Excessive consumption of sugar has been associated with a variety of negative health effects, including increased risks for obesity, cardiovascular disease, type 2 diabetes, and dementia [1]. In order to limit sugar intake, many people turn to low or no calorie sweeteners. However, there have been reports linking the consumption of some of these non-nutritive sweeteners to the risk of many of the same adverse events, such as insulin resistance, and cardiovascular disease [2; 3]. As a result, the World Health Organization does not recommend the use of non-nutritive sweeteners for weight management [4]. This suggests that non-nutritive sweeteners may not necessarily be better for metabolic health, but what do we know about their impacts on brain health?
The short answer is that we know surprisingly little about how long-term consumption of low or no calorie sweeteners affects cognition. Brain imaging studies indicate that consumption of non-nutritive sweeteners affects the activity of brain regions involved in processing sweet taste and reward [5; 6]. This can lead to different behavioral effects in different people. Some people may feel less satisfied following consumption of a non-nutritive sweetener, resulting in increased desire for calorie dense foods [7]. The brain changes may decrease the pleasure associated with sweet foods, leading to lower or higher consumption of sugary snacks, depending on the person.
The major way that non-nutritive sweeteners impact the brain appears to stem from its potential impacts on the gut microbiome [8]. While non-nutritive sweeteners cannot be utilized as an energy source by the human body, they can be broken down by some bacteria living in the gut microbiome. Some of these breakdown products, called metabolites, can potentially impact brain function. The exact composition of the breakdown products depends on the chemical nature of the sweetener as well as the particular species of bacteria present in a given person. As a result, the effects are highly individualized.
In the majority of people, most of the non-nutritive sweeteners do not have any significant physiological effects. However, studies have found that some people are particularly sensitive to certain non-nutritive sweeteners, resulting in adverse metabolic effects, such as insulin resistance, and that these metabolic effects have been attributed to effects of the sweeteners on the gut microbiome [9].
Meta-analyses of clinical trials examining the impact of non-nutritive sweeteners on metabolic health have largely found that they have marginal to no significant effect on most metabolic parameters, such as weight, blood lipids, and blood glucose [10; 11; 12]. In contrast, epidemiological studies have found that increased consumption of artificially sweetened beverages is associated with increased risk for insulin resistance, cardiovascular disease, stroke, and dementia [13; 14; 15]. The difference in the findings may stem from differences in the study populations and level of consumption. The clinical trials primarily assess short-term consumption in healthy individuals, whereas epidemiological studies capture long-term consumption in a broader population, including many who may have switched to the use of no calorie sweeteners due to underlying metabolic disease or other health conditions.
Together, these studies suggest that the potential health effects of non-nutritive sweeteners should be considered with a similar degree of caution as nutritive sweeteners, such as sugar. When consumed in moderation, non-nutritive sweeteners do not appear to strongly impact measures of health in the majority of people, though some individuals may be especially sensitive to particular sweeteners due to their unique genetics and microbiome. Just like with sugar, the risk for adverse effects appears to increase with increasing levels of consumption, especially in those with pre-existing conditions. Due to the strong links between metabolism, the heart, and the brain, there may be a similar dose-dependent risk relationship with respect to cognitive health.
The healthiest way to satisfy one’s craving for sweet is through the consumption of naturally sweet whole foods, such as fruit and vegetables, which also contain protective components such as fiber and antioxidants.
Betsy Mills, PhD, is a member of the ADDF's Aging and Alzheimer's Prevention program. She critically evaluates the scientific evidence regarding prospective therapies to promote brain health and/or prevent Alzheimer's disease, and contributes to CognitiveVitality.org. Dr. Mills came to the ADDF from the University of Michigan, where she served as the grant writing manager for a clinical laboratory specializing in neuroautoimmune diseases. She also completed a Postdoctoral fellowship at the University of Michigan, where she worked to uncover genes that could promote retina regeneration. She earned her doctorate in neuroscience at Johns Hopkins University School of Medicine, where she studied the role of glial cells in the optic nerve, and their contribution to neurodegeneration in glaucoma. She obtained her bachelor's degree in biology from the College of the Holy Cross. Dr. Mills has a strong passion for community outreach, and has served as program presenter with the Michigan Great Lakes Chapter of the Alzheimer's Association to promote dementia awareness.
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