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Tocotrienol: High Performance ‘Super Vitamin E’

Vitamin E is an essential nutrient, that protects cells from oxidative stress, and which cannot be made by the body. Oxidative stress results from the overproduction of free radicals, which cause oxidative damage to cells, and con-tributes to the development of chronic dis-ease. The term vitamin E refers to a family of eight closely related compounds: four tocotrienols (alpha-, beta-, delta-, and gamma-tocotrienol) and four tocopherols (alpha-, beta-, delta-, and gamma-tocoph-erol). Figure 1 shows the molecular struc-tures for tocotrienol and tocopherol, which are quite similar in that they both consist of a chromanol ring and a phytyl side chain. The only difference is tocotrienol possess-es an unsaturated side chain (indicated by the presence of double C=C bonds), where-as tocopherol has a saturated side chain (absence of double C=C bonds). Hence, to-cotrienol is also known as the unsaturated form of vitamin E.

The unsaturated side chain of tocotrienol allows the molecule to be more flexible and penetrate inside of cells more efficiently (where it is utilized as an anti-oxidant) compared to the saturated tocopherol form of vitamin E (1). Tocotrienol has been found to provide unique health benefits including brain health (2–7), liver health (7–9), cardiovascular health (10–11), skin health (12–15), and hair regrowth in participants with hair loss. These unique health benefits have been reported in published human clinical studies. Due to these unique health benefits, tocotrienol has been dubbed ‘super vitamin E’ and ‘vitamin E for the 21stcentury’.

Brain Health

Brain health has been investigated by one of the largest tocotrienol/tocopherol human clinical trials ever conducted (121 participants) (2). This study showed that supplementation for two years with EVNol SupraBio™ (a natural full-spectrum vitamin E palm tocotrienol complex designed to enhance the absorption of tocotrienol by 250%) slowed the development of white matter lesions (WMLs) in the brain. WMLs are an indication of a fragile brain vascular network and are an independent risk factor for a full-blown stroke and cognitive dysfunction or impairment. This study showed that EVNol SupraBio™ contributed to brain health in a pre-stroke setting.In a post-stroke setting, studies conducted at the Ohio State University Medical Center and funded by the US National Institute of Health showed that EVNol SupraBio™ mitigated neurological injuries arising from stroke. These meticulous studies conducted over the past 16 years demonstrated that tocotrienols contributed to neuroprotective benefits and reduced stroke-induced neurological injuries.Additionally, a group of European researchers published studies that showed that the full-spectrum tocotrienol/tocopherol complex was more effective than tocopherol alone at mitigating mild cognitive impairment and lowering Alzheimer’s disease risk. These four large population studies with over 600 elderly participants suggested that high plasma levels of full-spectrum vitamin E (tocotrienol and tocopherol) is associated with improved cognitive function in advanced age people and highlight a role for tocotrienol at reducing the risk of Alzheimer’s disease (3–6).


Figure 1: Legend
Molecular Structure of Tocotrienol and TocopherolTocotrienol, the unsaturated form of vitamin E, is distinct from tocopherol due to the presence of an unsaturated phytyl side chain that contains double C=C bonds (*).

Liver Health

EVNol SupraBio™ was first shown to mitigate fatty liver (liver stenosis) in study participants with non-alcoholic fatty liver disease (NAFLD) in 2013 (7). In this study, 64 patients with fatty liver were randomized to receive oral supplementation with EVNol SupraBio™ or placebo for a year. At the end of the study, 50% of participants supplemented with tocotrienol had a normalized fatty liver ultrasound, while only 23.5% of participants from the placebo group demonstrated normalization. In another study conducted in the Philippines, three months of daily supplementation with mixed tocotrienol (100 mg EVNol SupraBio™) coupled with lifestyle modification (healthy diet and exercise) improved liver stiffness among fatty liver patients four times more effectively compared to an intervention of lifestyle modification alone (8).

