Natural Versus Synthetic Vitamin B Complexes in Human

Study Overview
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Brief Summary
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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
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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.

Official Title
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Pilot Study for the Evaluation of the Effectiveness of Natural Versus Synthetic Vitamin B Complexes in Humans.

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

Intervention / Treatment
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* Dietary Supplement: Natural Panmol-B-Complex
* Dietary Supplement: Synthetic Vitamin B-Complex


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Natural Panmol-B-Complex first, then synthetic Vitamin B-complex<br>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. | Dietary Supplement: Natural Panmol-B-Complex<br>* Natural 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) - 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)<br>|
| Active Comparator: Synthetic Vitamin B-complex first, then Natural Panmol-B-Complex<br>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. | Dietary Supplement: Synthetic Vitamin B-Complex<br>* 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 (8.85µg) - Natural 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)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Thiamine | Serum Thiamine in microgram per liter Minimum: 36 Maximum: 98 | 20 weeks | 
| Serum Riboflavin | Serum Riboflavin in microgram per liter Minimum: 190 Maximum: 341 | 20 weeks | 
| Serum Pyridoxine | Serum Pyridoxine in microgram per liter Minimum: 3.8 Maximum: 161.8 | 20 weeks | 
| Serum Folic Acid | Serum Folic acid in nanogram per liter Minimum: 2.20 Maximum: 58.10 | 20 weeks | 
| Serum Cobalamin | Serum Cobalamin in picogram per liter Minimum: 159 Maximum: 1230 | 20 weeks | 

Secondary Outcome Measures

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