- an essential trace element

- an essential

trace element

Basics

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

Close chemical relationship

Sodium selenite =

Na2SeO3 • 5 H2O

an inorganic salt of selenium

so-called sodium salt of selenous acid(as pentahydrate)

Important inorganic selenium compounds

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 ZnS2. in rare minerals3. technical: lead chamber slurry

(1817 Berzelius)4. drinking water (selenite, selenate;

e.g. < 2 µg/l)

organic 1. protein-bound:vegetable: predominantly as SeMetanimal: predominantly as SeCys

Daily kidney?

(circa data on selenium in µg/100g)

Meat, fish ca. (µg):liver (beef) 21filet (beef) 35trout 25herring 43kidney (beef) 112

Milk, eggs, milk products cow‘s milk 1Camembert, 45% F.i.d.m. 3

Fruit banana 1grape 2

Vegetable ca. (µg):brussels sprouts 1boletus 184

Bread, bakery products rye bread 3pasta (containing eggs) 20

Grain rye 1wheat bran 2oat flakes 10

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)

Source: Deutsche Gesellschaft für Ernährung e. V.: "Selen - Schätzwerte für eine angemessene Zufuhr“ , 2000.

Age Selenium µg/day

infants 0 to 4 months 5 - 154 to 12 months 7 - 30

children 1 to 4 years 10 - 404 to 7 years 15 - 457 to 10 years 20 - 5010 to 15 years 25 - 60

Recommendations of the DGE (German Society for Nutrition)

Source: Deutsche Gesellschaft für Ernährung e. V.: "Selen - Schätzwerte für eine angemessene Zufuhr“ , 2000.

Age Selenium µg/day

adolescents 15 to 65 years 30 - 70+ adults

pregnancy 30 - 70lactation 30 - 70

Toxicology

Source: SCF, (2000): Opinion of the scientific committee on food on the tolerable intake level of selenium. SCF/CS/NUT/UPPLEV/25 Final

“Lowest observed adverse effect level”1200 µgselenium / day

LOAEL

850 µgselenium / day

NOAEL“No observable adverse effect level”

300 µgselenium / day

UL“Tolerable upper intake level”

Safe total daily intake

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 according to age groups

“Tolerable upper intake level”

Age group UL (Tolerable upper intake level)

1 - 3 years 60 µg selenium / day 4 - 6 years 90 µg selenium / day 7 - 12 years 130 µg selenium / day

13 - 14 years 200 µg selenium / day 15 - 17 years 250 µg selenium / day

adults 300 µg selenium / day

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

Source: Biesalski HK, Köhrle J, Schümann K, (2002): Vitamine, Spurenelemente und Mineralstoffe. Prävention und Therapie mit Mikronährstoffen. Georg Thieme Verlag, Stuttgart

Selenium content of human organs and body fluids:

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

Reduced selenium supply

nutritional conditions and habits - extremely unbalanced nutrition- vegetarians- vegans

parenteral nutrition diets

Disturbed selenium intake

gastro-intestinal diseases maldigestion, malabsorption,

celiac disease

Increased selenium demand

pregnancy lactation high physical strain or stress elder persons immune deficiency

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)

Increased exogenous strain with noxa

workplace heavy metals (e.g. amalgam) chemotherapy radiotherapy alcohol, nicotine

Diagnosis of the selenium status

The determination from the whole bloodhas been proven for the measurement of the selenium level.

Hair isn‘t that suitable as examination material as it‘s not actively involved inthe metabolism.

Special laboratories measure theselenium content as a matter of routine and relatively low-priced.

Selenium status

Recommendations for laboratory analysis (Germany)

Serum: Short-term parameterdeficient < 65 μg/l = < 0.81 μmol/lnormal 50 - 120 μg/l = 0.81 - 1.25 μmol/loptimal 101 - 135 μg/l = 1.26 - 1.71 μmol/l

Whole blood: Long-term parameterdeficient < 85 μg/l = < 1.06 μmol/lnormal 60 - 120 μg/l = 1.06 - 1.50 μmol/loptimal 121 - 162 μg/l = 1.51 - 2.05 μmol/l

Source: Gröber U, (2003): Selen. OM. Z. f. Orthomolekulare Medizin 4, 25-26

1973 - 2002 Selenoproteins with known enzymatic function:glutathione peroxidasethioredoxin reductasedeiodase

Modified according to: Schomburg L, Schweizer U, Köhrle J, (2005): Selen und Selenoproteine. Humboldt Spektrum 3, 12-18

