Reward deficiency syndrome in obesity: A preliminary cross-sectional trial with a genotrim variant

Abstract

Obesity is the second largest preventable cause of death in the United States. Even though it was classified as a disease in 1985, traditionally, obesity has been treated primarily as a behavioral problem that requires only modifications in diet and exercise. Similar to research on obesity, clinical studies have elucidated the role of biologic and genetic factors in alcoholism and other conditions previously classified as behavioral. These studies showed that behavioral adjustments alone may not address underlying genetic causes. We hypothesize that biologic and genetic factors must be addressed synergistically while behavioral modifications are implemented to adequately treat obese patients. We hypothesize that a predisposition to glucose craving and obesity is due to inadequate dopaminergic activity in the reward center of the brain. This defect drives individuals to engage in activities of behavioral excess, which, in turn, enhance brain dopamine function. Consumption of large quantities of alcohol or carbohydrates (carbohydrate bingeing) stimulates production and usage of dopamine within the brain; the term reward deficiency syndrome (RDS) may be used to categorize such biologic influences on behavior. We propose that a novel approach to nutritional supplementation may be required to target the role of RDS in obesity. In this regard, GenoTrim, a DNA-customized nutritional solution, has been developed and is currently under investigation in several clinical studies. Through its mechanism of action, GenoTrim addresses the genetic influence of RDS on obesity. In this cross-sectional study, 24 subjects were studied after they had completed a case report format questionnaire. For this assessment, we used a novel assessment tool-a path analysis. This statistical regression model is used to (1) examine the effectual relationships between various systems within a multisystem matrix, and (2) measure the contributory roles of those relationships in obesity, enabling the development of targeted and effective therapeutic interventions.

LG839: Anti-obesity effects and polymorphic gene correlates of reward deficiency syndrome

“…[24][25][26] Furthermore, a loss of 2.5 kg in only 80 days is quite statistically robust especially when considering guidelines from the US FDA regarding meaningful weight loss of any medically approved anti-obesity pharmaceutical.…”

“…24 Subsequent prospective studies have demonstrated that PCAL-103 significantly increased weight loss, decreased food cravings and binge eating, prevented weight regain after a period of fasting, and also reduced stress and enhanced general well-being. 25,26 In light of these early hypothesis-generating studies, and the paucity of research involving neurotransmitter manipulation of the brain reward system coupled with genetic polymorphic identification, we designed a pilot study to evaluate the process of DNA-customization of a nutritional solution for weight management. We carried out this experiment cognizant that larger randomized, placebo-controlled studies are warranted before any solid conclusions can be drawn from the present evaluation.…”

“Liking” and “wanting” of sweet and oily food stimuli as affected by high-fat diet-induced obesity, weight loss, leptin, and genetic predisposition

“…The hypersensitivity hypothesis suggests that the more reward a food generates, the more we eat, with apparently no upper limit of reward (3,19). The hypo-sensitivity or reward-deficit hypothesis suggests that increased intake of palatable food is an attempt to reach a certain reward set point by compensating for hypo-functioning reward generation, specifically for reduced mesolimbic dopamine transmission (12,32,33,48,65,77). Although the prospective studies in humans with genetically reduced dopamine signaling and the one observation in preobese obesity-prone rats suggest that genetic predisposition is an important factor in determining the response to palatable food, the contributions of these two competing hypotheses to the development of obesity, with no known genetic anomaly, is not well understood.…”

Invited Commentary: In a Genomic Era, Should We Promote Dopamine Homeostasis to Treat Opiate/ Opioid Abuse, Instead of Blocking Brain Dopamine Function?

“…Notably, of all the results and gene polymorphisms tested, only the DRD2 gene polymorphism (A1 allele) had a significant Pearson correlation with treatment days (r = 0.42, p = 0.045), so that there was a modest relationship between the occurrence of the A1 allele and the length of treatment days This 2-fold increase is a significant genotype for treatment compliance (Blum, Chen et al, 2006, 2007.…”

“…Further findings, which point to the need for additional research, using a Path Analysis (non-customized KB220Z), also indicated significant connections with anti-obesity behaviors. In a one-year cross-sectional, open trial study of 24 unscreened subjects, using an oral KB220Z variant, the following beneficial outcomes occurred: decreased stress; sleep improvement; increased energy; universal well-being; decreased cravings (sugar/carbohydrates); enhancement in mental focus/memory; enhancement in blood sugar levels; decreased food intake; decreased waist circumference; weight loss; decreased blood pressure; enhanced exercise performance; decreased drug-seeking; decreased hyperactivity; and decreased cholesterol levels (Blum, Chen et al, 2006). Although opioid medications effectively treat acute pain and help relieve chronic pain for some patients (Moore, Derry, Eccleston, & Kalso, 2013), their addiction risk presents a dilemma for healthcare providers seeking to relieve suffering, while preventing drug abuse and addiction.…”