Vitamin E Family in Health & Disease (the Science) part 2

Be sure to also check out this article (Vitamin E: the Science part 1) for the tocopherols part of the story.

Here are five Scientific Research Papers revealing why the current doctrine of giving Vitamin E status and units to only alpha tocopherol is flawed and needs to be updated. Vitamin E consists of 8 similar structure compounds that have common synergistic functions as well as unique and different actions. ref Divided into two groups, tocopherols and tocotrienols, here are some of the vital functions for tocotrienols:

1.  Tocotrienols in health and disease: the other half of the natural vitamin E family

Mol Aspects Med. 2007 Oct-Dec;28(5-6):692-728. Epub 2007 Mar 27.

http://www.ncbi.nlm.nih.gov/pubmed/17507086  

Structurally, natural vitamin E includes 8 molecules:

alpha-, beta-, gamma- and delta-tocopherol;

alpha-, beta-, gamma- and delta-tocotrienol.

Symptoms caused by alpha-tocopherol deficiency can be alleviated by tocotrienols. Taken orally, tocotrienols are bioavailable to all vital organs. Oral tocotrienol protects against stroke-associated brain damage in vivo.

Palm oil and rice bran oil represent two major nutritional sources of natural tocotrienol.

The tocotrienol forms of natural vitamin E possesses powerful hypocholesterolemic, anti-cancer and neuroprotective properties that are often not exhibited by tocopherols.

Disappointments with outcomes-based clinical studies testing the efficacy of alpha-tocopherol need to be handled with caution and prudence recognizing the untapped opportunities offered by the other forms of natural vitamin E. Although tocotrienols represent half of the natural vitamin E family, work on tocotrienols account for roughly 1% of the total literature on vitamin E. The current state of knowledge warrants strategic investment into investigating the lesser known forms of vitamin E.    PMID: 17507086

 2. Tocotrienol: the natural vitamin E to defend the nervous system       

    http://www.ncbi.nlm.nih.gov/pubmed/?term=Ann+N+Y+Acad+Sci.+2004+Dec%3B1031%3A127-42.

"Vitamin E is essential for normal neurological function. It is the major lipid-soluble, chain-breaking antioxidant in the body, protecting the integrity of membranes by inhibiting lipid peroxidation. Mostly on the basis of symptoms of primary vitamin E deficiency, it has been demonstrated that vitamin E has a central role in maintaining neurological structure and function. Orally supplemented vitamin E reaches the cerebrospinal fluid and brain. Vitamin E is a generic term for all tocopherols and their derivatives having the biological activity of RRR-alpha-tocopherol, the naturally occurring stereoisomer compounds with vitamin E activity. In nature, eight substances have been found to have vitamin E activity: alpha-, beta-, gamma- and delta-tocopherol; and alpha-, beta-, gamma- and delta-tocotrienol. Often, the term vitamin E is synonymously used with alpha-tocopherol. Tocotrienols, formerly known as zeta, , or eta-tocopherols, are similar to tocopherols except that they have an isoprenoid tail with three unsaturation points instead of a saturated phytyl tail. Although tocopherols are predominantly found in corn, soybean, and olive oils, tocotrienols are particularly rich in palm, rice bran, and barley oils. Tocotrienols possess powerful antioxidant, anticancer, and cholesterol-lowering properties. Recently, we have observed that alpha-tocotrienol is multi-fold more potent than alpha-tocopherol in protecting HT4 and primary neuronal cells against toxicity induced by glutamate as well as by a number of other toxins. At nanomolar concentration, tocotrienol, but not tocopherol, completely protected neurons by an antioxidant-independent mechanism. Our current work identifies two major targets of tocotrienol in the neuron: c-Src kinase and 12-lipoxygenase. Dietary supplementation studies have established that tocotrienol, fed orally, does reach the brain. The current findings point towards tocotrienol as a potent neuroprotective form of natural vitamin E."                       PMID: 15753140

 3. Tocotrienols: constitutional effects in aging and disease

Free Radic Biol Med. 2010 Nov 30;49(10):1542-9. doi: J Nutr. 2005 Feb;135(2):151-4.

