Oxidative Stress (OS) in Post-Traumatic Stres (PTSD) & Traumatic Brain Injury (TBI) Pilot Study: An effort to naturally treat veterans and victims of PTSD and TBI with natural healing methods by addressing the underlying oxidative stress with antioxidants. Working with the premier expert on OS, Dr. Donald Armstrong, VFNH is actively pursuing a pilot study using the latest medical developments in OS to improve veterans health in aging and age related diseases, diabetes, cancers, Parkinson’s disease, Alzhiemer’s, Post Traumatic Stress, Traumatic Brain Injury, prenatal care and more.
Executive Summary
It is understandable why some veterans may be discouraged from attaining treatment that initiates adoption of prescription drugs and the stigma of “mental disability.” Such a stigma may lead to a delayed discharge, affect employment opportunities and lead to drug dependence. Post-Traumatic Stress is not necessarily a disorder, but after prolonged or substantial duress, the damage to the body’s molecular structure may lead to more severe conditions and Oxidation. As with many disease states, an “imbalance” exists between oxidized cells and free radical scavenging antioxidants. Often weakened by poor nutrition, the body’s shortage of nutrients, minerals and antioxidants can cause the damage to spread like a spot of rust in the rain. This proposal calls for modification of the PTSD Treatment Experience through management of oxidative damage and nutrient supplementation to bring the mind and body naturally into balance by addressing cellular destruction through antioxidant supplementation.
Oxidative stress (OS) has been implicated in the pathogenesis of various disease conditions, and may be a common pathogenic mechanism underlying PTSD, as the brain has comparatively greater susceptibility to oxidative damage. “It is a condition where an imbalance exists between the production of reactive oxidizing species and the body’s ability to neutralize these intermediates, resulting in cellular damage. The body has designed several physiological responses to oxidative stress including counterbalances such as enzymes, variously functionalized that effectively neutralize these damaging species. These antioxidants can be either water or lipid soluble, and are localized transiently throughout various tissues, cells and cell types. Multi-dimensional data support the role of oxidative stress in diverse psychiatric disorders. These data suggest that oxidative mechanisms may form unifying common pathogenic pathways in psychiatric disorders. (Ng F, Ber M, et al 2008 Sep) ” This proposal introduces new targets for the development of therapeutic interventions for PTSD that serve as an alternative to psychiatric prescription drugs.
Applying the latest state-of-the-art research and technology in OS we can accurately treat the patient’s nutritional deficiencies, identify, arrest and reverse the effects of post-traumatic stress using the most advanced applied clinical research.
This revolutionary opportunity proposes to bring the VA & Military Medical community to the forefront of clinical research in Oxidative Stress for clinical practice and will dramatically increase the cost-effectiveness of treatment for PTSD.
Clinical Pilot Study Approach
Volunteer veterans, spouses and or non-combat employees of the medical center are recruited by a notification describing the study which is posted on the Bulletin Board at high- traffic sites.
The goal of the study will be enrollment of 400 patients constituting 4 treatment Arms which represent 20 % African American, 20% Hispanics and 60% Caucasian. Half will be females and half will be males (see appendix 4). Volunteers will sign Informed Consent and undergo a preliminary exam to determine age, height, weight, brief medical history, food habits and smoking status, plus fill out a PTSD questionnaire. A blood sample will be drawn for a routine chemistry in the VAH Lab to confirm normality, or in unknown at- risk individuals.
Combat volunteers and normal controls will take the PTSD Self-Test (see below) that focus on irritability, fearfulness, anger, guilt, nightmares, loss of interest and depression. Those with a prior diagnosis of schizophrenia or bipolar disorder will be excluded from the study.
Study participants will be weighed on each successive Monday. Urine will be collected on-site from 8 AM to noon on Mondays and Fridays for 1 month and analyzed for free radical activity and total antioxidant reserve. The evening sample will be brought in the following morning along with the regular next day AM sample. The treatment groups will consist of a Control group (no intervention), those consuming their regular diet at home and those assigned to the Antioxidant Supplement groups. Phone calls will be made once per week to enhance retention.
Veterans and normal controls who volunteer for this proposal are screened at the participating medical facilities. The test strips will be evaluated by the Primary Investigator, Dr. Donald Armstrong, who is a polymath with over 40 years of oxidative stress experience and has written over 165 journal articles and edited 11 methods books with Humana Press and 29 on the oxidative stress bench-to-bedside approach with a series of books that are in- press or in -production covering 2010- 2014 with Springer Sciences Publishing Co on how biomarkers can be used in disease. Out-of-range results are discussed in consultation with an Internal Medicine physician at the 2 week window and at the conclusion of the study, to determine whether follow-up is necessary with more sophisticated and definitive analysis to confirm the potentially abnormal, original screening procedures. The literature indicates that 10% of the population will have abnormal tests. A random urine sample is turned in by the volunteer to our Technician.
