to cytostatics
+ chemoprotective effect
+ cytostatic efficacy is not influenced
+ improvement of the quality of life
Lowered selenium levels in tumour patients

mostly before the tumour is diagnosed

oxidative stress is reinforced by the chemotherapy
 increased radical strain
healthy patient
tumour patient
= selenium concentration in blood
Chemotherapy
Cytostatic action approaches and effects:
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inhibition of replication and transcription
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induction of the apoptosis
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antimetabolite effect
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inhibition of the development of the mitotic spindle
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inhibition of the cell division
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formation of radicals
side effects
chemotherapy as exogenous source
of free radicals
Possible side effects of a chemotherapy
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nausea, vomiting, loss of appetite
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diarrhea, constipation
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loss of hair
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tiredness, exhaustion
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increase in infections

chronic organ damages
sodium selenite
oxidative stress
Reduction of side effects
healthy body cell
 side effects
 quality of life
No reduction of the cytostatic efficacy
Example etoposide and bronchogenic carcinoma cells
Source: Schroeder CP, Goeldner EM, Schulze-Forster K, Eickhoff CA, Holtermann P, Heidecke H,
(2004): Effect of Selenite combined with chemotherapeutic agents on the proliferation of human
carcinoma cell lines. Biological Trace Element Research 99 (1-3), 17-25
Increase in anti-tumour efficacy of cytostatics
Example 5-Fluorouracil (5-FU)-sensitive colon carcinoma cells
Source: Schroeder CP, Goeldner EM, Schulze-Forster K, Eickhoff CA, Holtermann P, Heidecke H,
(2004): Effect of Selenite combined with chemotherapeutic agents on the proliferation of human
carcinoma cell lines. Biological Trace Element Research 99 (1-3), 17-25
Selective effect of selenium
Processes in the tumour cell
+ Na-Selenite
high GSH-concentration intracellularly
 a lot of GSH leads to sensitivity for selenium
 administration of selenium results in formation of GS-Se-GS
 consequence

1. tumour cell becomes impoverished in GSH
2. multidrug resistance is prevented
3. cells, resistant to cytostatics, are resensitized
4. high concentrations of GS-Se-GS induce apoptosis
Selective effect of selenium
Processes in the normal cell
+ Na-Selenite
normal GSH-concentration intracellularly
 normal selenium sensitivity
 no increased formation of GS-Se-GS
 consequence

1. no impoverishment in GSH
2. selenium is available for selenium-dependent enzyme systems
3. the antioxidative defence works
4. increased resistance to cytostatics
5. no induction of apoptosis
Advantages of a selective sodium selenite therapy
+ reduction of the side effects
+ better compliance, fewer abruptions of the therapy
+ improvement of the quality of life
+ inhibition of inflammatory processes
+ lower susceptibility to infections
+ good tolerability
Dosage recommendations
Chemotherapy
days(s) before the first chemotherapy:
duration 1 - 2 days
900 µg selenium/day
directly successive treatment day(s):
duration 1 up to max. 5 days 900 µg selenium/day
from 6th day of treatment
300 µg selenium/day
treatment-free days:
duration variable
300 µg selenium/day
and cancer
Radiotherapy
Selenium and radiotherapy
PRO selenium
+ stabilisation of the immune system
+ reduction of side effects
+ radioprotective effect
+ improvement of the quality of life
Radiotherapy and possible consequences
Possible side effects of a radiotherapy

damages to mucous membranes, inflammations

damaging the blood count

dysfunctions of the organs in the radiation area,
such as diarrhea (intestines), micturition difficulties
(bladder), breathlessness (lung), difficulties in
swallowing (throat)

