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. 2021 Dec 17;13(2):530–558. doi: 10.1093/advances/nmab123

TABLE 5.

Studies assessing association between vitamin B-12 and secondary outcomes1

First author, year (ref) Model or population Comparison Function Other outcomes
In vitro studies
 Xu, 2018 (23) In vitro CC vs. MC vs. control Secondary functions: MC and CC promoted lipid, terpenoid, and polyketide metabolism, and degradation of exogenous substances; and inhibited the synthesis of transcription factors and secondary metabolitesTertiary functions: MC and CC promoted pathways for DNA repair and recombinant protein (ko03400) and decreased nitrogen metabolism (ko00910) and starch with sucrose metabolism (ko00500)Tertiary functions: Control group increased ABC transporter (ko02010) pathway SCFAs: MC was positively correlated with propionate and butyrate in canonical correspondence analysisEnzyme activity2: Control had higher protease activity than MC or CC; amylase activity was more stable in control, protease activity fluctuated more in MC, and cellulase activity fluctuated more in CCSCFAs: MC and CC had higher total SCFAs, while control had higher acetate; propionate decreased in control, increased in MC, and did not change in CC; butyrate was highest in MC on day 1 then decreased, and did not change in control or CC
 Zheng, 2021 (24) In vitro High and low CC supplement (CC-high, CC-low) and CC-enriched spinach (CCspinach-high, CCspinach-low) vs. control; within-group changes Secondary functions:CC-high: lower glycan biosynthesis and metabolismCCspinach-high: lower enzyme family; higher xenobiotics and metabolism, glycan biosynthesis and metabolism, transport and catabolism, lipid metabolism SCFAs: CCspinach-low had higher acetate and butyrate vs. other groups
Murine studies
 Kelly, 2019 (25) C57BL/6 mice (8–16 wk old) CC vs. control Not reported Cecum SCFAs: not significant Transcriptome (IL-1β, IL-6, IL-10, TNF-α, IL-12p70, IFN-γ, mKC): not significantCorrinoid concentrations (cecum): higher cecum cobalamin, MeS-ADE; no difference in cecum Me-ADE or cobinamide
Post- vs. pre-CC Not reported Corrinoid concentrations (stool): lower fecal Me-ADE, MeS-ADE and ADE; higher cobinamide and cobalamin; no difference in control group
 Lurz, 2020 (27) C57BL/6 mice age 3 wk CC high (B12++), medium (B12+), and deficient (B12−) dose, and within-group changes Not reported Transcriptome (IL-10, TNF-α): not significant
 Siddharth, 2017 (29) Wistar rats B12 concentrations Lower K00947 (“none,” metabolism) and K02803 [“PTS system, N-acetylglucosamine-specific IIB component (EC:2.7.1.69),” carbohydrate metabolism] Proteomics:Higher Notch1, complement factor B, thrombospondin-4, IL-1beta, contactin 1, and melanoma inhibitory activityLower endoplasmic reticulum aminopeptidase 1, alpha S1 casein, chromobox protein homolog 5, proteasome subunit alpha2, nucleoside diphosphate kinase A, IL-17 receptor D, osteoprotegerin ligand/TRANCE, mitochondrial ATP synthase beta-subunit, non-receptor tyrosine kinase c-abl oncogene 1, amnionless, parathyroid hormone, neutral ceramidase, and X-linked ectodysplasin-A2 receptor
 Zhu, 2019 (26) Male C57BL/6 mice (10 wk old) CC vs. MC vs. control Not significant Not reported
Human studies
 Mörkl, 2018 (33) Females (18–40 y), not pregnant or lactating B12 intake (continuous, above vs. below median) Not reported Higher zonulin concentrations in serum (indicator of gut permeability) with higher continuous B12 intake and above vs. below median, but not significant by tertiles of B12 intake
 Tamura, 2017 (34) Healthy older adults (65–84 y) B12 intake Not reported Lower quercetin degradation, after 7 h incubation of stool samples with quercetin
1

ADE, adenine cobamide; B12, vitamin B-12; CC, cyanocobalamin; Me-ADE, 2-methyladenine cobamide; MeS-ADE, 2-methylmercaptoadenine cobamide; MC, methylcobalamin; mKC, murine keratinocyte-derived chemokine; ref, reference; TRANCE, tumor necrosis factor-related activation-induced cytokine.

2

No statistical test reported, based on study authors or systematic review authors interpretation of figures