Table 1.
Vitamin C, oxidative stress and brain development.
| Species | Intervention | Measurements | Outcome | Reference | |
|---|---|---|---|---|---|
| In Vivo Studies | |||||
| SVCT2(−/−) mice (ED: 18.5–19.5). | Dams: 0.33 g/L VitC in drinking water. | VitC content, MDA, F2-isoprostanes and F4-neuroprostanes in brain (cortex). Additional IHC. | The SVCT2(−/−) fetuses: Increased F2-isoprostanes (p < 0.001), F4-neuroprostanesincreased (p < 0.05), isoketal staining, apoptotic cells and hemorrhages. Decreased collagen-IV staining and VitC content (p < 0.001). | [7] | |
| Dunkin Hartley guinea pigs (6/7 to 60/61days). Postnatal deficiency. | VitC in diet: 923 mg/kg or 100 mg/kg feed. | Asc, DHA, glutathione, MDA and SOD in brain. Quantitation of hippocampal neurons. Functional assessment in MWM. | Decreased performance in MWM (p < 0.05) and reduced number of neurons in hippocampus (p < 0.05) in VitC deficient animals. | [1] | |
| Dunkin Hartley guinea pigs (GD: 18). Prenatal deficiency. | VitC prenatal: 900 mg/kg diet or 100 mg/kg diet. Postnatal: 750 mg/kg or 100 mg/kg. | Asc, DHA and MDA in brain. Hippocampal neurogenesis and volume. Functional assessment in MWM. | Significant and persistent lower hippocampal volume (p < 0.001). | [9] | |
| Dunkin Hartley guinea pigs (2 days to 3 weeks). | VitC in diet: 1036 mg/kg or 36 mg/kg. | Asc, DHA, glutathione, SOD, MDA, α- and γ-tocopherol, protein carbonyls, 8-oxo-deoxyguanosine and base excision repair in brain. | VitC deficiency caused significant reductions in Asc (p < 0.001), DHA (p = 0.034), MDA (p < 0.001) and protein carbonyls (p = 0.003) and an increase in base excision repair (p = 0.014). | [5] | |
| Design and Subjects | Intervention | Measurements | Outcome | Reference | |
| Clinical Studies | |||||
| Cohort Studies | 92 preterm children (7.86 ± 0.7 years, birth weight: 1475.13 ± 556.44 g) 40 age-matched controls. | Cognitive testing: Spatial pattern/Recognition, Intradimensional/Extra Dimensional Set-Shifting task, Tower of London task, Spatial Working Memory task, Spatial Memory Span task, and a Psychomotor screening. | Preterm children had decreased performance in Psychomotor test (p < 0.01), Recognition test (p < 0.01), Spatial Memory Span (p < 0.01), and Spatial Working Memory (p < 0.001) | [90] | |
| 13 IUGR preterm infants (gestational age 33–34 weeks) and 12 controls. | Maternal blood, umbilical cord blood and placental samples: SOD, GSH-Px, MDA, AOP, ADA, CAT and XO. | All markers, except GSH-Px and AOP were elevated in umbilical cord blood. IUGR mothers differed significantly in all markers other than CAT. Placental samples were significantly changed in all markers, except SOD and ADA (p < 0.01 or less). | [96] | ||
| Controlled trials | Randomized clinical trial: 160 women in high risk for pre-eclampsia (16–22 weeks pregnant) and 32 controls. | VitC (1000 mg/day) and VitE (400 IU/day) or placebo. | Plasma VitC, PAI-2, placenta growth factor, 8-epi-prostaglandin F2α, leptin, PAI-1/2 ratio. | Vitamin supplemented: VitC, 8-epi-prostaglandin F2α, leptin, and PAI-1/-2 equal to controls; whereas placebo-treated displayed decreased VitC, PAI-2, and placenta growth factor and increased 8-epi-prostaglandin F2α, leptin, and PAI 1/-2 ratio. | [104] |
| Randomized clinical trial: 283 women with high risk of pre-eclampsia (16–22 weeks pregnant). | VitC (1000 mg/day) and VitE (400 IU/day) or placebo. | PAI-1 and -2 measured every month until delivery. Pre-eclampsia assessed by the development of proteinuric hypertension. | VitC + E supplementation was associated with a decrease in the PAI-1/PAI-2 ratio (p = 0.015) and a significantly decreased risk of pre-eclampsia (p = 0.002). | [107] | |
| Double blind randomized clinical trial: 100 women in high risk of pre-eclampsia (14–20 weeks pregnant). | VitC (1000 mg/day) and VitE (400 IU/day) or placebo. | Incidence of pre-eclampsia. | No significant effect of VitC + E treatment. | [105] | |
| Double blind randomized clinical trial: 1365 women in high risk for pre-eclampsia (14–22 weeks pregnant). | VitC (1000 mg/day) and VitE (400 IU/day) or placebo. | Occurrence of pre-eclampsia defined as hypertension and onset of proteinuria. | Supplementation with VitC + E did not reduce risk of pre-eclampsia. | [106] | |
Abbreviations: VitC, vitamin C; VitE, vitamin E; Asc, ascorbate; DHA, dehydroascorbic acid; PAI, plasminogen activator inhibitor; MDA, malondialdehyde; GSH-Px, glutathione peroxidase; AOP, antioxidant potential; ADA, adenosine deaminase; CAT, catalase; XO, xanthine oxidase; SOD, superoxide dismutase; MVM, Morris Water Maze; IUGR, intrauterine growth restriction; IHC, immunohistochemistry; ED, embryonic day; GD, gestational day; SVCT, sodium-dependent vitamin C transporter.