A collection of technical documents for customers wishing to understand more of the science behind our products.

Written by:  Dr Tom Shurlock for and on behalf of GWF Nutrition Limited.

Copyright GWF Nutrition Limited March 2019 - Not for reproduction.

Vitamin E is a generic term frequently used to group together eight different molecules, namely: α-, β-, ϒ- and δ- tocopherol (T) and the corresponding tocotrienols (TE). They are distinguished by their overall shape and bonding:

Tocotrienols: The Other Vitamin E Family

March 2019

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Figure 1. Structural forms of tocopherol and tocotrienol.

Both types have a chromanol ring and a 16-carbon phytyl-like side chain, in which tocopherols are saturated and tocotrienols have three double bonds. Positioning of H- or CH3- on the chromanol ring give rise to the four isotypes. Of the 8 forms it is only α-tocopherol that has been recognised as having deficiency symptoms and, as such, has been the subject of much research and commercial supplementation. Generally regarded as the Vitamin E, α-tocopherol has been widely reported as being a major antioxidant and has been shown to interact with selenium to optimise its effect.

 

Vitamin(s) E are synthesised by plants and, being lipid soluble, are found in plant oils; α-tocopherol is more associated with monounsaturated fats, whilst ϒ-tocopherol more so with polyunsaturates, and particularly hempseed oil.  Tocotrienols, however, are less widely found, especially in nut, or cereal oils. They are present in oats, at a level 2-3X that of α-tocopherol; this means that the Oatinol system, which is characteristic of, and unique to GWF Nutrition products has a good range of both tocopherols and tocotrienols, which gives significant properties beyond that classically associated with “Vitamin E”. As the major vitamin E forms in the food, αT and γT are more abundant than other

tocopherols or tocotrienols in tissues. On the other hand, despite variations in food sources, it has long been observed that αT is the predominant form of vitamin E in the body’ probably due to its resistance to catabolism.

 

All E forms are absorbed as chylomicrons and transported to tissues via the lymphatic system, with TE having higher absorbability than α-T; as reported in the Oatinol Delivery System, the presence of polar lipids and oat-based emulsions, uptake of E will be high. Uptake into tissues is through lipoprotein mediated mechanisms, which result in some specific effects. Whilst α-tocopherol is found at high levels in the plasma, ϒ-tocopherol appears to accumulate in the skin and adipose tissue, whilst tocotrienols are widely distributed through the cell membranes of all tissues. As such, and being unsaturated, tocotrienols have a specific role in combatting oxidation in stressed cell membranes, especially those lining the absorptive surfaces of the gut. E forms that are not absorbed into the tissues are subsequently metabolised in the liver.

 

Where α-tocopherol is bound to α-tocopherol-transfer protein (TTP) and incorporated into a lipoprotein for transport into cells, non-α T and the TE forms are catabolised to carboxychromanols via cytochrome P-450 (CYP4F2)-initiated side-chain ω- oxidation; these bioactives have significant effects beyond the antioxidative effects of Vitamin E. Once α-T is linked to TTP it is stored in an inert form; As its turnover is low, accumulation indicates the Vitamin E status of the animal.

All E forms are anti-oxidative, as well as the ω-hydroxy forms of the carboxychromanols. Tocopherols and tocotrienols are potent lipophilic antioxidants by scavenging lipid peroxyl radicals via donating hydrogen from the phenolic group on the chromanol ring. Vitamin E forms with an un-substituted 5-position including γT may trap electrophiles such as NO2 or peroxynitrite to form 5-nitro-γ-tocopherol (5-NγT). Additionally, tocotrienols prevent the nonenzymatic oxidation of various cell components (e.g. unsaturated fatty acids) by molecular oxygen and free radicals such as superoxide (O2 −) and hydrogen peroxide (H2O2). The various biochemical functions of tocotrienols

are related either directly or indirectly to Its antioxidant property. They are essential for membrane structure and integrity of the cell. Tocotrienols prevent the peroxidation of polyunsaturated fatty acids in various tissues and membranes and protects the red blood cells from hemolysis by oxidizing agents. It increases the synthesis of heme by enhancing the activity of enzymes δ-aminolevulinic acid (ALA) synthase and ALA dehydratase. It is required for cellular respiration through electron transport chain and is believed to stabilize coenzyme Q. It prevents the oxidation of vitamin A and carotenes and also LDL and thus may be helpful in the prevention of some chronic diseases. Tocotrienols also protect the liver from being damaged by toxic compounds such as CCL4

