PMC Collaborated Micronutrient Research

Department of the Navy - United States Marine CorpsNaval Health Research Center – Extreme Environments

PMC antioxidant micronutrient formulation decreased the levels of certain markers of oxidative damage in some 1st Tank Marines during 12-weeks of training. This study was performed in collaboration with Dr. Jim Hodgdon of the Naval Health Research Center, San Diego.

PMC Antioxidant Micronutrient Program for Biological Protection Against Combat and Non-Combat Environmental Stressors – Naval Health Research Center (NHRC), San Diego, CA and Marine Corps Systems Command, Quantico, VA

Increased oxidative stress due to enhanced production of free radicals derived from oxygen and nitrogen is involved in the initiation and progression of most acute and chronic human illnesses including mental disorders. During training, troops are exposed to extreme environmental conditions such as high altitude, extreme temperatures, and increased physical activity leading to exhaustion and muscle fatigue. It has been estimated that most personnel experience some adverse conditions during training that may be primarily related to increased oxidative damage. In combat, they additionally may be exposed to diesel fumes, hydrocarbons, solvents, explosives, blast waves, as well as to infective agents. The exposure to these agents produces extensive amounts of free radicals and significantly increases oxidative stress. Agents such as explosives and infective agents may also induce inflammation. These effects may suppress immune function thereby increasing the risk of infection, impair performance, decrease feelings of well-being, and the ability to focus and delay response to impending risks. Therefore, attenuation of the levels of oxidative damage and inflammation may be essential for reducing acute and long-term adverse consequences of environmental stressors.

Antioxidants are known to reduce oxidative damage in both animal and human studies. Therefore the use of appropriate antioxidants appears to be a rational choice to reduce these effects during training and in combat. Most human studies to date have utilized a single antioxidant such as vitamin E or beta-carotene. As expected, this design produced inconsistent results because any individual antioxidant when administered to high risk populations with a high internal oxidative environment becomes oxidized and acts as a free radical. This does not happen if the same antioxidant is taken in a multiple antioxidant preparation. In a recent prospective randomized clinical study, the PMC Optimal Health formulation reduced oxidative damage and increased immune function in normal volunteers. PMC has recently completed a randomized double-blind placebo-controlled trial that showed daily supplementation with PMC’s military formulation can reduce markers of oxidative damage in a subgroup of military personnel at the Mountain Warfare Training Center, 29 Palms, CA.

Naval Medical Center – Treating Injured Marines Returning From Iraq

PMC antioxidant micronutrient formulation increased the efficacy of standard therapy (steroids, physical therapy, vestibular rehabilitation and supportive care) over a 12-week period in Marines with mild to moderate concussive head injury returning from Iraq.

Antioxidant Micronutrients Improve Neuro-Vestibular Recovery After Concussive Blast Injuries in Combat – Naval Medical Center (NMC), San Diego, CA

U.S. Marine Corps personnel suffering mild to moderate head injuries in Iraq were transported back to the Naval Medical Center in San Diego for care. They were prospectively randomized into two groups: one received standard medical treatment including physical therapy, steroids and supportive care and the other received the same standard medical treatment in addition to consuming the PMC formulation twice daily. The treating doctors and therapists were blinded as to which Marines were receiving the antioxidants. Time points were at 4, 8 and 12 weeks and the outcome measures were sensory organization (computerized dynamic posturography), dynamic gait index, balance system scoring, dizziness handicap index, activities balance confidence, symptoms resolution, exercise tolerance and return to full duty status.

Results: There were no negative side effects from the PMC formulation. The antioxidant group had significantly higher scores on sensory organization, dynamicposturography and exercise tolerance at each study time point (P values by Students t-test). The antioxidant group also had higher scores in all the other measures.

In summary, the PMC formulation is a unique, proprietary micronutrient combination based on the highest level of antioxidant science. It has been studied under Congressional funding with federal laboratories and military institutes and has been shown to be effective against oxidative damage from several sources. The potential benefits of this strategy could positively affect individuals in many occupational settings and lays the ground work for preventive supplementation as well as micronutrient use as an adjunct to disease treatment and to improve the quality of life.

