Effect of Pycnogenol® on attention-deficit hyperactivity disorder (ADHD) : study protocol for a randomised controlled trial

Background: Methylphenidate (MPH), the first choice medication for attention-deficit hyperactivity disorder (ADHD), is associated with serious adverse effects like arrhythmia. Evidence on the association of ADHD with immune and oxidant-antioxidant imbalances offers potential for antioxidant and/or immunomodulatory nutritional supplements as ADHD therapy. One small randomised trial in ADHD suggests, despite various limitations, therapeutic benefit from Pycnogenol (R), a herbal, polyphenol-rich extract. Methods: This phase III trial is a 10-week, randomised, double-blind, placebo and active treatment controlled multicentre trial with three parallel treatment arms to compare the effect of Pycnogenol r to MPH and placebo on the behaviour of 144 paediatric ADHD and attention-deficit disorder (ADD) patients. Evaluations of behaviour (measured by the ADHDRating Scale (primary endpoint) and the Social-emotional Questionnaire (SEQ)), immunity (plasma cytokine and antibody levels, white blood cell counts and faecal microbial composition), oxidative stress (erythrocyte glutathione, plasma lipid-soluble vitamins and malondialdehyde and urinary 8-OHdG levels, as well as antioxidant enzyme activity and gene expression), serum zinc and neuropeptide Y level, urinary catecholamines and physical complaints (Physical Complaints Questionnaire) will be performed in week 10 and compared to baseline. Acceptability evaluations will be based on adherence, dropouts and reports of adverse events. Dietary habits will be taken into account. Discussion: This trial takes into account comorbid behavioural and physical symptoms, as well as a broad range of innovative immune and oxidative biomarkers, expected to provide fundamental knowledge on ADHD aetiology and therapy. Research on microbiota in ADHD is novel. Moreover, the active control arm is rather unseen in research on nutritional supplements, but of great importance, as patients and parents are often concerned with the side effects of MPH

Dietary polyphenols targeting arterial stiffness : Interplay of contributing mechanisms and gut microbiome-related metabolism

Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.Increased arterial stiffness is a degenerative vascular process, progressing with age that leads to a reduced capability of arteries to expand and contract in response to pressure changes. This progressive degeneration mainly affects the extracellular matrix of elastic arteries and causes loss of vascular elasticity. Recent studies point to significant interference of dietary polyphenols with mechanisms involved in the pathophysiology and progression of arterial stiffness. This review summarizes data from epidemiological and interventional studies on the effect of polyphenols on vascular stiffness as an illustration of current research and addresses possible etiological factors targeted by polyphenols, including pathways of vascular functionality, oxidative status, inflammation, glycation, and autophagy. Effects can either be inflicted directly by the dietary polyphenols or indirectly by metabolites originated from the host or microbial metabolic processes. The composition of the gut microbiome, therefore, determines the resulting metabolome and, as a consequence, the observed activity. On the other hand, polyphenols also influence the intestinal microbial composition, and therefore the metabolites available for interaction with relevant targets. As such, targeting the gut microbiome is another potential treatment option for arterial stiffness.publishersversionPeer reviewe

Selenium Status in Elderly People: Longevity and Age-Related Diseases

International audienc

Can Biomarkers of Oxidative Stress in Serum Predict Disease Severity in West Nile Virus Infection? A Pilot Study

West Nile virus (WNV) can cause asymptomatic infection in humans, result in self-limiting febrile illness, or lead to severe West Nile Neuroinvasive disease (WNND). We conducted a pilot study to compare selected biomarkers of oxidative stress in sera of viremic West Nile virus patients and asymptomatic infected blood donors to investigate their potential as predictors of disease severity. We found that total oxidant status was elevated in WNND and in uncomplicated WNV infections (median 9.05 (IQR 8.37 to 9.74) and 7.14 (7.03 to 7.25) µmol H2O2 equiv./L, respectively) compared to asymptomatic infections (0.11 (0.07 to 0.19) µmol H2O2 equiv./L) (p = 0.048). MDA levels showed a similar trend to TOS, but differences were not significant at α = 0.05. Total antioxidant status did not differ significantly between different disease severity groups. Oxidative stress appears to be associated with more severe disease in WNV-infected patients. Our preliminary findings warrant prospective studies to investigate the correlation of oxidative stress with clinical outcomes and severity of WNV infection

