The science of the ‘next generation’ vitamin E

The vitamin E family​

Tocotrienols are a form of vitamin E that have traditionally been in the shadow of the more popular vitamin E form – tocopherols.

Overall, there are eight forms of vitamin E: four tocopherols (alpha, beta, gamma, delta) and four tocotrienols (alpha, beta, gamma, delta). Alpha-tocopherol (alpha-Toc) is the main source found in supplements and in the European diet, while gamma-tocopherol (gamma-Toc) is the most common form in the American diet.

Tocotrienols (TCT) are only minor components in plants, although several sources with relatively high levels include palm oil, cereal grains and rice bran.

While most research on vitamin E has focused on alpha-Toc, studies into tocotrienols account for less than one per cent of all research into vitamin E.

In an interview with NutraIngredients last year, Barrie Tan, PhD​, president of American River Nutrition explained that the only differentiation between a tocotrienol and a tocopherol is the tail, and that the tail of a tocopherol is longer, “so it anchors deeply in the [cell] membrane to protect the membrane from oxidation – most people know this - but the tail of the tocotrienol is shorter and it actually moves around in the membrane […] and it can actually cross over membranes”​.

“In terms of benefits to the body, [tocotrienols] would protect a larger area of membrane in a cell, than a tocopherol that stays stationary in one place,”​ added Dr Tan.

John Kurstjens from Lipid Nutrition, one of a handful of tocotrienol suppliers, told NutraIngredients that despite a lot of research being done, “the science needs to be developed much more before any health claims can be made”​.

Heart disease​

One of the earliest reports to link tocotrienols to heart health – via cholesterol reduction – was a paper by Dr Asaf Qureshi at the USDA. Writing in the Journal of Biological Chemistry​ (Vol. 261, pp. 10544-10550.) in 1986, Dr Qureshi and his co-workers reported that the a cereal’s ability to reduce cholesterol concentrations was directly linked to its tocotrienol concentrations, with barley and oats coming out on top, followed by rye, wheat and then corn.

Another study of note followed in 1992 from researchers at Bristol-Meyers Squibb (again involving Dr Qureshi), which reported that gamma-tocotrienol was 30 times more active than the alpha-tocotrienol form at inhibiting cholesterol synthesis.

Human studies followed, with Dr Qureshi again leading the charge. In 1991 a pilot study (Am. J. Clin. Nutr​.​, Vol. 53, pp. 1021S-1026S) reported that supplementation with palm-derived tocotrienols was associated with a reduction in cholesterol levels in hypercholesterolemic subjects, with gamma-tocotrienol again identified as “the most potent cholesterol inhibitor in the [tocotrienol-enriched fraction of palm oil used in the study]”​.

The presence of tocopherol in the mix is a source of debate, with a study from 1995 in Lipids​ (Vol. 30, pp. 1171-1177) reporting that alpha-tocopherol “attenuated the cholesterol-suppressive action of the tocotrienols”​.

Indeed, a review by Mark Houston from Vanderbilt University School of Medicine last year explained: “Tocotrienol and tocopherol concentrates, often referred to as ‘tocotrienols-rich fractions’ (TRFs), are obtained from rice bran or palm oil and contain about 30 to 50 percent tocopherols.​

“If the TRFs contain more than 20 percent tocopherols, the cholesterol-lowering effect is diminished.”​ (Prog Cardiovasc Dis, ​Vol. 52, pp. 61-94).

Tocotrienols from rice bran have also been linked to improved heart health, with a 2001 study, again from Dr Qureshi, reporting that rice bran-derived tocotrienols may inhibit atherosclerotic lesions mice (Journal of Nutrition,​ 2001, Vol. 131, pp. 2606-2618).

Carotech, the biggest player in the sector, lists the cardiovascular benefits associated with tocotrienols as improved arterial compliance, improved blood pressure, and increased antioxidant activity to improve ventricular function.

And recently, scientists from tocotrienol supplier Davos Life Sciences and Malaysia Palm Oil Board reported that palm-derived gamma and delta tocotrienols may lower triglyceride levels by 28 percent in the blood of human after two months of supplementation (Journal of Atherosclerosis and Thrombosis​, Vol. 17, pp.1019-1032)

Cancer​

Next to the cardiovascular health, cancer is the other main area of science commonly linked to tocotrienols. Specific types of cancer reported to be affected by tocotrienols include prostate and breast cancer. In a review in The Journal of Nutritional Biochemistry​ (2002, Vol. 13, pp. 2-20) Dawn Schwenke from Wake Forest University School of Medicine noted that the science does not support a potential anti-breast cancer role for alpha-tocopherol. On the other hand, “studies in breast cancer cells indicate that alpha-, gamma-, and delta-tocotrienol, and to a lesser extent delta-tocopherol, have potent anti-proliferative and proapoptotic effects that would be expected to reduce risk of breast cancer”​, she wrote.

