Sugar Substitutes/Artificial Sweeteners Explained

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Posted: 13/07/2019

Updated: 13/07/2019

Next article: Artificial sweeteners & health

Artificial sweeteners, also known as non-nutritive sweeteners, non-caloric sweeteners or non-caloric high-intensity sweeteners have become a staple in the food industry and has seeped its way into thousands of products commonly seen in the supermarket including:

  • Soft drinks and other beverages (list of amount

  • Baked goods

  • Candy

  • Puddings

  • Canned foods

  • Jams and jellies

  • Dairy products

  • Home baking/cooking

 

With the introduction of the sugar tax adding to the cost of production, more and more manufacturers are reformulating their products with artificial sweeteners to reduce cost. Revenue from the artificial sweetener market is increasing exponentially and expected to be around USD 3 billion by the end of 2025.

There are a lot of controversies surrounding artificial sweeteners as social media is constantly sensationalising headlines that artificial sweeteners cause type 2 diabetes, are carcinogenic and can cause disruption to the microbiome. In this article, we will look at the safety of use of all approved artificial sweeteners available in the market.

 

Approved Sweeteners

The Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA) has approved the following artificial sweeteners in the US and UK respectively.

US Approved (FDA)

Generally Recognised as Safe (GRAS):

  1. Acesulfame potassium

  2. Advantame

  3. Aspartame

  4. Neotame

  5. Saccharin

  6. Sucralose

 

The following does not have a GRAS distinction as there is not enough evidence:

  1. Steviol glycosides

  2. Luo Han Guo (Monk fruit) fruit extracts

UK Approved (EFSA)

  1. Acesulfame potassium

  2. Advantame

  3. Aspartame

  4. Aspartame-acesulfame salt *

  5. Cyclamate *

  6. Neohesperidine Dihydrochalcone *

  7. Neotame

  8. Saccharin

  9. Steviol glycosides

  10. Sucralose

  11. Thaumatin *

* Not mentioned in this article.

Acesulfame Potassium (Ace-K)

 
  • Brand: Sunett®, Sweet One®

  • Sweetness: 200 times sweeter than sugar

  • ADI: 15 mg/kg/bw/d by the FDA and 9 mg/kg/day in Europe = 23 packets

  • Products: soft drinks, protein shakes, drink mixes, frozen desserts, baked goods, candy, gum, and table-top sweeteners

  • Food label: acesulfame K, acesulfame potassium, Ace-K, E950 (Europe)

Acesulfame potassium (ACE-K) or acesulfame K was approved by the FDA in 1988 and is 200 times the sweetness of table sugar. It is often found in combination with other sweeteners like aspartame or sucralose to mask the bitter aftertaste when used alone. As it is heat-stable, it is frequently used in foods that need to be cooked as ACE-K can retain sweetness at high temperatures.

Unlike aspartame, ACE-K is almost completely absorbed and distributed via the blood throughout the body. ACE-K is not metabolised and is excreted primarily via the kidneys into urine within 24 hours after consumption (1).

Gut microbiota

ACE-K consumption resulted in changes in the gut microbiota in mice dosed with 37.5 mg/kg/d for 4 weeks which is significantly more than double the recommended ADI for ACE-K. Interestingly, weight gain was only seen in male but not female mice (2). However, the dosage given was very unrealistic to the amount that a human would be consuming, and animal studies do not always translate very well to humans.

According to the FDA, more than 90 studies have demonstrated the safety of ACE-K use (3).

The ADI for ACE-K is 15 mg/kg body weight per day which is equivalent to about 30 to 32 cans of diet soda every day.

Advantame

 
  • Brand: N/A

  • Sweetness: 20000 times sweeter than table sugar

  • ADI: 0-5 mg/kg/bw/d = 4920 packets

Advantame, developed by a Japanese company, was recently approved for general use except for in meat and poultry products by the FDA in 2014. It is synthesised from isovanillin and aspartame (4).

As advantame is chemically related to aspartame, it is metabolised into aspartic acid and phenylalanine. Lower levels of advantame are consumed in order to reach the same level of sweetness as aspartame and hence, products do not require a warning label for people with phenylketonuria (PKU) (5).

