Clinical trial NCT04016337: Evaluation of New Beverages Rich in Bioactive Compounds for the Modulation of Energetic Metabolism in Overweight Adults
Official title: Evaluación Del Efecto de Bebidas Ricas en Compuestos Bioactivos Para Modular el Metabolismo Energético en Adultos Con Sobrepeso
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Inflammation
Insulin Sensitivity
Keywords: sweeteners
stevia
sucralose
polyphenols
maqui
bioavailability
inflammation
gut hormones
biomarkers
Lead sponsor: Universidad Católica San Antonio de Murcia
Sponsor class: OTHER
Collaborators: name: National Research Council, Spain
First posted: 2019-07-11
Enrollment: 138
Sex: ALL
Minimum age (years): 35
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The chronic study consisted on a 60 days consumption of a beverage (330 mL) made with lemon and maqui and added a particular sweetener.
Primary purpose: PREVENTION

Brief summary: During last decades, an excessive intake of sugars has been observed in westernized countries, mainly due to the consumption of sugar-rich soft drinks. Epidemiological studies have pointed out a positive correlation between the consumption of such drinks and the risk of obesity, diabetes, and cardiovascular diseases. Therefore, there is a growing trend looking for new non-caloric alternatives (sweeteners) in order to reduce the sugar content of foodstuffs without losing their sweetness and tastefulness. However, some questions regarding sweeteners have recently arisen as their effects after long-term consumption have not been fully unravelled. They could also contribute to a higher caloric intake and to disrupt the gut microbiota. Besides seeking new alternatives for the high intake of sugar-rich drinks, there is a need for increasing the consumption of fruits and vegetables among general public. Developing new products to stretch the shelf-life of fresh fruits, preserving their nutrients, and reducing the energetic content of fruit juices should also be accomplished. In this sense, lemon juice has been proposed as an interesting ingredient in the elaboration of soft drinks due to its distinctive aroma and high nutritive value. Its combination with maqui berry juices contributes to stabilize the colour and phenolic compounds that both products contain (mainly flavanones for lemon juice and anthocyanins for maqui). The beneficial effects of these vegetal foodstuffs and their phenolic substances on glucose intolerance have been reported.The aim of BEBESANO is studying the beneficial effects of sugar-free, rich-in-phytochemicals drink consumption on postprandial hyperglycaemia, in order to provide alternatives to excessive sugar intake and counteract the postprandial response linked to sugar consumption in subjects with low levels of chronic inflammation such as overweight people. Moreover, BEBESANO will shed light on the interactions of food constituents with the main pathways involved in the lipid and glucose metabolism, oxidative stress, inflammation, and hormonal regulation in overweight population.

Detailed description: The effect of the consumption of fruit-based drinks, sweetened and rich in bioactive compounds has been evaluated in acute and chronic clinical studies. They have been carried out at the Catholic University of Murcia, in accordance with the Helsinki Declaration of Human Studies and approved by the official Ethical Committee of Clinical Studies (CEIC).

All participants were informed on the characteristics of the study and they signed the written-informed consent. Dietetic and life style habits were recorded from all participants. There were no drop-outs during the whole period of the study and no adverse effects were reported. Safety clinical parameters (hepatic enzymes, renal function) were measured as well.

Acute study The acute study has determined markers of intake such as metabolites generated from ingested polyphenolic compounds, as well as markers of effect, such as markers of inflammatory processes, oxidative stress, glycemic and lipid homeostasis and hormones. Specifically, the analysis of incretines in plasma using LC-MS techniques has been included.

A double-blind, randomized, cross-over clinical study has been conducted in a population of 20 overweight individuals. After an initial phase of 3 days of wash-out with a strict diet free of polyphenols and added sugars, 330 mL of the problem drink was administered on fasting conditions:

* Drink made with lemon and maqui and sweetened with saccharose
* Drink made with lemon and maqui and sweetened with sucralose
* Drink made with lemon and maqui and sweetened with stevia

Blood samples were then taken at various times (0, 15, 30, 60, 90, 120, 210 minutes). Urine samples were collected 24 hours earlier (0 point) as well as in 0-4, 4-8, 8-12, 12-24 h tranches.

After 7 days, the process was repeated again, for each volunteer to take another drink, until all the drinks were consumed by all the volunteers.

Chronic study Prolonged consumption of beverages over several weeks will allow the later modification markers, such as parameters related to inflammation or oxidative status and long-term hormonal response, to be evaluated.

The trial is randomized, double-blind, parallel, with 3 groups of 46 subjects each. The groups were randomized stratified by sex, BMI, and age. Recruitment has taken place at various Health Centers and at UCAM. Those who are able to participate have been informed of the study and asked to sign informed consent.

The study includes beverages already studied in acute intervention:

* Drink made with lemon and maqui and sweetened with saccharose
* Drink made with lemon and maqui and sweetened with sucralose
* Drink made with lemon and maqui and sweetened with stevia

Participants were advised not to change their dietary habits during the study period.

Each individual was given a type of drink (330 mL/day) for 60 days. Blood samples were taken, as well as 24h-urine, at day 0 and at the end of the study (60 days), to perform the various assessments.

Eligibility criteria: Inclusion Criteria:

* healthy volunteers,
* body mass index (BMI) between 25 - 29.9 kg/m2 (overweight according to WHO criteria)
* 35-55 years,
* absence of disease.

Exclusion Criteria:

* Hypertension
* Dislipemia
* Smoking

Primary outcomes:
measure: Changes in markers of inflammation (cytokines)
timeFrame: Changes observed from baseline at day 0 compared to 60 days
measure: Changes in markers of inflammation (c-reactive protein)
timeFrame: Changes observed from baseline at day 0 compared to 60 days
measure: Changes in markers of lipid metabolism
timeFrame: Changes observed from baseline at day 0 compared to 60 days
measure: Changes in markers of glycemic metabolism
timeFrame: Changes observed from baseline at day 0 compared to 60 days
measure: Insulin resistance
timeFrame: Changes observed from baseline at day 0 compared to 60 days
measure: Changes in hormone response
timeFrame: Changes observed from baseline at day 0 compared to 60 days
measure: Changes in anthropometric parameters
timeFrame: Changes observed from baseline at day 0 compared to 60 days
Secondary outcomes:
Other outcomes:
Locations:
city: Guadalupe
country: Spain
facility: Universidad Católica de Murcia (UCAM)
state: Murcia
Study officials:
affiliation: Universidad Católica de Murcia (UCAM)
name: Débora Villaño Valencia, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Villano D, Zafrilla P, Garcia-Viguera C, Dominguez-Perles R. A UHPLC/MS/MS method for the analysis of active and inactive forms of GLP-1 and GIP incretins in human plasma. Talanta. 2022 Jan 1;236:122806. doi: 10.1016/j.talanta.2021.122806. Epub 2021 Aug 19.