Azimut The Premex Newsletter #1
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The Importance of selenium to human health The essential trace mineral, selenium, is of fundamental importance to human health.
Azimut #1 — The Premex Newsletter
author Margaret P. Rayman (“The Lancet. Vol 356: 233-41, July 15, 2000), Centre for Nutrition and Food Safety, School of Biological Sciences, University of Surrey, UK
As a constituent of selenoproteins, selenium has structural and enzymic roles, in the latter context being best known as an antioxidant and catalyst for the production of active thyroid hormone. Selenium is needed for the proper functioning of the immune system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS. It is required for sperm motility and may reduce the risk of miscarriage. Deficiency has been linked to adverse mood states. Findings have been equivocal in linking selenium to cardiovascular disease risk although other conditions involving oxidative stress and inflammation have shown benefits of a higher selenium status. An elevated selenium intake may be associated with reduced cancer risk. Large clinical trials are now planned to confirm or refute this hypothesis. In the context of these health effects, low or diminishing selenium status in some parts of the world, notably in some European countries, is giving cause for concern. The trace mineral selenium is an essential nutrient of fundamental importance to human biology. This has become increasingly obvious, as new research has shown a hitherto unsuspected role for this element in areas important to human health. As selenocysteine, the 21st aminoacid, selenium is a component of selenoproteins, some of which have important enzymic functions.1 It has now been recognized that all these enzymes are selenium-dependent, generally with selenocysteine at the active site.1 Here selenium functions as a redox centre, for instance when the selenoenzyme, thioredoxin reductase, reduces nucleotides in DNA synthesis and helps control the intracellular redox state,2 or when the selenium-dependent iodothyronine deiodinases produce active thyroid hormone from inactive precursor.1 The best-known example of this redox function is the reduction of hydrogen peroxide and
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«Selenium is needed for the proper functioning of the immune system»
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damaging lipid and phospholipid hydroperoxides to harmless products (water and alcohols) by the family of selenium-dependent glutathione peroxidases.1–3 This function helps to maintain membrane integrity,3,4 protects prostacyclin production,4 and reduces the
Azimut #1 — The Premex Newsletter
likelihood of propagation of further oxidative damage to biomolecules such as lipids, lipoproteins, and DNA with the associated increased risk of conditions such as atherosclerosis and cancer.3,4 About 35 selenoproteins have been identified, though many have roles that have not yet been fully elucidated.5 Table 1 details known selenoproteins that carry out nutritional functions of selenium.1–3,5–9 Selenium has additional important health effects particularly in relation to the immune response and cancer prevention, which are almost certainly not exclusively linked to these enzymic functions. Health conditions associated with selenium deficiency Recognition of the important role of selenoproteins in metabolism helps to explain the adverse consequences of selenium deficiency in human and animal health. Selenium enters the food chain through plants, which take it up from the soil. Selenium deficiency has therefore been identified in parts of the world notable for their low soil content of selenium, such as volcanic regions.10 Acid soils and complexation, frequently with iron or aluminum, also reduce the uptake of selenium by plants, as in many parts of Europe.10 Animal deficiency-diseases have been identified since the 1950s on a wide scale in livestock in countries, including the UK, that have such soil conditions, examples being reproductive impairment, growth depression (ill-thrift), and whitemuscle disease, a myopathy of heart and skeletal muscle principally affecting lambs and calves.10 These disorders have had such serious economic consequences that measures to increase selenium intake (such as top dressing of pasture land with selenised fertilizers, mineral mixes, boluses, drenches) are now applied to prevent their occurrence.10
4
gnized in some regions: Keshan disease, an endemic cardiomyopathy, and Kashin-Beck disease, a deforming arthritis, were first identified in an area of China where the soil is extremely low in selenium.10
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Human dietary intakes also range from high to low according to geography. Human selenium-deficiency diseases have been reco-
Both these conditions are believed to have other causative cofactors. There is evidence that less-overt selenium deficiency can have adverse consequences for disease susceptibility and the maintenance of optimal health. Low selenium status may contribute to the etiology of the disease process but in some cases it may be an outcome of the condition itself and may exacerbate disease progression (eg, HIV infection). These difficulties are largely overcome in prospective epidemiological studies, particularly where the first few years of follow-up are excluded from the analysis, and in randomized controlled
Selenoprotein
Function
Glutathione peroxidases (GPx1, GPx2, GPx3, GPx4)
Antioxidant enzymes: remove hydrogen peroxide, and lipid and phospholipid hydroperoxides (thereby maintaining membrane integrity, modulating eicosanoid synthesis, modifying inflammation and likelihood of propagation of further oxidative damage to biomolecules such as lipids, lipoproteins, and DNA).1,2,3,6
(Sperm) mitochondrial capsule selenoprotein
Form of glutathione peroxidase (GPx4): shields developing sperm cells from oxidative damage and later polymerizes into structural protein required for stability/motility of mature sperm.7
Iodothyronine deiodinases (three isoforms)
Production and regulation of level of active thyroid hormone, T3, from thyroxin, T4.1
Thioredoxin reductases (probably three isoforms)
Reduction of nucleotides in DNA synthesis; regeneration of antioxidant systems;2 maintenance of intracellular redox state, critical for cell viability and proliferation;2 regulation of gene expression by redox control of binding of transcription factors to DNA.2
Selenophosphate synthetase, SPS2
Required for biosynthesis of selenophosphate, the precursor of selenocysteine, and therefore for seleoprotein synthesis.2
Selenoprotein P
Found in plasma and associated with endothelial cells. Appears to protect endothelial cells against damage from peroxynitrite.1,2,8
Selenoprotein W
Needed for muscle function.1,2
Prostate epithelial selenoprotein (15kDa)
Found in epithelial cells of ventral prostate. Seems to have redox function (resembles GPx4), perhaps protecting secretory cells against development of carcinoma.9
DNA-bound spermatid selenoprotein (34 kDa)
Glutathione peroxidase-like activity. Found in stomach and in nuclei of spermatozoa. May protect developing sperm.9
18 kDa selenoprotein
Important selenoprotein, found in kidney and large number of other tissues. Preserved in selenium deficiency.5
Azimut #1 — The Premex Newsletter
trials of selenium supplementation.
