A Review of Sweetener Alternatives as Sugar Replacements in Food & Beverage Products
Prepared in support of the KDD’s Metabolic Reengineering Initiative
Sweetener Review was drafted and written by Sawsan Abusharkh, and supervised and edited by Rachel Gow, PhD in support of a Dasman Diabetes Institute (DDI) Clinical Trial funded by a Kuwait Foundation for the Advancement of Science (KFAS) grant to the Kuwaiti Danish Dairy Company.
October 6, 2022
Table of Contents
Sweetener Alternatives to Sugar. 6
6.4 Adverse Side Effects and Health Concerns. 25
Food Additives as Modifying Agents. 28
Concluding Remarks and Future Direction. 37
Table of Abbreviations
| ADI |
Acceptable daily intake
|
| DKP | Di-ketopiperazine |
| EFSA |
European Food Safety Authority
|
| EC/SCF |
European Commission Scientific Committee on Food
|
| US FDA |
The United States Food and Drug Administration
|
| GMP |
Good Manufacturing Practice
|
| GRAS |
Generally Recognized as Safe
|
| GSO, GCC |
Gulf Cooperation Council) Standardization Organization
|
| HbA1c |
Hemoglobin A1c
|
| JECFA |
Joint FAO/WHO Expert Committee on Food Additives
|
| SCFA | Short Chain Fatty Acids |
Introduction
The increase in the prevalence of type 2 diabetes is currently one of the major threats to public health worldwide. Kuwait is among the top ten countries with the highest rates of diabetes, with almost 20% of individuals diagnosed, and many more estimated to be unaware of their condition. A number of factors influence the progression of type 2 diabetes, namely a sedentary lifestyle and the habitual consumption of ultraprocessed foods and simple carbohydrates (e.g., sucrose and fructose) (Chukwuma et al., 2018). Excess sugar consumption is associated with an increased risk of poor metabolic health, e.g., weight gain, obesity, and type 2 diabetes (Moore & Fielding, 2016). Reducing sugar intake has been the focus of several international health campaigns and more recently is being addressed by major food production organizations. Although the food industry has previously shifted its focus towards low-calorie food products and zero-calorie sugar alternatives, these are now being called into question.
KDD has implemented a significant initiative to re-engineer its portfolio for optimal metabolic impact. A metabolic matrix (featured elements at https://metabolicmatrix.info) has been developed by KDD and its Scientific Advisory Team (SAT). The pillars of this matrix are “Support the Brain, Protect the Liver, and Feed the Gut.” Reducing sugar and determining sugar alternatives are requirements specified in a “Tiers” document that features 38 criteria in five levels structured to improve the metabolic impact of KDD’s products. Two criteria specifically include “no more than 2 grams of added fructose per serving” and “no more than 4 grams of added glucose per serving.” A broader criterion of “no additives with health risks” is also included to target ingredients such as sweeteners.
Determining alternatives to sugar was an effort performed by KDD’s SAT and Human & Environmental Health, Product Development, and Marketing departments. Any alternatives to sugar were measured in terms of metabolic impact, biochemistry for formulations, availability and costs, regulatory and labeling requirements, and market feedback. Products formulated with alternatives to sugar were tested internally and externally for sensory acceptance. Additionally, shelf-life studies and product development trials were conducted by the Product development team to assess the viability of the products. KDD’s standards for quality require that “no-added-sugar” products are expected to taste as good as the sugar-added versions, with no compromise in quality or taste.
This review provides a detailed overview of commercially available sugar alternatives, both synthetic and natural options, with a focus on metabolism, health impacts, side effects, and regulatory practice. The review was used to determine the optimal sugar alternative solutions for use in KDD products.
Sweetener Alternatives to Sugar
1 | Erythritol
1.1 Overview
Erythritol is a natural sweetener that belongs to the sugar alcohol (polyol) family (Munro, Berndt, et al., 1998). Polyols such as sorbitol, xylitol, and mannitol are naturally present in fruits and vegetables and fermented foods such as soy sauce. The global shift towards using polyols in food formulations can be broadly attributed to their non-nutritive properties. Sugar alcohols can act as sweeteners but have been designated to the nonnutritive category due to their low-calorie content (Msomi et al., 2021). Erythritol is the most widely used sugar alcohol in food preparations. It differs from other polyols because it can be produced industrially via various biological processes, while other polyols are produced chemically (Munro, Bernt, et al., 1998).
The Scottish chemist John Stenhouse first discovered Erythritol in 1848. One hundred years later in 1950, traces of erythritol were found in blackstrap molasses that had been fermented by yeast (Regnat et al., 2018). Erythritol is produced via enzymatic hydrolysis, in which wheat or corn starch is transformed into glucose and then added to yeast for fermentation purposes (Rzechonek et al., 2018). The microbial cells are discarded, and the erythritol crystals are separated and concentrated to produce the sweetener (Rzechonek et al., 2018).
Erythritol crystals possess 60-80% of the sweetness of sugar. Erythritol is marketed as a zero-calorie sweetener and is added to food formulations to improve mouthfeel and mask unwanted and bitter aftertastes of other intense sweeteners (Regnat et al., 2018). It retains moisture, is heat stable, and is unaffected by alkaline or acidic pH (Regnat et al., 2018). All of which makes it more advantageous to food manufacturers. The physical and chemical properties of erythritol render it suitable for use in no-added sugar, reduced-sugar, and sugar-free food products, including non-alcoholic beverages, chocolate, and chewing gum (Regnat et al., 2018).
1.2 Metabolism
Erythritol cannot be metabolized by the body and is excreted unchanged in the urine. Following ingestion, 90% of erythritol is absorbed from the proximal intestine by passive diffusion (i.e., moving from an area of a higher concentration to an area of lower concentration) (Hiele et al., 1993). Unabsorbed erythritol is transported to the large intestine, where it is fermented by gut microbiota to short-chain fatty acids (SCFA) (Munro, Bernt, et al., 1998).
1.3 Health Impacts
Toxicity. Several experimental animal studies and human clinical trials have investigated erythritol’s safety and health impacts (Msomi et al., 2021; Munro, Berndt, et al., 1998). The safety report issued by the European Food Safety Authority (EFSA) has confirmed that erythritol is safe for human consumption. No evidence supports any toxicity impacts (Authority, 2010). However, the results of a study conducted by Bornet and others (1996) demonstrated that ingesting a single large dose of 0.8 grams per kilogram body weight (g/kg bw) of erythritol caused abdominal rumblings, flatulence and nausea (Bornet et al., 1996). Based on this result, the EFSA standardized maximum tolerable daily limits of erythritol to 0.8g/ kg bw.
Blood Glucose Reduction. Several studies investigating the effects of erythritol on blood glucose and insulin levels in non-diabetic and diabetic individuals reported no significant adverse impacts (Livesey, 2003; Msomi et al., 2021; Wölnerhanssen et al., 2020). Ishikawa and others (1996) reported that the daily erythritol ingestion (20g) by diabetic patients for 14 days was linked to a decrease in both fasting blood sugar and serum hemoglobin A1c (HbA1c), which is considered advantageous for glycemic control in diabetic patients (Ishikawa et al., 1996).
Endothelial Function. A pilot study by Flint et al. (2014) recruited 24 participants to investigate potential positive impacts in patients with diabetes mellitus. They found that 12g of erythritol consumed three times daily had favorable effects on small vessel endothelial vasodilator function, hypertension, and central aortic stiffness suggesting an improvement in vascular health status. However, two significant limitations of this study are the absence of a control group and the small sample size (n=24) (Flint et al., 2014).
Gut health. A recent search on the clinical database PubMed revealed no published studies investigating erythritol’s impact on gut microbiota. However, it has been hypothesized that since the sweetener is undigested in the body, it is not likely to affect gut microbial composition (Wölnerhanssen et al., 2020). Further studies are needed to support this hypothesis.
