2. - an essential
trace element

3. Basics

4. What is selenium? 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

5. Close chemical relationship

6. Important inorganic selenium compounds
Sodium selenite =
an inorganic salt of selenium
so-called sodium salt of selenous acid
(as pentahydrate)
Na2SeO3 • 5 H2O

7. Selenium intake
Selenium
Selenium
Selenium
Selenium

8. 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

9. Selenium intake in Europe
Rayman MP (2000):
The importance of selenium to human health. Lancet Vol 356,

10. 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: predominantly as SeMet
animal: predominantly as SeCys

11. Daily kidney? (circa data on selenium in µg/100g) Meat, fish ca. (µg):
liver (beef) 21
filet (beef) 35
trout 25
herring 43
kidney (beef) 112
Milk, eggs, milk products
cow‘s milk 1
Camembert, 45% F.i.d.m. 3
Fruit
banana 1
grape 2
Vegetable ca. (µg):
brussels sprouts 1
boletus 184
Bread, bakery products
rye bread 3
pasta (containing eggs) 20
Grain
rye 1
wheat bran 2
oat flakes 10
Elmadfa, Muskat, Fritzsche, (2004/05): Die große GU-Nährwertkalorientabelle, Neuausgabe

12. 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

13. Recommendations of the DGE (German Society for Nutrition)
Age Selenium µg/day
infants 0 to 4 months
4 to 12 months
children 1 to 4 years
4 to 7 years
7 to 10 years
10 to 15 years
Source: Deutsche Gesellschaft für Ernährung e. V.:
"Selen - Schätzwerte für eine angemessene Zufuhr“ , 2000.

14. Recommendations of the DGE (German Society for Nutrition)
Age Selenium µg/day
adolescents 15 to 65 years
+ adults
pregnancy lactation
Source: Deutsche Gesellschaft für Ernährung e. V.:
"Selen - Schätzwerte für eine angemessene Zufuhr“ , 2000.

15. Toxicology
“Lowest observed adverse effect level”
1200 µg
selenium / day
LOAEL
850 µg
selenium / day
NOAEL
“No observable adverse effect level”
300 µg
selenium / day UL
“Tolerable upper intake level”
Source: SCF, (2000): Opinion of the scientific committee on food on the tolerable intake level of
selenium. SCF/CS/NUT/UPPLEV/25 Final

16. Safe total daily intake
Safe total daily intake according to age groups
“Tolerable upper
intake level”
Age group UL (Tolerable upper intake level)
1 - 3 years 60 µg selenium / day years 90 µg selenium / day years 130 µg selenium / day years 200 µg selenium / day years 250 µg selenium / day adults 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

17. Selenium metabolism Modified according to: Windisch, Gabler,
Kirchgeßner, (1997):
Umwelttoxikologie
(VO )
Systemkomponente “Tier”:
Selen WS (2004/05)

18. How does selenium reach the protein?
Modified according to:
Windisch, Gabler,
Kirchgeßner, (1997):
Umwelttoxikologie
(VO )
Systemkomponente “Tier”:
Selen WS (2004/05)

19. 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

20. Selenium deficiency situations
Possible reasons of an absolute or relative selenium deficiency
reduced selenium supply
disturbed selenium intake
increased selenium losses
increased selenium demand
increased endogenous strain with radicals and peroxides
increased exogenous strain with noxa

21. Reduced selenium supply
nutritional conditions and habits - extremely unbalanced nutrition - vegetarians - vegans
parenteral nutrition
diets

22. Disturbed selenium intake
gastro-intestinal diseases
maldigestion, malabsorption, celiac disease

23. Increased selenium demand
pregnancy
lactation
high physical strain or stress
elder persons
immune deficiency

24. Increased selenium demand
chronical destructive diseases, above all tumour diseases
rheumatism-related diseases (arthritis, arthroses)
cardiovascular diseases (coronary heart disease, cardiomyopathy, atherosclerosis)
inflammatory diseases of the gastro-intestinal tract (pancreatitis, Crohn‘s disease, ulcerative colitis)

25. Increased exogenous strain with noxa
workplace
heavy metals (e.g. amalgam)
chemotherapy
radiotherapy
alcohol, nicotine

26. Diagnosis of the selenium status
The determination from the whole blood has been proven for the measurement of the selenium level.
Hair isn‘t that suitable as examination material as it‘s not actively involved in the metabolism.
Special laboratories measure the selenium content as a matter of routine and relatively low-priced.

