Tocotrienols is a chemical compound, lipophilic molecule and amphiphilic lipid, which includes vitamin E, but is structurally different, synthesised by photosynthetic organisms via enzymes. It is generally produced from vegetable oils by Soxhlet extraction using hexane, but also by different multi-step processes. This ingredient is a mixture of alpha, gamma and delta tocopherol.

Tocotrienols are a form of vitamin E known for their potent antioxidant and anti-inflammatory properties. Belonging to the family of tocopherols and tocotrienols, tocotrienols are less common than tocopherols but offer unique benefits due to their ability to penetrate more easily into cell membranes. They are extracted from natural sources such as palm oil, rice bran oil, and barley, and are used in cosmetics and dietary supplements to protect the skin from oxidative damage, improve skin elasticity, and promote cell regeneration.

Chemical Composition and Structure
They have a chemical structure similar to tocopherols but with an unsaturated isoprenoid side chain, which makes them more mobile within cell membranes. There are four types of tocotrienols: alpha, beta, gamma, and delta, each with varying antioxidant capabilities. This unique structure allows tocotrienols to neutralize free radicals and protect cells from lipid peroxidation damage.

Physical Properties

Tocotrienols are fat-soluble, meaning they dissolve in fats and oils, making them ideal for oil-based cosmetic formulations. They are yellowish or brown oily liquids and can be easily incorporated into creams, serums, oils, and lotions for skin care. Their lightweight molecular structure allows for greater skin penetration compared to traditional tocopherols.

Production Process

Tocotrienols are extracted from plant-based sources, such as palm or rice bran oil, through extraction and purification processes. After extraction, tocotrienols can be concentrated into an oil form for use in cosmetic formulations or dietary supplements. The extraction process is carefully monitored to preserve the antioxidant integrity of the tocotrienols.

• Selection of Raw Materials: Tocotrienols are primarily extracted from plant sources such as palm oil, rice bran oil, and wheat germ. These ingredients are chosen for their high tocotrienol content.

• Extraction: Tocotrienols are extracted from seeds or fruits through a solvent extraction process, using appropriate solvents such as ethanol or hexane. The plants are crushed and immersed in the solvent, which helps dissolve the tocotrienols and separate them from other components.

• Filtration: After extraction, the mixture is filtered to remove undissolved solids, resulting in a liquid extract containing tocotrienols.

• Purification: The obtained extract is further purified using techniques such as chromatography, which allows for the isolation of pure tocotrienols from remaining plant compounds and impurities.

• Concentration: The purified tocotrienols may be further concentrated through evaporation or other methods to obtain a final product with a higher concentration of active tocotrienols.

• Quality Control and Packaging: Finally, tocotrienols undergo rigorous quality control checks to verify their purity, stability, and efficacy. After analysis, they are packaged in appropriate containers for distribution and use in dietary supplements and cosmetic products.

Applications

• Skincare: Tocotrienols are used in creams, lotions, and serums for their powerful antioxidant properties, helping to reduce signs of aging, improve skin elasticity, and promote cell regeneration.

• Anti-aging Products: Due to their ability to combat oxidative stress, tocotrienols are ideal for reducing wrinkles and fine lines while protecting the skin from environmental damage and UV exposure.

INCI Functions:

Light stabilizer. It prevents light from degrading light-sensitive components and slows down degradation reactions that have already begun. The mechanism is, in a way, similar to antioxidants and the effectiveness depends on the.complexity of the formulation and the density of the product.

Oral care agent. This ingredient can be placed in the oral cavity to improve and/or maintain oral hygiene and health, to prevent or improve a disorder of the teeth, gums, mucous membrane.

Skin conditioning agent - Miscellaneous. This ingredient has the task of modifying the condition of the skin when it is damaged or dry by reducing its flakiness and restoring its elasticity.

• Regenerative Products: Tocotrienols promote cell renewal and tissue repair, helping the skin regain vitality and softness.

Health and Safety Considerations

Safety in Use
Tocotrienols are considered safe for use in cosmetics and dietary supplements. No significant side effects are known to be associated with their use. Regulatory authorities such as the European Union and the FDA approve their use in cosmetic and nutritional products.

Allergic Reactions
Allergic reactions to tocotrienols are rare. However, it is recommended to perform a patch test before using products containing tocotrienols, especially on sensitive skin.

Toxicity and Carcinogenicity
In fact, tocotrienols have been studied for their potential anticancer properties due to their ability to reduce oxidative damage and improve cellular health.

