Selenium Toxicity Selenium is toxic in a large portion of the population at about 5,000 mcg/day if taken chronically, maybe requiring years of exposure. Symptoms are garlic breath, hair falling out, brittle nails, nausea, and nervousness. As little as 2,000 mcg/day may have negative effects in some people after a year. 750 mcg/day forever is considered safe. The most sensitive person out of 13 had negative effects after taking 30,000 mcg/day for 11 days. One random person taking 20,000 mcg for 70 days showed no noticeable effects.
Effect on NSCLC Lung Cancer, sept 2009 research
50% of H157 (squamous cell) died in 20 hour when exposed to 5 uM selenite in test tube. At 50 uM, 70% died. Another form of NSLC had only 10% die. It works when cysteine is present extracellularly, causing a reducing solution, possibly turning selenite to selenide for easy transport inside. Selenite works best on cancer cells that transport cystine inside the cell so that outside the cysteine/cystine ratio is high (reducing). The difference in effectiveness of selenite appears to be based only on how well it is transported inside cancer cells. Cancers that are resistant to chemo are less resistant to selenite. Combing chemo and selenite will be good in some cases and completely negate the effectiveness of both compounds in others. This seems to clear up a lot of confusion of the past 5 years. See quote below from the bought paper.
http://www.pnas.org/.../11400.abstract
Amount to take for CancerI have not yet look up absorption and excretion of sodium selenite. It would be good if someone could do that. Using 100% absorption and 100% retention, 3,750 mcg sodium selenite will result in 5 uM in 5 liters of blood. This is exactly the protocol described by tham's report of someone using it with tremendous success. To have 5 uM distributed equally in a 70 kg solution, it would require 13,000 mcg, only 4 days if all is absorbed and somehow none were excreted. 3,750 mcg seems very safe for a month, even a year if you're comparing it to terminal cancer. It is actually given to SIRS patients by I.V. Ironically, SIRS may result from chemo. So someone might have some interesting data out there already on using selenite in cancer patients. Personally, I would try 10,000 mcg for 2 weeks, then switch to 5,000 mcg until I thought I might be seeing negative effects. Selenite pills are about 0.5% sodium selenite.
September 2009 article
"Drug-resistant tumor cells have been shown to be particularly sensitive to selenite toxicity, with growth-inhibiting effects observed at low concentrations harmless to cell type– or patient-matched normal cells...Selenite (SeO3) efficiently inhibits the growth of malignant cells and studies suggest an inverse relationship between resistance to cytotoxic drugs and sensitivity to selenite (SeO3) (1, 2). A major mechanism of selenite cytotoxicity is thought to be the generation of oxidative stress through intracellular redox cycling of the selenium metabolite selenide with oxygen and cellular thiols, producing nonstoichiometric amounts of superoxide and cellular disulfides. The induction of oxidative stress and consequent apoptosis has been demonstrated in numerous cancer cell lines (2–8), but why this occurs only in malignant cells at easily achievable selenium plasma concentrations remains unclear....early findings clearly demonstrated that cancer cells enrich selenium in vivo. These findings, combined with current knowledge of selenite’s toxic effects on malignant cells, raise the possibility of a cancer-specific high-affinity selenium
uptake mechanism that might explain cancer-specific selenite cytotoxicity at therapeutic selenite concentrations (uM range).....The availability of cysteine is the limiting step in GSH synthesis (13), and thus high cysteine
availability is also important in the cellular defense against oxidative stress and may aid drug resistance. In extracellular plasma, cysteine levels are low (10 uM), and cystine levels are almost 10-fold higher (14), giving xc
