August 8, 2023

expert reaction to study looking at sugar-sweetened drinks, artificially-sweetened drinks, and liver cancer and chronic liver disease

A study published in JAMA looks at sugar-sweetened and artificially-sweetened beverages and risk of  liver cancer and chronic liver disease in postmenopausal women.

Dr Pauline Emmett, Senior Research Fellow (Honorary), Centre for Academic Child Health, Population Health Sciences, Bristol Medical School, University of Bristol, said:

Does the press release accurately reflect the science?

“Yes.

Is this good quality research?  Are the conclusions backed up by solid data?

“This analysis uses data from a well-respected long-running study in USA, the Women’s Health Initiative.  The diet data was collected prospectively, and the disease outcomes were incident cases carefully collected and verified.  This is a good quality study well-executed.

How does this work fit with the existing evidence?

“Not much work has been done in this area but another large study in the USA had a similar finding with sugar-sweetened soft drinks intake being associated with increased risk of liver cancer.

Have the authors accounted for confounders?  Are there important limitations to be aware of?

“The literature has been used to identify confounders and they have been accounted for correctly.  The main limitation is that this is observational data which provides associations which suggest a relationship but cannot tell if it is causal.

What are the implications in the real world?  Is there any overspeculation?

“The authors have been very careful not to speculate.  Although this study is observational so can’t give cause and effect, we know from a body of evidence that it is worth thinking twice before choosing to drink sugar-sweetened beverages every day.”

Dr Duane Mellor, Registered Dietitian and Senior Lecturer, Aston Medical School, Aston University, said:

“This is an interesting analysis of an observational study of nearly 100,000 women in the US whose soft drink intake was measured in the 1990s, and then their risk of death from liver disease or liver cancer was measured 20 years later.  As such, it cannot show any causality, only a potential association between daily sugar-sweetened drink intake and liver cancer and risk of death from chronic live disease.  It is important to note that this association was only seen when comparing those who drank sugar-sweetened drinks daily and those who drank them fewer than 3 times per month.  When comparing those who drank up to 6 sugar-sweetened drinks per week and those drinking fewer than 3 drinks per month no associated increase in risk was seen.

“It is also perhaps interesting that no relationship was seen in women who drank artificial sweetened drinks daily and those who drank them fewer than 3 times per month and liver disease or cancer.

“This study attempted to consider confounding factors such as energy intake, smoking, alcohol intake and weight with some analyses looking at overall effect of diet.  However, it is limited by the relatively low number of cases of deaths resulting from liver cancer, the limited approach it took to measure different types of soft drinks and types of sugar and sweetener, meaning it is difficult to apply to countries such as the UK where less sugar is used to sweeten soft drinks.

“This study only considered sugar-sweetened drink consumption at the start of the study, so changes in intake were not recorded, and as types and sugar content of soft drinks has varied over the past 20 years this could mean that this study may not reflect accurately the participants sugar intake over the 20 year follow up period.  Finally the authors acknowledge that other potential causes of liver cancer and chronic liver disease such as hepatitis infections were not recorded in the study, and due to limited data on liver disease they could only consider liver cancer and deaths from liver disease.  We can see that the authors weren’t able to adjust the data adequately for other factors known to increase risk of liver disease, because the association with sugar-sweetened drinks disappears when variables including alcohol are added to the model for deaths caused by chronic liver disease.  Although when the same approach is applied to liver cancer the risk associated with liver cancer and sugar-sweetened drinks remains.

“Although this study may show an increased risk associated with daily sugar-sweetened drink intake and death from liver disease and liver cancer, the relationship is not clear.  However, this does not take away from the general public health message that sugar-sweetened drinks are associated with increased risk of weight gain and problems with oral health.  So, although this study does not provide clear evidence of increased risk of liver related disease and sugar-sweetened drinks, we know from other evidence looking at other aspects of health that we should continue to restrict our intake of these products.”

Prof Tom Sanders, Professor emeritus of Nutrition and Dietetics, King’s College London, said:

“This report from the Women’s Health Initiative (WHI) study finds chronic liver disease and liver cancer to be associated with high intakes of sugar sweetened beverage (there was no association with artificially sweetened beverages) in postmenopausal women.  The study used 20 year follow up data from the Women’s Health Initiative study which was originally designed to test a low fat diet in risk of breast cancer.

“The main causes of chronic liver disease and liver cancer are infection with hepatitis viruses, particularly Hepatitis B/C.  Viral hepatitis can be acquired from contaminated blood and is also sexual transmitted.  A history of alcohol abuse is strongly linked to the development of fatty liver, cirrhosis and liver cancer.  Metabolic dysfunction-associated steatotic liver disease (MASLD – formerly referred to as NASH in this paper) is associated with obesity, especially in the presence type 2 diabetes, has become much more prevalent in recent years in the USA and becoming a significant cause of liver cancer.

“High intakes of sugar do increase the amount of fat stored in the liver in experimental animals so the effect of sugar sweetened beverages might be causal providing enough sugar is consumed.  However, the top level of intake reported was more than 1 serving a day (e.g., more than 30 g/d) which does not seem much given average intakes are 100-120 g/d.  The potential limitations of this study are undisclosed alcohol abuse/hepatitis infection which may be related to the lower socioeconomic status of those reporting higher intakes of sweetened drinks.  It is also notable that the self-reported prevalence of type 2 diabetes was three times higher in those consuming the most sugar sweetened drinks compared to the reference group.  However, the authors have attempted to adjust for this in the analysis.”

‘Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Liver Cancer and Chronic Liver Disease Mortality’ by Longgang Zhao et al. was published in JAMA at 16:00 UK time on Tuesday 8 August 2023.

DOI: 10.1001/jama.2023.12618

Declared interests

Dr Pauline Emmett: “In my role as a Nutritional Epidemiologist and Dietitian, I was a member of the European Food Safety Authority working group on Dietary Sugars.  The final report “The scientific opinion on the Tolerable Upper Intake Level of dietary sugars” was published in 2022.”

Dr Duane Mellor: “No conflicts of interest to declare.”

Prof Tom Sanders: “I used to be a consultant for aspartame more than a decade ago.

Prof Tom Sanders is now emeritus but when he was doing research at King’ College London, the following applied: Tom does not hold any grants or have any consultancies with companies involved in the production or marketing of sugar-sweetened drinks.  In reference to previous funding to Tom’s institution: £4.5 million was donated to King’s College London by Tate & Lyle in 2006; this funding finished in 2011. This money was given to the College and was in recognition of the discovery of the artificial sweetener sucralose by Prof Hough at the Queen Elizabeth College (QEC), which merged with King’s College London. The Tate & Lyle grant paid for the Clinical Research Centre at St Thomas’ that is run by the Guy’s & St Thomas’ Trust, it was not used to fund research on sugar. Tate & Lyle sold their sugar interests to American Sugar so the brand Tate & Lyle still exists but it is no longer linked to the company Tate & Lyle PLC, which gave the money to King’s College London in 2006.”

For all other experts, no reply to our request for DOIs was received.