1.4 Side Effects
Polyols can cause laxative effects, flatulence and abdominal pain when consumed in excess (Rice et al., 2020). Since the body absorbs erythritol more readily compared to other polyols, it is thought to produce less intestinal discomfort and nausea (Lenhart & Chey, 2017). Studies have been conducted to assess tolerance in humans and to determine the maximum tolerated concentration of erythritol (Bornet et al., 1996; Storey et al., 2007). Bornet and others (1996) reported an estimate of 0.8g/kg bw/day in adult subjects (Bornet et al., 1996). EFSA assessed the maximum tolerated concentration of erythritol in children aged 4-6 and estimated these to be 0.71g/kg bw/day (Authority, 2010).
1.5 Regulations
The European Commission supported recommendations by EFSA and set the maximum level of use of erythritol (E 968) as a food additive at 1.6% (Authority, 2010). The Joint FAO/WHO Expert Committee on Food Additives (JECFA) has set a “not specified” acceptable daily intake (ADI) for erythritol. The Food and Drug Administration (FDA) in the United States regards erythritol as Generally Recognized as Safe (GRAS) for use in food products. The GCC Standardization Organization (GSO) lists a “not specified” amount for erythritol in food preparations. However, the general requirements for using sweeteners in food and beverages state that the maximum limit for erythritol in beverages shall not exceed 2.5% for purposes other than sweetening. The GSO also specifies the need for the inclusion of a warning statement on products that contain erythritol, stating that the “increased consumption of erythritol can cause diarrhea.” The maximum levels of use of erythritol in food products as indicated by GSO are included in Table 1 of the appendix.
2| Maltitol
2.1 Overview
Maltitol is a disaccharide produced from maltose that comprises a glucose and sorbitol unit. Maltitol also belongs to the polyol family (Saraiva et al., 2020). This sugar-alcohol occurs naturally in different fruits and vegetables, roasted malt, and chicory leaves. Maltitol is industrially produced through enzymatic hydrogenation (i.e., the addition of hydrogen to a chemical molecule in the presence of an enzyme) of cereal starch from corn, wheat, and potatoes (Saraiva et al., 2020).
Maltitol is favored over other polyols by food manufacturers due to its similar sweetness to sugar (Saraiva et al., 2020). Maltitol has 75-90% of the sweetness of sugar and equivalent water solubility, viscosity, and mouthfeel. Maltitol differs from other sugar-alcohols in that it has low hygroscopic properties (i.e., the ability to absorb moisture from surrounding environments), and unlike sugar, it is non-reducing. In other words, it does not react with amino acids when heated to produce caramelizing molecules (Saraiva et al., 2020). The conversion of maltose to maltitol enhances the thermo-chemical stability of maltitol, making it suitable for many heat-dependent food applications (Saraiva et al., 2020). In addition to acting as a sweetener, maltitol acts as a bulking agent, humectant, emulsifier, stabilizer, and thickener. Maltitol has a lower calorie content than sugar, i.e., 2.4 kcal/g compared to 4kcal/g obtained from sugar. For that reason, maltitol is commonly used in sugar-free and sugar-reduced chocolate, dairy, baked products, and sweets.
2.2 Metabolism
Like other polyols, maltitol is also poorly absorbed by the small intestine and only partially absorbed by the proximal intestine. It then enters the lower intestine and colon, where it is fermented slowly by gut flora into glucose and sorbitol (Oku et al., 1991; Rérat et al., 1991). The glucose is absorbed into the portal vein and then circulated around the body for use in multiple functions. Whereas sorbitol is absorbed minimally by the body and then enzymatically metabolized in liver cells into fructose and later into glycogen or glucose. Unabsorbed sorbitol gets fermented by the gut microbiota into SCFA and gases (Levine et al., 1978). Very small amounts of maltitol are passed unchanged in the urine.
2.3 Health Impacts
Anti-hyperglycemic properties. Several studies have suggested that maltitol may have anti-hyperglycemic properties (Mimura et al., 1972; Msomi et al., 2021; Thabuis et al., 2015). Thabuis and colleagues (2015) recruited 12 healthy individuals and allocated them a single dose of 50g of maltitol. The findings of this small case-control study reported lower glycemic and insulin responses in the experimental group compared to the intervention group that consumed glucose (Thabuis et al., 2015). Comparably, in a study conducted by Mimura and others (1972), diabetic patients who consumed a single dose of 30 or 50g of maltitol had lower glucose and insulin responses compared to diabetic patients who consumed maltose or glucose (Mimura et al., 1972). The mentioned studies are limited by small participant sizes and short evaluation periods. Chronic evaluations with bigger sample sizes are required to clarify the anti-hyperglycemic property of maltitol.
Weight management. Quilez and colleagues (2007) tested the impact of consuming two types of muffins on the feeling of satiety in healthy but overweight participants over one week. The experimental group received a muffin that contained 22.6g maltitol and high-amylose corn starch, and the intervention group received a muffin that contained sugar. The results reported reductions in insulin, lipidaemic, and glucose responses and increased satiety rates compared to sugar-sweetened muffins (Quílez et al., 2007). It is important to note that the results of this study were based on a single consumption and had a small participant number (n = 14). For these reasons, further investigation and replication are warranted to suggest that maltitol might be advantageous for weight management.
2.4 Side Effects
Sugar alcohols are known to cause laxative effects. Maltitol can cause diarrhea, flatulence, and mild intestinal rumbling when consumed in large doses. For example, a 40g dose may cause an intolerable laxative effect in adults, and 15g may cause an intolerable laxative effect in children (Ruskoné-Fourmestraux et al., 2003; Thabuis et al., 2010). Grabitske and Slavin (2009) reviewed published studies on the gastrointestinal effects of maltitol consumption and reported that the consumption of maltitol concentrations above 60-70g was associated with diarrhea and abdominal bloating (Grabitske & Slavin, 2009).
2.5 Regulations
The EFSA and the Codex Alimentarius Commission have established the safety of maltitol for human consumption and use as a sweetener in food products after examining data from various toxicological studies. The JECFA has also determined maltitol as safe for human consumption. However, the ADI of the additive was determined as “not specified.” Maltitol is certified GRAS by the US FDA for use in food products. The GSO has set a “not specified” ADI for maltitol. The European Commission, FDA, and GSO all require the inclusion of an advisory statement on food products containing maltitol listing that “excessive consumption may produce laxative effects.”
3| Stevia
3.1 Overview
Stevia is a genus within the family of Asteraceae, which includes 230 species of perennial shrubs native to Brazil, Paraguay and Argentina (Goyal et al., 2010). The sweetening compounds produced by different Stevia species vary in sweetness, with S. rebaudiana Bertoni compounds ranking as the sweetest.
In the 1990s, Stevia extract was available in the United States as a dietary supplement in health food stores; however, the unpurified extracts possessed a strong off taste and efforts were made to purify extracts, so they only produced the sweetening component (Haida & Hakiman, 2020). Stevia preparations are now available in the marketplace in many different forms, e.g., Stevia leaves, leaf powder, extracts, and liquid concentrates.
Countries such as Japan, Canada, Australia, and the United States have adopted the use of Stevia as a sugar alternative. Stevia is naturally sourced and estimated to be approximately 200-300 times sweeter than sugar (Goyal et al., 2010). The chemical components – steviol diterpene glycosides – are responsible for the sweetness in Stevia. Stevia leaves contain up to 40 different steviol glycosides, including sativoside (4-13%) and rebaudioside A (2.3-3.8%), which are the most abundant, and others, such as rebaudioside (Reb) A, B, C, D, E, and M and dulcoside A. Some steviol glycosides are also manufactured from sugarcane using precision fermentation technology to make rebaudiosides such as Reb M, with significant improvements in taste and bitterness, and produced on a commercial scale.
Stevia is non-caloric and stable at temperatures as high as 198 C (Pawar et al., 2013).
Some forms of Stevia have a bitter aftertaste which is attributable to the rebaudioside A molecule. Rebaudioside M forms lack the bitter aftertaste, eliminating the bitterness concern associated with Stevia (Guo et al., 2022). Bulking agents such as sugar alcohols and fibers are used in combination with Stevia to mimic the texture effects of sugar (Goyal et al., 2010). Stevia is most commonly used in flavored and carbonated drinks, dairy products including fermented milk products, edible ices, tabletop sweeteners, fruit and vegetable preparations, jams and jellies, cocoa and chocolate products, confectionery and chewing gum (Peteliuk et al., 2021).
