Tocotrienols - Tocotrienols and Radiation Countermeasures

Tocotrienols and Radiation Countermeasures

When radiation strikes, be it from warfare (which is always a threat), disaster (as in Japan’s recent earthquake and tsunami), or therapy (as in cancer), the bone marrow is the first to be compromised. Those lethally affected die immediately, whereas those who are critically affected may survive the first 30 days, and survival is predominantly dependent on the bone marrow regenerating itself. Severe side effects include acute radiation syndrome (ARS) and bone marrow failure syndrome (BMFS). If the bone marrow regenerates fast enough, new blood from the marrow will replenish arteries and veins, replacing old blood that was extremely compromised. This is true for radiation in warfare, disaster or cancer.

In the past six years, the Armed Forces Radiobiology Research Institute (AFRRI) has performed extensive research on tocotrienol —a form of vitamin E — as radiation countermeasure agent. Tocotrienols occur naturally as four distinct molecules designated α-, β-, γ- and δ-tocotrienol. Of these, δ- and γ-tocotrienol are the most effective radioactive countermeasure agents. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are the primary source of radiation-induced damage, and – as potent antioxidants – tocotrienols are effective radioprotectors, supporting the hypothesis that “strong antioxidants make strong radioprotectors”. However, amelioration of radiation lethality goes beyond tocotrienol’s antioxidant properties. δ- and γ-tocotrienol display an unambiguous stimulatory effect on hematopoietic (blood-forming) tissue, with delta-tocotrienol performing better than gamma-tocotrienol. Following total body irradiation of mice, both δ- and γ-tocotrienol regenerated blood-borne cells by increasing the total white blood cell count; only δ-tocotrienol regenerated lymphocytes. Tocotrienols almost fully restored bone marrow cellularity to normal levels following radiation, while overall cellularity in untreated controls remained depleted. In both cases, prophylactic treatment 24 hours pre-radiation was more effective than post-radiation treatment. These results suggest that tocotrienols, especially of the δ- and γ-isoforms, could be used as powerful radioprotectors in first responders to nuclear fallout areas, radiation workers, and cancer radiotherapy patients. Annatto tocotrienol is are the only source containing exclusively δ-tocotrienol (90%) and γ-tocotrienol (10%) that may be useful for radiation countermeasures, tocotrienols from rice bran contain all four: alpha, beta, gamma and delta.