Novel relationships between B12, folate and markers of inflammation, oxidative stress and NAD(H) levels, systemically and in the CNS of a healthy human cohort

Abstract

Objective: To evaluate the relationship between folate, cobalamin (Cbl), and homocysteine (Hcy), and markers of inflammation and oxidative stress within the periphery and central nervous system (CNS) of a healthy human cohort.

Methods: Thirty-five matched cerebrospinal fluid (CSF) and plasma samples were collected from consenting participants who required a spinal tap for the administration of anaesthetic. Plasma concentrations of Hcy and both plasma and CSF levels of folate, Cbl, nicotinamide adenine dinucleotide (NAD(H)) and markers of inflammation (interleukin-6, IL-6), and oxidative stress (F₂-isoprostanes, 8-hydroxy-2′-deoxyguanosine (8-OHdG), and total antioxidant capacity (TAC)) were quantified.

Results: In the peripheral circulation, positive associations were observed between plasma folate and Cbl, and plasma TAC (P ≤ 0.01; P ≤ 0.01) and plasma NAD(H) (P ≤ 0.05; P ≤ 0.05) levels, respectively. Plasma folate was inversely associated with plasma Hcy concentrations (P ≤ 0.05); however, no statistically significant relationships were observed between plasma Hcy and plasma markers of inflammation, oxidative stress, or [NAD(H)].

Within the CNS plasma Hcy correlated positively with CSF IL-6 (P ≤ 0.01) and negatively with CSF NAD(H) (P ≤ 0.05) concentrations. An inverse association was observed between CSF folate and CSF levels of IL-6 (P ≤ 0.05). Unexpectedly, a positive association between CSF Cbl and CSF 8-OHdG levels was also found (P ≤ 0.01).

Discussion: These results indicate that folate and Cbl concentrations may influence the levels of oxidative damage, inflammation, and NAD(H), both systemically and within the CNS.

Keywords:

• Cobalamin
• Folate
• Homocysteine
• Inflammation
• Oxidative stress
• Nicotinamide adenine dinucleotide
• Central nervous system
• Brain

Acknowledgements

This study was supported by a grant to R.G. and J.G. from the BUPA Health Foundation. The authors thank the anaesthetists of Sydney Adventist Hospital who kindly assisted in the collection of all samples.

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Contributors

J.G.: Study design, participant recruitment, sample collection/analysis, data analysis, and manuscript preparation. A.B.: Data analysis and manuscript revision. B.H.: Sample analysis, data analysis, and manuscript revision. T.M.: Sample analysis and manuscript revision. K.C.: Sample analysis and manuscript revision. R.G.: Study design, sample analysis, study supervision, and manuscript preparation.

Funding

None.

Conflicts of interest

There are no conflicts of interest.

Ethics approval

This study was conducted in accordance with the Helsinki declaration. Ethical approval was obtained from the Human Research Ethics Committee, Sydney Adventist Hospital (EC00141, project number 2011-005).