3.2 Metabolism
Steviol glycosides are not digested in the human gastrointestinal tract. Instead, microbiota hydrolyzes sugar moieties within steviol glycosides in the colon, leaving the steviol backbone behind. Steviol is then absorbed into the liver and excreted in the urine. The released sugar moieties are not absorbed by the body and serve as an energy source for gut microbes (Samuel et al., 2018).
3.3 Health Impacts
Purified Stevia extracts have been considered safe for human consumption as sweeteners in food products and beverages. Many reviews have discussed the functionality and health impacts of Stevia on glycemic control, blood pressure, energy intake, gut microbiota, oral health, and brain function (Chavushyan et al., 2017; Peteliuk et al., 2021; Samuel et al., 2018; Urban et al., 2015)
Blood Homeostasis. Gregersen et al. (2004) found that the consumption of stevioside with a meal was associated with a reduction in postprandial (i.e., following a meal) blood glucose and an increase in insulin secretion in diabetic individuals who had stopped their antidiabetic medication (Gregersen et al., 2004). Contrarily, 250mg of rebaudioside A consumed four times daily by type 2 diabetes patients over 16 weeks was reported not to influence blood glucose and insulin levels or resting blood pressure (Maki et al., 2008). Similarly, the consumption of steviol glycoside three times daily for three months by healthy individuals and type 1 and type 2 diabetes patients with normal and low-normal blood pressure was demonstrated to have no adverse effects on blood glucose homeostasis and blood pressure (Barriocanal et al., 2008). Conversely, Chan and others (2000) reported that the consumption of 250mg of stevioside three times daily over a year resulted in a significant reduction in the blood pressure of hypertensive participants (Chan et al., 2000). Comparably, Hsieh et al. (2003) reported that the intake of 500mg of stevioside three times daily over two years in stage 1 hypertensive patients was associated with a significant reduction in systolic and diastolic blood pressure compared to those in the placebo group (Hsieh et al., 2003). The data exploring the impact of steviol glycoside consumption on blood glucose homeostasis and blood pressure is conflicting, and further research is needed to draw any firm conclusions.
Energy intake. Farhat and others (2021) have reported that a typical consumer belief concerning nonnutritive sweeteners is that due to their non-caloric nature, they are perceived to increase energy intake and appetite (Farhat et al., 2021). Contrary to that belief, research by Anton and others (2010) found that consumption of stevia-sweetened meal-preload was associated with a reduced energy intake during meal consumption in lean and obese individuals compared to a sucrose meal preload. The authors of this study further suggested that Stevia consumption may be a suitable sugar alternative for healthy weight management (Anton et al., 2010).
Gut microbiota. Very few studies have investigated steviol glycosides’ impact on gut microbiota composition in vitro (Gardana et al., 2003; Mahalak et al., 2020). In a study by Gardana et al. (2003), the incubation of human fecal matter with 40mg of stevioside and 40mg of rebaudioside A, did not significantly alter the composition of human gut microbiota. However, the authors reported that stevioside had a slight inhibitory effect on total aerobic bacteria, while rebaudioside A slightly inhibited total aerobes and coliforms (Gardana et al., 2003). Mahalak and others (2020) reported that the inoculation of human stool samples with 6.2mg/kg per day (based on an average adult weight of 68kg) of Splenda Naturals plus Stevia had no significant impact on human microbial composition. The authors reported that the Splenda Naturals plus Stevia sample consisted majorly of erythritol with approximately 1% or less of the steviol glycoside rebaudioside D. The low concentration of steviol glycosides is a significant limitation of their findings (Mahalak et al., 2020).
Antioxidant effects. Ruiz Ruiz and others (2014) reported that the biochemical composition analysis of Stevia leaves demonstrated the presence of phenolic compounds, namely polyphenols and flavonoids, which possess antioxidant properties (Ruiz Ruiz et al., 2014). The phenolic compounds in Stevia leaves were reported to have the ability to neutralize free radicals and chelate transition metal ions, suggesting a protective antioxidant effect against free-radical formation (Ruiz Ruiz et al., 2014). However, further studies are needed to fully explore Stevia’s antioxidant capabilities in humans.
3.4 Side Effects
The plants within the Asteraceae family are known to induce hypersensitivity reactions through inhalation, ingestion, and other exposure routes. However, this allergenic reaction is caused by the entire plant instead of a purified extract (Urban et al., 2015). A literature search provided no evidence to support the allergenic potential of purified steviol glycosides. Furthermore, regulatory agencies, including EFSA and Health Canada, are not concerned about potential allergic reactions of purified steviol glycosides when used as a food additive. Regulatory bodies have specified that steviol glycosides contain at least 95% purity in all food preparations.
3.5 Regulations
Regulatory authorities have set a high specification for stevia at ≥ 95% purity for use as a sweetener in food products and beverages. The JECFA set the safe level of use of steviol glycosides with a minimum purity of 95% in beverages, including soft and fruit drinks, as 600mg/kg for nine approved steviol glycosides. The FDA has categorized highly purified steviol glycosides obtained from stevia leaves as GRAS for use as a sweetener in food. An ADI was set as 0-4mg steviol equivalents (SEs)/ kg/ day by EFSA as all steviol glycosides get metabolized into steviol hence making the ADI applicable to all steviol glycosides. The GSO has set the standard for adding stevia in food preparations, specifically steviol glycosides, to be in the range of 0 to 4 mg/kg bw.
4| Monk Fruit
4.1 Overview
Monk fruit, also known as Luo Han Guo (Buddha fruit) or Siraitia grosvenorii, is a perennial herb indigenous to China and Indonesia (Pandey & Chauhan, 2020). Siraitia grosvenorii species is mainly cultivated in the Guangxi province of China and accounts for more than 90% of the global production of Monk fruit (Pandey & Chauhan, 2020). Traditionally, the Chinese population has used the fruit as a natural sweetener in food and a household remedy for nourishing the lungs and treating sunstroke, thirst, constipation, sore throat, cough and cold (Pandey & Chauhan, 2020). Although the fruit has been used for centuries, it was not approved for use as a sweetener by the FDA until 2010.
Monk fruit contains natural sugars, namely fructose and glucose, and its intense sweetness derives from unique antioxidants called mogrosides. Mogroside extracts are thought to have anti-inflammatory effects and, due to their antioxidant content, may help protect against oxidative stress and damage from free radicals to DNA. During the processing of extracts, the mogrosides are separated from the freshly pressed juice; therefore, monk fruit sweetener does not contain fructose or glucose. A specific type of mogroside called mogroside V is the primary component of monk fruit sweetener. Monk fruit extract may be 100-250 times sweeter than table sugar. Many food and beverage manufacturers mix monk fruit extract with other natural products such as inulin or erythritol to reduce the intensity of the sweetness. Monk fruit extract is used as a standalone sweetener, flavor enhancer, and ingredient in food and beverage products.
Monk fruit extract is a natural sweetener that is low in calories, heat stable and unaffected by pH ranging from 3-10 (Younes et al., 2019). Unlike Stevia, Monk fruit extract is not as widely used in food products due to the limited cultivation capacity of the fruit in countries other than China and Indonesia (Pandey & Chauhan, 2020). Monk fruit is available in two primary forms (i) Monk fruit juice concentrate, a natural fruit juice containing 56% sugar that is 15-20 times sweeter than sugar and (ii) Monk fruit extract, containing zero percent sugar, which is 150-200 times sweeter than sugar, and available in a concentrated powder form.
4.2 Metabolism
The body minimally absorbs mogrosides within Monk fruit. A sugar moiety and a metabolite known as mogrol get released by digestive enzymes and intestinal bacteria in the small intestine upon mogroside digestion (Murata et al., 2010). The resulting metabolites get excreted in the feces.
