What serious effects the sweetener has on our microbiome and our health

The sweetener sucralose is increasingly suspected of having harmful effects on humans. But what is really true? Is it mere scaremongering, or are there study-based facts to support it?

Drinks, dairy products, confectionery, baked goods, frozen products, condiments, sauces, nutritional supplements, protein shakes – the list of foods in which sucralose is used as a sweetener seems almost endless. That’s because sucralose has the highest sweetening power of any conventional sweetener. Compared to table sugar, sucralose is 400 to 600 times sweeter.

This has two major advantages: firstly, even substances that do not taste particularly good can be made edible with only small quantities, and secondly, the low quantities used mean that the agent is inexpensive. The food industry therefore benefits from this in two ways.

In one kilogram of protein powder, the typical amount is between 0.1 and 0.5 grams. This means that a 50-gram serving of protein powder contains about 5 to 25 milligrams of sucralose. This may seem like a small amount at first glance, but it is not.

Approval process and false assumptions: What went wrong with sucralose?

When the original approval was granted by the US Food and Drug Administration (FDA) in 1998, it was based on the following assumptions:

• Stability in the body: Sucralose is almost completely and unchanged when it passes through the intestines and is excreted again.
• No effect on the gut microbiome: Sucralose should be inert, i.e. biologically inactive, and have no influence on the bacteria.
• No impairment of the intestinal barrier: Sucralose should not have any harmful effect on the intestinal wall.
• No bioaccumulation: sucralose should not accumulate in the body.
• No effect on glucose or insulin metabolism: Sucralose should not interact with blood sugar levels.
• No carcinogenic properties: Sucralose should not increase the risk of cancer.

Today we know that all these assumptions appear to be false. This is confirmed by studies conducted on humans and animals.

Discovery and marketing: sucralose – a chance discovery with enormous potential

Sucralose was discovered by a researcher at Tate & Lyle, working with the University of London, in 1976 when he was testing the compound by mistake and noticed its extremely sweet taste. The company focuses on specialty ingredients for the food and beverage industry. The huge commercial potential was quickly recognized, and initial safety and efficacy tests were followed by an aggressive market launch in the 1990s, initially under the brand name Splenda.

Natural or artificial? Sucralose compared to other sweeteners

The sweetener is considered a synthetic sweetener, as opposed to stevia, which is classified as a natural sweetener. Sucralose does not occur in nature and is produced by modifying table sugar to replace certain hydroxyl groups with chlorine atoms. This chlorination significantly changes the structure. The FDA also classifies sucralose as an artificial sweetener.

Which form of sucralose is harmful?

Contrary to the FDA approval at the time, pure sucralose is already harmful. This has been unequivocally demonstrated in various studies. It is particularly harmful when taken over long periods of time. However, because it is used as a sweetener in so many products, continuous intake is quickly established.

In addition, sucralose is partially converted into sucralose-6-acetate in the intestine. This metabolite is also present in low but relevant concentrations in commercially available sucralose. Sucralose-6-acetate is considerably more harmful than sucralose itself.

Interactions between sucralose and the microbiome: what happens in the gut?

There are two main interactions between sucralose and the microbiome:

The bacteria promote the breakdown product sucralose-6-acetate .

This is a hypothesis that is currently being tested. In this case, the microbiome would directly support the conversion of sucralose into the more harmful form sucralose-6-acetate. This seems likely because microorganisms have the necessary enzymes. The acidic environment of the stomach could also play a role, as could products formed by the microbiome that could then interact with the sucralose to form sucralose-6-acetate.

Direct effect of sucralose on the microbiome

The primary negative influence of this is on the microbiome. Not only does it change, but studies have shown that, in particular, the beneficial intestinal bacteria such as Lactobacillus and Bifidobacterium have been deliberately reduced, while the growth of pro-inflammatory bacteria has been promoted. A microbiome that has been thrown out of balance is the cause of many diseases and should be avoided as far as possible.

Further health damage caused by sucralose

But sucralose and its breakdown product cause much more than a negative influence on the microbiome. In the following, only the three most significant health risks associated with consumption will be shown.

A. Compromised intestinal integrity

Sucralose and, to an even greater extent, its breakdown product sucralose-6-acetate can weaken the intestinal wall through various mechanisms, such as oxidative stress, disruption of cell connections, inflammatory reactions and changes in the microbiome. This contributes to the dreaded “leaky gut syndrome”, in which bacteria and their toxins enter the bloodstream from the intestines.

The intestinal wall is a very important protective barrier against the large numbers of bacteria present in the intestine. If this barrier breaks down, the bacteria, toxins and undigested food particles enter the bloodstream. This can lead to a variety of health problems, such as inflammatory reactions, autoimmune diseases and hormonal imbalances.

The patient notices this primarily through gastrointestinal complaints, fatigue, headaches, skin problems and a variety of other health issues.

Leaky gut syndrome can be detected by various diagnostic tests, as, for example, certain substances are found in increased amounts in the bloodstream. Treatment of leaky gut syndrome is possible, but requires a holistic approach.

B. Impairment of glucose metabolism

Sucralose can affect the release of insulin from the pancreas. When sucralose is ingested, more insulin is released. An excessive insulin response over a prolonged period of time eventually leads to insulin resistance. As a result, less sugar is absorbed from the blood into the muscle, fat and liver cells, causing the blood sugar level to rise. Type 2 diabetes is the result.

