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Tocotrienols: A More Potent (and Safe) Form of Vitamin E

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Tocotrienols: A More Potent (and Safe) Form of Vitamin E

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Virtually everyone reading this has heard of vitamin E. In fact, many of you are likely taking it as a supplement, either in a multivitamin or on its own.

But did you know that supplementing with the most common form of vitamin E, alpha-tocopherol, doesn’t improve health over the long term—and, in fact, can actually increase the risk of cancer and heart disease? 

The good news is that thanks to a breakthrough discovery by scientists about 20 years ago, we now know of another form of vitamin E—called tocotrienols—which has far more potent health benefits and does NOT carry any of the long-term risks of tocopherols.

Read on to learn more about how tocotrienols can help you stay healthy, avoid disease, and live a long life!

A brief history of Vitamin E

Today, we know that Vitamin E is a family of eight separate but related molecules. There are four tocopherols (alpha, beta, delta, and gamma) and four tocotrienols (alpha, beta, delta, and gamma). 

But this understanding of vitamin E is relatively new. It was first discovered 100 years ago, in 1922, by researchers at UC Berkeley who were studying fertility in rats. They found a compound in vegetables required for rats to bring a fetus to full term. The researchers originally called this compound the “anti-sterility factor” but later renamed it tocoperhol, which means “to carry a pregnancy” in Greek. 

Over the next several decades, all of the research performed on vitamin E was on the tocopherol form. Tocotrienols were partially discovered in the 1960s, but at the time, researchers still believed they were simply different types of tocopherols.

It wasn’t until about 20 years ago, in the early 2000s, that scientists identified tocotrienols as a completely distinct form of Vitamin E with different properties than tocopherols. 

The molecular structure of tocotrienols is different than tocopherols: they have shorter tails and heads and don’t anchor deeply into the cell membrane. These differences allow tocotrienols to more easily enter cells and intercept free radicals—which explains why tocotrienols are 40–50 times more potent than tocopherols as antioxidants

Most foods or plants that contain Vitamin E have a mixture of different forms of tocopherols and tocotrienols. For example, rice contains 35 percent delta- and gamma-tocotrienol, 15 percent alpha- and beta-tocotrienol, and 50 percent tocopherol. The figure below is excerpted from Dr. Barrie Tan’s excellent eBook, The Truth About Vitamin E.

The annatto plant is the only source of Vitamin E that contains pure delta- and gamma-tocotrienol. This is important because we know that delta and gamma are the most potent forms of tocotrienols when it comes to their effects on human health.

The problem with tocopherols (the most common form of vitamin E)

We get about 10-15 mg/d of tocopherols in our diet, mostly from foods like nuts, seeds, and vegetable oils. At this level, tocopherols have a beneficial or neutral effect.

However, studies over the past several years have shown that supplementing with alpha-tocopherol either doesn’t work or may cause harm—by increasing the risk of cancer and heart disease

For example, a systemic review of randomized, controlled trials published in JAMA Internal Medicine found that supplementing with the alpha-tocopherol form of vitamin E increased the risk of death from all causes. (1

More recently, the American Heart Association published a scientific statement suggesting that long-term supplementation with alpha-tocopherol can increase the risk of prostate cancer and heart failure. (2

Another issue with supplementing with alpha-tocopherol is that high doses of tocopherols interfere with the beneficial effects of tocotrienols. With too much alpha-tocopherol in the system (from supplements), tocotrienols are blocked from absorption and entry into the bloodstream.

This interference won’t happen with the amount of tocopherol we get from the diet (i.e. 10–15 mg/d), but it can happen with the amount that one might get from typical Vitamin E supplements and multivitamins.

The diverse benefits of tocotrienols: A better form of vitamin E

Since tocotrienols were only distinguished from tocotrienols about twenty years ago, we are still learning about their unique functions and effects. But there is already a large body of evidence showing that they have remarkably potent and diverse impacts on human health.

Tocotrienols help maintain healthy metabolic function

Tocotrienols have a wide range of benefits on metabolic function. They reduce blood sugar, triglycerides, blood pressure, and accumulation of fat in the liver and abdominal area. They also improve insulin sensitivity and may assist with weight loss. (3, 4, 5)

Tocotrienols help maintain healthy lipid levels and cardiovascular health

Tocotrienols have multiple effects on cardiovascular function and lipid metabolism. They reduce the activity of the HMG-CoA reductase enzyme, which is also targeted by statin drugs. Tocotrienols have a more gentle effect on this enzyme, however, so they do not typically cause the side effects that are associated with statin drugs. (6, 7)