Table 1: Known selenoproteins that carry out nutritional functions of selenium
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Immune function Numerous studies suggest that deficiency of sele-
cytes and natural-killer cells, thereby facilitating
nium is accompanied by loss of immunocompe-
their interaction with interleukin-2. This interac-
tence, probably not unconnected with the fact that
tion is crucial for clonal expansion and differentia-
selenium is normally found in significant amounts
tion into cytotoxic T cells. Even at so-called replete
in immune tissues such as liver, spleen, and lymph
levels of plasma selenium produced by normal die-
nodes. Both cell-mediated immunity and B-cell
tary intake in the USA (120–134 mcg/L), supplemen-
function can be impaired.6 By way of contrast, supplemen-
tation with 200 mcg selenium per
«Selenium enters
day has considerable immunoen-
“selenium-replete” individuals,
the food chain
have been demonstrated by the
has marked immunostimulant
through plants,
same research group in patients
which take it up
neck cancer.
tation with selenium, even in
effects, including an enhancement of proliferation of activated T cells (clonal expansion). 11 Lymphocytes from volunteers
from the soil»
supplemented with selenium (as
undergoing therapy for head and Additionally, cells of the immune system may have an important functional need for
sodium selenite) at 200 mcg per day showed an
selenium. Activated T cells show upregulated
enhanced response to antigen stimulation and an
selenophosphate synthetase activity, 12 direc-
increased ability to develop into cytotoxic lympho-
ted towards the synthesis of selenocysteine, the
cytes and to destroy tumor cells. Natural-killer-
essential building block of selenoproteins, which
cell activity was also increased. Supplementation
shows the importance of selenoproteins to activa-
resulted in a 118% increase in cytotoxic-lympho-
ted T-cell function and the control of the immune
cyte-mediated tumor cytotoxicity and an 82%
response. The mRNAs of several T-cell-associated
increase in natural-killer-cell activity compared
genes (eg, interleukin-2-receptor α-subunit, CD4)
with baseline.11
have the theoretical capacity to encode functional
The mechanism appears to be closely related to
selenoproteins, suggesting that the roles of sele-
the ability of selenium to upregulate the expression
nium in the immune system may be more diverse
of receptors for the growth-regulatory cytokine
than previously suspected.13
interleukin-2 on the surface of activated lympho-
6
hancing effects.11 Such effects
be explained.15 Selenium seems to be a crucial nutrient for HIV
Selenium deficiency is linked to the occurrence,
infected individuals. It is a potent inhibitor of HIV
virulence, or disease progression of some viral
replication in vitro.17 The progress of HIV can be
infections.14
thought of as being synonymous with the progres-
Beck and colleagues have shown that in a sele-
sive loss of CD4 helper T cells. More than 20 papers
nium deficient host harmless viruses can become
report a progressive decline in plasma selenium
virulent,1
in parallel with the on-going loss of CD4 T cells in
Selenium seems
Keshan disease. When selenium-
to be a crucial
deficient mice were inoculated with a benign strain of the cox-
nutrient for HIV
sackie virus (CVB3/0), mutations
infected indivi-
occurred in the genome to give a cardiovirulent form of the virus
duals
that caused myocarditis with simi-
HIV-1 infection.18 This decline in selenium occurs even in early stages of disease when malnutrition or malabsorption cannot be a factor.18 In fact, plasma selenium is a strong predictor of the outcome in HIV infection. Baum and colleagues showed that selenium-deficient HIV patients
larities to that seen in human beings. Furthermore,
are nearly 20 times more likely (p<0·0001) to die
when the virus from these mice was inoculated into
from HIV-related causes than those with adequate
mice that had adequate selenium, it still induced
levels.19 Selenium deficiency is defined by these
heart damage, showing the irreversibility of the
workers as a plasma concentration at or below 85
mutation. In the case of the Coxsackie virus, six
mcg/L, a concentration not attained in many nor-
separate point mutations were identified with the
thern European countries—eg, a mean concentra-
development of virulence, causing myocarditis in
tion of 60 mcg/L was found in a Scottish study.20
the host. A similar study on mice that were unable
Baum and colleagues showed that low plasma
to make glutathione peroxidase (GPx1-knock-out
selenium is a significantly greater risk factor for
mice) showed that this enzyme is essential for the
mortality than low helper-T-cell count, by a fac-
avoidance of oxidative damage to the RNA-viral
tor of 16, and confers a more significant risk than
genome that results in the myocarditic mutations.16
deficiency of any other nutrient investigated. In
Coxsackie virus has been isolated from the blood
HIV-infected children, low levels of plasma sele-
and tissues of people with Keshan disease and is
nium were significantly and independently related
thought likely to be a cofactor in the development
to mortality (relative risk 5·96; p=0·02) and faster
of the cardiomyopathy.15,16 It seems probable, the-
disease progression.21
refore, that human selenium deficiency similarly
Selenium also appears to be protective in indi-
affects the viral genome resulting in the development of the heart pathology. If these findings were to be applicable to other RNA viruses, such as poliovirus, hepatitis, influenza, or HIV, there would be considerable
Azimut #1 — The Premex Newsletter
5 a situation that is likely to be relevant to the development of
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Viral infection
viduals infected with hepatitis
Selenium deficiency is linked to progression of some viral infections.14
public-health implications. The
virus (B or C) against the progression of the condition to liver cancer.22,23 Viruses may be capable of hijacking the selenium supply of the host by incorporating selenium into viral selenoproteins,
steady emergence of new strains of influenza virus
thereby reducing the ability of the host to mount
in China with its selenium-deficient belt, or the
an effective immune response. There is experimen-
first crossing over of HIV to human beings in the
tal evidence that this is possible from the work of
selenium-deficient population of Zaire, might also
Moss’s group in the case of the pox virus, mol-
7
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luscum contagious, which makes
Studies have
long as there is enough selenium
theoretical and experimental evi-
shown that in a
high and the host cell will be less
dence from Taylor’s group that the
selenium defi-
likely to die (by apoptosis). The
proteins (such as GPx) is common
cient host har-
replicate at very low levels and
to many human viral pathogens
mless viruses can
establish a persistent infection.
