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The Three Great Eras of Vitamin E

Vitamin E products have evolved from a product based on alpha-tocopherol to complete formulas that are bio-enhanced, non-GMO and derived from vegetable oils.

WH Leong, Bryan Seeand 1 more

March 23, 2018

7 Min Read
The Three Great Eras of Vitamin E

Vitamin E is an essential nutrient to support fertility and a powerful fat-soluble antioxidant, which protects cell membranes against damage caused by free radicals. It was one of the first two antioxidant compounds to be sold as dietary supplements, the second being vitamin C. The term vitamin E encompasses a group of eight compounds, called tocopherols and tocotrienols, with various subsets of each, that comprise the vitamin E complex as it is found in nature. Each of these different compounds has distinct chemistries and biological effects, such as neuroprotection,1,2,3 liver protection,4 hair growth5,6 and cholesterol-lowering activities by tocotrienols7,8,9.

First Era of Vitamin E

While there are eight vitamin E isoforms in nature, the vitamin E used in dietary supplements in the early days (the 1960s to 1990s) was the form of alpha-tocopherol, either synthetic (dl-alpha-tocopherol) or natural (d-alpha-tocopherol)—as it was erroneously thought to have the highest vitamin E activity. According to the Food and Nutrition Board of the National Academy of Science (“Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium and Carotenoids”), the other forms of vitamin E (non-alpha-tocopherols such as gamma-tocopherol and tocotrienols) did not have international unit (IU) of vitamin E activity. Only alpha-tocopherol contributes to IU of vitamin E activity: 1 mg of natural alpha-tocopherol is equivalent to 1.49 IU of vitamin E activity.

Hence, the first era of vitamin E science and products were focused on the single isoform of natural/synthetic alpha-tocopherol with high level on IU of vitamin E activity, such as vitamin E products with 400 IU, 800 IU, 1,000 IU and 2,000 IU.

Second Era of Vitamin E

In mid-late 1990s/early 2000, as more research was conducted on non-alpha-tocopherol forms of vitamin E (such as gamma-tocopherol and tocotrienols), the scientific community began to realize that while they do not contribute to IU of vitamin E activity, they do possess unique and stronger biological activities, physiologically, than alpha-tocopherol.

In addition, at around the same time, published studies and bad press of vitamin E started to appear in mainstream media, such as Journal of the American Medical Association,10,11,12,13,14 with the latest in October 2010—the Selenium and Vitamin E Cancer Prevention Trial (SELECT), which reported vitamin E 400 IU/d (from natural or synthetic alpha-tocopherol) did not help reduce the risk of cardiovascular and prostate diseases.15 Such studies had unfortunately resulted in a bad or negative impression of vitamin E to consumers alike, and caused the decline in interest and sales of vitamin E, in general.

As a result, scientists, formulators, supplement companies and nutritionists started to look into the science of vitamin E, and rationalize that with the unique and stronger biological activities of gamma-tocopherol and tocotrienols, the most ideal formula for vitamin E is a product that combines both mixed tocopherol (with lower IU of vitamin E activity, such as vitamin E 200 IU) and mixed-tocotrienols.

Vitamin E Transport Mechanism—Tocopherol Transport Protein (TTP)

One of the main concerns of vitamin E complete formulas is the issue of tocopherol transport proteins (TTP)—the known transport mechanism for vitamin E isoforms. As TTP has low affinity to tocotrienols, they were thought to not be efficiently absorbed into the plasma, or that tocopherols compete with tocotrienols for the same transport protein. This has since been debunked by a group of researchers from Ohio State University Waxner Medical Center who conducted a study on TTP-knockout mice.16 This study revealed that tocotrienol was transported to and accumulated in vital organs, even without the presence of TTPs. In short, there is a secondary transport mechanism for tocotrienol. Further, a human tissue distribution study published in 2012 using bio-enhanced palm tocotrienol/tocopherol complex (as EVNol SupraBio™ from ExcelVite)17 showed tocotrienols were effectively transported to and accumulated in vital human organs such as the brain, liver, heart and skin, even in the presence of alpha-tocopherol.

Third Era of Vitamin E

With the sophistication of the dietary supplement market, perhaps it is time to revisit the vitamin E that we have right now. Is this the best form of vitamin E? What can be done to make it more meaningful to consumers, based on current trends and scientific evidence? What do consumers—particularly Millennials—expect from the industry? Here are a few factors that may influence consumers’ selection of a vitamin E product:

  • Origin of the product (natural, plant-derived vitamin E);

  • Full-spectrum vitamin E (d-mixed tocopherols + d-mixed tocotrienols) with the right ratio;

  • Non-GMO (genetically modified organism);

  • Bioavailability/better uptake;

  • Science-based; and

  • Non-IU-based.

