Table 3 Potential sources of bias and methods to reduce risk of bias

Selection bias

A randomization sequence will be generated before data collection using secure web-based software. Randomization will follow a 1:1 allocation ratio. An individual at arm’s length from the study will generate the randomization sequence and stratify according to sex. Delegated personnel in charge of screening and enrolling participants will contact this individual to obtain the group allocation

Performance bias

Supplements will be pre-packaged and coded by industrial suppliers. Code details will be provided to the above individual and withheld from other personnel involved in the study. Placebo and experimental supplements will look similar thereby preventing participants and study personnel from determining group assignment

Observer bias

While we can blind personnel to group type, the research team cannot be blinded to the timing of the study (i.e., baseline, pre-, post-surgery). In order to reduce the risk of possible observer bias, biological samples and images will be coded by statistician prior to analysis to prevent study personnel analyzing samples/data from known timepoints. Once laboratory analysis is completed, coded data will be analyzed and reports of the data and statistical results (e.g., descriptive summaries, confidence intervals, inferential) will be delivered to the research team without deanonymizing subject codes

Attrition bias

Analyses will follow both intention to treat and per protocol analysis (secondary outcomes) and perform a sensitivity analysis using multiple imputation across a range of plausible assumptions. We will record and report the number, timepoint, and reasons for participant dropout or removal

Reporting bias

This trial was registered through ClinicalTrials.gov prior to data collection (NCT06233825). This publicly registered information includes a list of our primary and secondary outcomes, a brief description of our study design, and a detailed statistical plan, all of which has been expanded within the present document