I have been doing some research into the literature on omega 3 fatty acids and attention deficit disorder in kids. The literature is pretty clear that this is a metabolic/genetic/environmental/structural problem that runs the gamut as far as presentation of symptoms. Neuroscientists largely agree that there probably is a nutritional component also, with ADD kids almost always showing below normal serum levels of essential fatty acids. A few studies (see below) have suggested that supplementation with Omega 3 PUFAs may improve behavior in some kids with this disorder. I will continue to search the literature for reliable information on this topic. I suspect many of you are already aware of this, but I just wanted you to know this is another area of interest on my part. I have attached the abstracts of several relevant studies with the important conclusions highlighted and the sites on PubMed where they can be found. Let me know if this stuff is helpful. I will be addressing this in next months blog posting and newsletter.

Ron Eaker,M.D.





http://www.ajcn.org/cgi/content/abstract/71/1/327S

American Journal of Clinical Nutrition, Vol. 71, No. 1, 327S-330S
Long-chain polyunsaturated fatty acids in children with attention-deficit hyperactivity disorder1,2
John R Burgess, Laura Stevens, Wen Zhang and Louise Peck
From the Department of Foods and Nutrition, Purdue University, West Lafayette, IN.
Attention-deficit hyperactivity disorder (ADHD) is the diagnosis used to describe children who are inattentive, impulsive, and hyperactive. ADHD is a widespread condition that is of public health concern. In most children with ADHD the cause is unknown, but is thought to be biological and multifactorial. Several previous studies indicated that some physical symptoms reported in ADHD are similar to symptoms observed in essential fatty acid (EFA) deficiency in animals and humans deprived of EFAs. We reported previously that a subgroup of ADHD subjects reporting many symptoms indicative of EFA deficiency (L-ADHD) had significantly lower proportions of plasma arachidonic acid and docosahexaenoic acid than did ADHD subjects with few such symptoms or control subjects. In another study using contrast analysis of the plasma polar lipid data, subjects with lower compositions of total n–3 fatty acids had significantly more behavioral problems, temper tantrums, and learning, health, and sleep problems than did those with high proportions of n–3 fatty acids. The reasons for the lower proportions of long-chain polyunsaturated fatty acids (LCPUFAs) in these children are not clear; however, factors involving fatty acid intake, conversion of EFAs to LCPUFA products, and enhanced metabolism are discussed. The relation between LCPUFA status and the behavior problems that the children exhibited is also unclear. We are currently testing this relation in a double-blind, placebo-controlled intervention in a population of children with clinically diagnosed ADHD who exhibit symptoms of EFA deficiency.



http://www.ncbi.nlm.nih.gov/pubmed/16962757

Omega-3 fatty acid status in attention-deficit/hyperactivity disorder.
Antalis CJ, Stevens LJ, Campbell M, Pazdro R, Ericson K, Burgess JR.
Department of Foods and Nutrition, West Lafayette IN 47909-2059, USA.
Abstract
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.


http://www.ncbi.nlm.nih.gov/pubmed/17629918


Nutr J. 2007 Jul 13;6:16.
Effects of an open-label pilot study with high-dose EPA/DHA concentrates on plasma phospholipids and behavior in children with attention deficit hyperactivity disorder.
Sorgi PJ, Hallowell EM, Hutchins HL, Sears B.
Hallowell Center, Sudbury, MA 01776, USA.
Abstract
BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is the most common neurological condition in children. This pilot study evaluated the effects of high-dose eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on the isolated plasma phospholipids and behavior in children with ADHD (primarily inattentive subtype and combined subtype). METHODS: Nine children were initially supplemented with 16.2 g EPA/DHA concentrates per day. The dosage was adjusted dependent on the ratio of arachidonic acid (AA) to EPA in the isolated plasma phospholipids at four weeks to reach a level normally found in the Japanese population. RESULTS: At the end of the eight-week study, supplementation resulted in significant increases in EPA and DHA, as well as a significant reduction in the AA:EPA ratio (20.78 +/- 5.26 to 5.95 +/- 7.35, p < 0.01). A psychiatrist (blind to supplement compliance or dosage modifications) reported significant improvements in behavior (inattention, hyperactivity, oppositional/defiant behavior, and conduct disorder). There was also a significant correlation between the reduction in the AA:EPA ratio and global severity of illness scores. CONCLUSION: The findings of this small pilot study suggest supplementation with high-dose EPA/DHA concentrates may improve behavior in children with ADHD.





