VITAMIN E as DELTA-TOCOTRIENOLS
…and why you should not use alpha-tocopherol
All multivitamins have Vitamin E, and thousands of research papers have been written about it—enough that this post could easily be expanded into a (very boring) book. Luckily for you, the information we want to convey about Vitamin E can be summarized in three points:
- There are actually eight types of vitamin E: four tocopherols (alpha, beta, gamma, delta) and four tocotrienols (alpha, beta, gamma, delta). Most multivitamins use only tocopherols– and up until a few years ago they only used alpha-tocopherol
- You should not supplement with alpha-tocopherol.
- The best type of Vitamin E for maintaining normal healthy cell signaling and apoptosis is delta-tocotrienol. (Gamma-tocotrienol and gamma tocopherol get honorable mention.)
To make things more manageable, we have divided this into two sections:
Why You Shouldn’t Supplement with Alpha-Tocopherol
Advance warning: this post gives more detail than most of you really want. The entire story can be summed up as follows:
- Be careful what form of Vitamin E you use.
- Supplementing with tocotrienols or gamma-tocopherol is much more likely to support normal healthy cell function.
- Curos Essential uses only tocotrienols, from a specific source that contains almost exclusively delta-tocotrienol.
If you want the nitty gritty details, read on…
WHY YOU SHOULDN’T TAKE ALPHA-TOCOPHEROL
Synthetic vs. Natural E, and the Eight Isomers of E
It’s important to clarify that Vitamin E is not just one vitamin. There are at least eight forms of Vitamin E. Four are called tocopherols: alpha, beta, gamma and delta tocopherol, and four are called tocotrienols (again, alpha through delta).
The eight forms are not inter-convertible in humans, and they have different chemical structures, functions, biological activity and clinical effects. However, nearly all of the large trials that have been performed on vitamin E (including SELECT) have studied only alpha-tocopherol.
That’s strange, because in food, we generally find much higher concentrations of gamma-tocopherol than alpha, so one would think that gamma tocopherol would have attracted more attention.
To confuse things further, the natural alpha-tocopherol found in food is not even the same as the type of alpha-tocopherol found in many supplements. Natural alpha-tocopherol is known as d-alpha tocopherol; the “d” is chemistry nomenclature indicating the orientation of the molecule. But synthetic alpha-tocopherol contains both the d-form and its mirror image, the L-form. This synthetic mixture of “d and l”-alpha tocopherol (also called ‘racemic’ alpha tocopherol) is cheaper than natural d-alpha-tocopherol—and therefore is usually the form used in large trials, even though it’s not the kind we ingest in food.
Is the difference between synthetic and natural alpha-tocopherol clinically relevant?
It sure looks that way. Natural d-alpha tocopherol is more potent than the synthetic form in its anti-inflammatory, antioxidant and cell signaling effects.2,3,4 In addition, synthetic d,l-alpha-tocopherol may have adverse effects. Studies suggest that when administered alone at high doses, synthetic alpha-tocopherol:
- interferes with the biological activity of natural d-alpha tocopherol and lowers HDL-cholesterol (the “good” cholesterol)
- inhibits glutathione S-transferase, an enzyme important in the detoxification of medications and other toxins6
And what about the other seven forms of vitamin E?
The foods we eat do not contain much alpha-tocopherol: natural d-alpha-tocopherol comprises only about 15% of total vitamin E found in the U.S. diet (and synthetic d,l-alpha tocopherol isn’t found in food at all). Gamma-tocopherol is the most common form of vitamin E in the US diet and in many plant seeds. There is a growing body of data to suggest that gamma-tocopherol, and the tocotrienols, are much more useful in maintaining health than alpha-tocopherol.4,8
Gamma-tocopherol has some unique properties that alpha-tocopherol does not have, including the ability to maintain healthy cell function by suppressing the expression of the ras-p21 gene.
Until very recently, all four tocotrienol isomers, have been virtually ignored in the human trials. And tocotrienols seem to be even better at maintaining healthy cell function than gamma tocopherol. We discuss tocotrienols in the other part of this post; our main focus here is to explain why you should throw out your multivitamin if it has a lot of alpha-tocopherol in it.
