HOW SWEET IT ISN'T? Examining the link between artificial sweeteners, obesity and diabetes mellitus

Jing Chao, MD

The United States is facing the greatest epidemic of obesity and diabetes ever in its history. The Centers for Disease Control and Prevention (CDC) reports 25.8 million people as having diabetes and projects that if current trends continue, one of three U.S. adults will have diabetes by 2050. The data on obesity appear even grimmer, with more than one third of U.S. adults and 17 percent of children and adolescents meeting the medical definition of obese. Projections for the future suggest that over half of U.S. citizens will be in the obese weight category by 2030.

Enter artificial sweeteners
Eating too many sweet treats is considered one of the culprits for obesity and can certainly contribute to worsened glycemic control in people with diabetes. Wouldn’t it be great if we could eat and drink whatever we wanted without having to pay the price with weight gain or uncontrolled blood sugar? However, that’s not the case. To satisfy the craving for sweetened foods and drinks, U.S. manufacturers responded by widely introducing artificial sweeteners into various food items in the 1980s.

The perceived benefits behind this movement included the artificial sweeteners’ low cost, reduced caloric intake, and the potential for weight reduction and normalization of blood sugar levels. Various medical societies and their guidelines — including the American Diabetes Association, the American Heart Association and the Dietary Guidelines for Americans — either endorse or hold a neutral stance toward the consumption of artificial sweeteners. However, rather than seeing a decline in the prevalence of obesity and diabetes after the introduction of artificial sweeteners, the U.S. continues to see rates of both exploding over the past two to three decades.

Obesity and Diet Beverages
Having witnessed these growing trends, researchers have wanted to test the theory as to whether artificial sweeteners can help promote better health. The earliest such research occurred in 2008, in which 24- hour dietary recall from more than 5,000 San Antonio, Texas participants found that consuming more than 21 diet beverages a week was associated with twice the risk of becoming obese.

Another study consisting of more than 16,000 middle aged adults found that the consumption of diet soda was adversely associated with the development of metabolic syndrome, a health condition that includes a number of risk factors such as high blood sugar, high blood pressure, unhealthy cholesterol levels and abdominal fat.

Although the findings seem to cast doubts on the benefits of diet beverages, these studies only found associations between consumption of diet beverages and obesity and do not prove that one is a direct cause of the other.

The science behind sweetener studies
Earlier studies on artificial sweeteners showed that they are biologically inactive, passing through the digestive tracts of animals and humans unchanged. The reason that animals and humans do not absorb these artificial sweeteners is the lack of the specific types of enzymes required by the stomach to metabolize these carbohydrates (sugars) into types of sugars and starches that may be absorbed by the body. When the artificial sweeteners move further down the gastrointestinal tract, they encounter the bacteria that inhabit the gut, which appear to be altered after taking in artificial sweeteners. A study from 2008 showed that rats ingesting Splenda® developed intermittent episodes of diarrhea, had inflammation in their colon and lost 80 percent of the lactobacilli bacteria in the guts (lactobacilli are traditionally viewed as the “beneficial” gut bacteria). When the rats stopped ingesting Splenda® for three months, they recovered from the inflammation. Although there has not been a similar study in humans, the study in rats would suggest that the artificial sweeteners are not simply moving in and out of the digestive tracts with no effects.

In September 2014, media reports brought attention to a study that provided evidence that artificial sweeteners induce glucose (sugar) intolerance — a slight increase in blood sugars to above normal — in mice and humans by altering the composition of bacteria in the gut. The experiment found that mice who were fed artificial sweeteners developed glucose intolerance compared with mice fed glucose and saccharin. When researchers used antibiotics to kill the bacteria in the gut of these mice, the mice recovered their normal glucose tolerance. When the feces from mice that were fed artificial sweeteners were transplanted into bacteria-free (germ-free) mice, these mice also developed glucose intolerance similar to that seen in their donors. The researchers found a shift in the bacteria in the mice’s guts, and the increase in the particular types of bacteria may be linked to some metabolic pathways leading to obesity and type 2 diabetes.

The same researchers looked at the effects of long-term artificial sweetener use in non-diabetic individuals by using a food questionnaire to assess their intake of artificial sweeteners, comparing these individuals’ weights, measurement of waist-to-hip ratio, fasting blood sugar and A1c (a measure of blood sugars over time) and testing how well a sugary drink was metabolized by the body. The difference in A1c between those who chose artificial sweeteners and those who did not was quite modest. The researchers tested the artificial sweeteners’ effects on glucose metabolism in healthy study volunteers who did not use artificial sweeteners. These volunteers were given artificial sweeteners to use for six days, and glucose tolerance testing was done daily for seven days. (The standard glucose tolerance test consists of consuming a sugary drink at the starting time point and administering blood tests of glucose level before the drink and then at regular intervals for the next two hours.)

Four of the seven participants developed higher than normal glucose levels between 30 to 90 minutes after the drink; however, their baseline and two-hour glucose levels remained unchanged. These same four volunteers’ gut bacteria changed. But the other study volunteers did not show an increase in their glucose levels despite using the same amount of artificial sweeteners. Although it may be quite tempting to conclude that the majority of the study participants showed a poorer glucose response, we need to recognize that the increase seen in glucose would not be considered in the range of diabetes blood sugar levels.

So, what’s the bottom line?
Replacing the carbohydrates (sugars and starches) in your diet with artificial sweeteners may not be the answer to preventing obesity or getting your blood sugars under control if you have diabetes. However, it’s still too early to conclude that artificial sweeteners may lead to diabetes and obesity. Associations between the use of artificial sweeteners and weight, or other measures such as waist-to-hip ratio, fasting glucose and A1c, cannot answer a cause-effect question. The studies discussed above included very few people and were of very short duration. The bottom line is that we still do not have enough evidence to endorse or ban the use of artificial sweeteners. One thing we do know with certainty is that the choice of a healthy and balanced diet combined with consistent physical activity is beneficial to our health.

Dr. Jing Chao is an acting Instructor and Senior Fellow in the Division of Metabolism, Endocrinology, and Nutrition at the University of Washington in Seattle. She actively engages in clinical research, investigating the relationship between testosterone deficiency and insulin sensitivity. Her clinical interests include osteoporosis and endocrinopathies related to the thyroid and pituitary glands. She is an active member of the The Endocrine Society, AACE, the American Thyroid Assoication, and ISCD. Upon completion of her fellowship in June 2015, she will become a Clinical Assistant Professor and leader of the inpatient diabetes team at the University of Washington.