Division of Nutrition, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, India.
Medical Student, St. John's Medical College, St. John's National Academy of Health Sciences, Bangalore, India.
Clin Nutr ESPEN. 2024 Aug;62:76-80. doi: 10.1016/j.clnesp.2024.04.024. Epub 2024 May 13.
BACKGROUND & AIMS: Metformin is a widely prescribed first line drug for the treatment of type 2 diabetes mellitus (DM). Studies have shown that the use of metformin is often associated with a decrease in vitamin B (B) levels in patients with DM. Few studies have shown that this effect could be mitigated with calcium supplementation. In the present study, we quantified the effect of metformin, and metformin co-administered with calcium on B absorption using a novel stable isotope [C] cyanocobalamin tracer.
A pilot crossover study was conducted to estimate the bioavailability of B in healthy subjects, using [C] cyanocobalamin as a tracer. In the study, [C] cyanocobalamin was administered orally to the participants followed by hourly venous sampling to measure the concentration of the tracer and estimate bioavailability. This protocol was followed for three experiment days, each separated by a one month wash out period. As part of the study, all participants received the tracer alone for the control day (C), metformin 850 mg along with the tracer for the metformin day (M) and metformin 850 mg with calcium 500 mg and the tracer for the metformin calcium day (MC).
Seven participants completed all three experiment days. The mean B bioavailability (±SD, n = 7) was 42.6 ± 10.2% for the control day (C), 30.8 ± 15.3% for the metformin day (M) and 46.4 ± 8.6% for the metformin-calcium day (MC). Repeated measures ANOVA was done and the pairwise comparison showed a significant difference in the B bioavailability between control and metformin day (C vs M p = 0.010), and between the metformin and metformin with calcium day (M vs MC p = 0.003).
B bioavailability reduced significantly from baseline (C) when metformin (M) was administered and this reduction was reversed when calcium was co-administered (MC) in healthy participants. In patients using metformin, calcium supplementation as a strategy to prevent B deficiency needs to be further studied.
二甲双胍是治疗 2 型糖尿病（DM）的一线药物，被广泛应用。研究表明，二甲双胍的使用常导致 DM 患者维生素 B（B）水平下降。少数研究表明，钙补充剂可以减轻这种影响。本研究采用新型稳定同位素[C]氰钴胺素示踪剂，定量研究二甲双胍及与钙联合使用对 B 吸收的影响。
采用前瞻性交叉研究，用[C]氰钴胺素示踪剂估计健康受试者的 B 生物利用度。在研究中，给参与者口服[C]氰钴胺素，随后每小时进行静脉取样，以测量示踪剂的浓度并估计生物利用度。该方案在三个实验日进行，每个实验日之间间隔一个月的洗脱期。作为研究的一部分，所有参与者在对照日（C）单独接受示踪剂，在二甲双胍日（M）接受 850mg 二甲双胍加示踪剂，在二甲双胍加钙 500mg 日（MC）接受 850mg 二甲双胍和示踪剂。
7 名参与者完成了所有三个实验日。（n=7），对照组（C）的 B 生物利用度（±SD）为 42.6±10.2%，二甲双胍组（M）为 30.8±15.3%，二甲双胍加钙组（MC）为 46.4±8.6%。进行重复测量方差分析，两两比较显示对照组和二甲双胍组之间的 B 生物利用度有显著差异（C 与 M，p=0.010），以及二甲双胍组和二甲双胍加钙组之间的差异（M 与 MC，p=0.003）。
在健康参与者中，当给予二甲双胍（M）时，B 生物利用度从基线（C）显著降低，当联合给予钙时（MC）则逆转。对于正在使用二甲双胍的患者，钙补充作为预防 B 缺乏的策略需要进一步研究。
