Life Extension Magazine

Life Extension Magazine November 2006

Abstracts

ADHD

Treatment of ADHD with French maritime pine bark extract, Pycnogenol((R)).

Attention Deficit/Hyperactivity Disorder (ADHD) is the most common psychiatric disorder in children. Pycnogenol((R)), an extract from the bark of the French maritime pine, consisting of phenolic acids, catechin, taxifolin and procyanidins, has shown improvement of ADHD in case reports and in an open study. Aim of the present study was to evaluate the effect of Pycnogenol((R)) on ADHD symptoms. Sixty-one children were supplemented with 1 mg/kg/day Pycnogenol((R)) or placebo over a period of 4 weeks in a randomised, placebo-controlled, doubleblind study. Patients were examined at start of trial, 1 month after treatment and 1 month after end of treatment period by standard questionnaires: CAP (Child Attention Problems) teacher rating scale, Conner’s Teacher Rating Scale (CTRS), the Conner’s Parent Rating Scale (CPRS) and a modified Wechsler Intelligence Scale for children. Results show that 1-month Pycnogenol((R)) administration caused a significant reduction of hyperactivity, improves attention and visual-motoric coordination and concentration of children with ADHD. In the placebo group no positive effects were found. One month after termination of Pycnogenol((R)) administration a relapse of symptoms was noted. Our results point to an option to use Pycnogenol as a natural supplement to relieve ADHD symptoms of children.

Eur Child Adolesc Psychiatry. 2006 May 13

Sleep hygiene and melatonin treatment for children and adolescents with ADHD and initial insomnia.

OBJECTIVE: To evaluate the efficacy of sleep hygiene and melatonin treatment for initial insomnia in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: Twenty-seven stimulant-treated children (6-14 years of age) with ADHD and initial insomnia (>60 minutes) received sleep hygiene intervention. Nonresponders were randomized to a 30-day double-blind, placebo-controlled, crossover trial of 5-mg pharmaceutical-grade melatonin provided by the study’s sponsor. RESULTS: Sleep hygiene reduced initial insomnia to <60 minutes in 5 cases, with an overall effect size in the group as a whole of 0.67. Analysis of the trial data able to be evaluated showed a significant reduction in initial insomnia of 16 minutes with melatonin relative to placebo, with an effect size of 0.6. Adverse events were generally mild and not different from those recorded with placebo treatment. The effect size of the combined sleep hygiene and melatonin intervention from baseline to 90 days’ posttrial was 1.7, with a mean decrease in initial insomnia of 60 minutes. Improved sleep had no demonstrable effect on ADHD symptoms. CONCLUSION: Combined sleep hygiene and melatonin was a safe and effective treatment for initial insomnia in children with ADHD taking stimulant medication.

J Am Acad Child Adolesc Psychiatry. 2006 May;45(5):512-9

Magnesium VitB6 intake reduces central nervous system hyperexcitability in children.

OBJECTIVE: Ionic magnesium (Mg(2+)) depletion has long been known to cause hyperexcitability with convulsive seizures in rodents, effects that have been reversed by treatment with magnesium (Mg). Metabolic disorders and genetic alterations are suspected in this pathology, in which Mg(2+) transport and intracellular distribution may be reduced without change in serum Mg(2+) concentrations. We evaluated the effects of Mg(2+)/vitamin B6 regimen on the behavior of 52 hyperexcitable children (under 15 years of age) and their families. METHODS: To assess intracellular Mg(2+), we measured intra-erthrocyte Mg(2+) levels (ERC-Mg). Our reference values for normal subjects were 2.46 to 2.72 mmol/L. In 30 of the 52 hyperactive children, there were low ERC-Mg values: 2.041 +/- 0.279 mmol/L). Combined Mg(2+)/vitamin B6 intake (100 mg/day) for 3 to 24 weeks restored normal ERC-Mg values (2.329 +/- 0.386 mmol/L). RESULTS: In all patients, symptoms of hyperexcitability (physical aggressivity, instability, scholar attention, hypertony, spasm, myoclony) were reduced after 1 to 6 months treatment. Other family members shared similar symptoms, had low ERC-Mg values, and also responded clinically to increased Mg(2+)/vitamin B6 intakes. Two typical families are described. CONCLUSION: This open study indicates that hyperexcitable children have low ERC-Mg with normal serum Mg(2+) values, and that Mg(2+)/vitamin B6 supplementation can restore normal ERC-Mg levels and improve their abnormal behavior.

