The "bitter" effects of artificial sweeteners

Artificial sweeteners have grown in popularity as ‘safe’ alternatives to sugar (sucrose). They are extensively used by the beverage industry to make ‘diet’ sodas, they are also used in various packaged foods, drugs and mouthwashes. The most popular artificial sweeteners include saccharin, sucralose, aspartame, stevia, acesulfame potassium (acesulfame—K ) and neotame.

Figure 1. Popular artificial sweeteners. Link

These products are many times sweeter than sucrose: saccharin is roughly 300 times sweeter than sucrose; aspartame is about 200 times sweeter than sucrose; sucralose (which is derived from sucrose by substituting chlorine for three hydroxyl groups present in the structure of sucrose) is 600 times sweeter than sucrose. Neotame, by the way, takes things to a whole new level – neotame is considered the most potent sweetener on the market, it is roughly 7000 times sweeter than sucrose.

Figure 2. A comparison of the chemical structure of sucrose and sucralose. Link

One thing common to all of these products (apart from extreme sweetness) is that they have negligible or caloric value and they can activate the sweet taste receptors in the mouth at very low concentrations.

A couple of factors are considered responsible for the sheer ubiquity of these sweeteners. In the age of exponential rise in the incidence of obesity and diabetes largely due to our modern eating habits, products which are marketed as safe alternatives to sugar certainly appeal to so many people.

Most people would love to be able to do whatever they wanted if they were assured of no negative consequences, and this applies especially to our eating habits. We certainly want to keep consuming our sweetened foods and drinks without putting on weight or becoming diabetic. But as the old saying goes,"if it sounds too good to be true, it probably is."

We will examine some of the research findings on artificial sweeteners to see if they are really as safe as we have long been led to believe.

The negative effects of artificial sweeteners

1. Weight gain:

One of the main claims made by the manufacturers of artificial sweeteners and the diet beverage industry, which would love to put these sweeteners in every can of beverage, is that artificial sweeteners (being non-nutritive) promote weight loss in individuals that are overweight and obese and help to maintain normal body weight.

On the surface, this claim makes sense when you consider this fact: out of the six artificial sweeteners approved by the United States Food and Drug Administration and classified under the ‘Generally Recognised as Safe’ (GRAS) category, only aspartame can be metabolised by the body and it yields only 4 calories per gramme. The other artificial sweeteners are usually excreted unchanged. The expectation is that since these sweeteners contribute zero or negligible calories to the body, they should not contribute to any additional weight gain.

Recall that, roughly speaking, weight gain is a function of energy intake relative to energy expenditure: all else being equal, when energy intake exceeds energy expenditure, a person gains weight. The reverse is true when energy expenditure exceeds energy intake.

The description above is an oversimplification of the complex metabolic processes that take place in the human body but it paints a pretty good picture.

The Body Mass Index (BMI) is a statistical tool that measures the weight of an individual in relation to their height and determines if the person is of normal weight, overweight or obese. The BMI has its flaws (for example, it doesn’t factor in race, ethnicity or sex) but it is convenient and largely gives a good approximation of a person’s weight profile.

Several epidemiologic studies have found positive correlation between long-term consumption of artificial sweeteners and weight gain by taking BMI measurements of the subjects at the beginning of the study and a few years later at follow-up.

The San Antonio Heart study involving 3,682 adults carried out over a 7 to 8 year period in the 1980s found that consumers of the artificial sweeteners had consistently higher BMI values that varied with the amount consumed. Adults who consumed higher amounts of artificial sweeteners had consistently higher BMI values than adults who consumed lower amounts of artificial sweeteners. [3]

A similar large scale study by the American Cancer Society in the early 1980s involving 78,694 women, very similar in age, ethnicity, socio-economic status and lack of pre-existing conditions found statistically significant increase in weight (2.7% to 7.1%) in the group that regularly consumed artificial sweeteners compared to the non-users of artificial sweeteners after one year.[8]

How does the consumption of artificial sweeteners lead to weight gain?

Several explanations have been advanced based on experimental results. A few of these will be explored in this section.

• Increased appetite:

Sweet-tasting products have been shown experimentally to increase human appetite. A study found that aspartame-sweetened water significantly increased the subjective appetite ratings in adults with normal body weight; aspartame capsule however failed to have any significant effect on subjective hunger ratings, suggesting that the recorded increase in hunger ratings was primarily due to the sweet taste of the aspartame-sweetened water. [1]

• Increased hunger:

Another study found that aspartame significantly increased subjective hunger ratings compared to glucose or water. [2]

• Increased energy intake:

When consumed before meal, artificial sweeteners have been found to significantly increase energy intake compared to glucose and sucrose, which caused a decrease in energy intake in moderately restrained eaters. [4]

2. Hyperglycaemia:

Diabetics, in attempts to keep their blood glucose levels within the recommended range, have widely adopted artificial sweeteners as safe alternatives to sugar-laced foods and beverages. As we all know, Diabetes (especially type 2 diabetes mellitus) has been rising steadily worldwide. The idea behind the consumption of artificial sweeteners instead of sugar is quite logical.

Artificial sweeteners, unlike sugar, are not converted to glucose and so should not lead to elevated blood glucose levels (hyperglycaemia) which would result in insulin resistance over a period of time.

The reality though is a little bit different.