http://www.ncbi.nlm.nih.gov/pubmed/18072818


Altern Med Rev. 2007 Sep;12(3):207-27.
Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids.
Kidd PM.
University of California, Berkeley, California, USA.
Abstract
The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are orthomolecular, conditionally essential nutrients that enhance quality of life and lower the risk of premature death. They function exclusively via cell membranes, in which they are anchored by phospholipid molecules. DHA is proven essential to pre- and postnatal brain development, whereas EPA seems more influential on behavior and mood. Both DHA and EPA generate neuroprotective metabolites. In double-blind, randomized, controlled trials, DHA and EPA combinations have been shown to benefit attention deficit/hyperactivity disorder (AD/HD), autism, dyspraxia, dyslexia, and aggression. For the affective disorders, meta-analyses confirm benefits in major depressive disorder (MDD) and bipolar disorder, with promising results in schizophrenia and initial benefit for borderline personality disorder. Accelerated cognitive decline and mild cognitive impairment (MCI) correlate with lowered tissue levels of DHA/EPA, and supplementation has improved cognitive function. Huntington disease has responded to EPA. Omega-3 phospholipid supplements that combine DHA/EPA and phospholipids into the same molecule have shown marked promise in early clinical trials. Phosphatidylserine with DHA/EPA attached (Omega-3 PS) has been shown to alleviate AD/HD symptoms. Krill omega-3 phospholipids, containing mostly phosphatidylcholine (PC) with DHA/EPA attached, markedly outperformed conventional fish oil DHA/EPA triglycerides in double-blind trials for premenstrual syndrome/dysmenorrhea and for normalizing blood lipid profiles. Krill omega-3 phospholipids demonstrated anti-inflammatory activity, lowering C-reactive protein (CRP) levels in a double-blind trial. Utilizing DHA and EPA together with phospholipids and membrane antioxidants to achieve a triple cell membrane synergy may further diversify their currently wide range of clinical applications.



http://www.ncbi.nlm.nih.gov/pubmed/16188207

Reprod Nutr Dev. 2005 Sep-Oct;45(5):549-58.
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.
Young GS, Conquer JA, Thomas R.
Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario N1G 5B6, Canada.
Abstract
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.





http://www.ncbi.nlm.nih.gov/pubmed/19436468

Paediatr Child Health. 2009 Feb;14(2):89-98.
Omega-3 fatty acid treatment of children with attention-deficit hyperactivity disorder: A randomized, double-blind, placebo-controlled study.
Bélanger SA, Vanasse M, Spahis S, Sylvestre MP, Lippé S, L'heureux F, Ghadirian P, Vanasse CM, Levy E.
Department of Pediatrics, CHU Ste-Justine, Montréal, Québec.
Abstract
BACKGROUND: Although several clinical trials have evaluated the impact of n-3 polyunsaturated fatty acid (PUFA) on patients with attention-deficit hyperactivity disorder (ADHD), changes in plasma PUFA composition were not always assessed following n-3 supplementation. Furthermore, no reports are available on the efficacy of n-3 PUFA in Canadian youth with ADHD. OBJECTIVES: To determine fatty acid (FA) composition, and the efficacy and safety of n-3 PUFA supplementation on ADHD clinical symptoms in French Canadian primary school children. PATIENTS AND METHODS: The Strengths and Weaknesses in ADHD and Normal Behaviors (SWAN) and Conners' questionnaires were used to assess changes in ADHD symptoms in 37 children (only 26 children completed the study from zero to 16 weeks). They were divided into two groups (A and B), and participated in a 16-week, double-blind, one-way, crossover randomized study. In the first phase, group A received the n-3 PUFA supplement and group B received n-6 PUFA (sunflower oil) as a placebo. During the second phase, group B received the active n-3 PUFA supplement that was continued in group A. FA composition and lipid profile were assessed during the phases of the study. RESULTS: FA differences between groups were observed in the 26 patients. Supplementation with n-3 PUFA resulted in significant increases in eicosapentaenoic and docosahexaenoic acids in group A, while group B was enriched with alpha-linolenic, gamma-linolenic and homo-gamma-linolenic acids. The n-3 PUFA supplement was tolerated without any adverse effects. A statistically significant improvement in symptoms was noted based on the parent version of the Conners' questionnaire from baseline to the end of phase 1, and this amelioration continued from phases 1 to 2, although the latter changes from phases 1 and 2 were not statistically significant in any of the subscales except for the subscale measuring inattention in group B. The improvement was greater in patients from group A in phase 1 and in patients from group B in phase 2. A subgroup of eight patients (four in each group) displayed a statistically significant clinical improvement following the administration of the n-3 PUFA supplement, particularly for the inattention and global Diagnostic and Statistical Manual of Mental Disorders, Fourth edition, total Conners' subscales. CONCLUSIONS: A subgroup of children with ADHD who used n-3 PUFA supplements achieved and maintained symptom control. The data of the present study also supported n-3 PUFA safety and tolerability, but limited changes were noted in the FA profile in French Canadians with ADHD.