Safety

The safety of advantame is evidenced by 37 animal and human studies at a variety of doses. These studies have found no evidence for carcinogenicity or developmental toxicity when high doses were administered (6). Though there are no negative effects, there are still concerns over the long-term use of advantame. There were 4 human trials included with small sample sizes and with the longest-running for only 12 weeks. Long-term trials with more people are needed to establish the health effects of this artificial sweetener in the future (7).

Like neotame, advantame is ranked as “safe” by the Center for Science in the Public Interest (CSPI) (8). However, according to a senior scientist at CSPI, the number of mice that survived in one key study was below the FDA’s recommendations and is therefore inadequate to provide confidence in the safety of a chemical likely to be consumed by millions of people (9).

The ADI of advantame is 5 mg/kg body weight per day.

Aspartame

 
  • Brand: Nutrasweet®, Equal®, and Sugar Twin®, AminoSweet

  • Sweetness: 200 times sweeter than table sugar

  • ADI: 50 mg/kg/bw/d by the FDA and 40 mg/kg/bw/d by the EFSA = 75 packets (60kg person)

  • Products: diet soda, sugar-free ice cream, fruit juice, gum, yoghurt, sugarless candy

Aspartame is 200 times the sweetness of table sugar and is the most commonly used sweetener in the world. It was approved by the FDA in 1981 and found in more than 6000 products. Virtually all sweet-enhanced foods have a varying amount of aspartame.

Some major concerns come from aspartame’s broken-down constituents which include methanol, phenylalanine and aspartic acid (10, 11).

Methanol has been stirring up the most concern because it can be toxic in very high amounts as it is converted into formaldehyde in the body. However, there is no evidence that this conversion results in any harmful levels of formaldehyde in the body as the amount of methanol you get from aspartame is very insignificant (12). There is more methanol in fruits and vegetables than in a can of diet soda (13). The body also produces formaldehyde on its own and at levels thousands of times higher with no harmful effects.

Who should avoid

Both phenylalanine and aspartic acid are amino acids found in most protein sources and there is no harm in eating them.

However, for those who have a rare genetic disorder called phenylketonuria (PKU) that causes high levels of phenylalanine in the blood due should limit their intake of aspartame as it can cause intellectual disability and other health problems.

 

It is best to be avoided for those who take schizophrenia medications as it may trigger tardive dyskinesia (TD), a disorder that causes uncontrolled muscle movements (14).

Cancer

Long-term studies have linked the consumption of aspartame with an increased risk of lymphomas and leukaemia but in rats (15, 16). However, the American cancer society points out that there are is no strong link between aspartame and cancer risk (17).

Possible effects

Health complaints such as headache, dizziness, digestive symptoms, changes in mood, Alzheimer’s disease, birth defects, diabetes, Gulf War syndrome, attention deficit disorders, Parkinson disease, lupus, multiple sclerosis, and seizures have been reported but studies have not found evidence to support claims (18).

The acceptable daily intake (ADI) according to the FDA for aspartame is 50 milligrams per kilogram per day while the EFSA recommends 40 milligrams per kilogram per day. However, these amounts are far more than what most people consume a day. That accounts for roughly 21 cans of diet soda for a man that weighs 80 kg for the rest of his life with no health risks.

Neotame

 
  • Brand: Newtame®

  • Sweetness: 7000 to 13000 times sweeter than table sugar

  • ADI: 0.3 mg/kg/bw/d = 23 packets (10,000x sweetness of table sugar)

  • Products: soft drinks, dairy products, frozen desserts, baked goods

  • Food label:  E961

Neotame was approved as an artificial sweetener in 2002 by the FDA and as a flavour enhancer in 2010 in the European Union but it is not yet widely used in food products.

Neotame is chemically related to aspartame with an additional 3,3-dimethylbutyl. Neotame is metabolised into de-esterified neotame and a negligible amount of methanol. Both are eliminated rapidly in the urine and faeces (19).

 

This modified version blocks the enzyme responsible for breaking the bond between aspartic acid and phenylalanine. Consequentially it reduces the release of phenylalanine making neotame safer for consumption for those who have phenylketonuria (PKU). Hence, neotame is not required to carry the PKU warning on its label (20).

