|Year : 2016 | Volume
| Issue : 1 | Page : 4-9
Nonnutritive sweeteners: Pros and cons
Avinash Agarwal1, Manish Gutch2, Sukriti Kumar3, Syed Razi Mohd2, Gupta Abhinav Kumar2, Keshav Gupta Kumar2
1 Department of Medicine, KGMU, Lucknow, Uttar Pradesh, India
2 Department of Endocrinology, LLRM Medical College, Meerut, Uttar Pradesh, India
3 Department of Radiodiagnosis, SGPGI, Lucknow, Uttar Pradesh, India
|Date of Web Publication||22-Dec-2015|
D-15, LLRM Medical College, Meerut - 250 004, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Nonnutritive sweeteners (NNSs) are the substances having an intense sweet taste with no or very low calories and are used as substitutes for simple sugars for reduction of energy intake. The consumption of NNSs is increasing at an alarming rate because of the ever evolving pandemic of obesity and Type 2 diabetes mellitus. NNSs have various positive and negative metabolic consequences on the health of the consumers. There are misconceptions and myths regarding the use of NNSs for which various professional bodies have issued guidelines. However, the overall long-term effects of the NNSs are still an area of debate and discussion.
Keywords: Nonnutritive sweeteners, obesity, type 2 diabetes mellitus
|How to cite this article:|
Agarwal A, Gutch M, Kumar S, Mohd SR, Kumar GA, Kumar KG. Nonnutritive sweeteners: Pros and cons. CHRISMED J Health Res 2016;3:4-9
|How to cite this URL:|
Agarwal A, Gutch M, Kumar S, Mohd SR, Kumar GA, Kumar KG. Nonnutritive sweeteners: Pros and cons. CHRISMED J Health Res [serial online] 2016 [cited 2022 May 19];3:4-9. Available from: https://www.cjhr.org/text.asp?2016/3/1/4/172394
| Introduction|| |
Type 2 diabetes mellitus (T2DM) and obesity are growing at alarming rates in modern times with 366 million diabetics worldwide and T2DM responsible for 4.6 million deaths annually across the globe. Insulin resistance resulting from over nutrition and sedentary life style remains one of the root pathophysiological factors for obesity and T2DM.
Excessive consumption of simple sugars and sugar sweetened beverages increases the risk of obesity resulting in the increase in diabetes mellitus. Therefore, avoidance of energy dense foods rich in simple carbohydrates like sugar sweetened beverages is one of the cornerstones for prevention and management of T2DM and for the reduction of associated cardio-metabolic risk factors. The USDA guidelines suggest to curtail the amount of added sugars to <15% of the total consumed calories.
Since the preference for sweetness is innate and universal and represents a biological response to the safe source of energy, but reduction of excess calories of simple added sugars is not easy especially in context to ancient cultures like India where many religious beliefs and cultural values are attached with the sweet taste and sweet is considered as auspicious. The curtailment of excess calories present in added simple sugars can be brought about by the use of nonnutritive sweeteners (NNSs) without compromising the sweet taste and palatability of the food.
| Definitions|| |
NNSs can be defined as the substances with a higher degree of sweetness per gram as compared to caloric sweeteners such as sucrose, corn syrups, and fruit juice concentrates. Since NNS are used in only meager quantities for replacement, these provide no or few calories.
Acceptable daily intake
Acceptable daily intake (ADI) can be defined as the amount of an NNS expressed as mg per kg body weight that is considered to be safe to consume every day for a life time.
Usually, ADI is 100 times lower than the sweetener dose that caused toxicity in animal studies.
Estimated daily intake
Estimated daily intake (EDI) can be defined as the amount of sweetener. If EDI of an NNS is below ADI, then it is considered safe for the human consumption.
