In a cohort of more than 98 000 postmenopausal women, the incidence of liver cancer was nearly 2-fold higher among those who consumed ≥1 daily serving of sugar sweetened beverages compared with those who consumed ≤3 servings monthly. Chronic liver disease-related mortality among the regular daily consumers of sugary drinks was more than 1.5 times higher than among the low monthly consumers.
The findings, which were statistically significant, come from a prospective analysis of data on beverage consumption among participants enrolled in the Women’s Health Initiative (WHI) from 1993 to 1998. The authors reported no similar results among women who consumed artificially sweetened beverages during the same period.
The study was published online August 8, 2023, in JAMA.
The annual incidence of liver cancer in the US increased 3-fold from 1985 – 2015, investigators noted. Approximately 40% of individuals with hepatocellular carcinoma, however, do not have the most common risk factors, eg, hepatitis B and C, metabolic disorders such as obesity and type 2 diabetes, and alcohol use disorder, added lead author Xuehong Zhang, ScD, of the department of nutrition at the Harvard TH Chan School of Public Health, in Boston, MA, and colleagues.
Zhang et al cite 3 additional observations as motivation for their current study. First, few epidemiological studies exist on links between diet and liver cancer or death from chronic liver disease and those few have excluded women; second, there is evidence of an association between consumption of sugar-sweetened drinks and risk of other cancers, ie, breast, colorectal, and prostate cancer; and third, animal studies on the effects of artificially sweetened beverages have found a link with nonalcoholic fatty liver disease (NAFLD), despite conventional wisdom that they represent a healthier choice.
The resulting prospective cohort analysis of postmenopausal women aged 50 – 79 years from the WHI followed participants enrolled between 1993-1998 up to March 1, 2020. Data from food frequency questionnaires administered at baseline provided the measure of sugar sweetened beverage intake over the study period that was defined as the sum of regular soft drinks and fruit drinks, excluding fruit juice. Investigators measured total intake of artificially sweetened beverages at the 3-year follow-up.
Zhang and colleagues defined the study’s 2 primary outcomes as incident liver cancer and mortality due to chronic liver diseases including 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 demographic and lifestyle confounders.
The final cohort numbered 98 786 postmenopausal women. During a median follow-up of 20.9 years, the research team observed 207 incident cases of liver cancer and 148 deaths from chronic liver disease. At baseline, they reported, approximately 6.8% of participants consumed ≥1 daily serving of sugar-sweetened beverage; at the 3-year follow-up, 13.1% consumed ≥1 daily serving of artificially sweetened beverage at the 3-year follow-up.
Liver cancer. Investigators observed 18.0 cases of liver cancer per 100 000 person-years among women who consumed ≥1 daily serving of sugar sweetened beverages compared with 10.3 cases per 100 000 among women who consumed ≤3 servings of sugar sweetened beverages monthly (Ptrend = .02) and calculated the increased risk of liver cancer at 85% for the former group (aHR, 1.85; 95% CI, 01.16 – 2.96; P=.01).
Liver disease mortality. Zhang and colleagues reported a slightly lower but still significantly increased risk of 68% for mortality from chronic liver disease among women consuming ≥1 daily serving of sugar sweetened beverage compared with those consuming ≤3 monthly servings (17.7 deaths vs 7.1 deaths per 100 000 person-years (P for trend <.001) (aHR 1.68; 95% CI, 1.03 – 2.75; P = .04).
Artificial sweetener. Among women who reported consuming artificially sweetened beverages, drinking ≥1 daily was not associated with a statistically significant increase in risk of liver cancer vs drinking <3 beverages monthly (aHR, 1.17; 95% CI, 0.70 – 1.94; P = .55). Similarly, comparing the levels of artificially sweetened drink intake resulted in no significant increase in risk of chronic liver disease-related mortality (aHR, 0.95; 95% CI, 0.49-1.84; P = .88)
“To our knowledge, this is the first study to report a positive association between sugar sweetened beverage intake and chronic liver disease mortality,” Zhang et al wrote in the study’s discussion. Their findings being shown among older women are noteworthy in the context of evidence they cite that in 2019, “chronic liver disease was the fourth leading cause of death for women aged 45 to 54 years.”
Limitations to the study the authors note are the observational design, the limited number of questions posed about both sugar- and artificially sweetened beverages, and the potential for limited statistical power based on the small number of liver cancer cases and deaths from chronic hepatic disease.
Biologic pathways. The investigators pointed out that the study was not designed to explore biologic pathways that may lead from regular sugar-sweetened beverage intake to adverse liver outcomes but suggest a range of possible avenues, citing evidence of links between sugary drinks and obesity, hyperglycemia, accumulation of liver fat, and more. “Future studies should confirm these findings and identify the biological pathways of these associations,” they concluded.