Natural, vegetable-based, full-spectrum tocopherol extracts are commonly derived from soy and rapeseed, whereas palm oil is the richest source of full-spectrum tocotrienol. For the Non-GMO project-verified vitamin E, rapeseed and palm oil are the preferred options.

Being a fat-soluble compound, absorption is a common issue for vitamin E tocopherols and tocotrienols. For example, the absolute absorption rate for gamma- and delta-tocotrienol is less than 10 percent18. To have better uptake of vitamin E in the body, a good, self-emulsifying delivery system is essential.

Finally, FDA has unveiled a new nutrition facts label—where the labeling for vitamin E activity will change from IU to “mg,” effective Jan 1, 2020. This new labeling system will enhance consumer’s awareness as to the right recommended daily vitamin E amount and help consumers choose the right form of vitamin E to consume.

WH Leong is CEO of ExcelVite (excelvite.com), Bryan See is business development manager at ExcelVite Inc. USA), and Diyanah Roslan is a nutritionist at ExcelVite Sdn. Bhd., Malaysia.


  1. Selvaraju, T et al. “The neuroprotective effects of tocotrienol rich fraction and alpha tocopherol against glutamate injury in astrocytes.” Bosnian Journal of Basic Medical Sciences, 14(4),195.

  2. Khanna, S. et al. “Neuroprotective Properties of the Natural Vitamin E -Tocotrienol.” Stroke 2005,36(10),e144-e152.

  3. Khanna S et al. “Characterization of the potent neuroprotective properties of the natural vitamin E α-tocotrienol.” Journal of Neurochemistry 2006,98(5),1474-1486.

  4. Patel, V et al. “Oral Tocotrienols Are Transported to Human Tissues and Delay the Progression of the Model for End-Stage Liver Disease Score in Patients.” The Journal of Nutrition 2012,142(3),513-519.

  5. Beoy L et al. “Effects of tocotrienol supplementation on hair growth in human volunteers.” Tropical Life Sciences Research 2010,21(2),91.

  6. Ahmed N et al. “Epidermal E-Cadherin Dependent β-Catenin Pathway Is Phytochemical Inducible and Accelerates Anagen Hair Cycling.” Molecular Therapy 2017,25(11),2502-2512.

  7. Yuen, K. H., Wong, J. W., Lim, A. B., Ng, B. H., & Choy, W. P. Effect of mixed-tocotrienols in hypercholesterolemic subjects. Functional Foods in Health and Disease 2011,1(3),106-117.

  8. Cn J., Guthrie N. “Effect of citrus flavonoids and tocotrienols on serum cholesterol levels in hypercholesterolemic subjects.” Alternative Therapies In Health And Medicine 2007,13(6),44.

  9. Ajuluchukwu et al. “Comparative study of the effect of tocotrienols and-tocopherol on fasting serum lipid profiles in patients with mild hypercholesterolaemia: a preliminary report.” The Nigerian Postgraduate Medical Journal 2007,14(1),30-33.

  10. Meagher E et al. “Effects of vitamin E on lipid peroxidation in healthy persons.” Jama 2001, 285(9),1178-1182.

  11. Graat J, Schouten E, Kok, F. “Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial.” Jama 2002, 288(6),715-721.

  12. Eidelman R et al. “Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease.” Archives of Internal Medicine 2004,164(14),1552-1556.

  13. Lee I et al. “Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s Health Study: a randomized controlled trial.” Jama 2005,294(1),56-65.

  14. Lippman S et al. “Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).” Jama 2009,301(1),39-51.

  15. Klein E et al. “Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).” Jama 2011,306(14),1549-1556.

  16. Khanna S et al. “Delivery of orally supplemented α-tocotrienol to vital organs of rats and tocopherol-transport protein deficient mice.” Free Radical Biology and Medicine 2005,39(10),1310-1319.

  17. 17. Patel V et al. “Oral Tocotrienols Are Transported to Human Tissues and Delay the Progression of the Model for End-Stage Liver Disease Score in Patients.” The Journal of Nutrition 2012,142(3),513-519.

  18. Yap S, Yuen K, Wong J. “Pharmacokinetics and bioavailability of α-, γ- and δ-tocotrienols under different food status.” Journal of Pharmacy and Pharmacology 2001,53(1),67-71.



About the Author(s)

WH Leong

WH Leong is CEO of ExcelVite (excelvite.com).

Bryan See

Bryan See is business development manager at ExcelVite Inc. USA.

Diyanah Roslan

Diyanah Roslan is a nutritionist at ExcelVite Sdn. Bhd., Malaysia.


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