Table 1.
Characteristics of included studies.
| Author | Design | Country | Primary Goal | Study Groups (Mean Age ± SD, % Male) | B12 Markers | Oxidative Stress Markers | Supports Antioxidant Properties of B12 |
|---|---|---|---|---|---|---|---|
| Misra et al. 2017 [59] | CC Human | India | Assess oxidative stress markers in B12-deficient patients compared to healthy volunteers and examine correlation among included markers. | 51 serum B12 deficient patients (45.78 ± 2.19 years, 70.6% male) 53 healthy volunteers (44.28 ± 2.20 years, 77.8% male) |
Serum B12 Serum Hcy |
Plasma GSH Serum TAC Plasma MDA |
Yes |
| Waly et al. 2016 [55] | CC Human | Egypt | Evaluate B-vitamins in relation to hyperhomocysteinemia and oxidative stress in cardiac patients compared to healthy volunteers. | 25 cardiac patients (54.72 ± 10.3 years, 48.0% male) 25 healthy volunteers (53.81 ± 6.8 years, gender not specified) |
Serum B12 Serum Hcy |
Serum GSH Serum TAC Serum NN Serum MDA |
Yes |
| Boanca et al. 2014 [51] | CC Human | Romania | Evaluate the impact of the lacto-ovo diet on oxidative stress compared to non-vegetarians regarding B12 status. | 48 lacto-ovo vegetarians (28.4 ± 8.6 years, 33.3% male) 38 non-vegetarian volunteers (29.8 ± 1 0.1 years, 34.2% male) |
Serum B12 | Erythrocyte SOD Serum MDA |
Unclear |
| Özcan et al. 2008 [56] | CC Human | Turkey | Investigate the relationship between B12 status and cell membrane composition regarding oxidative stress, cholesterol, and phospholipid content in schizophrenic patients compared to healthy volunteers. | 18 schizophrenic patients (31 ± 7 years, 55.6% male) 20 healthy volunteers (30 ± 8 years, 50.0% male) |
Serum B12 Urine MMA Plasma Hcy |
Membrane MDA | Yes |
| Vener et al. 2010 [57] | CC Human | Italy | Determine if folate and/or B12 depletion can lead to hyperhomocysteinemia and contribute to oxidative stress in chronic myeloproliferative disorders compared to healthy volunteers. | 51 CMPD patients (median 64 years (range 40–84 years), 52.9% male) 53 healthy volunteers (median 50 years (range 30–84 years), 64.2% male) |
Serum B12 Serum holo-TC Serum Hcy |
Serum TAC Serum ROS |
Yes |
| Al-Maskari et al. 2012 [53] | CC Human | Oman | Evaluate the status of folate and B12 in relation to serum Hcy and oxidative stress indices in T2D patients compared to healthy volunteers. | 50 T2D patients (51.43 ± 7.9 years, 50% male) 50 healthy controls (48.94 ± 6.02 years, 50% male) |
Serum B12 Serum Hcy |
Serum GSH Serum TAS Serum catalase Serum GPx Serum SOD |
Yes |
| Güney et al. 2015 [58] | CC with one-armed intervention Human |
Turkey | Determine the effect of B12 deficiency on oxidative stress compared to healthy controls, and to determine the effect of 1-month cyano-Cbl treatment for B12 deficient patients on oxidative stress (without placebo or control). | 40 B12 deficient patients (43.1 ± 1 5.9 years, 25% male) 40 healthy controls (40.1 ± 16.9 years, 42.5% male) |
Serum B12 Serum MMA Urine MMA Plasma Hcy |
Plasma TOS Plasma TAS OSI |
No |
| Lee et al. 2016 [54] | CS Human |
Taiwan | Investigate the correlation between vitamin B12 status and oxidative stress and inflammation in diabetic vegetarians and omnivores. | 54 T2D vegetarians (65.1 ± 11.3 years, 30% male) 100 T2D omnivores (57.5 ± 10.5 years, 45% male) |
Serum B12 | Plasma MDA Serum Ox-LDL-C Erythrocyte SOD Erythrocyte GPx Erythrocyte catalase |
