Natural Versus Synthetic Vitamin B Complexes in Human

• Sponsor: Medical University of Graz (Other)
• Overall Status: Completed
• CT.gov ID: NCT03444155
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 2
• Actual Duration (Months): 6.3
• Patients Per Site Per Month: 4.7

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
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	Dietary Supplement: Natural Panmol-B-Complex; Dietary Supplement: Synthetic Vitamin B-Complex	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• 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)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
• Official Title: Pilot Study for the Evaluation of the Effectiveness of Natural Versus Synthetic Vitamin B Complexes in Humans.
• Actual Study Start Date: May 8, 2017
• Actual Primary Completion Date: Oct 3, 2017
• Actual Study Completion Date: Nov 17, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Natural Panmol-B-Complex first, then synthetic Vitamin 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.	Dietary Supplement: Natural Panmol-B-Complex; 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)
Active Comparator: Synthetic Vitamin B-complex first, then Natural Panmol-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.	Dietary Supplement: Synthetic Vitamin B-Complex; 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)

Outcome Measures

Primary Outcome Measures

1. Serum Thiamine [20 weeks]

   Serum Thiamine in microgram per liter Minimum: 36 Maximum: 98

2. Serum Riboflavin [20 weeks]

   Serum Riboflavin in microgram per liter Minimum: 190 Maximum: 341

3. Serum Pyridoxine [20 weeks]

   Serum Pyridoxine in microgram per liter Minimum: 3.8 Maximum: 161.8

4. Serum Folic Acid [20 weeks]

   Serum Folic acid in nanogram per liter Minimum: 2.20 Maximum: 58.10

5. Serum Cobalamin [20 weeks]

   Serum Cobalamin in picogram per liter Minimum: 159 Maximum: 1230

Secondary Outcome Measures

1. Serum Total Peroxides [20 weeks]

   Serum Total peroxides in micromol per liter Minimum: 23 Maximum: 443

2. Serum Total Antioxidant Capacity [20 weeks]

   Serum total antioxidant capacity in millimole per liter Minimum: 0.31 Maximum: 2.45

3. Serum Endogenous Peroxidase-activity [20 weeks]

   Serum endogenous peroxidase-activity in milliunits per milliliter Minimum: 0.79 Maximum: 9.87

4. Serum Polyphenols [20 weeks]

   Serum Polyphenols in millimole per liter Minimum: 7.45 Maximum: 10.91

5. Total Homocysteine [20 weeks]

   Total Homocysteine in Micromole Minimum: 4.00 Maximum: 40.40

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wonisch Willibald	Graz	Styria	Austria	8036

Sponsors and Collaborators

• Medical University of Graz

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 13, 2017

More Information

Publications

None provided.

• Responsible Party: Priv.-Doz. Mag. Dr. Willibald Wonisch, Principal Investigator, Medical University of Graz
• ClinicalTrials.gov Identifier: NCT03444155
• Other Study ID Numbers: Medical University of Graz
• First Posted: Feb 23, 2018
• Last Update Posted: Apr 26, 2021
• Last Verified: Apr 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Metabolic Diseases; Vitamin B 12 Deficiency; Folic Acid Deficiency; Vitamin B 6 Deficiency; Folic Acid; Vitamin B Complex

Study Results

Participant Flow

Recruitment Details	36 subjects were screened for eligibility at an Outpatient Clinic in Laßnitzhöhe, Styria, Austria
Pre-assignment Detail	Of 36 enrolled participants, 30 met inclusion criteria and were randomized to treatment, i.e., to receive a natural (n=15) or synthetic vitamin B complex (n=15) after a 3 weeks run-in phase.