A 2008 study by Davos Life Sciences (Br. J. Cancer​, Vol. 99, pp. 1832-1841) reported a potential mechanism by which tocotrienols may suppress the growth and spread of prostate cancer.

An animal study using Carotech’s Tocomin ingredient (Nutrition and Cancer​, Vol. 62, pp. 789-794) revealed that mice fed tocotrienols had a significantly lower occurrence of prostate tumors compared to the control.

A study by Andreas Constantinou from the University of Cyprus was said to be the first of its king to study “the efficacy and mechanism of apoptosis modulated by the 8 vitamin E homologs”. ​The cell-based study found that delta-tocotrienol (obtained from annatto oil, Deltagold 50, American River Nutrition) was the most potent form of vitamin E for inducing cell death in certain prostate cancer cell lines (Nutrition and Cancer​​, Vol. 61, pp. 864-874).

The benefits may be related to DNA protection, according to a 2007 study from Malaysian researchers. Their findings, published in the journal Nutrition​, indicated that daily supplementation with a tocotrienol-rich supplement (Tri E Tocotrienol) showed greater effects in the older subjects, a sub-population with higher rates of DNA damage, considered an important trigger in cancer development.

"The effect of Tri E Tocotrienol is more obvious in older age, possibly reflecting a greater need for supplementation or a greater profound effect due to the larger amount of damage present,"​ wrote the authors, led by Siok-Fong Chin.

Immune health​

Only recently, Malaysian researchers reported the benefits of vitamin E tocotrienols to boost the immune response and immune function in healthy women following a vaccination.

Results published in the European Journal of Clinical Nutrition​ (doi:10.1038/ejcn.2010.184), women who received daily supplements of a palm tocotrienol complex for one month prior to a single tetanus toxoid (TT) vaccine experienced improvements in their immune response, compared with women who received placebo prior to the vaccine.

The study used Carotech’s TocominSupraBio-branded ingredient and the study was supported financially by the Malaysian Palm Oil Board and the International Medical University in Kuala Lumpur.

This follows a study published in the Journal of Nutrition​ in July 2010 by researchers at Tufts University. Using (Vol. 140, pp. 1335-1341) C57BL/6 Mice and Carotech’s Tocomin mixed tocotrienol ingredient, the researchers reported that daily supplements of a mixture of the four types of tocotrienol led to improvements in the T cell function in old mice

“This is the first study, to our knowledge, reporting that tocotrienol enhances T cell function,”​ wrote the researchers in the journal.

Brain health​

Neuroprotective effects of tocotrienol have also been reported, and alpha-tocotrienol has again been highlighted for its activity. A study by researchers from Ohio State University found that alpha-tocotrienol may inhibit an enzyme from releasing fatty acids that eventually kill neurons (Journal of Neurochemistry​, 2010, doi: 10.1111/j.1471-4159.2009.06550.x).

“Our research suggests that the different forms of natural vitamin E have distinct functions. The relatively poorly studied tocotrienol form of natural vitamin E targets specific pathways to protect against neural cell death and rescues the brain after stroke injury,”​ said Professor Chandan Sen, lead researcher of the study.

What is said to be the world’s largest clinical trial into the potential for brain health and tocotrienols is currently underway in Malaysia with a target recruitment of 200 people, and a daily supplement of 200 mg of softgel tocotrienol twice a day (Tocovid). The study is a collaboration between the University of Science Malaysia and the Malaysia Palm Oil Board.

Male pattern baldness​

A novel area gaining attention has been the potential of tocotrienols to increase hair growth in people with male pattern baldness. A study supported by tocotrienol supplier Carotech and performed at the School of Pharmaceutical Sciences at the University of Science Malaysia reported that eight months of supplementation with the company’s vitamin E complex (total tocotrienol intake of 100 mg) was associated with a 42 percent increase in hair growth. The study is yet to be published in a peer-review journal and NutraIngredients.com has not seen the full data.

Hovid – Carotech’s parent company – patented a hair growth formulation in 2007 (US Patent No. 7,211,274). “In one embodiment, a composition for promoting hair growth and reducing hair loss according to the present invention comprises mixed tocotrienols and a pharmaceutically acceptable excipient,”​ reads the patent.

Our series on tocotrienols will continue will a look at the market.

DISCLAIMER: This article represents a short summary of the science of tocotrienols. It is not intended to be exhaustive or replace a thorough scientific review. If studies or ingredients have been omitted it is not intentional.​