Discovering healthy sweetness, through an understanding of what it is not

Much has been said on the topic of sweetness, and how we can best reduce the burden of chronic disease by influencing dietary choices. This has led to an appropriate focus on the role of sugar. However, most of the current efforts from lawmakers are designed to chase people away from sugar, without a clear direction for these consumers to move, or even a clear understanding of what constitutes ‘healthy’ sweetness in the first place. Typically, the discussion focuses on sugar, calories and the glycemic index, or on the differences between artificial and natural sweeteners. Consumers, meanwhile, are beginning to move ahead of this curve, and are increasingly deciding which products they best trust to deliver this outcome.

Below are a few key differentiators that may help you to build some ideas into a long-term solution for healthy sweetness, providing the opportunity for consumers to select your product as a natural part of this transition:

Are all sugars the same?

The answer is no.

While we could rate sugars in terms of their calorific content or their glycemic index, their metabolic rate would be far more relevant. Theoretically, we can say that glucose, fructose and saccharose have the same number of calories (4kcal/g) and that tagatose is a lower calorie monosaccharide (arguably between 1.5 and 3 kcal /g (EFSA, 2016)).  We can also note that fructose and tagatose do not possess a high glycemic index, while glucose and saccharose do.

Do these differences make fructose and tagatose healthier molecules than sugar or glucose? Based on research, they do not.

Sucrose – or sugar, as it is better known, is comprised of glucose and fructose. Glucose metabolism allows for two key outcomes.

  1. Storage as glycogen in multiple tissues (including muscle)
  2. Creation of a feedback loop that tightly regulates glucose and its metabolites

 

Blood glucose rises as a response to meals, and insulin is secreted to allow proper glucose uptake by cells. When there is dysfunction in this pathway, such as insulin resistance (pre-diabetes), the levels and duration of blood glucose elevations are higher. Fructose consumption on its own does not acutely trigger a blood glucose and insulin response. However, ironically, one key cause of chronic insulin resistance is overconsumption of fructose. – which also acts the trigger for the creation of this issue in animal testing conditions.

Glucose and fructose are centrally metabolized by the liver into triglycerides, both by downregulating beta oxidation (fat burning) and by up-regulating the genetic pathways of de novo lipogenesis (DNL) (Rebollo et al, 2014).  This increases blood triglycerides, as well as visceral fat accumulation, impacting the functions of those affected organs – the liver and the pancreas in particular. Fructose has been demonstrated to generate more liver fat more rapidly, versus glucose and sucrose, due to both DNL and to increased endotoxin-induced inflammation (Herck et al, 2017; Bergheim et al, 2008).

Fructose is also related to a depletion of inorganic phosphate (Abdelmalek et al 2012), which therefore negatively affects the ATP (or energetic potential) of our cells, causing an intracellular stress response.  Tagatose, while lower in calories, follows the same metabolic pathway as fructose (EFSA, 2016). In order to fulfil the ultimate goal of improving health through the regulation and labeling of sugars, this process should be carefully reviewed in order to provide the right stimuli and differentiation within different sugar molecules, both for consumers and for food formulators. While consumer demand may move more swiftly than regulatory change, those who take the lead in this process are likely to reap the rewards.

 

Artificial sweeteners are not metabolized by our body, so do they behave as inert compounds?

Sucralose is a compound with a misleadingly natural-sounding name, as it is the result of an artificial chlorination of sugar. Because sucralose cannot be metabolized by our bodies, we assume it to be inert. According to a growing body of research however, it is becoming apparent that it is anything but inert. The synthetic triple chlorination of the sugar molecule produces the sucralose molecule – which possess a high affinity for our sweet receptors T1R2-T1R3.

Sweetness is a highly regulated process triggered in our mouths, which sends signals to our brain and initiates a cascade of reactions, including of course, the specific place and time where sweet molecules should be metabolized. The way sweetness is perceived by our cell receptors is not trivial, much like the subsequent responses of our metabolisms.

Many sweet molecules are degraded and metabolized after being sensed. Sugars and other naturally originated sweeteners, such as stevia, are instead partially or completely degraded as they pass through the digestive process. Compound such as saccharin and sucralose, on the other hand, are not degraded by our metabolism.