 

Following on from these properties the ramifications can be further discussed.; as with many anti-oxidative functions, there is a strong inter-relationship with inflammation; free radicals are closely associated with oxidative stress. In epithelial cells, macrophages and neutrophils, γT, δT and γTE modestly inhibit PGE2 and LTB4 without inhibiting COXs and 5-LOX activity. Carboxychromanols inhibit COX-1/COX-2 and 5-LOX enzyme activity. In neutrophils, vitamin E forms suppress ionophore- or S1P (sphingosine 1-phosphare)-stimulated calcium influx and its downstream signalling. In lung epithelial cells, macrophages and some cancer cells, γTE inhibits activation of NF-κB and STAT6/3 as well as their regulated genes including cytokines and chemokines. There is therefore, a wide range of anti-inflammatory activity depending on the form of the Vitamin E.

 

Tocotrienols are also involved in immunomodulation. Stimulation of immunoglobulins (IgA & IgG), from the release of interleukins, T-cell stimulation and suppression of TNF-α are a further pathway of tocotrienol function.

 

Tocotrienols are also reported as having neuroprotective (α-TE) and cardiovascular protective roles (α- & ϒ-TE), tocotrienols being more effective than tocopherols. In the case of neuroprotection, this gives rise to a potential non-oxidative pathway, preventing glutamate induced apoptosis (Fig 2)

Figure 2. Representation of tocotrienol involvement in neuroprotection.

Tocotrienols prevent the increase in expression of TNF-α and nitric oxide (NO) due oxidative stress and inflammation and thus prevent osteoclast formation. Tocotrienols also downregulate the

expression of Receptor activator of nuclear factor kappa-B (RANK) and Receptor activator of nuclear factor kappa-B ligand (RANKL). Osteoporosis and glucocorticoids also decrease the calcium ion concentration in bone leading to bone desorption. Tocotrienols prevent the desorption of calcium ions from bone, thus increasing the bone strength. Tocotrienols also increase the expression of interleukin-8 (IL-8), IL-17, granulocyte colony stimulating factor (G-CSF) which in turn lead to the formation of bone osteoblasts (Fig 3.).

References

Ahsan H, Ahad A, Iqbal J, Siddiqui WA. Pharmacological potential of tocotrienols: a review. Nutrition & Metabolism 2014, 11:. 52-74

 

Comitato R, Ambra R, Virgili F. Tocotrienols: A Family of Molecules with Specific

Biological Activities. Antioxidants 2017, 6, 93-107

 

Qing Jiang. Natural forms of vitamin E: metabolism, antioxidant and antiinflammatory

activities and the role in disease prevention and therapy. Free Radic Biol Med. 2014 July ; 72: 76–90

 

Muid, S.; Ali, A. M.; Yusoff, K.; Nawawi, H. Optimal antioxidant activity with moderate concentrations of tocotrienol rich fraction (TRF) in assays. International Food Research Journal. 20 2. 687-694. 2013

Shu-Ping Lee Guang-Yuan Mar /lean-Teik Ng . Effects of tocotrienol-rich fraction on exercise endurance capacity and oxidative stress in forced swimming rats. European Journal of Applied Physiology. November 2009, Volume 107, Issue 5, pp 587–595

van den Broeck  HC, Londono DM, Timmer R, Smulders MJM, Gilissen LHWJ, van der Meer IM. Profiling of Nutritional and Health-Related Compounds in Oat Varieties. Foods 2016, 5, 2-13

Figure 3. Involvement of tocotrienols in bone homeostasis.

There are several other reported effects of tocotrienols including gastroprotective, hepatoprotective and nephroprotective properties. Additionally, the above effects, particularly the antioxidant and anti-inflammatory routes do support reported positive effects on muscular endurance.

 

Whilst α-tocopherol is the headline act in the Vitamin E family, due to its known deficiency systems, the accumulation of ϒ-tocopherol, the tocotrienols and their metabolites in all tissues and particularly cell membranes provide a wid- ranging oxidative protection system, mopping up free radicals and supporting the physiological balance of pro- and anti-oxidative enzymes all support the role of α-tocopherol. The diversity of their role in oxidative processes are the reason why they are regarded as being more “effective”, as well as rolling out their impact on inflammation, immunomodulation and various protective parameters.

 

Under the Oatinol System, naturally occurring tocopherols and tocotrienols will supply a supportive range of anti- oxidative and -inflammatory mechanisms that play a beneficial role in a full spectrum of metabolic/physiological processes.

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