http://www.ncbi.nlm.nih.gov/pubmed/14669965

Lipids. 2003 Oct;38(10):1007-21.
EFA supplementation in children with inattention, hyperactivity, and other disruptive behaviors.
Stevens L, Zhang W, Peck L, Kuczek T, Grevstad N, Mahon A, Zentall SS, Arnold LE, Burgess JR.
Department of Foods & Nutrition, Purdue University, West Lafayette, Indiana 47907, USA.
Abstract
This pilot study evaluated the effects of supplementation with PUFA on blood FA composition and behavior in children with Attention-Deficit/Hyperactivity Disorder (AD/HD)-like symptoms also reporting thirst and skin problems. Fifty children were randomized to treatment groups receiving either a PUFA supplement providing a daily dose of 480 mg DHA, 80 mg EPA, 40 mg arachidonic acid (AA), 96 mg GLA, and 24 mg alpha-tocopheryl acetate, or an olive oil placebo for 4 mon of double-blind parallel treatment. Supplementation with the PUFA led to a substantial increase in the proportions of EPA, DHA, and alpha-tocopherol in the plasma phospholipids and red blood cell (RBC) total lipids, but an increase was noted in the plasma phospholipid proportions of 18:3n-3 with olive oil as well. Significant improvements in multiple outcomes (as rated by parents) were noted in both groups, but a clear benefit from PUFA supplementation for all behaviors characteristic of AD/HD was not observed. For most outcomes, improvement of the PUFA group was consistently nominally better than that of the olive oil group; but the treatment difference was significant, by secondary intent-to-treat analysis, on only 2 out of 16 outcome measures: conduct problems rated by parents (-42.7 vs. -9.9%, n = 47, P = 0.05), and attention symptoms rated by teachers (-14.8 vs. +3.4%, n = 47, P = 0.03). PUFA supplementation led to a greater number of participants showing improvement in oppositional defiant behavior from a clinical to a nonclinical range compared with olive oil supplementation (8 out of 12 vs. 3 out of 11, n = 33, P = 0.02). Also, significant correlations were observed when comparing the magnitude of change between increasing proportions of EPA in the RBC and decreasing disruptive behavior as assessed by the Abbreviated Symptom Questionnaire (ASQ) for parents (r = -0.38, n = 31, P < 0.05), and for EPA and DHA in the RBC and the teachers' Disruptive Behavior Disorders (DBD) Rating Scale for Attention (r = -0.49, n = 24, P < 0.05). Interestingly, significant correlations were observed between the magnitude of increase in alpha-tocopherol concentrations in the RBC and a decrease in scores for all four subscales of the teachers' DBD (Hyperactivity, r = -0.45; Attention, r= -0.60; Conduct, r = -0.41; Oppositional/Defiant Disorder, r = -0.54; n = 24, P < 0.05) as well as the ASQ for teachers (r = -0.51, n = 24, P < 0.05). Thus, the results of this pilot study suggest the need for further research with both n-3 FA and vitamin E in children with behavioral disorders.




http://www.ncbi.nlm.nih.gov/pubmed/20491709
Acta Paediatr. 2010 May 19.
EPA supplementation improves teacher-rated behaviour and oppositional symptoms in children with ADHD.
Gustafsson PA, Birberg-Thornberg U, Duchén K, Landgren M, Malmberg K, Pelling H, Strandvik B, Karlsson T.
.Department of Child Psychiatry, Linköping University, Linköping, Sweden.
Abstract
Abstract Aim: Measure efficacy of eicosapentaenoic acid (EPA) in children with attention deficit hyperactivity disorder (ADHD). Methods: Randomized controlled trial (RCT) of 0.5 g EPA or placebo (15 weeks) in 92 children (7-12 years) with ADHD. Efficacy measure was Conners' Parent/Teacher Rating Scales (CPRS/CTRS). Fatty acids were analysed in serum phospholipids and red blood cell membranes (RBC) at baseline and endpoint with gas chromatography. Results: EPA improved CTRS inattention/cognitive subscale (p = 0.04), but not Conners' total score. In oppositional children (n = 48), CTRS total score improved >/=25% in 48% of the children receiving EPA vs. 9% for placebo [effect size (ES) 0.63, p = 0.01]. In less hyperactive/impulsive children (n = 44), >/=25% improvement was seen in 36% vs. 18% (ES 0.41, n.s.), and with both these types of symptoms 8/13 with EPA vs. 1/9 for placebo improved >/=25% (p = 0.03). Children responding to treatment had lower EPA concentrations (p = 0.02), higher AA/EPA (p = 0.005) and higher AA/DHA ratios (p = 0.03) in serum at baseline. Similarly, AA/EPA (p = 0.01), AA/DHA (p = 0.038) and total omega-6/omega-3 ratios (p = 0.028) were higher in RBC, probably because of higher AA (p = 0.011). Conclusion: Two ADHD subgroups (oppositional and less hyperactive/impulsive children) improved after 15-week EPA treatment. Increasing EPA and decreasing omega-6 fatty acid concentrations in phospholipids were related to clinical improvement.

