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3. Urinary catecholamines in children with attention deficit hyperactivity
disorder (ADHD): modulation by a polyphenolic extract from pine bark
(pycnogenol)
Dvoráková M et al.
Nutr Neurosci. 2007 Jun-Aug;10(3-4):151-7.
Our study tested the hypothesis that treatment with a potent polyphenol
complex not only reduces hyperactivity of children, but also
catecholamine excretion and oxidative stress. Urine catecholamine
concentrations were measured in attention deficit hyperactivity
disorder (ADHD) children and healthy controls. ADHD children received
either placebo (PL) or Pycnogenol (Pyc), a bioflavonoid extract from
the pine bark, for one month. The study was performed in a randomized,
double-blind, PL controlled design. Concentrations of catecholamines
were higher in urine of ADHD patients compared to those of healthy
children. Moreover, noradrenaline (NA) concentrations positively
correlated with degree of hyperactivity of ADHD children. In ADHD
patients, adrenaline (A) and NA concentrations positively correlated
with plasma levels of oxidized glutathione. The treatment of ADHD
children with Pyc caused decrease of dopamine (D) and trend of A and NA
decrase and increased GSH/GSSG ratio. In conclusion, the data provide
further evidence for the overactivity of the noradrenergic system in
ADHD and demonstrate that A release may be increased, as well.
Treatment of ADHD children with Pyc normalized catecholamine
concentrations, leading to less hyperactivity, and, consequently, to
reduced oxidative stress.
PMID: 18019397
4. The effect of polyphenolic extract from pine bark, Pycnogenol on the
level of glutathione in children suffering from attention deficit
hyperactivity disorder (ADHD)
Dvoráková M, Sivonová M, Trebatická J, Skodácek I, Waczuliková I, Muchová J, Duracková Z.
Redox Rep. 2006;11(4):163-72.
Attention deficit hyperactivity disorder (ADHD) belongs to the
neurodevelopmental disorders characterized by impulsivity,
distractibility and hyperactivity. In the pathogenesis of ADHD genetic
and non-genetic factors play an important role. It is assumed that one
of non-genetic factors should be oxidative stress. Pycnogenol, an
extract from the pine bark, consists of bioflavonoids, catechins,
procyanidins and phenolic acids. Pycnogenol acts as powerful
antioxidant, chelating agent; it stimulates the activities of some
enzymes, like SOD, eNOS, and exhibits other biological activities. AIM:
The aim of this randomized, double-blind, placebo-controlled trial was
to investigate the influence of administered Pycnogenol or placebo on
the level of reduced (GSH) and oxidized (GSSG) glutathione in children
suffering from ADHD and on total antioxidant status (TAS). This is the
first investigation of the redox glutathione state in relation to ADHD.
RESULTS: One month of Pycnogenol administration (1 mg/kg body
weight/day) caused a significant decrease in GSSG and a highly
significant increase in GSH levels as well as improvement of GSH/GSSG
ratio in comparison to a group of patients taking a placebo. TAS in
children with ADHD was decreased in comparison with reference values.
Pycnogenol administration normalizes TAS of ADHD children.
PMID: 16984739
5. Omega-3 fatty acid status in attention-deficit/hyperactivity disorder
Antalis CJ, Stevens LJ, Campbell M, Pazdro R, Ericson K, Burgess JR.
Prostaglandins Leukot Essent Fatty Acids. 2006 Oct-Nov;75(4-5):299-308.
Lower levels of long-chain polyunsaturated fatty acids, particularly
omega-3 fatty acids, in blood have repeatedly been associated with a
variety of behavioral disorders including
attention-deficit/hyperactivity disorder (ADHD). The exact nature of
this relationship is not yet clear. We have studied children with ADHD
who exhibited skin and thirst symptoms classically associated with
essential fatty acid (EFA) deficiency, altered plasma and red blood
cell fatty acid profiles, and dietary intake patterns that do not
differ significantly from controls. This led us to focus on a potential
metabolic insufficiency as the cause for the altered fatty acid
phenotype. Here we review previous work and present new data expanding
our observations into the young adult population. The frequency of
thirst and skin symptoms was greater in newly diagnosed individuals
with ADHD (n = 35) versus control individuals without behavioral
problems (n = 112) drawn from the Purdue student population. A follow
up case-control study with participants willing to provide a blood
sample, a urine sample, a questionnaire about their general health, and
dietary intake records was conducted with balancing based on gender,
age, body mass index, smoking and ethnicity. A number of biochemical
measures were analyzed including status markers for several nutrients
and antioxidants, markers of oxidative stress, inflammation markers,
and fatty acid profiles in the blood. The proportion of omega-3 fatty
acids was found to be significantly lower in plasma phospholipids and
erythrocytes in the ADHD group versus controls whereas saturated fatty
acid proportions were higher. Intake of saturated fat was 30% higher in
the ADHD group, but intake of all other nutrients was not different.
Surprisingly, no evidence of elevated oxidative stress was found based
on analysis of blood and urine samples. Indeed, serum ferritin,
magnesium, and ascorbate concentrations were higher in the ADHD group,
but iron, zinc, and vitamin B6 were not different. Our brief survey of
biochemical and nutritional parameters did not give us any insight into
the etiology of lower omega-3 fatty acids, but considering the
consistency of the observation in multiple ADHD populations continued
research in this field is encouraged.
PMID: 16962757
6. Oxidative stress in psychiatric disorders: evidence base and therapeutic implications
Ng F, Berk M, Dean O, Bush AI.
Int J Neuropsychopharmacol. 2008 Jan 21:1-26.