Department of the Navy - United States of AmericaNaval Medical Research Center – Blast Injury & Hyperbaric Oxygen Exposure

PMC Antioxidant Micronutrient Program for Biological Protection Against Blast Exposure and Hyperbaric Oxygen Toxicity – Naval Medical Research Center (NMRC), Silver Spring, MD and Naval Medical Center (NMC), San Diego, CA

Study 1. The majority of acute and chronic injuries to troops currently in combat are caused by improvised explosive devices of varying strengths. Blast (high energy impulse noise wave) is characterized by a sudden increase in atmospheric pressure for a short time followed by a gradual decay to ambient level. Extensive studies suggest that blast exposure produces damage by two mechanisms: 1) direct effect (energy transfer to organs), causing mechanical injury primarily to air-containing organs (lung, ear, intestinal tract), that may lead to death within a short period of time; and 2) indirect effects through generation of excessive amounts of free radicals (inorganic and organic), and release of pro-inflammatory cytokines and prostaglandins during acute inflammatory reactions. Such molecules may aggravate acute structural organ damage, increase the rate of progression of damage, reduce the rate of recovery from injuries and increase the risk of chronic diseases including mental disorders, diabetes, cancer, and heart disease. Blast exposure also reduces the baseline antioxidant levels in animal models. Therefore, the use of appropriate antioxidants appears to be one of the rational choices to reduce blast-induced initial damage to various organs, decrease the rate of progression of damage during transport to medical facilities, and may enhance the rate of recovery after standard medical interventions. Animal studies were initiated with NMC to investigate the effects of PMC’s antioxidant formula on blast injuries (survival and damage to ear, lung and brain) in 2006.

Preliminary results show that PMC Formulation prevented the rise in inducible nitric oxide synthase (iNOS) activity, a marker of inflammation, in lung tissue following a lethal dose of blast exposure in rats. This increases the production of nitric oxide which is oxidized to form peroxynitrite, a deadly form of free radical.

Study 2. Naval Special Forces may be exposed to hyperbaric oxygen continuously for several hours during training and in combat. It is well established that breathing pure oxygen generates excessive amounts of free radicals that can cause transient disorientation, feeling of dizziness, as well as increase the risk of lung injuries and infection. They can also increase the risk of chronic medical conditions long after breathing pure oxygen. Thus, the use of antioxidant micronutrients may also be an effective against hyperbaric oxygen toxicity. PMC in collaboration with NMRC has recently completed a randomized double-blind, placebo-controlled trial with a PMC formulation to test the efficacy of this formulation in an animal model of hyperbaric oxygen toxicity. These animal studies are appropriate since blast wave and hyperbaric oxygen toxicity experiments cannot be performed directly in humans.

Department of the Army - United States of AmericaUS Army Medical Institue of Chemical Defense – Chemical Warfare Protection

Mustard gas, referred to as HD (bis-(2-chloroethyl) sulfide), is a vesicant that causes blistering of the skin and mucous membranes upon contact. It is a potent alkylating agent which has been used as a chemical warfare agent in at least 18 conflicts since World War I. It has re-emerged as a potential threat to both military and civilian personnel due to an increase in terrorist activities around the globe.

HD can damage DNA, RNA, proteins and other cellular components and be lethal. The onset, type and severity of clinical symptoms depend upon the form of mustard agent, route of exposure and concentration. Inhalation of HD can damage lung, gastrointestinal tract and hematopoetic organs that can cause lethality depending upon the concentration of this agent. Exposure to high doses of HD can also damage the central nervous system causing death within a short period of time. Many of these signs, symptoms and damage resemble those produced by ionizing radiation; therefore, mustard agents have also been referred to as radiomimetic agents. The latent adverse effects of HD may include increased risk of cancer, cataracts, somatic (during your life time) and heritable (passing genetic defects from one generation to another) mutations, birth defects, and mental and developmental retardation (if fetuses are exposed).

Although promising therapies have been examined, there are no effective pharmacological countermeasures available to reduce damage when administered either before or after exposure to mustard agents. Therefore, the development of countermeasures against these chemicals has become an urgent issue, because of the increased threat of use by the terrorists against military and civilian personnel.

In order to develop an effective countermeasure, it is essential to understand the mechanisms that are involved in the initiation and progression of damage following exposure to sulfur mustard. Besides the alkylation of DNA, increased oxidative damage, and inflammation may contribute to acute and chronic damage produced by sulfur mustard. HD also depletes glutathione one of the most important intracellular antioxidants for protection against free radical damage. Therefore, supplementation with antioxidants appears to be a rational choice for reducing the damage following HD exposure. Indeed, a few studies have shown that supplementation with glutathione-elevating agents such as n-acetylcysteine or other free radical scavengers prior to exposure to HD provides a degree of protection.