Arm/Group Title	Natural Panmol-B-Complex First, Then Synthetic Vitamin B-complex	Synthetic Vitamin B-complex First, Then Natural Panmol-B-Complex
Arm/Group Description	Participants first received 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 (8.85µg) each morning for 6 weeks. After a washout period of 2 weeks, they then received 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) each morning for 6 weeks.	Participants first received 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) each morning for 6 weeks. After a washout period of 2 weeks, they then received 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) each morning for 6 weeks.
Period Title: First Intervention (6 Weeks)
STARTED	15	15
COMPLETED	14	15
NOT COMPLETED	1	0
Period Title: First Intervention (6 Weeks)
STARTED	14	15
COMPLETED	14	15
NOT COMPLETED	0	0
Period Title: First Intervention (6 Weeks)
STARTED	14	15
COMPLETED	14	15
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Natural Panmol-B-Complex First, Then Synthetic Vitamin B-complex	Synthetic Vitamin B-complex First, Then Natural Panmol-B-Complex	Total
Arm/Group Description	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 (3.38mg), 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.	Participants first received a synthetic vitamin B complex i.e. 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.	Total of all reporting groups
Overall Participants	14	15	29
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	14 100%	15 100%	29 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	11 78.6%	10 66.7%	21 72.4%
Male	3 21.4%	5 33.3%	8 27.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	14 100%	15 100%	29 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	14 100%	15 100%	29 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Austria	14 100%	15 100%	29 100%

Outcome Measures

1. Primary Outcome

Title	Serum Thiamine
Description	Serum Thiamine in microgram per liter Minimum: 36 Maximum: 98
Time Frame	20 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panmol-B-Complex	Synthetic Vitamin B-complex
Arm/Group Description	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.	Participants first received a synthetic vitamin B complex i.e. 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.
Measure Participants	14	15
Baseline	50.21 (8.07)	48.33 (6.51)
1.5 hours	51.21 (8.11)	50.60 (8.72)
4 hours	53.57 (7.45)	51.07 (7.20)
7 hours	52.00 (7.06)	50.27 (8.74)
6 weeks	61.86 (9.81)	61.33 (9.39)
8 weeks	70.14 (12.04)	72.33 (10.75)
8 weeks - 1.5 hours	70.21 (8.94)	69.13 (9.77)
8 weeks - 4 hours	64.71 (8.91)	65.13 (10.95)
8 weeks - 7 hours	64.64 (8.14)	64.20 (7.27)
14 weeks	58.86 (10.50)	61.60 (9.91)
20 weeks	58.43 (10.52)	59.20 (9.70)

2. Primary Outcome

Title	Serum Riboflavin
Description	Serum Riboflavin in microgram per liter Minimum: 190 Maximum: 341
Time Frame	20 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panmol-B-Complex	Synthetic Vitamin B-complex
Arm/Group Description	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.	Participants first received a synthetic vitamin B complex i.e. 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.
Measure Participants	14	15
Baseline	231.93 (10.97)	234.67 (21.87)
1.5 hours	233.86 (17.91)	245.60 (21.88)
4 hours	240.36 (18.14)	254.33 (27.63)
7 hours	247.21 (20.08)	252.87 (27.03)
6 weeks	264.21 (17.62)	265.00 (28.83)
8 weeks	232.29 (13.29)	238.73 (14.18)
8 weeks - 1.5 hours	230.43 (9.72)	233.27 (21.63)
8 weeks - 4 hours	237.36 (13.11)	243.20 (15.42)
8 weeks - 7 hours	244.64 (8.11)	250.13 (14.71)
14 weeks	258.14 (15.68)	271.07 (20.66)
20 weeks	257.93 (12.75)	274.67 (28.30)

3. Primary Outcome

Title	Serum Pyridoxine
Description	Serum Pyridoxine in microgram per liter Minimum: 3.8 Maximum: 161.8
Time Frame	20 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panmol-B-Complex	Synthetic Vitamin B-complex
Arm/Group Description	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.	Participants first received a synthetic vitamin B complex i.e. 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.
Measure Participants	14	15
Baseline	23.11 (13.18)	24.31 (25.80)
1.5 hours	35.45 (20.64)	33.80 (29.23)
4 hours	32.96 (17.95)	33.28 (28.81)
7 hours	36.66 (21.89)	36.59 (25.83)
6 weeks	46.44 (20.10)	48.94 (39.41)
8 weeks	29.23 (26.99)	26.99 (33.38)
8 weeks - 1.5 hours	33.79 (20.71)	36.93 (36.49)
8 weeks - 4 hours	39.14 (28.20)	35.76 (32.58)
8 weeks - 7 hours	42.93 (27.35)	40.41 (39.87)
14 weeks	42.24 (20.64)	39.97 (26.30)
20 weeks	28.38 (26.26)	21.39 (26.69)

