Beverage Consumption and Ulcerative Colitis: A Case-Control Study from Saudi Arabia

Round 1

Reviewer 1 Report

In this work, authors provide an interesting look into potential modifiable risk factors which, if confirmed by further research, could improve the IBD social and economic burden. While the manuscript is clear, concise and well written, I believe some modifications should be made to improve the quality of the work.

In the manuscript authors use “UC extension” as a proxy for “UC severity”, while UC severity is usually calculated by the Mayo index score and not strictly correlated with the extension (i.e. patients can present a mild pancolitis or a severe proctitis). If authors collected the data, it could be interesting to investigate an association with the disease severity using the Mayo score, otherwise UC severity should be replaced with "UC extension" all over the manuscript. Moreover, authors refer to “people at high risk of UC” without explaining what it means (i.e. people with relatives affected by IBD?).

In the abstract authors state "people at high risk of UC should consume more coffee and tea and less soft drinks". Given the limitations of the study design it can't be establish an undoubted causal relationship between these factors and IBD development and for that reason a such strong statement can't be made.

In the methods section is stated that all the controls had no confirmed or suspected ibd, malignancy, diverticulosis or polyposis, but is not explained how these conditions were ruled out (i.e. Have they all undergone a colonoscopy?).

In the introduction authors briefly mention environmental and nutritional risk factors but don't expand on these topics. A more in-depth look is therefore recommended.

In the discussion the biological plausibility of the potential protective role of coffee and tea is well illustrated. However, authors fail to provide a good explanation of the potential mechanisms for the harmful effects of soft drinks.

Author Response

In this work, authors provide an interesting look into potential modifiable risk factors which, if confirmed by further research, could improve the IBD social and economic burden. While the manuscript is clear, concise and well written, I believe some modifications should be made to improve the quality of the work.

In the manuscript authors use “UC extension” as a proxy for “UC severity”, while UC severity is usually calculated by the Mayo index score and not strictly correlated with the extension (i.e. patients can present a mild pancolitis or a severe proctitis). If authors collected the data, it could be interesting to investigate an association with the disease severity using the Mayo score, otherwise UC severity should be replaced with "UC extension" all over the manuscript. Moreover, authors refer to “people at high risk of UC” without explaining what it means (i.e. people with relatives affected by IBD?).

Response: Thank you for the valuable comments. We used UC extension across the whole manuscript. We removed the expression “people at high risk of UC”.

In the abstract authors state "people at high risk of UC should consume more coffee and tea and less soft drinks". Given the limitations of the study design it can't be establish an undoubted causal relationship between these factors and IBD development and for that reason a such strong statement can't be made.

Response: We removed this claim.

In the methods section is stated that all the controls had no confirmed or suspected ibd, malignancy, diverticulosis or polyposis, but is not explained how these conditions were ruled out (i.e. Have they all undergone a colonoscopy?).

Response: All patients (cases and controls) were questioned for their symptoms and had laboratory investigations including urine and stool analysis and serum complete blood count, C-reactive protein, erythrocyte sedimentation rates, bilirubin, alanine aminotransferase, creatinine, alkaline phosphatase. Those who had symptoms and laboratory investigations that did not apply to UC were assigned as controls while those with probable UC diagnosis were subjected to endoscopy with biopsies.

In the introduction authors briefly mention environmental and nutritional risk factors but don't expand on these topics. A more in-depth look is therefore recommended.

Response: We introduced some examples of these risk factors.

In the discussion the biological plausibility of the potential protective role of coffee and tea is well illustrated. However, authors fail to provide a good explanation of the potential mechanisms for the harmful effects of soft drinks.

Response: Thank you. We added more explanations to the association between soft drinks and UC.

Reviewer 2 Report

This study investigated the association between beverage intake and ulcerative colitis. Some of the results in this paper are consistent with previous reports, but has some problems.

Major comments;

#1. The definition of "soft drink" varies from country to country and the definition is somewhat ambiguous. The definition of a soft drink should be more clearly presented in the paper. Is it limited to carbonated drinks or anything containing sugar?