Safety

Over 100 corporate-sponsored studies in animals and humans confirm the safety of neotame. These experimental studies show that neotame usage is non-genotoxic, carcinogenic, teratogenic and safe for both healthy and type 2 diabetic patients (21).

Additionally, neotame and advantame are the only artificial sweeteners ranked as “safe” by the Center for Science in the Public Interest (CSPI) (22).

As much of these studies are industry-funded, there is a chance that they are poorly designed and biased. Hence, more trustworthy, independent research is needed to confirm these claims.

Possible effects

It also appears that the chemical structure of neotame deems it to be a more dangerous neurotoxin, immunotoxin and excitotoxin than aspartame.

3,3-dimethylbutyl is a toxin found on the most hazardous list of the Environmental Protection Agency (EPA). It is classified as a highly flammable irritant to the eyes, skin and respiratory system (23).

Like aspartame, methanol is converted into formaldehyde, a known carcinogen. It can produce cancer of the throat, pharynx and lung even in low doses (24, 25).

On your plate

Neotame is not sold to the public but as a cheaper substitute, it is widely used by manufacturers in prepared foods.

Neotame marketed as Sweetos has been substituted for molasses in animal feed companies so animal products are potentially laced with neotame residues (26).

The established ADI for neotame is 0.3 mg/kg body weight per day.

Saccharin

 
  • Brand: Sweet and Low®, Sweet Twin®, Sweet'N Low®, and Necta Sweet®

  • Sweetness: 200 to 700 times sweeter than table sugar

  • ADI: 15 mg/kg/bw/d = 45 packets (400x sweetness of table sugar)

  • Products: diet drinks, candies, jams, jellies, medicines

  • Food label:  E954

Saccharin use has been dated back to the 1900s, but it is not very commonly used in food and beverages now. Saccharin has been mostly replaced in foods by the more popular sweeteners aspartame and sucralose. It was once is approved by the FDA but banned in some countries. Only since 2014, saccharin was extended from its approval from table-top sweeteners to use in unstandardised food and beverages in Canada (27).

Roughly 85% to 95% of saccharin is absorbed and excreted in the urine and faeces (28).

 

Cancer

Previously saccharin consumption was linked to bladder cancer, but trials were performed in laboratory rats (29). Subsequent observational human studies were done to demonstrate that results were not relevant to humans (30, 31).

Saccharin was then delisted from the National Toxicology Program (NTP) in 2000 as a human carcinogen (32).

However, many health experts claim that observational studies are insufficient to confirm that saccharin is 100% safe for consumption.

Gut microbiota

From a 2014 study, researchers found that saccharin modulated microbiota composition and contributed to higher blood sugar levels in mice. This indicates glucose intolerance and could potentially lead to type 2 diabetes.

Similarly, they conducted a 7-day experiment giving 7 healthy people the maximum ADI of saccharin at 5 mg/kg body weight per day. After 7 days, 4 of the 7 subjects did experience microbial imbalances and abnormally high blood glucose levels (33).

It is speculated that a type of bacteria which is efficient at turning food into energy feeds on saccharin and hence, more calories are available for the body. However, more studies are needed to explore how saccharin can affect the gut microbiota.

Saccharin’s established ATI is 5 mg/kg body weight per day which translates into 9 to 12 packets of sweet’ n low every day.

Sucralose

 
  • Brand: Splenda®

  • Sweetness: 600 times sweeter than sugar

  • ADI: 5 mg/kg/bw/d = 23 packets

  • Products: frozen desserts, gum, gelatins, coffee, tea

  • Food label: E955 (EU food addictive numbering system)

Sucralose was approved by the FDA in 1999 and is found in Splenda in combination with dextrose and maltodextrin. Like Ace-K, it is heat-stable and used in many baked goods. Sucralose is poorly absorbed and undergoes little metabolism and is excreted primarily in the faeces in all species (34).

Blood glucose and insulin

Studies done in vitro shows that sucralose can stimulate intestinal entero-endocrine to release glucagon-like peptide 1 (GLP-1) and glucose-dependent insulin atrophic peptides which are hormones which enhances the secretion of insulin. So, this has led to a thought that artificial sweeteners can cause a release of insulin (35). In another study with 17 obese subjects who do not normally consume artificial sweeteners found that sucralose actually increased blood glucose and insulin levels (36). However, other studies done in normal-weight people have found no effects (37, 38).

