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

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.

Salivary and plasma native and non-urate total antioxidant capacity versus oral health status in older non-smoking adults.

OBJECTIVE: The aim of this study was to evaluate the salivary C-reactive protein and native and non-urate total antioxidant capacity (TAC) of saliva and plasma in relation to various oral health status indexes in older non-smoking adults. DESIGN: Oral health status indices involved the Decayed, Missing, Filled Teeth index, the number of decayed teeth, Approximal Plaque Index, Plaque Index and Community Periodontal Index with Treatment Needs. Sixty older patients (67.0 ± 4.5 years) with different levels of oral health were examined. Salivary C-reactive protein was assessed. The Ferric Reducing Ability of Saliva/Plasma (FRAS/FRAP) and 2.2-diphenyl-1-picryl-hydrazyl test of saliva/plasma (DPPHS/DPPH) were used to assess the native and non-urate salivary (FRAS, non-urate FRAS, DPPHS, non-urate DPPHS, and plasma TAC (FRAP, non-urate FRAP, DPPH, non-urate DPPH). RESULTS: Salivary C-reactive protein, native TAC and non-urate TAC did not correspond to any oral health status index. No relation was found for plasma native and non-urate TAC either. In multivariate analyses, age was the only independent predictor of DPPHS and salivary uric acid (p < 0.05) while non-urate DPPH was only negatively predicted by Body Mass Index (p < 0.001). None of oral health status indices was selected as an independent predictor of salivary and plasma TAC or C-reactive protein of saliva. CONCLUSION: Oral health status indexes did not appear to influence the native or the non-urate local antioxidant status of saliva, or the systemic antioxidant status of plasma; they had no local effect related to salivary C-reactive protein. However, lower plasma non-urate antioxidant potential was related to overweight/obesity.

Plasma and Salivary Non-Urate Total Antioxidant Capacity Does Not Depend on Dietary Vitamin C, E, or ß-Carotene Intake in Older Subjects.

The native Total Antioxidant Capacity (TAC) of plasma and saliva is generally determined by uric acid (UA). Several studies have assessed the impact of habitual dietary antioxidative vitamin intake on TAC, but it remains unknown whether it influences Non-Urate Total Antioxidant Capacity (Nu-TAC), i.e., TAC after enzymatic UA elimination. The purpose of this study was to assess whether the intake of antioxidative vitamins C, E, and ß-carotene, provided with usual daily food rations, affects plasma and salivary Nu-TAC. The study involved 56 older subjects (aged 66.9 ± 4.3 years), divided into two age- and sex-matched groups: group 1 (n = 28), with lower combined vitamin C, E, and ß-carotene intake, and group 2 (n = 28), with higher intake. A 24 h dietary recall was obtained from each individual. Nu-TAC was assessed simultaneously with two methods in plasma (Ferric Reducing Ability of Plasma­Nu-FRAP, 2.2-diphenyl-1-picryl-hydrazyl­Nu-DPPH) and in saliva (Nu-FRAS and Nu-DPPHS test). No differences were found in the Nu-TAC parameters between the groups, either in plasma (Nu-FRAP, Nu-DPPH) or in saliva (Nu-FRAS, Nu-DPPHS) (p > 0.05). No plasma or salivary Nu-TAC indices correlated with dietary vitamin C, E, or ß-carotene intake or with other nutrients. Habitual, not extra-supplemented dietary intake does not significantly affect plasma or salivary Nu-TAC.

Hemodialysis Decreases the Concentration of Accumulated Plant Phenols in the Plasma of Patients on Maintenance Dialysis: Influence of Residual Renal Function.

Plant phenols may accumulate in end-stage kidney disease. The effect of hemodialysis on their plasma concentration remains poorly determined. Contingent on concentration, health-promoting or noxious effects occur; therefore, we assessed plasma concentration in hemodialyzed patients. In total, 21 maintenance hemodialyzed patients with diuresis < 500 mL per day (with oliguria), nine hemodialyzed patients with diuresis ≥ 500 mL per day (without oliguria) and 31 healthy volunteers were included. Nine phenolic acids were identified with high-performance liquid chromatography and total polyphenol concentration was determined with the Folin-Ciocalteu method in pre- or post-hemodialysis plasma and pre- or intra-hemodialysis dialysate. The concentration of total polyphenols was 27% higher in pre-hemodialysis plasma than in that of controls (0.95 ± 0.18 mmol/L [P < 0.0001]). The concentration of total polyphenols was higher in patients with oliguria (1.01 ± 0.17) than in those without (0.84 ± 0.13 mmol/L), despite the former having more intense hemodialysis (Kt/V 1.29 ± 0.31 and 0.77 ± 0.25, respectively). Pre-hemodialysis phenolic acid concentration in patients undergoing dialysis exceeded reference values by 3 to 34 times (3-hydroxyphenylacetic acid and vanillic acid, respectively), from 0.69 (dihydrocaffeic acid) to 169.3 µmol/L (hippuric acid). The concentration of six phenolic acids (3-hydroxyhippuric, caffeic, dihydrocaffeic, hippuric, homovanillic, and vanillic acid) was 1.1 (homovanillic) to 11.3 (3-hydroxyhippuric) times higher in patients with oliguria than in those without. 4-hydroxyhippuric acid occurred more in the plasma of patients with oliguria than in those without oliguria. A single hemodialysis session decreased total polyphenol concentration by 16% and phenolic acids from 30% (caffeic) to 58% (vanillic and 3-hydroxyphenylacetic acid) and these compounds appeared in the dialysate. The percentage decrease (Δ%) of creatinine concentration correlated with the Δ% of total polyphenols and five phenolic acids (3-hydroxyphenylacetic, dihydrocaffeic, hippuric, homovanillic, and vanillic acid). Urea Δ% and Kt/V correlated only with the Δ% of homovanilic acid. The results demonstrate that phenols accumulate variably in hemodialyzed patients and are differently eliminated during hemodialysis. Residual renal function ensures a lower concentration of plasma phenols.

