Efficacy of D-allulose on Weight and Fat Loss and Insulin Resistance in Non-diabetic Obese Subjects
Efficacy of D-allulose on Weight and Fat Loss and Insulin Resistance in Non-diabetic Obese Subjects
Prospective, randomized, double-blind, controlled-trial 30 subjects in each groups Group - I
 consume pure D-allulose 5 g 3 times a day before meal to right after meal (with any liquid)
 and Group - II control group with non-calorie sweetener erythritol 5 g 3 times a day before
 meal to right after meal (with any liquid) Total number: n = 60 Either males or females,
 non-diabetic, aged > 18 years old with BMI ≥ 25 kg/m2

 Primary objectives Efficacy

 1. Compare the efficacy of pure D-allulose (psicose) plus conventional therapy on 1.1
 visceral fat area (VFA), subcutaneous fat area (SFA), total fat area (TFA) change 1.2 body
 weight, BMI and body fat percentage (with impedance method) change after 24 weeks of
 D-allulose (psicose) consumption to erythritol consumption and between pre- and
 post-intervention.

 Secondary objectives 1. Efficacy of pure D-allulose (psicose) plus conventional therapy
 versus erythritol plus conventional therapy on 1.1 insulin resistance, fasting plasma
 glucose, HbA1c 1.2 adiponectin, leptin and tumor necrosis factor-alpha, lipid profiles (total
 cholesterol, HDL-C, LDL-C, triglyceride, very low-density lipoprotein, LDL, chylomicron),
 apolipoprotein AI, apolipoprotein AII,apolipoprotein B48, apolipoprotein CIII and
 apolipoprotein E, free fatty acids 1.4 waist circumference, hip circumference, waist/hip
 ratio

 Safety

 1. Safety of the study by comparing with conventional therapy, monitoring blood pressure,
 pulse rate, hematological parameters and urinalysis
Subjects and methods Study product The test product is the pure D-allulose which is a rare
 sugar. The control product is the non-calorie sweetener erythritol.

 Study design This is a single center, prospective, randomized, control trial. After informed
 consent is obtained, history taking and physical examination will be performed to ensure that
 the patients met all inclusion criteria and had no exclusion criteria.

 At the screening day, venous blood samples will be collected following an overnight fasting
 of at least 8 hours. Complete blood count (CBC), chemistry including fasting plasma glucose
 (FPG), glycated hemoglobin (HbA1c), insulin, blood urea nitrogen (BUN), creatinine, lipid
 profiles (total cholesterol, HDL-C, LDL-C, triglyceride, very low-density lipoprotein), blood
 urea nitrogen, creatinine, total protein, Albumin, albumin/globulin ratio, glutamine
 oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) , Gamma-glutamyl
 transpeptidase (GGT), lactate dehydrogenase (LDH), total bilirubin (including Direct and
 Indirect), alkaline phosphatase, uric acid, plasma amylase, cholinesterase, Sodium, Chloride,
 potassium, carbon dioxide , Calcium, inorganic phosphate, magnesium, plasma iron will be
 measured.

 Urine will be collected for urinalysis and urine pregnancy test will be performed to exclude
 pregnant women from the study.

 Visceral fat area (VFA), subcutaneous fat area (SFA), total fat area (TFA) will be measured
 with abdominal CT scan at umbilical level (L4) and bioelectrical impedance at D-7 or
 screening visit.

 The eligible subjects will be randomized with an equal probability of receiving either pure
 D-allulose 5 g 3 times a day from 30 min before meal to right after meals (with any liquid)
 plus conventional therapy or placebo (non-calorie sweetener erythritol) 5 g 3 times a day
 from 30 min before meal to right after meal (with any liquid) plus conventional therapy for
 24 weeks. Both the subjects and the investigator will be blinded to the type of the product.
 Subjects in both groups will be instructed to modify their lifestyle to control their diet to
 1200 kcal for women and 1500 kcal for men and increase physical activity.

 Subjects will be asked to do 3-d food record per week (2 working days and 1 weekend) entire
 of the study. Subjects will need to record any exercise they do including type and duration
 during in the study. Subjects will be asked to visit every 4 weeks for follow-up for totally
 9 visits including screening day or D -7, D0, end of week 4, 8, 12, 16, 20, 24 and 4 weeks
 post intervention (at the end of week 28) in 29 weeks duration.

 Assessment of insulin resistance index (IRI) was calculated from the homeostasis model
 assessment of insulin resistance (HOMA-IR) using FPG (mmol/L) multiply by fasting insulin
 (U/ml) divided with 22.5.

 The satisfaction of the product will be asked at 4 weeks, 12 weeks and 24 weeks after
 consumption of the study products.

 From the visit 1 to visit 8, same blood samples as the screening will be measured.

 At the screening visit, visit 4 and visit 7, CT abdomen measurements will be conducted.

 At the visit 1 and visit 7, adiponectin, leptin, tumor necrosis factor -alpha will be
 measured.

 At the visit 1, visit 4, visit 7 and visit 8, other lipid profiles will be measured including
 very low-density lipoprotein and Chylomicron fractionation , Apolipoprotein (AI, AII，C-III,
 E), Apolipoprotein (B48, B100), nonesterified fatty acid

 Adverse Event Assessment At each visit, subjects will be asked an open question as if he/she
 has experienced any abnormal symptoms. Any symptom reported by the subject will be recorded
 as an adverse events with details of the event, its severity, start and stop dates, and
 relationship to study products.

 Withdrawal criteria

 1. Consume study product less than 90% during treatment period

 2. Start taking any medication that may affect body weight during in the study.
Inclusion Criteria:

 1. Male or female, age > 18 years and legal age of consent.

 2. If female, the subject is either post-menopausal or surgically sterilized, or has a
 negative urine pregnancy test within 7 days prior to enrollment and will use adequate
 contraception during the study.

 3. Obesity, defined as BMI ≥ 25 kg/m2

 4. Stable weight (weight change no more than 5% within 3 months)

 5. If subject has been treated with medications that might cause weight change (such as
 corticosteroid, antidepressant, antipsychotics, oral contraceptive pills) prior to
 admission, he/she must have taken the medication regularly at a steady dose for at
 least 8 weeks up.

 6. The subject has provided written informed consent prior to admission to the study.

 Exclusion Criteria:

 A subject will be excluded from the study for any of the following reasons:

 1. Pregnancy or lactation

 2. Diagnosed with diabetes mellitus

 3. Weight change ≥ 5 % within 3 months prior to admission to the study

 4. Has taken any weight loss medications within 3 months prior to admission to the study

 5. Immunocompromised status, including a debilitated state or malignancy

 6. Active liver, renal, thyroid diseases

 7. Frequent alcoholic consumption more than twice a week; with beer > 360 mL, alcohol >
 45 mL, wine > 150 mL for female, or beer > 720 mL, whisky > 90 mL, wine > 300 mL for
 male each time

 8. Has gastrointestinal symptoms such as nausea, vomiting, loss of appetite, premature
 satiety, diarrhea, or chronic constipation

 9. Lack of ability or willingness to give informed consent

 10. Taken any medications than might cause weight loss or weight gain such as
 corticosteroid, antidepressant, antipsychotics, oral contraceptive pills < 8 weeks or
 change the dose of these medication with 8 week prior to admission

 11. Enrolled in any other clinical study within 3 months before enrolment