Mass Balance of Orally Administered [14C] (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one

Objective: To determine the mass balance of (3S,4S,5R)-1,3,4,5,6-Pentahydroxy-hexan-2-one (low GI sweetener) in healthy volunteers.

Study design: Single centre, open-label, non-randomised, single oral administration study Study population: 8 healthy males and females (18-65 y, BMI 18.5-25 kg·m-2) Intervention: Orally ingestion of 14C-labelled (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one, followed by a 72-hour test period during which all urine and faeces will be collected, as well as repeated sampling of blood and expired air, as well as indirect calorimetry measurements.

Main study parameters/endpoints: Mass balance of (3S,4S,5R)-1,3,4,5,6-Pentahydroxy-hexan-2-one following 14C-(3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one ingestion. Secondary endpoints: content of 14C-labelled metabolites in carbohydrate metabolism pathways, routes of elimination of (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one. Ventilated hood measurements will be used as proof of concept to assess caloric value of carbohydrates.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Insertion of the catheters in a vein is comparable to a normal blood draw and the only risk is a small local hematoma. (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one ingestion might lead to gastro-intestinal discomfort. During the adaptation period participants will consume food-grade (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one, which is safe for human consumption.

Inclusion criteria

• Healthy males and females using contraception during and for 3 months after the study, aged from 18-65 years at the time of signing the informed consent
• 18.5<BMI<25kg.m2
• Willing and able to communicate and participate in the whole study, including consumption of (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one and meals offered during study conduct
• Regular bowel movements (i.e. average stool production of ≥1 and ≤3 stools per day)
• Usually eat 3 meals per day (i.e. breakfast, lunch and dinner)

Exclusion criteria

• Any diagnosed metabolic Impairment (e.g. Type 1 or 2 diabetes)
• Any diagnosed cardiovascular disease
• Hypertension (≥140 mmHg systolic and/or ≥90 mmHg diastolic)
• History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastro-intestinal disease, immunodeficiency, endocrine, neurological or psychiatric disorders
• Any diagnosed respiratory disease, such as COPD or asthma
• Any previous motor disorders or disorders in muscle and/or lipid metabolism
• Known severe kidney problems
• Presence of an ulcer in the stomach or gut and/or strong history of indigestion
• Recent or chronic history of diarrhoea
• Known anaemia
• A personal or family history of thrombosis (clots), epilepsy, seizures, or schizophrenia.
• Regular use of dietary supplements (>3 times per week)
• Chronic use of any prescribed or over the counter pharmaceuticals (excluding oral contraceptives and contraceptive devices)
• History of any drug or alcohol abuse in the past two years
• Drug use
• Claustrophobia
• On a weight loss diet (including intermittent fasting) or following a high calorific/high protein diet in order to gain weight
• Functional constipation
• Any known food allergies or intolerances to the 14 major food allergens (celery, cereals containing gluten, crustaceans, eggs, fish, lupin, milk, molluscs, mustard, tree nuts, peanuts, sesame seeds, soybeans, sulphur dioxide and sulphites) or history of a malabsorption syndrome including coeliac disease
• Regular gastrointestinal complaints including abdominal pain, stomach upsets and borborygmi or known or suspected irritable bowel syndrome
• Currently taking part in other scientific research
• Received a product with 14C in the past 12 months
• Pregnant or breastfeeding
• Smoking or having used nicotine-containing products in the 6 months prior to the study.
• Taken antibiotics within the 60 days prior to the adaptation period.
• Currently involved in a structured progressive resistance training programme (>3 times per week)
• Sedentary lifestyle as assessed using the International Physical Activity Questionnaire [IPAQ].
• Employed or undertaking a thesis or internship at the department of Human and Animal Physiology or TNO (department of Metabolic Health Research)
• Unable to give consent