Dietary Vitamin C, E and ß-Carotene Intake Does Not Significantly Affect Plasma or Salivary Antioxidant Indices and Salivary C-Reactive Protein in Older Subjects.

It is not clear whether habitual dietary intake influences the antioxidant or inflammatory status. The aim of the present study was to assess the impact of antioxidative vitamins C, E, and ß-carotene obtained from daily food rations on plasma and salivary Total Antioxidant Capacity (TAC), uric acid and salivary C-reactive protein (CRP). The study involved 80 older subjects (66.9 ± 4.3 years), divided into two groups: group 1 (n = 43) with lower and group 2 (n = 37) with higher combined vitamins C, E and ß-carotene intake. A 24-h dietary recall was obtained from each individual. TAC was assessed simultaneously with two methods in plasma (Ferric Reducing Ability of Plasma-FRAP, 2.2-diphenyl-1-picryl-hydrazyl-DPPH) and in saliva (FRAS and DPPHS test). Lower vitamin C intake corresponded to higher FRAS. There were no other correlations between vitamins C, E or ß-carotene intake and antioxidant indices. Salivary CRP was not related to any antioxidant indices. FRAS was decreased in group 2 (p < 0.01) but no other group differences for salivary or for plasma antioxidant parameters and salivary CRP were found. Habitual, not extra supplemented dietary intake does not significantly affect plasma or salivary TAC and salivary CRP.

Addition of strawberries to the usual diet increases postprandial but not fasting non-urate plasma antioxidant activity in healthy subjects.

Strawberries can augment plasma antioxidant activity, but this may be confounded by selection of methods, time of blood sampling and concomitant dietary restrictions. We examined the effect of strawberry consumption on ferric reducing ability (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (DPPH-test) of native and non-urate plasma in healthy subjects on their usual diet. Eleven subjects consumed strawberries (500 g daily) for 9 days. Fasting and 3-h postprandial plasma and 24-h urine collection were obtained before, during and after strawberry course for FRAP, DPPH-test and polyphenols determination. Fifteen subjects served as a control in respect to plasma antioxidant activity changes and effect of 300 mg of oral ascorbate. First, 5th and 9th strawberry dose increased 3-h postprandial DPPH-test by 17.4, 17.6 and 12.6%, and FRAP by 15.5, 25.6 and 21.4% in comparison to fasting values in non-urate plasma (p<0.05). In native plasma only a trend was observed to higher postprandial values for both tests. Strawberries increased urinary urolithin A and 4-hydroxyhippuric acid whereas plasma polyphenols were stable. No changes of FRAP and DPPH-test were noted in controls and after ascorbate intake. Strawberries transiently increased non-urate plasma antioxidant activity but this cannot be attributed to direct antioxidant effect of polyphenols and ascorbate.

Consumption of strawberries on a daily basis increases the non-urate 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging activity of fasting plasma in healthy subjects.

Strawberries contain anthocyanins and ellagitanins which have antioxidant properties. We determined whether the consumption of strawberries increase the plasma antioxidant activity measured as the ability to decompose 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) in healthy subjects. The study involved 10 volunteers (age 41 ± 6 years, body weight 74.4 ± 12.7 kg) that consumed 500 g of strawberries daily for 9 days and 7 matched controls. Fasting plasma and spot morning urine samples were collected at baseline, during fruit consumption and after a 6 day wash-out period. DPPH decomposition was measured in both deproteinized native plasma specimens and pretreated with uricase (non-urate plasma). Twelve phenolics were determined with HPLC. Strawberries had no effect on the antioxidant activity of native plasma and circulating phenolics. Non-urate plasma DPPH decomposition increased from 5.7 ± 0.6% to 6.6 ± 0.6%, 6.5 ± 1.0% and 6.3 ± 1.4% after 3, 6 and 9 days of supplementation, respectively. The wash-out period reversed this activity back to 5.7 ± 0.8% (p<0.01). Control subjects did not reveal any changes of plasma antioxidant activity. Significant increase in urinary urolithin A and 4-hydroxyhippuric (by 8.7- and 5.9-times after 6 days of supplementation with fruits) was noted. Strawberry consumption can increase the non-urate plasma antioxidant activity which, in turn, may decrease the risk of systemic oxidants overactivity.