27. Selenium status Recommendations for laboratory analysis (Germany)
Serum: Short-term parameter
deficient < 65 μg/l = < 0.81 μmol/l
normal μg/l = μmol/l
optimal μg/l = μmol/l
Whole blood: Long-term parameter
deficient < 85 μg/l = < 1.06 μmol/l
normal μg/l = μmol/l
optimal μg/l = μmol/l
Source: Gröber U, (2003): Selen. OM. Z. f. Orthomolekulare Medizin 4, 25-26

28. State of selenoprotein research
Selenoproteins with known enzymatic function:
glutathione peroxidase
thioredoxin reductase
deiodase
2003 Selenogenome:
human: 25 genes
rodent: 24 genes
drosophila: 4 genes
C. elegans: 1 gene
2005 Selenoproteome: forms
Modified according to: Schomburg L, Schweizer U, Köhrle J, (2005): Selen und Selenoproteine. Humboldt Spektrum 3, 12-18

29. Selenium-containing proteins in humans
Selenoproteins:
Proteins, specifically containing selenocysteine
Enzymes glutathione peroxidase
thioredoxin reductase
deiodase
selenophosphate synthetase 2
Selenium-binding selenoprotein P protein
Proteins with still selenoprotein W
unexplained function several other selenoproteins

30. Selenium-containing proteins in humans
Proteins, containing non-specifically integrated selenium
muscle proteins
globin
other tissue proteins

31. Glutathione peroxidase
1973 identified as selenoprotein
contains 4 Se-atoms, bound as selenocysteine in the active centre
can be found everywhere in the organism
catalytic activity: reduction of peroxides

32. Origin and effect of radicals
UV-radiation
inflammations (phago-cytosis, PG-synthesis)
X-rays
metabolic processes
elimination of foreign substances
O2-transport (Hb)
reper-fusion
damage of cell membrane DNA damage
protein cross-linking cell destruction

33. Glutathione peroxidase
Peroxide detoxification by glutathione peroxidase
GSH = reduced glutathione
GSSG = oxidised glutathione
E = enzyme

34. Glutathione peroxidases
Function
protect the organism from the toxicity of endogenous and exogenous peroxides

35. 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.
atherosclerosis
cardiomyopathy
amyotrophic lateral sclerosis
rheumatism
infertility
cancer

36. 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

37. 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.
Hashimoto‘s thyroiditis
H2O2-dependent destruction of thyroid due to continuous stimulation by TSH
disorders in fetal brain development

38. 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)

39. 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

40. and cancer
Tumour prevention

41. 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

42. Chemopreventive effect of selenium
Fig. modified according to: Combs GF Jr, (1999): Chemopreventive mechanisms of selenium. Medizinische Klinik (Munich) 94 (Suppl. III), 18-24

43. Selenium has a tumour-preventive property
Tumour-preventive effect verified in large studies
Qidong-study: Primary hepatic cancer (China , primary hepatic cancer, placebo-controlled, 20,847 probands)
Linxian-study: Esophageal cancer (China , esophageal cancer, 29,584 probands)
Clark-study

44. 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),
Design: multicentre, randomised, double-blind, placebo-controlled
Probands: 1,312
Test centres: USA, low selenium regions
Period of surveillance: 4.5 years
Medication: µg selenium/day

45. Selenium has a tumour-preventive property
Results of the Clark-study
Reduced incidence for secondary carcinoma in skin cancer patients by selenium supplementation

46. and cancer
Kinds of cancer

47. Cancer figures in Germany
48,650
prostate
4,350
testes
55,150
mammary
gland
11,350
uterine corpus
6,500
cervix
9,950
ovary
Man
Woman
7,800
2,600
oral cavity and throat
32,550
12,450
lung
11,200
8,250
stomach
6,050
6,600
pancreas
35,600
35,800
large bowel and rectum
18,850
7,100
urinary bladder
900
850
Hodgkin‘s disease
5,850
6,250
Non-Hodgkin‘s lymphoma
5,500
4,750
leukemia
218,250*
206,000*
total
*Figures without non-melanotic skin cancer
Estimated number of cancer incidences in Germany 2002
Source: Gesellschaft der epidemiologischen Krebsregister e.V. in Zusammenarbeit mit dem Robert-Koch-Institut. 5. überarbeitete, aktualisierte Ausgabe Saarbrücken, 2006

48. Prostate carcinoma important role as chemopreventive agent
correlation between selenium deficiency and increased incidence to contract prostate cancer
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!

49. Mammary carcinoma tumour-protective characteristics in vivo
low selenium concentrations in the blood in case of mammary carcinoma patients
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

50. Ovarian carcinoma
second most frequent malignant disease of the female sexual organs
increase with rising age
9,950 incidences per year
1.7% risk to contract ovarian carcinoma in one‘s life

51. Bronchogenic carcinoma
selenium supplementation protects from lung carcinoma risk
low plasma selenium levels increase lung carcinoma risk

52. Colorectal carcinoma
selenium deficiency correlates with the risk to contract bowel cancer
higher plasma selenium levels are associated significantly with a lower risk of bowel cancer
induction of selenoprotein P and thus, cell protection
reduction of the risk of recurrence of a colorectal adenoma

53. Dosage recommendations

54. and cancer
Chemotherapy

55. 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

56. 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

57. chemotherapy as exogenous source
Cytostatic action approaches and effects:
inhibition of replication and transcription
induction of the apoptosis
antimetabolite effect
inhibition of the development of the mitotic spindle
inhibition of the cell division
formation of radicals
side effects
chemotherapy as exogenous source
of free radicals

