Inattention, hyperactivity and impulsivity constitute the core diagnostic criteria for attention deficit hyperactivity disorder (ADHD) children. Patients generally suffer from sleep disturbance and malnutrition that can account for tiredness during the day, poor concentration, poor eating and depressed mood, along with anemia and an n-3 polyunsaturated acid deficiency. The change of ADHD behavior in children (9–12) was studied, following 10 weeks of treatment with a polyunsaturated acid mixture on six variables: cooperation, mood, concentration, homework preparation, fatigue and sleep quality. Iron status was also examined. Polyunsaturated acid administration was associated with significant improvement in quality of life, ability to concentrate, sleep quality and hemoglobin levels.
No single treatment modality for attention deficit hyperactivity disorder (ADHD) (behavior therapy, neurofeedback, medications) has been shown to be conclusively effective for all ADHD patients. Although the research in the field of nutrients and ADHD is not well developed, and although there is no claim that nutritional deficits are the cause of ADHD, it is fairly well agreed that the nutritional deficits may worsen the symptoms of ADHD. Two major nutritional deficits may be of considerable interest, and may suggest the options for undertaking novel interventional alternatives: (1) essential fatty acids (EFA) deficiency, and (2) iron deficiency.
Several studies summarized by Burgess et al. (2000) demonstrate that some of the physical symptoms of ADHD children are similar to those observed in EFA deficiency in animals and humans. Some ADHD children suffer from EFA deficiency (Ross et al., 2003), especially the n-3 subgroup of fatty acids. Moreover, there is a high correlation between the severity of the EFA deficiency and the severity of ADHD symptoms (r=0.80). Supportive studies showed the relationships between EFA deficiency and ADHD (Stevens et al., 1995; Richardson and Puri, 2000; Farooqui and Horrocks, 2001) summarized two studies in which fatty acids supplement were given to ADHD children, with the EFA supplement effective in one study and having no effect in the other. Recently, Raz et al. (2009a) conducted a large scale study on the effects of EFA on ADHD symptoms, and found that both the placebo and the treated group had been improved. A survey of published studied in this field had been performed by Raz and Gabis (2009) and found mixing results.
Not much is known about the relationships between iron deficiency and ADHD. Burgess et al. (2000), Kidd (2000) and Sever et al. (1997) demonstrated the similarities between the effects of iron deficiency on the behavior of animal and human and ADHD symptoms.
We examined the effects of a supplementation of a specific mixture of EFAs on a group of ADHD children. The mixture was created in our laboratory after we had experimentally established that the ratio of omega-3 and omega-6 is critical for modulating behavioral and neuropharmacological functions. We used highly purified α-linolenic and linoleic acids to avoid the variations that occur in the composition of commercially-prepared fatty acid oils that may introduce possible confounding effects of other fatty acids or lipid mixtures. Our animal studies (conducted with rats that were given a normal diet, as recommended by American Institute of Nutrition) confirmed that a mixture of α-linolenic and linoleic acids with a ratio of 1:4 was the most effective in improving numerous cognitive and physiological indices. It is of interest to note that preliminary studies with radio-labeled polyunsaturated acid showed that the FA ratio is capable of crossing the blood-brain barrier and maintaining this ratio in the neuronal membranes (Yehuda et al., 1999).
Sleep disturbances, mainly difficulty to initiate and maintain sleep, are often reported by parents and by ADHD children (Owens, 2009). Detailed study on the sleep architecture among ADHD children showed a reduced sleep efficiently, more nocturnal awakenings and reduced percentage of rapid eye movement sleep (Sobanski et al., 2008).
In view of the conflicting results in the studies on the effects of EFAs on ADHD syndromes, we like to suggest that ADHD diagnosis is too wide and included many subgroups. One such subgroup is the EFAs-deprived group.
Another group, which was not studied before, is the sleep-deprived ADHD children.
We were able to show that a mixture of EFAs improved sleep disturbances in various populations (Yehuda, 2003) and, in particular, the mixture protects rats from the effects of rapid eye movement deprivation (Yehuda et al., 2007).
To address the effects of a mixture of essential fatty acid on sleep-deprived ADHD children, we recruited 78 sleep-deprived boys (ages 9–12), who were diagnosed as suffering from ADHD by two independent psychologists. The diagnosis was based on The American Academy of Pediatrics, that is, a child aged 6–12 years who displays inattention, hyperactivity, impulsivity, academic underachievement and/or behavior problems. A total of 40 children received treatment and 38 received placebo. An independent group of 22 non-affected boys, of corresponding age and socioeconomic status, served as a control group.
This study was approved by the Helsinki Committee, Jaffe Hospital, Hedera, Israel. Informed consent forms were signed by the parents of the subject.
The essential fatty acids mixture was composed of α-linolenic (0.95 g/ml) and linoleic (0.90 g/ml) free fatty acids, both 99% pure (Sigma, St Louis, MO, USA, (L2367 and L1376)). Each capsule contains 360 g of linoleic acid and 90 g of α-linoleic acid, in mineral oil. The placebo was composed of mineral oil in identical capsule. The subjects consumed two capsules per day. The treatments lasted 10 weeks.
Each subject completed a short questionnaire on day 1 of the study. The questions were answered on a ‘five-point scale’ for each of six variables: (1) the level of cooperation with other people, such as parents, teachers and friends. (2) The level of good mood in general. (3) The level of ability to concentrate during the day, mainly at school. (4) The degree of fatigue in general, experienced during the day. (5) The percentage of homework completed in general. (6) The quality of sleep.
For each scale, a score of zero signified a negative and poor status, whereas a score of five signified positive and excellent status. In addition, a blood assay was taken to measure hemoglobin levels. All participants took two capsules of the 1:4 FA compound while awake, twice daily, for 10 weeks. At the end of 10 weeks, the subjects were again asked to complete the questionnaire, and their hemoglobin level was tested again.
Statistical analysis was performed by two-way ANOVA.
The results (Table 1) show that administration of the FA ratio mixture for 10 weeks to sleep-deprived ADHD children significantly improved their quality of life. The most impressive improvement was in the quality of sleep. The children reported a marked improvement in their ability to concentrate and that they felt less fatigued. In addition, their mood and ability to cooperate with other people had improved. Such improvements were not observed in the control group or the placebo group. This study shows that sleep-deprived ADHD children suffer also from iron deficiency and that our FA treatment corrected the iron level in their blood. It is not clear if iron deficiency is one of the core symptoms of this group or it is a consequence of poor food intake habits. They eat junk food at night. In cafeteria study (unpublished study), the sleep-deprived children consumed 20% carbohydrates, 5% proteins and 75% lipids. Non-sleep deprived children consumed 60% carbohydrates, 20% proteins and 20% lipids.
Except for three cases of transient stomach upset and diarrhea, and two cases of dizziness, no major side effects were reported. All subjects continued their participation in the study.
We thank The Rose K Ginsburg Chair for Research into Alzheimer's disease and The William Farber Center for Alzheimer Research for their support.
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