4.3 Health Impacts
The use of Monk fruit extract as a sweetener is relatively new to the commercial marketplace, and therefore it has not been as extensively studied as other sweeteners such as erythritol and Stevia. A review by Pandry & Chauhun (2020) has investigated the health impacts of Monk fruit extract and reported that its mogroside extracts may have antihyperglycemic, antidiabetic and antioxidant properties (Pandey & Chauhan, 2020). Although, these purported health benefits were extrapolated from limited in vivo and in vitro animal studies and minimal human clinical trial research.
Antihyperglycemic and Antidiabetic effects. Studies in a diabetic mouse model suggest that Monk fruit extract may help reduce blood sugar levels. The mice taking the Monk fruit extract had lower blood sugar levels and measures of oxidative stress as well as higher HDL (good) cholesterol (Qi et al., 2008; Xiangyang et al., 2006; Xu et al., 2013). Although Monk fruit extract is likely to have some health benefits due to its antioxidant and anti-inflammatory properties, dose-response studies in humans are needed to fully ascertain any potential health benefits.
The EFSA safety report on Monk fruit extract addressed the antidiabetic property of the sweetener in humans (Younes et al., 2019). The consumption of a single 200mg/kg bw dose of Monk fruit extract was suggested to have no adverse effects on blood glucose or liver enzymes in a human clinical trial. However, these findings were limited by the very small participant size (n=6) and short supplementation periods.
4.4 Regulations
The US FDA approved Monk fruit extract for use as a nonnutritive sweetener and flavor enhancer and generally recognized it as safe (GRAS) in 2010. The evaluation of the safety of Monk fruit extract by JECFA was scheduled in 2016. However, as no data was submitted for the additive, it was consequently removed from the agenda. There was no further follow-up on the safety of Monk fruit extract by JECFA.
The EFSA conducted a safety report on Monk fruit extract; however, the panel concluded that the toxicity data on Monk fruit extract was insufficient to conclude its safety as a food additive. The approval of Monk fruit extract in Europe has been delayed until the safety of the sweetener can be confirmed. The GSO has yet to approve Monk fruit extract for use as a sweetener in food products.
5| Sucralose
5.1 Overview
Sucralose is a popular, zero-calorie, artificial sweetener that is widely available. It is made from a multistep chemical process in which three hydrogen-oxygen atoms are substituted with chlorine atoms creating a tri-chlorinated disaccharide (Schiffman & Rother, 2013). Although sucralose is structurally like sucrose, the artificial sweetener differs in many chemical aspects. For instance, sucralose is 400-700 times the sweetness of sugar. Hence smaller concentrations of sucralose can replace sugar while achieving the same sweetness. Sucralose has no nutritional value and zero calories. The chemical structure of sucralose prevents it from getting digested by the same enzymes that digest carbohydrates (Roberts et al., 2000b). Sucralose has many physiochemical properties, which render it suitable for processed food preparations. The sweetener is highly water soluble, readily soluble in ethanol and methanol, stable at high temperatures and has a negligible effect on pH and viscosity. The companies Tate & Lyle and Johnson & Johnson jointly developed Splenda products using sucralose, adding them to thousands of products worldwide (Schiffman & Rother, 2013). Splenda contains the carbohydrates dextrose (glucose) and maltodextrin, bringing the calorie content up to 3.36 per gram.
5.2 Metabolism
The metabolic fate of sucralose is similar in human and animal models. It is poorly absorbed into the blood and rapidly eliminated unchanged in the feces and, to a lesser extent, in the urine (Roberts et al., 2000a). The urine excreted portion of sucralose can contain minimal concentrations of sucralose metabolites, likely produced within body tissues and not in the gut lumen. Sucralose does not accumulate in the body upon continuous ingestion. One study showed that an intake of large concentrations of sucralose may lead to lower bodily absorption (Roberts et al., 2000a).
5.3 Health Impacts
Glucose Homeostasis. The impact of sucralose consumption on glucose homeostasis has been reported in multiple studies (Baird et al., 2000; Grotz et al., 2003; M. Yanina Pepino et al., 2013; Romo-Romo et al., 2018).
For example, Baird et al. (2000) assessed sucralose consumption over 13 weeks with varying doses (e.g., 125mg/day for weeks 1-3, 250mg/day for weeks 4-7, and 500mg/day for weeks 8-12) in healthy individuals and reported no adverse effects on blood glucose and insulin concentrations (Baird et al., 2000). A study conducted by Romo-Romo and others (2018) concluded that an intake of 15mg/kg per day of sucralose in healthy participants over 14 days was associated with a reduction in insulin sensitivity compared to the control group (Romo-Romo et al., 2018).
In obese individuals, a single sucralose intake of 48mg increased glucose and insulin concentrations while reducing insulin sensitivity compared to water consumption (M. Yanina Pepino et al., 2013). Grotz and others (2003) demonstrated that the repeated-daily consumption of 667mg of sucralose for three months by type 2 diabetic participants had no significant effect on fasting HbA1c, plasma glucose, and insulin levels compared to the placebo.
Risdon and colleagues have described the proposed mechanism by which sucralose impacts glucose and insulin concentrations (2011). Sucralose stimulates the release of the insulin-regulating hormone incretin through interacting with the sweet taste receptor located in the intestine and pancreas. The release of incretin regulates the amount of insulin secreted after eating. This mechanism has been drawn based on in vitro and in vivo animal studies and so cannot be extrapolated to humans (Risdon et al., 2021).
Weight control. Sucralose may have some potential to assist in weight control. The body weight of healthy obese individuals consuming sucralose over 12 weeks was significantly lower than those consuming other sweeteners such as sucrose and saccharine (Higgins & Mattes, 2019). Another study concluded that consuming beverages sweetened with sucralose and acesulfame-K was associated with a reduction in weight gain in children compared to classically sugar-sweetened beverages (de Ruyter et al., 2012). Although these results suggest that sucralose may be helpful for weight control, the studies are limited by interacting factors, such as the presence of a second sweetener. A small study by Pepino and others (2013) in 17 individuals with severe obesity who did not consume these sweeteners regularly reported that sucralose ingestion increased blood sugar levels by 14% and insulin levels by 20% (M. Y. Pepino et al., 2013). A review of randomized controlled trials reported that artificial sweeteners collectively may reduce body weight by around 1.7 pounds (0.8 kg) on average (Miller & Perez, 2014).
Gut microbiota. Although most artificial sweeteners journey through the digestive system undigested and are secreted unchanged, they were thought to have no or little effects on the body. However, recent emerging research has revealed that artificial sweeteners may influence human health by altering the balance of bacteria in the gut. Scientists have found that artificial sweeteners, including Splenda, cause changes in gut microbes in animal studies (Abou-Donia et al., 2008). However, one study with human participants reported that sucralose consumption (780mg/day over seven days) did not impact the gut microbiome (Thomson et al., 2019). More human studies are required to determine the exact effect of sucralose consumption on gut health.
Other experimental animal model studies have found that mice given 14.2mg/kg bw of sucralose daily for eight weeks reported a significant reduction in the butyrate-producing Clostridium cluster species Clostridium XIVa (Uebanso, 2017). Wang et al. (2018) reported that mice fed a high-fat diet alongside a daily sucralose dose of 3.3mg/kg bw over eight weeks had an altered gut microbiota, specifically an increase in the growth of the microbial species Firmicutes (Wang et al., 2018).
The clinical relevance of the findings from animal studies is likely unsubstantial as microbial composition differs between humans and animals (Nguyen et al., 2015).
5.4 Side Effects
Sucralose has been associated with an elevation in body weight, adiposity and insulin resistance in children of pregnant women (Azad et al., 2020). Furthermore, the maternal consumption of sucralose has been linked to offspring microbiota dysbiosis and the promotion of low-grade intestinal inflammation (Dai et al., 2020). Evidence supporting adverse health outcomes appears to be growing, and further experimental and longitudinal clinical studies during pregnancy are needed to confirm these findings.