J Am Coll Nutr. 2004 Oct;23(5):545S-548S

Effect of MAGNE-B6 on the clinical and biochemical manifestations of the syndrome of attention deficit and hyperactivity in children.

MAGNE-B6 was used for the therapy of a group of 31 children aged from 6 to 12 with attention deficiency and hyperactivity syndrome. The control group included 20 children with similar manifestations of the same pathology, which received a polyvitamin complex. The efficacy of therapy was assessed in the 30th day with the aid of a complex clinical-neuropsychological and biochemical investigations. It was established that the administration of MAGNE-B6 led to improvements in the behavior, decreased the level of anxiety and aggression, improved both large- and small-scale mobility, decreased the level of synkinesis, increased the characteristics of attention, corrected the magnesium homeostasis, and favored normalization of the blood electrolytes. Reliable differences (p < 0.01 or 0.001) between the test and control groups in the degree of expression of the indicated disorders were observed.

Eksp Klin Farmakol. 2006 Jan-Feb;69(1):74-7

Supplementation with flax oil and vitamin C improves the outcome of Attention Deficit Hyperactivity Disorder (ADHD).

Considerable clinical and experimental evidence now supports the idea that deficiencies or imbalances in certain highly unsaturated fatty acids may contribute to a range of common developmental disorders including Attention Deficit Hyperactivity Disorder (ADHD). Few intervention studies with LCPUFA supplementation have reported inconsistent and marginal results. This pilot study evaluates the effect of alpha linolenic acid (ALA)-rich nutritional supplementation in the form of flax oil and antioxidant emulsion on blood fatty acids composition and behavior in children with ADHD. Post-supplementation levels of RBC membrane fatty acids were significantly higher than pretreatment levels as well as the levels in control. There was significant improvement in the symptoms of ADHD reflected by reduction in total hyperactivity scores of ADHD children derived from ADHD rating scale.

Prostaglandins Leukot Essent Fatty Acids. 2006 Jan;74(1):17-21

Effect of the herbal extract combination Panax quinquefolium and Ginkgo biloba on attention-deficit hyperactivity disorder: a pilot study.

OBJECTIVE: A combination herbal product containing American ginseng extract, Panax quinquefolium, (200 mg) and Ginkgo biloba extract (50 mg) (AD-FX; CV Technologies, Edmonton, Alta.) was tested for its ability to improve the symptoms of attention-deficit hyperactivity disorder (ADHD). DESIGN: Open study. PATIENTS: 36 children ranging in age from 3 to 17 years who fit the diagnostic criteria for ADHD. INTERVENTIONS: AD-FX capsules were taken twice a day on an empty stomach for 4 weeks. Patients were instructed not to change any other medications during the study. OUTCOME MEASURES: At the beginning of the study, after 2 weeks, and then at the end of the 4-week trial, parents completed the Conners’ Parent Rating Scale--revised, long version, a questionnaire that assesses a broad range of problem behaviours (and was used as an indication of ADHD symptom severity). RESULTS: After 2 weeks of treatment, the proportion of the subjects exhibiting improvement (i.e., decrease in T-score of at least 5 points) ranged from 31% for the anxious-shy attribute to 67% for the psychosomatic attribute. After 4 weeks of treatment, the proportion of subjects exhibiting improvement ranged from 44% for the social problems attribute to 74% for the Conners’ ADHD index and the DSM-IV hyperactive-impulsive attribute. Five (14%) of 36 subjects reported adverse events, only 2 of which were considered related to the study medication. CONCLUSIONS: These preliminary results suggest AD-FX treatment may improve symptoms of ADHD and should encourage further research on the use of ginseng and ginkgo biloba extracts to treat ADHD symptoms.