The problem with high doses of alpha-tocopherol
Many studies on vitamin E – even those that used natural alpha-tocopherol – used high doses (over 400 IUs a day). Why is this a problem?
It’s a problem because the in the liver, the tocopherol transfer protein is crucial for transporting the various forms of vitamin E – and it has a 10-fold greater affinity for alpha tocopherol compared to gamma tocopherol. So by taking too much alpha tocopherol, you are likely reducing your ability to utilize gamma-tocopherol, and the tocotrienols.11,12
This means that taking high doses of alpha-tocopherol isn’t just “neutral”: it may decrease your cells’ ability to stay healthy – which is probably why every study of high dose alpha tocopherol has had a bad outcome. The SELECT trial was merely the latest example of this.
Is there any dose of alpha-tocopherol that is safe?
In 2006 another big study, the ATBC (Alpha Tocopherol Beta Carotene) Trial, found that higher levels of (natural) serum alpha-tocopherol can help lower mortality — but only to a point:
…regression analysis of serum alpha-tocopherol values indicated greater risk reductions with increasing concentrations up to 13–14 mg/L, after which no further benefit was noted. Conclusion: Higher circulating concentrations of alpha-tocopherol within the normal range are associated with significantly lower total and cause-specific mortality in older male smokers.13
How much alpha-tocopherol would be needed to keep your serum level at that “sweet spot” of 13-14mg/L?
That has been studied as well. In an extensive comment on the above article, it was noted:
We now have a critical piece of information – that is, serum alpha-tocopherol concentrations of 13–14 mg/L optimally reduce mortality due to chronic disease. Now all we have to do is estimate how much alpha-tocopherol to consume to achieve that serum concentration. … serum alpha-tocopherol concentrations… could be raised to 14.2 mg/L by the consumption of 100 IU (alpha tocopherol) supplements.14
In other words, it seems that 100 IUs/day should be the upper limit of your alpha-tocopherol supplementation. If you recall, the SELECT trial used 400 ius.
Further data showing synthetic alpha-tocopherol is bad
These observations have been validated again and again:
In 2005, a meta-analysis of 19 vitamin E studies conducted between 1993 and 2004 was published in Annals of Internal Medicine. The authors concluded that people who take daily doses of 400 iu’s or more of “Vitamin E” have a 10% increased risk of death compared to people who take small doses or no “Vitamin E”. But which type of E was used in those trials? In his rebuttal to the Annals article, Dr Mark Houston pointed out that the Vitamin E used in Miller’s meta-Analysis was entirely alpha-tocopherol, and mostly synthetic d,l-alpha tocopherol:
None of the 19 studies in Miller’s review included any of the other seven forms of vitamin E, and, in fact, most of them used synthetic d,l-alpha tocopherol.17
Yet researchers have nevertheless been fixated on re-testing the same point: even after that 2005 meta-analysis, another “negative” vitamin E study was published in JAMA on Nov 9, 2008– yet again using high-dose synthetic d, l-alpha tocopherol.18
And so when the SELECT study came out, it was roughly the 21st trial of high-dose synthetic, dl-alpha tocopherol with a negative outcome. It’s fair to say that we don’t need any more research on that issue. Do yourselves a favor:
- Do not use multivitamins that include synthetic (d,l) alpha-tocopherol,
- If you use natural alpha-tocopherol, do not exceed 100iu’s per day, because it will lower your absorption of the more helpful forms of vitamin E: gamma tocopherol and the tocotrienols.
- Curos Essential uses only Tocotrienols, as “delta Gold,” a specialized form that contains mostly delta-tocotrienols. We get into further detail about tocotrienols below.
Why Gamma- and Delta-Tocotrienols are the Best Forms of Vitamin E
To understand why we chose delta-tocotrienols for Curos Essential, we need to discuss the concept of apoptosis.
