This randomized phase I trial studies the side effects and the best dose of Se-methyl-seleno-L-cysteine or selenomethionine in preventing prostate cancer in healthy participants. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of Se-methyl-seleno-L-cysteine or selenomethionine, two different types of selenium compounds, may prevent prostate cancer from forming.

PRIMARY OBJECTIVES:

I. To determine the individual toxicity profiles of Se-methyl-seleno-L-cysteine (methyl selenocysteine; MSC) and selenomethionine (SeMet) administered to cohorts of men daily for twelve weeks, with dose escalation with each successive cohort.

SECONDARY OBJECTIVES:

I. To measure the pharmacokinetics of selenium, according to form (MSC vs SeMet): MSC and SeMet impacts on plasma, albumin, and urinary concentrations of selenium over 48 hours on dosing days 1 and 84.

II. To evaluate the pharmacodynamics of selenium by form (MSC vs SeMet): plasma, albumin, and urinary Selenoprotein P (Sepp1) concentrations and glutathione peroxidase (GPx) activity over 48 hours on dosing days 1 and 84.

III. To store plasma and formed elements (red cells plus platelets) for future analysis of methyl selenol and other key selenium species, when those assays become available.

OUTLINE: This is a dose-escalation study. Participants are randomized to 1 of 3 treatment arms.

ARM I: Participants receive Se-methyl-seleno-L-cysteine orally (PO) on days 1-84.

ARM II: Participants receive selenomethionine PO on days 1-84.

ARM III: Participants receive placebo PO on days 1-84.

After completion of study treatment, patients are followed up on day 112.

Inclusion Criteria:

• Total body weight between 50 and 115 kg (110 and 250 lbs)
• Hemoglobin (Hgb) > 12 mg/dL
• Platelet count > 100,000/μL
• Absolute neutrophil count (ANC) > 1000/μL
• Creatinine =< institutional upper limit of normal (ULN)
• Serum glutamate pyruvate transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) < 2.0 x ULN
• Total bilirubin =< ULN (participants with a higher level of bilirubin presumed due to familial metabolism will be considered on an individual basis)
• Life expectancy greater than 3 years
• Participants must agree to use adequate contraception (barrier method of birth control; abstinence) from time of screening until study completion (i.e., for at least 2 weeks after last dose of study drug)
• Ability to understand and the willingness to sign a written informed consent document
• Agree to refrain from use of selenium (Se) supplements (other than the 100 mcg dose common in multivitamins) or Se-containing drugs while on study between 30 days before study drug initiation and Day 84

Exclusion Criteria:

• Not willing to remain at Roswell Park Cancer Institute (RPCI), and in follow up, as required
• Presence of medical conditions which, in the opinion of the investigator, would place either the participant or the integrity of the data at risk
• Serum creatinine > ULN, SGOT or SGPT >= 2.0 x ULN, or bilirubin > ULN
• Treatment with an investigational drug within 30 days prior to the dose of study drug
• Use of selenium [Se] supplements greater than the 100 mcg dose common in multivitamins between 30 days before study drug initiation and Day 84
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to investigational agent (e.g., reaction to other Se supplements)
• Participants who have donated 1 unit of blood within 30 days prior to the first dose of investigational agent
• Eastern Cooperative Oncology Group (ECOG) performance status > 1
• Diagnosed with cancer, other than non-melanoma skin cancer, in last 2 years
• Under treatment for any cancer
• Use of glucose-lowering agents or a condition that would make a fast from 10:00 pm the evening before until 11:00 am on days 1 and 84 hazardous
• American Urological Association (AUA) total symptom score > 10 or any individual symptom score of greater than or equal to 4
• Psychiatric illness which would prevent compliance with the intervention or would prevent the patient from providing informed consent
• Medical conditions which in the opinion of the treating physician would make this protocol unreasonably hazardous for the participant