Do low-calorie sweeteners help with weight management? And are they safe for long-term use?
This is one of the most controversial topics in nutrition science. In early May 2023, the World Health Organization issued a statement warning against the use of non-sugar sweeteners for weight loss, except for people who have pre-existing diabetes.
WHO based its new recommendation on a 2022 systematic review and meta-analysis of scientific studies on the consumption of sweeteners other than sugar in humans. This type of study examines a large body of research to draw a broad conclusion.
Based on its interpretation of that large-scale review, WHO recommended not using artificial sweeteners for weight control and concluded that there may be health risks associated with habitual consumption of non-sugar sweeteners over the long term. However, WHO has also acknowledged that existing evidence is not conclusive and that more research needs to be done.
As neuroscientists, we study how dietary factors such as sweeteners affect the brain’s ability to perform critical functions, including metabolism, appetite, learning and memory.
We found the WHO warning surprising based on the equivocal results of the studies. Determining the answers to these questions is extremely challenging, and public health messages about recommendations can send mixed messages.
Healthy sugars versus unhealthy sugars
Natural sugars like glucose and fructose, along with fiber and other nutrients, are found in many food sources considered healthy, such as fruit. However, these simple carbohydrates have increasingly been added to manufactured food products, especially beverages. Sugary drinks are usually high in calories and offer little else in the way of nutrition.
In the early 20th century, food and beverage manufacturers began incorporating naturally and chemically derived substances that satisfy cravings for sweets but contain significantly fewer calories than naturally occurring sugars, and in some cases, zero calories. Sugar substitutes became especially popular in the 1950s with the growing popularity of diet sodas. Since then, consumers have increasingly turned to these sugar substitutes in their daily lives.
Sugar substitutes go by many names, including high-intensity sweeteners, artificial sweeteners, non-nutritive sweeteners, low-calorie sweeteners and, as defined in the WHO report, non-sugar sweeteners. These include synthetic compounds such as sucralose, acesulfame potassium and aspartame as well as naturally derived ones, such as those from the plant Stevia rebaudianaamong many others.
Each nonsugar sweetener has a unique chemical structure, but they all activate sweet taste receptors at very low concentrations. This means you only need to add a small amount to sweeten your coffee or tea, instead of piling on the spoonfuls of natural sugar.
Sugar substitutes and the quest for weight loss
Obesity and associated metabolic conditions, such as diabetes and cardiovascular disease, are now among the leading causes of preventable death in the United States. The obesity epidemic has been linked in part to increased consumption of added sugars over the past century.
To help address this, WHO issued specific recommendations in 2015 to reduce sugar intake and adopt healthier diets.
But humans are hardwired to find the sweet taste of sugars pleasurable, and the goodness of real sugar makes it difficult for most of us to remove it from our diets.
Sugar substitutes were designed to help. The math seems simple: Replacing your favorite 12-ounce sugary drink that contains 150 calories with an artificially sweetened drink of the same volume that contains zero calories should allow you to reduce the number of calories you take in each day and reduce your body weight over time. .
But the science is not that simple. Research in animal and human models indicates that habitual consumption of non-sugar sweeteners can lead to long-term negative metabolic outcomes and body weight gain.
However, there are conflicting studies in animal and human models that have not found significant body weight gain associated with the consumption of non-sugar sweeteners.
Health impact analysis
Regardless of the potential benefits non-sugar sweeteners may have for weight control, their use must also be considered in the context of overall health.
Agencies such as the WHO and the US Food and Drug Administration periodically review the available evidence and evaluate the safety of various food additives, including non-sugar sweeteners, for use in foods and beverages within what is called a limit of acceptable daily intake. In this context, the acceptable daily intake is based on the estimated amount of a specific non-sugar sweetener that can be safely consumed daily throughout life without adverse health effects.
Each agency establishes its daily allowance based on the best data available. But since these experiments cannot explain all the possible conditions under which these substances are used in real life, it is imperative that scientists continue to study the health effects of food additives.
The authors of the WHO report relied on three main types of published research studies to determine whether consumption of unsweetened sweeteners was linked to adverse health effects. The gold standard for assessing causation is what are called randomized controlled trials.
In these studies, people are randomly assigned to an experimental group that receives the test substance, such as a nonsugar sweetener, or a control group that receives a placebo or a different substance. Participants in both groups are then monitored over a period of time, usually weeks or months. Most studies involving randomized controlled trials of unsweetened sweeteners to date involve this type of comparison, with unsweetened sweeteners replacing the consumption of natural sweetened beverages.
The analysis of nearly 50 randomized controlled trials on which WHO based its recommendation found modest benefits of using non-sugar sweeteners for weight loss and determined that habitual use of these non-sugar sweeteners did not led to symptoms of diabetes or indicators of cardiovascular disease. But it found that the use of non-sugar sweeteners was associated with a higher ratio of total cholesterol to HDL, short for high-density lipoprotein, which is considered the “good cholesterol.”
This means that habitual consumers of the artificial sweetener had more low-density lipoprotein, or LDL version, in their system. That form of bad cholesterol is a risk factor for heart disease.
However, other potential adverse consequences of consuming non-sugar sweeteners may take longer to manifest than can be identified in the limited time frame of a randomized controlled trial.
The authors also evaluated what are called prospective cohort studies. These studies track participants’ self-reported use of sweeteners along with health outcomes, often over many years. They also considered case-control studies, which identify people with or without a particular health problem, such as cancer, and then use available medical records and interviews to determine the extent of non-sugar sweetener use in the population. their past.
Examination of cohort and case-control studies found that regular consumption of non-sugar sweetener was associated with increased fat accumulation, higher body mass index, and higher incidence of type 2 diabetes. These results differ from the results of randomized control trials.
The analysis of cohort and case-control studies also concluded that a history of regular use of non-sugar sweeteners was linked to a higher frequency of stroke, hypertension, other cardiovascular adverse events, and, in pregnant women, an increased risk of premature birth. The frequency of cancer in consumers of non-sugar sweeteners was generally very low, although saccharin, an FDA-approved sweetener found in many food products, was associated with bladder cancer.
Warnings and takeaways
At first glance, these results are alarming, but they must be taken with a grain of salt. As the WHO report points out, these studies have significant limitations that need to be considered.
Take, for example, in cohort and case-control studies, that higher body mass index, or BMI, was associated with higher intake of non-sugar sweeteners and worse health outcomes. One possibility is that people with obesity used non-sugar sweeteners to help cut calories more than others without obesity. This makes it difficult to determine whether the disease is caused by prolonged use of artificial sweeteners or by other underlying conditions associated with obesity.
Also, how non-sugar sweeteners are consumed is not controlled for in these types of studies. So the negative health outcomes could be associated with other associated harmful behaviors, such as more sugar or fat in the diet.
The picture is very mixed about both the benefits of non-sugar sweeteners for weight loss and their links to adverse health problems. The WHO recommendation appears to have weighed cohort and case-control studies versus randomized controlled ones, a decision we found puzzling in light of the limitations of these studies for assessing whether non-sugar sweeteners play a causal role in disease.
As with all health-related choices, the science is complex. In our opinion, taking a diet drink to offset the calories in a slice of chocolate cake every now and then probably won’t be harmful to your health or lead to significant weight change.
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