Methylcobalamin
Dietary SupplementTreatment with Methylcobalamin during 12 weeks
Recruiting
NCT Number: NCT05785585
Effect of Methylcobalamin and Cyanocobalamin Consumption on Vitamin B12 Nutritional Status
Vitamin B12 (B12, Cobalamin) is an essential micronutrient that humans are not capable of synthesizing and therefore must be ingested through food. In nature, B12 is basically only present in foods of animal origin.
B12 deficiency is a clinically important condition that is associated with several metabolic disorders such as megaloblastic anemia, hyperhomocysteinemia, and cardiovascular, cerebrovascular, and neurological disorders. Therefore an optimal intake of B12 is important.
B12 deficiency occurs when B12 stores are depleted due to inadequate dietary intake or impaired absorption of B12. Because B12 is only present in foods of animal origin, following an unbalanced vegetarian diet is associated with increased risk of developing nutritional deficiencies due to the exclusion of meat and fish from their diet, including vitamin B12 deficiency.
There are a variety of forms of vitamin B12 used in vitamin B12 supplements. All these forms share the structure of Cobalamin but contain different ligands. Cyanocobalamin (CNCbl) is a synthetic, stable, and inexpensive form widely used in B12 supplements. MethylCobalamin (MeCbl) is a physiological form of cobalamin, called metabolically active form of vitamin B12. Interest in substituting CNCbl form with the physiological form MCbl has recently increased, assuming that it will be more effective.
The main objective of the study is to evaluate the effect of Methylcobalamin consumption, compared to Cyanocobalamin consumption, on the nutritional status of vitamin B12 in a vegetarian population with marginal vitamin B12 deficiency.
The secondary objectives of the study are to evaluate the effects of Methylcobalamin consumption, compared to Cyanocobalamin consumption, on markers of vitamin B12 deficiency: Holotranscobalamin, Methylmalonic acid, Homocysteine and 4cB12.
During the study there will be 8 visits: a preselection visit (V0; day -7) and 7 study visits during the consumption of the treatments, which will take place on the first day of the study (V1; day 1), after 8 days of treatment (V2; day 8), at 15 days of treatment (V3; day 15), at 29 days of treatment (V4; day 29), at 43 days of treatment (V5; day 43), at 64 days of treatment (V6; day 64), and at 85 days of treatment (V7; day 85).
Recruiting
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Request InfoKey information
Conditions
Age range
18 year and older
Sex eligibility
All sexes
Study type
Interventional
Phase
Not applicable
Primary location
Fundació Eurecat, Reus, Tarragona, Spain
Loading trial locations.
Who can participate
Healthy volunteers accepted: Yes
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
- Men and women aged 18 years or older who follow a vegetarian diet.
- Present serum vitamin B12 levels of 148-221 pmol/L and absence of symptoms associated with vitamin B12 deficiency.
- Sign the informed consent.
- Read, write and speak Catalan or Spanish.
Exclusion criteria
- Present diagnosed diseases that may interfere with vitamin B12 markers, including gastrointestinal diseases (such as inflammatory bowel disease, celiac disease, ileal resection, Crohn's disease, constipation or atrophic gastritis), pancreatic diseases, kidney diseases, liver diseases, diabetes, cardiovascular diseases, pernicious anemia and cancer.
- Medical history of abdominal surgery that may influence the absorption of vitamin B12 (such as bariatric surgery).
- Being on hemodialysis treatment.
- Present values of body mass index ≤ 18.5 kg/m^2 or ≥ 35 kg/m^2.
- Present anemia (hemoglobin ≤ 13 g/dL in men and ≤ 12 g/dL in women).
- Having consumed or consume vitamin B12 or folate supplements for more than 2 months before inclusion in the study.
- Have taken medications that affect the absorption and therapeutic response of vitamin B12 (such as methotrexate, metformin, proton pump inhibitors, H2 receptor antagonists, histamine, nitrous oxide, colchicine, neomycin, biguanides, cholestyramine, aminosalicylic acid, chloramphenicol and other bone marrow depressants) one month before inclusion in the study.
- Be a smoker or ex-smoker in the last 6 months before inclusion in the study.
- Take 2 or more Standard Beverage Units (SBU) daily or 17 SBU weekly for women, or take 4 or more SBU daily or 28 SBU weekly for men.
- Present allergy or intolerance to the study products (microcrystalline cellulose, vitamin B12 or cobalt).
- Being pregnant or intending to become pregnant.
- Being in breastfeeding period.
- Participate in or have participated in a clinical trial or nutritional intervention study in the last 30 days before inclusion in the study.
Treatment and study plan
Cyanocobalamin group
Dietary SupplementTreatment with Cyanocobalamin during 12 weeks
Control group
Dietary SupplementTreatment with microcrystalline cellulose during 12 weeks
Primary outcomes
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Levels of total vitamin B12 in blood.
Time frame: At day -7 (pre-selection visit), day 8 (visit 2), day 15 (visit 3), day 29 (visit 4), day 43 (visit 5), day 64 (visit 6) and day 85 (visit 7).
Serum total vitamin B12 will be measured by chemiluminescence immunoassay.
Secondary outcomes
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Levels of Holotranscobalamin in blood.
Time frame: At day -7 (pre-selection visit), day 8 (visit 2), day 15 (visit 3), day 29 (visit 4), day 43 (visit 5), day 64 (visit 6) and day 85 (visit 7).
Serum Holotranscobalamin will be measured by chemiluminescence immunoassay.
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Levels of Methylmalonic acid in blood.
Time frame: At day -7 (pre-selection visit), day 8 (visit 2), day 15 (visit 3), day 29 (visit 4), day 43 (visit 5), day 64 (visit 6) and day 85 (visit 7).