This is relevant, as despite the fact that we do not feel ‘sweetness’ in our livers, our pancreas’ or our fat cells, these organs remain totally capable of sensing this sweetness and can modify metabolic performance as a result. This means that, in effect, any molecule that has not been metabolized or degraded will eventually interfere and stimulate other cells in our body, out of reach of our otherwise finely tuned metabolism.

Recent research demonstrates that sucralose triggers an enhanced insulin response from our bodies when fed together with sugars (Letrit et al, 2018) and enhances the glucose uptake capacity through the enhanced synthesis of sweet receptors in lipid cells (Sanchez Tapia et al, 2019), negatively modifying the microflora profile of our guts (Freeley et al, 2014; Bian X et al, 2017).

Once we understand how profoundly sweetness impacts the coordinated metabolism of glucose and how it involves the disappearance or inactivation of the stimuli, we grasp the negative impact of an inert, un-metabolizable, artificial molecule such as sucralose. This is not the case, however, for natural stevia, which is instead degraded into steviol, and which has no negative effects along our digestive system, microflora and metabolism (Philippaert et al, 2017; Gardana et al, 2003). Furthermore, stevia is non-calorific, and thus does not feed into the metabolic pathways of sucrose nor fructose.

Considering the increasing weight of knowledge arising in the field of sweetness and sweeteners, we should once again consider the categories in which we group sweeteners. There are, absolutely, extremely relevant concepts arising beyond intensity of sweetness, calorific reward, naturality and glycemia. These concepts should seriously be taken into consideration as part of the various ongoing sugar replacement laws and bills that are currently under discussion worldwide.

Those who implement smart policies and smart business strategies, consistent with serious scientific evidence about healthy sweetness, will be rewarded.

 

References:

Abdelmalek MF, Lazo M, Horska A, et al. Higher dietary fructose is associated with impaired hepatic adenosine triphosphate homeostasis in obese individuals with type 2 diabetes. Hepatology. 2012;56(3):952-960. doi:10.1002/hep.25741

Bian X, Chi L, Gao B, Tu P, Ru H, Lu K. Gut Microbiome Response to Sucralose and Its Potential Role in Inducing Liver Inflammation in Mice. Front Physiol. 2017;8:487. Published 2017 Jul 24. doi:10.3389/fphys.2017.00487

Bergheim I. et al, (2008), ‘Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: Role of endotoxin’, Journal of Hepatology, 48:6, pp. 983-992

EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2016. Draft Scientific Opinion on the energy conversion factor of D-tagatose for labelling purposes. EFSA Journal 2016;volume(issue):NNNN, 14 pp. doi:10.2903/j.efsa.2016.NNNN

Feehley, T., Nagler, C. The weighty costs of non-caloric sweeteners. Nature 514, 176–177 (2014). https://doi.org/10.1038/nature13752

Gardana C, Simonetti P, Canzi E, Zanchi R, Pietta P. Metabolism of stevioside and rebaudioside A from Stevia rebaudiana extracts by human microflora. J Agric Food Chem. 2003 Oct 22;51(22):6618-22. doi: 10.1021/jf0303619. PMID: 14558786.

Lertrit A, Srimachai S, Saetung S, Chanprasertyothin S, Chailurkit LO, Areevut C, Katekao P, Ongphiphadhanakul B, Sriphrapradang C. Effects of sucralose on insulin and glucagon-like peptide-1 secretion in healthy subjects: a randomized, double-blind, placebo-controlled trial. Nutrition. 2018 Nov;55-56:125-130. doi: 10.1016/j.nut.2018.04.001. Epub 2018 Apr 21. PMID: 30005329.

Philippaert, K., Pironet, A., Mesuere, M. et al. Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity. Nat Commun 8, 14733 (2017). https://doi.org/10.1038/ncomms14733

Rebollo, A. et al. Liquid fructose downregulates Sirt1 expression and activity and impairs the oxidation of fatty acids in rat and human liver cells. Biochim. Biophys. Acta 1841, 514–524 (2014).

Sánchez-Tapia M, Martínez-Medina J, Tovar AR, Torres N. Natural and Artificial Sweeteners and High Fat Diet Modify Differential Taste Receptors, Insulin, and TLR4-Mediated Inflammatory Pathways in Adipose Tissues of Rats. Nutrients. 2019;11(4):880. Published 2019 Apr 19. doi:10.3390/nu11040880

Van Herck, M.A. et al, (2017), Animal Models of Nonalcoholic Fatty Liver Disease—A Starter’s Guide, Nutrients, 9(10): 1072