Studies have shown that tocotrienols reduce LDL particle number, LDL cholesterol, and triglycerides. They also reduce the oxidation of LDL particles and inhibit their adhesion to artery walls. (Conversely, alpha-tocopherol oxidizes LDL, which may in part explain why supplemental tocopherols are associated with an increased risk of heart disease.) Tocotrienols reduce inflammatory cytokines associated with cardiovascular disease and their gene expression, including tumor necrosis factor αlpha, and interleukins 2, 4, 6, and 8. (8, 9, 10)

Tocotrienols promote healthy brain function

Tocotrienols help maintain a healthy brain as we age. They reduce the pool of two proteins—FPP and GGPP—that have been shown to promote the development of Alzheimer’s disease. Studies also indicate that tocotrienols may improve mental clarity. (11, 12)

Tocotrienols help reduce inflammation and oxidative stress

Inflammation and oxidative stress are at the root of all chronic, modern diseases, and they are also primary drivers of the aging process. As noted above, tocotrienols are powerful antioxidants—in fact, they are 40–50 times more potent as antioxidants than tocopherols. They’ve been shown to increase total antioxidant status in the body, and they may even protect against radiation exposure—both from environmental exposure and from chemotherapy. (13, 14)

Tocotrienols inhibit the production of inflammatory compounds like Nuclear Factor kappa-Beta (NFkB), Tumor Necrosis Factor-alpha (TNF-a), C-reactive Protein (CRP), nitric oxide, and Interleukin 2, 4, 6 and 8. (15, 16)

Tocotrienols help maintain healthy bones

Tocotrienols dampen inflammation and prevent oxidative damage, both of which are primary drivers of bone loss. Clinical trials have shown that tocotrienols decrease bone resorption and increase bone turnover rate. Tocotrienols also improve osteoblast number, bone formation, mineral deposition, and bone microarchitecture. It’s worth noting that alpha-tocopherol, the most common vitamin E form in supplements, may have harmful bone formation effects. (17, 18)

Tocotrienols support healthy immune function and protect against cancer

At higher doses, tocotrienols have shown great potential against a wide range of cancers, including breast, ovarian, prostate, colon, pancreatic, and skin cancers. They inhibit angiogenesis, vascular endothelial growth factor (VEGF), and induction of apoptosis through the caspase-3 pathways. They also reduce cancer cell proliferation and induce cancer cell death (i.e. apoptosis), with the most malignant forms of cancer appearing to be most sensitive to the actions of tocotrienols. (19, 20, 21, 22)

Unlike tocopherols, tocotrienols have no known contraindications or long-term adverse effects.

How to get the benefits of tocotrienols

Unlike other essential nutrients like vitamin A and vitamin C, and even vitamin E tocopherols, there is no significant source of vitamin E tocotrienols in the diet. Palm oil and rice do contain some delta- and gamma-tocotrienol, but not at high enough doses to be therapeutic. These foods also contain tocopherols, which can cancel out the benefits of tocotrienols. 

This means that, in order to get the considerable benefits of tocotrienols, we need to take them as a supplement. Delta- and gamma-tocotrienols are the most potent form, and annatto is the only known plant that contains 100 percent delta- and gamma-tocotrienol, with no other forms of tocotrienols and no tocopherols. 

It’s also important to ensure that you are not taking more than 30 mg/d of tocopherols from other supplements. Most multivitamins and vitamin E supplements contain tocopherols, rather than tocotrienols, so check the labels of your current supplements. 

The following table shows the recommended dosages of tocotrienol for various uses based on the current clinical evidence.

Condition Recommended Daily Dose of Tocotrienol
Inflammation 250–300 mg/d
High cholesterol or lipid abnormalities 250–300 mg/d
Blood sugar and metabolic issues 250–300 mg/d
Cancer protection 400–900 mg/d
Bone health 300 mg/d
Brain health 250–300 mg/d
Arhtritis and joint pain 250–300 mg/d
Radiation exposure 250–300 mg/d
Recommended daily tocotrienol dosage by health condition/goal

What to look for in a tocotrienol supplement

Here’s what to look for in a tocotrienol supplement:

  • It should contain 100 percent delta- and gamma-tocotrienol (since those are the most potent forms of tocotrienols)
  • It should be sourced from the annatto plant (since that is the only known plant source that contains nearly 100 percent delta- and gamma-tocotrienol)
  • It should contain no tocopherols (since tocopherols can interfere with the functions and benefits of tocotrienols)
  • It should contain a dose that is high enough to be therapeutic
  • It should contain no gluten‚ dairy‚ soy, GMO, or artificial ingredients

Tocotrienols are one of the most exciting nutritional compounds that I’ve come across in my 15-year career, and they’ve become an essential part of my daily routine, as well as a powerful tool in my clinical practice. I hope you will see as many benefits from them as my patients and I have!

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