gamma-linolenic-acid and Attention-Deficit-Disorder-with-Hyperactivity

Concerns about growth retardation and unknown effects on long-term brain development with stimulants have prompted interest in polyunsaturated fatty acid supplementation (PUFA) as an alternative treatment. However, randomized controlled trials (RCTs) and meta-analyses of PUFA supplementation in ADHD have shown marginal benefit, and uncertainty exists as to which, if any, PUFA might be effective in alleviating symptoms of ADHD. We conducted an updated meta-analysis of RCTs in ADHD together with multivariable meta-regression analyses using data on PUFA content obtained from independent fatty acid methyl ester analyses of each study PUFA regimen. The PubMed, Embase and PsycINFO databases were searched with no start date and up to 28th July 2013. Study inclusion criteria were: randomized design, placebo controlled, PUFA preparation as active intervention, reporting change scores on ADHD rating-scale measures. Rating-scale measures of inattention and hyperactive-impulsive symptoms were extracted, study authors were contacted to obtain missing data, studies not reporting negative findings had these data imputed, and study quality was assessed using the Jadad system plus other indicators. Random-effects models were used for pooled effects and for meta-regression analyses. Standardized mean differences (SMD) in inattention, hyperactive-impulsive and combined symptoms were assessed as rated by parents, teachers or all raters. The influence of study characteristics and PUFA regimen content was explored in multivariable meta-regression analyses. The overall pooled estimate from 18 studies showed that combined ADHD symptoms rated by all raters decreased with PUFA supplementation; SMD -0.192 (95% CI: -0.297, -0.086; P<0.001). However, when analyzed by rater, only parent-rated symptoms decreased significantly. Multivariable meta-regression showed that longer study duration, γ-linolenic acid (GLA), and the interaction between GLA and eicosapentaenoic acid (EPA) were associated with significant decreases in inattention; however, PUFA regimen content was unrelated to changes in hyperactive-impulsive symptoms. Certain fatty acids present in placebo preparations may potentially have been psychoactive. This meta-analysis provides modest evidence of PUFA effectiveness in ADHD, especially GLA and EPA for inattention symptoms; however, evidence of reporting bias, publication bias, variable methodological quality, and use of potentially psychoactive placebos limit the generaliza

Topics: Adolescent; Attention; Attention Deficit Disorder with Hyperactivity; Child; Child, Preschool; Eicosapentaenoic Acid; Female; gamma-Linolenic Acid; Humans; Male; Randomized Controlled Trials as Topic

The essential fatty acid deficiency (EFA) gives rise to many pathologic states and may predispose for certain disease development. One of the most frequently deficient EFA is gamma-linolenic acid. The gamma-linolenic acid supplementation brings some hopeful effects in treatment of diabetic neuropathy, eczema, cyclic mastalgia, rheumatoid arthritis, osteoporosis and ADHD. Many double blind trials have been performed for defective assessment of GLA efficiency. Some of them have proved statistically significant efficacy, the others have led to some doubts. There is a necessity to perform more trials. The gamma-linolenic acid is completely safe, non-toxic, and non-cancerogenic substance. It can be an interesting alternative for supporting treatment.

Topics: Arthritis, Rheumatoid; Attention Deficit Disorder with Hyperactivity; Diabetic Neuropathies; Dietary Supplements; Eczema; gamma-Linolenic Acid; Humans; Osteoporosis; Treatment Outcome

Zinc is an important co-factor for metabolism relevant to neurotransmitters, fatty acids, prostaglandins, and melatonin, and indirectly affects dopamine metabolism, believed intimately involved in attention-deficit/hyperactivity disorder (ADHD). To explore the relationship of zinc nutrition to essential fatty acid supplement and stimulant effects in treatment of ADHD, we re-analyzed data from an 18-subject double-blind, placebo-controlled crossover treatment comparison of d-amphetamine and Efamol (evening primrose oil, rich in gamma-linolenic acid). Subjects were categorized as zinc-adequate (n = 5), borderline zinc (n = 5), and zinc-deficient (n = 8) by hair, red cell, and urine zinc levels; for each category, placebo-active difference means were calculated on teachers' ratings. Placebo-controlled d-amphetamine response appeared linear with zinc nutrition, but the relationship of Efamol response to zinc appeared U-shaped; Efamol benefit was evident only with borderline zinc. Placebo-controlled effect size (Cohen's d) for both treatments ranged up to 1.5 for borderline zinc and dropped to 0.3-0.7 with mild zinc deficiency. If upheld by prospective research, this post-hoc exploration suggests that zinc nutrition may be important for treatment of ADHD even by pharmacotherapy, and if Efamol benefits ADHD, it likely does so by improving or compensating for borderline zinc nutrition.

Topics: Antioxidants; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Cross-Over Studies; Dextroamphetamine; Double-Blind Method; Fatty Acids, Essential; gamma-Linolenic Acid; Humans; Linoleic Acids; Male; Nutritional Status; Oenothera biennis; Plant Oils; Zinc

In a Latin-square double-crossover with random assignment to sequence, 18 boys, aged 6-12 years, with attention-deficit hyperactivity disorder received 1 month each of placebo, D-amphetamine, and Efamol (evening primrose oil containing gamma-linolenic acid, with vitamin E as preservative). Parents' ratings were noncontributory. Teachers' ratings showed a trend of Efamol effect between placebo and D-amphetamine. The trend reached significance (p less than 0.05) only on Conners Hyperactivity Factor. Dosage may be crucial; 8 Efamol capsules per day were used in this study. Heuristic data scrutiny suggested possible interaction (sequence effect). Further study with a different design and dose is suggested. This study does not establish Efamol as an effective treatment.

Topics: Attention Deficit Disorder with Hyperactivity; Child; Clinical Trials as Topic; Dextroamphetamine; Double-Blind Method; gamma-Linolenic Acid; Humans; Linolenic Acids; Male; Random Allocation

Thirty-one children, selected for marked inattention and overactivity, were studied in a double-blind, placebo-controlled crossover study of essential fatty acid (EFA) supplementation. Subjects received the active treatment and placebo conditions for 4 weeks each and were assessed on a variety of cognitive, motor, and standardized rating scale measures. EFA supplementation (evening primrose oil; Efamol) resulted in significantly lower levels of palmitoleic acid (a nonessential fatty acid) and higher concentrations of dihomogammalinolenic acid, an EFA previously found to be deficient in some hyperactive children. Supplementation was also associated with significant changes on two performance tasks and with significant improvement to parent ratings on the subscales designated as Attention Problem and Motor Excess of the Revised Behavior Problem Checklist. However, a variety of eight other psychomotor performance tests and two standardized teacher rating scales failed to indicate treatment effects. When the experiment-wise probability level was set at .05, only 2 of 42 variables showed treatment effects. Baseline EFA concentrations appeared to be unrelated to treatment response. It was concluded that EFA supplementation, as employed here, produces minimal or no improvements in hyperactive children selected without regard to baseline EFA concentrations.

Topics: 8,11,14-Eicosatrienoic Acid; Attention Deficit Disorder with Hyperactivity; Child; Clinical Trials as Topic; Double-Blind Method; Fatty Acids, Essential; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Humans; Linoleic Acids; Male; Oenothera biennis; Palmitic Acids; Plant Oils; Psychomotor Performance