There are many things that we have been eating without knowing their advantages and disadvantages. Non-nutritive sweetener is a one that has been made a lot of controversial. As we drink coffee, we usually like to add a little sweetness to it. People who want to lower their calorie intake would use non-nutritive sweetener for their diet (Liauchonak, et al., 2019). However, do we know what is a non-nutritive sweetener exactly? What are their structures look like? What is microbiome and glucose tolerance mean? Well, you can find the best explanation in my blog, so keep diving with me into this topic.

A non-nutritive sweetener or sugar substitutes contain carbohydrates but lower energy than table sugar, which is sucrose, that use to enhance the flavor of food (Liauchonak, et al., 2019). It first introduces in 1878 to replace normal table sugar (Walbolt & Koh, 2020). The non-nutritive sweetener can increase the chance of getting type 2 diabetes, and cardiovascular (Walbolt & Koh, 2020). The authors (Walbolt & Koh, 2020) state, for those products labeled as “no sugar” or “diet” usually contain non-nutritive sugar). There are four types of sugar substitutes: saccharine, sucralose, stevia, and aspartame. Its structure can be found at the end of this blog.

Using non-nutritive sweeteners in a long-term will affect our microbiome (Wang, et al., 2022). According to my knowledge, a microbiome is a community or a microorganism of fungus, bacteria, genes, and viruses that live in our body and on our skin. The human microbiome is a complex system that has been never fully explored. While we have not yet discovered all its functions, research has shown that it is involved in many aspects of human wellness. A healthy microbiome can protect us from pathogens and keep our immune systems strong.  

Glucose tolerance is the ability of processing glucose in a person. Glucose tolerance refers to how well an individual can handle blood sugar levels in their body. It is the increased rate at which type of sugar is metabolized in the bloodstream, and cells can use it to turn it into energy. A good glucose tolerance reflex is how well a person’s insulin receptors are working. A poor glucose tolerance reflexes that person is in prediabetes. It is important to mark diabetes as soon as we can because diabetes can turn complicated if left untreated. Doctors can help us check our insulin resistance by using the Oral Glucose Tolerance Test or OGTT (Eyth et al., 2022).

The relationship between microbiota and glucose tolerance are remain controversial. According to (Cohen, 2020), molecules control how our liver sends glucose into the bloodstream. Higher intake of carbohydrate will decrease the Blautia genus in the gut which will lower glucose intolerance (Egshatyan et al., 2016). Blautia is a genus of anaerobic bacteria in our intestines that help maintain our health and alleviate metabolic syndrome (Liu et al. 2021). Diabetes people have higher Blautia genus abundance exist in their bodies (Egshatyan et al., 2016).  Although many studies established the relationship between glucose tolerance and sugar substances, there is still controversial of these sugar on human health. Some of research demonstrates that sugar substances change microbial metabolic pathways which leads to glucose intolerance in humans (Suez et al., 2014).

When we are taking food, our blood sugar will be raised rapidly and over time, it will get back to normal. In this case, some people might misunderstand non-nutrient sweeteners. They overthink that these substitutes will help them to lower calorie intake and manage their blood sugar properly.  Non-nutrient sweeteners have a great impact on our health and body. The four main types of NNS include sucralose stevia, saccharin, and aspartame. To answer the concern, a group of scientists decides to research this special problem. The definition of basic glucose tolerance is a part of glucose tolerance that controls how sharply that blood glucose level will rise. It could depend on either genetics or your body’s metabolism. A person who is impaired with glucose tolerance will take a longer time to get back to the normal level of blood glucose. Also, their blood sugar will rise more rapidly and sharply.

First, to start the study, they divide people into six groups. There are about 20 people per group. These groups include four types of sugar substitutes, one non-supplement control group, and a glucose group. They test only glucose to see if itself related to the problem. The experiment happens in 28 weeks, and all participants are in good health condition. In the first 2 weeks, they let them drink sweet drinks in the morning. These people, also have to wear continuous glucose monitors. The last week is to get the blood sugar back to normal. The scientists also did some blood tests on the first day, middle and last day. Glucose tolerance testing is necessary.

According to the article, the saccharin and sucralose “significantly elevated glycemic response” compared to glucose tolerance (Suez et al., 2022). This can be proved in Figures 2 E and F, the curves change rapidly. Figure 2 I and J are almost the same, which is what we expected to see because it contains a non-supplement group. In the stevia group, the curve is kind of moving downward which is different from others. The Aspartame group looks just like the glucose group.