4. Primary Outcome

Title	Serum Folic Acid
Description	Serum Folic acid in nanogram per liter Minimum: 2.20 Maximum: 58.10
Time Frame	20 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panmol-B-Complex	Synthetic Vitamin B-complex
Arm/Group Description	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.	Participants first received a synthetic vitamin B complex i.e. 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.
Measure Participants	14	15
Baseline	7.45 (3.29)	6.00 (2.79)
1.5 hours	25.21 (10.17)	20.75 (8.32)
4 hours	12.87 (4.67)	10.93 (2.96)
7 hours	10.38 (3.54)	8.23 (2.62)
6 weeks	13.86 (2.77)	15.18 (4.96)
8 weeks	11.04 (2.80)	10.43 (3.04)
8 weeks - 1.5 hours	26.63 (10.52)	31.87 (14.51)
8 weeks - 4 hours	16.39 (6.82)	14.43 (2.29)
8 weeks - 7 hours	12.63 (2.48)	12.19 (2.10)
14 weeks	18.59 (11.64)	18.70 (14.42)
20 weeks	10.46 (2.33)	9.93 (3.36)

5. Primary Outcome

Title	Serum Cobalamin
Description	Serum Cobalamin in picogram per liter Minimum: 159 Maximum: 1230
Time Frame	20 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panmol-B-Complex	Synthetic Vitamin B-complex
Arm/Group Description	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.	Participants first received a synthetic vitamin B complex i.e. 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.
Measure Participants	14	15
Baseline	381.71 (112.73)	440.47 (246.82)
1.5 hours	387.79 (122.48)	453.67 (235.70)
4 hours	384.50 (105.92)	447.00 (210.03)
7 hours	388.57 (116.72)	442.27 (213.16)
6 weeks	442.36 (142.74)	506.47 (166.44)
8 weeks	414.79 (125.67)	450.33 (143.61)
8 weeks - 1.5 hours	414.57 (132.69)	454.07 (141.05)
8 weeks - 4 hours	389.21 (115.06)	432.07 (131.89)
8 weeks - 7 hours	404.93 (111.60)	453.13 (129.37)
14 weeks	483.57 (139.02)	564.27 (170.41)
20 weeks	421.07 (134.95)	494.80 (176.79)

6. Secondary Outcome

Title	Serum Total Peroxides
Description	Serum Total peroxides in micromol per liter Minimum: 23 Maximum: 443
Time Frame	20 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panmol-B-Complex	Synthetic Vitamin B-complex
Arm/Group Description	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.	Participants first received a synthetic vitamin B complex i.e. 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.
Measure Participants	14	15
Baseline	100.00 (46.17)	111.17 (96.01)
1.5 hours	101.64 (38.65)	112.67 (88.23)
4 hours	132.55 (43.72)	137.08 (95.05)
7 hours	122.18 (46.42)	132.75 (108.81)
6 weeks	97.36 (39.69)	99.58 (31.84)
8 weeks	79.27 (25.86)	71.25 (25.69)
8 weeks - 1.5 hours	97.27 (22.36)	86.92 (25.04)
8 weeks - 4 hours	99.91 (23.28)	92.50 (24.99)
8 weeks - 7 hours	89.18 (20.04)	90.17 (27.33)
14 weeks	102.91 (23.78)	115.83 (64.46)
20 weeks	104.91 (39.91)	116.33 (105.86)

7. Secondary Outcome

Title	Serum Total Antioxidant Capacity
Description	Serum total antioxidant capacity in millimole per liter Minimum: 0.31 Maximum: 2.45
Time Frame	20 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panmol-B-Complex	Synthetic Vitamin B-complex
Arm/Group Description	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.	Participants first received a synthetic vitamin B complex i.e. 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.
Measure Participants	14	15
Baseline	1.15 (0.43)	1.45 (0.23)
1.5 hours	1.27 (0.31)	1.24 (0.24)
4 hours	1.13 (0.33)	1.23 (0.34)
7 hours	1.22 (0.44)	1.39 (0.40)
6 weeks	1.45 (0.38)	1.54 (0.22)
8 weeks	1.20 (0.22)	1.31 (0.29)
8 weeks - 1.5 hours	1.68 (0.52)	1.86 (0.30)
8 weeks - 4 hours	1.14 (0.38)	1.30 (0.34)
8 weeks - 7 hours	1.38 (0.32)	1.18 (0.57)
14 weeks	1.46 (0.32)	1.48 (0.33)
20 weeks	1.34 (0.28)	1.47 (0.38)

