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pregnant, lactating, or female and wish to become a parent during the study; regularly took probiotics; were hypersensitive to any of the com- ponents of the test product; were severely immune-compromised (i.e. HIV positive, transplant patient, antirejection medications, on a steroid for >30 days, or underwent chemotherapy or radiotherapy within the last year); had Type 1 or Type 2 Diabetes Mellitus; had a history of bariatric surgery; had taken anti-obesity medication in the previous 12-weeks; were actively, or has within the last 3 months, participating in a weight loss program or incurred a weight change of more than 3 kg during the past 3 months; had a life-threatening illness; was on Met- formin, anti-psychotic drugs or any medication that the investigator de- termined could impact the results of the study; had commenced use of anti-hypertensive drugs, anti-depressive drugs, statins or any other med- ication that the investigator determined could impact the results of the study within 3-months of randomisation date; had a history of co-ex- isting gastrointestinal, and/or gynaecological, and/or urologic pathol- ogy (e.g. colon cancer, colitis, Crohn's Disease, celiac, Endometriosis, prostate cancer) or lactose intolerance; had a history of drug and/or al- cohol abuse; was currently, or planning, to participate in another study during the study period; had a history of non-compliance; had been on antibiotics in the 12-weeks prior to randomisation; or consumed vitamin D supplements (>5000 IU/d). 17.3% of all screened participants were excluded due to these exclusion criteria. Subjects were removed from the study if they independently elected to withdraw; he/she developed any condition which contravened the original criteria; or was considered at any point to be unsuitable to con- tinue the study, at the discretion of the investigator. 3.3. Study setting and ethical approval The study was conducted in accordance with the ethical principles set forth in the current version of the Declaration of Helsinki (seventh version, October 2013), the International Conference on Harmoniza- tion E6 (R2) Good Clinical Practice (ICH GCP, November 2016) and all applicable local regulatory requirements (i.e. Clinical Research Ethics
Committee of the Cork Teaching Hospitals). This study was registered with ClinicalTrials.gov (NCT04042181). The CONSORT diagram of this study is depicted in Fig. 1 , the study layout is depicted in Figure S2 . This study was run by Atlantia Food Clinical Trials (Cork, Ireland) (study reference: AFRCO-088). 3.4. Randomisation and blinding The investigational product arrived on site labelled with randomisa- tion number. A randomisation list was generated by an independent sta- tistician. Participants were assigned a randomisation number in chrono- logical order from this randomisation list. The study team, participants and researchers were unaware which randomisation numbers were ac- tive or placebo. Blinding was undone after all data had been analysed. 3.5. Study recruitment Subjects were recruited through the database of Atlantia Food Clini- cal Research Trials, general practitioners ’ offices and by posting adverts in local newspapers. Subjects underwent an initial phone screen. Eligi- ble subjects were scheduled for a screening visit. Subjects received € 300 upon completion of the study to cover costs and expenses incurred. 3.6. Product formulation and dosage Bifidobacterium longum has been granted Qualified Presumption of Safety (QPS) status by the European Food Safety Authority (EFSA). B. longum APC1472 grown culture and the corresponding placebo were freeze-dried (Sacco SRI, Italy) and provided as hydroxypropylmethylcel- lulose (HPMC) capsules in PE bottles (Nutrilinea, Italy). The freeze-dried powder of the strain was blended with standard food-grade excipients to achieve the target dose of 1 × 10 10 CFU, which was based on pre- vious publications [52-54]. The excipients consisted of corn starch,
Fig. 1. Consort diagram. Number of healthy overweight/obese participants that were assessed for eligibility and excluded or allocated to the trial, treated, followed, and analysed.
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