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

<p><strong>Objective</strong>: 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.</p> <p><strong>Methods</strong>: 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.</p> <p><strong>Results</strong>: In the peripheral circulation, positive associations were observed between plasma folate and Cbl, and plasma TAC (<em>P</em> ≤ 0.01; <em>P</em> ≤ 0.01) and plasma NAD(H) (<em>P</em> ≤ 0.05; <em>P</em> ≤ 0.05) levels, respectively. Plasma folate was inversely associated with plasma Hcy concentrations (<em>P</em> ≤ 0.05); however, no statistically significant relationships were observed between plasma Hcy and plasma markers of inflammation, oxidative stress, or [NAD(H)].</p> <p>Within the CNS plasma Hcy correlated positively with CSF IL-6 (<em>P</em> ≤ 0.01) and negatively with CSF NAD(H) (<em>P</em> ≤ 0.05) concentrations. An inverse association was observed between CSF folate and CSF levels of IL-6 (<em>P</em> ≤ 0.05). Unexpectedly, a positive association between CSF Cbl and CSF 8-OHdG levels was also found (<em>P</em> ≤ 0.01).</p> <p><strong>Discussion</strong>: 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.</p>