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.

Eligibility Criteria:
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