Bioavailability Study of Folate in Healthy Subjects

A Double Blind, Randomized, Cross-over, Comparative Bioavailability Study of 3 Different Forms of Folate in Healthy Subjects

The aim of this prospective interventional study is to compare the bioavailability of the 6S-5-methyltetrahydrofolate (5-MTHF) glucosamine salt versus two other forms of 5- MTHF calcium salts by measuring serum 5-MTHF responses after a single ingestion of equivalent doses of the three folate forms in humans.

The hypothesis of this study is that the test products 5-MTHF glucosamine and calcium salts have equivalent bioavailabilities in serum 5-MTHF as measured by the area under the curve over a period of 24 hours (AUC0-24h) after consumption of a single dose of 5-MTHF (400μg).

Participants will receive a single dose of each of the following products separated by a 7-day wash-out period:

• 5-MTHF glucosamine salt
• 5-MTHF calcium salt 1
• 5-MTHF calcium salt 2

Study Overview

• Status: Terminated
• Conditions: Healthy
• Intervention / Treatment: Dietary supplement: 5-MTHF glucosamine salt; Dietary supplement: 5-MTHF calcium salt 1; Dietary supplement: 5-MTHF calcium salt 2

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Saint-Herblain, France, 44800
    • Biofortis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Body Mass Index (BMI) ≥18 and ≤25Kg/m²,
• For women: menopausal without hormone replacement therapy (HRT) or with HRT started from more than 3 months or non-menopausal with a negative blood pregnancy test and using reliable contraception since at least 3 cycles before the beginning of the study and agreeing to keep it during the entire duration of the study,
• Good general and mental health within the opinion of the investigator: no clinically significant and relevant abnormalities of medical history or physical examination,
• Able and willing to participate to the study by complying with the protocol procedures as evidenced by his/her dated and signed informed consent form,
• Affiliated with a social security scheme,
• Agree to be registered on the subjects in biomedical research file.

After V1 biological analysis the subjects will be eligible to the study on the following criteria:

- Adequate folate status (serum folate between 10 and 45nmol/L, erythrocyte (RBC) folate between 405 and 952 nmol/L),

Exclusion Criteria:

• Suffering from a metabolic disorder,
• Suffering from a severe chronic disease found to be inconsistent with the conduct of the study by the investigator,
• Suffering from diseases that could potentially interfere with folate absorption or metabolism,
• With a known or suspected food allergy or intolerance or hypersensitivity to any of the study products' ingredient,
• With a low venous capital of blood samples according to the investigator's opinion,
• Pregnant or was pregnant less than 6 months prior to the study, or lactating women or intending to become pregnant within 3 months ahead,
• Under treatment or regular use of treatment or dietary supplement which could significantly affect folate status or other study parameter(s),
• Use of supplements containing folate (i.e. folic acid, 5-MTHF) the last 3 months,
• With significant change in lifestyle, food habits, physical activity or medications in the 3 months before the V1 visit or not agreeing to keep them unchanged throughout the study,
• With a current or planned in the next 3 months' specific diet (hyper or hypocaloric, vegan, vegetarian…) or stopped less than 3 months before the study,
• With a personal history of anorexia nervosa, bulimia or significant eating disorders according to the investigator,
• Consuming more than 2 standard drinks of alcoholic beverage daily for men and women or not agreeing to keep his alcohol consumption habits unchanged throughout the study.
• Smoking,
• Having a lifestyle deemed incompatible with the study according to the investigator including high level physical activity,
• Taking part in another clinical trial or being in the exclusion period of a previous clinical trial,
• Having received, during the last 12 months, indemnities for clinical trial higher or equal to 4500 Euros,
• Under legal protection (guardianship, wardship) or deprived from his rights following administrative or judicial decision,
• Presenting a psychological or linguistic incapability to sign the informed consent,
• Impossible to contact in case of emergency.
• Who made a blood donation in the 3 months before the V0 visit or intending to make it within 3 months ahead.