Unclear |
| Hunaiti et al. 2016 [49] | CS Human |
Jordan | Assess the impact of B12 deficiency on lipid peroxidation and antioxidant capacity in patients with symptoms and signs of B12 deficiency. | 24 patients with B12 deficiency (mean 53 years, range 36–76 years, 37.5% male) | Serum B12 Serum Hcy |
Serum MDA Serum TAC |
Yes |
| Gariballa et al. 2013 [47] | RCT Human |
UAE | Test the effect of 3 months B-vitamins and antioxidant supplementation compared to placebo on antioxidant capacity and oxidative stress in obese T2D patients. | 50 T2D patients allocated to intervention (median 52 years, Q1–Q3 44–56 years, 46% male) 50 T2D patients allocated to placebo (median 51 years, Q1–Q3 42–60 years, 36% male) |
Serum B12 Plasma Hcy |
Protein carbonyl Plasma MDA Plasma GSH |
Unclear |
| Muss et al. 2015 [48] | RCT Human |
Austria | Test the neuroprotective effect of verum supplementation (measured at 3 and 6 months) compared to placebo with a focus on oxidative stress in healthy volunteers. | 116 volunteers allocated to intervention (42.4 ± 15.2 years, 39.7% male) 43 volunteers allocated to placebo (45.8 ± 15.5 years, 25.6% male) |
Serum B12 Serum Hcy |
Serum FORD Serum FORT Serum lipid peroxidation Serum SOD |
Unclear |
| Solomon 2015 [52] | RS Human |
USA | Explore the association between functional B12 deficiency and oxidative stress in elderly and younger patients. | 170 community-dwelling adults with serum B12 ≥ 400 pg/mL were retrospectively reviewed and stratified <70 years (n = 100, 42% male) and ≥70 years (n = 70, 54.3% male) | Serum MMA Plasma Hcy |
Oxidant risks | Yes |
| Solomon 2016 [50] |
RS Human |
USA | Examine the relationship between MMA/Hcy and oxidant risks in community-dwelling adults with low (≤200 pg/mL) and low-normal (201-300 pg/mL) serum B12. | 49 participants with low serum B12 (57 ± 19 years, 29% male) 187 participants with low-normal serum B12 (56 ± 17 years, 39% male) |
Serum MMA Plasma Hcy |
Oxidant risks | Unclear |
| Ghosh et al. 2016 [60] | Animal | Japan | Evaluate differential effects of severe and moderate B12 deficiency on several factors, including oxidative stress. | 10 severely B12 deficient mice 10 moderately deficient mice 10 control mice |
Plasma Hcy | Liver MDA Liver protein carbonyl Liver SOD Liver catalase |
Yes |
| Bito et al. (2017) [61] | Animal | India | Clarify levels of oxidative stress and induced damage when B12 deficiency is present using a C. elegans animal model. In addition, the relationship between B12 deficiency and memory impairment is investigated. | 12 B12-deficient worms 12 control worms |
Plasma Hcy | H2O2 NN MDA Protein carbonyls GSH Total SOD Catalase GPx |
Yes |
CC: case-control; B12: vitamin B12; Hcy: homocysteine; GSH: glutathione; TAC: total antioxidant capacity; MDA: malondialdehyde; NN: nitrates and nitrites; SOD: superoxide dismutase; MMA: methylmalonic acid; CMPD: chronic myeloproliferative disorder; holo-TC: holo-transcobalamin; ROS: reactive oxygen species; T2D: type 2 diabetes; TAS: total antioxidant status; GPx: glutathione peroxidase; TOS: total oxidant status; OSI: oxidative stress index; CS: cross-sectional study; Ox-LDL-C: oxidised low-density lipoprotein C; RCT: randomised controlled trial; UAE: United Arab Emirates; FORD: free oxygen radicals defence; FORT: free oxygen radicals test; RS: retrospective study; USA: United States of America.