The Presence of Caffeic Acid in Cerebrospinal Fluid: Evidence That Dietary Polyphenols Can Cross the Blood-Brain Barrier in Humans

Abstract

Epidemiological data indicate that a diet rich in plant polyphenols has a positive effect on brain functions, improving memory and cognition in humans. Direct activity of ingested phenolics on brain neurons may be one of plausible mechanisms explaining these data. This also suggests that some phenolics can cross the blood-brain barrier and be present in the brain or cerebrospinal fluid. We measured 12 phenolics (a combination of the solid-phase extraction technique with high-performance liquid chromatography) in cerebrospinal fluid and matched plasma samples from 28 patients undergoing diagnostic lumbar puncture due to neurological disorders. Homovanillic acid, 3-hydroxyphenyl acetic acid and caffeic acid were detectable in cerebrospinal fluid reaching concentrations (median; interquartile range) 0.18; 0.14 µmol/L, 4.35; 7.36 µmol/L and 0.02; 0.01 µmol/L, respectively. Plasma concentrations of caffeic acid (0.03; 0.01 µmol/L) did not correlate with those in cerebrospinal fluid (ρ = −0.109, p = 0.58). Because food (fruits and vegetables) is the only source of caffeic acid in human body fluids, our results indicate that the same dietary phenolics can cross blood-brain barrier in humans, and that transportation of caffeic acid through this barrier is not the result of simple or facilitated diffusion.

Polyphenol Rich Ajuga bracteosa Transgenic Regenerants Display Better Pharmacological Potential

“…Interestingly, a recent study demonstrated the presence of non-endogenous caffeic acid in the human CSF. These studies confirm that plant phenolics can cross the BBB in humans and reach the neurons and microglia [42]. However, the exact mechanisms by which they may permeate the BBB are not fully understood.…”

Dietary Phenolic Acids and Their Major Food Sources Are Associated with Cognitive Status in Older Italian Adults

“…Phenolic acids have been shown to modulate different factors associated with the pathogenesis of neurodegenerative diseases, such as systemic inflammation and oxidative stress, and thus indirectly affect cognitive health [ 40 ]. As suggested by the evidence from experimental studies, specific phenolic acids and their metabolites (i.e., caffeic acid, ferulic acid) have been found in cerebrospinal fluid, suggesting that these compounds may cross the blood–brain barrier and thus directly affect brain cells [ 41 , 42 ]. Moreover, new evidence suggests that there is an interaction between dietary polyphenols and gut microbiota and their effect toward the brain [ 43 , 44 ]: it has been determined that gut microbiota composition significantly affects the bioavailability of polyphenols including phenolic acids and consequently may mediate and modulate the effect of dietary polyphenols toward cognitive health [ 45 , 46 ].…”

Erythronium japonicum Alleviates Inflammatory Pain by Inhibiting MAPK Activation and by Suppressing NF-κB Activation via ERK/Nrf2/HO-1 Signaling Pathway

“…Additionally, chlorogenic acid was maintained in plasma and entered the CNS following intravenous injection in rats [52]. In a clinical study, individuals who had consumed foods containing caffeic acid showed increased caffeic acids levels in the CNS crossing the blood-brain barrier [53]. However, it remains unclear which bioactive component(s) with anti-microglial activation effects are present in the butanol fraction of EJE.…”