NUTRACORE, Glycaemic Index and Appetite
Condition: Hyperglycemia; Hyperglycemia, Postprandial; Appetitive Behavior; Hyperinsulinism; Consumer Preference
MeSH terms: Hyperglycemia; Hyperinsulinism
Study type: Interventional

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.
    

Detailed 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.
    

Intervention name(s): Same intervention for both groups: glycaemic index assessment of 3 biscuits recipes; Crossover: Recipe 4 before recipe 5; Crossover: Recipe 5 before recipe 4
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): 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.; 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.; Same as previous group, but starting with recipe 5
Other intervention name(s): Recipe 1,2,3; Recipe 4-5; Recipe 5-4
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This study is composed by 2 parts. The same participants are enrolled in a single arm study (5 days), followed by a cross-over part (2 days)
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Other