J Psychiatry Neurosci. 2001 May;26(3):221-8

Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder.

BACKGROUND: The most commonly used medications for attention deficit hyperactivity disorder (ADHD) are the psychostimulants. There is, however, considerable awareness in alternative, nonstimulant therapies, because some patients respond poorly to stimulants or are unable to tolerate them. Some studies suggest that deficiency of zinc play a substantial role in the aetiopathogenesis of ADHD. Therefore, to assess the efficacy of zinc sulfate we conducted treatment trial. METHODS: Patients with a primary DSM-IV diagnosis of ADHD (N=400; 72 girls, 328 boys, mean age=9.61+/-1.7) were randomly assigned in a 1:1 ratio to 12 weeks of double-blind treatment with zinc sulfate (n=202) (150 mg/day) or placebo (n=198). Efficacy was assessed with the Attention Deficit Hyperactivity Disorder Scale (ADHDS), Conners Teacher Questionnaire, and DuPaul Parent Ratings of ADHD. Primary efficacy variables were differences from baseline to endpoint (last observation carried forward) in mean ADHDS and Conners Teacher Questionnaire scores between the zinc sulfate and the placebo groups. Safety evaluations included monitoring of adverse events, vital signs and clinical laboratory values. RESULTS: Zinc sulfate was statistically superior to placebo in reducing both hyperactive, impulsive and impaired socialization symptoms, but not in reducing attention deficiency symptoms, as assessed by ADHDS. However, full therapeutic response rates of the zinc and placebo groups remained 28.7% and 20%, respectively. It was determined that the hyperactivity, impulsivity and socialization scores displayed significant decrease in patients of older age and high BMI score with low zinc and free fatty acids (FFA) levels. Zinc sulfate was well tolerated and associated with a low rate of side effect. CONCLUSIONS: Zinc monotherapy was significantly superior to placebo in reducing symptoms of hyperactivity, impulsivity and impaired socialization in patients with ADHD. Although by themselves, these findings may not be sufficient, it may well be considered that zinc treatment appears to be an efficacious treatment for ADHD patients having older age and high BMI score with low zinc and FFA levels.

Prog Neuropsychopharmacol Biol Psychiatry. 2004 Jan;28(1):181-90

Effect of randomized supplementation with high dose olive, flax or fish oil on serum phospholipid fatty acid levels in adults with attention deficit hyperactivity disorder.

Dietary intake of omega-3 fatty acids has been positively correlated with cardiovascular and neuropsychiatric health in several studies. The high seafood intake by the Japanese and Greenland Inuit has resulted in low ratios of the omega-6 fatty acid arachidonic acid (AA, 20:4n-6) to eicosapentaenoic acid (EPA, 20:5n-3), with the Japanese showing AA:EPA ratios of approximately 1.7 and the Greenland Eskimos showing ratios of approximately 0.14. It was the objective of this study to determine the effect of supplementation with high doses (60 g) of flax and fish oils on the blood phospholipid (PL) fatty acid status, and AA/EPA ratio of individuals with Attention Deficit Hyperactivity Disorder (ADHD), commonly associated with decreased blood omega-3 fatty acid levels. Thirty adults with ADHD were randomized to 12 weeks of supplementation with olive oil (< 1% omega-3 fatty acids), flax oil (source of alpha-linolenic acid; 18:3n-3; alpha-LNA) or fish oil (source of EPA and docosahexaenoic acid; 22:6n-3; DHA). Serum PL fatty acid levels were determined at baseline and at 12 weeks. Flax oil supplementation resulted in an increase in alpha-LNA and a slight decrease in the ratio of AA/EPA, while fish oil supplementation resulted in increases in EPA, DHA and total omega-3 fatty acids and a decrease in the AA/EPA ratio to values seen in the Japanese population. These data suggest that in order to increase levels of EPA and DHA in adults with ADHD, and decrease the AA/EPA ratio to levels seen in high fish consuming populations, high dose fish oil may be preferable to high dose flax oil. Future study is warranted to determine whether correction of low levels of long-chain omega-3 fatty acids is of therapeutic benefit in this population.

