Selenomethionine and methyl selenocysteine: multiple-dose pharmacokinetics in selenium-replete men

// James R. Marshall 1 , Raymond F. Burk 2 , Rochelle Payne Ondracek 1 , Kristina E. Hill 2 , Marjorie Perloff 3 , Warren Davis 1 , Roberto Pili 4 , Saby George 1 , Raymond Bergan 5 1 Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263, USA 2 Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, C2104 Medical Center North, Nashville, TN 37232, USA 3 National Cancer Institute, Bethesda, MD 20892, USA 4 Department of Medicine, Indiana University School of Medicine, R3 C516, Indianapolis, IN 46202, USA 5 Knight Cancer Institute, Oregon Health Sciences University, Portland, OR 97239, USA Correspondence to: James R. Marshall, email: james.marshall@roswellpark.org Keywords: selenium, selenomethionine, methyl selenocysteine, chemoprevention, pharmacokinetics Received: December 01, 2016      Accepted: February 06, 2017      Published: February 17, 2017 ABSTRACT According to the Nutritional Prevention of Cancer (NPC) trial, a selenized yeast supplement containing selenium, 200 mcg/day, decreased the incidence of total cancer, cancers of the prostate, colon and lung, and cancer mortality. The active agent in the selenized yeast supplement was assumed to be selenomethionine (SEMET), although the supplement had not been well speciated. The SELECT study, largely motivated by the NPC trial, enrolling nearly 40 times as many subjects, showed unequivocally that selenium 200 mcg/day, with selenium in the form of SEMET, does not protect selenium-replete men against prostate or other major cancer. The agent tested by SELECT, pure SEMET, could have been different from the selenized yeast tested in NPC. One of the selenium forms suspected of having chemopreventive effects, and which may have been present in the NPC agent, is methyl selenocysteine (MSC). This study, with 29 selenium-replete patients enrolled in a randomized, double-blind trial, compared the multiple-dose toxicity, pharmacokinetics and pharmacodynamics of MSC and SEMET. Patients were on trial for 84 days. No toxicity was observed. Although SEMET supplementation increased blood selenium concentration more than MSC did, neither form had a more than minimal impact on the two major selenoproteins: selenoprotein P(SEPP1) and glutathione peroxidase(GPX).