Salient features of nonnutritive sweeteners
Until date, there are six NNSs approved by the US-Food and Drug Administration (US-FDA), out of which five are artificial and only 1 is extracted from a plant. Currently, available NNSs are shown in [Table 1].
| Epidemiology of Consumption|| |
The exact amount of NNSs consumed by the general public is very difficult to assess and varies greatly depending on dietary, economic, education, and health care accessibility factors. The data regarding the amount of NNSs consumed in foods and beverages is difficult to estimate as most of the manufacturers only mention the name but not the exact amount of the NNS. So the consumption pattern of NNSs is assessed on the basis of the consumption of the pattern of foods and beverages using them.
The consumption of NNSs is increasing at an alarming rate which can be assessed by the fact that in 2003–2004 15% of Americans consumed NNSs as compared with 3% in 1965.
The most commonly consumed product sweetened by NNSs is beverages and their consumption has increased over time especially among females. Adults consume more nonnutritive beverages than adolescent and children. However, the consumption per unit body weight is highest in children. A recent systematic review estimates that 4–18% of the soft drinks consumed by the children are artificially sweetened., The increase in the consumption of the foods sweetened by NNSs is not parallel with a decrease in the consumption of the foods sweetened by caloric sweeteners.,
Metabolic consequences of nonnutritive sweeteners
Appetite and energy balance
The basic idea of using NNSs is to create energy deficit by substitution of sugar from the soft beverages  but there should be no compensation of calorie consumption in the form of extra calorie snacks and other sources. Mattes and Popkins  examined this issue of calorie compensation and suggested following eight different mechanisms for compensation:
- NNSs might affect the appetite by effecting the cephalic phase of gastric secretion
- Lower nutritive density and osmotic load as compared to sugars can alter the gastric emptying and other factors involved in digestion and absorption of nutrients which might change satiation
- NNSs result in reduced secretion of gut peptides as compared to simple sugars which theoretically could reduce satiety and could increase food intake
- NNSs typically increase the palatability of the food which could reduce satiety and increase hunger
- Over compensation could occur because of subsequent energy dense snacks and other foods in lieu of NNSs
- Disruption of sensory signal by sweet taste to brain may lead to altered energy balance and thereby promoting overcompensation
- Increase palatability of the food items using NNSs can cause overstimulation of reward center which could lead to overcompensation
- Repeated exposure to NNSs could stimulate liking for sweet foods including those containing simple sugars.
Although Mattes and Popkin proposed these mechanisms but at present the available evidence is either insufficient to accept these or refute these. The biggest issue is the complex methodology used in the intervention controlled feeding trials and cohort studies to study the compensation of calories lost by the use of NNSs. To make the matters worse most of the persons are unable to estimate the calories they consume as is seen in a study by the International Food Information Council Foundation that <10% of Americans can accurately estimate their per day calorie consumption.
In a meta-analysis of 12 studies by de la Hunty et al. on energy intake compensation, it was found that energy compensation in 24 h for foods using NNSs was 32% while it was 15% in four studies using non caloric beverages. Overall energy intake reduction is not observed in all the studies uniformly by the use of NNSs. A 4 weeks trial of diet soft drinks and regular soft drinks by Reid et al. revealed similar energy intake by both the groups of normal weight persons. Because of the limited human studies and inherent limitations of these studies more research is needed in the future on the issue of energy compensation.
Majority of the studies assessing the correlation of NNSs with the body weight involve the substitution of caloric sweeteners with NNSs in beverages, but scanty data is available regarding substitution in food. Fowler et al. 2008, as a part of San Antonio Heart Study, reported significant weight gain and risk of obesity in normal weight or overweight persons at baseline who consuming artificially sweetened beverages as compared to nonconsumers.
In another prospective study conducted over 2 years on 693 adolescents by Laska et al. 2012, it was found that diet soda consumption was significantly correlated to body mass index and percentage body fat when the cohort was examined cross sectionally. Neither of these studies failed to provide any evidence of the reduction of weight gain or increment in body fat percent., A review of 16 trials assessing the effect of NNSs on weight concluded that weight loss of 0.2 kg/week over 12 weeks could be achieved by reduction of 220 kcal/day through the use of aspartame.