In addition, a group of end-stage liver patients were randomized to receive daily supplementation with mixed tocotrienol (400 mg EVNol SupraBio™) or alpha-tocopherol alone. 50% of patients supplemented with EVNol SupraBio™ demonstrated significant improvement of liver functions (reduction in model for end-stage liver disease [MELD] scores – MELD is a scoring system that is used to determine the severity of chronic liver disease; a higher MELD score indicates poor liver function). Only 20% of the tocopherol-supplemented patients had a decreased MELD score. These results suggested that tocotrienol was the more liver-protective form of vitamin E. This study also marked the first ever human tissue distribution study that demonstrated the accumulation of tocotrienols in the liver, brain, heart, and skin (9).

Heart Health

Study participants with a high blood cholesterol level receiving daily supplementation with mixed tocotrienol (300 mg EVNol SupraBio™) had significant reductions in total and low density lipoprotein (LDL) cholesterol levels by the fourth month of supplementation. Continuous cholesterol level reduction was also observed in the fifth and sixth months of supplementation, with an overall reduction of approximately 17%. In contrast, participants in the placebo group were found to have negligible changes in their total and LDL cholesterol levels compared to baseline (10).

In another randomized controlled human clinical study, daily supplementation with mixed tocotrienol (50, 100 and 200 mg EVNol SupraBio™) for two months contributed to arterial compliance (determined by augmentation index and pulse wave velocity) among healthy adults. After two months of supplementation, all of the tocotrienol supplemented groups showed significant reduction in augmentation index of up to 8.7% from baseline. Participants receiving 100 mg and 200 mg of mixed tocotrienol showed significant reduction in pulse wave velocity up to 10% from baseline (11).

Skin Health

Dr. Nicholas Perricone (Dermatologist at the Yale Medical Center), in his New York Times’ best-selling book The Wrinkle Cure, advocated for the use of tocotrienols (as a form of ‘high performance vitamin E’) in cream to promote skin health and prevent skin aging. Vitamin E is used widely in cosmetic and personal care products. It is not surprising that tocotrienols, as the more potent form of vitamin E, is gaining the attention of researchers and formulators for anti-aging and skin care products. The main reason tocotrienols are used is that it possesses anti-oxidant properties, which protect the skin against the toxic effects of oxidative stress caused by free radicals and exposure to chemicals and ultraviolet (UV) rays.

Tocotrienol exhibits 40 to 60 times stronger antioxidative properties compared to tocopherol and thus, tocotrienol is one of the most important lipid-soluble chain breaking antioxidants in cell membranes (1). A study revealed that the skin naturally contains approximately 15% of the total tocotrienols in the body, but only 1% of tocopherols are distributed in the skin (12). This suggested that the distribution of tocotrienols may be tissue-specific and that tocotrienol is preferentially accumulated and distributed in the upper most layer
of the skin (strata cornea) (13). Hence, tocotrienols are the skin’s first line of defense against free radicals formed in the skin. A human clinical trial conducted in Italy and published in the Journal of the European Academy of Dermatology and Venereology showed that topical application prior to sun exposure (UV rays) of an antioxidant formulation (containing both tocotrienols and tocopherols) conferred greater protection from UV-induced skin damage than retinol (vitamin A) or other vitamin E free preparations. Results showed that pre-treatment with this new full-spectrum vitamin E topical formulation significantly reduced the signs and symptoms of UV-induced skin damage (lesions, erythema, oedema, itching, and vesciculation) in 30 participants. The researchers also noted that sufficient levels of protection to a UV-exposure test were achieved with a single application of the cream. The cream was found to be safe and did not cause any harmful side effects (14).

In another study, supplementation of participants with dry skin with a combination of 2 mg astaxanthin and 40 mg tocotrienols (EVNol™, a natural full-spectrum palm tocotrienol complex) had increased moisture level and reduced fine wrinkles and pimples after 4 weeks of treatment, compared to the control group. In contrast, supplementation of participants with placebo did not improve, and generally worsened, their skin condition during the test period (15).