Reprod Nutr Dev. 2005 Sep-Oct;45(5):549-58

The Oxford-Durham study: a randomized, controlled trial of dietary supplementation with fatty acids in children with developmental coordination disorder.

BACKGROUND: Developmental coordination disorder (DCD) affects approximately 5% of school-aged children. In addition to the core deficits in motor function, this condition is associated commonly with difficulties in learning, behavior, and psychosocial adjustment that persist into adulthood. Mounting evidence suggests that a relative lack of certain polyunsaturated fatty acids may contribute to related neurodevelopmental and psychiatric disorders such as dyslexia and attention-deficit/hyperactivity disorder. Given the current lack of effective, evidence-based treatment options for DCD, the use of fatty acid supplements merits investigation. METHODS: A randomized, controlled trial of dietary supplementation with omega-3 and omega-6 fatty acids, compared with placebo, was conducted with 117 children with DCD (5-12 years of age). Treatment for 3 months in parallel groups was followed by a 1-way crossover from placebo to active treatment for an additional 3 months. RESULTS: No effect of treatment on motor skills was apparent, but significant improvements for active treatment versus placebo were found in reading, spelling, and behavior over 3 months of treatment in parallel groups. After the crossover, similar changes were seen in the placebo-active group, whereas children continuing with active treatment maintained or improved their progress. CONCLUSIONS: Fatty acid supplementation may offer a safe efficacious treatment option for educational and behavioral problems among children with DCD. Additional work is needed to investigate whether our inability to detect any improvement in motor skills reflects the measures used and to assess the durability of treatment effects on behavior and academic progress.

Pediatrics. 2005 May;115(5):1360-6

Increased levels of ethane, a non-invasive marker of n-3 fatty acid oxidation, in breath of children with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) comprises a range of behavioural problems including inattention, hyperactivity and impulsivity. Diagnosis and treatment of the disorder is made difficult due to its unknown biological basis. Several studies have identified abnormalities in membrane fatty acids in some subjects with ADHD, and some success has been reported using lipid therapies. We have measured exhalant ethane levels, a non-invasive measure of oxidative damage to n-3 fatty acids, to probe biochemical alterations in ADHD. Patients with ADHD (N = 10) had higher levels of ethane in exhalant than in healthy volunteers (N = 12) with approximately 50% of ADHD cases being above the control range. In contrast, levels of butane, a marker of protein oxidation, were unaltered. Our data, although preliminary, suggests that some patients with ADHD have higher rates of oxidative breakdown of n-3 polyunsaturated fatty acids (PUFAs). Such a biochemical abnormality may underlie the previously observed fatty acid deficiencies, as well as providing further rationale for the use of anti-oxidant and/or lipid supplementation therapy in the treatment of ADHD. Larger studies of ADHD using this non-invasive assessment of oxidative stress appear warranted.

Nutr Neurosci. 2003 Oct;6(5):277-81

Prevalence and correlates of illicit methylphenidate use among 8th, 10th, and 12th grade students in the United States, 2001.

The prevalence and correlates of illicit methylphenidate use were examined within a nationally representative U.S. sample of 8th, 10th, and 12th graders. The annual prevalence of illicit methylphenidate use was 4%. Race, grade level, geographical region, grade point average, and substance use were all significantly associated with illicit methylphenidate use.

J Adolesc Health. 2004 Dec;35(6):501-4

Methylphenidate and dextroamphetamine abuse in substance-abusing adolescents.

The prevalence of methylphenidate and dextroamphetamine misuse and abuse was examined in 450 adolescents referred for substance abuse treatment. Twenty three percent reported nonmedical use of these substances and six percent were diagnosed as methylphenidate or dextroamphetamine abusers. Abuse was more common in individuals who were out of school and had an eating disorder. Methylphenidate and dextroamphetamine abuse appears to be much less common than abuse of most other substances. It does occur, however, and parents and schools need to exert greater control over the dispensing of these medications. Physicians are advised to prescribe non-stimulant medications (eg, bupropion) when treating attention deficit hyperactivity disorder in substance-abusing individuals.

Am J Addict. 2004 Jul-Sep;13(4):381-9