2003 Selenogenome:human: 25 genesrodent: 24 genesdrosophila: 4 genesC. elegans: 1 gene

2005 Selenoproteome: 30 - 70 forms

State of selenoprotein research

Selenoproteins:Proteins, specifically containing selenocysteine

Enzymes glutathione peroxidasethioredoxin reductasedeiodaseselenophosphate synthetase 2

Selenium-binding selenoprotein Pprotein

Proteins with still selenoprotein Wunexplained function several other selenoproteins

Selenium-containing proteins in humans

Proteins, containing non-specifically integrated selenium

muscle proteinsglobinother tissue proteins

Selenium-containing proteins in humans

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

Glutathione peroxidase

Origin and effect of radicalsUV-

radiationinflammations (phago-cytosis, PG-synthesis)

X-rays metabolic processes

elimination of foreign substances

O2-transport (Hb)

reper-fusion

damage of cell membraneDNA damage

protein cross-linkingcell destruction

Peroxide detoxification by glutathione peroxidase

GSH = reduced glutathioneGSSG = oxidised glutathioneE = enzyme

Glutathione peroxidase

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.

atherosclerosis cardiomyopathy amyotrophic lateral sclerosis rheumatism infertility cancer

Glutathione peroxidases

Function

activation (T4 to T3) and deactivation (T4 to rT3) of thethyroid hormones

provide appropriate levels of thyroid hormonesessential for growth, differentiation and metabolism

Deiodases


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

Deiodases

Function

play a decisive role in regulation of transcription (transcription factors NF-κB and AP-1)

regulate the cellular redox status, have a bearing onthe redox status of GSH (glutathione)

modulate folding (and consequently the function) of proteinshave a large substrate range (Trx, H2O2, dehydro-ascorbate, proteins)

Thioredoxin reductases

are involved in DNA biosynthesis


total knockout of the enzyme

Thioredoxin reductases

dysregulation of proliferation and differentiation of cells:is supposed to be part of the malignant transformation of cells

is considered to be a lethal factor in theearly embryonic stage

Tumour prevention

and cancer

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

Qidong-study: Primary hepatic cancer(China 1985-1989, primary hepatic cancer, placebo-controlled, 20,847 probands)

Linxian-study: Esophageal cancer(China 1986-1991, esophageal cancer, 29,584 probands)

Clark-study

Tumour-preventive effect verified in large studies


Design: multicentre, randomised, double-blind, placebo-controlled

Probands: 1,312Test centres: USA, low selenium regions

1983 - 1996Period of surveillance: 4.5 yearsMedication: 200 µg selenium/day

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


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

48,650prostate

4,350testes

55,150mammary

gland

11,350uterine corpus

6,500cervix

9,950ovary

Man Woman7,800 2,600oral cavity and throat

32,550 12,450lung11,200 8,250stomach

6,050 6,600pancreas35,600 35,800large bowel and rectum18,850 7,100urinary bladder

900 850Hodgkin‘s disease5,850 6,250Non-Hodgkin‘s lymphoma

5,500 4,750leukemia

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

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!

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

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

Bronchogenic carcinoma

selenium supplementation protects from lung carcinoma risk

low plasma selenium levels increase lung carcinoma risk

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 andthus, cell protection

reduction of the risk of recurrence ofa colorectal adenoma

Dosage recommendations

Chemotherapy

and cancer

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

side effects

chemotherapy as exogenous source of free radicals

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

Possible side effects of a chemotherapy

nausea, vomiting, loss of appetite diarrhea, constipation loss of hair tiredness, exhaustion increase in infections chronic organ damages

healthy body cell

Reduction of side effects

sodi

um s

elen

ite

oxid

ativ

e st

ress

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 seleniumProcesses in the tumour cell

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 GSH2. multidrug resistance is prevented3. cells, resistant to cytostatics, are resensitized4. high concentrations of GS-Se-GS induce apoptosis

+ Na-Selenite

Selective effect of seleniumProcesses in the normal cell

normal GSH-concentration intracellularly normal selenium sensitivity no increased formation of GS-Se-GS consequence

1. no impoverishment in GSH2. selenium is available for selenium-dependent enzyme systems3. the antioxidative defence works4. increased resistance to cytostatics5. no induction of apoptosis