become virulent
however, increased oxidative
a homologue of GPx,24 and both
capability of making viral seleno-
such as HIV-1 and 2, coxsackie virus B3, hepatitis B and C viruses, and the measles virus.25,26 Good
around, cellular immunity will be
best viral strategy is therefore to
Under low selenium conditions, stress and apoptosis activate the
selenium status may protect against HIV progres-
virus, which must replicate at higher rates to
sion by maintaining host immune competence and
escape from a dying cell thus leading to increased
appropriate redox control. Taylor suggests that as
pathogenic effects.
Mood Azimut #1 — The Premex Newsletter
In a study in the USA, selenium deprivation led There are a number of indications that selenium
to depressed mood and more hostile behavior as
is important to the brain : during selenium deple-
measured by a questionnaire.38 The lower the
tion the brain receives a priority supply;38 the
initial selenium status, the more the mood scores
turnover rate of some neurotransmitters is altered
decreased indicating a worsening of mood, as a
in selenium deficiency;39 supplementation with
result of the low selenium diet. In a second US study,
selenium reduced intractable epileptic seizures in
where individuals were fed either a low or a high
children;40,41 low plasma selenium concentrations
selenium diet for 15 weeks, those on the low sele-
in the elderly were significantly associated with
nium diet had significantly decreased clearheaded/
senility and accelerated cognitive decline;38,42
confused and elated/depressed subscores.43 (The
and brain selenium concentration in Alzheimer’s
dietary selenium intake on this low-selenium diet
patients was only 60% of that in controls.38 Fur-
was 32·6 mcg per day, similar to current UK intakes
thermore, the brain is deficient in catalase,41
of 29–39 mcg per day).45
thus peroxidation products such as hydrogen
selenoenzymes. A beneficial effect of
that
selenium status on mood
selenium
when selenium status is
has been shown, at least
is important
“marginal”. In three stu-
to the brain
tus was associated with
dies, low selenium staa significantly greater incidence of depression
and other negative mood states such as anxiety, confusion, and hostility.38,43,44
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Low selenium
1.05 1 0.95 0.9 0.85 re e ho abl st eile Cl ea r co he nf ad us ed Co ed* m p an ose xi dou Co s nfi de un n su tre de E pr la es te se dEn d* er ge t ti icre d
indications
ved by the antioxidant
High selenium
Ag
a number of
peroxides must be remo-
Ratio of mood scores weeks 11-14 : weeks 2-5
There are
1.1
peroxide and primary
Figure 1 : Influence of selenium content of diet on mood states, measured by the "Profile of Mood States—Bipolar Form" questionnaire The higher the score, the better the mood. *Significant difference between groups (p<0.05). (Bar chart constructed from reference 43.)
or supplementation with selenium appears
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high dietary selenium
In contrast to these findings, high dietary sele-
in weeks 11–14 to those in weeks 2–5, for both the
nium or supplementation with selenium appears to
high and low selenium diets. A similar finding was
improve mood. In the US study referred to above,43
obtained in a double-blind crossover study done
those on the high selenium (226·5 mcg per day) diet
in the UK, where a 100 mcg selenium supplement
significantly improved in the clearheaded/confused,
significantly decreased anxiety, depression, and
confident/unsure, and composed/anxious subs-
tiredness,44 the effect being greatest in those
cores, and total mood disturbance was significantly
whose diets were lowest in selenium.
less. The results of this study are shown in figure 1 as the ratio of mean mood scores (six categories)
Cardiovascular disease Selenium may be protective against cardio-
The balance is therefore tipped towards the
vascular disease.4 On theoretical grounds, this
proaggregatory state. In men with coronary artery
hypothesis is supported by the ability of GPx to
disease, platelet aggregability is inversely related to
combat the oxidative modification of lipids and to
selenium status.4,49
reduce platelet aggregation.4 GPx4 reduces hydro-
Prospective epidemiological studies have had
peroxides of phospholipids and cholesteryl esters
mixed findings. While Salonen and colleagues found
associated with lipoproteins48 and may therefore
a two-fold to three-fold increase in cardiovascular
reduce the accumulation of oxidized low-density
morbidity and mortality for individuals with serum
lipoproteins in the artery wall. GPx is required
selenium concentrations below 45 mcg/L compa-
for the metabolism of hydroperoxides produced
red with individuals above that concentration at
in eicosanoid synthesis by the lipoxygenase and
baseline,50 Virtamo’s group found no significant
cyclooxygenase pathways.6 In selenium deficiency,
associations with selenium concentrations above
a build-up of these hydroperoxides inhibits the
and below that cut-off point except for stroke
enzyme prostacyclin synthetase that is responsible
mortality.51 A study by Suadicani and colleagues
for the production of vasodilatory prostacyclin by
showed that middle-aged and elderly Danish men
the endothelium, but stimulates the production of
with serum selenium below 79 mcg/L had a signi-
thromboxane, which is associated with vasocons-
ficantly increased risk of ischemic heart disease.52
triction and platelet aggregation.4
However, about half a dozen other studies have not
Azimut #1 — The Premex Newsletter
to improve mood
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Selenium may be protective against cardiovascular
Azimut #1 â&#x20AC;&#x201D; The Premex Newsletter
disease
shown a clear association between cardiovascular
plasma selenium concentration might be expected
risk and low selenium, although these differ from
in people who have atherosclerosis, even before the
the above studies in having included few or no
occurrence of an event.
