The observational analyses revealed that postmenopausal women who consumed at least one sugar-sweetened beverage daily had an 85% higher risk of developing liver cancer and a 68% higher risk of dying from chronic liver disease, compared with those who consumed three servings or fewer per month.
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“If our findings are confirmed, reducing sugar-sweetened beverage consumption might serve as a public health strategy to reduce liver disease burden,” first author Longgang Zhao, PhD, with Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said in an interview.
When looking at consumption of artificially sweetened drinks, however, Dr. Zhao and colleagues found no strong association between intake and risk for liver cancer or death from chronic liver disease. Because the sample size for the artificially sweetened beverage analysis was limited, Dr. Zhao said, “these results should be interpreted with caution and additional studies are needed to confirm our study findings.”
The new study was published online in JAMA.
About 40% of people with liver cancer do not have one of the well-known disease risk factors, such as chronic hepatitis B or C infection, type 2 diabetes, or obesity. In the current analysis, Dr. Zhao and colleagues wanted to determine whether sugar-sweetened or artificially sweetened beverages, consumed by a large swath of the population, could be a risk factor for liver cancer or chronic liver disease.
Two previous studies have found only a “potential association” between sugar-sweetened beverage intake and a person’s risk for liver cancer, the authors explained.
In July, the International Agency for Research on Cancer officially classified the artificial sweetener aspartame as a possible carcinogen, but cancer epidemiologist Paul Pharoah, MD, PhD, commented that “the evidence that aspartame causes primary liver cancer, or any other cancer in humans, is very weak.”
To provide greater clarity about a potential link, the study team used the Women’s Health Initiative to evaluate sugary beverage consumption among 98,786 postmenopausal women and artificially sweetened drink intake among 64,787 followed for up to a median of 20.9 years. The primary outcomes were liver cancer incidence and mortality from chronic liver disease, defined as nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, alcoholic liver diseases, and chronic hepatitis.
Among these women, nearly 7% consumed at least one sugar-sweetened beverage daily and 13% consumed one or more artificially sweetened beverage servings daily.
Over the follow-up period, 207 women developed liver cancer and 148 died from chronic liver disease in the sugary beverage group while 133 women developed liver cancer and 74 died from chronic liver disease in the artificial sugar group.
Compared with women consuming three servings or fewer of sugar-sweetened beverages per month, those consuming one or more servings per day had a significantly higher risk for liver cancer (18.0 vs. 10.3 per 100,000; adjusted hazard ratio, 1.85; P = .01) and for chronic liver disease mortality (17.7 vs. 7.1 per 100,000; aHR, 1.68; P = .04).
Compared with women consuming three servings or fewer of artificially sweetened beverages per month, those drinking one or more servings per day did not have a significantly increased risk for liver cancer (11.8 vs. 10.2 per 100,000; aHR, 1.17; P = .55) or chronic liver disease mortality (7.1 vs. 5.3 per 100,000; aHR 0.95; P = .88).
The authors noted several limitations to the study, including not tracking potential changes in beverage consumption over time or details on the specific sugar content or sweetener types consumed.
Corresponding author Xuehong Zhang, ScD, also with Brigham and Women’s Hospital and Harvard Medical School, said it’s not surprising that sugar-sweetened beverages may raise the risk of adverse liver outcomes.
“Intake of sugar-sweetened beverage[s], a postulated risk factor for obesity, diabetes, and cardiovascular disease, may drive insulin resistance and inflammation, which are strongly implicated in liver carcinogenesis and liver health,” Dr. Zhang said in an interview.
The lack of an association between artificially sweetened beverages and liver outcomes is also not particularly surprising, Dr. Zhang said, “given that the consumption level of artificially sweetened beverages is low, the sample size is relatively small,” and “the dose response relationship remains unknown.”
Nancy S. Reau, MD, who was not involved in the research, said the authors should be “congratulated for trying to clarify liver-related health risk related to artificial or sugar-sweetened beverages.”
In her view, the most important finding is the association between daily consumption of sugar-sweetened beverages and liver health.
“Regardless of whether this is a surrogate marker for liver disease risk (such as fatty liver disease) or a consequence of the drink itself, it is an easy measure for clinicians to capture and an easy behavior for patients to modify,” Dr. Reau, a hepatologist at Rush Medical College, Chicago, said in an interview.
However, Dr. Reau noted, “I do not feel that this article can be used to advocate for artificially sweetened beverages as a substitute.”
It is possible, she explained, that this population was too small to see a significant signal between artificially sweetened beverages and liver health. Plus, “natural, low-caloric beverages as part of a healthy diet combined with exercise are always going to be ideal.”
Weighing in as well, Dale Shepard, MD, PhD, a medical oncologist at the Cleveland Clinic, noted that “this is another study that points to the need for moderation.”
In his view, avoiding excess consumption of sugary or artificially sweetened drinks is the best course of action, but other factors, such as smoking, excessive alcohol, sun exposure without adequate sunscreen, obesity, and inactivity “are more likely to increase one’s risk for cancer,” Dr. Shepard said.
In a statement from the U.K.-based Science Media Centre, Pauline Emmett, PhD, from the University of Bristol (England), commented that this is a “good-quality” study and “the authors have been very careful not to speculate.”
“The main limitation is that this is observational data which provides associations which suggest a relationship but cannot tell if it is causal,” Dr. Emmett said. However, “we know from a body of evidence that it is worth thinking twice before choosing to drink sugar-sweetened beverages every day.”
The study had no commercial funding. Dr. Zhao, Dr. Zhang, Dr. Reau, and Dr. Shepard reported no relevant financial relationships. Dr. Emmett is a member of the European Food Safety Authority working group on dietary sugars.
A version of this article appeared on Medscape.com.