Travis
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I have some ideas. On the beach now. Getting natural E to interact with the Vit E succinate which I just started taking
It is most certainly the succinate group in particular that is responsible for this activity. This can be demonstrated in a few ways, and one being how tocopheryl succinate (left) compares to cholesteryl succinate (right):
This dose–response curves are nearly superimposable, something which had been observed in multiple cell lines and in multiple studies.⁽¹⁾⁽²⁾ Because cholesterol is fully saturated and thus cannot sequester free radicals, the anticancer effect of α-tocopheryl is entirely independent of its antioxidant function.
'The fact that butylated hydroxyanisole, which inhibited the proliferation of NB cells, did not affect basal or PGE₁-stimulated AC activity in NB cells, suggests that inhibition of PGE₁-stimulated adenyl cyclase by α-TS is not due to its antioxidant action.' ―Prasad⁽³⁾
Considering its mechanism of action as a calcium ionophore, and apparent lack of antioxidant activity, it is perhaps misleading to group it under vitamin E. Instead: perhaps it is best named in a way that highlights its succinate group, such as succininyl-α-tocopherol (although this would be technically incorrect because α-tocopherol should take precedence on account of its greater mass).
But stressing is function and similarity to cholesteryl succinate is not to discount it in any way. This molecule's anticancer effect is as significant as it's selective, and this is safe to use. If you scroll down to Table 1 in this⁽⁴⁾ article, I think you'd be amazed by how selective it really is.
Although safe, effective, and available, γ-tocopherol is actually more effective than succininyl-α-tocopherol at the same dose level. This may seem like an arrogant, or even blasphemous, thing to say but it's more-or-less true regardless: These two have ve been compared directly head-to-head, side-by-side, and γ-tocopherol had emerging the winner:⁽⁵⁾
Although they hadn't been tested in combination, there is every reason to think the results would compound. Gamma-tocopherol and succinyl-α-tocopherol have different mechanisms of action, which perhaps is best illustrated by their effects on prostaglandin E activity. Gamma-tocopherol and its CEHC metabolite can lower prostaglandin E by adducting with peroxynitrite,⁽⁶⁾⁽⁷⁾ a cyclooxgenase substrate,⁽⁸⁾ while succinyl-α-tocopherol can prevent its receptor from working by inhibiting adenylate cyclase.⁽⁹⁾ [It probably doesn't inhibit adenyl cyclase directly but through the Ca²⁺ ions—which are known for this—that it's been shown to increase.]
The significant effect of γ-tocopherol is yet another thing out many that illustrates the central role reactive nitrogen species have in carcinogenesis. Heme is also illustrative, as the carcinogenicity of this most likely derives from its ability to oxidize nitric oxide (Ṅ=O) into the more carcinogenic nitrosonium ion (N≡O⁺). Free iron is less carcinogenic in the colon, although this is well-known for creating hydroxyl radicals (ȮH⁻). Vitamin C serves as a partial antidote to heme by reducing (+e⁻) nitrosylhemochrome, releasing the iron-bound nitric oxide as the less-dangerous nitroxyl ion (N=O⁻) and not nitrosonium. Phytic acid also serves to combat intestinal nitrosamine formation: Upon being attracted to heme's central iron atom phytic acid can bind it, sever the two histidine bonds, and pull it slightly out-of-plane.
[1] Djuric, Z. "Growth inhibition of MCF-7 and MCF-10A human breast cells by α-tocopheryl hemisuccinate, cholesteryl hemisuccinate and their ether analogs." Cancer letters (1997)
[2] Fariss, M. "The selective antiproliferative effects of α-tocopheryl hemisuccinate and cholesteryl hemisuccinate on murine leukemia cells result from the action of the intact compounds." Cancer research (1994)
[3] Prasad, K. "α-tocopheryl succinate, the [second] most effective form of vitamin E for adjuvant cancer treatment: a review." Journal of the American College of Nutrition (2003)
[4] Neuzil, J. "Selective cancer cell killing by α-tocopheryl succinate." British journal of cancer (2001)
[5] Galli, F. "The effect of α-and γ-tocopherol and their carboxyethyl hydroxychroman metabolites on prostate cancer cell proliferation." Archives of biochemistry and biophysics (2004)
[6] Jiang, Q. "γ-Tocopherol, but not α-tocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats." The FASEB Journal (2003)
[7] Christen, S. "γ-Tocopherol traps mutagenic electrophiles such as NOx and complements α-tocopherol: physiological implications." Proceedings of the National Academy of Sciences (1997)
[8] Beharka, A. "Mechanism of vitamin E inhibition of cyclooxygenase activity in macrophages from old mice: role of peroxynitrite." Free Radical Biology and Medicine (2002)
[9] Sahu, S. "Effect of alpha tocopheryl succinate on adenylate cyclase activity in murine neuroblastoma cells in culture." Journal of the American College of Nutrition (1988)
[2] Fariss, M. "The selective antiproliferative effects of α-tocopheryl hemisuccinate and cholesteryl hemisuccinate on murine leukemia cells result from the action of the intact compounds." Cancer research (1994)
[3] Prasad, K. "α-tocopheryl succinate, the [second] most effective form of vitamin E for adjuvant cancer treatment: a review." Journal of the American College of Nutrition (2003)
[4] Neuzil, J. "Selective cancer cell killing by α-tocopheryl succinate." British journal of cancer (2001)
[5] Galli, F. "The effect of α-and γ-tocopherol and their carboxyethyl hydroxychroman metabolites on prostate cancer cell proliferation." Archives of biochemistry and biophysics (2004)
[6] Jiang, Q. "γ-Tocopherol, but not α-tocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats." The FASEB Journal (2003)
[7] Christen, S. "γ-Tocopherol traps mutagenic electrophiles such as NOx and complements α-tocopherol: physiological implications." Proceedings of the National Academy of Sciences (1997)
[8] Beharka, A. "Mechanism of vitamin E inhibition of cyclooxygenase activity in macrophages from old mice: role of peroxynitrite." Free Radical Biology and Medicine (2002)
[9] Sahu, S. "Effect of alpha tocopheryl succinate on adenylate cyclase activity in murine neuroblastoma cells in culture." Journal of the American College of Nutrition (1988)
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