people with low selenium concentrations.4,53 That a low selenium status may be relevant was suggested by the findings of Kardinaal and colleagues in the ten-centre EURAMIC study where a significant inverse association between toenail selenium
Selenium behaves both as an antioxidant and
levels and risk of myocardial infarction was shown
anti-inflammatory agent. This is because selenium
only for the centre with the lowest selenium (Ger-
in its antioxidant role, notably as GPx, can: reduce
many).54 Thus the effect may only be apparent in
hydrogen peroxide, lipid and phospholipid hydro-
populations of low selenium status, lower than the
peroxides, thereby dampening the propagation of
concentrations obtaining in the USA and a large
free radicals and reactive oxygen species; reduce
part of Europe. The disparity between studies may
hydroperoxide intermediates in the cyclooxyge-
also be explained to some extent by the status of
nase and lipoxygenase pathways diminishing the
other antioxidants such as vitamin E, which may
production of inflammatory prostaglandins and
compensate for a deficiency in selenium in protec-
leukotrienes; and modulate the respiratory burst,
tion against atherosclerosis.54
by removal of hydrogen peroxide and reduction of
A further factor to be taken into consideration
10
Other oxidative-stress or inflammatory conditions
superoxide production.6
when assessing these studies is that atheroscle-
Any condition associated with increased oxi-
rosis is an inflammatory state and will provoke the
dative stress or inflammation might be expected
acute phase response to a degree related to its seve-
to be influenced by selenium levels, which may
rity. Being an acute-phase reactant,55 some fall in
be the case in rheumatoid arthritis, pancreatitis,
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Selenium behaves both as an antioxidant and anti-inflammatory
and asthma. In a case-control study nested within
Selenium has also shown benefit in acute pan-
a Finnish cohort of 18 709 men and women who
creatitis. In a small controlled trial in Rostock,
had no arthritis at baseline, the adjusted relative
Germany, intravenous administration of selenium
risk between the highest and lowest tertiles of
to patients with acute necrotizing pancreatitis
serum selenium was 0·16 (p for trend=0·02) for
reduced mortality from 89% in controls to zero in
rheumatoid-factor-negative arthritis.56 There
the treatment group.59
was no association for rheumatoid-factor-positive
A protective relationship was found between
disease.56 In a double-blind randomized trial in a
dietary selenium intake and asthma in adults in
small group of patients with rheumatoid arthri-
a large population-based case-control study in
tis,56 supplementation with 200 mcg selenium
London (odds ratio per quintile increase=0·84;
as organic selenium for 3 months, significantly
p=0·002).60 In a small nested case-control study,
reduced pain and joint involvement.57
current wheeze among New Zealand children was
There is evidence for a protective effect of sele-
more common in those with low concentrations
nium in pancreatitis, a disorder associated with a
of selenium in serum samples collected 8 years
high level of oxidative stress. At Manchester Royal
previously (odds ratio=3·1).61 Another small study
Infirmary, administration of selenium (600 mcg
in intrinsic asthmatics showed significant clinical
per day) along with other antioxidants to patients
improvement on supplementation with selenium
with chronic and
at 100 mcg per day as sodium selenite.62
recurrent pancreatitis significantly reduced pain
Selenium supplementation may be of benefit in
and frequency of attacks. Treatment has been revo-
preventing ischemia-reperfusion injury: a seleniu-
lutionized by obviating the need for surgery for
menriched diet had a significant effect (p<0·05) in
pancreatic pain.58
preventing reperfusion-induced arrhythmias in an
Azimut #1 — The Premex Newsletter
agent
animal model.63
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Conclusions Recent evidence has reinforced the importance to health of adequate selenium status. Selenium intakes may be suboptimal with respect to disease risk, notably in populations of adults in the UK, parts of Europe and China, New Zealand, and even in the USA. Indications that this may be the case are strongest for cancer—where selenium intake at a much higher level than that required to saturate the selenoenzymes would appear to be beneficial—and HIV progression to AIDS. Further research is needed to clarify the optimal nutrition level with respect to selenium. In this context, the planned PRECISE and SELECT trials should give the definitive answer on the ability of selenium to reduce cancer risk. If similar results were to be obtained to those of
Azimut #1 — The Premex Newsletter
the NPC trial, addition of selenium to the food sup-
12
ply in countries such as the UK would be a possible outcome. This has been achieved in Finland, where selenium intakes were formerly very low, by addition of selenium to fertilizers since 1984.
and subcellular distribution of selenium and selenoproteins. In: Roussel AM, Favier A, Anderson RA, eds. Trace elements in man and animals 10: proceedings of the tenth international symposium on trace elements in man and animals. New
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5.Behne D, Pfiefer H, Rothlein D, Kyriakopoulos A. Cellular
York: Plenum Press, 2000: 29–33. 6.Spallholz JE, Boylan LM, Larsen HS. Advances in understanding selenium’s role in the immune system. Ann NY Acad Sci 1990; 587: 123–39. 7.Ursini F, Heim S, Kiess M, et al. Dual function of the selenoprotein PHGPx during sperm maturation. Science 1999; 285: 1393–96. 8.Arteel GA, Briviba K, Sies H. Protection against peroxynitrite. FEBS Lett 1999; 445: 226–30. 9.Behne D, Kyriakopoulos A, Kalcklosh M, et al. Two new selenoproteins found in the prostatic glandular epithelium and the spermatid nuclei. Biomed Environ Sci 1997; 10: 340–45. Academic and Professional, 1996. 11.Kiremidjian-Schumacher L, Roy M, Wishe HI, Cohen MW, Stotzky G. Supplementation with selenium and human immune cell functions. Biol Trace Elem Res 1994; 41: 115–27. 12.Guimaraes MJ, Peterson D, Vicari V, et al. Identification of a novel SelD homolog from eukaryotes, bacteria, and archea: is there an autoregulatory mechanism in selenocysteine metabolism? Proc Natl Acad Sci USA 1996; 93: 15068–91. 13.Taylor EW, Nadimpalli RG. Chemoprotective mechanisms of selenium in cancer and AIDS: evidence for the involve-
Azimut #1 — The Premex Newsletter
10.Reilly C. Selenium in food and health. London: Blackie
ment of novel selenoprotein genes. Info Onkologi 1999; 2: 7–11. 14.Taylor EW, Nadimpalli RG, Ramanathan CS. Genomic
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29.Hidiroglou M. Trace element deficiencies and fertility in
seizures. Neuropediatrics 1994; 25: 217–23.
