Ross BryanMedical Student MS IIIMercer UniversityAugust 2012

Effect of Supplementation With High-Selenium Yeast on Plasma LipidsAnnals of Internal Medicine

Funding

• The Cancer Research Campaign (now Cancer Research UK) and the University of Surrey

• Funding for the original Pilot study fell through

Background/ Objective:

Selenoproteins, such as glutathione peroxidase, have been shown tocombat the oxidative damage caused by circulating lipids and reduceinflammation

There is good scientific rationale for optimal selenoprotein levels, however, the evidence for selenium supplementation has been ambiguous

BACKGROUND CONTINUED

Selenoproteins share a common biosynthetic pathway with cholesterol, although the pathways by which this alters lipid profiles is not clear.

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

Atheromatous Plaque Formation

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

Endpoints included in analysis:

1) Total cholesterol

2) Non-HDL cholesterol

3) HDL cholesterol

4) Total-HDL cholesterol ratio

Exclusions:

1) Southwest Oncology Score < 1 2) HIV diagnosis3) Active liver or kidney disease4) Previous diagnosis of cancer5) Diminished mental capacity6) Receipt of selenium supplements (>50mcg/d)

Results:

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!?!?!?

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)

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%

Hypothetical Experiment Assumption

Assumption: surgery is not effective:

a) per protocol overestimates surgical benefits (16.7%)

b) ITT is more accurate

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

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

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???

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.

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.