A Possible Clue As To Why Tocotrienols May Be Harmful

Discussion in 'E' started by haidut, Oct 21, 2014.

  1. haidut

    haidut Member

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    As we all know Ray does not like the tocotrienol members of the vitamin E family and does not recommend supplementing with them. He said something along the lines of tocotrienols being unsaturated and that unsaturatedness causing liver enlargement in animal studies. It looks like Ray is once again on the right track. This study claims that the unsaturatedness of tocotrienols interferes with the function of vitamin K2 (MK-4, menatetrenone), which would explain the liver enlargement since MK-4 is so protective of liver function.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3735929/

    "...The α-tocopheroxyl radical is relatively long-lived (178), and it can be reduced to α-tocopherol by water-soluble antioxidants, such as ascorbic acid (179). Other forms of vitamin E, when they become radicals, are more reactive and can readily form adducts that are potentially cytotoxic. The safety of α-tocopherol can also be inferred from the relative lack of specific mechanisms for its metabolism. The other non-α-tocopherol forms are readily metabolized by xenobiotic pathways, likely because these forms are not effective as antioxidants and therefore should be removed promptly from the body. The tocotrienols may be a special case, because the unsaturated tail potentially could interfere with MK-4’s role in carboxylating vitamin K-dependent proteins in tissues."

    Perhaps equally importantly, the above study makes a strong argument that some of the tocopherols are also not entirely safe. In other words, ONLY alpha tocopherol is the isomer the body has a use for, and that the other tocopherol isomers (gamma, beta and delta tocopherols) may be toxic. This is backed up by the fact that the tocopherol isomers other than alpha are metabolized by xenobiotic pathways and quickly excreted, suggesting the body sees them as poison. Here is the study from reference [180] above that digs deeper into the tocopherol issue.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1450130/

    Thoughts?
     
  2. M Scott

    M Scott Member

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    The paper speculates that tocotrienols might interfere with the function of vitamin k2 but there is as of yet no evidence confirming this (afaik). However, the paper provides evidence that a-tocopherol can interfere with vitamin k:

    "The liver converts phylloquinone to menadione, which is then converted to MK-4 synthesis by UbiA prenyltransferase containing 1 (UbiA1) (168, 169). Importantly, it appears that vitamin E interferes with this process, as extrahepatic tissue vitamin K1 and MK-4 concentrations were lower in rats fed a high vitamin E diet (170) or injected with vitamin E (171). Additionally, high-dose vitamin E (a-tocopherol) supplementation (1,000 IU) in humans increased the degree of under-γ-carboxylation of prothrombin (proteins induced by vitamin K absence-factor II, PIVKA-II) (172). The mechanism by which vitamin E interferes with vitamin K status is unknown"

    Honestly I'm not convinced of the safety of one form of vitamin E versus others, despite some of the compelling inferences in that paper. I do suspect the safety of all forms largely requires they be properly balanced with other compounds, particularly other lipophillic nutrients like vitamin k and coq10, so that's sort of where my skepticism comes from.
     
  3. BingDing

    BingDing Member

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    Noting that I have never even seen the word "arylating" before, the second reference seems to say that gamma tocopherol is really bad stuff. Shoot, we're on the cutting edge of not knowing what's healthy, LOL.

    The long thread on the best vitamin E has links to some high alpha tocopherol products and there are some posts about experimenting with both. Maybe that is the way to go. Haidut, do you have any idea of the time frame that one could tell the difference? Like two weeks of high alpha, could one feel it?
     
  4. Such_Saturation

    Such_Saturation Member

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  5. OP
    haidut

    haidut Member

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    I posted another study that showed alpha tocopherol interferes with the conversion of K1 into MK-4. It did not deplete existing levels of MK-4. Btw, most of the studies back in the early 20th century used vitamin E from wheat germ oil, which has a ratio of alpha to the other tocopherols of about 10:1 in favor of alpha.
    Maybe someone can ask Ray what he thinks?
     
  6. johns74

    johns74 Member

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    That's upside down. Alpha tocopherol alone is the one that's toxic because it depletes gamma tocopherol and leaves you more exposed to prostate cancer, since gamma tocopherol protects against that cancer.

    Taking gamma tocopherol -even by itself, without the other tocopherols- increases the level of both alpha and gamma tocopherol. (*) That said, whether gamma tocopherol is toxic after a certain amount, I don't know if that was studied yet.

    A clue that tocotrienols might be toxic is that they block cholesterol production. Tocopherols apparently reduce cholesterol through other mechanisms.

    (*) EDIT: I think I was wrong about this. This page makes the claim, but studies say otherwise. There are more studies on the issue.
     
  7. johns74

    johns74 Member

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    I experimented with ratios. I didn't do enough experiments, but so far I feel a stronger effect from a 2:1 gamma:alpha ratio than a 1:1 ratio. Ideally I would do blood tests to see which ratio increases the blood level more, but I don't have money now.