#2. The authors concluded “People at high risk of UC should consume more coffee and tea but less soft drinks. However, I considered this expression to be an overstatement, because this study had several limitations and did not examine a direct relationship of UC and beverage. The authors should revise their wording.

Author Response

#1. The definition of "soft drink" varies from country to country and the definition is somewhat ambiguous. The definition of a soft drink should be more clearly presented in the paper. Is it limited to carbonated drinks or anything containing sugar?

Response: We modified this term to carbonated soft drinks and added a definition in the methods section. In this study, soft drinks were defined as sweetened or non-sweetened carbonated soft drinks.

#2. The authors concluded “People at high risk of UC should consume more coffee and tea but less soft drinks. However, I considered this expression to be an overstatement, because this study had several limitations and did not examine a direct relationship of UC and beverage. The authors should revise their wording.

Response: We agree with you. We removed this claim.

Reviewer 3 Report

In this study, the authors recorded trends in beverage consumption in ulcerative colitis patients or controls in the Saudi population. They found that UC patients tend to consume higher quantities of soft drinks than the control group, which was inclined to consume greater quantities of coffee and tea.

This study has many serious limitations, also addressed by the authors in Lines 173-187.

Additionally, the researchers did not record the type of tea, coffee, or soft drinks the participants consumed. For example, the different chemical compositions of different types of tea could influence the outcome. In this vein, there is a plethora of available soft drinks.

Another comment is that the claims in Lines 43-44 and 190-191 could be omitted. A prospective clinical study of the effects of beverage consumption on the onset of UC could better support these claims.  

Other points that require clarification are:

Line 84: what type of urine/stool analysis was performed?

Lines 98-99: Which is this questionnaire? Can the authors provide more information, or maybe include it in a supplementary file?

Table 1: please change ‘Ever smoking’ to ‘Smoking’.

Author Response

In this study, the authors recorded trends in beverage consumption in ulcerative colitis patients or controls in the Saudi population. They found that UC patients tend to consume higher quantities of soft drinks than the control group, which was inclined to consume greater quantities of coffee and tea.

This study has many serious limitations, also addressed by the authors in Lines 173-187.

Additionally, the researchers did not record the type of tea, coffee, or soft drinks the participants consumed. For example, the different chemical compositions of different types of tea could influence the outcome. In this vein, there is a plethora of available soft drinks.

Response: Thank you for your comments. We modified soft drinks to carbonated soft drinks across the study and included a phrase describing that tea included all kinds of tea.

Another comment is that the claims in Lines 43-44 and 190-191 could be omitted. A prospective clinical study of the effects of beverage consumption on the onset of UC could better support these claims.  

Response: We agree with you. We added the following to the abstract and discussion sections “A population-based prospective cohort study is needed to confirm our findings”.

Other points that require clarification are:

Line 84: what type of urine/stool analysis was performed?

We clarified this point. Both analyses were made to detect possible inflammatory biomarkers.

Lines 98-99: Which is this questionnaire? Can the authors provide more information, or maybe include it in a supplementary file?

Response: We added more details about the questionnaire.

Table 1: please change ‘Ever smoking’ to ‘Smoking’.

Response: We changed it as requested.

Round 2

Reviewer 3 Report

The resubmitted manuscript still has serious limitations and major faults in the research design and methodology.

As I mentioned in my first review the researchers did not record the type of tea, coffee, or soft drinks the participants consumed. The authors in the resubmitted manuscript mentioned that tea included all kinds of tea, such as black and green tea while carbonated soft drinks included sweetened and non-sweetened carbonated soft drinks (lines 101-103). How many patients consumed black tea or green tea? Green tea has been linked with reduced inflammation associated with Crohn's disease and ulcerative colitis. Is it the same for black tea or coffee? In the same context, did the authors record any differences between sweetened and non-sweetened carbonated soft drinks consumption and UG association? Notably, they mentioned that sugar intake in a previous prospective study could increase the risk of UC (line 180). Clearly, the chemical composition of different types of beverages could influence the outcome of the experiment. Therefore, making general statements is leading and inaccurate.

Author Response

Response: Thank you for this comprehensive comment. Unfortunately, we have no data on the subtypes of tea, coffee, and carbonated soft drinks. We added this point as a limitation to our manuscript.