ruminants: a review. J Dairy Sci 1979; 62: 1195–206.
42.Berr C, Balansard B, Arnaud J, Roussel AM, Alperovitch
30.Barrington JW, Lindsay P, James D, Smith S, Roberts A.
A. Cognitive decline is associated with systemic oxidative
Selenium deficiency and miscarriage: a possible link? Br J
stress—the EVA study. J Am Geriat Soc 2000 (in press).
Obstet Gynaecol 1996; 103: 130–32.
43.Finley JW, Penland JG. Adequacy or deprivation of dietary selenium in healthy men: clinical and psychological findings. J Trace Elem Exp Med 1998; 11: 11–27. 44.Benton D, Cook R. Selenium supplementation improves mood in a double-blind crossover trial. Biol Psychiatry 1991; 29: 1092–98.
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Joint Food Safety and Standards Group, UK Ministry of Agriculture Fisheries and Food (MAFF), October, 1997. 46.Olivieri O, Girelli D, Azzini M, et al. Low selenium status in the elderly influences thyroid hormones. Clin Sci 1995; 89: 637–42.
56.Knekt P, Heliövaara M, Aho K, Alfthan G, Marniemi J,
47.Vanderpas JB, Contempré B, Duale NL, et al. Iodine and
Aromaa A. Serum selenium, serum alpha-tocopherol and
selenium deficiency associated with cretinism in Northern
the risk of rheumatoid arthritis. Epidemiology 2000 (in
Zaire. Am J Clin Nutr 1990; 52: 1087–93.
press).
48.Sattler W, Maiorino M, Stocker R. Reduction of HDL-
57.Peretz A, Néve J, Duchataeu JP, Famaey JP. Adjuvant
and LDL-associated cholesterylester and phospholipid
treatment of recent onset rheumatoid arthritis by selenium
hydroperoxides by phospholipid hydroperoxide glutathione
supplementation: preliminary observations. Br J Rheumatol
peroxidase and Ebselen (PZ 51). Arch Biochem Biophys 1994;
1992; 31: 281–86.
309: 224–21.
58.McCloy R. Chronic pancreatitis at Manchester, UK: focus
49.Salonen JT, Salonen R, Seppaenen K, et al. Relationship
on antioxidant therapy. Digestion 1998; 59 (suppl 4): 36–48.
of serum selenium and antioxidants to plasma lipoproteins,
59.Kuklinsky B, Schweder R. Acute pancreatitis, a free radi-
platelet aggregability and prevalent ischemic heart disease
cal disease; reducing the lethality with the sodium selenite
in Eastern Finnish men. Atherosclerosis 1988; 70: 155–65.
and other antioxidants. J Nutr Environ Med 1996; 6: 393–94.
50.Salonen JT, Alfthan G, Pikkarainen J, Huttunen JK, Puska
60.Shaheen SO, Sterne JAC, Thompson RL, et al. Dietary
P. Association between cardiovascular death and myco-
antioxidants and asthma in adults. Eur Respir J 1999; 14
cardial infarction and serum selenium in a matched pair
(suppl 30): 141s.
longitudinal study. Lancet 1982; ii: 175–179.
61.Shaw R, Woodman K, Crane J, Moyes C, Kennedy J, Pearce
51.Virtamo J, Valkiela E, Alfthan G, Punsar S, Huttunen JK,
N. Risk factors for asthma symptoms in Kawerau children. N
Karvonen MJ. Serum selenium and the risk of coronary heart
Zealand J Med 1994; 107: 387–91.
disease and stroke. Am J Epidemiol 1985; 122: 276–82.
62.Hasselmark L, Malmgren R, Zetterstrom O, Unge G.
52.Suadicani P, Hein HO, Gyntelberg F. Serum selenium
Selenium supplementation in intrinsic asthma. Allergy 1993;
concentration and risk of ischemic heart disease in a
48: 30–36.
prospective cohort study of 3000 males. Atherosclerosis
63.Tanguy S, Boucher F, Besse S, Ducros V, Favier A, de
1992; 96: 33–42.
Leiris J. Trace elements and cardioprotection: increasing
53.Salvini S, Hennekens CH, Morris JS, Willet WC, Stampfer
endogenous glutathione peroxidase activity by oral sele-
MJ. Plasma levels of the antioxidant selenium and risk of
nium supplementation in rats limits reperfusion-induced
myocardial infarction among US physicians. Am J Cardiol
arrhythmias. J Trace Elem Med Biol 1998; 12: 28–38.
Azimut #1 — The Premex Newsletter
technique
45.Food Surveillance Information Sheet, No 126. London:
1995; 76: 1218–21. 54.Kardinaal AFM, Kok FJ, Kohlmeier L, et al. Association between toenail selenium and risk of myocardial infarction in European men: the EURAMIC Study. Am J Epidemiol 1997; 145: 373–79. 55.Nicol C, Herdman J, Sattar N, et al. Changes in concentrations of plasma selenium and selenoproteins after minor elective surgery: further evidence for a negative acute phase response. Clin Chem 1998; 44: 1764–66.