Serum Methylmalonic acid will be measured by Liquid Chromatography coupled to tandem Mass Spectrometry.
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Levels of Homocysteine in blood.
Time frame: At day -7 (pre-selection visit), day 8 (visit 2), day 15 (visit 3), day 29 (visit 4), day 43 (visit 5), day 64 (visit 6) and day 85 (visit 7).
Plasma Homocysteine will be measured by Liquid Chromatography coupled to tandem Mass Spectrometry.
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Levels of 4cB12 marker.
Time frame: At day -7 (pre-selection visit), day 8 (visit 2), day 15 (visit 3), day 29 (visit 4), day 43 (visit 5), day 64 (visit 6) and day 85 (visit 7).
The 4cB12 marker will be calculated from the blood levels obtained for total vitamin B12, Holotranscobalamin, Methylmalonic acid and Homocysteine using the formula log10((B12 x Holotranscobalamin)/(Methylmalonic acid x Homocysteine)).
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Levels of folate in blood.
Time frame: At day -7 (pre-selection visit) and day 85 (visit 7).
Serum folate will be measured by chemiluminescence immunoassay.
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Levels of vitamin B6 in blood.
Time frame: At day -7 (pre-selection visit) and day 85 (visit 7).
Plasma vitamin B6 will be measured by Ultra High Performance Liquid Chromatography coupled to tandem Mass Spectrometry.
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Health related quality of life.
Time frame: At day 1 (visit 1) and day 85 (visit 7).
Health related quality of life will be assessed using the SF-36 questionnaire (36-item short form survey) in Spanish. The SF-36 questionnaire consists of the subscales general health (5 items), mental health (5 items), emotional role (3 items), social function (2 items), vitality (4 items), physical function (10 items), physical role (4 items) and bodily pain (2 items). The items on the scale are ordered in such a way that the higher the score, the higher the state of health. Scores on each of the SF-36 scales range from 0 to 100.
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Dietary habits and caloric intake.
Time frame: At day 1 (visit 1) and day 85 (visit 7).
Nutritional habits and caloric intake will be determined based on the results obtained from the 3-day dietary record.
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Consumption of foods with vitamin B12.
Time frame: At day 1 (visit 1), day 8 (visit 2), day 15 (visit 3), day 29 (visit 4), day 43 (visit 5), day 64 (visit 6) and day 85 (visit 7).
Consumption of foods with vitamin B12 by the volunteers will be determined by analyzing the questionnaire on the frequency of consumption of foods with vitamin B12.
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Compliance with dietary recommendations.
Time frame: At day 8 (visit 2), day 15 (visit 3), day 29 (visit 4), day 43 (visit 5), and day 64 (visit 6).
The adherence to the dietary recommendations by the volunteers will be determined by analyzing the 24h dietary recall.
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Physical activity.
Time frame: At day 1 (visit 1) and day 85 (visit 7).
Physical activity will be evaluated through the International Physical Activity Questionnaire (IPAQ)-short for physical activity questionnaire.
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Concomitant medication.
Time frame: At day 1 (visit 1), day 8 (visit 2), day 15 (visit 3), day 29 (visit 4), day 43 (visit 5), day 64 (visit 6) and day 85 (visit 7).
The consumption of concomitant medication by te volunteers will be controlled by the record of concomitant medication in the case report form.
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Consumption of food supplements.
Time frame: At day 1 (visit 1), day 8 (visit 2), day 15 (visit 3), day 29 (visit 4), day 43 (visit 5), day 64 (visit 6) and day 85 (visit 7).
The consumption of food supplements by te volunteers will be controlled by the record of food supplements in the case report form.
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Body weight.
Time frame: At day 1 (visit 1) and day 85 (visit 7).
Body weight measured by standardized method.
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Height.
Time frame: At day -7 (pre-selection visit).
Height measured by standardized method.
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Body Mass Index.
Time frame: At day 1 (visit 1) and day 85 (visit 7).
Weight and height will be combined to report Body Mass Index in kg/m^2.
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Age.
Time frame: At day -7 (pre-selection visit).
The age of the volunteers will be recorded in the case report form.
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Gender.
Time frame: At day -7 (pre-selection visit).
The gender of the volunteers will be recorded in the case report form.
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Intervention compliance.
Time frame: At day 43 (visit 5) and day 85 (visit 7).
The intervention compliance by te volunteers will be assessed by counting the number of remaining capsules and applying the formula (Number of capsules consumed/Number of capsules to consume)x100.
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Adverse events.
Time frame: At day 8 (visit 2), day 15 (visit 3), day 29 (visit 4), day 43 (visit 5), day 64 (visit 6) and day 85 (visit 7).
Possible adverse events derived from taking study's products will be recorded in the case report form.
Study contacts
Contact information is provided by the study sponsor or research team.
Anna Crescenti
CONTACT
Antoni Caimari, PhD
CONTACT
Sponsors and collaborators
Lead sponsor
Fundació Eurecat
Other
Collaborators
- Health Tech Bio Actives, S.L.U.
- Laboratorio Echevarne
Registry information
Official study title
Effect of Methylcobalamin and Cyanocobalamin Consumption on Vitamin B12 Nutritional Status in Vegetarians With Marginal Vitamin B12 Deficiency. Randomized, Parallel, Placebo-Controlled, Triple-Blind Clinical Trial.
Acronym: NORMB12
Important dates
- Study start
- 2023
- Primary completion
- 2025
- Study completion
- 2025
- First posted
- Mar 27, 2023
- Registry last updated
- Oct 30, 2024
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.