Environmental Considerations
Tocotrienols are extracted from renewable natural sources such as sustainable palm oil and rice bran oil. It is important to ensure that the raw materials are harvested sustainably to minimize environmental impact and preserve natural ecosystems.

Regulatory Status
Tocotrienols are approved for use in cosmetics and dietary supplements by major regulatory authorities, including the European Union and the FDA in the United States. They are commonly used in skincare products and anti-aging formulations.

References__________________________________________________________________________

Patel V, Rink C, Khanna S, Sen CK. Tocotrienols: the lesser known form of natural vitamin E. Indian J Exp Biol. 2011 Oct;49(10):732-8. 

Abstract. A recent and growing body of research has shown that members of this vitamin E family posses unique biologic functions. Tocotrienols have garnered much of this recent attention, and in particular alpha-tocotrienol has been shown to be the most potent neuroprotective form of vitamin E. Protection exclusively mediated through tocotrienols has been arbitrated to many mechanisms including inhibition of 12-LOX, c-Src, PLA2 and through up-regulation of MRP1. Further, tocotrienols have recently been shown to induce arteriogenesis through induction of TIMP1 and decreased activation of MMP2. However, the unique therapeutic potential of tocotrienols is not limited to neuroprotection. Tocotrienols have been shown to have molecular targets including: apoptotic regulators, cytokines, adhesion molecules, enzymes, kinases, receptors, transcription factors, and growth factors. In spite of this large and unique therapeutic potential, scientific literature on tocotrienols only accounts for approximately 1% of vitamin E research. Given the potential of tocotrienols and relatively scant literature, further investigation is warranted.

Prasad K. Tocotrienols and cardiovascular health. Curr Pharm Des. 2011;17(21):2147-54. doi: 10.2174/138161211796957418. 

Abstract. This review emphasizes the effects of tocotrienols on the risk factors for atherosclerosis, plaque instability and thrombogenesis, and compares these effects with tocopherol. Tocotrienols reduce serum lipids and raise serum HDL-C. Alpha-tocopherol, on the other hand, has no effect on serum lipids. Tocotrienols have greater antioxidant activity than tocopherols. Both reduce the serum levels of C-reactive protein (CRP) and advanced glycation end products, and expression of cell adhesion molecules. The CRP-lowering effects of tocotrienols are greater than tocopherol. Tocotrienols reduce inflammatory mediators, δ-tocotrienol being more potent, followed by γ- and α-tocotrienol. Tocotrienols are antithrombotic and suppress the expression of matrix metalloproteinases. They suppress, regress and slow the progression of atherosclerosis, while tocopherol only suppresses, and has no effect on regression and slowing of progression of atherosclerosis. Tocotrienol reduces risk factors for destabilization of atherosclerotic plaques. There are no firm data to suggest that tocotrienols are effective in reducing the risk of cardiac events in established ischemic heart disease. Alpha-tocopherol is effective in primary prevention of coronary artery disease (CAD), but has no conclusive evidence that it has beneficial effects in patients with established ischemic heart disease. Tocotrienols are effective in reducing ischemia-reperfusion cardiac injury in experimental animals and has the potential to be used in patients undergoing angioplasty, stent implantation and aorto-coronary bypass surgery. In conclusion, experimental data suggest that tocotrienols have a potential for cardiovascular health, but long-term randomized clinical trials are needed to establish their efficacy in primary and secondary prevention of CAD.

Szewczyk K, Chojnacka A, Górnicka M. Tocopherols and Tocotrienols-Bioactive Dietary Compounds; What Is Certain, What Is Doubt? Int J Mol Sci. 2021 Jun 9;22(12):6222. doi: 10.3390/ijms22126222. PMID: 34207571; 

Abstract. Tocopherols and tocotrienols are natural compounds of plant origin, available in the nature. They are supplied in various amounts in a diet, mainly from vegetable oils, some oilseeds, and nuts. The main forms in the diet are α- and γ-tocopherol, due to the highest content in food products. Nevertheless, α-tocopherol is the main form of vitamin E with the highest tissue concentration. The α- forms of both tocopherols and tocotrienols are considered as the most metabolically active. Currently, research results indicate also a greater antioxidant potential of tocotrienols than tocopherols. Moreover, the biological role of vitamin E metabolites have received increasing interest. The aim of this review is to update the knowledge of tocopherol and tocotrienol bioactivity, with a particular focus on their bioavailability, distribution, and metabolism determinants in humans. Almost one hundred years after the start of research on α-tocopherol, its biological properties are still under investigation. For several decades, researchers' interest in the biological importance of other forms of vitamin E has also been growing. Some of the functions, for instance the antioxidant functions of α- and γ-tocopherols, have been confirmed in humans, while others, such as the relationship with metabolic disorders, are still under investigation. Some studies, which analyzed the biological role and mechanisms of tocopherols and tocotrienols over the past few years described new and even unexpected cellular and molecular properties that will be the subject of future research.