Apoptosis is the death of cells that occurs as a normal and controlled part of your growth or development. In the average human adult, around 60 billion cells die every day – that’s normal. When cells aren’t needed any more, or when they become unhealthy, our bodies get rid of them efficiently, so that they cannot cause disease. Apoptosis cannot stop once it has begun, so the process is tightly controlled by cell signaling.
So, supporting normal cellular apoptosis is critical to keeping the whole organism (that’s you!) healthy. The question is, can naturopathic treatments help in that regard?
The argument for using supplements or naturopathic treatments has nothing to do with the fact that they’re “natural.” (Hemlock and wolf’s bane are natural, but you wouldn’t want to eat them.)
The reason for supplements and naturopathic interventions is that prescription drugs are not typically designed to maintain health; rather, they’re designed to treat disease. If you want to maintain normal, healthy cell function, there are few, if any, prescription drugs available for you. There will be one day: researchers are closing in on true anti-aging treatments, and someone will eventually patent one. But until that day, pharmaceuticals do not have a significant role to play in healthy people. Why is that?
One reason is simply that the worldview of Western medicine is very “disease-centric.” But there is another reason: prescription medications are usually designed to target a single receptor. Our bodies, however, are complex systems with a multitude of interwoven genetic and molecular pathways. Hitting one receptor works fine if you want to target the symptom that appears at the tail end of a cascade of events. A single receptor, however, is almost always inadequate to address the underlying dysregulated cell signaling pathways that caused that cascade of events to begin– so a single receptor cannot be harnessed prophylactically to maintain health.
To illustrate, let’s take a look at two images.
First, look at this diagram put together by the Kyoto Encyclopedia of Genes and Genomes:
That is a diagram of the cell signaling system involved in maintaining normal cellular apoptosis.
As you scroll around the image, it becomes quickly apparent: our cells have a lot of genes, pathways and receptors involved in regulating apoptosis!
So if you were aiming to keep your cells healthy, knowing how many receptors, genes and pathways are involved, would you choose to target just one receptor? Or would you choose to target as many as possible?
Now compare that to this image from a research article discussing tocotrienols. Tocotrienols are a specific form of Vitamin E that are almost never used in multivitamins. We wanted them for Curos, despite the expense, and here is why:
Source: Biochem Pharmacol. 2010 Dec 1; 80(11): 1613–1631., Fig 3a
The image shows all of the pathways that are targeted by tocotrienols. You will see that tocotrienols are perfectly comfortable amidst the vast complex of signaling molecules involved in apoptosis! 13, 22
There are four types of tocotrienols: alpha through delta. For apoptosis support, the best form is delta tocotrienols, followed by gamma.21,23,24,25,28
There are also other benefits to delta-tocotrienol over the other seven forms of vitamin E.
This is why we use a formulation that is almost exclusively delta tocotrienols (90% delta, 10% gamma) in Curos Essential.
Tocotrienols are not the only “multitalented” Curos ingredient; many phytochemicals share the same quality of targeting multiple cellular pathways. Berberine, Green Tea and Siliphos, three other Curos Essential ingredients, are similarly versatile, which is why interest in them has exploded over the past 15 years.
Why DeltaGoldTM Tocotrienols?
Six of the Curos ingredients are trademarked, including this one, DeltaGoldTM tocotrienols. (The other trademarked ingredients are Siliphos, selenoExcell, Kaneka Ubiquinol, and the Albion minerals Zinc and Boron.) Trademarked ingredients are expensive, but in each case there is a reason we wanted to use the trademarked brand. Usually that reason is: the trademarked version has proven superior absorption. However in the case of tocotrienols, we wanted DeltaGold for a different reason: it’s the only brand we could find that contains almost entirely (90%) delta tocotrienols, with no tocopherols. Other brands, if you read the label, have alpha tocopherol mixed in, and alpha and beta tocotrienols as well. Since we are focused on apoptosis support, delta-tocotrienols are what we want.21
A bottle of Curos Essential gives you 200mg per day of DeltaGold.TM We chose that dose because of two human studies that support this to be the best possible dose to support healthy cellular functions.