5.5 Regulations
The European Commission Scientific Committee on Food (EU/SCF) and JECFA set the ADI for sucralose to 0-15mg/kg bw/day (Food, 2016). Before JECFA set the current ADI, an ADI of 0-3.5mg/kg bw/day was established based on minimal toxicological data. The European Commission employed the recommended ADI set by the EU/SCF for sucralose as a sweetener. In Europe, sucralose is authorized as a sweetener in several food categories at quantum satis (i.e., an amount that is enough). The US FDA has an ADI of 5mg/kg bw/day based on 110 toxicity studies. The GSO has established a range for sucralose as a sweetener in food products to 0-5 mg/kg bw. Specific maximum limits for different food categories can be viewed in Table 1 in the appendix.
6| Aspartame
6.1 Overview
Aspartame is a low-calorie, artificial sweetener used in sugar-free and sugar-reduced food and diet-soda beverage formulations. It is arguably one of the most popular nonnutritive sweeteners in the marketplace; however, its use in food and beverage products remains controversial. Aspartame is sold under the brand names NutraSweet and Equal. It is an odorless white powder approximately 200 times sweeter than sugar, meaning very small amounts are required to give food products a sweet flavor. The main chemical components of aspartame are phenylalanine (an essential amino acid naturally present in most protein sources) and aspartic acid (a nonessential amino acid). Aspartame is chemically formulated comprising the methyl ester of a dipeptide which consists of the amino acids L-aspartic acid and L-phenylalanine, which both occur naturally in fruits, vegetables, nuts, and dairy products (Ahmad, Friel, & Mackay, 2020). Aspartame has the same calories per gram as sucrose (4cals/g), but significantly lower amounts are needed to achieve the same sweetness rendering the calorie content insignificant (Czarnecka et al., 2021). Aspartame has two forms: alpha and beta, but only the alpha form is sweet. The sweetness of aspartame differs from sucrose and the flavor takes longer to appear, leaving a notable aftertaste. Aspartame is frequently combined with other sweeteners to mask the bitter taste and enhance the sweetness (Czarnecka et al., 2021).
Due to the instability of aspartame, the use of the sweetener in food products is limited. Aspartame gets degraded when subjected to high temperatures or pH above 6 and loses its sweetness upon interaction with other flavorings, aldehydes, or ketones. To stabilize aspartame in food and pharmaceutical preparations, the sweetener can either be encapsulated in modified starch, gelatin, agar, etc., or it can be converted to its salt equivalent or metal complex to avoid decomposition (Czarnecka et al., 2021). Aspartame is commonly used in tabletop sweeteners, beverages such as sodas and flavored waters, dairy products, nutrition bars, desserts, chewing gum, sauces, and syrups.
6.2 Metabolism
Following the oral ingestion of aspartame, the sweetener gets enzymatically hydrolyzed within the gastrointestinal tract and no intact aspartame molecules reach the bloodstream. Following enzymatic digestion of aspartame, the metabolites methanol (10%) and the amino acids aspartic acid (40%), and phenylalanine (50%) are absorbed into the bloodstream (Hooper et al., 1994). Methanol is enzymatically digested to formaldehyde, which is enzymatically converted to formic acid. Formic acid can be excreted via urine or metabolized to carbon dioxide and eliminated via exhalation (Butchko et al., 2002).
Aspartic acid can be converted to oxaloacetate inside intestinal cells (Bender, 2012). Oxaloacetate and aspartate take part in the urea cycle and glucose production in the body. Other essential amino acids such as methionine, threonine, isoleucine, and lysine are synthesized using aspartate (Bender, 2012). Aspartate can also act as a neurotransmitter by stimulating the N-methyl-D-aspartate receptors (receptors essential for spatial memory and learning). Any excess aspartate will get excreted in the urine (Bender, 2012).
The amino acid phenylalanine gets absorbed by mucosal cells in the gastrointestinal tract and circulates to the liver (Bender, 2012). In the liver, phenylalanine gets enzymatically converted to the amino acid tyrosine. Tyrosine can be converted to the neurotransmitters dopamine, norepinephrine, and epinephrine (Bender, 2012). Those neurotransmitters are essential for cognitive function. Absorbed phenylalanine can be circulated and distributed throughout the body to the brain for growth and development. Excess phenylalanine gets eliminated in the urine (Bender, 2012).
6.3 Health Impacts
Glucose Homeostasis. The effect of single-dose and repeated doses of aspartame on glucose metabolism has been assessed in healthy and diabetic participants (Ahmad, Friel, & Mackay, 2020). The consumption of 2.7g of aspartame daily with meals over 18 weeks in both type 1 and 2 diabetic participants was demonstrated to have no change on blood glucose or HbA1c levels compared to the control group consuming 20mg of corn starch (Nehrling et al., 1985). Similar findings were reported by Higgins et al. when healthy individuals consumed 350mg or 1050mg of aspartame daily for 12 weeks (Higgins & Mattes, 2019).
Weight loss. A study by Blackburn and others (1997) reported that obese women following a multi-disciplinary weight-control program with aspartame-sweetened products experienced weight loss and long-term maintenance of reduced body weight compared to controls (Blackburn et al., 1997). Although the reduction in body weight found in this study may have been linked to aspartame, given the complex nature of weight loss and metabolism alongside the multi-disciplinary model, it makes it problematic to isolate one variable as the sole cause.
Gut microbiota. Most studies investigating the effect of aspartame on gut health have been conducted in animal and human fecal studies (Ahmad, Friel, & Mackay, 2020). However, one recent study by researchers at the University of Manitoba in Winnipeg, Canada, examined the effects of aspartame and sucralose at levels reflecting a habitual high diet soda intake in 17 healthy participants (the equivalent of three 335 ml cans of soda per day for 14 days). They reported that the daily intake of beverages sweetened with 136 mg per day of sucralose or 425 mg/day of aspartame did not significantly alter the gut microbiota in healthy participants (Ahmad, Friel, & MacKay, 2020).
An experimental animal study by Palmnas and others (2020) demonstrated that an 8-week low-dose aspartame consumption (5-7mg/kg/day) in diet-induced obese rats was associated with an increased total bacterial content and alterations in the bacterial composition of gut microbiota (Palmnäs et al., 2014). Due to its rapid digestion in the gut, aspartame is not circulated intact in the body, which presents a challenge for testing the impact of the sweetener on gut health.
6.4 Adverse Side Effects and Health Concerns
Collectively there have been a large number of claims with varying scientific validity that aspartame may be linked to side effects and adverse health outcomes, including but not restricted to weight gain, seizures, allergies, skin problems, depression, ADHD, dizziness, increased appetite, chronic kidney disease, poor blood glucose control, gut dysbiosis, heart disease, lupus, congenital disabilities, and high blood pressure. Given the inconsistency and volume of high-quality scientific studies in the published literature, ongoing research is currently exploring whether aspartame can be conclusively linked with robust scientific certainty to any of these reported adverse health outcomes. This review has selected to report data from only a few of the published studies.
Toxicity. Aspartame metabolites can be harmful when consumed excessively, with disadvantageous consequences. For instance, methanol poisoning can cause liver damage at high doses, and its metabolites, namely formaldehyde and formic acid, can destroy liver cells (Rogers et al., 2013). Moreover, the accumulation of formate can cause metabolic acidosis (i.e., the buildup of acid in the body), leading to depression of the central nervous system, coma, and death from respiratory system paralysis (Rogers et al., 2013; Rycerz & Jaworska-Adamu, 2013). Although aspartame metabolism can lead to damaging health effects, those effects are considered dose-dependent. Human trials investigating the metabolism of aspartame consumption at doses above the ADI demonstrated that an individual can’t consume enough aspartame to significantly raise blood formate concentrations (Food, 2013).
Individuals with a rare genetic disease called Phenylketonuria (PKU) should not ingest products containing aspartame. This is because people with PKU cannot properly process phenylalanine (one of the metabolites of aspartame) (van Spronsen et al., 2021). A buildup of phenylalanine can accelerate brain dysfunction leading to severe intellectual disability, epilepsy and behavioral problems (van Spronsen et al., 2021). Any products containing aspartame must have a clear label stating that it contains phenylalanine. Patients taking medication for schizophrenia should also avoid aspartame as phenylalanine may precipitate the uncontrolled muscle movements of a condition called Tardive dyskinesia. Pregnant women and individuals with advanced liver disease should also avoid aspartame.