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Azimut #1 â&#x20AC;&#x201D; The Premex Newsletter
organic minerals are more efficient than inorganic minerals for animal supplementation 16
product
The effect of supplemental Selenium Determination of the effect of supplemental Selenium source and level on commercial layer performance parameters and on table egg Selenium content
Maria Alejandra Velásquez.
Introduction The table egg industry is continuously searching for strategies
Animal Husbandry Specia-
leading to product differentiation, for consumers to distinguish
list, National University,
enhanced eggs from traditional eggs. On the other hand, one consu-
Medellín, Colombia.
mer sector is showing a growing interest for foods leading to improved nutrition/health status, i.e.: the so called "functional" foods”.
Carlos González. Animal Husbandry Specialist.
One of the strategies explored by the animal nutrition sector to
Professor, National Univer-
fulfill both producer needs and consumer demands for differentiated
sity, Medellín, Colombia.
products is using mineral organic sources in feeds. The basis of feeding animals with organic resources revolves around the theory that
Paula A. Toro. MSc. Animal Husbandry, Premex SA. Javier Chica Peláez. MSc. Animal Husbandry, Premex SA.
organic minerals are more similar to the forms found in live animals therefore they tend to be more biologically available than inorganic sources. If organic compounds are more stable in the digestive tract, then minerals given this way can be protected from complexing with other dietary components that can interfere with their absorption
Azimut #1 — The Premex Newsletter
Researchers
(Dudley-Cash, 1997). This way, improved mineral status can be obtained in the birds. Generally, organic minerals are more efficient than inorganic minerals for animal supplementation, but their positive responses are conditioned by several aspects, including: The organ or tissue selected to measure their activity, the dietary level used to fulfill the requirements of the species being supplemented, the timing and length of supplying the mineral source being evaluated, and the micromineral in question (Gutiérrez, 2000; Dudley-Cash, 1997). This trial was performed as an attempt to prove that organic mineral supplementation increases the transfer of Selenium (Se) to table eggs, leading to modulating nutrient egg contents. This allows for product differentiation that end consumers can perceive.
17
product
General objective Evaluating the effect of dietary Selenium supplementation source and level on Selenium content in commercial layer eggs.
Specific objectives Comparing the effectiveness of different Selenium sources on the transfer of Selenium to the egg. Determining the effect of feed Selenium supple-
Experimental treatments
mentation levels on the concentration of Selenium in commercial layer eggs.
Materials and methods
Table 1 describes the different treatments. Table 1. Selenium sources and levels used in the different experimental treatments
Azimut #1 — The Premex Newsletter
A total of 192 thirty-week-old Lohmann Brown commercial laying hens was used. Birds were housed in San Pablo experimental farm, Medellín
Feeds
Sodium Selenite (ppm)
Prokel™ Selenium (ppm)
Section, National University of Colombia, located in
Treatment 1
0.10
0.0
the municipality of Rionegro, Antioquia, Colombia.
Treatment 2
0.30
0.0
Treatment 3
0.0
0.10
Treatment 4
0.0
0.30
The experimental period lasted for 6 weeks, including 2 phases. Phase I (adaptation phase) lasted for 2 weeks, during which birds were adapted to the experimental treatments. Phase II (evaluation period) lasted for 4 weeks, during which determinations were performed in accordance with the experimental design. Birds were housed in laying cages, within the experimental house. Each treatment included 4 repetitions, 12 birds per repetition, housed in 4 adjacent cages, 3 birds per cage.
During the experimental period birds were fed to meet daily nutrient requirements as established by both the primary breeder and the National Research Council (NRC, 1994). Throughout the experimental period, birds in all treatment groups received the same corn/ soybean meal/wheat bran-based diet, as described in Table 2, the only variation being Selenium sources and inclusion levels, as described in Table 1. Prior to the adaptation period, one feed sample per treatment was analyzed in order to compare Se supplementation levels designed with those actually found in the feeds, in order to assure that experimental diets were actually as planned. During the experimental period the effect of the different treatments on average egg weight, egg yolk pigmentation, and egg Selenium contents were evaluated.
18
Results
the last experimental day. For this purpose, 4 eggs
Productive variables, average feed intake (bird/
per repetition (one egg per cage) were collected at
day), average egg weight, and egg yolk pigmentation
random. Total eggs per repetition (yolk + albumin)
were not affected by Selenium source or Selenium
were pooled then subjected to Selenium quantita-
concentration in the feed. This could lead to conclu-
tive analysis by the Service Laboratory, Faculty of
ding that in accordance with this study (Table 3),
Exact and Natural Sciences, Chemistry Institute,
supplemental Selenium source/level in commercial
Antioquia University, Colombia, using pulse diffe-
layer diets do not cause positive or negative effects
rential polarography.
on these select performance parameters.
Results were subjected to analysis of variance
Table 3. The effect of supplemental Selenium
following a 2 x 2 factorial design, the first factor
source/level on select performance parameters
being Selenium supplementation level (0.1 and
in laying hens
product
For egg Selenium content analysis, a sample was taken from each repetition of each treatment on
0.3 ppm), and the second factor was the Selenium Selenium source
All variables with a significant difference (P<0.05)
and level
were subjected to a Tukey's test. Table 2. Nutritional supply and feedstuffs used in the manufacturing of the basal diet used in all experimental treatments Nutrient
Dietary level
Protein, % ME, kcal/kg Lysine, % Methionine + Cystine, % Tryptophane, % Threonine, % Calcium, % Available phosphorus, % Na, % Cl, % K, %
16.5 2.800 0.83 0.69 0.20 0.62 3.8 0.37 0.18 0.26 0.70
Egg weight
(g/bird/day)
(g)
0.10 ppm Sodium Selenite 0.30 ppm Sodium Selenite 0.10 ppm ProkelTM Selenium 0.30 ppm ProkelTM Selenium
116.59 115.79 115.76 113.50
64.62 64.46 65.28 64.74
12.44 12.56 12.38 12.44
Probability
NS
NS
NS
(Treatments)
pigmentation
Contrary to performance parameter observations, egg Selenium content was significantly (P<0.001) influenced by both the source and level of Selenium supplemented in hen feeds. This means that as dietary Selenium concentration is increased –regardless of its source– Selenium transfer to the egg is increased. A 34.50% difference was found between 0.1 and 0.3 ppm Selenium supplemen-
Ingredient, % Corn Soybean meal Extruded soy Wheat bran Monocalcium phosphate Calcium carbonate Marine salt Myco-Ad Vitamins/minerals DL-methionine Lysine, HCl Rovabio AP Zink bacitracin Phytase
Egg yolk
Feed Intake
Azimut #1 — The Premex Newsletter
source (Sodium Selenite or ProkelTM Selenium).
