A longitudinal analysis of a large cohort suggests an association between artificial sweetener intake and several markers of adiposity, such as visceral fat .
Artificial sweeteners were invented to provide a healthier alternative to sugar and other high-calorie sweeteners, especially in the wake of the obesity epidemic, which causes more than 300 thousand deaths per year in the US alone. Those compounds were touted as safe, but with time, concerns about their potential health risks began to emerge. Alarmingly, there is a possibility that artificial sweeteners might exacerbate the same conditions that they were designed to alleviate, such as weight gain .
In May, World Health Organization (WHO) issued a new guideline on artificial sweeteners, which advises against using them to control body weight or reduce the risk of diseases. Two months later, in July, the organization singled out the artificial sweetener aspartame as a possible carcinogen. However, the scientific debate is ongoing.
This new study, published in Nature, aims to elucidate the connection between artificial sweeteners and body composition and stands out due to its interesting design. The researchers used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, which began in the 80s and followed more than 5000 people for 20 years.
About 3000 people from the study also completed diet history questionnaires at baseline, year 7, and year 20, which enabled the researchers to perform longitudinal analyses and discover trends. The mean age of this cohort was 25 years, and their mean body-mass index (BMI) was a borderline normal 24.5. Calculations were adjusted for demographic and lifestyle factors, total energy intake, and diet quality.
Endpoints included BMI, incidence of obesity, and gain in three types of adipose tissue: visceral (VAT), intermuscular (IMAT), and subcutaneous (SAT). Subcutaneous fat is considered the least dangerous, while the two other types, especially VAT, have been implicated in a variety of health problems . The researchers investigated the endpoints’ associations with total artificial sweetener intake along with consumption of aspartame, saccharine, sucralose, and artificially sweetened drinks.
Numerous positive associations
Total intake of artificial sweeteners, as well as intake of aspartame, saccharin, and diet beverages, showed significant positive associations with VAT, SAT, and IMAT volumes. While no associations were observed for sucralose intake, this sweetener was recently implicated in accelerating aging.
Saccharin, aspartame, diet beverages, and overall sweetener intake were also associated with greater BMI, body weight, waist circumference, and their increases over a 25-year period. All artificial sweeteners and diet soda, but not saccharine, were associated with greater risks of becoming obese over the follow-up period (median follow-up time was 17.5 years):
Like any observational study, this one cannot establish a causal relationship. However, it has many strengths such as its longitudinal character and a substantially long follow-up period. Importantly, the effect sizes were not huge, with approximately 8–15% greater volumes of fat of all types in people in the top quintiles compared to people in the bottom quintiles.
Reason to be more cautious
The researchers note that their results, like the results of several previous observational studies, contradict the conclusions of most randomized controlled trials, which tend to report a negative correlation between artificial sweetener intake and adiposity . However, this could be due to study design problems, such as a healthy diet or calorie control being imposed on the participants; while this study tried to control for diet quality and calorie intake, no control is perfect. It is also possible that the clinical trials were too short in duration to reflect the potential long-term effects of artificial sweetener intake.
“This is an especially timely study, given the World Health Organization’s recent warning of the potential health risks of aspartame,” said Lyn Steffen, a professor in the School of Public Health in the University of Minnesota and a principal investigator on the study. “These findings underscore the importance of finding alternatives to artificial sweeteners in foods and beverages, especially since these added sweeteners may have negative health consequences.”
While it is probably too early to give up artificial sweeteners altogether, it may be wise to follow this research closely and substitute sugar substitutes with even healthier dietary choices.
 Steffen, B. T., Jacobs, D. R., Yi, S. Y., Lees, S. J., Shikany, J. M., Terry, J. G., … & Steffen, L. M. (2023). Long-term aspartame and saccharin intakes are related to greater volumes of visceral, intermuscular, and subcutaneous adipose tissue: the CARDIA study. International Journal of Obesity, 1-9.
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 Stefan, N. (2020). Causes, consequences, and treatment of metabolically unhealthy fat distribution. The lancet Diabetes & endocrinology, 8(7), 616-627.
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