All four types have greatly affected microbiome function according to the research ((Suez et al., 2022). Especially, sucralose and saccharine are the most effect on the microbiome (Figure 3 A&C). For sucralose, the most effective can be found in isoprene biosynthesis I, and methylerythritol phosphate II. The less effective is glycolysis I. Isoprene biosynthesis I is 5 carbon isomers that are responsible for building important terpenoids such as cholesterol, steroids, etc. Methylerythritol phosphate II is a pathway for building 5 carbon that blocks isoprenoids. In saccharin, the most effective is in glycolysis VI which is to produce energy. The less effective is lysine biosynthesis I which is an amino acid and building block of proteins. In aspartame, arginine biosynthesis II is the most effective. It is responsible for protein synthesis as amino acids. The gluconeogenesis III functions is decreases.  In stevia, the arrow goes opposite direction which decreases compared to others. It goes negative direction but still has a great impact on the microbiome, especially in phospholipid biosynthesis I. Its function can be defined as maintaining of plasma membrane bilayer of cells. The author states that none of these microbiome features are related to glucose and the NSC group ((Suez et al., 2022).

All four types of sugar substitutes have different bacteria. These bacteria are shown in Figure 4. The yellow highlighted bacteria are possibly impacted related to glucose tolerance testing (GTT). And purple highlighter is a negative impact. Some of them are positive changes in GTT and some of them are negative changes in GTT. Even if it is positive or negative, it still causes a significant impact on the metabolism (last, year). Stevia and saccharine are shown commonly in prevotella bacteria. Saccharine has fewer positive bacteria. related to GTT while stevia has the most bacteria which is positive for GTT. In saccharin there is one common bacterium related to reducing glycolysis II.

To determine if the change in glucose has anything to do with the change in the microbiome gut, they did a small test on Germ-free mice (GF mice) called a fecal transplant. They use gut bacteria from 4 people per group and let the mice taste it through “oral gavage with microbiome extract from stool sample” (Suez et al., 2022). As we can see in Figure 5 F which is the NSC group, the two lines are almost overlapping and close together. The most responsive groups are saccharin and stevia. As in Figure 5 G which is saccharin, it still effects on human microbiome even with weak responders. In the last panel, it changes in gut microbiome but itself. It provides a little change in glucose metabolism even with no bacteria. In panel K, which is glucose from bottom responder, two lines are overlap with each other. It means it is not a big effect.

In conclusion, NNS may inhibit microbial growth, and some types affect directly the human microbiome (Suez et al., 2022). This effect could affect directly GTT and glucose metabolism. NNS is not good as they advertise on TV or the Internet. Some products are labeled sugar-free, but it is not 100% no calories. It even rises your blood sugar more than normal products because they could use NNS.  You should avoid NNS products, stevia substitute with little amount. Try to avoid sugar if unnecessary. And intake maple syrup, sugar in fruits instead. There are some fruits and vegetables you should take to maintain blood sugar level such as broccoli, almond, spinach, kale, etc.

Reference

Cohen D., Krisko H., and Krisko T. (2020). Gut Microbiome Controls Blood Glucose Levels
Through the Liver. Weill Cornell Medicine, https://news.weill.cornell.edu/news/2020/02/gut-
microbiome-controls-blood-glucose-levels-through-the-liver
Egshatyan et al. (2016). Gut microbiota and diet in patients with different glucose tolerance.
Endocrine Connections, https://ec.bioscientifica.com/view/journals/ec/5/1/1.xml
Eyth E., Basit H., and Swift C. (2022). Gluscose Tolerance Test. National Library of Medicine,
https://www.ncbi.nlm.nih.gov/books/NBK532915/
Liauchonak, I., Qorri, B., Dawoud, F., Riat, Y., and Szewczuk, M.R. (2019). Non-Nutritive
Sweeteners and Their Implications on the Development of Metabolic Syndrome. National
Library of Medicine,
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471792/
Liu X., Mao B., Gu J., Wu J., Cui S., Wang G., Zhao J., Zhang H., and Chen W. (2021), Blautia-
a new functional genus with potential probiotic properties. National Library of Medicine,
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872077/
Suez et al. (2014) Artificial sweeteners induce glucose intolerance by altering the gut microbiota.
National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/25231862/Suez, J. et al. (2022) “Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance,” Cell, 185, 3307-3328.
Walbolt, J., and Koh, Y. (2020). Non-nutritive Sweeteners and Their Associations with Obesity
and Type 2 Diabetes. National Library of Medicine,
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338497/
Wang, W., Nettleton J., Gangzle M., and Reimer R. (2022). A Metagenomics Investigation of
Intergenerational Effects of Non-nutritive Sweeteners on Gut Microbiome. National Library of
Medicine, https://pubmed.ncbi.nlm.nih.gov/35096940/

This is my drawing of examples of fruits and vegetable you should eat to maintain blood sugar.