DNAcustomized Geno Trim neuronal dopamine release activator results

DNA-customized Geno. Trim™ [neuronal dopamine release activator] results in significant reductions in weight, appetite, sugar cravings in an overweight population in the Dietary Investigation to Evaluate Treatments (D. I. E. T. ) pilot study. Polymorphic gene correlates of Reward Deficiency Syndrome (RDS). Kenneth Blum 1, 2, 5*, Brian Meshkin 2, Thomas J Prihoda 3, B William Downs 4, Roger L Waite 2, Eric R. Braverman 5, Lisa White 6, 7, Lonna Williams 2 1 Department of Physiology & Pharmacology, Wake Forest University School Of Medicine, Winston –Salem, NC , 2 Salugen, Inc. San Diego, CA, 3 Department of Pathology, University Of Texas Health Science Center, San Antonio, TX, 4 Allied Nutraceutical Research, Lederach, PA, 5 Path Research Foundation, New York, 6 Baylor College of Medicine, Houston TX, 7 DNA Services of America, Lafayette, LA. Background Approximately 1/3 of American adults are estimated to be obese, and 60% are overweight. Experts from Harvard Medical School and Massachusetts General state that 70% of 80% of weight problems are due to genes influencing appetite and metabolism. While at the same time, a survey conducted by Thomson Med. Stat of 11, 000 Americans suggests that normal weight and obese persons eat, exercise vigorously, snack and read nutrition labels similarly. Various types of individuals having “Reward Deficiency Syndrome (RDS)“ related behaviors including sugar craving (e. g. overweight) have been described and heredity has been shown to be involved in some of these types. An important role of the mesolimbic dopamine system has been suggested in the reinforcing effects of a number of addictive substances (i. e. alcohol, nicotine, sugar, etc. ) and recent genetic studies are implicating genes in RDS and in particular weight problems. Objective In that a CB 1 blocking agent (i. e. rimonabant, brand name “Acomplia”) has been recently rejected by the FDA, our objective is to find a better weight-loss agent that actually stimulated feelings of wellbeing and happiness with weight loss, instead of suicidal thoughts or depression. We systematically evaluated the effects of a novel DNA-customized nutraceutical (Geno. Trim ® possessing dopaminergic release activation properties), on weight management outcomes and attempted to correlate at least five candidate genes with these multiple outcomes. Methods A total of 1, 058 self–identified obese subjects of Dutch-decent were genotyped for polymorphisms of five candidate genes: PPAR gamma 2, MTHFR C 677 T, 5 -HT 2 a, Leptin OB, and DRD 2 to receive an experimental DNA-customized nutraceutical, Geno. Trim®. Out of these subjects, 27 responded to a request to complete a survey about their experience with Geno. Trim. Responses derived from a modified standardized questionnaire and a Likert scale designed to obtain information were entered into a computer database and analyzed for significance. Figure 1. Genotypic comparisons between the 1, 058 obesity sample, the 27 subset of obese subjects, and literature controls* Percent Prevalence Figure 3. Average Weight Loss on Geno. Trim Equals 2. 5% in 80 days Frequency For Gene Mutant (Het&Hom) Obesity Sample Literature Control WT Sample Mutant Sample PPARgamma 4/23 (17. 4) 265/1058 (25. 1) 314/2244 (14. 0) 0. 90 0. 10 5 -HT 2 a 16/25 (64. 0) 679/1058 (64. 2) 173/283 (61. 1) 0. 56 0. 44 MTHFR 16/25 (64. 0) 739/1058 (69. 9) 54/100 (54. 0) 0. 60 0. 40 DRD 2 9/23 (39. 1)* 403/1058 (38. 1) 945/3258 (29. 0) 0. 76 0. 24 Leptin OB*** 14/25 (56. 0) 800/1058 (75. 6)** 94/206 (45. 6) O. 60 0. 40 *Due to missing data instead of n=27 the mean was n=23. **Significantly different from n=23 sample by Fisher’s exact test. *** Cognizant that many studies on the LEP gene argue its association with obesity Figure 2. Brain Reward Cascade Figure 4. Overall Changes on Geno. Trim Assessment Area and Question N Mean Changea SD p-value Appetite (On a scale of 1 to 5, how would you rate your appetite before (and after) taking Geno. Trim? With 1 being Low Appetite and 5 being Very High Appetite) 25 -0. 