INTRODUCTION
Obesity is a significant medical issue affecting individuals of all ages, races, and ethnicities. In the United States, the prevalence of obesity among adult men and women increased substantially between 1980 and 2000.
Although the overall prevalence has remained stable since 2000, there is a concerning trend towards female obesity and extreme obesity.
The etiology of obesity is complex and involves both intrinsic host characteristics and extrinsic environmental factors.
Several factors, such as consuming high-energy foods, overeating, leading a sedentary lifestyle, alterations in gut flora, having a diet high in fat and/or sugar, and the use of artificial sweeteners, have been identified as contributing factors to obesity.
Recent studies have shown that the causes of obesity are more intricate than previously believed and require a better understanding of the role of internal and external factors in its development.
Artificial Sweetener Types :
There has been an increase in the use of AS over the past several decades, with over 6000 products available in the USA alone.
The first artificial sweetener was created in 1879 at Johns Hopkins University and is known as "saccharin".
It is used frequently in soft drinks, candies, salad dressings, chewing gum, and non-edible items including toothpaste, mouthwash, and pharmaceuticals. It is 200 - 700 times sweeter than sucrose.
Aspartame, second-generation sweetener that is around 200 times sweeter than sucrose and was approved by the FDA in 1981.
Sucralose, which has a sweetness equivalent to 300 times that of sucrose, is 600 times sweeter.
There are more newer AS on the market, such as stevia and fermented sugar alcohols like sorbitol and xylitol, which can cause constipation when ingested in significant doses.
The consumption of AS has generally increased exponentially over the past 20 years, with carbonated diet beverages being the main source.
The Effects of Artificial Sweeteners on the Microbiome :
Structure and Function of the Microbiome
The microbiome is a heterogeneous population of bacteria which has animmense spatial distribution throughout the gastrointestinal tract covering a surface area of approximately 300 to 400 m2. The internal milieu of the host and the external environment significantly influence the diversity and virulence genes of the host intestinal flora.
Studies of the microbiome are now possible because of advances in genebased sequencing techniques. Using a 16S ribosomal RNA sequence, a significant number of bacteria have been identified that were previously not found using culture techniques alone.
Further application of gene sequencing methods allows investigators to study the impact of AS onthe microbiomeand examine downstream effects on the host metabolism and nutrient absorption.
The microorganisms in the gut employ specific enzymes that are not encoded in the human genome that enable the host to extract calories from otherwise indigestible foods.
Alterations in the microbiome lead to changes in energy extraction and influence the body fat composition of the host . The gut microbiome is predominantly inhabited by strict anaerobic bacteria with lower levels of facultative anaerobes and aerobes.
In humans and rodents, most of these bacteria reside in the colon and are dominated by bacteroidetes and firmicutes.
Prior studies suggest that obese rodents have a lower abundance of bacteroidetes and a greater abundance of firmicutes compared to their lean counterparts.
Artificial Sweeteners' Effects on the Microbiome: Rat Model
The impact of low-dose aspartame ingestion on the microbiota and body fat composition was investigated.
The aspartame group's fecal examination after 8 weeks revealed a higher concentration of enterobacteriaceae and clostridium leptim.
Rats fed a high-fat diet showed an elevated firmicutes-to-bacteroidetes ratio, and aspartame exposure reduced this ratio in those rats.
In spite of eating less calories and putting on less weight, aspartame-treated rats showed greater fasting hyperglycemia and a more noticeable impairment in insulin tolerance testing.
Showed that consumption of AS (saccharin, sucralose, and aspartame) rather than water, glucose, or sucrose-containing water increases glucose intolerance in both lean and obese mice.
The mice who received the fecal transplant from the saccharin group displayed higher decreased glucose tolerance compared to the control group when the feces were transplanted into
normal chow-consuming germfree mice.
These results show that changes in the microbiota are at least partially responsible for the effect of AS on metabolic markers, including insulin resistance.
Human Studies on the Microbiome and Artificial Sweeteners :
When mice consume AS, bacteroides are more prevalent and clostridiales are less prevalent, which is comparable to what is observed in people with type 2 diabetes.
Scientists looked at how AS affected blood glucose management in seven healthy volunteers who had never consumed a lot of AS before.
When compared to the first 4 days of exposure, four out of seven participants showed lower glucose tolerance after 5 to 7 days.
According to this study's findings, some people may be more susceptible than others to developing glucose intolerance after being exposed to AS due to the variability in their microbiomes.
Artificial Sweeteners' Effects on the Gut-Brain Axis :
Neuro-Hormonal Changes After Consumption of Sugar and Artificial Sweeteners : The Reward Phenomenon
Because of its subsequent impacts on behavioral and neurochemical pathways, such as adjustments in dopamine, opioid receptor binding, and acetylcholine release in the nucleus accumbens, sugar has a high potential for addiction.
These neural modifications ultimately cause excessive sugar consumption by
triggering the "reward phenomenon".
Food reward involves both post-ingestion and sensors pathways.
Two G-protein receptors (T1R2 and T1R3) that make up the sweet taste receptor in the oropharynx are a part of the sensory pathway .
When sugar or AS is consumed, the sweet taste receptor is activated, and signals are sent to the hypothalamus and the amygdala, which are linked to reward and satisfaction .