Oxidative stress has been implicated in the pathogenesis of diverse
disease states, and may be a common pathogenic mechanism underlying
many major psychiatric disorders, as the brain has comparatively
greater vulnerability to oxidative damage. This review aims to examine
the current evidence for the role of oxidative stress in psychiatric
disorders, and its academic and clinical implications. A literature
search was conducted using the Medline, Pubmed, PsycINFO, CINAHL PLUS,
BIOSIS Previews, and Cochrane databases, with a time-frame extending to
September 2007. The broadest data for oxidative stress mechanisms have
been derived from studies conducted in schizophrenia, where evidence is
available from different areas of oxidative research, including
oxidative marker assays, psychopharmacology studies, and clinical
trials of antioxidants. For bipolar disorder and depression, a solid
foundation for oxidative stress hypotheses has been provided by
biochemical, genetic, pharmacological, preclinical therapeutic studies
and one clinical trial. Oxidative pathophysiology in anxiety disorders
is strongly supported by animal models, and also by human biochemical
data. Pilot studies have suggested efficacy of N-acetylcysteine in
cocaine dependence, while early evidence is accumulating for oxidative
mechanisms in autism and attention deficit hyperactivity disorder. In
conclusion, multi-dimensional data support the role of oxidative stress
in diverse psychiatric disorders. These data not only suggest that
oxidative mechanisms may form unifying common pathogenic pathways in
psychiatric disorders, but also introduce new targets for the
development of therapeutic interventions.
PMID: 18205981
7. ADHD, Genes & Environment.
8. ADHD & Environment.
9. Pollutants and oxidative stress: Autism Research Institute.
10. Air particulates, Diesel exhaust, Human brain: Oxidative stress: Autism Research Institute.
11. Pollutants in Placenta, Cord Blood, and Breast Milk of Humans: Autism Research Institute
12. Antioxidant enzyme activities following acute or chronic methylphenidate treatment in young rats
Gomes KM et al.
Neurochem Res. 2008 Jun;33(6):1024-7. Epub 2007 Nov 30.
Methylphenidate (MPH) is psychostimulants used to treat
Attention-Deficit/Hyperactivity Disorder and can lead to a long-lasting
neurochemical and behavioral adaptations in experimental animals. In
the present study, the cerebral antioxidant enzymatic system,
superoxide dismutase (SOD) and catalase (CAT) was evaluated at in
different age following MPH (1, 2 or 10 mg/kg MPH, i.p.) treatment in
young rats. In the acute treatment the SOD activity decreased in the
cerebral prefrontal cortex with opposite effect in the cerebral cortex;
and the CAT activity decreased in hippocampus. In the chronic treatment
the SOD activity increased in the hippocampus and cerebral cortex and
decreased in the striatum. The observed changes on the enzyme
activities in rat brain were dependent on the structure brain region
and duration of treatment with MPH. Probably, the activity of enzymes
was not be enough to prevent MPH-induced oxidative damage in specific
regions from brain, such as observed for us in another recent study.
PMID: 18049893
13. A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology
Rohdewald P.
Int J Clin Pharmacol Ther. 2002 Apr;40(4):158-68.
OBJECTIVES: An increasing body of evidence indicates that Pycnogenol
(PYC), a standardized extract of French maritime pine bark, has
favorable pharmacological properties. This is a review of studies with
both PYC and components of the preparation, that have helped to
elucidate target sites and possible mechanisms for activity in men.
METHODS: Studies appearing in peer reviewed literature, as well as
results presented at international meetings not yet available as
published papers, are included in this review. Additional data from
published sources in German and French languages that are not widely
available are also included. RESULTS: Chemical identification studies
showed that PYC is primarily composed of procyanidins and phenolic
acids. Procyanidins are biopolymers of catechin and epicatechin
subunits which are recognized as important constituents in human
nutrition. PYC contains a wide variety of procyanidins that range from
the monomeric catechin and taxifolin to oligomers with 7 or more
flavonoid subunits. The phenolic acids are derivatives of benzoic and
cinnamic acids. The ferulic acid and taxifolin components are rapidly
absorbed and excreted as glucuronides or sulphates in men, whereas
procyanidins are absorbed slowly and metabolized to valerolactones
which are excreted as glucuronides. PYC has low acute and chronic
toxicity with mild unwanted effects occurring in a small percentage of
patients following oral administration. Clinical studies indicate that
PYC is effective in the treatment of chronic venous insufficiency and
retinal micro-hemorrhages. PYC protects against oxidative stress in
several cell systems by doubling the intracellular synthesis of
anti-oxidative enzymes and by acting as a potent scavenger of free
radicals. Other anti-oxidant effects involve a role in the regeneration
and protection of vitamin C and E. Anti-inflammatory activity has been
demonstrated in vitro and in vivo in animals. Protection against
UV-radiation-induced erythema was found in a clinical study following
oral intake of PYC. In asthma patients symptom scores and circulating
leukotrienes are reduced and lung function is improved.
Immunomodulation has been observed in both animal models as well as in
patients with Lupus erythematosus. PYC antagonizes the vasoconstriction
caused by epinephrine and norepinephrine by increasing the activity of
endothelial nitric oxide synthase. Dilation of the small blood vessels
has been observed in patients with cardiovascular disease, whereas in
smokers, PYC prevents smoking-induced platelet aggregation and reduces
the concentration of thromboxane. The ability to inhibit
angiotensin-converting enzyme is associated with a mild
antihypertensive effect. PYC relieves premenstrual symptoms, including
abdominal pain and this action may be associated with the spasmolytic
action of some phenolic acids. An improvement in cognitive function has
been observed in controlled animal experiments and these findings
support anecdotal reports of improvement in ADHD patients taking PYC
supplements. CONCLUSIONS: There is much evidence showing that PYC has
beneficial effects on physiological functions. Results from ongoing
clinical research are required to confirm and extend previous
observations.
PMID: 11996210
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