Tocotrienols Prevent DNA Damage and Combat Aging

Tocotrienols are potent forms of vitamin E that help block DNA damage associated with aging.^1-4

DNA damage is a major degenerative factor.

Human studies demonstrate that tocotrienols help maintain youthful brain, bone and arterial structure, along with healthy immune function.

A review concluded that tocotrienol supplementation in middle-aged and elderly people can markedly reduce age-associated DNA damage.³

The Most Potent Form of Vitamin E

Tocotrienols are emerging as interesting and complex members of the vitamin E family.

Tocotrienols come in four varieties:⁵

• Alpha-tocotrienol
• Beta-tocotrienol
• Gamma-tocotrienol
• Delta-tocotrienol

These forms of vitamin E are different from “regular” forms of vitamin E that are called tocopherols.⁵

Tocotrienols generally have higher potency than tocopherols, and they act on a wider range of targets.

For example, alpha-tocotrienol prevents neuro-degeneration at very small concentrations.⁵

Aging and DNA Damage Prevention

The unique structure and potency of tocotrienols make them valuable for defending aging tissues. A primary tocotrienol mechanism is the ability to protect against DNA damage, an underlying factor in most aging processes.¹

In a randomized, clinical trial, middle-aged and older adults took either 160 mg of mixed tocotrienols/tocopherols or a placebo for six months. By three months, there was a significant reduction in DNA damage, a benefit that persisted through the six-month mark.¹

The ability to reduce DNA damage shows that tocotrienols can help slow aging at the cellular level.³

Because DNA damage contributes to cellular senescence, supplementing with tocotrienols represents a unique way to delay age-related decline.

Human studies have shown that tocotrienols can help lower the risk of cardiovascular disease, support bone health, and preserve cognitive function. These benefits make this unique form of vitamin E an interesting player in the fight against premature aging and disease.^3,5-10

Cardiovascular Disease Risk Reduction

DNA damage contributes to the aging of blood vessels—a major risk factor for heart attacks and strokes.^11-13

High levels of cholesterol and triglycerides contribute to plaque buildup on artery walls that causes arteries to become hard and stiff. This restricts blood flow and increases the risk of cardiovascular complications.

Tocotrienols act in numerous ways to lower the risk of cardiovascular disease. This was shown in a study of people on chronic hemodialysis for kidney failure. Kidney failure patients have an extremely high risk of cardiovascular disease.

The patients took either a daily dose of 180 mg of tocotrienols plus 40 mg of tocopherols (traditional vitamin E) or a placebo for 16 weeks. In the supplemented group, by week 12, triglyceride levels had declined by a significant 33 mg/dL and then dropped by 36 mg/dL at 16 weeks. No change was found in the placebo group.¹⁴

Tocotrienols have also been shown to decrease arterial stiffness. When patients took 100 mg/day and 200 mg/day of tocotrienols, they experienced significant reductions in two measures of arterial stiffness after just two months, substantially reducing cardiovascular risk.¹⁵

Boosting the Aging Immune System

DNA damage directly contributes to immune senescence, or a dysfunctional immune system.^16,17

Immune senescence increases an older person’s risk of infections, while also increasing the likelihood of an inappropriate immune response that can lead to excessive inflammation and autoimmune disorders.¹⁸

Another consequence of immune senescence is poor response to vaccines. This puts lives at risk because we rely on vaccines to prevent viral infections.

A randomized, placebo-controlled trial showed that taking 400 mg of mixed tocotrienols/tocopherols daily significantly enhanced the immune response to a test dose of a vaccine. This was seen through increased production of protective interferon gamma, increased production of antibodies following the vaccine, and a reduction in immune-dampening IL-6.¹⁹

These results suggest that tocotrienol/tocopherol supplementation can reverse major components of immune senescence, lowering the risk for preventable infections and malignancies.

Neuroprotection

DNA damage is one of the earliest detectable events in neurodegenerative diseases like Alzheimer’s, Parkinson’s, and ALS (amyotrophic lateral sclerosis) also known as Lou Gehrig’s disease. The white matter lesions associated with dementia are also DNA damage related.^20,21

In one study, adults with white matter lesions were randomly assigned to take either 200 mg of mixed tocotrienols or a placebo twice daily for two years. While the lesions grew significantly in placebo recipients during that time, they remained stable in supplemented people. This demonstrates the ability of tocotrienols to help slow the progression of the disease.²²

Animal studies have also shown that tocotrienol supplementation led to improved learning and memory as a result of reduced DNA damage.²

Better Bone Health

DNA damage in bone tissue promotes bone mineral loss, or osteoporosis, by elevating inflammatory markers and reducing the numbers of bone-forming cells.^23,24

Animal studies have shown that tocotrienols protect bone tissue. These benefits were confirmed by a recent study of postmenopausal women (a group at high risk for osteoporosis).