The amount of energy in the food or drink being taken affects the post-ingestion route.
The sweet taste receptors are stimulated when AS are consumed instead of sugar, but the rise in blood glucose and insulin production do not happen to the same extent.
The post-ingestion pathway is drastically changed by AS, either because they do not contain any energy or because they are not digested.
Due to a lack of caloric energy, AS only partially engage the food reward pathway and the post-ingestion pathway while activating the oral taste receptors.
Changes in these pathways ultimately result in an increase in appetite, food cravings, and calorie intake.
Conflicting Data in Human Studies Regarding Changes in Glucose Homeostasis :
17 obese, insulin-sensitive people who had never used artificial sweeteners were tested to see how sucralose consumption affected them.
In comparison to the control group who drank water 10 minutes before to a glucose load, sucrose consumption increases peak plasma glucose concentrations and insulin secretion.
Unlike the previous trial, scientists examined the effects of stevia, aspartame, and sucrose in 19 healthy, lean, and 12 obese people before lunch and dinner.
The aspartame and stevia groups did not overcompensate by overeating at lunch and supper, and all groups experienced comparable levels of self-reported hunger and satiety.
The stevia group, in contrast to the aspartame and sucrose groups, had remarkably decreased postprandial glucose levels.
Examined the impact of various sugar- and artificially-sweetened beverages on type 2 diabetes incidence.
Using an analysises, it was found that switching to unsweetened tea, coffee, or water instead of artificially sweetened liquids resulted in a substantial decrease in the incidence of acquiring diabetes.
In a prospective trial, aspartame, monk fruit, stevia, or beverages sweetened with sucrose were randomly assigned to one of four groups, each consisting of 30 healthy males.
After consuming the allocated beverage, blood sugar and insulin levels as well as daily calorie intake were assessed using food diaries.
Compared to the artificial sweetener groups, the sucrose-containing beverages cause higher rises in serum glucose and insulin within the first hour after consumption, but there were no changes in the total area under the curve for either glucose or insulin during the following three hours.
Hormonal Changes After Consumption of Artificial Sweeteners: Human Studies Previous :
According to studies, consuming AS increases subjective ratings of motivation to eat and subjective appetite in comparison to controls.
More recent research indicates that AS have several downstream consequences on digestion, food absorption, and metabolism in addition to not inducing satiety in the same manner as sugar does.
According to a study by scientists glucose consumption activated GLP-1 and GIP at higher levels than sucralose administration.
The delayed stomach emptying and elevated satiety were both related to the stimulation of these gut hormones.
In conclusion, research indicates that AS interferes with fundamental learnt behaviors.
After consuming AS, changes in the post-ingestion pathway and the stimulation of sweet taste receptors limit anticipatory reactions that often help to maintain physiological homeostasis following a sugar load.
Artificial Sweeteners' Relationship to Obesity :
There is an abundance of evidence that suggests AS affects typical physiological functions related to metabolism and nutrition absorption and, as a result, affect alterations in body adiposity.
Rodent Studies on the Impacts of Obesity
According to scientists research, consumption of either saccharin or aspartame was linked to increased weight gain and adiposity without being connected to caloric intake.
According to scientists, mice given artificial sweeteners similarly saw increases in adiposity after 4 weeks of receiving sucrose supplementation, which enhanced hyperglycemia, weight gain, and adiposity.
Effects on Obesity : Human Studies
The use of artificial sweeteners is positively associated with higher BMI in a dose-dependent manner, according to a number of large-scale prospective cohort studies.
According to research drinking artificially sweetened beverages while pregnant was linked to a higher infant body mass index (BMI).
During 2009 and 2012, the study enrolled 3033 healthy women, and during those years it evaluated the consumption of artificial sweeteners and sugar-sweetened beverages based on dietary evaluations made during pregnancy.
The study found a twofold increased risk of being overweight at age 1 for those who regularly consume artificially sweetened beverages.
A recent meta analysis of 11 studies found that patients who consumed sugar-containing soda had a pooled relative risk (RR) of obesity of 1.18 (95% CI, 1.10-1.27) compared to patients who consumed artificially sweetened soda, who had an RR of 1.59 (95% CI, 1.22-2.08).
Adults who consumed AS based on dietary recall in a cohort study of 1454 adults from 1984 - 2012 with a median follow-up of 10 years had a significantly higher BMI and waist circumference than non-users.
CONCLUSION
Despite the fact that AS were developed as a sugar alternative to aid in weight loss and the reduction of insulin resistance, a large body of evidence indicates that AS have a dramatic effect on the host microbiota, gut-brain axis, glucose homeostasis, energy expenditure, overall weight gain, and body obesity.
Despite the fact that AS are promoted as a healthy alternative to sugar, the vast bulk of evidence refutes this assertion.
The fact that consumption of AS is frequently relied on dietary recall is one of the key constraints that makes it difficult to evaluate the results in human studies.
Customers might not be aware that they are consuming AS because so many goods, including mouthwash, toothpaste, sauces, and frozen dinners, contain it.
Given that the microbiome appears to be one of the primary factors influencing nutritional absorption and glucose metabolism, future research on the more recent plant-based sweeteners should concentrate on alterations in the microbiome.
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