Effects of Akkermansia Muciniphila and Berberine Supplementation on Insulin Sensitivity in Night-shift Workers

Official title

Effects of Akkermansia Muciniphila and Berberine Supplementation on Insulin Sensitivity in Night-shift Workers: a Double-blind, Randomised, Placebo-controlled, Crossover Study Within the Shift2Health Project

Overview

Night shift work is associated with an increased risk of obesity, insulin resistance, and cardiometabolic disorders, largely due to circadian misalignment, disrupted sleep, and altered eating patterns. These behavioral and physiological disturbances impair glucose metabolism and are further influenced by the gut microbiota. In particular, the bacterium Akkermansia muciniphila has been linked to improved metabolic health, including enhanced insulin sensitivity, lipid regulation, and maintenance of intestinal barrier integrity. Berberine, a bioactive plant-derived compound, has demonstrated metabolic benefits, including upregulation of A. muciniphila, improvement of insulin sensitivity, and modulation of lipid metabolism. Together, these complementary mechanisms suggest that combined A. muciniphila supplementation and berberine administration may synergistically improve metabolic health in shift workers by targeting gut microbiota composition and circadian-regulated metabolic pathways. Based on this rationale, a double-blind, randomized, placebo-controlled, crossover study is being conducted in 200 night-shift workers from healthcare and industrial sectors in Austria and Denmark. Participants are stratified by age, sex, and work sector and randomly assigned to intervention sequences. Each participant receives either the combined supplement or placebo for 12 weeks, followed by a four-week washout, after which the alternate intervention is administered for another 12 weeks, with a total participation of 28 weeks. Assessments are performed at four study visits and include anthropometry, body composition, blood pressure, and collection of blood, urine, and feces. Participants complete validated questionnaires on dietary intake, lifestyle, work schedules, and general health to monitor behavioral patterns throughout the study. Dietary intake is recorded for four days prior to each sampling visit in consideration of shift schedules. Sleep duration and quality are monitored via diaries and actigraphy and aligned with dietary records. Circadian variation is minimized by standardizing sampling times and implementing a fasting and synchronization period prior to visits. The primary outcome is insulin sensitivity, measured by HOMA-IR. Secondary exploratory outcomes include gut microbiota composition and diversity, biomarkers of intestinal permeability and inflammation, lipid profiles, body composition, sleep quality, and dietary behavior. These measures collectively provide a comprehensive evaluation of the metabolic, microbiome, and circadian effects of combined A. muciniphila and berberine supplementation in night-shift workers.

Interventions

• Dietary supplement Verum (A)
  1 capsule of A. muciniphila (pasteurized, initial quantity of 10\^30 TFU, heat inactivated) and 1 capsule of 500 mg berberine hydrochloride per day.
• Dietary supplement Placebo (B)
  1 capsule of A. muciniphila placebo and 1 capsule of berberine placebo (both identical to verum regarding the shape, size, colour, and matched in excipients) per day.

Primary outcome measures

• Change of 3-months supplementation with A. muciniphila and berberine on insulin resistance using HOMA-IR compared to placebo [Time frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)]

Secondary outcome measures (12)

• Change in gut microbiom composition between the baseline and endpoint change in the two periods [Time frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)]
• Change in FABPi between the baseline and endpoint change in the two periods [Time frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)]
• Change in zonulin between the baseline and endpoint change in the two periods [Time frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)]
• Change in LPB between the baseline and endpoint change in the two periods [Time frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)]
• Change in CRP between the baseline and endpoint change in the two periods [Time frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)]
• Change in stool short-chain fatty acids (SCFA) between the baseline and endpoint change in the two periods [Time frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)]
• Change in blood lipid profile and cardiovascular markers between the baseline and endpoint change in the two periods [Time frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)]
• Change in blood pressure between the baseline and endpoint change in the two periods [Time frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)]
• Change in melatonin between the baseline and endpoint change in the two periods [Time frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)]
• Change in BMI between the baseline and endpoint change in the two periods [Time frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)]
• Change in body composition between the baseline and endpoint change in the two periods [Time frame: At the beginning and the end of each intervention period (week 0, 12, 16, 28)]
• Change in metabolomics at the end of the two periods [Time frame: At the beginning and the end of each intervention period (week 12, week 28)]

Eligibility criteria

Inclusion criteria

• Health care or industrial shift worker
• Employed or self-employed working ≥ 24 h/week
• Current night shift work (night shift defined as a work schedule that includes at least 3 hours of work between 00:00 and 5:00) with at least 2 consecutive nights/month
• Night shift work duration > 3 years
• 4 or more night shifts/month

Exclusion criteria

• BMI of 40 kg/m² or higher
• Pregnancy or planned pregnancy within 6 months of enrolment or breastfeeding women
• Bariatric surgery
• Surgery in the 3 months prior to the study or planned surgery in the next 6 months that, in the opinion of the investigators, could potentially affect the outcome of the study
• Diagnosed diabetes type 1 or type 2
• Uncontrolled thyroid disease (confirmed by clinically significant abnormal TSH/T4 levels without stable medication for more than 3 months)
• Chronic diseases (renal failure, active hepatitis, liver cirrhosis, myocardial infarction within the last 2 years, stroke, chronic obstructive pulmonary disease or cancer)
• Immunodeficiency syndrome, active autoimmune or autoinflammatory disease (e.g. multiple sclerosis, lupus, rheumatoid arthritis), inflammatory bowel disease (e.g. IBS or ulcerative colitis) and acute episodes of atopic diseases (atopic dermatitis, asthma, type 1 allergies such as hay fever). Grave's disease, Hashimoto thyroiditis, Celiac disease, sarcoidosis, Lichen planus, are allowed, if well treated and stable
• Regular intake of anticoagulants
• Known allergy to any inactive or active ingredients in the study products
• Participation in other clinical intervention trials during the study
• Current or planned participation in a weight loss program (including intermittent fasting), extreme diet, or vigorous exercise (e.g., running, fast cycling, swimming laps, or playing intense sports that quickly raise your heart rate)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Quadruple blind

Primary purpose

Basic science

Study locations

Austria · 1 center

• FH JOANNEUM University of Applied Sciences — Graz

Identifiers

NCT: NCT07440147 · 1306/2025 · 101080788

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