Tocotrienols

While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy.

Related Terms

  • 6-Hydroxy-2-methyl-2-phytylchroman, 6-O-carboxypropyl-alpha-tocotrienol (T3E), A-84, A HMG-CoA reductase inhibitor, alpha-T3, alpha-T3 H, alpha-tocopherol, alpha-tocopheryl, alpha-tocotrienol, alpha-tocotrienol alpha-plus gamma-complex tocotrienol, beta tocotrienol, beta-tocotrienol, carboxychromanols, carotenoids, delta tocotrienol, delta-tocotrienol, eta-tocopherols, farnesylated benzopyran, gamma tocotrienol, gamma-carotenes, gamma-oryzanol, gamma-tocopheryl, gamma-tocotrienol, gamma-tocotrienyl 2-phenylselenyl succinates, herpigon, high gamma-complex tocotrienol isoprenoid, P25-complex, palm oil, palm olein, palmolein, PalmVitee® tocotrienol, phytonutrients, phytosterols, RBO, TCT, tocochromanols, tocopherols, tocotrienol-rich fraction (TRF), tocotrienol-rich fraction (TRF25), tocotrienols, tocotrienols (PalmVitee®), tocotrienyl acetate supplements, TRF, TRF25, triterpene alcohols, vismione B, vitamin E, vitamin E acetate, vitamin E succinate, vitamin E tocotrienol (TCT), xanthones, zeta.

Background

  • Vitamin E is an essential fat-soluble nutrient that belongs to the family of tocotrienols and tocopherols. Tocotrienols are found in high concentrations in cereal grains (e.g., oat, barley, rye, and rice bran). The highest level found in crude palm oil. Commercial tocotrienols are primarily obtained from natural sources, such as palm or rice bran oil.

  • The best food sources of vitamin E are vegetable oils (sunflower and olive), nuts, seeds, and fortified cereals. Tocotrienol supplements are available in capsule and tablet form.

  • Among vitamin E compounds, tocotrienols are best known for their antioxidant, heart-protective, and anticancer effects. Tocotrienols may also have cholesterol-lowering effects. Research suggests that it is common for cancer patients to combine vitamin E (mixed tocopherols and tocotrienols) and chemotherapy.

Scientific Evidence

Uses

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Antioxidant

Tocotrienols have been studied for their antioxidant properties. However, few clinical trials have been conducted. Based on limited research, PalmVitee®, a tocotrienol- and tocopherol-enriched fraction of palm oil, demonstrated antioxidant properties in patients with cerebrovascular disease. Additional high-quality clinical studies are needed before a firm conclusion can be drawn.

Cardiac abnormalities (autonomic/hypertensive crises and cardiac instability associated with familial dysautonomia)

Familial dysautonomia (FD) is an inherited, fatal neurodegenerative disorder with symptoms of severe increases in blood pressure and cardiac instability. Patients with this condition make insufficient amounts of at least two proteins. Ingestion of tocotrienols can raise the levels of these proteins in these patients. Additional high-quality clinical studies are needed before a firm conclusion can be drawn.

Diabetes

According to limited research, intake of tocotrienols may result in a decreased risk of type 2 diabetes. Additional high-quality clinical studies are needed before a firm conclusion can be drawn.

High cholesterol

There is mixed clinical evidence on the role of tocotrienols in reducing cholesterol levels. Additional high-quality clinical studies are needed before a firm conclusion can be drawn.

*Key to grades:

Tradition

The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious and should be evaluated by a qualified health care professional.

  • Aging (prevention), Alzheimer’s disease, angiogenesis (the growth of new blood vessels from preexisting vessels), atherosclerosis (hardening of the arteries), burns (cosmetic improvement), cancer, colon cancer, hair loss (baldness), kidney failure, neuroprotection, scar healing, stroke, wound healing.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

  • For high cholesterol, 200-250 milligrams of alpha-, gamma-, or delta-tocotrienyl acetate supplements has been taken by mouth daily for 4-8 weeks. The tocotrienol-enriched fraction of palm oil (200 milligrams of PalmVitee® capsules) has been taken by mouth daily. Three milligrams per kilogram of body weight of a tocotrienol-enriched fraction has been taken by mouth for 60 days.

  • For scars, an unspecified dose of ointment has been applied twice daily for four weeks.

Children (under 18 years old)

  • There is no proven safe or effective dose for tocotrienols in children.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

  • Avoid with known allergy or hypersensitivity to sources of vitamin E, tocopherols, tocotrienols, or products containing these compounds. Skin reactions such as contact dermatitis and eczema have been reported with topical vitamin E preparations, such as ointments or vitamin E containing-deodorants.

Side Effects and Warnings

  • Tocotrienols may lower blood sugar levels. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Blood glucose levels may need to be monitored by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.

  • Tocotrienols may increase the risk of bleeding. Caution is advised in patients with bleeding disorders or those taking drugs, herbs, or supplements that may increase the risk of bleeding. Dosing adjustments may be necessary.

  • Use doses higher than 400 international units (IU) daily cautiously, as high doses may increase the risk of death.

  • Use medicinal amounts cautiously in pregnant and breastfeeding individuals, due to a lack of safety information.