C. Cancer promotion

The breakdown product of sucralose, sucralose-6-acetate, and to a lesser extent sucralose itself, have shown increased genotoxicity in studies. This damages the DNA in the cells, which in turn triggers mutations and can potentially cause cancer. The sweetener also has a direct effect on the repair mechanism, i.e. cells are less able to repair DNA damage, which basically occurs all the time. Increased mutations and cancer are the result.

Genotoxicity is probably the most drastic health effect, because it is directly relevant at the DNA level. It is important to keep this in mind: here is a substance that has the potential to damage the DNA in our cells. In addition, it also inhibits the repair of the genetic damage that it itself has caused. A truly toxic system.

What concentration of sucralose in the body is harmful?

As always, the dose makes the poison, even with sucralose. So the question is: can sucralose and its breakdown product already harm health in common concentrations? Can sucralose affect the microbiome in the process? The answer is a clear yes!

Genotoxic effects, i.e. damage to DNA, were observed at as low a level as 0.15 µg/person/day. This is a level that is exceeded by just a single sucralose-containing drink. In addition, both sucralose and sucralose-6-acetate bioaccumulate, i.e. accumulate in the body over a longer period of time.

Why isn’t sucralose banned yet? A look behind the scenes

The main problem is that sucralose has already been approved. Revoking this approval is a complex regulatory process in which many economic interests play a role, as do potential legal claims. However, the investigations for the approval all took place in the 1990s, when the molecular biological methods that are used today were not yet available.

Furthermore, the genotoxicity experiments were carried out on in vitro cell cultures or in animal models and are therefore not comparable with human studies. However, this highlights a problem of our time: there is an increasing demand for cell culture studies to replace human studies and animal testing on ethical grounds. But if these “replacement studies” show a hazard, no action is taken because the corresponding human studies are lacking.

But would you – in the case of sucralose – explicitly conduct experiments on humans? And isn’t it sufficient if concentrations that are common when sucralose is consumed show damage to DNA in cell cultures and animal experiments? Is it really necessary to transfer this to humans, which, however, for the reasons mentioned, is unlikely to happen in this form?

A negative cycle is created: consequences are only drawn when there is proof in human studies, which, however, are not carried out because negative consequences are to be feared. Until then, nothing will happen! Sucralose will continue to be allowed, and people will be endangered by it. Cancer rates will continue to rise, and since cancer has multifactorial causes and can rarely be traced to a single cause, the statistics show an increase in cancer rates – but sucralose is unlikely to be banned in the near future given its prior FDA approval and corporate lobbying. The victims here are the uninformed consumers.

Why do we even have sweeteners?

But once again, the problem goes deeper than that. The use of sucralose and other sweeteners is only a response to the market. It is a symptom, not a cause. The problem is the consumer desire for everything to taste as “good” as possible, in other words, sweet. The extent to which the food industry has trained consumers in this regard is not something that should be discussed here. However, the fact is that consumers are not willing to compromise: Food should be low in calories but still taste good.

It is easy for industry to use sucralose to improve the flavor of a product that doesn’t taste good on its own, such as a sugar-free juice or a protein mixture. And they do it because otherwise their products would not be accepted by most consumers, who in turn have become accustomed to sweetness in food due to the food industry’s use of sugar in high concentrations for many years.

This devil’s spiral must be broken. And that can only be done through independent investigation. (JS)

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Further reading:

Romo-Romo et al. (2018):
Romo-Romo, A., Aguilar-Salinas, C. A., Brito-Córdova, G. X., Gómez-Díaz, R. A., & Almeda-Valdes, P. (2018). Sucralose decreases insulin sensitivity in healthy subjects: A randomized controlled trial. American Journal of Clinical Nutrition, 108(3), 485–491. doi: 10.1093/ajcn/nqy152​.

Pepino et al. (2013):
Pepino, M. Y., Tiemann, C. D., Patterson, B. W., Wice, B. M., & Klein, S. (2013). Sucralose affects glycemic and hormonal responses to an oral glucose load in obese subjects. Diabetes Care, 36(9), 2530–2535. doi: 10.2337/dc12-2221​.

Li et al. (2020):
Li, X., Liu, Y., Wang, Y., Li, X., Liu, X., Guo, M., … & Jiang, M. (2020). Sucralose promotes colitis-associated colorectal cancer risk in a murine model along with changes in microbiota. Frontiers in Oncology, 10, Article 710. doi: 10.3389/fonc.2020.00710​.

Bian et al. (2017):
Bian, X., Chi, L., Gao, B., Tu, P., Ru, H., & Lu, K. (2017). Gut microbiome response to sucralose and its potential role in inducing liver inflammation in mice. Frontiers in Physiology, 8, Article 487. doi: 10.3389/fphys.2017.00487​.

Schiffman & Rother (2013):
Schiffman, S. S., & Rother, K. I. (2013). Sucralose, a synthetic organochlorine sweetener: Overview of biological issues. Journal of Toxicology and Environmental Health, Part B, 16(7), 399-451. doi: 10.1080/10937404.2013.842523​.

Schiffman et al. (2023):
Schiffman, S. S., Scholl, E. H., Furey, T. S., & Nagle, H. T. (2023). Toxicological and pharmacokinetic properties of sucralose-6-acetate and its parent sucralose: In vitro screening assays. Journal of Toxicology and Environmental Health, Part B, 26(6), 307-341. doi: 10.1080/10937404.2023.2213903​.