In 2011 a study by Mozaffarian et al. observed 120,877 US men and women from three different cohorts Nurse's Health Study (NHS), NHSII and Health Professionals Follow-up Study (HPFS) for 12–20 years for change in weight with diet and life style. The study found that there was no significant change in weight with one serving of diet soda per day in NHS cohort while there was a modest but significant change of 0.25 lb/4 years in NHSII and HPFS cohorts after adjusting for all the demographic variables.
Findings from prospective cohort studies and controlled intervention trials remain inconsistent. The major drawback of controlled interventions is their short duration along with differences from real life eating patterns and more awareness in intervention subjects while prospective cohort can predict the association between NNSs and either weight gain or loss but remain unable to predict the causation. As obese and diabetic persons tend to switch to NNSs more frequently than normal healthy so whether NNSs cause obesity and T2DM or it was present before their use always remains a mystery. So both intervention and prospective cohort studies are complementary to each other in assessing the effects on NNSs on the general population weight trends.
Cardio-metabolic effects and Type 2 diabetes mellitus
Many prospective and intervention studies try to find out the association between the use of NNSs and the cardio-metabolic and glycemic variables. In NHS, consumption of ≥2 diet soft drink daily was significantly associated with the development of coronary heart disease and chronic kidney disease as compared to diet soft drink consumption of <1 serving monthly when followed for 11–12 years.,
Another large prospective multicentric study called Northern Manhattan Study (2012) observing >2500 subjects for 10 years for the consumption of soft drinks and risk factors and vascular events concluded with increased risk of vascular events among diet soft drink consumers but there is a high suspicion of reverse causality. Coronary Artery Risk Development in Young, a prospective study comprising 5115 subjects aged between 18 and 30 years started in 1985–1986 with an aim of assessing the clinical and subclinical cardiovascular (CV) disease and its risk factors included two study groups on taking Western food and another taking healthy food with or without diet beverages. The study follow-up of 20 years revealed that having elevated blood sugar and low- and high-density lipoprotein was lower in the group consuming a healthy diet with diet soft drinks than in the other groups.
The data from the two large prospective studies namely E3N Study and HPFS study revealed that the risk of development of diabetes was more than double among the participants in the highest quartiles of NNS consumption than nonconsumers, though the risk of T2DM development was significantly higher among consumers of regular calorie beverages, but the comparison in both studies were made complex by the differences in the types of beverages consumed in the two studies., Data from NHS also suggests that risk of development of T2DM is enhanced in those consuming at least one NNS or regular sweetener containing beverage per day.
European prospective investigation into cancer and nutrition is one of the largest prospective study conducted on 519,978 subjects over 23 centers in 10 European countries estimated increased risk of T2DM in subjects consuming at least one soft drink per day either sweetened by NNSs or normal regular sugar.
Nonnutritive sweeteners are projected in social media as a panacea for obesity and reduction of weight but these are plagued with various acute and chronic side effects.
Aspartame is most widely used NNS but it is also most controversial among the NNSs. It is associated with acute side effects such as nausea, vomiting, headache especially migraine, and dry mouth. Mukhopadhyay et al., established that aspartame is associated with a significant increase of up to 2.5–4.2-fold in chromosomal aberration. Long-term consumption of aspartame can cause hepatocellular injury, alter the hepatic antioxidant balance and also alter behavior in rats, but the issue is debatable. Aspartame present in beverage cans stored at high temperatures and at pH >6, it can break into its metabolite deketopiperazine which is a central nervous system carcinogen and is under active research.
Potential toxicities of acesulfame potassium (Ace-K) are nausea, headache, mental confusion, depression, loss of appetite, etc. Mukherjee and Chakrabarti (1997) found Ace-K to be genotoxic to rats but on further studies they found it safe.
Cyclamate was banned by US-FDA in 1960s due to its carcinogenic effects in animal studies but in 1984 FDA concluded that the amounts used by humans are noncarcinogenic. Martins et al. (2010) found fetal developmental retardation and hypertrophy of exocrine pancreas in rat fetuses on exposure to cyclamate. Humans convert cyclamate into cyclohexylamine which is a toxic metabolite over long-term consumption, and a high dose of cyclohexylamine can cause testicular atrophy in rats.