tation. Likewise, it was determined that using 60.70 18.68 6.37 3.0 0.67 9.49 0.38 0.25 0.20 0.15 0.06 0.005 0.04 0.009
Prokel™ Selenium (organic Selenium) results in increased egg Selenium concentration (8.4% higher than that obtained with Sodium Selenite-the Selenium source traditionally used as a feed Selenium supplement) (Table 4). In addition to the effect of Selenium level/source, results from this trial also showed a significant (P< 0.001) Selenium level x source interaction on egg Selenium content (Table 4).
19
product
This interaction shows that supplementing 0.1 ppm Sele-
Bibliography
nium in the feed does not pose a difference between Selenium sources on the content of this mineral, but higher
• Ashmead, H.D. 1993. The roles of Amino
concentrations (i.e.: 0.3 ppm) result in higher transfer levels
Acid Chelates in Animal Nutrition. Noyes
when Prokel™ Selenium is used, for a difference of up to
Publications, Park Ridge, Il.
11.50% when compared with Sodium Selenite. Table 4. The effect of supplemental Selenium source/ level on egg Selenium content
• Dudley-Cash, W.A. 1997. Organic form of Zinc may provide additional benefits in poultry. Feedstuffs, December 1. p 11, 17.
Feed concentration
Azimut #1 — The Premex Newsletter
Mineral source
Average source
0.10
0.30
ppm
ppm
Sodium Selenite
0.115x
0.148y
0.131a
ProkelTM Selenium
0.118x
0.165Z
0.142b
Average concentration
0.116x
0.156b
Probabilities Source effect Level effect Interaction
<0.001 <0.001 <0.001
Nuevas fuentes suplementarias para el ganado. Rev. Cubana Ciencia Agrícola. Vol 34. Nº 4. p 283-288. • National Research Council, 1994. Nutrient Requeriments of Poultry. 9th Rev. Edition. Natl. Acad. Press, Washingtong, DC. • Stanton, W.J.; Etzel, M.J. y Walker, B.J.
Conclusions Neither the level nor the source of supplemental Selenium
1992. Fundamentos del Marketing. 9th Ed. México, McGrawHill, New York, NY. • Zinpro. 1997. A new Class of organic
in commercial layer feeds affect performance parameters
trace minerals. Focus Trace Mineral
including average daily feed intake, egg weight or egg yolk
Zinpro. Vol 3. Issue 1. p 17.
pigmentation. As dietary Selenium supplementation level increases, egg Selenium content increases regardless of the source used. Using Prokel™ Selenium (organic source) increases Selenium transfer to the egg, as compared to Sodium Selenite. As layer feed Selenium concentration increases, the difference in Selenium transfer to the egg increases, when comparing the 2 Selenium sources evaluated, in favor of Prokel™ Selenium. Results from this trial lead to establishing the use of Prokel™ Selenium as a better, more efficient nutritional strategy for table egg Selenium enrichment than Sodium Selenite.
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• Gutiérrez, O. 2000. Minerales orgánicos:
Azimut #1 â&#x20AC;&#x201D; The Premex Newsletter
Results from this trial lead to establishing the use of Prokelâ&#x201E;˘ Selenium as a better, more efficient nutritional strategy for table egg Selenium enrichment than Sodium Selenite.
21
feedback
Nutrition Feedback events Last September, right after the Space 2013 in France, Mr. David Sanchez, Technical Manager of the Specialties Unit of Premex made a very productive visit to Minh Hung Agricultural Materials Trading and Services in Vietnam and Eurotec Nutrition in Thailand. In Vietnam we visited an actual customer of Prokel Se (premixer),
Azimut #1 — The Premex Newsletter
giving technical support and explaining them the highly advantage of using our product compared with other organic mineral structures. After this visit, we visited an actual client of Vitamin Alpha D3 that is using it in fish diets. He explain us his great results and his new idea to perform a new trial with Alpha D3 in the small fishes. What he
About Malaysia Agriculture: Peninsular Malaysia—rubber, palm oil, cocoa, rice; Sabah—subsistence crops, rubber, timber, coconuts, rice; Sarawak—rubber, pepper, timber. Labor force: 12.92 million; agriculture 11.1%, industry 36%, services 53.5% (2012 est.). Industries: Peninsular Malaysia—rubber and oilpalm processing and manufacturing, light manufacturing industry, electronics, tin mining and smelting, logging, timber processing; Sabah—logging, petroleum production; Sarawak— agriculture processing, petroleum production and refining, logging. Natural Resources: tin, petroleum, timber, copper, iron ore, natural gas, bauxite.
