Natural Versus Synthetic Vitamin B Complexes in Human
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
MeSH terms: Metabolic Diseases; Vitamin B 12 Deficiency; Folic Acid Deficiency; Vitamin B 6 Deficiency
Study type: Interventional

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.
    

Intervention name(s): Natural Panmol-B-Complex; Synthetic Vitamin B-Complex
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 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); 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)
Intervention MeSH terms: Folic Acid; Vitamin B Complex
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)
Primary purpose: Basic Science