Mayhew et al. (2003) found change in the body weight with consumption to neotame but it was later found due the unpalatibility of the foods in which it was added, and neotame was free from toxic side effects.
Saccharin was banned by US-FDA on the basis of two generation study on rats by Arnold proving saccharin to be carcinogenic producing bladder cancer but the ban was lifted when carcinogenicity was refuted. However, the products using saccharin had to carry a label for potential carcinogenicity until 2000. There are reports about hepato-toxicity of saccharin.
Sucralose is associated with significant involution of thymus and migraine. Sucralose is also associated with DNA damage in gastrointestinal organs, hepato-toxicity, nephrotoxicity, fetal, and placental development retardation.
Stevia being natural sweetener does not found to have no carcinogenic, genotoxic, developmental, and reproductive side effects.
NNSs have various potential advantages which are as follows:
- NNSs do not increase appetite or energy intake 
- Foods and beverages sweetened by NNSs reduce energy intake as compared to energy dense foods 
- NNSs cause modest weight loss along with a reduction in fat mass and waist circumference ,
- NNSs have beneficial effects on postprandial glucose and insulin in healthy individuals and diabetics 
- NNSs are not fermented in the oral cavity by the bacteria and reduce the rate of teeth demineralization.
There are many misconceptions and myths regarding NNSs in the society because there is a lack of scientific information regarding these products among the masses as most of the information is provided by the social media and commercial companies. Common misconceptions, especially among illiterate regarding NNS tablets, are that:
- These tablets are one of the OHAs or anti-obesity drugs
- These tablets can reduce body weight tremendously without dietary and life style modifications
- These can result in infertility, feto-toxicity, CV events, and carcinoma
- NNSs have abuse potential
- NNSs have no upper safe limit of consumption.
These misconceptions about the NNSs can be removed from the masses by creating social awareness in the society regarding their composition, use, advantages, side effects, and limit of safe consumption. There should be proper scientific information and guidelines issued by various professional bodies made available in mass media for the knowledge of common men.
Consensus statements by International and National Organizations
American academy of pediatrics (2010)
Health benefits of NNSs are inadequately assessed in children and adolescent and as such they should not form a significant part of a child's diet.
Indian guidelines (2011)
NNSs could be used in moderate amounts. There are no nutrient benefits and long-term safety data are inadequate.
Academy of nutrition and dietetics (2012)
Currently, available NNSs approved by the US-FDA are safe and can be taken by the individuals according to the federal nutrition recommendations, individual goals, and preferences. NNSs also reduce dental caries.
American Diabetes Association and American Heart Association (2012)
At present, data available are not sufficient to conclude that use of NNSs in foods and beverages to displace caloric sweeteners is beneficial to reduce carbohydrate intake or energy balance, body weight or cardio-metabolic risk factors. Some data suggests the use of NNSs in a structured way may cause modest calorie reduction and weight loss. The potential benefits of energy intake reduction could only be realized if there is no compensatory increase in energy consumption from other sources. The effects of addition of NNSs on overall quality of diet should be taken into consideration when assessing overall risks and benefits.
International Sweeteners Association (2014)
NNSs do not increase appetite, reduce energy intake, enhance weight loss, benefit postprandial glucose, and insulin levels in diabetics and are beneficial for dental caries.
| Conclusion|| |
The use of NNSs is increasing. These can reduce the calorie intake if energy compensation is absent. Long-term RCTs on these agents are difficult because of the technical complexities and different human eating patterns. The use of NNSs is safe as stated by various professional bodies. These agents have various additional advantages such as enhanced weight loss, beneficial effect on postprandial glucose and insulin levels in diabetics, and are beneficial for dental caries. So NNSs can be cautiously used in place of caloric sweeteners to achieve health benefits in the form of calorie and weight reduction, but still long-term data are needed to study all the aspects of NNSs.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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