Cancer. Aspartame is an unstable sweetener that can be negatively impacted by moisture, pH, temperature, and storage time. The prolonged storage of aspartame in high temperatures and pH above six can produce several impurities, including 5-benzyl-3,6-dioxo-2-piperazine acetic acid, commonly known as Di-ketopiperazine or DKP (Rycerz & Jaworska-Adamu, 2013). Data from animal studies has linked DKP to cancers of the lymphatic system, blood cells, brain and spinal cord, and the nervous system (Roberts, 1997; Soffritti et al., 2006). To minimize safety concerns arising from DKP, the European Commission has set an ADI of 7.5mg/kg bw/ day for DKP.
Pre-term birth risks. A prospective cohort study associated the intake of beverages artificially sweetened with aspartame with an increased possibility of preterm delivery in normal-weight and overweight women (Halldorsson et al., 2010). This finding was based on the consumption of artificially sweetened beverages in general, but no firm specifications for the consumption of aspartame (Halldorsson et al., 2010). The non-specificity of artificial sweeteners in beverages consumed by the participants in this study renders the finding problematic to draw any firm and specific conclusions regarding the impact of aspartame on preterm delivery.
6.5 Regulations
The US FDA has set an ADI of 50mg/kg bw per day for the consumption of aspartame, while both JECFA and the EU/SCF have established a slightly lower ADI of 40mg/kg body weight (bw)/day. These ADI values were established for healthy individuals. Individuals with phenylketonuria (PKU) must avoid and restrict their intake of phenylalanine. FDA, EFSA, and GSO regulations require the inclusion of a statement indicating the presence of phenylalanine on the label of food containing aspartame. The GSO set the allowed use levels of aspartame as a sweetener in food preparations to range between 0-40mg/kg bw/day.
Food Additives as Modifying Agents
Sucrose is added to food and beverage products for the primary purpose of sweetening, but it is also added for other functional purposes. For example, sugar acts as a preservative, texture modifier, fermentation substrate, flavoring, coloring, and a bulking agent (Koivistoinen & Hyvönen, 1985). Other food additives, such as polydextrose, maltodextrin, and soluble corn fiber, may potentially compensate for the texture properties of sugar.
1| Polydextrose
Overview and Metabolism
Polydextrose is synthesized from glucose and sorbitol in the presence of citric acid. It is a highly branched, randomly bonded polysaccharide (i.e., carbohydrate molecule that consists of multiple simple sugars) consisting of glucose units (Tiihonen et al., 2011). Polydextrose is not sweet; it has a neutral taste and performs different functions in food products, such as bulking, thickening and acting as a humectant (Peng & Yao, 2017). Human digestive enzymes cannot digest polydextrose in the small intestine. Polydextrose passes into the colon to get partially fermented by the microbiota, while 60% gets excreted in the feces (do Carmo et al., 2016). The fermentation of polydextrose produces SCFA and provides an energy of 1 kcal/g (Auerbach et al., 2007). The low caloric property of polydextrose makes it advantageous for use in reduced sugar preparations, including baked goods, confectionery, dairy products, and functional beverages. Besides providing a low-calorie content, polydextrose is favorable for use as a food additive as it is highly soluble and results in non-viscous (i.e., not thick or sticky) solutions. The fiber is also thermally stable and can absorb moisture from the surrounding environment, providing chemical and physical properties attractive to food manufacturers (Peng & Yao, 2017).
Health Impacts and Side Effects
Potential prebiotic effects. Some dietary fibers and non-digestible oligosaccharides (NDOs) are referred to as prebiotics. Prebiotics and probiotics are known to improve the health of the gut microbiota by encouraging the growth of beneficial microorganisms or reducing the growth of harmful ones (Davani-Davari et al., 2019). Polydextrose has been thought to beneficially modify the microbial composition and activity in vitro, in vivo and in the human gut (Röytiö & Ouwehand, 2014). In a study conducted by Costabile and others (2011), the consumption of 8g of polydextrose daily for three weeks in healthy volunteers was associated with altered microbiota composition. The authors reported specific increases in the SCFA-producing Ruminococcus intestinalis and Clostridium bacteria and a reduction in the fecal Lactobacillus-Enterococcus group (Costabile et al., 2012). The SCFA butyrate was suggested to have a role in inhibiting colonic carcinogenesis (i.e., the transformation of normal cells into cancer cells), inflammation, and oxidative stress (Hamer et al., 2008).
Mineral absorption. The consumption of polydextrose at 5% of the diet given to female rats for four weeks increased the absorption of magnesium and calcium compared to the control group (Legette et al., 2012). Similarly, Albarracin and others (2014) reported that the ingestion of polydextrose (5g per 100g) in rats for 60 days had a higher calcium absorption rate compared to the control group (Albarracín et al., 2014). The increased production of SCFA due to polydextrose digestion was suggested to lower the luminal pH in the colon and consequently increase the solubility and absorption of calcium (Röytiö & Ouwehand, 2014). Although multiple animal studies have investigated the effect of polydextrose consumption on mineral absorption, human trials are necessary to confirm the validity of these effects.
Gastrointestinal function. In addition to potentially improving mineral absorption, producing SCFA through the metabolism of polydextrose may improve gastrointestinal function. A study by Hengst and others (2009) demonstrated that consuming 8g of polydextrose daily for three weeks in healthy participants may relieve constipation by easing the excretion process (Hengst et al., 2009). Similarly, the daily intake of 10g polydextrose by hemodialysis patients (i.e., patients that underwent a procedure for the removal of waste products and excess fluid following kidney failure) for eight weeks was suggested to relieve constipation and ease bowel movement through softer stools production and increased weekly bowel movement compared to the control (Shimada et al., 2015).
Blood Glucose. In a human intervention, consuming 15-18g of polydextrose daily for 28 days reduced postprandial glucose response in healthy participants (Jie et al., 2000). Konings and others (2014) reported that the replacement of 30% of dietary carbohydrates with a single intake of 56.7g polydextrose for a day in overweight healthy participants was associated with a reduction in peak glucose and postprandial insulin response compared to a full carbohydrates diet (Konings et al., 2014). Conversely, Schwab and others reported (2006) that the consumption of a drink enriched with 16g polydextrose with a meal daily for 12 weeks in participants with diet-treated type 2 diabetics or participants with a high risk of developing diabetes bore no significance on measures of plasma glucose and insulin levels compared to the control group (Schwab et al., 2006). The contradictory data available on the impact of polydextrose on glucose and insulin response needs to be clarified by further human investigations.
Energy intake. King and others (2005) demonstrated that consuming yoghurt supplemented with 25g polydextrose daily for ten days may suppress food intake in healthy volunteers compared to the sucrose-supplemented control (King et al., 2005). Similarly, a study by Hull and Others (2012) demonstrated that healthy volunteers consuming 200mL yoghurt drinks enriched with 12.5g of polydextrose over three weeks reported a significantly reduced energy intake and an increased satiety rate during meal consumption. The authors reported that the reduction in energy intake did not cause compensation in energy intake in the following meal (Hull et al., 2012). In another study by Olli and colleagues, obese healthy participants consuming carbonated beverages supplemented with 15g of polydextrose as part of a high-fat meal resulted in an increased production of the satiety hormone and a reduced hunger rate compared to the placebo group (Olli et al., 2015).
Side effects. Polydextrose can cause intestinal discomfort, flatulence, bloating and diarrhea when taken as a single dose of more than 50 grams or as a daily dose of 90 grams (Joint et al., 1997).
Regulations
Polydextrose is a food additive approved for direct addition to food by the US FDA, the European Commission and GSO. Both the JECFA and the EC/SCF have allocated “not specified” ADI for polydextrose, as toxicological studies proved that the consumption of the additive does not cause any adverse effects. JECFA and EC/SCF have set a laxative threshold of 90g/day or 50g as a single dose for polydextrose.
