Clinical trial NCT05785585: Effect of Methylcobalamin and Cyanocobalamin Consumption on Vitamin B12 Nutritional Status
Official 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Vitamin B12 Nutritional Deficiency
Keywords: Vitamin B12
Methylcobalamin
Cyanocobalamin
Vegetarians
Holotranscobalamin
Methylmalonic acid
Homocysteine
4cB12
Lead sponsor: Fundació Eurecat
Sponsor class: OTHER
Collaborators: name: Laboratorio Echevarne
name: Health Tech Bio Actives, S.L.U.
First posted: 2023-03-27
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Levels of total vitamin B12 in blood.
timeFrame: 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).
Secondary outcomes:
measure: Levels of Holotranscobalamin in blood.
timeFrame: 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).
measure: Levels of Methylmalonic acid in blood.
timeFrame: 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).
measure: Levels of Homocysteine in blood.
timeFrame: 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).
measure: Levels of 4cB12 marker.
timeFrame: 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).
measure: Levels of folate in blood.
timeFrame: At day -7 (pre-selection visit) and day 85 (visit 7).
measure: Levels of vitamin B6 in blood.
timeFrame: At day -7 (pre-selection visit) and day 85 (visit 7).
measure: Health related quality of life.
timeFrame: At day 1 (visit 1) and day 85 (visit 7).
measure: Dietary habits and caloric intake.
timeFrame: At day 1 (visit 1) and day 85 (visit 7).
measure: Consumption of foods with vitamin B12.
timeFrame: 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).
measure: Compliance with dietary recommendations.
timeFrame: At day 8 (visit 2), day 15 (visit 3), day 29 (visit 4), day 43 (visit 5), and day 64 (visit 6).
measure: Physical activity.
timeFrame: At day 1 (visit 1) and day 85 (visit 7).
measure: Concomitant medication.
timeFrame: 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).
measure: Consumption of food supplements.
timeFrame: 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).
measure: Body weight.
timeFrame: At day 1 (visit 1) and day 85 (visit 7).
measure: Height.
timeFrame: At day -7 (pre-selection visit).
measure: Body Mass Index.
timeFrame: At day 1 (visit 1) and day 85 (visit 7).
measure: Age.
timeFrame: At day -7 (pre-selection visit).
measure: Gender.
timeFrame: At day -7 (pre-selection visit).
measure: Intervention compliance.
timeFrame: At day 43 (visit 5) and day 85 (visit 7).
measure: Adverse events.
timeFrame: 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).
Other outcomes:
Locations:
city: Reus
country: Spain
facility: Fundació Eurecat
state: Tarragona
city: Reus
country: Spain
facility: Eurecat
Study officials:
affiliation: Fundació Eurecat
name: Antoni Caimari, PhD
role: PRINCIPAL_INVESTIGATOR
References: