Se-methylselenocysteine and cancer

Selenium compounds as establishd by in vitro and in vivo experimental models show than that selenium is an effective anticancer agent. Clinical trials, however, have not shown that selenium supplementation in humans is an effective way to prevent cancer.

The transsulfuration pathway metabolizes L-selenomethionine which is the food form of selenium. L-selenomethionine is stored in the body through replacing L-methionine in proteins. Selenium not exiting L- selenomethionine can explain why selenium supplemenation, heretofore, has not been an effective way to prevent cancer in humans.

Tte transsulfuration pathway metabolizes homocysteine. High homocsyteine levels point to the transsulfurtation pathway being dsyregulated. High homocysteine levels are associated with cancer. High homocysteine levels in cancer would then point to the transsulfuration pathway being dysregulated in cancer. With the transsulfuration pathway dysregulated in cancer L-selenomethionine is not metabolized. As L-selenomethione is not metabolized selenium supplementation in the form of L-selenomethionine is not an effective way to prevent cancer in humans.

Se-methylselenocysteine is a very effective anti-cancer agent. Se-methylselenocysteine is a form of selenium that is not metabolized via the transsulfuration pathway but rather is metabolized by kynurenine aminotransferase, which is not an enzyme in the transsulfuration pathway, so formation of selenoproteins from Se-methylselenocysteine is not stopped by dysregulation of the transsulfuration pathway. Se-methylselenocysteine could be an effective anti-cancer agent in experimental models and also in humans.

Choosing an appropriate dosing scheduls is a key to effective selenium supplementation. Supranutrional selenium can increase activity of thioredoxin reductase. There is an end of dosarge effect with selenium apparently due to declines, during the day, in activity of thioredoxin reductase. For the prevention of cancer 100 micrograms of Se-methylselenocysteine taken twice a day would be a more effective selenium supplmentation schedule than 200 micrograms of of selenium from Se-methylselenocysteine taken once a day.

Measuring selenium in prostate cancer

There are conflcting reports about selenium levels in prostate cancer. Rearch indicates that there are reduced levels of selenoprotein P in prostate cancer. High levels of selenoprotein P are also associcated with low risk of high grade prostate cancer. Other research indicates that circulating selenium levels are high in advanced prostate cancer.

I have been arguing that in many illnesses that the transsulfuration pathway is dysregulated. Besides synthesizing L-cysteine from homocysteine the transsulfuration pathway also metabolizes L-selenomethionine which is the food form of selenium. L-selenomethionine is stored in the body via replacing methionine in proteins. If selenium never makes it out of selenomethionine there could be both high selenium levels and low selenoprotein levels. High levels of circulating selenium in advanced prostate cancer could paradoxcially indicate that there are selenoprotein deficiencies in prostate cancer which appears to be the case both for selenoprotein P and glutathione peroxidase. Glutathione peroxidase, another selenoprotein, is also reduced in prostate cancer.

Se-methylselenocysteine is a form of selenium that is not metabolized via the transsulfuration pathway so formation of selenoproteins from Se-methylselenocysteine would not be impeded by dysregulation of the transsulfuration pathyway. While supplemental selenomethionine apparently does not reduce the risk of prostate cancer supplemental Se-methylselenocysteine could reduce the risk of prostate cancer. The advantage of Se-methylselenocysteine as a cancer preventive could be exactly due to metabolism of Se-methylselenocysteine not depending on the transsulfuration pathway.

Selenium and osteoporosis

Selenium intake in a dose-response manner is negatively correlated with osteoporosis. Compared with the lowest quartile tho odds ratios of osteoporosis were 0.72, 0.72 and 0.47 for the second, third and fourth quartiles of dietary Se intake, respectively. See also this paper.

In my paper on osteoporosis on the Osteoporsis page I argue that the transsulfuration pathway is dysregulated in osteoporosis. Dysregulation of the transsulfuration pathway would dysregulate selenium metabolsim as the food form of selenium, selenomethionine is metabolized via the transsulfuration pathway. Se-methylselenocysteine can be metabolized by kynurenine aminotransferase whereby Se-Methyl-L-selenocysteine + H2O <=> Pyruvate + Ammonia + Methaneselenol. Kynurenine aminotransferase is an enzyme that is not in the transsuluration pathway whereby Se-methylselenocysteine is the prefecred form of supplemental selenium as selenium from Se-methylselenocysteine is biovailable. Dosages of Se-methylselenocysteine should not exceed 200 micrograms a day. More is not better.

In schizophrenia all paths lead to the transsulfuration pathway

With a dysregulation of the transsulfuration pathway (homocysteine to L-cysteine) sufficient L-cysteine for iron-sulfur cluster formation is not synthesized. Sulfur for iron-sulfur cluster biogenesis is derived from L-cysteine. Supplemental iron increases levels of iron-sulfur proteins. Supplemental iron can partly compensate for dysregulation of the transsulfuration pathway in schizophrenia. Selenomethionine, the food form of selenium is metabolized by enzymes in the transsulfuration pathway. Metabolism off Se-methylselenocysteine by-passes the transsulfuration pathway whereby Se-methylselenocysteine can provide bioavailable selenium for individuals with schizophrenia. Taurine is synthesized from L-cysteine. With L-cysteine not synthesized appropriately taurine will not be synthesized at appropriate levels. Taurine is needed to form various bile acids, With low levels of taurine there will not be sufficient taurine conjugated bile acids. Fat absorption requires bile acids. With low levels of taurine due to low levels of L-cysteine fat absorption will be impaired. Supplemental taurine and supplemental essential fatty acids will compensate for low levels of taurine due to low levels of L-cysteine which are in turn due to dysregulation of the transsulfuration pathway. Taurine by sparing L-cysteine will also increase levels of L-cysteine.

An Important Warning: No supplements that contain L-cysteine or L-methionine should be supplemented. And no supplements that reduce cystine to L-cysteine, such as lipoic acid, should be supplemented. See the Treatment page for supplements that can be of assistance in the treatment of schizophrenia.

The association of APOE-ε4 with Alzheimer’s disease could be due to a connection of APOE-ε4 with selenium transport into cells.

Carriers of of the apoE ε4 allele have significantly lower selenium levels in nails and brains. Selenoprotein P is a selenium transport protein. Apolipoprotein E receptor 2 by binding to selenoprotein P regulates uptake of selenium into cells. Both apolipoprotein E receptor 2 and apolipoprotein E regulate transport of selenoprotein P into cells. Selenoprotein P provides protection from amyloid β (Aβ), the main component of amyloid plaques seen in Alzheimer’s disease. The association of apoE ε4 with Alzheimer’s disease could be due to apoE ε4 not being as effective in regulation of selenium transport into cells via apolipoprotein E receptor 2 as other alleles of apoE.