2| Maltodextrin
Overview
Maltodextrin is a white powder made from corn, wheat, potato, and tapioca. Although it belongs to a class of carbohydrates that can be sourced from various plant species, it is highly processed (Chronakis, 1998). The starch from these sources can be modified through enzymatic methods or acid hydrolysis to produce maltodextrin (Hofman et al., 2016). After moistening with acids at 140 C to 160 C, the starch is hydrolyzed with enzymes to break down bonds within the starch molecule (Junaida Astina & Suwimol Sapwarobol, 2019). The resultant products undergo a filtration step to remove any impurities and then get spray-dried (i.e., the process of drying a liquid by subjecting it to a hot surface) and packaged. Maltodextrins are closely related to corn syrups; however, their sugar content differs. Maltodextrin can cause spikes in blood sugar levels and therefore should be consumed with caution by people with diabetes. It should also be avoided by those individuals who are pre-diabetic or insulin resistant.
Maltodextrin supplies four calories of energy per gram, similar to table sugar or sucrose (Takeiti et al., 2010). It is frequently used as a thickener or filler to increase the volume of foods and also to preserve shelf-life. It is often combined with artificial sweeteners to further sweeten desserts, canned fruits, and powdered drinks. Maltodextrin is often used as a substitute for sucrose as its physiochemical properties make it ideal for food preparations, including ice cream, baked goods, dried instant food formulations, cereals, beverages, and non-calorie tabletop sweeteners, e.g., Splenda (Hofman et al., 2016). Maltodextrin is water soluble and has gelling abilities that make it suitable for texture modification and thickening applications. Its ability to form smooth, fat-like gels, its non-crystalizing ability and its relatively high viscosity make maltodextrin advantageous for use as a fat replacer (Peng & Yao, 2017).
Metabolism
Maltodextrin cannot be absorbed directly into the small intestine. Instead, it must first be digested by the enzymes α-amylase and maltase to release maltose and a two-linked D-glucose sugar (Hofman et al., 2016). Maltose can be taken up directly by the outer layer in the gut or broken down further into free glucose (Hofman et al., 2016). The released glucose gets transported into the blood. Glucose can either be converted to lactic acid by small intestinal cells or be used for energy in organs such as the liver, muscle, brain, and red blood cells. The excess glucose will either get stored in the liver glycogen, or the muscles to be regulated by insulin or converted into fat (Hofman et al., 2016).
Health Impacts
Inflammation. A study by Laudisi and colleagues (2019) tested maltodextrin consumption for 45 days in mice at concentrations of 1-5%. The results suggested that maltodextrin increased intestinal inflammation compared to the control group (Laudisi, Di Fusco, et al., 2019). Maltodextrin was also associated with a reduction in the biosynthesis of mucin, which is secreted in the intestine to create a protective barrier against disease-causing bacteria (Laudisi, Di Fusco, et al., 2019).
Gut health. A study by Nickerson and McDonald (2012) suggested that maltodextrin may negatively alter gut microbiota in a way that increases susceptibility to disease by suppressing the growth of probiotics which are critical for immune health (Nickerson & McDonald, 2012). The researchers also reported that maltodextrin can increase the growth of harmful bacteria such as E. coli which is associated with autoimmune disorders such as Crohn’s disease (Nickerson & McDonald, 2012). A review paper published in 2019 suggested that maltodextrin may impair the release of intestinal mucus, which may increase the risk of colitis (Laudisi, Stolfi, et al., 2019).
A study by Rodriguez-Palacios et al. (2018) demonstrated that the consumption of 1.08mg/mL of the non-calorie sweetener Splenda (which consists of 99% maltodextrin and 1% sucralose) by mice increased the predominance of dysbiotic Proteobacteria, leading to intestinal and epithelial dysfunction (Rodriguez-Palacios et al., 2018). The consumption of Splenda was also associated with an increase in the release of the enzyme myeloperoxidase, which plays a part of the immune response that degrades disease-causing bacteria (Rodriguez-Palacios et al., 2018). Myeloperoxidase catalyzes the reaction of hydrogen peroxide with chloride ions to form hypochlorous acid, which serves to destruct bacterial invaders (Davies & Hawkins, 2020). However, hypochlorous acid produced in the body can cause tissue damage and lead to inflammation. The resulting inflammation can lead to the progression of symptoms in individuals with Crohn’s disease (Davies & Hawkins, 2020).
The consumption of maltodextrin-based infant formula in preterm piglets was reported to cause modifications in gut microbiota and trigger an intestinal pro-inflammatory response resulting in necrotizing enterocolitis (i.e., an intestinal disease that affects preemies) (Thymann et al., 2009). Although much of the current data supporting the influence of maltodextrin intake on gut dysbiosis and intestinal dysfunction is in animals, it should probably be avoided by those with autoimmune or digestive disorders. Maltodextrin does not contain gluten and can be tolerated by those with celiac disease or other gluten-related conditions.
Blood Glucose. The consumption of drinks supplemented with 50g of maltodextrin by health participants was reported to have no effect on postprandial glucose and insulin response compared controls receiving the same drink supplemented with glucose (Astina & Sapwarobol, 2020). The influence of maltodextrin on blood glucose levels has not been widely reported in animal and human trials; hence further studies are needed. However, although maltodextrin is considered safe in small doses, it can cause rapid increases in blood sugar levels and, for that reason, should ideally be avoided by people with diabetes. This sweetener is also a carbohydrate with no nutritional value, but depending on the levels consumed, it may lead to weight gain.
Regulations
The US FDA has classified maltodextrin as GRAS for use as a food additive with no limitations other than the current good manufacturing practice (GMP). Modified starches, including maltodextrin, have a “not limited” ADI set by the JECFA. Maltodextrin is not legally defined in Europe as an individual food additive, but it is grouped within starch hydrolysates which are permitted for use in food and beverage preparations. Wheat-sourced maltodextrin was determined by EFSA not to cause any allergic concerns and can be consumed by individuals with allergies related to wheat (European Food Safety, 2004). The use of maltodextrin as an additive in food preparations is not regulated currently by GSO.
3| Soluble Corn fiber
Overview
Soluble corn fiber (SCF) is a non-digestible carbohydrate used in various foods to provide sweetness and improve the texture and volume of processed foods. It is often used as a sugar replacement due to its low glycemic index. It is frequently used in low-carbohydrate, keto-friendly products. Soluble corn fiber, also referred to as resistant maltodextrin, is a dietary fiber produced from cornstarch (Tan et al., 2020). What differentiates resistant maltodextrin from regular maltodextrin is the presence of indigestible chemical bonds in the former. Those bonds form through subjecting moistened starch to enzymatic hydrolysis at temperatures as high as 140 to 160 C with the addition of acid. The resultant fiber is filtered from additional glucose, purified further, then spray-dried and packaged (J. Astina & S. Sapwarobol, 2019). The chemical bonds make resistant maltodextrin hard to digest, reducing its energy value to 2-2.5kcal/g (Baer et al., 2014). SCF has been used in food preparations as a thickening agent due to its low viscosity, high water solubility and high pH and heat stability. The addition of SCF provides food manufacturers the advantage of adding dietary fiber to food formulations, thus potentially enhancing their dietary value. SCF is an additive in food products such as processed cereals, baked goods, frozen foods, salad dressings, and carbonated beverages.
Metabolism
Resistant maltodextrin is indigestible by human enzymes and instead gets fermented by the gut microbiota into short chain fatty acids (SCFA), including acetate, propionate and butyrate (Junaida Astina & Suwimol Sapwarobol, 2019).
