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URL: http://www.mskcc.org/aboutherbs
© 2003 Memorial Sloar-Kettering Cancer Center (Monograph)
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Full Text |
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Barrie Cassileth
and K. Simon Yeung
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Selenium
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| Clinical Summary |
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Selenium
is an essential trace element required by the glutathione-peroxidase
pathway. It acts as an antioxidant and regulates thyroid hormone action
and the reduction of vitamin C. Selenium is used to treat and prevent
cancer, boost the immune system, and for cardiovascular and rheumatic
disease. Bioavailability is dependent on organic versus inorganic
supplements, ranging from 50% to nearly 100%. A recent analysis of five
brands of commercially available selenium found that almost all contained
up to 19% less than the labeled dosage. Methylation is the primary route
of metabolism with a majority eliminated via the kidneys. Clinical studies
have evaluated the role of selenium in cancer prevention with intriguing
results. SELECT (Selenium and Vitamin E Cancer Prevention Trial),
conducted by the Southwest Oncology Group, is enrolling 32,400 men to
study the effects of supplementation on the risk of prostate cancer;
enrollment began in July 2001. Adverse events from selenium are usually
gastric in nature, although chronic selenosis can occur with doses greater
than 1000 mcg/day. This toxicity is characterized by muscle weakness,
fatigue, peripheral neuropathy, skin rash, nail and hair changes,
irritability, and possibly hepatic necrosis. Daily recommended intake is
55 mcg, which is usually provided by seafood, meat, and fortified grain
products. The tolerable limit is 400 mcg, although all studies to date
have been conducted with a maximum of 200 mcg doses.
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| Also Known As |
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Selenocysteine,
selenomethionine, selenate, selenite
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Food Sources
[1], [2] |
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Brazil
nuts, seafood, muscle and organ meats, cereals and grains
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| Purported Uses |
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• Cancer
prevention
• Cancer
treatment
• Cardiovascular
disease
• Immunostimulation
• Rheumatoid
arthritis
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Mechanism Of Action
[2], [3] |
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Selenium
is an essential structural element of the antioxidant enzyme
glutathione-peroxidase that takes part in a system to convert aggressive
oxidation products and intracellular free radicals into less reactive or
neutral components. Other biological functions of selenium include
regulation of thyroid hormone action and regulation of the reduction
status of vitamin C.
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Pharmacokinetics
[2] |
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Absorption:
Absorption of selenium is efficient and not regulated. More than 90
percent of selenomethionine, the major dietary form of the element, is
absorbed by the same mechanism as methionine itself. Selenocysteine
appears to be absorbed very well also. Of the inorganic forms, selenate is
almost completely absorbed, but with a significant fraction lost in the
urine before incorporation into tissue. Selenite has a more variable
absorption probably related to interactions with substances in the gut
lumen, but it is better retained, once absorbed, than selenate. Absorption
of selenite is generally greater than 50 percent. Selenate and selenite
are not major dietary constituents, but are commonly used to fortify foods
and as selenium supplements.
Distribution:
Selenomethionine enters the methionine pool in the body and shares the
fate of methionine until catabolized by the transsulfuration pathway
ultimately leading to the reduced form.
Metabolism / Excretion:
Ingested selenocysteine, selenate, and selenite are all apparently
metabolized by methylation to selenide. The selenide can be metabolized to
selenophosphate, the precursor of selenocysteine in selenoproteins. The
mechanism that regulates production of excretory metabolites has yet to be
elucidated. The excretory metabolites appear in the urine primarily.
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Warnings
[4] |
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A
recent analysis of five commercially available brands revealed actual
content variability to be between 81% and 123% of the stated dose. One
brand varied by 54% between different lots of the same supplement.
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Adverse Reactions
[2], [5] |
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Chronic
selenosis
(doses greater than 1000 mcg/day): Muscle weakness, fatigue, peripheral
neuropathy, dermatitis, nail and hair changes/loss, garlic breath/body
odor, irritability, growth retardation, hepatic necrosis
Toxicity: Acute toxicity via selenium poisoning has occurred
with either accidental or suicidal ingestion of gun blueing solution or
sheep drench. Consumption of gram quantities of selenium can cause severe
gastrointestinal disturbance, neurological disturbance, acute respiratory
distress syndrome, myocardial infarction, and renal failure.
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Drug Interactions
[5] |
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Supplement
Interactions:
High doses of selenium may decrease vitamin C
absorption.
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| Literature Summary And Critique |
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Clark
LC, et al. Effects
of selenium supplementation for cancer prevention in patients with
carcinoma of the skin. A randomized controlled trial. JAMA
1996;276:1957-63.
A prospective, randomized evaluation of skin cancer prevention for
patients with a history of either basal cell or squamous cell carcinoma.
1312 patients were randomized to receive either selenium 200 mcg or a
placebo daily and return to the clinic every 6 months for follow-up
evaluation. Enrollment began in 1983 and was completed December 1993. The
only adverse event involved gastrointestinal disturbances that lead to the
withdrawal of consent in 21 selenium patients and 14 placebo. No chronic
selenosis was noted. A total of 8271 person-years of follow-up was
accumulated and indicated no significant difference between treatment
groups on the recurrence of squamous or basal cell carcinomas. The authors
did note that there was a statistically significant reduced relative risk
of carcinoma incidence (lung, colorectal, prostate) for patients receiving
selenium, however additional studies are need to validate.
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| References |
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[1] Whitney
EN, et al. Understanding Normal & Clinical Nutrition, 4th
ed. Belmont (CA): West Publishing; 1994.
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[2] Dietary
Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids.
Washington (DC): National Academy Press; 2000.
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[3] Suadicani
P, Hein HO, Gyntelberg F. Serum selenium concentration and risk of
ischaemic heart disease in a prospective cohort study of 3000 males. Atherosclerosis
1992;96:33-42.
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[4] Feifer
AH, Fleshner NE, Klotz L. Analytical accuracy and reliability of commonly
used nutritional supplements in prostate disease. J Urol 2002;168:150-4.
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[5]
Pronsky
ZM. Power's and Moore's Food-Medication Interactions, 11th ed.
Pottstown (PA): Food Medication Interactions; 2000.
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[6]
Ip
C. Lessons from basic research in selenium and cancer prevention (Review).
J Nutr 1998;128:1845-54.
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[7]
El-Bayoumy
K. The protective role of selenium on genetic damage and on cancer
(Review). Mutat Res 2001;475:123-39.
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[8]
Klein
EA, et al. SELECT: the selenium and vitamin E cancer prevention trial:
rationale and design. Prostate
Cancer Prostatic Dis
2000;3:145-51.
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(9)
Duffield-Lillico
AJ, et al. Baseline characteristics and the effect of selenium
supplementation on cancer incidence in a randomized clinical trial: a
summary report of the Nutritional Prevention of Cancer Trial. Cancer
Epidemiol Biomarker Prev 2002;11:630-9. |
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| Written |
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11/01/2001 |
| Updated |
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10/02/2002
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