Ross Bryan Medical Student MS III Mercer University August 2012
Effect of Supplementation With High-Selenium Yeast on Plasma Lipids
Annals of Internal Medicine
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Funding The Cancer Research Campaign (now Cancer Research UK)
and the University of Surrey Funding for the original Pilot study
fell through
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Background/ Objective: Selenoproteins, such as glutathione
peroxidase, have been shown to combat the oxidative damage caused
by circulating lipids and reduce inflammation There is good
scientific rationale for optimal selenoprotein levels, however, the
evidence for selenium supplementation has been ambiguous
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BACKGROUND CONTINUED Selenoproteins share a common biosynthetic
pathway with cholesterol, although the pathways by which this
alters lipid profiles is not clear.
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Why is this important? 1) Higher LDL is associated with
elevated risk for cardiovascular disease by participating in the
formation of plaques in artery walls 2) Higher HDL is associated
with lower risk for heart disease by transporting lipids back to
the liver for excretion from the body Therefore, lipid profiles are
important in determining the risk for heart and vascular
disease
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Atheromatous Plaque Formation
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Study Design and Setting: A) Randomized Double-blind B)
Placebo-controlled C) 4 parallel group study at locations in the UK
D) Men and Women 60-74 years of age E) 6 month trial period
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Endpoints included in analysis: 1)Total cholesterol 2)Non-HDL
cholesterol 3)HDL cholesterol 4)Total-HDL cholesterol ratio
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Exclusions: 1)Southwest Oncology Score < 1 2)HIV diagnosis
3)Active liver or kidney disease 4)Previous diagnosis of cancer
5)Diminished mental capacity 6)Receipt of selenium supplements
(>50mcg/d)
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Results:
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Intention-to-treat analysis This study employs a method called
intention to treat analysis This means that people who discontinued
the treatments were still included in the analysis as long as they
can be followed WHAT!?!?!?
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ITT Preserves Randomization and Prevents Bias Consider a
hypothetical experiment: Outcome --> X disease prevention Group
1 --> Medicine + Surgery (100 ppl) * surgery scheduled 1 month
after randomization Group 2 --> Medicine (100 ppl)
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ITT Hypothetical Experiment Group 1 -10/100 do not go through
with surgery -5 of these suffer disease X in trial period -15/90
that have surgery suffer disease -If the ten that drop out are
excluded: total disease risk = 15/90 = 16.7% Group 2 -5 get disease
in first month -15 get disease in subsequent trial period total
disease risk = 20/100 = 20%
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Hypothetical Experiment Assumption Assumption:surgery is not
effective: a) per protocol overestimates surgical benefits (16.7%)
b) ITT is more accurate
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Disclaimer ITT is controversial and has flaws Example: -what if
surgery completely prevented disease X? -then, 5 ppl in group 1
would have been included in analysis as having disease -would
underestimate benefit of surgery
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Conclusion: Selenium supplementation was associated with modest
reductions in total and non- HDL lipoprotein cholesterol levels. At
higher doses, selenium was associated with increases in HDL
cholesterol
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Limitations: 1)Study fouses only on lipid profile and not
cardiovascular disease risk 2)Triglyceride levels were not measured
3)Trial period was only 6 months 4)Small sample size 5)ITT
analysis???
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Comments: Although the trial demonstrated a small improvement
in lipid profiles, the findings do not justify the use of selenium
supplementation for treatment of dyslipidemia because of the listed
limitations and possible side effects.
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Citation Rayman, P. Margaret et al. Effect of Supplementation
with High-Selenium Yeast on Plasma Lipids: A Randomized Trial. Ann
Intern Med 2011 May 17; Volume 145 Number 10; pg.656-664.