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Older, postmenopausal women are at a greater risk of liver cancer and chronic liver disease-related death when consuming ≥1 sugar-sweetened beverage daily.
According to new prospective cohort data from a team of US investigators, liver cancer incidence was nearly two-fold among postmenopausal women who consumed ≥1 serving of beverage with sugar sweetener daily versus those consumed ≤3 monthly. The findings from the Women’s Health Initiative (WHI) cohort implicate a possible biological pathway driving the significantly high incidence of liver disease burden in this population.
A team of investigators led by Longgang Zhao, PhD, of the department of epidemiology and biostatistics at the Arnold School of Public Health, University of South Carolina, and Xuehong Zhang, ScD, of the Channing Division of Network Medicine at Brigham and Women’s Hospital and Harvard Medical School, sought to interpret the link between sweetened beverage intake and incidence of liver cancer and chronic liver disease mortality among postmenopausal women enrolled in the WHI from 1993 – 1998.
The incidence of annual liver cancer cases had increased 3-fold among Americans from 1985 – 2015, investigators noted, with the increase of premeditating diseases including hepatitis B and C, type 2 diabetes, obesity, alcohol use disorder and aflatoxin contamination.
“Epidemiological studies on dietary factors and liver cancer and chronic liver disease mortality are limited,” they noted. “Therefore, it is important to identify dietary risk factors for liver cancer and chronic liver disease mortality.”
What’s more, sugar-sweetened beverages have been previously linked to heightened risk of breast, colorectal and prostate cancers. The impact of both sugar-sweetened and artificial-sweetened beverages on liver diseases remains poorly understood among humans—and what does exist in prior research has excluded the burden of disease in women.
The team conducted a prospective cohort analysis of nearly 100,000 postmenopausal women aged 50 – 79 years old from the WHI across 40 US clinical centers; participants were followed up to March 1, 2020. The original WHI excluded women participants with implausible total energy intake, a history of cancer at baseline, and those missing sugar-sweetened beverage intake or covariate data.
Zhao, Zhang and colleagues measured sugar-sweetened beverage intake based on a food frequency questionnaire administered to participants at baseline; relevant beverages included soft drinks and fruit drinks not including juice. They additionally measured artificially sweetened beverages at the 3-year follow-up period.
The study’s primary outcomes were incidence of liver cancer and mortality due to chronic liver diseases including nonalcoholic fatty liver disease (NAFLD), liver fibrosis, cirrhosis, alcoholic liver diseases and chronic hepatitis. They established multivariable hazard ratios (HRs) and 95% CI for incidences of both outcomes, with adjustments for potential confounders in participant demographics and lifestyle/clinical factors.
The final cohort included 98,786 women; median follow-up was 20.9 years. In the observed time period, 207 women developed liver cancer and 148 died from chronic liver disease. Just 6.8% of women consumed ≥1 daily serving of sugar-sweetened beverage at baseline; 13.1% consumed ≥1 daily serving of artificially sweetened beverage at 3-years follow-up.
Investigators observed 18.0 cases of liver cancer per 100,000 person-years among women who consumed ≥1 daily serving of sugar-sweetened beverages, versus 10.3 cases per 100,000 among women who consumed ≤3 servings of sugar-sweetened beverages monthly—indicating an 85% increased risk of liver cancer in the former group (aHR, 1.85; 95% CI, 01.16 – 2.96; P = .01).
For chronic liver disease mortality, investigators observed 17.7 cases per 100,000 person-years among women who consumed ≥1 daily serving of sugar-sweetened beverages, versus 7.1 per 100,000 among women who consumed ≤3 servings of sugar-sweetened beverages monthly—indicating a 68% increased risk of death from chronic liver disease in the former group (aHR, 1.68; 95% CI, 1.03 – 2.75; P = .04).
Women who consumed daily artificially sweetened beverages did not report significantly increased risks for neither liver cancer (aHR, 1.17; 95% CI, 0.70 – 1.94; P = .55) nor chronic liver disease mortality (aHR, 0.95; 95% CI, 0.49 – 1.84) compared to those who consumed ≤3 artificially sweetened beverages monthly.
“Chronic liver disease was the fourth leading cause of death for women aged 45 to 54 years and the fifth leading cause of death for men aged 45 to 64 years in 2019 in the US,” investigators wrote. “However, evidence for the associations between diet and chronic liver disease mortality is limited. To our knowledge, this is the first study to report a positive association between sugar-sweetened beverage intake and chronic liver disease mortality.”
Investigators stressed their findings did not discern biologic pathways associating regular sugar-sweetened beverages with adverse liver outcomes—though the link of such beverages to obesity, blood glucose, liver fat accumulation and more biomarkers of liver disease risk may be explored.
“In postmenopausal women, compared with consuming 3 or fewer servings of sugar-sweetened beverages per month, people who consumed 1 or more sugar-sweetened beverages per day had higher rates of liver cancer and higher rates of death due to chronic liver disease,” they concluded. “Future studies should confirm these findings and identify the biological pathways of these associations.”
This article was published by our sister publication HCP Live.
Zhao L, Zhang X, Coday M, et al. Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Liver Cancer and Chronic Liver Disease Mortality. JAMA. 2023;330(6):537–546. doi:10.1001/jama.2023.12618