Saturday, June 2, 2012

Tocotrienols: What They Are, What They Do & How They Work + Why the RDA of Palm Olein is NOT 1xCup Per Day

Image 1: If you wanted to get the tocotrienol levels a producer of respective supplements says are  "required", you would have to eat at least 200g palm fruits a day. Alternatively, you can resort to 4kg of oats, if you like those better... What? you are wondering that you are not dead by now? After so many years of tocotrienol deficiency from not getting your 4kg of oats?
The long lists of pathologies related to vitamin E deficiency include, among others, all sorts of degenerative diseases from ataxia over general muscle degeneration to degeneration of sperm and subsequent infertility. But despite the fact that there is a pretty substantial amount of evidence that would suggest that a diet rich in vitamin E could not just prevent the aforementioned pathologies, but would also protect us from many of the currently prevalent ailments of western society such as obesity and coronary vascular disease (Mishra. 2003; Rimm. 1993), respective trials with dietary supplements usually show no, or even negative effects. I have already addressed a couple of  reasons why the benefits of dietary vitamin E intake often cannot be replicated with supplements in previous posts. The most significant one, probably is the absence of the "right" mixture and ratio of alpha-, beta-, gamma- and delta-tocopherols and, as an emerging contributer, the total absence of tocotrienols in the vast majority of vitamin E supplements and almost 99.9% of the pertinent trials.

What are tocotrienols? And what do they do?

I could now rant about the structural differences between the two, with the tocotrienols being an unsaturated variety of the tocopherols with a isoprenoid side chain, but I guess it is enough to know that due to  differences in their molecular structure, they also differ in their effects on the human body, of which you may already have apprehended that their cholesterol lowering effects were the first to attract the attention from researchers (Qureshi. 1986). Within the last 26 years researchers from all around the world have identified additional health benefits, the most prominent of which are...
  • Anti-cancer effects (Kato. 1985; Sundram. 1989; Weng. 2009),
  • General antioxidant effects (Newaz. 1999),
  • Brain specific antioxidant effects (Khanna. 2003),
  • Exercise-specific antioxidant effects (Lee. 2009),
  • Cardiovascular disease (Shibata 2009)
  • Diabetic neuropathy (Kuhad. 2009)
  • Bone health (Ahmad. 2005)
  • Metabolic syndrome (Weng. 2011)
  • Antithrombotic effects (Qureshi. 2011)
  • Endocrine health (Yu. 2005)
  • Liver health (Patel. 2012)
The purpose of today's SuppVersity article is yet not so much to compile the most extensive list of potential, purported or demonstrated benefits of tocotrienols, the major dietary sources of which are (Kobayashi. 1975; Tan. 2011)
  • rice bran oil (50:50 tocopherol:tocotrienol ratio), 
  • palm oil (25:75 tocopherol:tocotrienol ratio), and 
  • annatto (0.1:99.9 tocopherol:tocotrienol ratio) oil
  • human breast milk (!) [though this is probably no major source for you ;-]
but rather to take a look at an intriguing chart of the various molecular targets (Aggarwal. 2010) and discuss the implications:
Figure 1: Molecular targets (left) and proteins that directly interact with tocotrienols (right; adapted from Aggarwal. 2010)
As you can see  without even looking really close at the above graphic, the number of those targets is vast. Another thing you should see right away is that the effect of the tocotrienols is mostly inhibitory (red ovals in the left) and include a couple of old foes, such as:
  • the inflammatory cytokines & transcription factors: IL-1, IL-6, TNF-alpha, nf-kappabeta, IL-8 (probably involved in auto-immune reactions), PF-A4 (increases platelet aggregation and thus thrombosis risk)
  • factors involved in angiogenesis and cardiocascular disease: VEGF (vascular growth factor, involved in CVD) and its receptor VEGF-r, VCAM-1 (increases adhesion of immune cells to the endothelial wall)
  • kinases involved in the cell cycle and apoptotic regulators: CDK's, PKC, pERK, etc. & survivin, IAP-1 & 2 etc., but also telomerase, which are all involved in the proliferation of cancer
  • enzymes involved in inflammatory processes: eNOS, iNOS, COX-2, etc.
On the upregulatory side of things, we have
  • enzymes from the CYP cascade, which are among other involved in the clearance of estrogen, and other hormone like substances and the metabolism of drugs,
  • MAPK and JNK, which exert anti-catabolic effects on muscle tissue, or 
  • GPX and SOD, two of the major enzymes involved in the antioxidant defenses
Now, if we take a look at all these, you may remember that low COX-2 levels have only recently been identified with profound overtraining (cf. "Overtraining inflammation insufficient repair"), that AKT (not mentioned above, but in figure 1) is one of the driving forces of skeletal muscle anabolism and telomerase, extends cell life in general, not just in cancer cells. Which brings us back to the issue of ... much anti-oxidants do we actually need?

Figure 2: Total tocopherol and tocotrienol content of high vitamin E foods / oils (top) and tocopherol ratios (bottom) , data based on Whittle. 1967 and Slover. 1971
Or, in this particular case, how much tocotrienols are still beneficial? Neither I, nor anybody else knows the exact answer to this question. And against this fact, the recommendations I came across on the website of a major producer of respective supplements, which state that you would need
  • 80g of palm oilen (cooking oil),
  • 160g of rice bran oil,
  • 3kg of barley,
  • 1.5kg of wheatgerm, or 
  • 4kg of oats
to (I quote) "achieve the required [my emphasis] level of tocotrienols" should tell any reasonable person that those "required" levels (~150mg) are probably required to generate the target revenue of the said company, yet probably not required for you or any other human being to thrive.

Do not stack one more, but take one out!

Instead of adding another overpriced (and probably overdosed) tocotrienol supplement to your regimen, it is thus probably wiser to simply drop any superflous and potentially harmful alpha-tocopherol only supplements which do would offset the alpha- to gamma- and delta- tocopherol ratio (this could potentially be ameliorated by taking a natural blend) and limit the total tocopherol intake to reasonable levels, as the latter has also been shown to hamper the absorption and retention of tocotrienols (Ikeda. 2003). In this context it is also noteworthy that Ping Tou Gee writes in a 2011 paper with the aptly chosen title "Unleashing the untold and misunderstood observations on vitamin E" that this fact alone would suggest that "there is a need to review critically on the dietary reference intakes recommendations" for alpha tocopherol (α-T). His bold statement that
[i]t is not known whether α-T is still essential to humans in long terms, α-T3 [alpha tocotrienol] diet appeared to produce healthy rats over five generations.
is yet probably an attribution to Palm Nutraceuticals Sdn. Bhd. (which is not the aforementioned company which wants to force-feed you either their supplements or 2 cups of rice bran oil), of which he states in the acknowledgments that he thanks them "for permission to publish this paper" and further evidence for how pathetic parts of the research in the medical field is - awful this science business, isn't it?

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