The antioxidant supplements chosen for this pilot trial are intended to approximate a typical healthy diet. These will be purchased from Life Extension, Inc in Ft. Lauderdale, FL who markets a high level of evidence-based nutraceuticals. One capsule from each of the 4 supplements will be taken in the morning and before retiring in the evening (8 / day ) for 1 month. The technician will dispense antioxidant capsules to each volunteer and record that information. Antioxidants chosen for this unique study are as follows ”
1) Super Omega-3: EPA / DHA enteric coated (cat. no. 01484) which emulates the Mediterranean diet. It lowers the inflammatory response which is the most probable cause of sub-clinical disease that theoretically should still be asymptomatic.
2) Life Extension Mix ( cat. no. 01654 ) is a multiple -antioxidant containing vegetable extracts, water and fat soluble vitamins plus important minerals for general health.
3) Life Extension Berry Complete ( cat. no. 01406 ) is derived from colored fruits and berries and should increase the total antioxidant capacity (reserve).
4) Life Extension Mitochondrial Energy Optimizer with BioPQQ ( cat.no. 0156) should decrease free radical generation in mitochondria for optimal health.
There is precedence for giving multiple antioxidants to individuals. A similar approach was reported by Susan Machado using a nutrient “cocktail” which appeared in the May 2012 issue of Life Extension magazine. It emphasized the value of using several antioxidants for maximum effect in a sub-population with risk factors. The author suggests the multiple approach helps explain why a single dose often does not work in treatment and cites extensive publications. On her list of antioxidant compounds, 3 were specific for inflammation which we propose is the “triggering” event for OS. Dysfunctional mitochondria might also generate excess free radicals and supplement #4 was chosen for its dual effect on disease where symptoms are still sub-clinical.
Results of the study will be given to each participant at the termination of the study. Expected outcomes are that the antioxidant reserve will increase and free radical values will decrease. Statisticians and Epidemiologists on staff at the participating facility will evaluate the data. We will look for those with results above or below the mean that may or may not correlate with the physician assessment.
Supporting Technical Analysis
This innovation rises above the current state of practice by offering a mental health treatment that focuses on the underlying Oxidative pathophysiology that leads to PTSD. The pilot’s Oxidative Stress protocol is the latest technology for mental health treatment and enables deployment of simple testing procedures for prospective patients and preferred natural health management strategies that offer no side effects. This strategy takes into consideration cellular damage, nutrient and mineral depletions that would otherwise continue to contribute to greater health challenges for trauma victims to improve and normalize mental function. This is particularly important when we consider the nutrient and mineral depletions often faced by combat veterans, which when accompanied by stress often results in oxidation of human tissues affecting both physical and mental health. This pilot focuses on treatment of cellular damage that effectively resolves or lessens the effects of mental stress at the base-line molecular level.
Reliance upon forensic psychology may inherently deter potential veterans from seeking and maintaining treatment as many patients maybe daunted by treatment involving habit forming or addictive prescription drugs. Oxidative Stress protocols suggested by this pilot provide the latest clinical research applications to naturally heal the damage caused by traumatic stress.
Two new improved assays from Oxford Biomedical Research, Inc. which Dr. Armstrong, their Senior Scientific Advisor who helped develop kits which are now commercially available for analysis on a random urine sample. They measure: 1) free radical activity (see appendix 1) and 2) total antioxidant capacity (see appendix 2), using high tech dipsticks similar to ones used in swimming pools and hot tubs and microplate technology for high throughput screening (Piletska, EV et al, 2012) .
The non-invasive urine collection eliminates inconvenience to patients and normal volunteers by not having a blood draw and processing as done with plasma. The tests on urine samples are economical and can be run by a properly trained non-technical lab assistant. Results are calculated in a hand-held ” reader ” and compared to a scale indicating potential free radical damage due to underlying disease plus an estimated intake of essential dietary antioxidants. In normal individuals the balance between the two are equal but in abnormal people even without symptoms, the radical value should increase and the antioxidant value decrease ( De La Fuente, M. et al, 2009 ).
For the first time our protocol will allow field testing of a uniquely novel oxidative stress status model and provide scientific evidence that returning combat veterans can actually be at risk for PTSD by our screening profile. We propose that improvements in diet (De Costa, LA, et al, 2012) especially antioxidant rich fruits and vegetables, together with stress reduction to reduce behavioral effects, which can have a beneficial effect on PTSD to improve the veterans quality of life (Park, S., et al, 2012).