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told us is that he wants to improve the bone development from small fishes until the end of the growing period. Hopefully he will keep building more new knowledge with our product in order to obtain more protein, with more quality and a lower cost. Also we had a discussion with one of the technical and sales persons in the company. The main topic was the different strategies to avoid PSE syndrome in pigs (Pale, Soft and Exudative). We already know some information in poultry that could be considered, during slaughter process. Throughout the scientific literature, dark colored muscles have been associated with high muscle pH (Livingston and Brown, 1981). Yang and Chen (1993) confirmed this observation by reporting that ground chicken meat with high pH was darker, redder, and more yellow in color than meat with low pH. In this study, upon increasing the pH of chicken meat using trisodium phosphate, the meat became darker in color and upon lowering the pH using citric acid, the meat became visually lighter. Another important issue that affects color meat is stress before slaughter process, because stress increases the conversion of glucose into lactic acid in muscles that reduces pH on meat. In these cases PROKEL Cr can help reducing stress behavior of pigs followed by PROKEL Se reducing oxidation of packed meat improving shelf life.
feedback product and will start a trial for 12 weeks with Alpha D3. After customer visit, we trained the sales team by In Thailand we visited several companies to promote our product Vitamin Alpha D3.
explaining them how Alpha d3 works and the different metabolic issues in layers, breeders and broi-
In one of the clients (feed mill producer) that was
lers. Also a huge congratulation to Eurotec Nutrition,
focused in layer and breeders feed, we presented
as they are doing a fantastic job in promoting Alpha
the product while explaining Ca and P metabolism.
D3 in Thailand!!!
Our main focus was to decrease eggshell quality problems, in order to obtain a greater profitability.
Azimut #1 â&#x20AC;&#x201D; The Premex Newsletter
We congratulate Minh Hung stuff as they are doing a phenomenal work in Vietnam!!!
Quality Feedback Events:
Also we did a huge emphasis on safety features as our main competitor is building a discredit strategy
Dr. Jose Ignacio Barguil was in Malaysia last Sep-
with non-true arguments and false information.
tember participating in the Feed Safety Seminar
After showing them scientific human and ani-
organized by our distributor Rhone Ma.
mal research papers with such positive and great
Dr. Barguil´s presentation was â&#x20AC;&#x153;Microbial contami-
results, they decided to start a new trial with Alpha
nation issues in feed mil during storage and produc-
D3 in layers.
tion stage, Common microbial contamination in raw
In other customers that were already running the
materials, How to minimize microbial contamination
trails, we explained several important topics for
in finished feed and Selection of inhibitors for feed
layer formulation, regarding Ca and P formulation.
mill operatioThis event was very successful because
After the presentation, the customer decided to try
it changed the concept that raw materials were not
Alpha D3 matrix for broilers also.
important in finished feed contamination. The main
The last client visited was really interested in the
concern was the contamination in the vegetable ori-
23
feedback Azimut #1 â&#x20AC;&#x201D; The Premex Newsletter
Dr. Jose Ignacio Barguil was in Malaysia last September participating in the Feed Safety Seminar organized by our distributor Rhone Ma. gin raw materials and the importance of controlling them as it was shown with scientific data and investigation about the contamination with E.Coli and Salmonella in corn and soybean meal.
24
Also, our product Inhimold L50 CF was presented as a great option to control microbiological contamination in stored grains, and the importance of using it. We were giving support to Rhone Ma in the Asia Live Stock Show and also we did some visits to clients presenting our safety in the food chain proposal. KEY Photos: Jose Ignacio Barguil visit to Malaysia.
that raw materials were not important in finished feed contamination.
FEEDBACK
because it changed the concept
Premex - Azimut #1 - janvier Ă juin 2013
This event was very successful
25
leadership
Leadership It is "well-being" to generate "wellness".
Our corporation is committed to the integral development of human
Azimut #1 — The Premex Newsletter
beings. It is committed to leadership development of its members, of
author Mauricio Cardona E Senior Consultant Corporate culture evolution and transformation maucardona@une.net.co
their self-leadership. We understand that to be a force in the world that nourishes wellness to mankind and all living beings, first of all, we have to be, ourselves, that same inner strength that mobilizes us to co-create, and strengthen all that infinite resources we have received, and always giving the best of ourselves. Contribute to the welfare and well-being is a commitment to be genuine so that our work is consistent and has a sustainable impact. It is "well-being" to generate "wellness". The one does not exist without the other. And be ourselves firstly that powerful and positive personal strength is the commitment to cultivate our personal internal power, that is, our genuine power. Genuine power is the alignment between personal energy that animates us forever (or soul) and our personality formed in our short span of personal history. It is to be aligned from the being that each one is with the purposes of life itself and the continuous process of evolution in a consciousness of the expanded historical happening in which we participate. To be aligned is to be aware of our being in relation. We are relation. I (our self) is in relation, noticing it or not, like it or not, with oneself, with others, with the cosmos and with the creative energy that animates all creation (this is why it is a cosmotheandric relationship).
26
leadership genuine power is that our internal life is consciously aligned with the rhythms
Premex - Azimut #1 - December - June 2013
of life and the universe.
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Premex - Azimut #1 - December - June 2013
We relation Specifically, genuine power is that our
It is to lead
internal life is consciously aligned with the
our lives from
rhythms of life and the universe. The genuine
becoming what
are and the whole scenario of the life and his-
and internal power is an awareness of who we
we are called
tory in which we participate co-creating. It is
to be.
institutions, society, life, the Earth, the cos-
Azimut #1 â&#x20AC;&#x201D; The Premex Newsletter
are
a conscious alignment between us, the groups, mos and the creative force of everything.
This consciousness is the basis of giving and contributing to wellbeing for wellness. Â It is aware that life and existence is to be in relation and participate in something greater, full of meaning and purpose. It is aware that to participate is to be co-creating all times, by initiative or reaction, by act or omission, and for better or worse (evolution or involution). It is to lead our lives from becoming what we are called to be, and from the people who are called to be facing the society and life in the future. It is to know how to respond, or be responsible, to the call of the entire creation so that our lives contribute and do not hinder the processes of society and life itself.
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We are inspired by the possibility of transforming microingredients into macroresults to nourish wellness in people.