1. Selenium in Health
and Disease
Cecilia A. Alamag
MS Applied Nutrition
Institute of Human Nutrition and Food, College of Human Ecology,
University of the Philippines,
College Los Baños, Laguna
CAALAMAG | Selenium in Health Disease
2. OUTLINE
CAALAMAG | Selenium in Health Disease
I. INTRODUCTION
A. History and Chemical Background
B. Sources
C. Dietary Requirements
D. Biological Activity, Utilization and Excretion
E. Functions
F. Laboratory Assessment
G. Deficiency and Toxicity
II. SELENIUM EFFECTS TO HUMAN HEALTH
A. Cancer
B. Cardiometabolic Health
C. Arthritis
D. HIV
E. Reproductive Health
3. HISTORY
CAALAMAG | Selenium in Health Disease
• integral part of the selenoenzyme
cytoplasmic glutathione peroxidase
(cGPX)
1817
1957
1973
• discovered by Jöns Jacob Berzelius
• named after the Greek Moon
goddess Selene
• essential nutrient for normal growth
and reproduction in animals
12. FUNCTIONS
CAALAMAG | Selenium in Health Disease
Anti-oxidant activity and glutathione synthesis
Hydroperoxides are
toxic product of various
oxidative processes and
potentially harmful
oxidizing agent.
13. FUNCTIONS
CAALAMAG | Selenium in Health Disease
Immune Function
• increased production of
interferon γ and other cytokines
• T cell proliferation
• increase in T helper cells
14. FUNCTIONS
CAALAMAG | Selenium in Health Disease
Thyroid activity: deiodinases
deiodinating T4 and T3
conversion of T4 to T3
Type I deiodinase
Type II deiodinase
Type III deiodinase
responsible for T4 conversion
to T3 in the brain
responsible for deactivating T4
and T3
16. DEFICIENCY AND TOXICITY
CAALAMAG | Selenium in Health Disease
Keshan Disease
Kashin-Beck Disease
growth retardation
cataract formation
lack of spermatogenesis
abnormal placental retention
cardiomyopathy
muscle inflammation
enhanced skin pallor
Deficiency Toxicity
garlic odor on the breath
gastrointestinal disorders
hair loss
sloughing of nails
Fatigue
Irritability
neurological damage
increased risk of type 2 diabetes
19. CANCER
CAALAMAG | Selenium in Health Disease
induce DNA repair and
synthesis in damaged cells
inhibit the proliferation
of cancer cells
In 1996, Clark et al. made a double-blind, randomized,
placebo-controlled trial involving 1312 patients who have
history of squamous cell carcinoma of the skin.
Individuals in the treatment arm were given 200 mg Se/day
for a mean of 4.5 years (average daily intake in the U.S. is
about 100 mg).
Patients receiving the Se-yeast supplement showed a much
lower prevalence of developing and dying from lung, colon
or prostate cancer.
20. CARDIOMETABOLIC HEALTH
CAALAMAG | Selenium in Health Disease
oxidative stress from free
radicals
heart disease
Selenium is one of a group
of antioxidants that may
help limit the oxidation of
LDL cholesterol and
thereby help to prevent
coronary artery disease.
21. CARDIOMETABOLIC HEALTH
CAALAMAG | Selenium in Health Disease
In the Flemish Study on Environment Genes and Health Outcomes,
higher blood selenium concentrations were associated with lower
systolic and diastolic BP levels at baseline and with a lower risk of
hypertension over 5.2 years of follow-up among men.
In a cross-sectional study conducted in Finland, a population with low
selenium status at the time of the study, serum selenium was also
inversely related to systolic BP levels in 722 middle-aged men.
In the HDL-Atherosclerosis Treatment Study (HATS) trial, selenium
(100 mg/d) was administered along with vitamin E (800 IU/d),
vitamin C (1000 mg/d), and b-carotene (25 mg/d), with no effect on
BP levels during three years of follow-up (Brown 2001 as cited by
Stranges 2010).
22. REPRODUCTIVE HEALTH
CAALAMAG | Selenium in Health Disease
Testicular tissue contains
high concentrations of
selenium.
Selenium is essential for
testosterone biosynthesis
and the formation and
normal development of
spermatozoa.
Phospholipid hydroperoxide
glutathione peroxidase
(PHGPx/GPx4) and
Selenoprotein P
23. REPRODUCTIVE HEALTH
CAALAMAG | Selenium in Health Disease
The study in 1984 by Bleau et al50 reported an optimal range between
50 and 60 mcg/mL in semen and a positive correlation between sperm
count and semen selenium concentration in 125 men from couples
being investigated for infertility.
In Scotland, a placebo-controlled randomized control trial (RCT) of 64
men demonstrated that sperm quality and fertility improved after
selenium supplementation.
Three small studies, from Poland and the United States, supplementing
(200-300 mg/d) with selenite, selenium-enriched yeast, or diets
naturally high in selenium reported that, although semen selenium
concentrations increased, there were no positive effects on sperm
characteristics or activity.
Figure ___ shows how selenoproteins can be produced in the body from a variety of selenium sources. Glutathione (GSH) is considered to be the main component of the selenium metabolism pathway, taking part in the first of a series of reduction reactions that convert selenite to hydrogen selenide (H2Se), which is regarded as the precursor for supplying selenium in an active form for synthesis of selenoproteins. The further metabolism of H2Se involves sequential methylation to methylselenide (CH3SeH), dimethylselenide ([CH3]2Se), trimethylselenonium ion ((CH3)3Se+). Selenite (SeO3 2; inorganic form of selenium) crosses the plasma membrane and reacts with cytoplasmicthiols in the reduction pathway; this forms selenide, which is then methylated, giving rise to methylated selenium derivatives that are excreted in urine, expired air via the lungs, and feces
2 molecules of glutathione reacts with organic hydroperoxide, when catalyzed by glutathione peroxidase (GSH–Px), yields glutathione disulfide (GSSG), an alcohol and water molecule. Hydroperoxides are toxic product of various oxidative processes and potentially harmful oxidizing agent. In erythrocytes, the unchecked buildup of peroxides results in premature cell lysis. Acts also in other organic peroxides.Heavy metal detoxification
interferons share several common effects; they are antiviral agents and can fight tumors.Interferons (IFNs) are proteins made and released by host cells in response to the presence of pathogens such as viruses,bacteria, parasites or tumor cells. They allow for communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors."interfere" with viral replication within host cellsT cells or T lymphocytes belong to a group of white blood cells known as lymphocytesT helper cells (Th cells) are a sub-group of lymphocytes, a type of white blood cell, that play an important role in the immune system, particularly in the adaptive immune system. They help the activity of other immune cells by releasing T cell cytokines. They are essential in B cell antibody class switching, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages.
selenoenzymes may modulate or control many aspects of thyroid hormone metabolism T4 – thyroxineT3 – triidothyronine active form of thyroid hormone
Serum levels reflect recent intake Erythrocyte levels are more indicative of remote exposure. Hair levels have been used in the diagnosis of deficiency