Conclusion

Researchers from the United States, Japan, Europe and Malaysia have reported the unique health properties of tocotrienol. However, tocotrienol cannot be produced in the body. As such tocotrienol must be obtained through diet or supplementation. In nature, palm oil (Elaeis guineensis) is the most abundant source of tocotrienol, containing up to 800 mg/kg. However, in order to attain a daily intake of 30–50 mg of tocotrienol via diet alone, one has to consume about 80,000 mg (80 g) of palm oil or 1.5–4.0 kg of wheat germ, barley or oats. This is practically impossible. Therefore, supplementation with tocotrienol through dietary supplements or tocotrienol fortified function foods is recommended to achieve a plasma level that supports overall health and well-being. The commercial applications of tocotrienols are diverse and represent a sizeable fraction of all health problems when taken together. Hence, full-spectrum palm tocotrienol complex is well positioned to potentially emerge as the most potent form of natural vitamin E.

References

1. Serbinova E, et al. Free radical recycling and intramembrane mobility in the antioxidant properties of alpha-tocopherol and alpha-tocotrienol. Free Radical Biology & Medicine. 1991;10:263-275.

2. Gopalan Y, et al. Clinical investigation of the protective effects of palm vitamin E tocotrienols on brain white matter. Stroke. 2014;45(5):1422-8.

3. Mangialasche F, et al. High plasma levels of vitamin E forms and reduced Alzheimer’s disease risk in advanced age. J Alzheimers Dis. 2010;20(4):1029-37.

4. Mangialasche F, et al. Tocopherols and tocotrienols plasma levels are associated with cognitive impairment. Neurobiology of Aging. 2012;33:2282-2290.

5. Mangialasche F, et al. Classification and prediction of clinical diagnosis of Alzheimer’s disease based on MRI and plasma measures of α-/α-tocotrienols and α-tocopherol. Journal of Internal Medicine. 2013(June);273(6):602-21.

6. Mangialasche F, et al. Serum levels of vitamin E forms and risk of cognitive impairment in a Finnish cohort of older adults. Exp. Gerontol. 2013(Dec);48(12):1428-1435.

7. Magosso E, et al. Tocotrienols for normalisation of hepatic echogenic response in nonalcoholic fatty liver: a randomised placebo-controlled clinical trial. Nutr. J. 2013(Dec);12(1):166.

8. Arguillas M, et al. Abstract: The effect of vitami E (mixed tocotrienol) on the liver stiffness measurement measured by transient elastography (fibroScan) among NAFLD patients. APAS Liver Week. Singapore.2013(June).

9. 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):513-9.

10. Yuen KH, et al. Effect of Mixed-Tocotrienols in Hypercholesterolemic Subjects. Functional Foods in Health and Disease. 2011;3:106-117.

11. Rasool AHG, et al. Arterial compliance and vitamin E blood levels with a self-emulsifying preparation of tocotrienol rich vitamin E. Arch. Pharm. Res. 2008;31(9):1212-1217.

12. Podda, M, et al. Simultaneous determination of tissue tocopherols, tocotrienols, ubiquinols and ubiquinones. Journal of Lipid Research. 1996;37(4):893-901.

13. Ikeda S, et al. Selective uptake of dietary tocotrienols into rat skin. J. Nutr. Sci. Vitaminol. (Tokyo). 2000;46(3):141-3.

14. Pedrelli VF, et al. Clinical evaluation of photoprotective effect by a topical antioxidants combination (tocopherols and tocotrienols). J. Eur. Acad. Dermatol. Venereol. 2012;26(11):1449-53.

15. Yamashita E. Cosmetic benefit of dietary supplements including astaxanthin and tocotrienol on human skin. Food Style. 2002;21(6):112-117.

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