A Narrative Review of Artificial Sweeteners

Gefei Zhang

Wuhan Britain China School, Wuhan, 430000, China

Keywords:

Nonnutritive Sweeteners, Artificial Sweeteners.

Abstract:

Nonnutritive sweeteners (NNS) are a class of food additives used by the food industry worldwide to combat

diseases such as weight gain and type 2 diabetes by maintaining their sweet taste while maintaining low or no

calorie intake. Artificial sweeteners have been widely used in food-production industry for their advantages

of supernal sweetness, no nutrition and low calorie. However, the safety and effectiveness of artificial

sweeteners remain controversial. This paper introduces the metabolic characteristics and detection methods

of five common artificial sweeteners, including Acesulfame-K, aspartame, neotame, saccharin and sucralose.

Suggestions on the development of artificial sweeteners were put forward to provide reference for further

rational development and safe use of artificial sweeteners.

1 INTRODUCTION

More than a century has passed since saccharin, the

oldest NNS (Mooradian, 2013) was first used.

American children are reported to be consuming

NNS every day, up from 30 percent in 2008. Public

interest in NNS has increased because they lessen the

energy density of the diet without loss of sweetness.

A variety of artificial sweeteners have been

discovered and applied in different fields, especially

in the production of beverages and foods, such as

baked goods, dairy products and beverages (Dunford,

2018)

By definition, NNS, also known as very low-

calorie sweeteners, artificial sweeteners, no-calorie

sweeteners and high-intensity sweeteners, are

sweeter than nutritional sweeteners like table sugar.

As a result, small amounts of NNS are needed to

create the sweetness needed by many nutritional

sweeteners. In this way, they do not offer or offer

low-calorie ones (Gardner, 2012).

The effects of NNS on human metabolic

responses are complex. Some studies have shown

positive effects, such as significant weight loss in the

short term and weight control in the long term (Li,

1997). Some have no effect on glycemic control in

patients with type 2 diabetes (Grotz, 2003). Some

studies have shown many adverse effects, including

cardiovascular, renal toxicity, obesity, and cognitive

effects (Lohner, 2017). There are some physiological

mechanisms for the occurrence of these symptoms,

such as intestinal microbes causing intestinal

inflammation and so on, thus promoting the

occurrence of these symptoms

A number of metabolic disorders associated with

obesity. This review aims to explain how artificial

sugars produce sweetness, introduce different types

of artificial sugars, their effects on human health, and

explore possible future research areas from articles

collected on Pubmed.

2 THE PRINCIPLE OF

ARTIFICIAL SWEETENERS

CREATE THE TASTE OF

SWEETNESS

These two G protein-coupled receptors of the c

family can detect all sweet compounds (GPCR) T1R2

and T1R3 expressed on the surface of mammalian

taste buds (Li, 2002). Studies have shown that Sac is

a single master site in mice that affects the response

to several sweet substances, including preference for

sucrose, acesulmae-K and dulcin (Fuller, 1974).

Sweet transduction of natural sweeteners may be

explained by the activation of adenylate cyclase,

adenosine 3', 5' -cyclic adenosine phosphate (cAMP)

dependent membrane generation (Streem, 1991), K+

channel inactivation (Avenet, 1998), and Ca2+

240

Zhang, G.

A Narrative Review of Artiﬁcial Sweeteners.

DOI: 10.5220/0012019000003633

In Proceedings of the 4th International Conference on Biotechnology and Biomedicine (ICBB 2022), pages 240-244

ISBN: 978-989-758-637-8

 2023 by SCITEPRESS – Science and Technology Publications, Lda. Under CC license (CC BY-NC-ND 4.0)

(Lindemann, 1996) depolarization after flavor

transducers bind to receptors. The opening of

voltage-gated Na+ and K+ channels leads to action

potentials in presynaptic neurons (Cummings, 1993).

Some studies have shown that artificial

sweeteners increase sweetness intensity by increasing

affinity for one or more sites on T1R2 and T1R3

receptors (Xu, 2004). Some studies have shown that

receptors T1R2 and T1R3 respond differently to

artificial sweeteners. Daly et al demonstrated that the

commonly used NNS sucralose, saccharin and

acesulfame K activated T1R2 and T1R3 in pigs,

while NNS aspartame and cyclohexylsulfamate did

not (Daly, 2001).

3 TYPES OF ARTIFICIAL

SWEETENERS

The five NNS approved by the FDA include

Acesulfames, aspartame, neotame, saccharin, and

sucralose (Brown, 2010). In addition, basic

information about these five non-nutritional

sweeteners is shown in Table 1.

Saccharin is the oldest artificial sweetener used. It

was developed by Johns Hopkins University in 1878.

The FDA approved it in 1879. It is 200 to 700 times

sweeter than sucrose (Bermann, 2017).

Aspartame was first discovered in 1965. It

consists of two amino acids, phenylalanine and

aspartic acid, with methanol as the main chain. It was

approved by FDA in 1981. It is 200 times sweeter

than table sugar. Aspartame's safety remains in

question as its metabolism ultimately leads to the

formation of formaldehyde, formic acid and

diketopiperazine.