76 1. 20 0. 004** Energy (On a scale of 1 to 5, how would you rate your energy level before taking Geno. Trim? With 1 being High Energy Level and 5 being Very tired or very low energy level) 25 -0. 84 1. 03 0. 0004*** Happiness (On a scale of 1 to 5, how would you rate your mood and overall feeling of happiness before (and after) taking Geno. Trim? With 1 being Very Happy and 5 being Very Unhappy) 25 -0. 36 0. 70 0. 017* Late night eating (How many times per week did you engage in late night eating (within 2 hours of going to sleep) before (and after) taking Geno. Trim? ) 25 -0. 84 1. 43 0. 007** Overate (On a scale of 0 to 5, how many times a week do you feel that you overate before (and after) taking Geno. Trim? With 0 being none and 5 bring 5 or more times) 25 -0. 72 1. 49 0. 023* Quality of Sleep (On a scale of 1 to 5, how would you rate your quality of sleep before (and after) taking Geno. Trim? With 1 being Very High and 5 being Very Low) 25 -0. 52 1. 00 0. 016* Snack (On a scale of 0 to 5, how many times a day did you snack between meals before taking Geno. Trim? With 0 being None and 5 being 5 or more times) 25 -0. 80 1. 29 0. 005** Sugar Craving (On a scale of 0 to 5, how would you rate your sugar craving before (and after) taking Geno. Trim? With 0 being None and 5 being Very High) 25 -0. 88 1. 51 0. 008** Waist (cm) 16 -0. 75 1. 73 0. 104 Weight (k) 26 -2. 62 4. 55 0. 006** ________________________ a While on Geno. Trim® minus before (baseline) on Geno. Trim®. *p<0. 05, ** p<0. 01, *** p<0. 001 Results Simple t-tests comparing a number of parameters before and 80 days on Geno. Trim were performed. The noteworthy significant results are as follows: average weight loss was 2. 5% of body weight or 6 lbs. or 1 -point reduction in BMI (p <0. 008); sugar craving reduction (p<0. 008); appetite suppression (p< 0. 004); snack reduction (p< 0. 005); reduction of late night binging (p<0. 007); increased perception of over-eating (p<0. 02)]; increased energy (p<0. 004); enhanced quality of sleep (p<0. 02) and increased happiness (p<0. 02). In the subset of 27 subjects having a similar genotype pattern of the entire sample, and of all the outcomes and gene polymorphisms, it is interesting to note that the DRD 2 gene polymorphism (A 1 allele vs. A 2 allele) had a significant Pearson correlation with days on treatment (r=0. 42, p=0. 045). DRD 2 A 1 - carriers had days on treatment of 51. 9 ± 9. 9 SE (95% CI, 30. 8 to 73. 0) and for the DRD 2 A 1+ carriers the number of days on treatment was 110. 6 ± 31. 1 (95% CI, 38. 9 to 182. 3 ). Thus, the attrition was highest in the A 1¯ genotype group. Therefore, the genotype may be a predictor of treatment persistency and compliance. Conclusion This study demonstrates that Geno. Trim, a DNAcustomized nutritional supplement for weight management, is a potentially effective agent in reducing weight and improving symptomatic RDS behaviors. We are also proposing that for persons possessing candidate reward gene polymorphisms resulting in physiological deficits in brain reward neurotransmitters, utilizing a dopaminergic type d 2 receptor agonist, such as Geno. Trim, can activate the neuronal release of dopamine in the nucleus acumbens. By activating neuronal DA release one would expect that an individual’s reinforcing effects derived from any natural reward (i. e. daily experiences, food, sex, love, etc. ) will be enhanced. We cautiously suggest that DNA directed targeting of certain regulator genes along with a customized nutraceutical intervention provides a unique framework and strategic modality to combat unwanted weight. Disclosures: Kenneth Blum, Brian Meshkin, Roger Waite, and Lonna Williams are stock holders and officers in Salugen, Inc. , the makers of Geno. Trim – a DNA-customized nutritional solution for weight management. For more information on Salugen or Geno. Trim, please visit www. salugen. com and www. genotrim. com.