1 Department of Physiology & Pharmacology, Wake Forest University School Of Medicine, Winston-Salem, NC and Department of Psychiatry, University of Florida School of Medicine, Gainesville, FLorida, USA. 2 Chang Jung Christian University, Taiwan, Republic of China 3 Clinical Neuroscience & Population Genetics, Ministry of Science, Israel 4 Department of Molecular Nutrition and Genetics, LifeGen, Inc. La Jolla, CA 5 Department of Clinical Neurology and Nutrition, Path Research Foundation, New York, NY 6 Department of Nutrigenomics, Synaptamine, Inc. San Antonio, TX 7 Department of Research, Comprehensive Pain Clinic of Modesto, Modesto, CA 8 Department of Rehabilitative Medicine, University of California Medical School, Davis, CA 9 Department of Neurological Surgery, Weill Cornell Medical College, NY 10 Department of Orthopedic Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 11 Boston University School of Medicine and VA Healthcare System, Boston, MA

Since 1990, researchers have proposed that genetic variants of dopaminergic genes and other "reward genes" are important common determinants of Reward Deficiency Syndrome (RDS). RDS refers to the breakdown of a cascade of neurotransmitters in the brain in which one reaction triggers another - the reward cascade - and resultant aberrant conduct. Association studies have amassed strong evidence implicating the D (2) dopamine receptor (DRD2) gene in harmful conditions such as alcoholism, and the DRD2 gene also has been found to be involved in other substance use disorders including cocaine, nicotine, and opioid dependence, as well as obesity. Brain dopamine has been implicated as the so-called "anti-stress molecule." The present study investigated anti-anxiety effects of Synaptamine Complex [KB220], a dopaminergic activator, in a randomized double-blind placebo controlled study in alcoholics and in polydrug abusers attending an in-patient chemical dependency program. In this randomized double-blind placebo controlled study of 62 alcoholic and polydrug abusers, we utilized skin conductance level (SCL) to evaluate stress responses. Patients receiving Synaptamine Complex [KB220] had a significantly reduced stress response as measured by SCL, compared to patients receiving placebo. Two factor ANOVA yielded significant differences as a function of Time (p<0.001), and Treatment (p<0.025) as well as a Time-by-Treatment interaction (p<0.01). The results of this study suggest that the Synaptamine Complex (TM) [KB220] may improve treatment response in an in-patient treatment setting by reducing stress related behaviors and warrants further investigation.

Genetic mediated physiological processes that rely on both pharmacological and nutritional principles hold great promise for the successful therapeutic targeting of reduced carbohydrate craving, body-friendly fat loss, healthy body recomposition, and overall wellness. By integrating an assembly of scientific knowledge on inheritable characteristics and environmental mediators of gene expression, we review the relationship of genes, hormones, neurotransmitters, and nutrients as they correct unwanted weight gain coupled with unhappiness. In contrast to a simple one-locus, one-mechanism focus on pharmaceuticals alone, we hypothesize that the use of nutrigenomic treatment targeting multi-physiological neurological, immunological, and metabolic pathways will enable clinicians to intercede in the process of lipogenesis by promoting lipolysis while attenuating aberrant glucose cravings. In turn, this approach will enhance wellness in a safe and predictable manner through the use of a Genetic Positioning System (GPS) Map. The GPS Map, while presently incomplete, ultimately will serve not only as a blueprint for personalized medicine in the treatment of obesity, but also for the development of strategies for reducing many harmful addictive behaviors and promoting optimal health by using substances compatible with the body's immune system.

This study systematically assessed the weight management effects of a novel experimental DNA-customized nutraceutical, LG839 (LifeGen®, Inc., La Jolla, CA, USA).

While it is well established that the principal ascending pathways for pain originate in the dorsal horn of the spinal cord and in the medulla, the control and sensitivity to pain may reside in additional neurological loci, especially in the mesolimbic system of the brain (i.e., a reward center), and a number of genes and associated polymorphisms may indeed impact pain tolerance and or sensitivity. It is hypothesized that these polymorphisms associate with a predisposition to intolerance or tolerance to pain. It is further hypothesized that identification of certain gene polymorphisms provides a unique therapeutic target to assist in the treatment of pain. It is hereby proposed that pharmacogenetic testing of certain candidate genes (i.e., mu receptors, PENK etc.) will result in pharmacogenomic solutions personalized to the individual patient, with potential improvement in clinical outcomes.

This meta-analysis was conducted to systematically review the efficacy and safety of the H-Wave® (Electronic Waveform Lab, Inc, Huntington Beach, CA, USA) device and programme as a non-pharmacological analgesic treatment in chronic soft tissue inflammation and neuropathic pain.

Summary The emerging field of nutritional genomics presents various clinical questions that require further investigations. One of those questions is whether nutrigenomic interventions reduce the cost of illness (COI). Prior to this study, there has been an absence of data evaluating the health economic implications of this new field of research. In this theoretical modeling study, we sought to evaluate the health economics implications of a nutrigenomic product for weight loss. We constructed a nutrigenomic economic model by linking 1) published study data related to the efficacy of a product and/or ingredients, 2) validated clinical assessments that have already been tied to health economics data, and 3) data involving condition prevalence and overall cost of illness. In this theoretical model, we demonstrate that LG839 variant positively reduces the cost of illness at the macroeconomic and microeconomic level based upon a cost-effectiveness and cost-benefit analysis. From this proposed model, we have forecasted the prognostic health economic implications of a nutrigenomic intervention to demonstrate a theoretical model of nutrigenomic economics. This study is hypothesis-generating and should be used in the definition of protocols to prospectively test the health economic benefits of nutrigenomics.

Based on neurochemical and genetic evidence, we suggest that both prevention and treatment of multiple addictions, such as dependence to alcohol, nicotine and glucose, should involve a biphasic approach. Thus, acute treatment should consist of preferential blocking of postsynaptic Nucleus Accumbens (NAc) dopamine receptors (D1-D5), whereas long term activation of the mesolimbic dopaminergic system should involve activation and/or release of Dopamine (DA) at the NAc site. Failure to do so will result in abnormal mood, behavior and potential suicide ideation. Individuals possessing a paucity of serotonergic and/or dopaminergic receptors, and an increased rate of synaptic DA catabolism due to high catabolic genotype of the COMT gene, are predisposed to self-medicating any substance or behavior that will activate DA release, including alcohol, opiates, psychostimulants, nicotine, gambling, sex, and even excessive internet gaming. Acute utilization of these substances and/or stimulatory behaviors induces a feeling of well being. Unfortunately, sustained and prolonged abuse leads to a toxic" pseudo feeling" of well being resulting in tolerance and disease or discomfort. Thus, a reduced number of DA receptors, due to carrying the DRD2 A1 allelic genotype, results in excessive craving behavior; whereas a normal or sufficient amount of DA receptors results in low craving behavior. In terms of preventing substance abuse, one goal would be to induce a proliferation of DA D2 receptors in genetically prone individuals. While in vivo experiments using a typical D2 receptor agonist induce down regulation, experiments in vitro have shown that constant stimulation of the DA receptor system via a known D2 agonist results in significant proliferation of D2 receptors in spite of genetic antecedents. In essence, D2 receptor stimulation signals negative feedback mechanisms in the mesolimbic system to induce mRNA expression causing proliferation of D2 receptors.