Natural Versus Synthetic Vitamin B Complexes in Human

• ClinicalTrials.gov Identifier: NCT03444155
• Recruitment Status: Completed
• First Posted: February 23, 2018
• Last Update Posted: April 17, 2018
• Sponsor: Medical University of Graz
• Information provided by (Responsible Party): Priv.-Doz. Mag. Dr. Willibald Wonisch, Medical University of Graz

Tracking Information

• First Submitted Date: January 8, 2018
• First Posted Date: February 23, 2018
• Last Update Posted Date: April 17, 2018
• Actual Study Start Date: May 8, 2017
• Actual Primary Completion Date: October 3, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 18, 2018)

• Serum Thiamine in µg/L [ Time Frame: 18 weeks ]
  A difference of p<0.05 between groups and time-points will be assessed as statistical significant.
• Serum Riboflavin in µg/L [ Time Frame: 18 weeks ]
  A difference of p<0.05 between groups and time-points will be assessed as statistical significant.
• Serum Pyridoxine in µg/L [ Time Frame: 18 weeks ]
  A difference of p<0.05 between groups and time-points will be assessed as statistical significant.
• Serum Folic acid in ng/mL [ Time Frame: 18 weeks ]
  A difference of p<0.05 between groups and time-points will be assessed as statistical significant.
• Serum Cobalamin in pg/mL [ Time Frame: 18 weeks ]
  A difference of p<0.05 between groups and time-points will be assessed as statistical significant.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 18, 2018)

• Serum Total peroxides in µmol/L [ Time Frame: 18 weeks ]
  A difference of p<0.05 between groups and time-points will be assessed as statitical significant.
• Serum Total antioxidant capacity in mmol/L [ Time Frame: 18 weeks ]
  A difference of p<0.05 between groups and time-points will be assessed as statitical significant.
• Serum Endogenous peroxidase-activity in mU/mL [ Time Frame: 18 weeks ]
  A difference of p<0.05 between groups and time-points will be assessed as statitical significant.
• Serum Polyphenols in mmol/L [ Time Frame: 18 weeks ]
  A difference of p<0.05 between groups and time-points will be assessed as statitical significant.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Natural Versus Synthetic Vitamin B Complexes in Human
• Official Title: Pilot Study for the Evaluation of the Effectiveness of Natural Versus Synthetic Vitamin B Complexes in Humans.
• Brief Summary: In a cross-over study the investigators evaluate the effects of natural (Panmol-B-Complex) versus synthetic vitamin B complexes to identify the bioavailability of distinct vitamins as well as long-term effects. The primary hypothesis for this study: "Natural Vitamin B-complexes are as effective as synthetic Vitamin B-complexes or better." For this reason 30 subjects (18 to 65y; BMI >19 to <29) were recruited for this study. The study population was divided into 2 groups of each 15 subjects in a cross-over trial. Vitamin supplementation consisted of Thiamine (2,77mg), Riboflavin (3,53mg), Niacin (40,32mg), Pantothenic acid (15,12mg), Pyridoxine (3,53mg), Biotin (0,13mg), Folic acid (0,50mg) and Cobalamin (6,3µg) per day in both groups. Blood samples are taken at baseline - 1.5h after vitamin supplementation - 4h - 7h - 6 weeks - wash out phase I (2 weeks); start cross-over: baseline - 1.5h after vitamin supplementation - 4h - 7h - 6 weeks - washout phase II (6 weeks). In case of main target criteria Thiamin, Riboflavin, Pyridoxine, Folic acid and Cobalamin were measured in serum as well as total peroxides (µmol/L), peroxidase-activity (U/L), total antioxidant status (mmol/L) and polyphenols (mmol/L).

Detailed Description

Design:

Monocentric double-blind experiment

Scientific background:

Vitamin B-complex is water-soluble and essential for humans. Vitamin B deficiency is associated with neurologic diseases, heart insufficiency, diminished hormone production and maldigestion. Due to the fact that literature search did not reveal distinct information about natural versus synthetic Vitamin B-complexes this study was initiated to investigate bioavailability and long-term effects of natural Vitamin B-complexes in comparison to synthetic Vitamin B-complexes.

Vitamin B complex was filled in capsules coated with gelatine (size 0, ivory-coloured). Daily dose = 3 capsules in the morning with 250ml water.

Blinding/Randomization:

The person in charge for manufacturing and blinding arranged an identical packaging of both verum as well as synthetic Vitamin B-complex. Each package consists of 126 capsules per subject and period. Each product was tagged with the subject-number and period (period I and period II).

Study-subjects were blinded by the person in charge for randomization through a sealed envelope. The allocation was in the relation of 1:1 between group A (verum in period I and synthetic Vitamin B-complex in period II) and group B (synthetic Vitamin B-complex in period I and verum in period II). The ultimate subject list was forwarded to the person in charge for randomization after the run-in phase.

Method:

Blood sampling:

Blood (max. 20ml) was collected in a seated position from an antecubital vein.

Time schedule:

Run-in-phase: 3 weeks (no supplementation) Determination of inclusion criteria, nutrition advice, randomization.