The technical simplicity of this proposal means that testing can be performed at any location. A future renewal study can evaluate veterans with Traumatic Brain Injury (McDonald, BC et al,2012) and Spinal Cord Injury ( Weaver, FM, et al, 2009 and Meyer, KS, et al, 2010; ) who develop PTSD. The relative values between normal controls and those with behavioral problems induced by combat, may have diagnostic and prognostic implications for future therapeutic intervention.
Antioxidant test strips can accurately measure antioxidant deficiencies and the presence of oxidative stress in human tissues. Using a fluid sample, (saliva, blood, urine), technologists can determine what antioxidants are depleted and indicate what antioxidant deficiencies could benefit from supplementation.
The clinical pilot timeline for study is 9 months from initiation and introduction to the medical center to completed results.
Impact & Benefits
This proposal seeks to fulfill the void of treatment options by expanding management strategies for PTSD. This may prove a major advantage for patients in need of solvency, but who have yet to identify suitable options. The impact of this study will provide a model for natural treatment of PTSD and PTSD prevention.
This pilot will provide the most up-to-date clinical research studies on Oxidative Stress for the participating center’s Medical Library. These reference tools will give care givers the applied clinical research to attain a greater understanding of the role Oxidative Stress plays in a series of illnesses and offer alternative treatment strategies for natural healing of common diseases in including atherosclerosis, chronic inflammatory disease, chronic renal failure, glaucoma, diabetes, cancer and other disease.
Furthermore, this treatment strategy may overwhelmingly reduce the cost for treatment of PTSD. OS treatment is an attractive option for patients providing a cost-effective alternative to expensive, potentially habit forming or addictive prescription psychiatric medication.
This strategy provides a more “attractive” solution to participants who prefer to engage in non-invasive, non-prescription drug treatment and help create a greater understanding of Oxidative Stress as it relates to mental health. The results of this pilot may have a significant impact on retaining. By focusing on the underlying cellular oxidation related to mental perturbations, we can work toward removing the damaging and deterring stigma of PTSD and encourage patients to seek the most advanced treatment available through the VA and military medical facilities, thereby retaining and ultimately healing more patients with no adverse side effects.
Support from the Medical Facility
For this clinical research pilot, support, patients and medical employees of the participating center will be needed. A Staff Psychiatrist, Statistician & Epidemiologist are requested to assist with the program. Publications for circulation will be provided to the hospital to identify participants and to educate the staff and patients on this revolutionary study and request participation.
Rough Order of Magnitude
Approximate funding for the following is requested:
Test kits are $ 165 + $ 400 for a 100 specimen / kit x 4 = $ 2,260.
The volunteer stipend for participation is $10 per subject per day = $80,000.
Life Extension antioxidant Omega-3 supplement = $168
Life Extension antioxidant Mix supplement = $608
Life Extension antioxidant Berry Complete supplement = $312
Life Extension antioxidant Mitochondrial Energy Optimizer supplement = $504
Oxidative Stress books by Scientific Advisor to place in VA libraries = $ 1,500
* these books will become the property of the medical center Library
Personnel
Project Directors & Assistant to Scientific Advisors: TBD = $13,000
Scientific Advisor : Donald Armstrong, EdD, PhD, DSc
= $ 20, 000 + $2000 for OSA overhead = $22, 000
** includes screening initial and follow-up results, calls to physicians, writing reports, discussing results with volunteers, preparing continuation grants and conducting an electronic search for new technology and presenting Seminars
Non-technical ( 50% FTE ) : $7,500 for maintaining files, recording log-in data, collecting the PTS Self-Test and dispensing antioxidant capsules
Equipment :Dedicated labtop computer = $ 2500
Printer = $ 425
Supplies = $250
Data mining applications for tracking and reporting purposes and
6 months hosting by Onstaff Tech, Ocala, FL = $ 8360
Travel for Scientific Advisor & Assistant= TBD
References:
De La Fuente, M and Miguel, J., Curr Pharm Design 2009 ; 15: 3003-3026
De Costa, LA, et al, Ann Nutr Metab, 2012 ; suppl 3: 27-36
McDonald, BC, et al, Brain Imaging Behav, 2012, May18, Epub ahead of print
Meyer, KS, et al, Psychiatr Clin North Am, 2010 ; 33: 783-796
Park, s, et al, Psychiatry Res, 2012 ; May 15, Epub ahead of print
Piletska, EV, et al, Arch Chem, 2012 ; Jan 17, Epub ahead of print
Richards, RS, et al, Med Hypotheses, 2011; 77: 605-609
Weaver, FM, et al, Arch Phys Med Rehabil, 2009 ; 90: 517-521
Ng F, Ber M, Dean O, Bush A. Int. J Neuropsychopharmacol 2008 Sep;11(6):851-76.
View Other Publications by Dr. Donald Armstrong