More than 140 million Americans use artificial sweeteners, a habit driven by the irrefutable fact that excess sugar is harmful. But I'm continually amazed by alarmist headlines on the topic.
In May, the World Health Organization (WHO) released a report to support its "conditional recommendation" against the use of non-sugar sweeteners (NSS) for weight control. Despite its goal "to provide evidence-informed guidance," the WHO report includes the disclaimer that "The recommendation is based on evidence of low certainty."
Low certainty is an accurate descriptor for the findings of many of the 280-plus studies in the report. That the guidance does not apply to patients with diabetes was easily lost in the repeated mentions of the perceived dangers of these sugar alternatives.
The review included various table-top and beverage sweeteners, including acesulfame K, aspartame, saccharin, sucralose, stevia, and stevia derivatives. Low-calorie sugars and sugar alcohols such as erythritol were excluded.
WHO looked at long- and short-term trials, randomized controlled trials (RCTs), prospective studies, and case-control studies measuring a wide range of endpoints, from dental caries to cancer. The report highlighted that some findings cannot be attributed directly to NSS use but may simply be due to their substitution for sugar. Differences in outcomes due to sex, ethnicity, and body weight status could not be assessed either. And WHO conceded the possibility of reverse causation in observational studies wherein higher-risk individuals may consume more NSS.
Nonnutritive sweeteners are given little credit for weight loss. "A significant difference in body weight and BMI was only observed in trials that reported a reduction in energy intake… rather than primarily by an inherent property of NSS that can modulate body weight (independently of energy intake)," the report reads. But isn't the desired effect of using an artificial sweetener instead of table sugar that you lower your calorie intake?
WHO noted that weight loss was not sustained — a finding in nearly every weight loss trial in history and something more attributable to human nature than the sweetener one chooses.
The document outlines that meta-analyses of prospective cohort studies show that higher intakes of NSS were associated with an increased risk for type 2 diabetes and elevated fasting glucose, while meta-analyses of randomized trials suggest no significant effect on "biomarkers used in the assessment and diagnosis of diabetes and insulin resistance, including fasting glucose, fasting insulin and hemoglobin A1c."
Similar disparities are noted with cardiovascular risk. Prospective trials suggest an increased risk for CVD, including stroke and its precursor, hypertension; but again, the RCT data found no evidence to suggest a significant effect "on biomarkers used in the assessment and diagnosis of CVDs, including blood pressure, low-density lipoprotein cholesterol and other blood lipids."
Splenda and Stevia Under Fire
Predictably, some in the nonnutritive sweetener industry are incensed.
Ted Gelov, CEO of Heartland Food Products Group, maker of Splenda, responded in a press release, "Every few years now it seems I have to come to you and clarify misleading headlines…Suggesting that sweeteners like Splenda cannot have long-term benefits is a disservice to healthcare providers, their patients, and all consumers."
Splenda has been on the US market since 1999, and Gelov reportedly uses three to eight packets daily in his coffee and tea.
I reached out to Heartland and they sent me an eight-page document consisting of over 50 statements, summaries, and clinical trials supporting the safety of artificial sweeteners, including sucralose, an ingredient in Splenda. In 2016, Gelov rebutted claims that sucralose was linked to cancer in Swiss male mice. These "dramatized headlines are based on one flawed study by an isolated Italian research laboratory, the Ramazzini Institute," Gelov wrote.
Another recent headline was about the DNA-damaging effects of sucralose-6-acetate (S6A) seen in an in vitro study published in the Journal of Toxicology and Environmental Health. According to the authors, commercial sucralose samples contain up to 0.67% S6A, a manufacturing impurity.
Despite many reports linking this study to Splenda, Heartland wrote that "Splenda and its ingredients were never studied or tested in this research. We, and our suppliers, rigorously and routinely test and monitor for any impurities in our products. We can confirm that S6A is not present in Splenda Brand sucralose down to the lowest detection limit possible, which is .001% sensitivity level."
Perry Wilson, MD, director of Clinical and Translational Research Accelerator at Yale and a regular Medscape contributor, took to Twitter to put this study in context: "The human exposure equivalent to sucralose would be 60 packets per day," he pointed out. And the blood levels of S6A with normal consumption would not "come close to the DNA damage threshold noted in the article."
Perhaps the most concerning scientific data suggesting a link between artificial sweetener use and ill health is a Cleveland Clinic study showing an association between higher blood levels of erythritol and adverse cardiovascular outcomes such as heart attack, stroke, or death. The researchers also found that erythritol, which is found in stevia and some keto food products, made platelet activation and clot formation easier.
When I asked about these findings, Heartland stated, "The study was primarily conducted on patients who were at an elevated risk of cardiovascular events due to their advanced age, elevated body mass and presence of pre-existing health conditions…the stated findings were only an association and cannot imply causation."
The main conclusion I've drawn on the topic of artificial sweeteners is that a lot of resources were wasted in performing underpowered, poorly designed trials on compounds that are already generally regarded as safe (GRAS) by the FDA. The WHO "conditional guideline" is, by its own description, based on a plethora of "low certainty" to "very low certainty" evidence.
The monies to produce the WHO report and many of these trials would have been better spent educating the public on the difference between simple and complex carbohydrates; the inflammatory and disease-producing effects of excess sugars; and how to prevent, diagnose, and treat diabetes.
If more trials on artificial sweeteners are planned, they should be performed on people doing human things — which does not include ingesting 60 packets of any sweetener in a single day.
In my personal N-of-1 trial, consuming sugar makes me crave more, feel sluggish, and gain weight. I don't believe that NSS alone will control my weight. But I'll continue to drink two cups of stevia-laced coffee every morning, take walks, avoid alcohol, eat my vegetables, and hope for the best.
Melissa Walton-Shirley, MD is a native Kentuckian who retired from full-time invasive cardiology. She enjoys locums work in Montana and is a champion of physician rights and patient safety. In addition to opinion writing, she enjoys spending time with her husband and daughters, and sidelines as a backing vocalist for local rock bands. Her Heartfelt column was the 2022 regional gold and national silver Azbee award winner.
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Cite this: In Defense of Artificial Sweeteners - Medscape - Jun 26, 2023.
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