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Haase G.M.,University of Colorado at Denver | Prasad K.N.,Premier Micronutrient Corporation | Cole W.C.,Premier Micronutrient Corporation | Baggett-Strehlau J.M.,Audiology and Hearing Health PC | Wyatt S.E.,EAR Foundation
American Journal of Otolaryngology - Head and Neck Medicine and Surgery | Year: 2011

Purpose: Although auditory disorders are complex conditions, device-related modalities dominate current treatment. However, dysfunction from the central cortex to the inner ear apparatus is increasingly thought to be related to biochemical pathway abnormalities and to free radical-induced oxidative damage and chronic inflammation. Therefore, considering appropriate biologic therapy as an adjunct to standard care against these damaging factors may provide rational expansion of treatment options for otolaryngologists and audiologists. Methods: This review outlines the biologic concepts related to some auditory and vestibular conditions and details the current rationale for utilizing antioxidants for a spectrum of hearing disorders. The strategy is based on the authors' collective experience in antioxidant science and supported with published research, pilot animal data and preliminary clinical observations. Results: A comprehensive micronutrient approach was developed to exploit these pathways, and demonstrated safety and efficacy against oxidative damage and inflammation and clinically relevant neuroprotection. Cooperative research with Department of Defense institutions used prospective, randomized designs to show (1) reduction in oxidative damage measured in plasma and urine over six months, (2) protection against oxidative damage during 12 weeks of intense military training, (3) protection against inflammation after total body blast exposure (rodents), (4) strong neuroprotection against chemically-induced Parkinson's disease (rodents), (5) nerve VIII function improvement after concussive head injury in military personnel, and (6) tinnitus improvement in majority of patients after 90-day evaluation. Conclusion: This systematic review of biologic strategies against hearing disorders combined with new animal and human observations may provide a rational basis for expanding current practice paradigms. © 2011 Elsevier Inc.


Haase G.M.,Aurora University | Haase G.M.,Premier Micronutrient Corporation | Prasad K.N.,Premier Micronutrient Corporation
Otology and Neurotology | Year: 2016

Importance: Excess free radical-induced oxidative stress and inflammatory processes are increasingly recognized as causative factors in hearing and balance disorders. Antioxidant micronutrients neutralize free radicals and, at adequate doses, reduce inflammation and demonstrate benefits in animal models and human trials. Therefore, it is reasonable to expect that biomarkers of oxidative damage and inflammation are appropriate correlative biological outcome parameters in clinical hearing intervention studies. Objective: To provide the otology investigator a selected panel of biomarkers from the large universe of available tests that can be used as reasonable secondary endpoints in hearing and balance research. Background Setting: The tenets of antioxidant science dictate that there are a great variety of free radicals and that they impact different cellular targets. They also demonstrate varying functions in different cellular environments. In addition, oxidative stress and inflammation may cause direct injury to tissues, cell membrane lipids, proteins and mitochondrial, and nuclear DNA. To accommodate these many pathways, the useful categories of potential biomarkers become extensive. The degree of injury is also reflected by separate markers of inflammation and measures of antioxidant levels. Therefore, to provide a reliable indication of oxidative damage, inflammation and antioxidant level, it is necessary to determine a broad spectrum of lipid peroxidation markers, adducts of DNA, oxidation levels of proteins and pro-inflammatory cytokines. Conclusion: This report highlights some of the most clinically relevant and well-studied biomarkers in each category of tissue damage. It also includes those markers with which the authors have had direct positive clinical experience. The outcome from these studies is intended to provide a list of adjunctive measures that can be recommended as a relevant biomarker panel in hearing disorder clinical trials. Copyright © 2016 Otology & Neurotology, Inc.


