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.

Overview

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).

Interventions

• Dietary supplement Methylcobalamin
  Treatment with Methylcobalamin during 12 weeks
• Dietary supplement Cyanocobalamin group
  Treatment with Cyanocobalamin during 12 weeks
• Dietary supplement Control group
  Treatment with microcrystalline cellulose during 12 weeks

Primary outcome measures

• 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).]

Secondary outcome measures (12)

• 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).]
• 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).]
• 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).]
• 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).]
• Levels of folate in blood. [Time frame: At day -7 (pre-selection visit) and day 85 (visit 7).]
• Levels of vitamin B6 in blood. [Time frame: At day -7 (pre-selection visit) and day 85 (visit 7).]
• Health related quality of life. [Time frame: At day 1 (visit 1) and day 85 (visit 7).]
• Dietary habits and caloric intake. [Time frame: At day 1 (visit 1) and day 85 (visit 7).]
• 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).]
• 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).]
• Physical activity. [Time frame: At day 1 (visit 1) and day 85 (visit 7).]
• 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).]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

Spain · 2 centers

• Fundació Eurecat — Reus
• Eurecat — Reus

Identifiers

NCT: NCT05785585 · NORMB12

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