NUTRACORE, Glycaemic Index and Appetite

Hyperglycemia Clinical Trial

— NTRCR-vivo  

Official title:

Glycemic Index Analysis of Functional Bakery Products on a Group of Healthy Volunteers, a NUTRACORE Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05528874
• Other study ID #: CE 054/2022
• Status: Completed
• Phase: N/A
• Start date: April 22, 2022
• Est. completion date: September 1, 2023

Study information

• Verified date: September 2023
• Source: Azienda Ospedaliero Universitaria Maggiore della Carita
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In recent decades, the world prevalence of obesity and type 2 diabetes (DMT2) has increased dramatically, resulting in a global epidemic. One of the aspects more connected to the etiology of these pathologies is undoubtedly the concept of the glycemic index (GI) and glycemic load (CG). It has been shown that, with the same CG, that is of carbohydrates contained in a food, a food with a higher GI tends to raise blood sugar more quickly (and consequently insulin), causing several negative effects on the body. We now have sufficient evidence to show that high GI diets are associated with increased incidence of DMT2, hyperlipoproteinemia, and cardiovascular disease. Although simple carbohydrates, namely sugars, have always been considered the major inducers of hyperglycemia and hyperinsulinemia, in reality also starches, or complex carbohydrates digestible by humans, may lead to an increase in blood sugar levels which is not as rapid but often equally harmful to health, since the GC is generally higher. The reason why a high GI diet is responsible for this increased risk of developing pathologies is not unambiguous. We can identify at least 4 probable mechanisms. 1. Sudden hyperglycemia tends to cause insulin to rise beyond what is necessary, leading subsequently to the risk of hypoglycemia and thus an excessive feeling of hunger. Increased energy intake and obesity. 2. Excess insulin secretion, aggravated by insulin resistance, represents an effort for the pancreas with the risk, over time, to arrive at a deficit of insulin-dependent diabetes type 2 insulin production 3. Hyperinsulinemia is also associated with reduced lipolysis and increased lipogenesis obesity and hyperlipoproteinemia 4. Fat accumulation, especially in the abdominal region, is associated with chronic inflammation and insulin resistance by type 2 diabetes tissues and metabolic syndrome In addition to these reasons, a high GI diet, typically called Western Diet, is also generally deficient in plant foods, rich in antioxidants and photo compounds with anti-inflammatory action, without which the process of chronic organic inflammation is accelerated, even in the absence of real obesity.

Description:

For these reasons, in recent years the food industry has tried, not always successfully, to experiment with alternative formulations for its products, implementing a series of techniques to reduce the GI of foods, in particular those based on cereal flour. There are different methods useful to reduce the GI; in particular, the most impacting aspects of the GI of food containing carbohydrates are the sugar content, the starch content, the type of starch, the cooking method, previous processing, pre-cooking, post-cooking cooling, soaking, particle size and fiber quantity. Increased consumption of soluble fiber is associated with reduced absorption of sugars in the intestine and therefore a reduced GI. On the contrary, most of the fibers contained in cereals and tubers are not soluble. For this reason, the direct effect of fibers on glycemic absorption is not significant. On the other hand, whole grains generally have a lower glycemic index than refined grains and this may be due to a combination of factors such as reduced digestibility, higher starch-content resistance, and the effects of other constituents of bran (such as lipids). Insoluble fibers are also attributed to a greater satiating effect. The determination of the glycemic index can be estimated in vitro with good accuracy through an artificial digestive apparatus, or dynamic gastric model (DGM) but the gold standard remains the analysis of the glycemic response on subjects in vivo, typically volunteers. The ISO standard 26642 guidelines of 2010 represent the gold standard for the analysis of GI in humans and consists of a few simple steps that require blood sampling to determine blood sugar at the time 0, 15, 30, 45, 60, 90, and 120 min. The GI is but the average of the proportions between the sum of the 7 areas created by placing time on the abscissa (in minutes) and the ordinate blood sugar levels at each T (expressed in mmol/L or mg/dl) after consuming the test food compared to the sum of the areas created after consuming the reference food, usually glucose. Secondly, the modulation of the intake of sugars and calories can also be managed through alternative methods. It has been seen that, for example, different stimuli related to the sense of taste can modulate the sense of hunger and consequently the calorie intake in the following hours. This is especially true with the bitter taste. Appetite modulation due to the administration of particular foods was primarily associated with particular polymorphisms of receptor genes associated particularly with a bitter taste (TAS2R) and sweet (T1R2-T1R3). At the same time, the discovery of extra-oral receptors to recognize bitterness (extra-oral TAS2R) led the researchers to test the effects of administering particular bitter foods without the potential confounding effect of oral ingestion. Among recent studies, some researchers have shown that the effect of reducing energy intake has not been statistically significant in a group of overweight women, at least for some types of encapsulated bitterness while others have proven that an intragastric infusion of bitters significantly reduced hunger in a group of normal-weight women. Another study, in the short term, showed instead that an administration of bitters encapsulated with the base of 'Gentiana Lutea' during the morning meal can significantly reduce the energy intake of the day. Different types of bitters can stimulate different receptors of the TAS2R family. A recent review showed that the bitters most tested and used to determine changes in hunger and energy intake were Quinine, Denatonium Benzoate, Naringin, Secoiridoid, Hops, and Gentian. Bitter compounds, in comparison to other flavors, have proved to be the most effective in influencing eating behavior. This highlights the potential preventive role of bitter flavors in the fight against epidemic obesity. However, further studies are needed to understand which bitters are most useful for this purpose, and which subcategories of the population are most effective. Artemisia Absinthium is an edible and non-toxic plant, commonly called wormwood, for which analgesic, anti-inflammatory, and antidiabetic effects are documented. The bitter extract of this plant, if properly encapsulated, could also affect appetite regulation.The purpose of the first phase of this study is to test the GI of 3 different formulations, in the form of dietary biscuits, on 12 healthy volunteer subjects in order to calculate an average GI necessary for the company that provides the product to enrich the label with a final IG and start marketing. In the second phase, the same subjects will participate in a crossover study to test the same parameters of the first phase, with the addition of an investigation on the effects on hunger with 2 formulations of biscuits different from the first 3, one containing bitter encapsulated Artemisia Absinthium base. The chemotype of Artemisia absinthium used for the extract used is thujoni-free and therefore has no documented contraindication.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: September 1, 2023
• Est. primary completion date: April 11, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Absence of allergies or intolerances to tested foods
• Absence of drugs that affect glucose metabolism. Stable doses of oral contraceptives, acetylsalicylic acid, thyroxine, mineral supplements, medications for hypertension or osteoporosis are accepted.