Health Impacts
Body weight management. Resistant maltodextrin was suggested to have a time and dose-dependent effect on body weight, body composition, satiety, and food intake in healthy and obese participants. A study by Guerin-Deremaux and others (2011) reported that the consumption of 17g of NUTRIOSE Soluble fiber (a commercial soluble corn fiber product) twice daily for 12 weeks by healthy overweight males resulted in bodyweight reductions, lower daily energy intake, and less hunger compared to the control (Guerin-Deremaux et al., 2011). Similarly, over three weeks, overweight females consuming NUTRIOSE Soluble fiber (8, 14, 18, 24g) demonstrated increased satiety through the reduction of hunger and appetite and an increase in time length to hunger between meals (Guérin-Deremaux et al., 2011). Furthermore, the consumption of 50g of NUTRIOSE twice a day with meals by 15 healthy participants resulted in a reduction in the secretion of the hunger hormone ghrelin for up to 10 hours following SCF consumption (Nazare et al., 2011). Although the mentioned studies may be limited by sample size, the conclusions implied regarding the effect of SCF on body weight management should be considered.
Glucose Homeostasis. The impact of SCF on glucose homeostasis parameters has been investigated in overweight and type 2 diabetic patients. Li and others (2010) demonstrated that the consumption of fruit juice supplemented with 17g of SCF twice daily over 12 weeks by overweight males resulted in decreased glucose, insulin, glycosylated hemoglobin, and homeostasis model assessment-estimated insulin resistance (i.e., a method for assessing B-cells function and insulin resistance from fasting glucose and insulin or C-peptide concentrations) compared to the control group (Li et al., 2010). Comparably, the consumption of 10g of NUTRIOSE by females with type 2 diabetes for eight weeks was reported to reduce fasting insulin, homeostasis model assessment-estimated insulin resistance, and pro-inflammatory protein levels (Aliasgharzadeh et al., 2015). These results suggest that resistant maltodextrin intake may positively impact glucose homeostasis in humans. The supportive research on the association of resistant maltodextrin with improved blood glucose control warrants further investigation to better establish the mechanisms at play.
Potential Prebiotic Effect. Like other dietary fibers, SCF is thought to have a positive prebiotic effect on gut health. Prebiotics can help feed beneficial gut bacteria. A study conducted by Hooda and colleagues on 20 healthy male participants who consumed 21 grams of soluble corn fiber per day resulted in increased strains of specific beneficial gut bacteria (Hooda et al., 2012).
Klosterbuer and others (2013) reported that the intake of 20-25g of resistant maltodextrin for seven days in healthy participants resulted in an increased production of the SCFA butyrate and an increase in the SCFA-producing Parabacteroides (Klosterbuer et al., 2013). In another study, the consumption of 50g of resistant maltodextrin by healthy males was reported to significantly increase the growth of the SCFA-producing bacterial groups, including lachnospiraceae, bacteriodes, parabacteriodes, bifidobacteria, clostridia, and coprococcus (Baer et al., 2014). Increased butyrate production has been linked to an increase in the beneficial strain of probiotic bacteria, namely Bifidobacterium, following the ingestion of SCF (Maathuis et al., 2009). This increase in Bifidobacterium in the gut has been associated with reduced gut permeability and a reduction in inflammation in patients with diabetes (Gomes et al., 2014).
Regulations
Dietary fiber has been defined by Codex Alimentarius Commission’s Committee on Nutrition and Foods for Special Dietary Uses as “carbohydrate polymers with ten or more monomeric units, which are not hydrolyzed by the endogenous enzymes in the small intestine of humans”. The FAO and WHO set the general recommendations for adequate fiber intake as 38 g for men and 25 g for women. These recommendations have been adapted in the US. The EFSA recommended 25g of fiber daily for normal laxation in adults. There have not been any specific regulations for using soluble corn fiber in food preparations by any regulatory bodies yet.
Concluding Remarks and Future Direction
Due to the increased rate of non-communicable diseases (NCD), such as diabetes mellitus, the replacement of sugar with sweetener alternatives has risen in popularity in both commercial industries and consumers. There are many available sugar replacement options from artificial and naturally sourced forms. Based on the current assessment of sugar replacers, naturally sourced nonnutritive sweeteners appear to have the highest potential as sugar replacements in food and beverage preparations. Erythritol and Stevia are both GSO-approved substances, arguably have the lowest side effects, and are potentially associated with positive health impacts compared to maltitol, sucralose, and aspartame. While artificial sweeteners are commonly used by individuals attempting to lose weight, they may be linked to weight gain in some people.
Scientific data remain sparse, and although the consumption of most nonnutritive sweeteners is considered safe and potentially beneficial, human studies have reported conflicting results. Furthermore, results from experimental animal studies have also been mixed. There are concerns that artificial sweeteners may increase insulin resistance and glucose intolerance (Suez et al., 2014). Several observational studies in humans have suggested that frequent, long-term consumption of artificial sweeteners may be associated with an increased risk of type 2 diabetes (Fagherazzi et al., 2017; Imamura et al., 2015; Swithers, 2013)
The consumption of maltitol has been linked with gastrointestinal problems such as diarrhea, bloating, and abdominal discomfort at varying concentrations. Sucralose has also been linked to gut dysbiosis and reduced insulin sensitivity, while aspartame consumption raises many concerns regarding the toxicity of its metabolites.
In the ongoing quest to reduce elements in the diet that have negative metabolic impacts, we must continuously look for the less metabolically harmful ingredients and, ideally, secure solutions that improve metabolic health.
The naturally sourced nonnutritive sweeteners can be used in combination to achieve the various functions of sweetening and texture modifications regularly achieved by sugar. The use of Stevia extract to replace sugar may fulfill the sweetening role of sugar; however, the addition of crystalline erythritol may also be necessary to improve the mouthfeel or provide other structural support to specific formulations. Polydextrose and SCF may be used as modifying agents to mimic the texture function of sugar in sugar-free formulations. Maltodextrin has been associated with adverse metabolic impacts similar to those caused by sugar, e.g., gut dysbiosis and intestinal inflammation. Therefore, its use in sugar-free food products should be approached with caution.
This review has provided an overview of commercially available sugar sweeteners and their varying potential metabolic health impacts. However, there remain many knowledge gaps concerning the long-term effects of nonnutritive sweeteners on human health, and further longitudinal clinical trials in humans are warranted.
New products with the recommended sugar alternatives are currently in development at KDD to support the Metabolic Reengineering effort at KDD. The Metabolic Reengineering work at KDD has been featured on the United Nations and World Economic Forum platforms and at an international conference on metabolic health and nutrition.
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Appendix
Table 1. The maximum levels of use in mg/kg of the sweeteners aspartame, sucralose, Stevia (steviol glycosides), Stevia (steviol equivalent), and polyols as set by GSO as stated in GSO 05/FDS 995/ /2019 describing the general requirements of permitted sweeteners in food.
| Sweeteners/products | Aspartame | Sucralose | Stevia (steviol glycoside) | Stevia (steviol equivalent) | Polyols |
| Non-alcoholic drinks | 600 | 300 | 600 | 198 | GMP |
| Breakfast cereals | 1000 | 400 | 1000 | 330 | GMP |
| Canned or bottled fruits | 1000 (except fruit nectar 600) | 300 (except frozen 400 dried 1500) | 1000 | 330 | GMP |
| Jams Jellies & marmalades | 1000 | 400 | 1000 | 200 | GMP |
| Edible ices | 800 | 320 | 800 | 200 | GMP |
| Confectionary, chocolate, pudding |
(Solid, soft, sweet, and powder mixtures of cocoa, cocoa templates, chocolate filling and coverage 3000 (mixture of cocoa as liquid 1000) |
1800 | Solid sweet 1000 soft sweet and cocoa 2000 | 270 | GMP |
| Chewing gum | 5500 | 3000 | 10000 | 3300 | GMP |
| Bakery product | 1700 | 700 | 1000 | 330 | GMP |
| Vinegar | 3000 | – | – | – | – |
| Sauces, mustard, mayonnaise | 350 | Sauce 450 mustard 140 | Sauce 350 mustard 350 | 120 | – |
| Food formula | Solid 2000 Liquid 600 Syrup type or Chewable 5500 | Solid 800 Liquid 240 Syrup type or chewable 2400 | – | Solid 670 Liquid 200 Chewable 1800 Syrup type or Chewable 1800 | Syrup type or chewable GMP |
| Soups and sauces | 110 | – | 110 | 36.3 | – |
| Nectar vegetables and concentrates | 600 | – | 200 | 100 | – |