-expressing cancer cells access to a larger pool of cysteine....Uptake was measured in cells treated with a dose of 5 uM for 5 h to explore whether selenium accumulation preceded cytotoxicity. The dose was chosen to be suitable for [lung cancer] cells with varying sensitivity to selenite, including highly toxic (H157), borderline toxic (U2020), and nontoxic (H611). Selenium accumulation was greatest in the H157 cells (280 +/- 6 ng/mg total protein), less in the U2020 cells (60 +/- 9 ng/mg total protein), and undetectable in the H611 cells. These results correspond closely to the toxicity at the given doses and suggest that selenite toxicity is determined by the level of selenium accumulation in cells. ... State. To explore the connection between selenium uptake and the extracellular redox state, we measured the total production of extracellular thiols from the cells over time (Fig. 1A). Extracellular thiol production was highest in the H157 cells, peaking at 110 uM at 10 h, and was lower in the U2020 cells, peaking at 40 uM at 20 h. Production in the H611 cells did not differ significantly from that seen in the control growth medium (10 uM). Extracellular thiol production showed a remarkable correlation with selenium uptake measured previously (R2 0.997) (Fig. 1B), suggesting a strong relationship between a reductive microenvironment and high-affinity selenium uptake. To verify this relationship and its connection to cytotoxicity, we artificially redox-modulated the extracellular compartment and treated the cells with 5 Mselenite. Viability measured at 20 h was used as an endpoint. Extracellular reduction through inclusion of the cell-impermeable reductantsGSHor Tris(2-carboxyethyl)phosphine (TCEP) led to increased selenite toxicity at equal concentrations
(75 uM) (Fig. 2A). Conversely, 500 uM 55-dithiobis-(2-nitrobenzoic acid) (DTNB) used as a cell-impermeable oxidant or
thiol scavenger protected the cells from any toxic effects of selenite compared with the DTNB control. Additional experiments also showed that the presence of DTNB increased the IC-50 for selenite from 4 uM to 40 uM in the sensitive H157 cells....The results clearly validate that the innate extracellular reductive capacity is crucial for selenite cytotoxicity and is mediated by an extracellular thiol–dependent high-affinity uptake mechanism....To verify that inhibition of cysteine secretion protects cells from selenite cytotoxicity, we treated cells with MSG and selenite. We found that MSG protected the cells from any toxic effects of selenite, an effect that could be reestablished by artificial reduction of the extracellular compartment...A significant fraction of intracellular cysteine is resecreted into the extracellular compartment by MRPs, causing a reductive extracellular microenvironment. Extracellular reduction of selenite leads to a high-affinity uptake of a reduced form of selenite, possibly selenide,
causing selenium accumulation and toxicity."
"In this work, viability measurements in different lung cancer cell lines showed that selenite was more effective compared to three different conventional cytotoxic drugs."
http://www.ncbi.nlm....pubmed/18405881"Selenium compounds show much promise in the prevention of prostate and other human cancers. Various selenium chemical forms have been shown to differ widely in their anticancer properties....By contrast sodium selenite caused phosphorylation of p53 serines 20, 37 and 46 known to mediate apoptosis. "
http://www.ncbi.nlm....pubmed/15274301"Our results demonstrate pronounced selective selenium-mediated apoptosis in therapy-resistant cells and suggest that redox regulation through the thioredoxin system is an important target for cancer therapy."
http://www.ncbi.nlm....pubmed/15037203Selenite used in combination with cancer chemotherapeutic agents to reduce side effects...
http://www.springerl...30373r56872512/"inclusion of selenite in a chemotherapeutic protocol can result in a significant enhancement of the efficacy of cisplatin in suppressing the growth of human ovarian tumor xenografts."
http://cat.inist.fr/...&cpsidt=1140006"Selenium (Se) compounds such as selenite are toxic to cancer cells; they inhibit growth, reduce mobility, and induce apoptosis. The molecular mechanism(s) for these effects are not fully understood but appear to involve multiple molecular targets."
http://www.aacrmeeti...ct/2005/1/207-b"Selenium (Se) has been shown in clinical trials to be effective in reducing the risk of different cancers including lung cancer. Consequently, the mechanism of this anticancer effect has been under active investigation. Although it is clear that Se induces apoptosis of cancer cells, the regulatory mechanism(s) of this effect is yet to be understood. "
http://aacrmeetingab...ct/2004/1/316-c
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