permanent damages to organs in the radiation area

skin damages

exhaustion, tiredness
Redox status
Tumour patient
lowered selenium
concentration in
blood and serum
reduced
glutathione peroxidase activity
• limited redox capacity
• balance between oxidation
and antioxidation is disturbed
reduction of the ability
to detoxify free radicals
Advantages of a selective sodium selenite therapy
+ in general fewer side effects
+ fewer severe infections
+ better quality of life
+ improvement of the radiation-induced
lymphedema
+ accelerated hematopoetic regeneration
+ good tolerability
Dosage recommendations
Radiotherapy
day(s) before the first radiotherapy:
duration 1 - 2 days
900 µg selenium/day
directly successive treatment day(s):
duration variable
300 µg selenium/day
treatment-free days:
duration variable
300 µg selenium/day
and thyroid
Position of the thyroid
epiglottis
larynx
hyoid bone
thyroid cartilage
thyroid
trachea
Source:
Forum Schilddrüse e.V.
60596 Frankfurt/Main
The thyroid, our organ with the
highest content of selenium
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essential for the function of the thyroid
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has a key role in the metabolisation of iodine
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protects the thyroid from destruction by
peroxides/radicals
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has an antioxidative und anti-inflammatory effect
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is supplied only inadequately with nutrition
Autoimmune diseases of the thyroid
Graves‘ disease
A form of hyperthyroidism appearing spontaneously.
The body forms antibodies, specifically directed to the thyroid, which
stimulate the thyroid for an increased production of thyroid hormones.
Frequently, the disease is combined with protruding eyes or other
symptoms of the thyroid-associated ophthalmopathy.
Thyroid-associated ophthalmopathy (TAO)
Most frequent accompanying symptom to Graves‘ disease.
From the clinical point of view, the appearance of hyperthyroidism and
TAO often is closely coupled. The orbital inflammatory process results in
a swelling of the orbital connective and muscle tissue leading to
mechanical complications in the orbits localized by bones (proptosis).
Hashimoto‘s thyroiditis
What is Hashimoto’s thyroiditis?
Hashimoto‘s thyroiditis =
Chronic autoimmune thyroiditis (AIT)
Disease starts from the immune system
Dr. Hakaru Hashimoto
(1881-1934)
- immigration of lymphocytes into the thyroid
Immune system attacks the thyroid
- shrinkage (= destruction and loss of glandular cells)
- replacement of glandular cells by connective tissue
AIT mostly chronic
Hashimoto‘s thyroiditis
The chameleon among the
thyroid diseases
The Hashimoto‘s thyroiditis cannot be regarded
as pure thyroid disease but as dysfunction of the immune
balance with consequences for many organ systems and
bodily functions.
For this reason, it is associated with numerous possibly
hardly tangible symptoms. Typical complaints of a
hypothyroidism, hyperthyroidism and of the autoimmune
disease can appear.
Hashimoto‘s thyroiditis
The chameleon among the
thyroid diseases