Prasad K.N.,Premier Micronutrient Corporation | Bondy S.C.,University of California at Irvine
Brain Research | Year: 2015

Post-traumatic stress disorder (PTSD) is a complex mental disorder with psychological and emotional components, caused by exposure to single or repeated extreme traumatic events found in war, terrorist attacks, natural or man-caused disasters, and by violent personal assaults and accidents. Mild traumatic brain injury (TBI) occurs when the brain is violently rocked back and forth within the skull following a blow to the head or neck as in contact sports, or when in close proximity to a blast pressure wave following detonation of explosives in the battlefield. Penetrating TBI occurs when an object penetrates the skull and damages the brain, and is caused by vehicle crashes, gunshot wound to the head, and exposure to solid fragments in the proximity of explosions, and other combat-related head injuries. Despite clinical studies and improved understanding of the mechanisms of cellular damage, prevention and treatment strategies for patients with PTSD and TBI remain unsatisfactory. To develop an improved plan for treating and impeding progression of PTSD and TBI, it is important to identify underlying biochemical changes that may play key role in the initiation and progression of these disorders. This review identifies three common biochemical events, namely oxidative stress, chronic inflammation and excitotoxicity that participate in the initiation and progression of these conditions. While these features are separately discussed, in many instances, they overlap. This review also addresses the goal of developing novel treatments and drug regimens, aimed at combating this triad of events common to, and underlying, injury to the brain. © 2014 Elsevier B.V.


Prasad K.N.,Premier Micronutrient Corporation | Bondy S.C.,University of California at Irvine
Current Aging Science | Year: 2013

Recently the relationship between oxidative stress and aging has been brought into question. It has been suggested that while oxidative events may play a role in the progression of age-related pathologies, it is not relevant to aging processes not involving specific diseases associated with senescence. The evidence in support of this concept is largely based on studies with the roundworm, Caenorhabditis elegans (C. elegans) that has been extensively used as a model system to study aging. This commentary evaluates data derived from C. elegans and documents that the preponderance of evidence from this species supports the role of pro-oxidant events as being a significant contributor to normal aging. Possible reasons for some anomalous findings conflicting with this concept, are discussed. © 2013 Bentham Science Publishers.


Prasad K.N.,Premier Micronutrient Corporation | Bondy S.C.,University of California at Irvine
Current Aging Science | Year: 2014

A link between Alzheimer's disease (AD) and an excess presence of oxidant free radicals in the brain has frequently been reported. It is generally assumed that such oxidative stress and related cellular damage is caused by inflammatory changes in the brain and is consequent to amyloid deposition. This review makes the argument that elevated oxidative stress in AD is an early causal event in the initiation and advancement of this disease. Oxidative stress can be decreased by enhancing antioxidant enzymes through activation of the cytoplasmic transcriptional factor (Nrf2)/ARE (antioxidant response element) pathway, and by dietary and endogenous antioxidant chemicals. Reduction in the binding ability of Nrf2 to ARE lowers antioxidant enzyme levels. Decreased levels of Nrf2 and augmentation of oxidative stress in AD suggest that the ROS-dependent mechanism of activating the Nrf2/ARE pathway has become unresponsive. A combination of agents that can either activate the Nrf2-ARE pathway by ROS-independent mechanisms, or by acting directly as antioxidant chemicals, may be necessary to reduce oxidative stress in AD. Earlier shortcomings of using individual antioxidants may be due to consideration of antioxidants as pharmacological agents, ignoring the fact that individual antioxidants can be transmuted in the highly oxidant milieu that is present in AD. Interactions between various cellular compartments may require simultaneous examination of more than one agent. The clinical utility of such a more integrative method can reveal interactive effects such as those found in nutritional research and this can compensate for any mechanistic shortcomings of simultaneous testing of more than a single agent. © 2014 Bentham Science Publishers.


