TOCOTRIENOLS AND IKAP – WHAT WE HAVE DISCOVERED:
The observation that despite the presence of the FD-causing mutation in the IKBKAP gene, FD-derived cells produce a small amount of the functional IKAP protein encoded by this gene, prompted us to begin a high throughput screening program aimed at identifying compounds capable of increasing the amount of IKAP RNA and protein produced in FD-derived cells. We discovered that the treatment of FD-derived cells with tocotrienols, a form of vitamin E, results in the increased production of functional IKAP. Currently, the most effective tocotrienol, tested by the FD Laboratory, is a product by Health Pro, called Tocotrienol-125. Several months later, we discovered that epigallocatechin gallate (EGCG), a compound present in green tea, also facilitates the production of the functional IKAP protein and that the treatment of FD-derived cells with the combination of EGCG and tocotrienols results in a synergistic production of the IKAP protein.
Publication: Tocotrienols induce IKBKAP expression: a possible therapy for familial dysautonomia (PDF)
TOCOTRIENOLS REVERSE IKAP AND MAO DEFICIENCIES – WHAT WE HAVE DISCOVERED:
Because of the FD mutation, individuals with FD make much less IKAP protein than they need for good health and autonomic stability. We also observed that they produce below normal levels of monoamine oxidase (MAO), an enzyme that breaks down biogenic amines (e.g., epinephrine, dopamine) and dietary monoamines (e.g., tyramine). High levels of epinephrine, dopamine or tyramine in an FD body can cause hypertensive crises, so this discovery was extremely important as it identified the triggers of these crises. Tyramine is present in many foods and the fact that an individual with FD has low MAO levels means that tyramine-containing foods must be avoided. A study of FD patients ingesting tocotrienols revealed that the tocotrienols mediate an increase in the level of IKAP as well as MAO.
Publication: Tocotrienols reverse IKAP and monoamine oxidase deficiencies in familial dysautonomia (PDF)
TOCOTRIENOLS IMPROVE AUTONOMIC STABILITY – WHAT WE HAVE DISCOVERED:
As ingestion of tocotrienols was observed to increase IKAP and MAO levels in FD patients (2005), we examined individuals with FD to study the impact of the tocotrienol ingestion on cardiac function and the frequency of hypertensive crises. Individuals with FD typically did not have an increase in pulse rate or a shortening of the QT interval after exercise. Tocotrienol administration was found to reverse these cardiac abnormalities in most of the FD patients studied. The tocotrienol administration also resulted in a significant decrease in the number of hypertensive crises occurring in the individuals, with about 40% of these patients no longer experiencing any crisis events. These results clearly demonstrated that tocotrienol ingestion improves autonomic stability in FD patients.
Publication: Can the Therapeutic Efficacy of Tocotrienols in Neurodegenerative Familial Dysautonomia Patients Be Measured Clinically? (PDF)
TOCOTRIENOL ADMINISTRATION IMPROVES AUTONOMIC STABILITY DURING SURGERY – WHAT WE HAVE DISCOVERED:
The scientific literature is replete with publications that document the extreme cardiovascular and autonomic instability observed in FD patients undergoing surgical procedures. Upon observing this instability in FD patients on the day of surgery, surgical teams have at times refused to perform surgical procedures on these patients. A planned surgical procedure on an FD patient who was ingesting tocotrienols and EGCG-containing green tea extract provided an opportunity to characterize the impact of these IKAP-enhancing compounds on cardiac and autonomic stability during and after surgery. As this patient had previously undergone a surgical procedure prior to beginning tocotrienol and green tea extract ingestion, a comparative analysis of this patient’s response to the two surgical procedures was performed. This analysis clearly revealed that the uninterrupted ingestion of the tocotrienols and green tea extract resulted in a dramatic improvement in the cardiac and autonomic stability of this patient.
This study, which was published in the journal Anesthesiology, recommends the uninterrupted administration of tocotrienols and green tea extract to FD patients who are scheduled to undergo a surgical procedure. While ingestion of the tocopherol form of vitamin E has been reported to impair the blood clotting process, no such effect of the related tocotrienols was observed in this patient. A study of the blood clotting efficiency in a group of FD patients ingesting 600 mg of tocotrienols daily revealed no reduction in the blood clotting response (manuscript in preparation).
Publication: Case Scenario: Perioperative Administration of Tocotrienols and Green Tea Extract in a Child with Familial Dysautonomia (PDF)
THE HEALTH BENEFITS OF TOCOTRIENOL ADMINISTRATION ON INDIVIDUALS WITH FD HAS ALSO BEEN REPORTED BY OTHERS – SEE:
1) Gold-von Simson, G, Axelrod, FB (2006) Familial dysautonomia: update and recent advances. Curr Probl Pediatr Adolesc Health Care 36:218-237.
2) D’Amico RA, Axelrod, FB (2011) http://emedicine.medscape.com/article/1200921-treatment