  • Avoid with known allergy or hypersensitivity to sources of vitamin E, tocopherols, tocotrienols, or products containing these compounds.

Pregnancy and Breastfeeding

  • Tocotrienols are likely safe in nonallergic women when consumed in amounts generally found in foods. Use medicinal amounts cautiously in pregnant and breastfeeding women, due to a lack of safety information. Human milk was found to contain naturally occurring tocopherols and tocotrienols.

Interactions

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs

  • Tocotrienols may lower blood sugar levels. Caution is advised when using medications that may also lower blood sugar. Patients taking insulin or drugs for diabetes by mouth should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.

  • Tocotrienols may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants (blood thinners) such as warfarin (Coumadin®) or heparin, antiplatelet drugs such as clopidogrel (Plavix®), and nonsteroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®).

  • Tocotrienols may interfere with the way the body processes certain drugs using the liver’s cytochrome P450 enzyme system. As a result, the levels of these drugs may be increased or decreased in the blood and may cause increased or decreased effects or potentially serious adverse reactions. Patients using any medications should check the package insert, and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.

  • Tocotrienols may also interact with agents that affect the immune system, anticancer agents, cholesterol-lowering agents, gastrointestinal agents, nerve protection agents, statins, or weight loss agents.

Interactions with Herbs and Dietary Supplements

  • Tocotrienols may lower blood sugar levels. Caution is advised when using herbs or supplements that may also lower blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.

  • Tocotrienols may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.

  • Tocotrienols may interfere with the way the body processes certain herbs or supplements using the liver’s cytochrome P450 enzyme system. As a result, the levels of other herbs or supplements may change in the blood. It may also alter the effects that other herbs or supplements potentially may have on the P450 system.

  • Tocotrienols may also interact with anticancer agents, antioxidants, cholesterol-lowering agents, citrus flavonoids, gastrointestinal herbs and supplements, herbs and supplements that affect the immune system, nerve protection herbs and supplements, or weight loss agents.

Author Information

  • This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

References

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

  1. Brigelius-Flohe R. Vitamin E and drug metabolism. Biochem Biophys Res Commun 2003;305(3):737-740. View Abstract
  2. Choudhury N, Tan L, Truswell AS. Comparison of palmolein and olive oil: effects on plasma lipids and vitamin E in young adults. Am J Clin Nutr 1995;61(5):1043-1051. View Abstract
  3. Gold-von Simson G, Leyne M, Mull J, et al. IKBKAP mRNA in peripheral blood leukocytes: a molecular marker of gene expression and splicing in familial dysautonomia. Pediatr Res 2008;63(2):186-190. View Abstract
  4. Guthrie N, Carroll KK. Inhibition of mammary cancer by citrus flavonoids. Adv Exp Med Biol 1998;439:227-236. View Abstract
  5. Guthrie N, Gapor A, Chambers AF, et al. Inhibition of proliferation of estrogen receptor-negative MDA-MB-435 and -positive MCF-7 human breast cancer cells by palm oil tocotrienols and tamoxifen, alone and in combination. J Nutr 1997;127(3):544S-548S. View Abstract
  6. Halliwell B, Rafter J, Jenner A. Health promotion by flavonoids, tocopherols, tocotrienols, and other phenols: direct or indirect effects? Antioxidant or not? Am J Clin Nutr 2005;81(1 Suppl):268S-276S. View Abstract
  7. McAnally JA, Gupta J, Sodhani S, et al. Tocotrienols potentiate lovastatin-mediated growth suppression in vitro and in vivo. Exp Biol Med (Maywood) 2007;232(4):523-531. View Abstract
  8. Parker RA, Pearce BC, Clark RW, et al. Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. J Biol Chem 1993;268(15):11230-11238. View Abstract
  9. Raghuram TC, Rukmini C. Nutritional significance of rice bran oil. Indian J Med Res 1995;102:241-244. View Abstract
  10. Rasool AH, Yuen KH, Yusoff K, et al. Dose dependent elevation of plasma tocotrienol levels and its effect on arterial compliance, plasma total antioxidant status, and lipid profile in healthy humans supplemented with tocotrienol rich vitamin E. J Nutr Sci Vitaminol (Tokyo) 2006;52(6):473-478. View Abstract
  11. Song BL, DeBose-Boyd RA. Insig-dependent ubiquitination and degradation of 3-hydroxy-3-methylglutaryl coenzyme a reductase stimulated by delta- and gamma-tocotrienols. J Biol Chem 2006;281(35):25054-25061. View Abstract
  12. Sugano M, Koba K, Tsuji E. Health benefits of rice bran oil. Anticancer Res 1999;19(5A):3651-3657. View Abstract
  13. Wada S. Chemoprevention of tocotrienols: the mechanism of antiproliferative effects. Forum Nutr 2009;61:204-216. View Abstract
  14. Wada S, Satomi Y, Murakoshi M, et al. Tumor suppressive effects of tocotrienol in vivo and in vitro. Cancer Lett 2005;229(2):181-191. View Abstract
  15. Zingg JM. Vitamin E and mast cells. Vitam Horm 2007;76:393-418. View Abstract

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.