Prasad K.N.,Premier Micronutrient Corporation
NATO Science for Peace and Security Series A: Chemistry and Biology | Year: 2013

There are two types of radiological weapon, "dirty bomb," and nuclear weapon (atom bomb). A dirty bomb can be made from one or more commercially available radioactive isotopes and it can be detonated using a conventional explosive, whereas an atom bomb consists of fissionable element, and it requires complex procedures for detonation. Explosion of a radiological weapon can cause a few injuries to mass casualties, depending upon the type of radiological weapon, and can increase the chronic health risks among survivors. Bio-Shield refers to chemicals or biologics that can prevent or mitigate radiation injury when administered before and/or after irradiation. During past decades, several radiation preventive and mitigating agents been identified. They can be grouped into following categories: (a) chemicals not approved by the FDA, (b) drugs approved by the FDA for other conditions, (c) certain biologics approved by the FDA, and (d) antioxidants and herbs not requiring FDA approval. An effective bio-shield that can be recommended to humans must satisfy the following three criteria: (1) chemicals or biologics should prevent and/or mitigate radiation damage in the laboratory experiments when administered before and/or after irradiation; (2) they should show at least some evidence that they can prevent or mitigate radiation damage in humans; and (3) they at radiation preventive or radiation mitigating doses must be safe in human when administered on a short- or long-term basis. Published data show that most radiation preventing and mitigating chemicals, drugs or herbs satisfy only the first criterion of an effective bio-shield, whereas antioxidants satisfy all three. © 2013 Springer Science+Business Media Dordrecht.


Prasad K.N.,Premier Micronutrient Corporation
Journal of the American College of Nutrition | Year: 2016

Despite extensive studies in cancer prevention, the incidence of cancer is increasing. We review studies that have identified several biochemical and genetic defects as well as potential carcinogens in the diet, environmental factors, and lifestyle-related habits. Two of the biochemical abnormalities increased oxidative stress and chronic inflammation, and chronic exposure to carcinogens and mutagens play a significant role in the initiation of multistage carcinogenesis. Therefore, attenuation of these biochemical defects may be useful in reducing the incidence of cancer. Activation of the transcriptional factor called nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which enhances the levels of antioxidant enzymes and phase-2-detoxifying enzymes by complex mechanisms, may be one of the ways to reduce oxidative stress and chronic inflammation. Antioxidant enzymes destroy free radicals by catalysis, whereas phase-2-detoxifying enzymes remove potential carcinogens by converting them to harmless compounds for elimination from the body. However, increasing the levels of antioxidant enzymes by activating Nrf2 may not be sufficient to decrease oxidative stress and chronic inflammation optimally, because antioxidant chemicals, which are decreased in a high oxidative environment, must also be elevated. This review discusses the regulation of activation of Nrf2 and proposes a hypothesis that an elevation of the levels of antioxidant enzymes and dietary and endogenous antioxidant chemicals simultaneously may reduce the incidence of cancer by decreasing oxidative stress and chronic inflammation. The levels of antioxidant chemicals can be increased by supplementation, but increasing the levels of antioxidant enzymes requires activation of Nrf2 by reactive oxygen species (ROS)-dependent and-independent mechanisms. Several phytochemicals and antioxidant chemicals that activate Nrf2 have been identified. This review also describes clinical studies on antioxidants in cancer prevention that have produced inconsistent results. It discusses the possible reasons for the inconsistent results and proposes criteria that should be included in the experimental designs of future clinical studies to obtain consistent results. Key teaching points: •Reducing oxidative stress and chronic inflammation optimally requires an elevation of the levels of antioxidant enzymes and phase-2-detoxifying enzymes as well as dietary and endogenous antioxidant chemicals. •How the levels of antioxidant enzymes and phase-2-detoxifying enzymes are regulated by a nuclear transcriptional factor Nrf2. •How the activation and transcription of Nrf2 is regulated. •Identification of antioxidants that activate Nrf2 by ROS-dependent and-independent mechanisms, those that destroy free radicals by scavenging, and those that exhibit both functions. •Possible reasons for the inconsistent results produced by the previous clinical studies on antioxidants in cancer prevention. •The criteria that should be included in the experimental designs of future clinical studies on antioxidants in cancer prevention in high-risk populations to obtain consistent results. © 2015, American College of Nutrition Published by Taylor & Francis Group, LLC.


Trademark
Premier Micronutrient Corporation | Date: 2013-02-15

Nutritionally fortified beverages.


Trademark
Premier Micronutrient Corporation | Date: 2013-02-21

Nutritionally fortified beverages.


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