Clinical trial NCT03444155: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: 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
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
First posted: 2018-02-23
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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)
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Serum Thiamine
timeFrame: 20 weeks
measure: Serum Riboflavin
timeFrame: 20 weeks
measure: Serum Pyridoxine
timeFrame: 20 weeks
measure: Serum Folic Acid
timeFrame: 20 weeks
measure: Serum Cobalamin
timeFrame: 20 weeks
Secondary outcomes:
measure: Serum Total Peroxides
timeFrame: 20 weeks
measure: Serum Total Antioxidant Capacity
timeFrame: 20 weeks
measure: Serum Endogenous Peroxidase-activity
timeFrame: 20 weeks
measure: Serum Polyphenols
timeFrame: 20 weeks
measure: Total Homocysteine
timeFrame: 20 weeks
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Wonisch Willibald
state: Styria
Study officials:
References:
citation: Lindschinger M, Tatzber F, Schimetta W, Schmid I, Lindschinger B, Cvirn G, Stanger O, Lamont E, Wonisch W. A Randomized Pilot Trial to Evaluate the Bioavailability of Natural versus Synthetic Vitamin B Complexes in Healthy Humans and Their Effects on Homocysteine, Oxidative Stress, and Antioxidant Levels. Oxid Med Cell Longev. 2019 Dec 12;2019:6082613. doi: 10.1155/2019/6082613. eCollection 2019.
citation: Lindschinger M, Tatzber F, Schimetta W, Schmid I, Lindschinger B, Cvirn G, Fuchs N, Markolin G, Lamont E, Wonisch W. [Bioavailability of natural versus synthetic B vitamins and their effects on metabolic processes]. MMW Fortschr Med. 2020 Mar;162(Suppl 4):17-27. doi: 10.1007/s15006-020-0230-4. Epub 2020 Mar 19. German.