Additional file 1: of A red yeast rice-olive extract supplement reduces biomarkers of oxidative stress, OxLDL and Lp-PLA2, in subjects with metabolic syndrome: a randomised, double-blind, placebo-controlled trial

Consolidated Standards of Reporting Trials (CONSORT) checklist. (DOC 219 kb

Additional file 1: of Effect of PycnogenolÂŽ on attention-deficit hyperactivity disorder (ADHD): study protocol for a randomised controlled trial

SPIRIT 2013 Checklist: recommended items to address in a clinical trial protocol and related documents*. (DOCX 100 kb

Clinical Investigation of French Maritime Pine Bark Extract on Attention-Deficit Hyperactivity Disorder as compared to Methylphenidate and Placebo : Part 1: Efficacy in a Randomised Trial

Objectives: Determine the effect of French Maritime Pine Bark Extract (PBE; Pycnogenol®) on Attention-Deficit Hyperactivity Disorder (ADHD) behaviour and co-morbid physical/psychiatric symptoms, compared to placebo and the medicine MPH, and to assess its tolerability. Behaviour (measured by the ADHD-Rating Scale (ADHD-RS) and Social-Emotional Questionnaire (SEQ)) and physical complaints were evaluated in weeks 5 and 10. Results: Eighty-eight paediatric ADHD patients (70 % male, mean age 10.1 years) were randomised to placebo (n = 30), PBE (n = 32) or MPH (n = 26). Teachers reported significant improvement of total and hyperactivity/impulsivity ADHD-RS scores by PBE and MPH after 10 weeks compared to placebo. MPH also improved inattention. SEQ ratings support ADHD-RS results. Adverse effects were reported five times more frequently for MPH than for PBE. Conclusions: PBE appears a good alternative for MPH in paediatric ADHD and especially in the primary school environment, a fortiori when considering its almost complete lack of adverse effects

Clinical Investigation of French Maritime Pine Bark Extract on Attention-Deficit Hyperactivity Disorder as compared to Methylphenidate and Placebo : Part 2: Oxidative Stress and Immunological Modulation

Objectives: To evaluate the effect of French Maritime Pine Bark Extract (PBE; Pycnogenol®) on immune, oxidative stress and neurochemical biomarkers in paediatric Attention-Deficit Hyperactivity Disorder (ADHD) as compared to methylphenidate (MPH) and placebo. Results: Paediatric ADHD patients (n = 88, 70 % male, mean age 10.1 years) were randomised (placebo (n = 30), PBE (n = 32) and MPH (n = 26)) receiving 20 mg/day if < 30 kg or 40 mg/day if ≥ 30 kg PBE, or 20 mg/day if < 30 kg or 30 mg/day if ≥ 30 kg MPH for 10 weeks. In the oxidative stress pathway, catalase (CAT) activity was nominally significant different in the PBE group with a p-value of 0.025 whereas the immunity biomarkers IgA and IgG2 were nominally significant different after MPH treatment with a p-value of 0.028 and 0.017 respectively, compared to baseline. Serum Neuropeptide Y (NPY) levels and weight were significantly lower after 10-weeks MPH. Conclusions: Loss of appetite and weight loss was observed for MPH, whereas no differences in NPY concentrations and a significant weight gain, which is to be an expected physiological process in this age group, was noticed for PBE. Firm evidence that PBE increases antioxidant levels, reduces oxidative damage and improves immune status in general as compared to placebo or MPH could not be obtained