Phase I: 6 weeks (supplementation) Group A - natural Vitamin B-complex supplementation every day Group B - synthetic Vitamin B-complex supplementation every day

Blood sampling:

First day:

Fasting value (basic) - Vitamin B-complex supplementation - After 1.5 hours After 4 hours After 7 hours After 6 weeks

Wash-out period: 2 weeks (without supplementation)

Phase II: 6 weeks (supplementation) Group A - synthetic Vitamin B-complex supplementation every day Group B - natural Vitamin B-complex supplementation every day

Blood sampling:

First day:

Fasting value (basic) - Vitamin B-complex supplementation - After 1.5 hours After 4 hours After 7 hours After 6 weeks

Wash-out period II: 6 weeks (without supplementation) Final exam - last blood sampling

Drop-out-criteria:

Drawback Compliance (<80% of Vitamin B-complexes) Supplementation of Vitamin B-complexes during run-in-phase or wash-out periods

Primary-target parameters:

Serum concentrations for vitamins B1, B2, B6, B9 and B12

Secondary-target biomarkers:

Serum concentrations for Total antioxidants, total peroxides, peroxidase-activity, polyphenols and homocystein.

Biometry:

Comparison of interventions in a cross-over approach descriptive and exploratory.

Group comparison: Parametric and non-parametric cross-over comparison Gaussian distribution - (Kolmogorov-Smirnov-test with Lilliefors-significances, alpha =10%).

Effect size: Two-sided 95%-confidence intervals

Analysis:

Intent-to-treat-analysis Per-protocol-analysis Full analysis set

Vitamin B and Homocysteine analysis was done in a routine laboratory. Antioxidants (TAC), peroxidase-activity (EPA), peroxides (TOC) and polyphenols (PPm) were measured by the use of commercially available microtitre assays at a wavelength of 450 vs. 620 nm. In case of PPm a wavelength of 766nm was used.

Implausible values will be scored as missing values. Missing values are not substituted.

Presentation of results:

Minimum-Median-Quartiles-Maximum-Mean-Standard deviation. Box Plots, Bar graph, tables.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

Vitamin B complex (natural vs. synthetic) administered in capsules each day for 6 weeks - 2 weeks wash-out phase I (2 weeks) - cross-over 6 weeks - wash-out phase II (6 weeks)

Masking: Double (Participant, Investigator)
Masking Description:

Masking was organized and supervised by the randomization person in charge. Group assignment was 1:1 (control vs. verum group) with identical packages for both Vitamin supplements with 126 capsules for each subject per phase. Randomization was done with sealed envelopes.

Primary Purpose: Basic Science

Condition

• Healthy
• Thiamine and Niacin Deficiency States
• Pyridoxine Deficiency
• Folic Acid Deficiency Anemia, Dietary
• Vitamin B 12 Deficiency
• Peroxidase; Defect
• Polyphenols
• Oxidative Stress
• Homocystine; Metabolic Disorder

Intervention

• Dietary Supplement: Panmol-B-Complex
  B1 (2,77mg), B2 (3,53mg), B3 (40,32mg), B5 (15,12mg), B6 (3,53mg), B7 (0,13mg), B9 (0,50mg), B12 (6,3µg) daily for 6 weeks.
• Dietary Supplement: Synthetic Vitamin B-Complex
  B1 (2,77mg), B2 (3,53mg), B3 (40,32mg), B5 (15,12mg), B6 (3,53mg), B7 (0,13mg), B9 (0,50mg), B12 (6,3µg) daily for 6 weeks.

Study Arms

• Active Comparator: Panmol-B-Complex
  B1 (2,77mg), B2 (3,53mg), B3 (40,32mg), B5 (15,12mg), B6 (3,53mg), B7 (0,13mg), B9 (0,50mg), B12 (6,3µg) daily for 6 weeks.
  Intervention: Dietary Supplement: Panmol-B-Complex
• Active Comparator: Synthetic Vitamin B-complex
  B1 (2,77mg), B2 (3,53mg), B3 (40,32mg), B5 (15,12mg), B6 (3,53mg), B7 (0,13mg), B9 (0,50mg), B12 (6,3µg) daily for 6 weeks.
  Intervention: Dietary Supplement: Synthetic Vitamin B-Complex

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 18, 2018): 30
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: November 17, 2017
• Actual Primary Completion Date: October 3, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male and female
• 18-65 y
• Healthy

Exclusion Criteria:

• Cholesterol >240mg/dl
• Study inclusion in the past 2 months
• Pregnancy and lactation period
• Clinical diagnosis of chronic infections
• Ingestion of trace elements, vitamin- and fatty acid supplements in the past 3 months
• Clinical diagnosis of cardiovascular disease
• Clinical diagnosis of cancer
• Clinical diagnosis of psychotic diseases
• Insulin dependent diabetes
• Clinical diagnosis of autoimmune diseases
• Maldigestion/Malabsorption
• Veganes cuisine
• > 1 Beer/day

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria

Administrative Information

• NCT Number: NCT03444155
• Other Study ID Numbers: Medical University of Graz
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Priv.-Doz. Mag. Dr. Willibald Wonisch, Medical University of Graz
• Study Sponsor: Medical University of Graz
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Medical University of Graz
• Verification Date: April 2018