    One thing that suggests the body is probably pretty good at handling gamma tocopherol is that it's the most abundant form in nature. That the body is not able to handle predominantly alpha tocopherol supplements I think has already been demonstrated by showing that it depletes gamma tocopherol.
     
  8. johns74

    johns74 Member

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    I'm interested in hearing Ray's thoughts though on the relationship between gamma tocopherol and nitric oxide. Maybe that suggests a mechanism as to how excess gamma tocopherol might be harmful? Gamma tocopherol increases nitric oxide synthase, but it's also a good detoxifier of nitric dioxide, unlike alpha tocopherol.
     
  9. OP
    haidut

    haidut Member

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    That's not what the study is claiming. I am aware of all the research showing beneficial effects of gamma, delta and even beta tocopherol. In fact, the studies I posted on estrogen reduction used a tocopherol mixture with at least 60% gamma.
    However, my interest is in a discussion as to why the organism seems to preferentially absorb alpha tocopherol and only alpha tocopherol accumulates in the liver and fat tissues. Any ideas?
     
  10. johns74

    johns74 Member

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    I guess because of the two most important forms of vitamin E, alpha and gamma tocopherol, alpha is rarer in nature. Gamma tocopherol doesn't accumulate because it's used faster, just like MK4 is used faster than MK7 (vitamin K), and that doesn't mean that either alpha tocopherol or MK7 is better.

    Another idea I read is that excretion of gamma tocopherol is beneficial because it has good effects on the intestine.
     
  11. OP
    haidut

    haidut Member

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    Interesting, can you please point me to a study or source of info discussing the effect of gamma tocopherol on intestines?
     
  12. johns74

    johns74 Member

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    Source
     
  13. Such_Saturation

    Such_Saturation Member

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    Aspirin also induces nitric oxide release from vascular endothelium. I don't think he would have much to say.
     
  14. johns74

    johns74 Member

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    It looks like you can have very different ratios of alpha:gamma in supplements and still increase the blood level of both.

    In this study they used a 1:5 alpha:gamma ratio and that increased the blood level of both. A 1:6 alpha:gamma ratio increased gamma tocopherol and didn't affect alpha tocopherol.

    In this study they used approximately a 2.3 : 1 alpha:gamma ratio and also increased both.
     
  15. johns74

    johns74 Member

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    Gamma and delta tocopherol are toxic in ways alpha tocopherol isn't, according to this paper.

    The cytotoxicity of vitamin E is both vitamer- and cell-specific and involves a selectable trait.
    Oh well, maybe there is a point where keeping taking mixed tocopherols is bad, and we don't know what that is.
     
  16. Kasper

    Kasper Member

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    http://ajcn.nutrition.org/content/74/6/714.full

    "Tocopherol is the major form of vitamin E in many plant seeds and in the US diet, but has drawn little attention compared with α-tocopherol, the predominant form of vitamin E in tissues and the primary form in supplements. However, recent studies indicate that γ-tocopherol may be important to human health and that it possesses unique features that distinguish it from α-tocopherol. γ-Tocopherol appears to be a more effective trap for lipophilic electrophiles than is α-tocopherol. γ-Tocopherol is well absorbed and accumulates to a significant degree in some human tissues; it is metabolized, however, largely to 2,7,8-trimethyl-2-(β-carboxyethyl)-6-hydroxychroman (γ-CEHC), which is mainly excreted in the urine. γ-CEHC, but not the corresponding metabolite derived from α-tocopherol, has natriuretic activity that may be of physiologic importance. Both γ-tocopherol and γ-CEHC, but not α-tocopherol, inhibit cyclooxygenase activity and, thus, possess antiinflammatory properties. Some human and animal studies indicate that plasma concentrations of γ-tocopherol are inversely associated with the incidence of cardiovascular disease and prostate cancer. These distinguishing features of γ-tocopherol and its metabolite suggest that γ-tocopherol may contribute significantly to human health in ways not recognized previously. This possibility should be further evaluated, especially considering that high doses of α-tocopherol deplete plasma and tissue γ-tocopherol, in contrast with supplementation with γ-tocopherol, which increases both. We review current information on the bioavailability, metabolism, chemistry, and nonantioxidant activities of γ-tocopherol and epidemiologic data concerning the relation between γ-tocopherol and cardiovascular disease and cancer."
     
  17. narouz

    narouz Member

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    Where the heck do ya get y-tocopherol?
     
  18. Blossom

    Blossom Moderator

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    I think that's the symbol for gamma.
     
  19. johns74

    johns74 Member

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    Here Peat argues against vitamins C and E supplements:

    Source
     
  20. lvysaur

    lvysaur Member

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    Interesting. I wonder how often and how much Peat doses vitamin E. I personally avoid taking any supplement on a daily basis.
     
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