Fontana F, Raimondi M, Marzagalli M, Moretti RM, Marelli MM, Limonta P. Tocotrienols and Cancer: From the State of the Art to Promising Novel Patents. Recent Pat Anticancer Drug Discov. 2019;14(1):5-18. doi: 10.2174/1574892814666190116111827. PMID: 30652648.

Schaffer S, Müller WE, Eckert GP. Tocotrienols: constitutional effects in aging and disease. J Nutr. 2005 Feb;135(2):151-4. doi: 10.1093/jn/135.2.151. 

Abstract. Tocotrienols, a class of vitamin E analogs, modulate several mechanisms associated with the aging process and aging-related diseases. Most studies compare the activities of tocotrienols with those of tocopherols ("classical vitamin E"). However, some biological effects were found to be unique for tocotrienols. Although the absorption mechanisms are essentially the same for all vitamin E analogs, tocotrienols are degraded to a greater extent than tocopherols. The levels of tocotrienols in the plasma of animals and humans were estimated to reach low micromolar concentrations. One hallmark in the origin of disease and aging is the overproduction of reactive oxygen species (ROS). Tocotrienols possess excellent antioxidant activity in vitro and have been suggested to suppress ROS production more efficiently than tocopherols. In addition, tocotrienols show promising nonantioxidant activities in various in vitro and in vivo models. Most notable are the interactions of tocotrienols with the mevalonate pathway leading to the lowering of cholesterol levels, the prevention of cell adhesion to endothelial cells, and the suppression of tumor cell growth. Furthermore, glutamate-induced neurotoxicity is suppressed in the presence of tocotrienols. This review summarizes the main antioxidant and nonantioxidant effects of tocotrienols and assesses their potential as health-maintaining compounds.

Sylvester PW, Kaddoumi A, Nazzal S, El Sayed KA. The value of tocotrienols in the prevention and treatment of cancer. J Am Coll Nutr. 2010 Jun;29(3 Suppl):324S-333S. doi: 10.1080/07315724.2010.10719847. 

Abstract. Tocopherols and tocotrienols represent the 2 subgroups that make up the vitamin E family of compounds, but only tocotrienols display potent anticancer activity. Although in vitro experimental evidence has been very promising, oral supplementation of tocotrienols in animal and human studies has produced inconsistent results. However, recent studies have now clarified the reasons for these discrepancies observed between in vitro and in vivo studies. Oral absorption of tocotrienols into the circulation is mediated in large part by carrier transporter systems that display saturation and apparently down-regulation when exposed to high concentrations of tocotrienols. To circumvent these limitations in oral absorption of tocotrienols, investigators have developed novel prodrug derivatives and nanoparticle delivery systems that greatly enhance tocotrienol bioavailability and therapeutic responsiveness. Additional studies have also demonstrated that combined treatment of tocotrienols with other traditional chemotherapeutic agents results in a synergistic anticancer response, and this synergistic response was further enhanced when these agents were encapsulated in a nanoparticle delivery system. Taken together, these findings clarify the limitations of oral tocotrienol administration and provide novel alternative drug-delivery systems that circumvent these limitations and greatly enhance the therapeutic effectiveness of tocotrienols in the prevention and treatment of cancer.

Jiang Q. Different Roles of Tocopherols and Tocotrienols in Chemoprevention and Treatment of Prostate Cancer. Adv Nutr. 2024 Jul;15(7):100240. doi: 10.1016/j.advnut.2024.100240. Epub 2024 May 10. PMID: 38734077; PMCID: PMC11215218.

Montagnani Marelli M, Marzagalli M, Fontana F, Raimondi M, Moretti RM, Limonta P. Anticancer properties of tocotrienols: A review of cellular mechanisms and molecular targets. J Cell Physiol. 2019 Feb;234(2):1147-1164. doi: 10.1002/jcp.27075. Epub 2018 Aug 1. PMID: 30066964.