58. Possible side effects of a chemotherapy
nausea, vomiting, loss of appetite
diarrhea, constipation
loss of hair
tiredness, exhaustion
increase in infections
chronic organ damages

59. Reduction of side effects
healthy body cell
oxidative stress
sodium selenite
side effects
quality of life

60. 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

61. 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

62. 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

63. 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

64. 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

65. Dosage recommendations
Chemotherapy
days(s) before the first chemotherapy:
duration 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

66. and cancer
Radiotherapy

67. Selenium and radiotherapy
PRO selenium
+ stabilisation of the immune system
+ reduction of side effects
+ radioprotective effect
+ improvement of the quality of life

68. Radiotherapy and possible consequences

69. 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

70. reduction of the ability to detoxify free radicals
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

71. 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

72. Dosage recommendations
Radiotherapy
day(s) before the first radiotherapy:
duration days 900 µg selenium/day
directly successive treatment day(s):
duration variable 300 µg selenium/day
treatment-free days:

73. and thyroid

74. Position of the thyroid
hyoid bone
epiglottis
larynx
thyroid
thyroid cartilage
trachea
Source: Forum Schilddrüse e.V Frankfurt/Main

75. The thyroid, our organ with the highest content of selenium
essential for the function of the thyroid
has a key role in the metabolisation of iodine
protects the thyroid from destruction by peroxides/radicals
has an antioxidative und anti-inflammatory effect
is supplied only inadequately with nutrition

76. 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

77. What is Hashimoto’s thyroiditis?
Dr. Hakaru Hashimoto
( )
Hashimoto‘s thyroiditis =
Chronic autoimmune thyroiditis (AIT)
Disease starts from the immune system
- 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

78. 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.

79. 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

80. 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

81. Consequence: Hypothyroidism
decreasing hormone production
hormone level
Hypothyroidism formation of insufficient thyroid hormones  slowdown of the metabolism
 increase in weight
 weak performance

82. Symptoms in case of thyroid hormone deficiency
Physical symptoms
Women
menstrual cycle disturbances
infertility
Men
loss of libido
impotency
Toddlers
growth retardation
backward intellectual development

83. Symptoms in case of thyroid hormone deficiency
Psychic symptoms
 general slowdown
 tiredness
 difficulty in concentrating
 weak memory
 listlessness
 depressed mood

84. Clinical studies Selenium and Hashimoto‘s thyroiditis
Design: placebo-controlled, randomised
Duration: 3 months
Patient collective: 70 female patients, TPO-Ab(antibodies against thyroidal peroxidase) > 350 IU/ml
Medication: all hormone substitution (LT4) 36 patients 200 µg Se/day
34 patients placebo
Main objective criteria: change of the concentration of TPO-antibodies (TPO-Ab = antibodies against thyroidal peroxidase)
Secondary end point: 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),

85. 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),

86. Clinical studies Follow-up study Design: cross-over follow-up
Duration: 6 months
Patient collective: 47 female patients (average age 41)
Medication: 13 patients (previously already verum): µg selenium/day
14 patients (previously placebo): 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),

87. 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),

88. 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

89. Treatment – Hashimoto’s thyroiditis
substitution - according
to the demand - of the lacking hormone quantity
Triiodothyronine
(T3)
selenium therapy with sodium selenite

90. Dosage recommendations
Hashimoto‘s thyroiditis
children 50 µg selenium/day
adolescents 150 µg selenium/day
adults µg selenium/day

91. and rheumatism

92. 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

93. Rheumatoid arthritis Development of a joint inflammation
presented antigen
T-cell
scavenger cell
substances supporting inflammation
Source:

94. Rheumatoid arthritis Development of a joint inflammation 1.
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 2.

95. Rheumatoid arthritis Development of a joint inflammation 3.
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)
IL:interlökin, IFN: interferon 4.
this way, scavenger cells receive the inflammation

96. Arachidonic acid metabolism
food (animal fats)
arachidonic acid
messengers supporting inflammation
development
(= support + strengthening)
of rheumatism
Romatizma çok fazla hayvansal besin almayan hastalarda görülür, hayvansal besinler araşidonik asit içerir.

97. 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

98. 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

99. 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

100. 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
Stiffness: tutukluk

101. Dosage recommendations
Rheumatic diseases
rheumatoid arthritis over 3 months µg selenium/day
acute attacks initially µg selenium/day then µg selenium/day
maintenance therapy µg selenium/day

102. and immune system

103. 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

104. 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,
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

105. 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.

106. 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 conse-quence will be the release of the programmed cell death (apoptosis).

107. 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

108. Selenium increases the NK cell activity
rise in the selenium level (standard value: 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

109. 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

110. Dosage recommendations
Immune system
adults µg selenium/day

111. 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