symptom-free to poor in symptoms

at the beginning, even hyperfunction is possible

is gradually replaced by a hypofunction

fluctuating hormone values, fluctuating TPO-Ab
values possible

complex disaease
Frequency
- up to 10% of the population
- women circa 10x more often
- in every age
- more frequently in selenium deficiency regions
- more often in case of high iodine supply
Consequence: Hypothyroidism
decreasing hormone production
Hypothyroidism
formation of insufficient thyroid hormones
 slowdown of the metabolism
 increase in weight
 weak performance
Symptoms in case of thyroid hormone deficiency
Physical symptoms
Women
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menstrual cycle disturbances
infertility
Men
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loss of libido
impotency
Toddlers
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growth retardation
backward intellectual development
Symptoms in case of thyroid hormone deficiency
Psychic symptoms
 general slowdown
 tiredness
 difficulty in concentrating
 weak memory
 listlessness
 depressed mood
Clinical studies
Selenium and Hashimoto‘s thyroiditis
Design:
Duration:
Patient collective:
Medication:
Main objective criteria:
Secondary end point:
placebo-controlled, randomised
3 months
70 female patients, TPO-Ab(antibodies
against thyroidal peroxidase) > 350 IU/ml
all hormone substitution (LT4)
36 patients 200 µg Se/day
34 patients placebo
change of the concentration of
TPO-antibodies (TPO-Ab =
antibodies against thyroidal peroxidase)
subjective quality of life
Source: Gärtner R, Gasnier BC, Dietrich JW, Krebs B, Angstwurm MW, (2002): Selenium
supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase
antibodies concentrations. J Clin Endocrinol Metab 87 (4), 1687-1691
Clinical studies
Results:
course of the TPO-Ab under
selenium substitution
change of the general
well-being
Source: Gärtner R, Gasnier BC, Dietrich JW, Krebs B, Angstwurm MW, (2002): Selenium
supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase
antibodies concentrations. J Clin Endocrinol Metab 87 (4), 1687-1691
Clinical studies
Follow-up study
Design:
Duration:
Patient collective:
Medication:
cross-over follow-up
6 months
47 female patients (average age 41)
13 patients (previously already verum):
200 µg selenium/day
14 patients (previously placebo):
200 µg selenium/day
11 patients (previously already placebo):
placebo
9 patients (previously selenium):
placebo
Source: Gärtner R, Gasnier BC, (2003): Selenium in the treatment of autoimmune thyroiditis.
Biofactors 19 (3-4), 165-170
Clinical studies
Results follow-up study:
course of TPO-Ab under selenium substitution
left column = start follow-up
right column = end follow-up after 6 months
Source: Gärtner R, Gasnier BC, (2003): Selenium in the treatment of autoimmune thyroiditis.
Biofactors 19 (3-4), 165-170
Conclusion of both studies
 selenium supplementation over a total of 9
months results in a significant decrease in
TPO-Ab
 discontinuation of selenium after 3 months
results in a significant reincrease in TPO-Ab
 remarkable improvement of the quality of life
due to selenium supplementation
 very good tolerability, especially with long-term
intake of selenium over months
Treatment – Hashimoto’s thyroiditis
substitution - according
to the demand - of the lacking
hormone quantity
Triiodothyronine
(T3)
selenium therapy with sodium selenite
Dosage recommendations
Hashimoto‘s thyroiditis
children
adolescents
adults
50 µg selenium/day
150 µg selenium/day
200 - 300 µg selenium/day
and rheumatism
Rheumatism
One name for many manifestations

inflammatory joint and spine diseases
(e.g. chronic polyarthritis, Bechterew‘s disease,
psoriasis arthritis)

degenerative joint and spine diseases
(e.g. arthrosis of the knee, hip, shoulder and finger
joints or the spine)

non-articular rheumatism (e.g. fibromyalgia)

metabolic disorders with rheumatic complaints
Rheumatoid arthritis
Development of a joint inflammation
presented
antigen
T-cell
scavenger
cell
substances
supporting
inflammation
Source: http://www.bgv-rheuma.de
Rheumatoid arthritis
Development of a joint inflammation
1.
2.

immune system discovers foreign substance
(antigen/virus)

scavenger cells take up the antigen and present
parts on the surface

T-cells recognise foreign substance,
search further foreign substances
in blood and tissue

T-cells react to endogenous
tissue properties in the
synovial membrane
Rheumatoid arthritis
Development of a joint inflammation
3.
4.

wrongly programmed T-cells release messengers
(among others IL-2, IFN)

thus, activation of further T-cells and scavenger
cells (and other immune cells / tissue and cartilage
cells)

this way, scavenger cells receive the inflammation
Arachidonic acid metabolism
food (animal fats)
arachidonic acid
messengers supporting
inflammation
development
(= support + strengthening)
of rheumatism
Inflammation metabolism
has an anti-inflammatory potential

