The regular consumption of sugar-sweetened beverages is associated with an increased risk of developing gastric cancer, yet a similar link is not observed with beverages containing artificial sweeteners, despite carcinogenic warnings about the sweeteners, new research showed.

“To our knowledge, this is the first study to demonstrate the association between sugar-sweetened beverage intake and gastric cancer incidence,” reported the authors in the study, published recently in Gastro Hep Advances.

“In this prospective cohort study with long-term follow-up, higher intake of sugar-sweetened beverages, but not [artificially] sweetened beverages, was associated with a higher risk of incident gastric cancer,” they wrote.

Sugar-sweetened beverages have previously been linked to a variety of cancers, including those of the colorectum, breast, and liver; however, research regarding gastric cancer has been lacking.

Meanwhile, artificial sweeteners have long been discussed as potentially having carcinogenic risks, yet evidence supporting any link has been weak and inconsistent.

Of note, artificial sweeteners including saccharin, aspartame, acesulfame potassium (acesulfame-K or Ace-K), sucralose, neotame, and advantame have approval from the FDA for use as food additives, based on evidence showing no link to cancer or other risks in humans.

To further evaluate the risks for gastric cancer, first author Andrew T. Chan, MD, MPH, of Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues conducted a prospective cohort study of participants in the Nurses’ Health Study (NHS), involving female registered nurses enrolled in 1976, and the Health Professionals Follow-Up Study (HPFS), including male health professionals enrolled in 1986.

Data on the patients were tracked through June 2021 for NHS and January 2022 for HPFS.

For the study, sugar-sweetened beverages included carbonated beverages, punch, lemonade, and sports drinks, while artificially sweetened beverages included low-calorie carbonated beverages.

Patients were categorized based on their reported beverage intake (one serving size, 8 ounces) based on having less than one serving per month (never use), one to three servings per month, one to three servings per week, four to seven servings per week, or more than one serving per day.

Of the 112,284 participants included in the final analysis, 68,311 were women and 42,973 were men; 278 cases of gastric cancer were recorded, including 140 in the NHS group and 138 in the HPFS group.

The results showed that among those consuming at least one sugar-sweetened beverage per day, the risk for gastric cancer was more than twice that of never users (hazard ratio [HR], 2.45), with increased rates in each gender group (NHS group: HR, 3.04; P for trend = .006 and HPFS group: HR, 1.99; P for trend = .035).

Looking specifically at the intake of fructose, found in many sugar-sweetened beverages, a positive association with gastric cancer risk was likewise observed in the total cohort (HR, 1.61).

However, the intake of artificially sweetened beverages showed no association with gastric cancer incidence in any of the categories after adjusting for age and other multivariate factors.

With Helicobacter pylori infection associated with an increased risk for gastric cancer, the authors evaluated incidence rates in a subset of 616 patients in the NHS group and 324 patients in the HPFS group.

While infection was found in about a third of patients, including 36.7% in the NHS group and 34.0% in the HPFS group, the consumption of neither sugar nor artificially sweetened beverages was associated with the presence of H pylori.

Mechanisms?

Among underlying mechanisms speculated to play a role in the association of sugar-sweetened (but possibly not artificially sweetened) drinks with gastric cancer, weight gain, insulin resistance, steroid hormone imbalances, inflammation, DNA damage, and dysbiosis are all possible contenders, the authors noted.

“It’s possible that some of the mechanisms linking sugar-sweetened beverages to cancer, like the metabolic effects of fructose or the calorie load contributing to weight gain, simply don’t apply to artificially sweetened beverages since they don’t contain the same sugars or calories,” Chan told Medscape Medical News.

However, “the precise mechanism of carcinogenic effects of sugar-sweetened beverages has yet to be investigated,” the authors added.

Likewise, much more needs to be understood about artificial sweeteners, including different effects among the various types, to better understand risks, Chan said.

“The evidence on artificial sweeteners and cancer risk overall is still evolving and somewhat mixed,” he said. “There is still more work to be done to understand whether there are associations [that] may differ [by] different sweetener types or by specific cancer sites.” 

Among the study’s limitations was the inability to assess factors like the possibility that those choosing sugar-sweetened over artificially sweetened beverages may also be less likely to make other food or lifestyle choices that could factor into a higher gastric cancer risk, Chan noted.

“A key caveat is that our associations may be due to potential confounding by other lifestyle or dietary risk factors associated with the intake of sugar-sweetened beverages rather than the beverages themselves,” he explained.

Findings Consistent With Other Cancers

Broader evidence supporting a link between sugar-sweetened beverages and other cancers has been described in pre-published results from a systematic review of 51 cohorts from the World Cancer Research Fund International’s Global Cancer Update Programme.

The review details evidence of associations with a variety of cancers, including colorectal and obesity-related cancers.

“The review provides evidence supporting probable causal associations of sugar-sweetened beverages with pancreatic and colorectal cancers, and of orange juice with skin cancers, with additional suggestive evidence for sugar-sweetened beverages with other obesity-related cancers, extending concerns about sugary drink consumption beyond cardiometabolic health to cancer risk,” the authors concluded.

However, “evidence for artificially sweetened beverages was less clear, with limited suggestive evidence of a positive association for leukemia,” they said.

First author of the review, Ahmad Jayedi, PhD, of the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, England, echoed the concern that the potential for reverse causation is a limitation of the body of research in general.

“I therefore do not think the current evidence supports treating artificially sweetened beverages as equivalent to sugar-sweetened beverages in terms of cancer risk,” he told Medscape Medical News.

“At the same time, absence of strong evidence of harm should not be interpreted as proof of long-term safety.”

Meanwhile, Jayedi noted that the new gastric cancer study “adds important prospective evidence to an area where the previous literature was limited.

“The magnitude of the positive association is notable, but the results were drawn from relatively small number of cases and further investigations on the topic accounting for key gastric cancer determinants, particularly H pylori infection and tumor subsite, are needed.”

Ultimately, “where possible, water and other unsweetened beverages are the most straightforward alternatives,” he said. 

“At the same time, clinicians should avoid overstating individual cancer risks,” Jayedi added.

“The current evidence is derived from population‑level observational studies, and the observed relative increases in risk are generally modest.”

Chan reported serving as a consultant for Pfizer and Boehringer Ingelheim and receiving grant support from Freenome Holdings outside the submitted work. Jayedi reported having no disclosures.