Intermittent Fasting and Probiotics in the Management of Prediabetes: A randomised controlled trial

Abstract

Background and aims: Obesity and diabetes are complex, multifactorial diseases with adverse effects on morbidity and mortality. Disordered gut microbiota is thought to be involved in the pathogenesis of these diseases. Most dietary advice around continuous caloric restriction are difficult to sustain, so novel approaches targeting gut microbiota requires investigation. The primary aim of the PROFAST trial was to determine whether probiotic supplementation during intermittent fasting could improve glycaemia and reduce weight among obese New Zealand adults with prediabetes. Methods: The PROFAST trial was a double-blinded, randomised, two-armed study conducted between 1/12/16 and 21/12/17 in Auckland, New Zealand. Participants aged 18-65 years, with HbA1c 40-50mmol/mol, and BMI 30-40kg/m2 (inclusive), were randomised, stratified for ethnicity and BMI, to receive either probiotic (Lactobacillus rhamnosus HN001, at a dose of 6x109 CFU/day) or placebo during 12 weeks of intermittent fasting. All participants were instructed to practice intermittent fasting as 5 days of ad libitum eating and 2 days of restricting calories to 600kcal/day for women and 650 kcal/day for men (IF 5:2). All participants received dietary advice and education regarding intermittent fasting, at baseline. Dietary support was provided to the participants throughout the 12 weeks, with fortnightly contact with each participant by the study dietitian via phone, text or email and with encouragement for participants to make contact whenever required in this period. A private, group Facebook page was made available for participants to join if they wished to do so. The primary outcome measure was HbA1c at 12 weeks. Secondary outcome measures included changes in weight and other anthropometric outcomes, body composition (dual energy X-ray absorptiometry), biochemistry (glucoregulatory markers, lipids, leptin, liver enzymes, inflammatory markers and gut hormones), food diaries (7-day food diaries and fasting food diaries), quality of life (Short Form-12), mood, eating behaviour, hunger and satiety scores. Fasting and 6-time point oral glucose tolerance test blood samples, body composition and questionnaires were undertaken at baseline and at 12 weeks post-intervention. Results:Thirty-three participants were randomised (placebo n=16, probiotic n=17) with a mean age of 52.3 years, BMI of 34.7kg/m2 and HbA1c of 43.5mmol/mol. Seven of the thirty-three participants randomised withdrew from the study before the follow up at 12 weeks. Baseline and 12-week data from twenty-six participants were analysed (placebo n=11, probiotic n=15). HbA1c decreased from 43 ± 2.7 mmol/mol to 41 ± 2.3 mmol/mol (p<0.001) after 12 weeks of intermittent fasting. Participants achieved an average weight loss from 95.5 ± 16.8 kg to 90.8 ± 16.5 kg (-5%) after 12 weeks of intermittent fasting (p<0.001). Significant improvements were also seen in various measures of body composition, glucose and insulin, leptin, quality of life measures and psychological outcomes after 12 weeks of intermittent fasting. No significant between-group differences were seen in the primary and secondary outcomes, however, probiotic supplementation further augmented improvements in quality of life measures, namely, social functioning (p=0.0499) and mental health (p=0.0069). Conclusion: Intermittent fasting results in significant weight loss and improved glycaemic control. Probiotics can further augment improvements in quality of life outcomes.