modulation of the prostaglandin and
leukotriene synthesis

restriction of the production of
inflammatory cytokines

inhibition of the pro-inflammatory
transcription factor NF-k(kappa)B

detoxification of peroxides
Risk factor: Selenium deficiency
Selenium status in patients suffering from rheumatic diseases
Selenium status (μmol/l; mean value ± SD) of patients with rheumatism and healthy
people (* JRA = juvenile rheumatoid arthritis)
Modified according to: Sill-Steffens R, (2003): Bedeutung und Einsatzmöglichkeiten von Selen bei
Rheuma. OM. Z. f. Orthomolekulare Medizin 4, 4-6
Risk factor: Selenium deficiency
Result

people suffering from rheumatism show lowered
selenium levels

in case of chronically increased inflammatory activity,
there are high strains with free radicals, which are
involved decisively in the destruction of the joints

low selenium levels correlate with a higher disease
activity

reduced glutathione peroxidase activities lead to
increased oxidative stress and thus, to a strengthening
of inflammatory processes
Advantages of a selective sodium selenite therapy
+ balances selenium deficits
+ ideal glutathione peroxidase activities
+ decrease in the inflammation or disease activity
+ pain reduction, less morning stiffness,
decline of joint swellings
+ saving of NSAIDs,
reduction of the corticoid demand
Dosage recommendations
Rheumatic diseases
rheumatoid arthritis
over 3 months
200 µg selenium/day
acute attacks
initially
then
900 µg selenium/day
300 µg selenium/day
maintenance therapy
200 µg selenium/day
and
immune system
Selenium and immune system
The well-coordinated immune system
responds particularly sensitively to
a selenium deficiency!
 antiviral defence
 antimicrobial defence
 better defence performance
 lower susceptibility to infections
Influence of the immune system – tumour diseases
Prospective study
Natural cytotoxic activity of peripheral-blood lymphocytes and cancer
incidence: an 11-year follow-up study of a general population.
Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K, (2000): Lancet 356, 1795-1799
Duration of study: 11 years
Patient collective: 3,625 patients
211 patients with cancer disease
Measurement:
cytotoxicity of the peripheral lymphocytes
 connection between activity of the immune system and
development of cancer
 risk of a cancer disease is lower in case of higher
cytotoxicity of the lymphocytes
NK cells
Definition
Natural killer cells are populations
of lymphocytes, which can be activated
to cause a significant cytotoxic
activity and high concentrations
of cytokines and chemokines.
Their function is among others to destroy malignant cells.
NK cells
Important immune parameter in oncology

A low NK cell activity is a risk factor for the development of
tumours.

The survival rate correlates with the intensity of the NK cell
activity.
Tumor patients with a high NK cell activity show a significantly
longer survival time without developing metastases than
patients with a low NK cell activity.

As part of the unspecific immune defence, the NK cells bind
to the target cells and initiate their lysis.
If the target cell possesses apoptosis receptors, the consequence will be the release of the programmed cell death
(apoptosis).
Selenium increases the NK cell activity
Practice study
Improvement of the immunocompetence of tumour patients
Erpenbach K, (2003): Practice study, unpublished
Patient collective: 70 chronically sick patients
Medication:
Cefasel® 300 µg daily
Measurement:
NK cell activity
 initial situation: clearly lowered values or basal
NK activities in tumour patients
 NK cell activity was increased significantly by
300 µg selenium
 significant improvement of the immunocompetence
Selenium increases the NK cell activity
rise in the selenium level (standard value: 74-139 µg/l) correlates
with an increase in the NK cell activity (desired value > 25%)
Source: Erpenbach K, (2003): Improvement of the immunocompetence of tumour patients.
Practice study, unpublished
Selenium and its effect on the immune system
 increases the activity and quantity of NK cells
 modulates the proliferation of lymphocytes
 raises the efficiency of the phagocytosis
 stimulates the synthesis of g-interferon
 increases the antibody synthesis
Dosage recommendations
Immune system
adults
100 - 200 µg selenium/day
Pharmacology
Pharmacological properties









antioxidative
immune-modulating
chemopreventive
influence on the metabolism of the tumour cell
support of DNA repair mechanisms
support of the apoptosis
anti-inflammatory
cardioprotective
detoxifying in case of heavy metal strain