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– Se-Methylselenocysteine (SeMC) – beyond selenate . . . beyond selenomethionine . . . beyond whole selenized yeast . . . page 2 PAGE 1 | PAGE 2 | PAGE 3 | PAGE 4 - REFERENCES continued from page 1 But if immune enhancement, carcinogen detoxification, antioxidant action, and even tissue concentrations don’t explain selenium’s vigilance on the “enemy within,” what does? To answer this question, scientists asked the next question. What happens metabolically to all of that “other” selenium – the selenium that is not being accumulated in the tissues, and which is not incorporated into proteins or into enzymes with antioxidant or detoxifying properties? As it turned out, the painstaking work of uncovering the answer to this question was not just an excuse for researchers to ask the government for more grant money. Understanding the way that selenium is processed by the body has led to a revolution in our understanding of how selenium fights cancer. And with this knowledge in hand, scientists have identified SeMC, the selenium supplement that maximizes the body’s production of a key anti-cancer metabolite, yet which minimizes the toxicity associated with some other forms of the mineral. While many scientists contributed to the ultimate revelation, the breakthrough insights and key experiments have come out of the labs of Dr. Clement Ip of the Roswell Park Cancer Institute and Dr. Howard Ganther of the University of Wisconsin’s Department of Nutritional Sciences.14,17,19-29 Other key research (spearheaded by Dr. John W. Finley of the USDA’s Grand Forks Human Nutrition Research Center,30-33 Dr. Henry Thompson of the AMC Cancer Research Center,25,34-39 Dr. Ranabir Sinha of the Baylor College of Medicine,40-43 and Dr. Julian Spallholz of the Texas Tech University Health Sciences Center,44-46) has helped make the full importance of these findings clear, integrating them into unexpected corners of cancer-nutrition research and revealing the mechanisms that underlie SeMC’s superiority. The Fork in the Road The metabolic pathways of different forms of selenium are pictured in Figure 2. As you can see, both selenomethionine and sodium selenite can be converted into hydrogen selenide (H2Se). However, much of the selenium in selenomethionine gets tied up into general body proteins, while this doesn’t happen with inorganic selenium salts (such as selenate or selenite). As a result, more hydrogen selenide is formed when you take selenate or selenite than when you take the same amount of selenium as selenomethionine. Since their research had shown that inorganic forms of selenium is the stronger cancer-fighter of the two,13,14,17 and that inhibiting selenomethionine’s incorporation into general bodily proteins (which frees up more selenium to be metaboblized into hydrogen selenide) makes it more effective in protecting against cancer,17 it seemed clear that the anti-cancer effect of these two forms of selenium was somehow dependent on their being converted into hydrogen selenide.
If the formation of hydrogen selenide is a critical step in the ability of inorganic forms of selenium and selenomethionine to fight cancer, then the next logical question is whether this fact is due to the hydrogen selenide itself, or is instead related to something that the body forms out of it. To answer this question, Ganther and Ip looked at its two major metabolic fates (see Figure 2). Much of the hydrogen selenide in the body is used to make the selenium-dependent antioxidant and detoxification enzymes. But once these enzymes are fully topped up, the body protects itself from the inherent toxicity of hydrogen selenide by using a biochemical reaction known as methylation to form the dramatically less-toxic methylselenol (CH3SeH) metabolite. And methylselenol, in turn, is metabolized into further, even more methylated derivatives (see Figure 2).
Of the three possible anticancer selenium compounds – hydrogen selenide itself, selenium-containing antioxidant and detoxification enzymes, or methylated selenium metabolites – Ganther and Ip were able to rule out the enzymes, as we’ve already discussed.13,14 So now there were two possibilities: hydrogen selenide, or one of the methylated selenium compounds. Ip and Ganther resolved the question simply and elegantly. They identified a series of forms of selenium which the body directly converts into the methylated forms of selenium, without passing through the hydrogen selenide step. If hydrogen selenide itself was the essential selenium metabolite, then these forms of selenium would be ineffective in fighting cancer. But if one of the methylated selenium compounds were the true secret of selenium’s dynamic protective activity, then the compound that most readily formed this metabolite would be pointing at the center of the labyrinth. The SeMC Solution The results of this research can be seen in Table 1. The bottom line: compounds which are most directly converted into methylselenol, such as methylseleninic acid, selenobetaine, and Se-Methylselenocysteine (SeMC), proved to be the most potent, and among the least toxic, forms of selenium. Using SeMC and other immediate precursors of methylselenol, less selenium is needed to get the same anti-cancer effect … and yet these forms of selenium are safe at doses where inorganic selenium is toxic. In fact, SeMC has a lack of toxicity similar to that of selenomethionine, which is much less effective at fighting cancer. And unlike selenomethionine, SeMC doesn’t build up in your tissues – a fact which resolves the curious finding that you can predict a person’s cancer risk from the amount of selenium in his or her diet or in the local soil and water, but not from the amount of the mineral in his or her tissues.
In terms of sheer potency, SeMC is clearly the best selenium source to use. But when you consider the potential toxicity of selenium, and the evidence from animal studies that the amount of selenium that’s most effective in fighting cancer is much higher than the doses usually used in supplements (see Figure 1),3 SeMC looks even better. If we think in terms of a “therapeutic window” between the toxic and the effective dose, there is nearly no room to maneuver when using inorganic selenium or selenomethionine, while a wide gap separates the therapeutic dose of SeMC and the dose at which toxicity emerges (Table 1). To put it another way: if we think in terms of a potency-to-toxicity ratio, SeMC undeniably comes out on top, its ratio being about twice as good as either selenite or selenomethionine. Forms of selenium (such as selenite,
selenate, and selenomethionine), which must jump through the
hoops of first forming hydrogen selenide and being methylated
before they can form methylselenol are less effective than
those forms (such as SeMC) whose path to methylselenol has
no obstacles. Likewise, selenium compounds (such as selenobetaine
methyl ester, dimethylselenoxide, and trimethylselenonium)
which can only be “retroconverted” into methylselenol
by stripping them of their “extra” methyl groups
(see the sidebar, Don’t Try This at Home, Kids!) are
poor cancer-fighters.23,26 There’s
only one conclusion that you can draw from all of this: methylselenol
is the critical metabolite for cancer prevention. Since methylselenol itself can’t
be used as an anti-cancer supplement (because this critical
metabolite is too chemically unstable to be used in this way),
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