This clinical trial showed that 12 weeks of supplementation with 430 mg/day or 860 mg/day of mixed tocotrienols decreased the excessive bone breakdown seen in osteoporosis and improved healthy bone turnover, compared with a placebo group.²⁵ Among the mechanisms were reductions in inflammation which, in turn, suppressed the aggressive bone resorption that typifies osteoporosis.

Anti-Aging Impact

Tocotrienols are complex nutrients with numerous interactions in cells and tissues.

This broad spectrum of actions means that tocotrienols can inhibit an array of unhealthy, destructive processes, reducing their negative impacts while potentially creating positive changes as well.

The following are six features of tocotrienols that contribute to their anti-aging properties:

• Tocotrienols reduce oxidative stress . Tocotrienols are potent antioxidants that protect against chemical- and radiation-induced DNA damage.^1,2,26-28
• Tocotrienols reduce the activity of HMG-CoA Reductase . This enzyme participates in chemical reactions that play a role in cholesterol production inside the body, in cancer, and in osteoporosis.^8,28-30
• Tocotrienols enhance immune function . They elevate production of signaling molecules that recruit immune cells and instruct them in their duties, as well as interferon-gamma, a signaling molecule that enhances anti-tumor surveillance.³¹
• Tocotrienols reduce inflammation. They act by suppressing major pro-inflammatory signaling pathways, including NF-kappaB, called the “master inflammation regulator.”⁸
• Tocotrienols reduce unwanted new blood vessel formulation. This is an important way to fight cancer (which needs new vessels for nutrition) and cardiovascular disease (in which tiny, new blood vessels that grow inside of atherosclerotic plaques contribute to the growth of those plaques).³² Tocotrienols fight the kind of new blood vessel formation that may contribute to cancer and heart disease.^10,33
• Tocotrienols boost mitochondrial energy production . This property has value in energizing heart and brain tissues during aging.³⁴

Summary

DNA damage is a common underlying factor in numerous age-related disorders.

Studies show that tocotrienols can fight DNA damage and slow the aging process in tissues throughout the body.

In human studies, tocotrienols have now demonstrated benefits in regard to DNA-damage-related aging, heart disease, immune regulation, neuroprotection, and bone health.

Formulations of mixed tocotrienols are available as supplements for those seeking this age-decelerating nutrient.

If you have any questions on the scientific content of this article, please call a Life Extension^® Wellness Specialist at 1-866-864-3027.

