Natural Versus Synthetic Vitamin B Complexes in Human

Not Applicable

Completed

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

Interventions: Dietary Supplement: Natural Panmol-B-Complex
Dietary Supplement: Synthetic Vitamin B-Complex

Registration Number: NCT03444155

Lead Sponsor: Medical University of Graz

Brief Summary: In a cross-over study the investigators evaluate the effects of natural (Panmol-B-Complex) (Pan \[Greek\] = all; moles \[Latin\] = molecules/particles - brand name) 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 (2.93 mg), Riboflavin (3.98 mg), Niacin (29.85 mg), Pantothenic acid (10.95 mg), Pyridoxine (3.38 mg), Biotin (0.108 mg), Folic acid (0.69 mg) and Cobalamin (8.85 µg) 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 hydroxypropylmethylcellulose capsules (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

End of first supplementation:

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

End of second supplementation:

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 homocysteine.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Natural Panmol-B-Complex first, then synthetic Vitamin B-complex	Natural Panmol-B-Complex	Participants first received a Natural Vitamin B-complex, i.e., Panmol-B-Complex - B1 (2.93 mg), B2 (3.98 mg), B3 (29.85 mg), B5 (10.95 mg), B6 (3.38 mg), B7 (0.108 mg), B9 (0.69 mg), B12 (8.85 µg) daily each morning for 6 weeks. After a wash-out period of 2 weeks, they then received a synthetic Vitamin B-complex - B1 (2.93 mg), B2 (3.98 mg), B3 (29.85 mg), B5 (10.95 mg), B6 (3.38 mg), B7 (0.108 mg), B9 (0.69 mg), B12 (8.85 µg) daily each morning for 6 weeks.The study finished after the second wash-out period for another 6 weeks.
Synthetic Vitamin B-complex first, then Natural Panmol-B-Complex	Synthetic Vitamin B-Complex	Participants first received a Synthetic Vitamin B-complex - B1 (2.93 mg), B2 (3.98 mg), B3 (29.85 mg), B5 (10.95 mg), B6 (3.38 mg), B7 (0.108 mg), B9 (0.69 mg), B12 (8.85 µg) daily each morning for 6 weeks. After a wash-out period of 2 weeks, they then received a natural Vitamin B-complex, i.e., Panmol-B-complex - B1 (2.93 mg), B2 (3.98 mg), B3 (29.85 mg), B5 (10.95 mg), B6 (3.38 mg), B7 (0.108 mg), B9 (0.69 mg), B12 (8.85 µg) daily each morning for 6 weeks.The study finished after the second wash-out period for another 6 weeks.

Primary Outcome Measures

Name	Time	Method
Serum Thiamine	20 weeks	Serum Thiamine in microgram per liter Minimum: 36 Maximum: 98
Serum Riboflavin	20 weeks	Serum Riboflavin in microgram per liter Minimum: 190 Maximum: 341
Serum Folic Acid	20 weeks	Serum Folic acid in nanogram per liter Minimum: 2.20 Maximum: 58.10
Serum Cobalamin	20 weeks	Serum Cobalamin in picogram per liter Minimum: 159 Maximum: 1230
Serum Pyridoxine	20 weeks	Serum Pyridoxine in microgram per liter Minimum: 3.8 Maximum: 161.8

Secondary Outcome Measures

Name	Time	Method
Serum Total Peroxides	20 weeks	Serum Total peroxides in micromol per liter Minimum: 23 Maximum: 443
Serum Total Antioxidant Capacity	20 weeks	Serum total antioxidant capacity in millimole per liter Minimum: 0.31 Maximum: 2.45
Total Homocysteine	20 weeks	Total Homocysteine in Micromole Minimum: 4.00 Maximum: 40.40
Serum Polyphenols	20 weeks	Serum Polyphenols in millimole per liter Minimum: 7.45 Maximum: 10.91
Serum Endogenous Peroxidase-activity	20 weeks	Serum endogenous peroxidase-activity in milliunits per milliliter Minimum: 0.79 Maximum: 9.87