Acesmeline K was first discovered in 1967 and

approved for use by the FDA in 2003. It is 120 times

sweeter than sucrose (Rymon, 1991). Because it is

thermally stable and has a bitter aftertaste when used

alone, it is used in cooking and baking. When used in

cooking and baking, it is often mixed with other

sweeteners, such as sucralose or aspartame (Horne J,

2002).

Neotame was approved by the FDA in 2002 and

is currently the most effective sweetener available. It

is chemically related to aspartame. It is 7000 times

sweeter than sucrose (Prakash I, 2007).

Sucralose was synthesized in 1976 by replacing

chlorine with three hydroxyl groups in sucrose and

was approved by the FDA in 1999. It is 600 times

sweeter than sucrose (Arora, 2009).

Table 1: The basic information of five Nonnutritive Sweeteners.

Sweetener

Chemical

formula

*Sweetness FDA-approved date

Saccharin C

S 200 - 700 1879

Aspartame C

200 1981

Acesulfame-K C

KNO

S 120 2003

Neotame C

7000 2002

Sucralose C

600 1999

*Sucrose=1 (Relative to a 10% sucrose solution) Different numbers indicate effect in different foods

4 ARTIFICIAL SWEETENERS

AND HUMAN HEALTH

4.1 Artificial Sweeteners and Obesity

Feijo et al., Foletto et al., and rats showed that intake

of saccharin or aspartame promotes weight gain

without significant changes in caloric intake, insulin

resistance, and fasting leptin (Feijo, 2013). A large

number of studies have shown that the use of NNS is

positively correlated with weight gain (Stellman,

1986). In a cohort study completed by Chia et al.,

NSS users significantly increased BMI and waist

circumference from 1984 to 2012 with a median

follow-up of 10 years of 1,454 participants (741

males, 713 females) (Liu, 1990). A cohort study

included 3,033 volunteers whose mothers consumed

artificially sweetened and sugary drinks between

2009 and 2012. Studies have shown an association

between daily intake of NNS and a two-fold

increased risk of being overweight at age 1

A Narrative Review of Artiﬁcial Sweeteners

241

4.2 Effects on Gut Microbes

The effects of NNS on microbes vary. Table 2 shows

the effects of five non-nutritive sweeteners on the gut

microbiome.

Due to the fast absorption and excretion rate of

acesulphine potassium into systemic circulation, it

has little effect on colon flora (Magnuson, 2016).

Similarly, aspartame has little effect on colonic flora

(Stegink, 1987) because it is rapidly absorbed in the

duodenum and jejunum. On the other hand, a small

amount of saccharin (less than 15%) is not absorbed

as a whole molecule and thus enters the colon,

affecting the microflora (Plaza-Diaz, 2020). In in

vitro model studies, saccharin increased the number

of bifidobacterium (Renwick, 1985). The minimum

amount of sucralose (less than 15%) is absorbed and

hardly metabolized. Thus, more than 85% of

sucralose reaches the colon. However, more than

94% were recovered from feces, and no structural

changes occurred, indicating no impact on microbial

community (Magnuson, 2016). The effect of

neotsuan on gut microbes has not been assessed, as

only trace amounts of neotsuan are needed to sweeten

foods. It can be metabolized quickly. Therefore,

neotame is unlikely to affect gut microbes.

Table 2: The effect on microbiome in the gut of Five

Nonnutritive Sweeteners.

Sweetener

Effect on microbiome in the

gut

Saccharin

Affect bacteria such as

Bifidobacterium

Aspartame

Almost no effect since large

amount is absorbed

Acesulfame-K

Almost no effect since large

amount is absorbed

Neotame -

Sucralose Almost no effect

4.3 Influence on Kidney

Recent studies have also found a relationship

between NNS intake and chronic kidney disease

(including proteinuria, the threshold of the

albumin/creatinine ratio >17mg /g in men and >25mg

/g in women) and decreased renal function. In a cross-

sectional analysis of 9358 subjects from 1999 to

2004, soda consumption and NNS may be associated

with proteinuria. In addition, a study of 3,318 women

from 1989 to 2000 found that drinking more than two

servings of artificially sweetened soda a day tripled a

woman's risk of kidney function decline.

5 CONCLUSION

This literature review combines systematic reviews,

prospective cohort studies, and meta-analyses to

illustrate the possible mechanisms of neural network

sweetness and the possible negative effects of neural

network on human body. Although NNS created as

an alternative to sugar attempts to provide the same

sweet intensity as the nutritional sweetener sucrose,

there is substantial evidence of profound negative

effects on the human body, including host microbes,

weight gain, and kidney health. Although NNS are

thought to be healthier than sugar, most data

contradict this claim.

Future research should include novel sweeteners

such as naturally occurring rare sugars, including D-

Allulose (D-Psicose), D-Tagatose, D-sorbide and D-

Allose, their effects on humans, and the feasibility of

using them in mass production.

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