Conventional models of weight management are built around the concept that “a calorie is a calorie” that overconsumption of calories from any source will lead to weight gain and that no macronutrient source has any special adverse effect on body composition. Overeating (any food) results in increased energy intake and physical inactivity results in lower energy expenditure, leading to increased circulating metabolic fuels (glucose, lipids) and ultimately manifesting as increased fat storage. Weight management strategies under this energy balance model are simple: eat less and exercise more.1
This model is overly simplistic and does not explain the current obesity epidemic or the difficulty that most people have losing weight and their ability in maintaining self-control when eating in modern society. An alternative view is that the types of calories consumed have a material influence on our ability to manage weight. Central to this is the role of high glycaemic index (GI) and glycaemic load (GL) carbohydrates that affect our hormonal responses and shift our energy management towards storage of energy rather than burning calories for energy. This model is known as the carbohydrate-insulin model.2-4
In response to the consumption of carbohydrates, our bodies secrete insulin, which moves glucose out of our blood stream into our cells for energy or for storage as either glycogen or fat in our liver, muscles, and adipose tissue. The amount of insulin released is correlated with the GL of the carbohydrates eaten – the higher the GL, the more insulin is released. The carbohydrate-insulin model proposes that when we eat foods that are rich in carbohydrates, especially high GI and GL carbohydrates like starch and sugar, we induce postprandial hyperinsulinaemia that promotes the deposition of calories in fat cells rather than the oxidation of calories in our lean tissues. Unlike the calorie in/calorie out energy-balance model, where overeating increases circulating metabolic fuels, postprandial hyperinsulinaemia decreases circulating fuels (glucose is taken out of circulation and stored as fat/glycogen), which increases hunger and predisposes us to weight gain.2-4
“The low calorie/low fat diets recommended by eat less/exercise more solutions are destined to fail in most people”
This is the fundamental difference between the models: the energy-balance model purports that overeating leads to fat deposition while in the carbohydrate-insulin model overeating is a consequence of increasing fat deposition, not the primary cause. The low calorie/low fat diets recommended by eat less/exercise more solutions are therefore destined to fail in most people as they will result in further restriction of energy available in the blood, triggering starvation responses of increased hunger, falling metabolic rates and elevated stress hormone levels.2
The role of insulin in weight management can be observed in both controlled and observational studies. Administration of insulin peripherally, as done in treatment of diabetes, typically increases fat deposition, increases hunger, and causes weight gain. Similarly, calorie-restricted animals that are treated with insulin still develop excess body fat.2
Furthermore, the energy balance model does not adequately explain the phenomenon that overeating balanced meals does not cause obesity. In the short term, overeating will result in weight gain, however in the long-term overeating leads to increased energy expenditure and decreased hunger making it difficult to consistently overeat. Clinical overfeeding studies have shown this, and participants report difficulty in complying with the overeating protocol. At the conclusion of these types of studies, body weight spontaneously returns to or near baseline weight. It is only when our energy homeostatic mechanisms are out of balance does body weight trend upwards with continual overeating.2
Maintaining this energy homeostasis is therefore critical in maintaining a healthy weight. Overconsumption of foods that have a high GL, leads to hyperinsulinaemia and weight gain. Many people that are overweight are also insulin resistant, and they need to make and release more and more insulin to remove glucose from the blood. High levels of insulin drives insulin resistance and may also lead to resistance to another hormone – leptin.5
Leptin is one of our main energy regulation hormones and controls how much we eat as well as our energy utilization. It is made by our adipose tissues and when we have excess fat, our leptin levels are high, lowering our desire to eat and increasing fat oxidation. Conversely, in situations of starvation, we feel the urge to eat, and our energy utilization slows.6
High levels of insulin combined with leptin resistance leads to a vicious cycle of weight-gain. Insulin spikes push calories into fat storage before they can be used for energy and lower circulating energy molecules leading to feelings of hunger; this is further exacerbated by leptin resistance. With low levels of leptin reaching the brain, our body goes into starvation mode further increasing the desire to eat and slowing down energy expenditure, making it almost impossible to follow the conventional eat less/exercise more solutions.
“Successful weight management strategies should seek to restore our energy hormone homeostasis and this starts by lowering postprandial hyperinsulinaemia”
Successful weight management strategies should therefore seek to restore our energy hormone homeostasis first. This process starts by lowering and limiting postprandial hyperinsulinaemia.2-4 This can be achieved through reducing refined starches and sugars in our diet and choosing low GL foods such as non-starchy vegetables, legumes, and low GL fruits. The focus should be on the quality not quantity of calories consumed to move away from storing our calories to metabolizing them. Once the balance is restored, energy in/energy out strategies can be successfully implemented.2, 7
The role of ingredients like Reducose® in maintaining a normal, healthy body weight and composition
Reducose® has been shown in several clinical trials to significantly lower the insulin response after consuming carbohydrates as well as lowering the glycemic index of food.8-10 This helps to put the body into fat burning mode and decreases glucose calories stored as fat. Reducose® has also been shown to increase insulin sensitivity11 and published literature report that the active compound in Reducose®, DNJ, increases leptin sensitivity.12
This combination of activities may help maintain a normal, healthy weight and body composition and may break the vicious cycle of weight gain, and for people trying to lose weight, Reducose® may have additional benefits. Reducose® blocks a portion of carbohydrate calories from a meal from getting into the body, allowing them to reach the distal small intestine which can stimulate the ileal brake.