Criteria for exclusion:

• diagnosis or history of diabetes or reduced glucose tolerance.
• surgery or severe and acute illness in the last 3 months
• use of steroids, protease inhibitors or antipsychotics

Related Conditions & MeSH terms

• Appetitive Behavior
• Consumer Preference
• Hyperglycemia
• Hyperglycemia, Postprandial
• Hyperinsulinism

Intervention

Dietary Supplement:
• Same intervention for both groups: glycaemic index assessment of 3 biscuits recipes
Following International standards ISO 26642 guidelines, subjects (at fasting) will have their glycemia measured and after will consume a solution containing 50g of glucose and 100g of water. In the following 2 hours, glycemia and other blood parameters will be taken 6 times (at 15, 30, 45, 60, 90, and 120 minutes). This protocol is repeated twice within 3 months. After these 2 days, with the same methods, they will come to our clinic to test 3 different recipes of biscuits (characteristics are presented on request). Subjects and investigators are not blinded to these biscuits characteristics.
• Crossover: Recipe 4 before recipe 5
After the assessment of fasting parameters, subjects will consume recipe 4 (chocolate biscuits) and perform a 180 min curve with blood taken at 15, 30, 45, 60, 90, 120, and 180 minutes. In this case, both investigators and patients are blinded to the presence of an additional "non-nutritive, non-toxic and without taste" encapsulated bitter compound (artemisia absinthium), that could be present in recipe 4 or recipe 5. On the second day (with at least a week gap), patients will consume recipe 5. Questionnaires and a food diary will also be requested for subjects for lunch and dinner.
• Crossover: Recipe 5 before recipe 4
Same as previous group, but starting with recipe 5

Locations

Country	Name	City	State
Italy	: Italy Pediatric Endocrine Service of AOU Maggiore della Carità of Novara; SCDU of Pediatrics, Department of Health Sciences, University of Eastern Piedmont	Novara

Sponsors (3)

Lead Sponsor	Collaborator
Azienda Ospedaliero Universitaria Maggiore della Carita	Albertengo Panettoni, Polo AgriFood - Miac Scpa

Country where clinical trial is conducted

Italy, 

References & Publications (10)

Chupeerach C, Tapanee P, On-Nom N, Temviriyanukul P, Chantong B, Reeder N, Adegoye GA, Tolar-Peterson T. The influence of TAS2R38 bitter taste gene polymorphisms on obesity risk in three racially diverse groups. Biomedicine (Taipei). 2021 Sep 1;11(3):43-49. doi: 10.37796/2211-8039.1175. eCollection 2021. — View Citation