+ Na-Selenite

Advantages of a selective sodium selenite therapy

+ reduction of the side effects

+ better compliance, fewer abruptions of the therapy


+ inhibition of inflammatory processes

+ lower susceptibility to infections

+ good tolerability


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/dayfrom 6th day of treatment 300 µg selenium/day

treatment-free days:duration variable 300 µg selenium/day

Chemotherapy

Radiotherapy

and cancer

Selenium and radiotherapy

PRO selenium+ stabilisation of the immune system

+ reduction of side effects

+ radioprotective effect


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

lowered selenium concentration in blood and serum

Tumour patient

• limited redox capacity

• balance between oxidation and antioxidation is disturbed

reduction of the ability to detoxify free radicals

reduced glutathione peroxidase activity


+ in general fewer side effects

+ fewer severe infections

+ better quality of life

+ improvement of the radiation-induced lymphedema

+ accelerated hematopoetic regeneration

+ good tolerability


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

Radiotherapy

and thyroid

Source: Forum Schilddrüse e.V.60596 Frankfurt/Main

Position of the thyroid

hyoid boneepiglottis

larynx

thyroid

thyroid cartilage

trachea

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

The thyroid, our organ with the highest content of selenium

Graves‘ diseaseA 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

Autoimmune diseases of the thyroid

What is Hashimoto’s thyroiditis?

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

Dr. Hakaru Hashimoto(1881-1934)


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 autoimmunedisease can appear.


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: Hypothyroidismhormone level

decreasing hormone production

Hypothyroidismformation of insufficient thyroid hormones

slowdown of the metabolism

increase in weight

weak performance

Symptoms in case of thyroid hormone deficiency

Physical symptomsWomen menstrual cycle disturbances infertility

Men loss of libido impotency

Toddlers 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: placebo-controlled, randomisedDuration: 3 monthsPatient collective: 70 female patients, TPO-Ab(antibodies

against thyroidal peroxidase) > 350 IU/mlMedication: all hormone substitution (LT4)

36 patients 200 µg Se/day34 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), 1687-1691

Clinical studies

Results:

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

change of the generalwell-being

course of the TPO-Ab under selenium substitution

Clinical studies

Follow-up study

Design: cross-over follow-upDuration: 6 monthsPatient collective: 47 female patients (average age 41)Medication: 13 patients (previously already verum):

200 µg selenium/day14 patients (previously placebo): 200 µg selenium/day11 patients (previously already placebo): placebo9 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:

Source: Gärtner R, Gasnier BC, (2003): Selenium in the treatment of autoimmune thyroiditis.Biofactors 19 (3-4), 165-170

course of TPO-Ab under selenium substitutionleft column = start follow-upright column = end follow-up after 6 months

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 - accordingto the demand - of the lacking hormone quantity

selenium therapy with sodium selenite

Triiodothyronine(T3)


children 50 µg selenium/day

adolescents 150 µg selenium/day

adults 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

Source: http://www.bgv-rheuma.de

presented antigen

T-cell

scavenger cellsubstances supporting inflammation

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

2. T-cells react to endogenous tissue properties in thesynovial membrane

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)

4. 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 deficiencySelenium 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


+ 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


rheumatoid arthritisover 3 months 200 µg selenium/day

acute attacksinitially 900 µg selenium/daythen 300 µg selenium/day

maintenance therapy 200 µg selenium/day

Rheumatic diseases

and immune system

Selenium and immune system

The well-coordinated immune systemresponds 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

Duration of study: 11 yearsPatient collective: 3,625 patients

211 patients with cancer diseaseMeasurement: cytotoxicity of the peripheral lymphocytes

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

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 activatedto cause a significant cytotoxic activity and high concentrationsof 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 conse-quence will be the release of the programmed cell death (apoptosis).

Selenium increases the NK cell activity

Practice study

Patient collective: 70 chronically sick patientsMedication: Cefasel® 300 µg dailyMeasurement: NK cell activity

Improvement of the immunocompetence of tumour patientsErpenbach K, (2003): Practice study, unpublished

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

Source: Erpenbach K, (2003): Improvement of the immunocompetence of tumour patients.Practice study, unpublished

rise in the selenium level (standard value: 74-139 µg/l) correlates with an increase in the NK cell activity (desired value > 25%)

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 -interferon

increases the antibody synthesis


adults 100 - 200 µg selenium/day

Immune system

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

Pharmacological properties

Pharmacology

- an essential trace element

Documents

selenium level

importance of selenium

selen ws

scientific committee

endogenous strain

umwelttoxikologie vo

systemkomponente tier

scfcsnutupplev25 finalmodified