Tocotrienols, a class of vitamin E analogs, modulate several mechanisms associated with the aging process and aging-related diseases. Most studies compare the activities of tocotrienols with those of tocopherols ("classical vitamin E"). However, some biological effects were found to be unique for tocotrienols. Although the absorption mechanisms are essentially the same for all vitamin E analogs, tocotrienols are degraded to a greater extent than tocopherols. The levels of tocotrienols in the plasma of animals and humans were estimated to reach low micromolar concentrations. One hallmark in the origin of disease and aging is the overproduction of reactive oxygen species (ROS). Tocotrienols possess excellent antioxidant activity in vitro and have been suggested to suppress ROS production more efficiently than tocopherols. In addition, tocotrienols show promising nonantioxidant activities in various in vitro and in vivo models. Most notable are the interactions of tocotrienols with the mevalonate pathway leading to the lowering of cholesterol levels, the prevention of cell adhesion to endothelial cells, and the suppression of tumor cell growth. Furthermore, glutamate-induced neurotoxicity is suppressed in the presence of tocotrienols. This review summarizes the main antioxidant and nonantioxidant effects of tocotrienols and assesses their potential as health-maintaining compounds.                  PMID: 15671205

          4. Potential role of tocotrienols in the treatment and prevention of breast cancer

          Biofactors. 2014 Jan-Feb;40(1):49-58. doi: 10.1002/biof.1116. Epub 2013 Jun 27.

Vitamin E is a generic term that refers to a family of compounds that is further divided into two subgroups called tocopherols and tocotrienols. Although all natural forms of vitamin E display potent antioxidant activity, tocotrienols are significantly more potent than tocopherols in inhibiting tumor cell growth and viability, and anticancer activity of tocotrienols is mediated independently of their antioxidant activity. In addition, the anticancer effects of tocotrienols are observed using treatment doses that have little or no effect on normal cell function or viability. This review will summarize experimental studies that have identified the intracellular mechanism mediating the anticancer effects of tocotrienols. Evidence is also provided showing that combined treatment of tocotrienol with other cancer chemotherapies can result in a synergistic inhibition in cancer cell growth and viability. Taken together, these findings strongly indicate that tocotrienols may provide significant health benefits in the prevention and/or treatment of cancer when used either alone as monotherapy or in combination with other anticancer agents.

© 2013 International Union of Biochemistry and Molecular Biology.              PMID: 23804535

5. Mechanisms mediating the antiproliferative and apoptotic effects of vitamin E in mammary cancer cells

          Front Biosci. 2005 Jan 1;10:699-709. Print 2005 Jan 1.

Tocopherols and tocotrienol represent the two subgroups within the vitamin E family of compounds, but only tocotrienols display potent anticancer activity at doses that have little or no effect on normal cell growth or function. Tocotrienols are potent antioxidants, but antitumor activity is independent of antioxidant activity. The exact reason why tocotrienols are more potent than tocopherols is not completely understood, but at least part of the reason is because of greater cellular accumulation. Furthermore, dose-response studies show that growth inhibitory doses of tocotrienols are 5-6 times lower than their corresponding lethal doses, suggesting that the antiproliferative and cytotoxic effects of tocotrienols are mediated through different mechanisms. Recent studies showed that tocotrienol-induced programmed cell death (apoptosis) results from the activation of specific intracellular cysteine proteases (caspases) associated with death receptor activation and signal transduction. Furthermore, combined treatment with specific caspase inhibitors blocked the cytotoxic effects of tocotrienols in malignant mammary epithelial cells. In contrast, tocotrienol inhibition of cell proliferation appears to involve the suppression of multiple hormone- and growth factor-receptor mitogenic signaling pathways. Although additional studies are required to clarify the intracellular mechanisms mediating the anticancer effects of tocotrienols, experimental evidence strongly suggests that dietary supplementation of tocotrienols may provide significant health benefits in lowering the risk of breast cancer in women.      PMID: 15569611

THESE 5 STUDIES SHOW THE INHERENT VALUE of CONSUMING ALL THE VITAMIN E FAMILY MEMBERS rather than just D’Alpha Tocopherol. While it is best to consume tocopherols and tocotrienols separately, as they compete for the same receptors at absorption sites, together is better than non at all and especially better than the "unbalanced" approach of only supplementing D' Alpha Tocopherol by itself. Natural foods often separate these two groups as well.  