8. Secondary Outcome

Title	Serum Endogenous Peroxidase-activity
Description	Serum endogenous peroxidase-activity in milliunits per milliliter Minimum: 0.79 Maximum: 9.87
Time Frame	20 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panmol-B-Complex	Synthetic Vitamin B-complex
Arm/Group Description	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.	Participants first received a synthetic vitamin B complex i.e. 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.
Measure Participants	14	15
Baseline	3.37 (1.74)	3.07 (1.09)
1.5 hours	3.35 (1.49)	3.90 (2.03)
4 hours	4.37 (1.26)	4.22 (1.03)
7 hours	5.31 (1.13)	4.84 (0.93)
6 weeks	4.36 (0.83)	4.34 (0.55)
8 weeks	6.05 (1.82)	5.15 (1.24)
8 weeks - 1.5 hours	3.97 (1.62)	3.60 (1.03)
8 weeks - 4 hours	3.99 (1.12)	3.93 (1.41)
8 weeks - 7 hours	4.35 (1.30)	5.48 (1.74)
14 weeks	3.89 (1.53)	4.95 (2.01)
20 weeks	3.04 (1.34)	2.96 (1.14)

9. Secondary Outcome

Title	Serum Polyphenols
Description	Serum Polyphenols in millimole per liter Minimum: 7.45 Maximum: 10.91
Time Frame	20 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panmol-B-Complex	Synthetic Vitamin B-complex
Arm/Group Description	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.	Participants first received a synthetic vitamin B complex i.e. 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.
Measure Participants	14	15
Baseline	9.88 (0.34)	9.57 (0.34)
1.5 hours	9.73 (0.45)	9.77 (0.67)
4 hours	9.97 (0.38)	9.81 (0.45)
7 hours	9.72 (0.31)	9.54 (0.43)
6 weeks	9.49 (0.35)	9.46 (0.41)
8 weeks	9.73 (0.29)	9.54 (0.53)
8 weeks - 1.5 hours	8.87 (0.66)	8.71 (0.42)
8 weeks - 4 hours	8.25 (0.70)	8.18 (0.70)
8 weeks - 7 hours	8.68 (0.35)	8.57 (0.40)
14 weeks	8.72 (0.52)	8.82 (0.44)
20 weeks	9.67 (0.34)	9.46 (0.64)

10. Secondary Outcome

Title	Total Homocysteine
Description	Total Homocysteine in Micromole Minimum: 4.00 Maximum: 40.40
Time Frame	20 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panmol-B-Complex	Synthetic Vitamin B-complex
Arm/Group Description	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.	Participants first received a synthetic vitamin B complex i.e. 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.
Measure Participants	14	15
Baseline	8.89 (1.99)	11.49 (7.57)
1.5 hours	8.96 (2.32)	11.89 (8.20)
4 hours	8.68 (1.98)	11.38 (8.01)
7 hours	8.91 (2.03)	11.31 (7.89)
6 weeks	7.76 (1.43)	7.85 (1.89)
8 weeks	7.89 (1.58)	8.16 (1.58)
8 weeks - 1.5 hours	7.91 (1.47)	7.97 (1.45)
8 weeks - 4 hours	7.34 (1.45)	7.39 (1.31)
8 weeks - 7 hours	8.00 (1.70)	8.13 (1.69)
14 weeks	7.01 (1.59)	7.44 (1.55)
20 weeks	7.62 (2.03)	7.95 (1.88)

Adverse Events

Time Frame	6 months
Arm/Group Title	Natural Panmol-B-Complex		Synthetic Vitamin-B-Complex
Arm/Group Description	Participants received a 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) daily each morning for 6 weeks.		Participants received a Synthetic Vitamin-B-Complex consisting of - 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 (matching the Natural Panmol-B-Complex).
All Cause Mortality
	Natural Panmol-B-Complex		Synthetic Vitamin-B-Complex
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)
Serious Adverse Events
	Natural Panmol-B-Complex		Synthetic Vitamin-B-Complex
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Natural Panmol-B-Complex		Synthetic Vitamin-B-Complex
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/30 (3.3%)		0/30 (0%)
Skin and subcutaneous tissue disorders
Flush	1/30 (3.3%)	1	0/30 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.