A large scale study in the U.K involving almost 25,000 people reported that the risk of type 2 diabetes was significantly elevated among consumers of diet soft drinks compared to non-consumers. Furthermore, the study concluded that a decrease in the risk of type 2 diabetes would not be achieved by switching from beverages sweetened with sugar to beverages containing artificial sweeteners. [5]

A smaller study involving young Japanese men found an almost two-fold increase in the risk of type 2 diabetes in the group that consumed diet sodas compared to the control group. [6]

Biological mechanisms behind the negative health effects of artificial sweeteners

People have sought to explain why the so-called ‘healthy’ sugar substitutes have produced such counter-intuitive effects documented by large scale studies. There is evidence of behavioural and physiological modifications associated with the consumption of artificial sweeteners.

Usually humans and animals quickly learn to associate sweet taste in the mouth with the arrival of sugar and calories in the gut. The anticipation of sugar in the gut kicks off a cascade of physiological processes that promote effective and efficient metabolism of the ingested sugars and also regulate the feeling of satiation.

When artificial sweeteners are consumed, the relationship between sweet taste and the arrival of calories in the gut is severely disrupted, and over time, the normal physiological responses to sweet taste become slower and less intense (e.g the secretion of useful hormones such as insulin and glucagon-like peptide 1 [GLP-1] is substantially reduced). This results in excessive intake of calories when real sugar is consumed, as the time taken to reach satiation is significantly longer.[9]

Recall that insulin helps to modulate blood glucose levels by increasing the uptake of glucose by cells and by inducing the conversion of excess glucose to glycogen in the liver. GLP-1 is released by L cells in the intestine following the intake of food and has the desirable effects of slowing down gastric emptying, suppressing the release of glucagon by the alpha cells of the pancreas. GLP-1 also acts in concert with insulin to ‘drive’ more glucose from the bloodstream into cells.

Another important mechanism by which artificial sweeteners promote weight gain and trigger elevated blood glucose levels has been traced to the gut – specifically, the large communities of micro-organisms such as bacteria, fungi and viruses that dwell in the gut (referred to as the gut microbiota).

The gut microbiota is important for regulating many physiological processes in the body (e.g., metabolism, immune function and growth). Due to the crucial roles played by the gut microbiota, any disruption to the delicate balance in the populations of the various microbial families could have significant effects on metabolism, immunity and other processes.

In a 2014 study by Suez and colleagues, [7] it was shown that regular consumption of artificial sweeteners such as saccharin, sucralose or aspartame resulted in glucose intolerance in mice (glucose intolerance is a marker of diabetes mellitus). The glucose intolerance was caused by alterations in the microbial populations in the gut of the mice, and was rapidly suppressed by antibiotic treatment.

Interestingly, when the researchers transferred the gut microbiota from the group of mice consuming artificial sweeteners into germ-free mice that had been raised under aseptic conditions, the germ-free mice also developed glucose intolerance. However, the transfer of gut microbiota from the control group (not fed any artificial sweeteners) into germ-free mice did not cause glucose intolerance in the germ-free mice. This study clearly shows that artificial sweeteners can disrupt the gut microbiota and induce glucose intolerance.

Final thoughts: I do not think it is feasible to completely avoid of artificial sweeteners, but the consumption of artificial sweeteners should certainly be minimised. Stay healthy!

References

1. Black, R. M., Leiter, L. A., & Anderson, G. H. (1993). Consuming aspartame with and without taste: differential effects on appetite and food intake of young adult males. Physiology & behavior, 53(3), 459–466.


2. Blundell, J. E., & Hill, A. J. (1986). Paradoxical effects of an intense sweetener (aspartame) on appetite. Lancet (London, England), 1(8489), 1092–1093.


3. Fowler, S. P., Williams, K., Resendez, R. G., Hunt, K. J., Hazuda, H. P., & Stern, M. P. (2008). Fueling the obesity epidemic? Artificially sweetened beverage use and long-term weight gain. Obesity (Silver Spring, Md.), 16(8), 1894–1900.


4. Lavin, J. H., French, S. J., & Read, N. W. (1997). The effect of sucrose- and aspartame-sweetened drinks on energy intake, hunger and food choice of female, moderately restrained eaters. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity, 21(1), 37–42.


5. O'Connor, L., Imamura, F., Lentjes, M. A., Khaw, K. T., Wareham, N. J., & Forouhi, N. G. (2015). Prospective associations and population impact of sweet beverage intake and type 2 diabetes, and effects of substitutions with alternative beverages. Diabetologia, 58(7), 1474–1483.


6. Sakurai, M., Nakamura, K., Miura, K., Takamura, T., Yoshita, K., Nagasawa, S. Y., ... & Nakagawa, H. (2014). Sugar-sweetened beverage and diet soda consumption and the 7-year risk for type 2 diabetes mellitus in middle-aged Japanese men. European journal of nutrition, 53(1), 251-258.


7. Suez J., Korem T., Zeevi D., Zilberman-Schapira G., Thaiss C.A., Maza O., Israeli D., Zmora N., Gilad S., Weinberger A, et al. (2014). Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 514, 181–186.


8. Stellman, S. D., & Garfinkel, L. (1986). Artificial sweetener use and one-year weight change among women. Preventive medicine, 15(2), 195–202.


9. Swithers S. E. (2015). Not so Sweet Revenge: Unanticipated Consequences of High-Intensity Sweeteners. The Behavior analyst, 38(1), 1–17.


10. Swithers S. E. (2016). Not-so-healthy sugar substitutes?. Current opinion in behavioral sciences, 9, 106–110.


11. Yang Q. (2010). Gain weight by "going diet?" Artificial sweeteners and the neurobiology of sugar cravings: Neuroscience 2010. The Yale journal of biology and medicine, 83(2), 101–108.