Miglitol, an α-glucosidase inhibitor, prevents the metformin-induced fall in serum folate and vitamin B12 in subjects with type 2 diabetes

Wolever, Thomas M. S.; Assiff, Lila; Basu, Tapan K.; Chiasson, Jean‐Louis; Boctor, Monica; Gerstein, Hertzel C.; Hunt, John A.; Josse, Robert G.; Lau, David C.W.; Leiter, Lawrence A.; Maheux, Pierre; Murphy, Liam; Rodger, N. W.; Ross, Stuart A.; Ryan, Edmond A.; Tildesley, Hugh D.; Yale, Jean‐François

doi:10.1016/s0271-5317(00)80025-1

Cited by 18 publications

(6 citation statements)

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“…As each 1000 mg/d metformin dose increment increased the risk of developing vitamin B 12 deficiency [4] , we chose metformin 2000 mg/d as the cut-off point in our subgroup analysis. The four trials [11] , [13] – [15] belonging to the lower dose group showed that metformin had a significant effect compared with other interventions (MD, −37.99 pmol/L; 95%CI, −57.44 to −18.54 pmol/L, P = 0.0001), without any heterogeneity. The other two trials [14] , [16] belonging to the higher dose group also showed a significant effect (MD, −78.62 pmol/L; 95%CI, −106.37 to −50.86 pmol/L, P<0.00001), with significant heterogeneity.…”

Section: Resultsmentioning

confidence: 96%

“…Two studies of RCTs didn't report any adverse event [11] , [15] . Among the other 4 studies, gastrointestinal side effects were the most common adverse events [13] , [14] , [16] .…”

Section: Resultsmentioning

confidence: 99%

“…Of these, 10 articles were RCTs and 33 were observational studies. Of the 10 RCTs, three reports were excluded because both groups received metformin as background treatment, and one was excluded because no major indices could be extracted, and eventually only six randomized controlled trials [11] – [16] met the inclusion criteria. Among the 33 observational studies, 15 were conference abstracts without available full texts [17] – [31] which could not provide sufficient information for quality assessment or data analysis, and 14 cross-sectional studies [3] , [32] – [44] and 1 case-control study [5] lacked data of changes in serum vitamin B 12 concentration from baseline, but vitamin B 12 concentration changes had been defined as the primary outcome of this study.…”

Section: Resultsmentioning

confidence: 99%

“…All of the 6 RCTs were adequate randomized without selective reporting and other biases. Allocation concealment of 2 studies [11] , [15] , blinding of outcome assessment of 3 studies [13] – [15] , and incomplete outcome data of 1 study [15] were all not described in details. In addition, blinding of participants and personnel was probably not been done in 2 studies [13] , [15] .…”

Section: Resultsmentioning

confidence: 99%

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Vitamin B12 Status in Metformin Treated Patients: Systematic Review

et al. 2014

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ObjectiveRandomized controlled trials and observational studies have yielded inconsistent results on the effects of metformin on vitamin B12 reduction. We therefore performed a systematic review to analyze the effects of metformin on vitamin B12 concentration.MethodsPubMed, Medline, Embase, and the Cochrane central registry of controlled trials were searched to identify randomized controlled trials and observational studies exploring the association between metformin and vitamin B12 concentration in patients with type 2 diabetes mellitus or polycystic ovary syndrome. The main outcome measure was changes in serum vitamin B12 concentration after 6–208 weeks of treatment with metformin, as compared with placebo or other anti-hyperglycemic therapy.ResultsSix randomized controlled trials met the inclusion criteria. Serum vitamin B12 concentrations were significantly lower in patients treated with metformin than in those who received placebo or rosiglitazone (mean difference [MD], −53.93 pmol/L; 95% confidence interval [CI], −81.44 to −26.42 pmol/L, P = 0.0001). Subgroup analysis identified four trials in which patients received a lower dose of metformin (<2000 mg/d) and two in which they received a higher dose (≥2000 mg/d), with MDs in vitamin B12 concentration after metformin treatment of −37.99 pmol/L (95% CI, −57.44 to −18.54 pmol/L, P = 0.0001) and −78.62 pmol/L (95% CI, −106.37 to −50.86 pmol/L, P<0.00001), respectively.ConclusionsThe reduction of vitamin B12 may be induced by metformin in a dose dependent manner.

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Section: Resultsmentioning

confidence: 96%

“…Two studies of RCTs didn't report any adverse event [11] , [15] . Among the other 4 studies, gastrointestinal side effects were the most common adverse events [13] , [14] , [16] .…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Vitamin B12 Status in Metformin Treated Patients: Systematic Review

et al. 2014

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“…However, because of the large quantity of folate present in the colon and its potential for manipulation by diet (eg, dietary fiber increasing the bacterial load and folate synthesis), we speculate that an individual’s dietary requirement for folate may differ depending on the consumption of dietary constituents that influence the size and composition of the gastrointestinal microbiome. Although there has been some evidence from animal and human studies that suggested that systemic folate concentrations are associated with bacterial folate biosynthesis, more research is required before changes to dietary recommendations should be considered (37–40). In addition, the current research suggests that a systematic investigation of the role of colonic folate on gut health, including gastrointestinal development during infancy and the prevention of colorectal cancer, is warranted.…”

Section: Discussionmentioning

confidence: 99%

Folate is absorbed across the human colon: evidence by using enteric-coated caplets containing 13C-labeled [6S]-5-formyltetrahydrofolate

Lakoff¹,

Fazili²,

Aufreiter³

et al. 2014

The American Journal of Clinical Nutrition

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Background Folate intakes that do not meet or greatly exceed requirements may be associated with negative health outcomes. A better understanding of contributors that influence the input side will help establish dietary guidance that ensures health benefits without associated risks. Colonic microbiota produce large quantities of folate, and [13C5]5-formyltetrahydrofolate infused during colonoscopy is absorbed. However, it is unclear if significant quantities of folate are absorbed in an intact microbiome. Objective We determined whether and how much of a physiologic dose of [13C5]5-formyltetrahydrofolate delivered in a pH-sensitive enteric caplet to an intact colonic microbiome is absorbed. Design Healthy adults ingested a specially designed pH-sensitive acrylic copolymer–coated barium sulfate caplet that contained 855 nmol (400 μg) [13C5]5-formyltetrahydrofolate. After a washout period ≥4 wk, subjects received an intravenous injection of the same compound (214 nmol). Serially collected blood samples before and after each test dose were analyzed by using a microbiological assay and liquid chromatography–tandem mass spectrometry. Results Caplet disintegration in the colon was observed by fluoroscopic imaging for 6 subjects with a mean (±SD) complete disintegration time of 284 ± 155 min. The mean (±SEM) rate of appearance of [13C5]5-methyltetrahydrofolate in plasma was 0.33 ± 0.09 (caplet) and 5.8 ± 1.2 (intravenous) nmol/h. Likely because of the significant time in the colon, the mean apparent absorption across the colon was 46%. Conclusions Folate is absorbed across the colon in humans with an undisturbed microbiome. This finding and previous observations of the size of the colonic depot of folate and its potential for manipulation by diet (eg, dietary fiber, oligosaccharides, and probiotics) suggest that an individual’s dietary folate requirement may differ depending on the consumption of dietary constituents that affect the size and composition of their gastrointestinal microbiota. In addition, a systematic investigation of the role of colonic folate on gastrointestinal development and the prevention of colorectal cancer is warranted. This trial was registered at clinicaltrials.gov as NCT00941174.

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