Fermented Foods and Bone Health: Investigating the Gut-Bone Axis in Premenopausal Vegan Women

NCT07645885 | Not Yet Recruiting

• 1 other identifier: 2026-00984
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 2

Brief Summary

Plant-based diets are increasingly adopted for health and environmental reasons, but they are associated with lower bone mineral density, higher fracture risk, and elevated bone turnover markers, particularly in women. These effects are partly explained by lower intakes of calcium and zinc, and higher concentrations of phytates and oxalates, substances that inhibit mineral absorption from plant foods. Evidence-based dietary strategies to support bone health in vegan populations beyond supplementation remain limited. Fermented plant-based foods may help address this gap through two complementary mechanisms: first, by delivering live microorganisms that beneficially modulate gut microbiota and promote the production of short-chain fatty acids, which support mineral absorption and reduce bone resorption, and second, by reducing antinutritional factors such as phytates during microbial fermentation, thereby improving mineral bioavailability. This study investigates whether the daily consumption of fermented plant-based foods, specifically lacto-fermented vegetables, calcium-fortified plant-based yogurt alternatives with live cultures, and Rhizopus-fermented tempeh, reduces bone resorption and improves calcium metabolism in premenopausal women following a vegan diet. Participants will follow each dietary condition (fermented or matched non-fermented control foods) for 12 weeks in randomized order, separated by an 8-week washout period. Blood, urine, and stool samples are collected at each study visit to assess bone turnover markers, gut microbiota composition, short-chain fatty acid production, inflammatory markers, and a range of metabolic and nutritional parameters.

Conditions

Bone; Bone Health

Keywords

Fermented foods; Bone health; Gut microbiota; Gut-bone axis; Premenopausal women; Plant-based diet; Vegan diet

Outcome Measures

Primary Outcomes (1)

• Fasting serum CTX concentration

  Within-subject difference in fasting serum C-terminal telopeptide of type I collagen (CTX) concentration between the end of the fermented food intervention phase and the end of the matched control phase, measured by electrochemiluminescence immunoassay (ECLIA).

  Baseline (Week 0), at the beginning and end of each 12-week intervention phase (Weeks 4, 16, 24, and 36)

Secondary Outcomes (6)

• Fasting serum P1NP concentration

  Baseline (Week 0), at the beginning and end of each 12-week intervention phase (Weeks 4, 16, 24, and 36)

• Fasting serum alkaline phosphatase (ALP) concentration

  Baseline (Week 0), at the beginning and end of each 12-week intervention phase (Weeks 4, 16, 24, and 36)

• Fasting serum parathyroid hormone (PTH) concentration

  Baseline (Week 0), at the beginning and end of each 12-week intervention phase (Weeks 4, 16, 24, and 36)

• Fasting serum 25-hydroxyvitamin D (25(OH)D) concentration

  Baseline (Week 0), at the beginning and end of each 12-week intervention phase (Weeks 4, 16, 24, and 36)

• Urinary calcium-to-creatinine ratio (CCR)

  Baseline (Week 0); Week 4, Week 16, Week 24, Week 36

Other Outcomes (33)

• Gut microbiota composition and diversity

  Baseline (Week 0), at the beginning and end of each 12-week intervention phase (Weeks 4, 16, 24, and 36)

• Fecal short-chain fatty acid (SCFA) concentrations

  Baseline (Week 0), at the beginning and end of each 12-week intervention phase (Weeks 4, 16, 24, and 36)

• Fasting plasma glucose

  Baseline (Week 0), at the beginning and end of each 12-week intervention phase (Weeks 4, 16, 24, and 36)

Study Arms (2)

Fermented Plant-Based Foods

EXPERIMENTAL

Participants consume three categories of fermented plant-based foods daily for 12 weeks: lacto-fermented vegetables, fermented plant-based yogurt alternatives with live cultures and calcium fortification, and Rhizopus-fermented tempeh, with a minimum combined weekly target of 14 portions.