References

1. Chin SF, Hamid NA, Latiff AA, et al. Reduction of DNA damage in older healthy adults by Tri E Tocotrienol supplementation. Nutrition. 2008;24(1):1-10.
2. Taridi NM, Abd Rani N, Abd Latiff A, et al. Tocotrienol rich fraction reverses age-related deficits in spatial learning and memory in aged rats. Lipids. 2014;49(9):855-69.
3. Georgousopoulou EN, Panagiotakos DB, Mellor DD, et al. Tocotrienols, health and ageing: A systematic review. Maturitas. 2017;95:55-60.
4. Pathak R, Bachri A, Ghosh SP, et al. The Vitamin E Analog Gamma-Tocotrienol (GT3) Suppresses Radiation-Induced Cytogenetic Damage. Pharm Res. 2016;33(9):2117-25.
5. Sen CK, Khanna S, Rink C, et al. Tocotrienols: the emerging face of natural vitamin E. Vitam Horm. 2007;76:203-61.
6. Ahsan H, Ahad A, Iqbal J, et al. Pharmacological potential of tocotrienols: a review. Nutr Metab (Lond). 2014;11(1):52.
7. Catalgol B, Batirel S, Ozer NK. Cellular protection and therapeutic potential of tocotrienols. Curr Pharm Des. 2011;17(21):2215-20.
8. Frank J, Chin XW, Schrader C, et al. Do tocotrienols have potential as neuroprotective dietary factors? Ageing Res Rev. 2012;11(1):163-80.
9. Rondanelli M, Faliva MA, Peroni G, et al. Focus on Pivotal Role of Dietary Intake (Diet and Supplement) and Blood Levels of Tocopherols and Tocotrienols in Obtaining Successful Aging. Int J Mol Sci. 2015;16(10):23227-49.
10. Wada S. Chemoprevention of tocotrienols: the mechanism of antiproliferative effects. Forum Nutr. 2009;61:204-16.
11. Li P, Hu X, Gan Y, et al. Mechanistic insight into DNA damage and repair in ischemic stroke: exploiting the base excision repair pathway as a model of neuroprotection. Antioxid Redox Signal. 2011;14(10):1905-18.
12. Bautista-Nino PK, Portilla-Fernandez E, Vaughan DE, et al. DNA Damage: A Main Determinant of Vascular Aging. Int J Mol Sci. 2016;17(5).
13. Pourrajab F, Vakili Zarch A, Hekmatimoghaddam S, et al. The master switchers in the aging of cardiovascular system, reverse senescence by microRNA signatures; as highly conserved molecules. Prog Biophys Mol Biol. 2015;119(2):111-28.
14. Daud ZA, Tubie B, Sheyman M, et al. Vitamin E tocotrienol supplementation improves lipid profiles in chronic hemodialysis patients. Vasc Health Risk Manag. 2013;9:747-61.
15. Rasool AH, Rahman AR, Yuen KH, 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):1212-7.
16. Picerno I, Chirico C, Condello S, et al. Homocysteine induces DNA damage and alterations in proliferative capacity of T-lymphocytes: a model for immunosenescence? Biogerontology. 2007;8(2):111-9.
17. Ross OA, Hyland P, Curran MD, et al. Mitochondrial DNA damage in lymphocytes: a role in immunosenescence? Exp Gerontol. 2002;37(2-3):329-40.
18. Stahl EC, Brown BN. Cell Therapy Strategies to Combat Immunosenescence. Organogenesis. 2015;11(4):159-72.
19. Mahalingam D, Radhakrishnan AK, Amom Z, et al. Effects of supplementation with tocotrienol-rich fraction on immune response to tetanus toxoid immunization in normal healthy volunteers. Eur J Clin Nutr. 2011;65(1):63-9.
20. Al-Mashhadi S, Simpson JE, Heath PR, et al. Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain. Brain Pathol. 2015;25(5):565-74.
21. Coppede F, Migliore L. DNA damage in neurodegenerative diseases. Mutat Res. 2015;776:84-97.
22. Gopalan Y, Shuaib IL, Magosso E, et al. Clinical investigation of the protective effects of palm vitamin E tocotrienols on brain white matter. Stroke. 2014;45(5):1422-8.
23. Chen Q, Liu K, Robinson AR, et al. DNA damage drives accelerated bone aging via an NF-kappaB-dependent mechanism. J Bone Miner Res. 2013;28(5):1214-28.
24. Kim HN, Chang J, Shao L, et al. DNA damage and senescence in osteoprogenitors expressing Osx1 may cause their decrease with age. Aging Cell. 2017;16(4):693-703.
25. Shen CL, Yang S, Tomison MD, et al. Tocotrienol supplementation suppressed bone resorption and oxidative stress in postmenopausal osteopenic women: a 12-week randomized double-blinded placebo-controlled trial. Osteoporos Int. 2018;29(4):881-91.
26. Osakada F, Hashino A, Kume T, et al. Alpha-tocotrienol provides the most potent neuroprotection among vitamin E analogs on cultured striatal neurons. Neuropharmacology. 2004;47(6):904-15.
27. Shrader WD, Amagata A, Barnes A, et al. alpha-Tocotrienol quinone modulates oxidative stress response and the biochemistry of aging. Bioorg Med Chem Lett. 2011;21(12):3693-8.
28. Schaffer S, Muller WE, Eckert GP. Tocotrienols: constitutional effects in aging and disease. J Nutr. 2005;135(2):151-4.
29. Deng L, Ding Y, Peng Y, et al. gamma-Tocotrienol protects against ovariectomy-induced bone loss via mevalonate pathway as HMG-CoA reductase inhibitor. Bone. 2014;67:200-7.
30. Yeganehjoo H, DeBose-Boyd R, McFarlin BK, et al. Synergistic Impact of d-delta-Tocotrienol and Geranylgeraniol on the Growth and HMG CoA Reductase of Human DU145 Prostate Carcinoma Cells. Nutr Cancer. 2017;69(4):682-91.
31. Ren Z, Pae M, Dao MC, et al. Dietary supplementation with tocotrienols enhances immune function in C57BL/6 mice. J Nutr. 2010;140(7):1335-41.
32. Zhu L, Fang L. AIBP: A Novel Molecule at the Interface of Cholesterol Transport, Angiogenesis, and Atherosclerosis. Methodist Debakey Cardiovasc J. 2015;11(3):160-5.
33. Eitsuka T, Tatewaki N, Nishida H, et al. Synergistic Anticancer Effect of Tocotrienol Combined with Chemotherapeutic Agents or Dietary Components: A Review. Int J Mol Sci. 2016;17(10).
34. Schloesser A, Esatbeyoglu T, Piegholdt S, et al. Dietary Tocotrienol/gamma-Cyclodextrin Complex Increases Mitochondrial Membrane Potential and ATP Concentrations in the Brains of Aged Mice. Oxid Med Cell Longev. 2015;2015:789710.