Deloose E, Janssen P, Corsetti M, Biesiekierski J, Masuy I, Rotondo A, Van Oudenhove L, Depoortere I, Tack J. Intragastric infusion of denatonium benzoate attenuates interdigestive gastric motility and hunger scores in healthy female volunteers. Am J Clin Nutr. 2017 Mar;105(3):580-588. doi: 10.3945/ajcn.116.138297. Epub 2017 Feb 1. — View Citation

Englyst KN, Vinoy S, Englyst HN, Lang V. Glycaemic index of cereal products explained by their content of rapidly and slowly available glucose. Br J Nutr. 2003 Mar;89(3):329-40. doi: 10.1079/BJN2002786. — View Citation

Kaur B, Ranawana V, Henry J. The Glycemic Index of Rice and Rice Products: A Review, and Table of GI Values. Crit Rev Food Sci Nutr. 2016;56(2):215-36. doi: 10.1080/10408398.2012.717976. — View Citation

Loper HB, La Sala M, Dotson C, Steinle N. Taste perception, associated hormonal modulation, and nutrient intake. Nutr Rev. 2015 Feb;73(2):83-91. doi: 10.1093/nutrit/nuu009. — View Citation

Ludwig DS. The glycemic index: physiological mechanisms relating to obesity, diabetes, and cardiovascular disease. JAMA. 2002 May 8;287(18):2414-23. doi: 10.1001/jama.287.18.2414. — View Citation

Peters HPF, Koppenol W, Schuring EAH, Gouka R, Mela DJ, Blom WAM. The effect of two weeks ingestion of a bitter tastant mixture on energy intake in overweight females. Appetite. 2016 Dec 1;107:268-273. doi: 10.1016/j.appet.2016.08.013. Epub 2016 Aug 10. — View Citation

Sivakamasundari SK, Priyanga S, Moses JA, Anandharamakrishnan C. Impact of processing techniques on the glycemic index of rice. Crit Rev Food Sci Nutr. 2022;62(12):3323-3344. doi: 10.1080/10408398.2020.1865259. Epub 2021 Jan 27. — View Citation

Soh NL, Brand-Miller J. The glycaemic index of potatoes: the effect of variety, cooking method and maturity. Eur J Clin Nutr. 1999 Apr;53(4):249-54. doi: 10.1038/sj.ejcn.1600713. — View Citation

Wang Q, Liszt KI, Depoortere I. Extra-oral bitter taste receptors: New targets against obesity? Peptides. 2020 Feb 21;127:170284. doi: 10.1016/j.peptides.2020.170284. Online ahead of print. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Weight	Assessment of weight in each day as a potential confounding factor during statistical analyses	At fasting for each of the 7 days
Other	Body circumferences	Assessment of body circumferences (waist and hip) in each day as potential confounding factors during statistical analyses	At fasting for each of the 7 days
Primary	Blood Glucose	Variation of glucose in time for each day after the ingestion of a certain food	Change from fasting glucose at time 15, 30, 45, 60, 90, 120, (180) minutes
Primary	COEQ (Control of Eating Questionnaire)	Variation of 20-item COEQ questionnaire 100mm VAS scales for each day after the ingestion of a certain food. Hunger, satiety, quality of life, and food craving were assessed through a 100 mm VAS-scale	Differences between VAS scores before food ingestion (h 9:00), before lunch (h: 13:00), and before dinner (h: 20:00)
Primary	Ghrelin	Variation of blood acylated and des-acylated ghrelin in time for each day after the ingestion of a certain food	Change from fasting ghrelin at time 15, 30, 45, 60, 90, 120, (180)
Primary	GLP-1	Variation of blood GLP-1 in time for each day after the ingestion of a certain food	Change from fasting GLP-1 at time 15, 30, 45, 60, 90, 120, (180)
Secondary	Insulin	Variation of blood Insulin in time for each day after the ingestion of a certain food	Change from fasting Insulin at time 15, 30, 45, 60, 90, 120, (180)
Secondary	C-Peptide	Variation of blood C-Peptide in time for each day after the ingestion of a certain food	Change from fasting C-Peptide at time 15, 30, 45, 60, 90, 120, (180)
Secondary	Leptin	Assessment of fasting leptin in each day	At fasting for each of the 7 days
Secondary	Glycated Hemoglobin (Hb1ac)	Assessment of fasting Hb1ac in each day	At fasting for each of the 7 days
Secondary	Customer preference and satisfaction	Assessment of subject personal taste and preferences after the ingestion of the biscuits recipes. Questions are regarding taste, smell, consistency and knowledge about functional foods	After the ingestion for each of the 5 days with biscuits