QUESTION: Why do the responsible Governmental nutritional agencies still cling to the 1940's decision to give the name "Vitamin E" and vitamin E units only to the alpha tocopherol fraction, just one of eight "vitamin E" family members in Nature?

ANSWER: In the 1940's, it was discovered that only the D'alpha tocopherol fraction remained in the blood at sufficient quantities after a relatively short period of time. The Scientists assumed that this meant that only the D'alpha tocopherol fraction was important, BUT did you notice in the above paragraph that the other vitamin E fractions enjoy greater uptake into cells? Maybe they have more important functions inside cells than to remain in the blood. Since alpha tocopherol is the only form with a protein carrier to keep it in blood longer, maybe this is a natural mechanism to keep it in the plasma longer and protect against fat oxidation. And next it moves to a protection mode around the outside of cell membranes and later inside cells at the mitochondria. Alpha tocopherol functions as an antioxidant quite efficiently at these sites. But, it functions are enhanced with some mixed tocopherols also present. Remember, gamma tocohperol may convert to alpha tocopherol if more alpha is needed, but not the other way around. This is still a debated issue.

SIDEBAR: A Heart Doctor measured the amount of the four tocopherols in the blood of heart patients and healthy subjects. He found that the alpha tocopherol levels were the same in both groups. Thus why would one think that adding more alpha tocopherol would be the answer for heart disease? It was gamma that was low in heart patients. Maybe gamma was converting to alpha to help out with oxygen antioxidant functions. This could jeopardize protection against nitrogen radicals where gamma is more efficient than alpha. The body may have a triage mentality to move nutrients where the greatest need occurs at the moment.

Of course D'alpha tocopherol is important, but to exclude the other 7 vitamin E family factors appears to be quite foolish according to the number of modern day diseases (cancer and dementia) where the other 7 outshine D'alpha tocopherol abilities. Nature functions best in team sports. Gamma makes alpha more effective. They each have synergistic roles to help each other out, as well as complementary roles where they could even have opposite counter-balancing roles. ref

CAUTION: Balance among vitamin E family members is needed. Only consuming d'alpha tocopherol or excess gamma tocopherol out of ratio with each other or the other vitamin E family members can be problematic, even though the other E family members are available and needed in only small amounts.

Excess gamma tocopherol out of balance with alpha tocopherol has been found to increase dementia in studies, much like only consuming alpha tocopherol has shown no effects on lowering cholesterol levels or protecting prostate without gamma tocopherol also present. They work and are both needed together for maximum benefits.

More research is needed on the many forms of vitamin E. Many of the mentioned studies were on animals that may not react the same in humans, but should at least be bring into play the precautionary principle.

This is another new factor. Vitamin E as alpha tocopherol appears to self correct against higher dosages and lowers it's own absorption percentage as dosages increase. Nature Smart. More is not often better for vitamins with higher dosages.

WRAP UP

Another recent Cancer review study noting forms matter. ref 

IT IS TIME TO REACH A CONCLUSION FROM THE Copious amount of VITAMIN E RESEARCH.

What the USA Government calls Vitamin E as only alpha tocopherol is severely flawed. While there are some vitamin E studies with positive results, far too many reveal negative. Since many of these negative results could be corrected with Vitamin E family members also present, the solo vitamin E products should be eliminated, especially at higher dosages.

In fact, this next study and review of other studies show that research using just the solo form of Vitamin E INCREASES heart disease and cardio artery disease.  ref ref

Early observational studies revealed that people with higher blood levels of vitamin E exhibited greater prevention from heart disease. But these may really have shown that higher levels of vitamin E family from food offered this protection and not supplements.

The latest on Tocotrienols and disease published in 2022 has many clarifying charts. ref

Real VITAMIN E is A FAMILY OF RELATED NUTRIENTS. 

Tocopherols:  Alpha, Beta, Delta, Gamma, and perhaps a new one, Epsilon

Tocotrienols:  Alpha, Beta, Delta, Gamma, and perhaps Epsilon

The actual and proper amounts or ratios between these vitamin E family members for low dose supplements is still under investigation. New research is vitally needed using all the natural family E members. Synthetic vitamin E contains only 17% real vitamin E and is not viable as a vitamin E supplement. Period!