The ileal brake is a nutrient-triggered inhibitory feedback mechanism that induces satiety. When macronutrients bind to receptors in the ileum, the ileal brake is triggered resulting in a slowing of upper gut motility, reduced appetite, and delayed gastric emptying. These activities are mediated through the release of peptide tyrosine tyrosine (PYY), cholecystokinin (CCK), and glucagon-like polypeptide 1 (GLP-1).13
Linked to the ileal brake is the second-meal effect. The second-meal effect is a phenomenon where the GI of one meal can influence the glycemic response to a subsequent meal. Having a low GI intake in one meal lowers the postprandial glycemic response (PPGR) in the subsequent meal. This effect is thought to be mediated through several interacting mechanisms, including through the actions of incretin hormones (GLP-1 & GIP) and by the fermentation of undigested carbohydrates to short-chain fatty acids by the microbiome and their subsequent absorption.14
The benefits of the second-meal effect, observable as a lower postprandial glucose response, extends to weight management. The second-meal effect increases the rate of fat oxidation and favors the use of fat to meet the body’s energy requirements, while people who eat high GI meals favor fat storage and the use of carbohydrates for energy.15
Reducose® therefore can play multiple roles in weight management products:
- Helps lower hyperinsulinaemia, favouring calorie metabolism over calorie storage
- Prevent the ‘sugar crash’ that drives hunger in the postprandial period
- Supports normal and healthy insulin and leptin sensitivity to help break the vicious cycle of weight gain
- Supports increase satiety through the ileal brake helping users bridge between meals when following a calorie restricted diet
- Stimulate the second-meal effect to help maintain a healthy, normal body composition through the increased oxidation of fat
- Schwartz MW, Seeley RJ, Zeltser LM, Drewnowski A, Ravussin E, Redman LM, et al. Obesity Pathogenesis: An Endocrine Society Scientific Statement. Endocr Rev. 2017;38(4):267-96.
- Ludwig DS, Apovian CM, Aronne LJ, Astrup A, Cantley LC, Ebbeling CB, et al. Competing paradigms of obesity pathogenesis: energy balance versus carbohydrate-insulin models. Eur J Clin Nutr. 2022;76(9):1209-21.
- Ludwig DS, Ebbeling CB. The Carbohydrate-Insulin Model of Obesity: Beyond “Calories In, Calories Out”. JAMA Intern Med. 2018;178(8):1098-103.
- Ludwig DS, Aronne LJ, Astrup A, de Cabo R, Cantley LC, Friedman MI, et al. The carbohydrate-insulin model: a physiological perspective on the obesity pandemic. Am J Clin Nutr. 2021;114(6):1873-85.
- Lustig RH, Sen S, Soberman JE, Velasquez-Mieyer PA. Obesity, leptin resistance, and the effects of insulin reduction. Int J Obes Relat Metab Disord. 2004;28(10):1344-8.
- Schwartz MW, Woods SC, Porte D, Jr., Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature. 2000;404(6778):661-71.
- Hall KD, Farooqi IS, Friedman JM, Klein S, Loos RJF, Mangelsdorf DJ, et al. The energy balance model of obesity: beyond calories in, calories out. Am J Clin Nutr. 2022;115(5):1243-54.
- Lown M, Fuller R, Lightowler H, Fraser A, Gallagher A, Stuart B, et al. Mulberry-extract improves glucose tolerance and decreases insulin concentrations in normoglycaemic adults: Results of a randomised double-blind placebo-controlled study. PLoS One. 2017;12(2):e0172239.
- Thondre PS, Lightowler H, Ahlstrom L, Gallagher A. Mulberry leaf extract improves glycaemic response and insulaemic response to sucrose in healthy subjects: results of a randomized, double blind, placebo-controlled study. Nutr Metab (Lond). 2021;18(1):41.
- Wang R, Li Y, Mu W, Li Z, Sun J, Wang B, et al. Mulberry leaf extract reduces the glycemic indexes of four common dietary carbohydrates. Medicine (Baltimore). 2018;97(34):e11996.
- Liu Y, Li X, Xie C, Luo X, Bao Y, Wu B, et al. Prevention Effects and Possible Molecular Mechanism of Mulberry Leaf Extract and its Formulation on Rats with Insulin-Insensitivity. PLoS One. 2016;11(4):e0152728.
- Kim J, Yun EY, Quan FS, Park SW, Goo TW. Central Administration of 1-Deoxynojirimycin Attenuates Hypothalamic Endoplasmic Reticulum Stress and Regulates Food Intake and Body Weight in Mice with High-Fat Diet-Induced Obesity. Evid Based Complement Alternat Med. 2017;2017:3607089.
- Maljaars PW, Peters HP, Mela DJ, Masclee AA. Ileal brake: a sensible food target for appetite control. A review. Physiol Behav. 2008;95(3):271-81.
- Fletcher J.A. PJ, Thyfault JP, Rector, RS. The second meal effect and its influence on glycemia. Nutritional Disorders & Therapy. 2012;2.
- Henry CJ, Kaur B, Quek RYC, Camps SG. A Low Glycaemic Index Diet Incorporating Isomaltulose Is Associated with Lower Glycaemic Response and Variability, and Promotes Fat Oxidation in Asians. Nutrients. 2017;9(5).