The PMC antioxidant mixture will be tested for protective efficacy against dilute HD inhalation toxicity in the dilute HD embulization model The mixture will be administered orally (50, 100 and 200 mg/kg) three days before and after exposure to 0.35 mg total dose of HD. At 4 and 24 hr lung tissue will be collected for histologic (right lung) and biochemical (left lung) analyses of oxidative damage and inflammation. Biochemical analysis will be done by PMC, and histopathologic analysis will be done by Comparative Pathology Branch, USAMRICD.

NASA – Radiation Protection and Leukemia-gene Studies

PMC Antioxidant Micronutrient Program for Biological Protection Against Ionizing Radiation Damage – National Aeronautic and Space Administration (NASA), Johnson Space Center, Houston, TX

NASA has identified oxidative damage as a risk to astronaut health, and has explored countermeasures to mitigate this risk. The potential health injuries to crew members during space flight include muscle fatigue, hearing damage, and chronic diseases such as cancer, cataracts and cognitive dysfunction. Oxidative damage due to increased production of free radicals plays a critical role in initiating these injuries. Astronauts, particularly those who perform extravehicular activity (EVA), are at increased risk for these effects since they are exposed to may different sources of oxidative stress including cosmic radiation. Astronauts’ exposure to oxidative stress is expected to increase in the future because of longer space missions, and the amount of EVA work required for the completion and maintenance of the International Space Station, as well as for planetary and solar system exploration. Some studies have been performed on astronauts in Low Earth Orbit, on in-vitro cell and tissue culture models in NASA-designed microgravity-analog bioreactors and on small animals in space analogs.

At present, there are no effective countermeasures against damage produced by cosmic radiation. Developing countermeasures against radiation –induced damage is essential for successful exploration of space and planetary environments. PMC in collaboration with NASA and the Russian Academy of Sciences, has completed a pilot study in which a PMC formulation containing both dietary and endogenous antioxidants increased the survival time, by 5-6 fold in irradiated sheep receiving a lethal dose of whole-body radiation. The irradiated animals not receiving antioxidants died in 7 days after irradiation. Rabbits receiving a lethal dose of whole body radiation died in 4 hours exhibiting CNS syndromes with or without antioxidant treatment; however, the damage to the lung in rabbits receiving antioxidants before irradiation was markedly reduced in comparison to those who received no antioxidants. The large animal studies performed in Russia are appropriate since radiation experiments cannot be performed directly in humans.

PMC Antioxidant Micronutrient Program for Biological Protection Against Proton- Radiation Damage – National Aeronautic and Space Administration (NASA), Ames Research Center, Moffett Field, CA

A pilot study was carried out with female Fruit flies ( Drosophila) carrying a leukemia-type gene that increases their sensitivity for the development of tumors. Proton irradiation increased the incidence of tumors in a dose-dependent manner. The PMC antioxidant micronutrient formulation mixed with the diet (100 µg/gram of diet) before proton irradiation completely protected Drosophila against radiation-induced tumor formation (in collaboration with Dr Sharmila Bhattacharya of Ames Research Center, NASA, Moffett Field, CA).

Meharry Medical College – Parkinson’s Disease

The results of a pilot study shows that PMC antioxidant micronutrient formulation reduces the incidence of Parkinson’s disease in MPTP-rat model. This model has been extensively used to understand the mechanisms of this disease. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a contaminant in certain recreational drugs also induces Parkinson’s disease in humans. (in collaboration with Dr. Clivel Charlton of Meharry Medical College, Nashville, TN).

Henry Ford Medical Center – Reducing Toxicity for Cancer Patients During Therapy

Between March, 1998 and December 2000, 48 patients with cancer of the breast (stage 0-III) were randomized prior to radiation therapy to receive PMC formulation and follow a 10% fat diet during the course of radiation therapy (modification arm) or to the control arm (no special diet or vitamins). The PMC formulation at reduced dose was continued for one year after the completion of radiation therapy. The results presented here reflect a 4-year follow-up.PMC antioxidant micronutrient formulation did not compromise the efficacy of radiation therapy in patients with breast cancer at 4-years follow-up as feared by most radiation oncologists. There was no significant difference in toxicity between two groups. This has led to the modification in the PMC Formulation to be used during therapy, the efficacy of which will be tested. This study was performed in collaboration with Dr J. H. Kim, Professor of Radiation Oncology at the Henry Ford Hospital, Detroit, MI.

University of Montevideo, Uruguay

A pilot study showed that PMC antioxidant micronutrient formulation gradually decreased oxidative damage in normal volunteers as measured by the level of lipid peroxidation product, MDA (malondialdehyde) in the urine and plasma, and increased immune competency as measured by the lymphocyte transformation assay in the same population. This study was performed in collaboration with Professor Zulema Coppes of University of Montevideo, Uruguay.