Study of the Reversibility of Glucose Intolerance Caused by Chronic Aspartame Consumption
Study of the Reversibility of Glucose Intolerance Caused by Chronic Aspartame Consumption
Experiments have shown that some artificial sweeteners like those in diet soda can cause
 changes in how the body responds to and uses sugar. These changes increase the chance of
 obesity, type 2 diabetes, and other metabolic diseases. In this study, the investigators plan
 to see if the most common artificial sweetener, aspartame (brand name Equal, NutraSweet),
 causes these changes. The investigators believe that if metabolic changes are observed in a
 person who consumes aspartame, then removing all aspartame from the diet might lead to a
 reversal of the changes and a normalization of test results.This would impact sweetener
 additives in our foods and thus decrease the incidence of obesity, diabetes, and the
 metabolic syndrome.
Experiments have shown that some artificial sweeteners like those in diet soda can cause
 changes in how the body responds to and uses sugar. These changes increase the chance of
 obesity, type 2 diabetes mellitus, and other metabolic diseases. In this study, the
 investigators plan to see if the most commonly used artificial sweetener, aspartame, affects
 the body's response to sugar. The investigators believe that if metabolic changes are
 observed in a person who consumes aspartame, then removing all aspartame from the diet might
 lead to a reversal of the changes and a normalization of test results.

 The investigators plan to study two (2) cohorts of healthy volunteers: 1) Those who regularly
 drink at least three cans per day of diet soda that contains aspartame (Cohort 1, Aspartame
 Consumers) and 2) participants who consume less than or equal to two (2) cans of diet soda
 per week (Cohort 2, Aspartame Naïve Participants).

 Phase I of the study, the investigators will ask participants questions about their usual
 diet, including how much diet soda they usually drink. Participants will be screened by a
 test called the oral glucose tolerance test, or OGTT. This test involves coming to the
 hospital to drink sugary syrup, then have blood sugar checked every thirty (30) minutes for
 five (5) hours. Before the test, participants must refrain from eating or drinking anything
 for ten (10) hours. If the OGTT shows a high value, then the participant in cohort 1
 (Aspartame Consumers) who regularly drink 3 or more cans per day of diet soda will be
 approached about continuing into the second phase of the study. For the participants in
 cohort 2 (consume less than or equal to two (2) cans of diet soda per week; Aspartame Naïve
 Participants), this will be the end of their participation in the study.

 Phase II of the study, blood tests, OGTT, stool samples, and weight and body fat measurements
 a few times a week will track any changes in the participants during the study. During the
 phase II five (5) week study, participants will receive all of their meals from the
 Rockefeller University Hospital and should not have any outside food or drinks. The diet used
 throughout this study phase (II) is the Prudent Metabolic Diet. Participants can leave the
 hospital and continue to work, but must come for all tests and to receive meals. During Week
 One, participants will eat only food provided by the hospital but will continue to drink
 three (3) cans of diet soda per day. In Weeks Two through Four, participants will continue to
 eat food given to them by the hospital and will not be allowed to consume any foods or drinks
 that contain aspartame. In Week Five, participants will continue on the hospital diet, but
 will again start drinking three (3) cans of diet soda per day.
Inclusion Criteria:

 1. Male or female aged 18 - 45

 2. Weight stable for at least 3 months prior to screening (< 5% weight change)

 3. BMI of 21 - 29

 4. Cohort 1 - Aspartame Consumers: Primary dietary sweetener is aspartame; consumes at
 least 36 ounces of diet soda in which aspartame is a primary ingredient (Diet Coke or
 Diet Dr Pepper) a day for at least 6 months duration prior to study enrollment
 (Primary dietary sweetener is aspartame" should be defined as: "840g per week sucrose
 equivalent from aspartame and less than 280 grams per week sucrose equivalent from all
 other sweeteners (non-caloric and caloric sweeteners). For reference, one 12oz soda is
 40g sucrose equivalent, and one teaspoon (one packet) of artificial sweetener is 4g
 sucrose equivalent.)"

 Cohort 2 - Aspartame Naïve Participants: Consumes less than or equal to 2 cans of diet
 soda per week

 5. Screening Visit #2 OGTT Outcome:

 -  0-h plasma glucose < 110 mg/dl AND

 -  2-h plasma glucose < 140 mg/dl

 6. Abnormal OGTT during the screening phase of the study (area under curve on the high
 end of distribution)

 7. Must be able to comply with a metabolic Prudent diet

 8. Willing to fast 10 hours before each OGTT and BodPod

 9. Current level of exercise (aerobic and/or resistance training) must be able to be
 sustained while an in-patient

 Exclusion Criteria:

 1. Any evidence of US National Cholesterol Education Program Adult Treatment Panel III

 Clinical Identification of the Metabolic Syndrome (must have 3 or more of the
 following risk factors):

 Abdominal Obesity, given as a waist circumference:

 -  Men >102 cm (>40 in)

 -  Women > 88 cm (>35 in)

 Triglycerides >150 mg/dl

 HDL Cholesterol:

 -  Men < 40 mg/dl

 -  Women <50 mg/dl

 Blood Pressure >130/ >85 mm Hg

 Fasting Glucose > 110 mg/dl

 2. Average systolic blood pressure (SBP) > 150 mmHg and / or diastolic blood pressure
 (DBP) > 90 mmHG (based on 3 BPs taken at screening visit #1),

 3. LDL-C > 240mg/dl

 4. Triglycerides > 400 mg/dl

 5. Evidence of a liver disorder (ALT > three fold of the ULN)

 6. Evidence of any renal disease

 7. Currently on a weight-loss diet

 8. Diabetes

 9. Self-reported history of thyroid dysfunction

 10. Sugar sweetened beverage consumption (> 84 ounces per week)

 11. Hemoglobin <13.0 g/dl for males and 12.0 g/dl for females

 12. Current, prior (within 2 months), or anticipated use of any of the following
 medications:

 antihyperlipidemic, hyperglycemic medications, Antineoplastics, Antiretrovirals,
 Selective Serotonin Reuptake Inhibitors, Diuretics, Antihypertensives,
 Anticonvulsants, Hormone therapy, Birth control

 13. Self-reported antibiotic use within the previous 3 months

 14. Currently pregnant or lactating

 15. History of cardiac disease

 16. Active illegal drug user (self-reported)

 17. History of GI surgery (gastric bypass, bariatric, Roux-en-Y, colon resection, etc.)

 18. Habitual ingestion of > 2 alcoholic beverages/day

 19. Ever diagnosed with an eating disorder (self-reported)

 20. Use of steroids or beta agonists (orally, intranasal or inhaled) within a week of any
 OGTT

 21. Positive Hepatitis Serology (Hep. B surface Antibody; Hep. B surface antigen; Hep. C
 surface antibody)

 22. HIV Positive

 23. Tobacco use within the past 3 months

 24. Any medical or social condition that, in the opinion of the Investigator, might pose
 additional risk to the participant or confound the results of the study