After V1 biological analysis the subjects will be non-eligible to the study on the following criteria:

• Presence of anemia (hemoglobin<12g/dL in women and 13g/dL in men),
• Vitamin B12 levels (serum cobalamin <148pmol/L),
• Serum total homocysteine levels≥15µmol/L,
• Serum creatinine >0,96mg/dL for women and >1,21mg/dL for men,
• Control record (Glycaemia, total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, GGT, ASAT, ALAT, Urea and CBC) with clinically significant abnormality according to the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5-MTHF glucosamine; 1 single dose (400µg)	Dietary supplement: 5-MTHF glucosamine salt; Active form of folate defined as (6S) 5-methyltetrahydrofolate (5-MTHF) glucosamine salt
Experimental: 5-MTHF calcium salt 1; 1 single dose (400µg)	Dietary supplement: 5-MTHF calcium salt 1; Active form of folate defined as (6S) 5-methyltetrahydrofolate (5-MTHF) calcium salt, crystal form 1
Experimental: 5-MTHF calcium salt 2; 1 single dose (400µg)	Dietary supplement: 5-MTHF calcium salt 2; Active form of folate defined as (6S) 5-methyltetrahydrofolate (5-MTHF) calcium salt, crystal form 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve (AUC) 0-24 hours of serum 5-MTHF concentrations	Comparison of AUC0-24 hours of serum 5-MTHF concentrations between the 3 study products	0-24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve (AUC) 0-24 hours of serum total folate concentrations	Comparison of AUC0-24 hours of serum total folate concentrations between the 3 study products	0-24 hours
Area under the curve (AUC) 0-8 hours of serum 5-MTHF and total folate concentrations	Comparison of AUC0-8 hours of serum 5-MTHF and total folate concentrations between the 3 study products	0-8 hours
Area under the curve (AUC) 0-infinity of serum 5-MTHF and total folate concentrations	Comparison of AUC0-infinity of serum 5-MTHF and total folate concentrations between the 3 study products	0-24 hours
Peak plasma concentrations (Cmax) of serum 5-MTHF and total folate	Comparison of peak plasma concentrations (Cmax) of serum 5-MTHF and total folate between the 3 study products	0-24 hours
Half-life time of serum 5-MTHF and total folate	Comparison of half-life time of serum 5-MTHF and total folate between the 3 study products	0-24 hours
Mean Residence Time (MRT) of serum 5-MTHF and total folate	Comparison of Mean Residence Time (MRT) of serum 5-MTHF and total folate between the 3 study products	0-24 hours
Area under the curve (AUC) 0-24 hours of serum 5-MTHF and total folate concentrations adjusted on sex	Comparison of AUC0-24 hours of serum 5-MTHF and total folate concentrations between the 3 study products after adjustment by sex	0-24 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frenquency of Treatment-Emergent Adverse events (TEAE)	Frequency of Treatment-Emergent Adverse events (TEAE) and their characteristics (severity, relationship to the research procedure or study product, action taken on the study product, evolution of AE and body system).	4 weeks (inclusion to last visit)
Frenquency of Serious treatment-emergent adverse events (STEAE)	Frequency of Serious treatment-emergent adverse events (STEAE) and their characteristics (severity, relationship to the research procedure or study product, action taken on the study product, evolution of AE and body system).	4 weeks (inclusion to last visit)
Frequency of adverse events (AE)	Frequency of adverse events (AE) occurring during the all duration of the study (AE, serious AE (SAE) and their characteristics (severity, relationship to the research procedure or study product, action taken on the study product, evolution of AE and body system)).	4 weeks (inclusion to last visit)

Collaborators and Investigators

• Sponsor: Lesaffre International
• Collaborators: BioFortis; Soladis
• Investigators: Principal Investigator: Isabelle Metreau, MD, Biofortis

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2023
• Primary Completion (Actual): May 6, 2023
• Study Completion (Actual): May 6, 2023

Study Registration Dates

• First Submitted: January 5, 2023
• First Submitted That Met QC Criteria: January 25, 2023
• First Posted (Actual): January 26, 2023

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 2, 2024
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: bioavailability; folate; comparative study; single dose
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin B Complex; Calcium; Calcium, Dietary; Tetrahydrofolates
• Other Study ID Numbers: PEC21152

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No