Other: Fermented Plant-Based Foods

Non-Fermented Control Foods

ACTIVE COMPARATOR

Participants consume non-fermented plant-based equivalents matched for portion size, energy, protein, and calcium content for 12 weeks: non-fermented calcium-fortified plant-based milk, fresh raw vegetables, and cooked non-fermented legumes.

Other: Non-Fermented Plant-Based Foods

Interventions

Fermented Plant-Based Foods OTHER

Daily consumption of three categories of fermented plant-based foods for 12 weeks: lacto-fermented vegetables, fermented plant-based yogurt alternatives with live cultures and calcium fortification, and Rhizopus-fermented tempeh. Minimum combined weekly target: 14 portions.

Fermented Plant-Based Foods

Non-Fermented Plant-Based Foods OTHER

Daily consumption of non-fermented plant-based equivalents for 12 weeks, matched to the intervention arm for portion size, energy, protein, and calcium content: non-fermented calcium-fortified plant-based milk, fresh raw vegetables, and cooked non-fermented legumes.

Non-Fermented Control Foods

Eligibility Criteria

• Age: 28 Years - 43 Years
• Gender Eligibility Details: Only female participants are eligible. The restriction to female participants is scientifically justified by the sex-specific effects of oestrogen on bone metabolism and the particular skeletal vulnerability of premenopausal vegan women. The biological mechanisms under investigation, including estrogen-dependent regulation of bone resorption, gut microbiota composition, and calcium metabolism, are sex-specific.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Female, aged 28-43years.
• Body mass index (BMI) between 18.5 and 24.9 kg/m².
• Premenopausal, with regular menstrual cycles. \*
• Adherence to a vegan diet for ≥1 year, confirmed by questionnaire.
• Willingness to consume both fermented and non-fermented plant-based study foods.
• Ability to comply with all study procedures, including run-in, washout, sample collection, and clinic visits.
• Signed written and oral informed consent.
• Regular menstrual cycles are defined as spontaneous menstrual bleeding occurring every 21-35 days, with cycle-to-cycle variability not exceeding 7-9 days over the prior three months, and bleeding duration of 3-8 days, in the absence of hormonal contraception or endocrine disorders.

You may not qualify if:

• Chronic diseases or conditions affecting bone metabolism (e.g., osteoporosis, thyroid disorders, chronic kidney and liver disease, menstrual cycles disorders affecting bone health, conditions associated with malabsorption).
• History of diagnosed eating disorders.
• Chronic inflammatory or gastrointestinal diseases (e.g., IBD, celiac disease).
• Recent antibiotic use (within 3 months prior to screening).
• Use of Vitamin D supplements exceeding 2000 IU/day.
• Abnormal DXA results (T-score ≤ -2.5).
• Pregnancy, intention to become pregnant, or lactation during the course of the study
• Use of hormonal contraceptives.
• Use of medications influencing bone metabolism (e.g., glucocorticoids, antiresorptives).
• BMI \<18.5 or \>24.9 kg/m².
• Known or suspected non-compliance, drug or alcohol abuse
• Inability to follow the procedures of the studies, e.g. due to language problems, psychological disorders, dementia, etc. of the participant or anticipated prolonged absence (e.g. extended travel).
• Participation in another clinical study within the last 3 months.
• Known allergy or intolerance to study foods.

Sponsors & Collaborators

• Isabelle Herter-Aeberli: lead
• Swiss National Science Foundation: collaborator
• Philhuman Foundation: collaborator
• Czech Science Foundation: collaborator
• Charles University, Czech Republic: collaborator

Study Sites (2)

Third Faculty of Medicine

Prague, Prague, 100 00, Czechia

Location

Swiss Federal Institute of Technology

Zurich, Canton of Zurich, 8092, Switzerland

Location

Central Study Contacts

Isabelle Herter-Aeberli, PhD

CONTACT

+41 44 632 74 81; isabelle.herter@hest.ethz.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior Scientist

Study Record Dates

• First Submitted: May 22, 2026
• First Posted: June 12, 2026
• Study Start: May 31, 2026
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: June 12, 2026

Record last verified: 2026-06

Locations

CZ (1); CH (1)