Gut microbiome

A study done in rats found that sucralose decreased beneficial bacteria by up to 50%. In addition, the number of bacteria did not recover to previous levels after 12 weeks of the treatment (39). As this study was done in rats, more trials are needed to see if these results are applicable in humans.

Cooking and baking

Sucralose is considered to be heat-resistant, but studies suggest otherwise. Once heated at high temperatures, Splenda was found to breakdown and release toxic compounds called chloropropanols which is linked to cancer (40). Sucralose is thermally stable up to 119C or 350F, but it may be better to use alternatives if heated above this temperature (41).

Interferes with medication

Sucralose may limit the absorption of therapeutic drugs for heart disease and cancer rendering them less effective (42).

However, reviews have concluded that sucralose has no carcinogenic properties, no effects on the reproductive and development function, neurotoxicity in both healthy individuals and type 2 diabetics (43, 44).

The established ADI for sucralose is 5 mg/kg body weight per day. This is around 31 packets of Splenda a day.

Stevia Leaf Extract (Steviol Glycosides)

 
  • Brand: Stevia

  • Sweetness: 200 to 400 times sweeter than table sugar

  • ADI: 4 mg/kg/bw/d = 9 packets (300x sweetness of table sugar)

Stevia or stevia leaf extract comes from the leaves of Stevia rebaudiana Bertoni has been traditionally used in South America and Asia for many years. It has also been referred to as Rebaudioside A, Reb-A, or rebina. This newly introduced zero-calorie sweetener has been given a very positive association as it is derived from nature.

 

However, bear in mind that this does not mean that it is good for you or that it is better than something that has been synthesised in the lab (45). In fact, stevia products found in stores are highly refined and retains little of the original leaf.

Stevia contains one or more sweet-tasting compounds called steviol glycosides such as stevioside and rebaudioside A which are about 200 times of the sweetness of table sugar. Multiple steviol glycosides are converted to steviol in the colon and transported to the liver. The major metabolite, steviol glucuronide, is then excreted in the urine (46).

Purified stevia glycosides also known as stevioside were given full ADI approval by the FDA. Stevia leaf and crude stevia extracts are however not approved for use in food by the FDA (47). Due to the recent emergence, the safety of steviol glycosides does not have the history and research that most artificial sweeteners have but it has been reviewed by literature and results has been inconclusive (48, 49).

The established ADI for steviol is 4 mg/kg body weight per day which translate to 40 packets of stevia a day.*

Monk Fruit (Luo Han Guo) Extracts

 
  • Brand: NectresseTM, PurefruitTM, Fruit-SweetnessTM, Monk Fruit in the Raw®

  • Sweetness: 100 to 250 times sweeter

  • ADI: Not specified

Monk fruit extract, also known as Siraitia grosvenorii Swingle fruit extract (SGFE) is native to Northern Thailand and Southern China. The seeds and skins are removed from the fruit and the juice or extract is collected. Antioxidants called mogrosides that makes up of 1% of the flesh of these fresh fruits contributes to 100 to 250 times of the sweetness of sugar (50).

Some studies have shown that mogrosides have anti-inflammatory properties that can help with cancer and diabetic complications (51). However, monk fruit extracts are often blended with other sweeteners and products such as dextrose (Monk Fruit in The Raw) and erythritol (Lakanto) for a better taste so it always wise to check the nutrition label.

The FDA categorises monk fruit extract as “generally recognized as safe” or GRAS in the US in 2010 (52). Even so, there are not many scientific studies to support the safe use of monk fruit extract.

Summary

 

Based on the FDA Table for High-Intensity Sweeteners (54).

ADI: the maximum amount that can be ingested daily that does not result in an adverse effect 

  • mg/kg/bw/d = milligram per kilogram of body weight per day

* Values proposed by the European Food Safety Authority (EFSA). Under EU law no low and no-calorie sweeteners are permitted for use in products made for small children aged up to three years.

Take-Home Message

References


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The use of artificial sweeteners remains controversial, but it comes down to what is your definition of safe. While artificial sweeteners are designed to help people satisfy their sweet tooth without adding the calories found in sugar, it is better to consume them in moderation, just like everything else!