http://www.ncbi.nlm.nih.gov/pubmed/20424008

J Atten Disord. 2010 Apr 27. [Epub ahead of print]
The Impact of Polyunsaturated Fatty Acids in Reducing Child Attention Deficit and Hyperactivity Disorders.
Transler C, Eilander A, Mitchell S, van de Meer N.
Sensation, Perception and Behavior Department.
Abstract
Objectives: To review the impact of polyunsaturated fatty acids (PUFA) in reducing ADHD symptoms in children. Methods: Peer-reviewed experimental literature published from 1980 to Mai 2009 is consulted (Psychinfo, Medline, and resulting reference lists). Results: Placebo-controlled studies with ADHD or hyperactive children show no effects on behaviors or cognition when only n- 6 (omega-6) PUFA, only docosahexaenoic acid (DHA), or n-6 and n-3 (omega-3) short-chain PUFA are supplemented. Yet three out of four studies suggest that a combination of long-chain n-3 and n-6 fatty acids (DHA, eicosapentaenoic acid [EPA], and gamma-linolenic acid [GLA]) supplemented daily for 3 to 4 months could lead to a reduction in ADHD symptomatology. Results on cognitive outcomes are inconsistent. Conclusions: Evidence is too limited to reach definitive conclusions but suggests that research on the impact of long-chain PUFA (n-3 and n-6) should continue with special focus on individual differences (genetic and fatty acid markers), mechanisms (brain imaging), and new enhanced methods of systematic observations of behaviors.



http://www.ncbi.nlm.nih.gov/pubmed/20146180


Tijdschr Psychiatr. 2010;52(2):89-97.
Omega-3 and omega-6 fatty acids in the treatment of children and adolescents with ADHD
Aben A, Danckaerts M.
Abstract
Background There is a growing trend towards the use of alternative forms of treatment for attention deficit hyperactivity disorder (adhd), such as the food supplements omega-3 and omega-6 fatty acids. AIM: To study biochemical aspects, important hypotheses regarding the role of these fatty acids in brain development, the mode of operation and research results concerning the effectiveness of treating adhd with these supplements. METHOD: A Medline search was performed using the Mesh-term 'fatty acids' and the search terms 'omega-3 and omega-6 fatty acids' and 'attention deficit hyperactivity disorder'. results Some rct's (randomised controlled trails) involving children with adhd didn't show any improvement after treatment with omega-3 and omega-6 fatty acids. Some other rct's, however, did show a reduction in adhd symptoms and learning difficulties, but the children concerned had not been officially diagnosed with adhd. A recent rct showed a substantial reduction in adhd symptoms in children with the inattentive type of adhd and in children with adhd and comorbid problems. CONCLUSION: There are indications that there is a theoretical rationale for the effectiveness of fatty acids in the treatment of adhd; research is ongoing. At the moment, however, treatment of adhd with omega-3 and omega-6 fatty acids is not recommended because it does not qualify as being evidence-based.




http://www.ncbi.nlm.nih.gov/pubmed/18448859

J Atten Disord. 2009 Mar;12(5):394-401. Epub 2008 Apr 30.
Omega-3/omega-6 fatty acids for attention deficit hyperactivity disorder: a randomized placebo-controlled trial in children and adolescents.
Johnson M, Ostlund S, Fransson G, Kadesjö B, Gillberg C.
Department of Child and Adolescent Psychiatry, Göteborg University, Göteborg, Sweden. mats.k.johnson@vgregion.se
Abstract
OBJECTIVE: The aim of the study was to assess omega 3/6 fatty acids (eye q) in attention deficit hyperactivity disorder (ADHD). METHOD: The study included a randomized, 3-month, omega 3/6 placebo-controlled, one-way crossover trial with 75 children and adolescents (8-18 years), followed by 3 months with omega 3/6 for all. Investigator-rated ADHD Rating Scale-IV and Clinical Global Impression (CGI) scale were outcome measures. RESULTS: A majority did not respond to omega 3/6 treatment. However, a subgroup of 26% responded with more than 25% reduction of ADHD symptoms and a drop of CGI scores to the near-normal range. After 6 months, 47% of all showed such improvement. Responders tended to have ADHD inattentive subtype and comorbid neurodevelopmental disorders. CONCLUSION: A subgroup of children and adolescents with ADHD, characterized by inattention and associated neurodevelopmental disorders, treated with omega 3/6 fatty acids for 6 months responded with meaningful reduction of ADHD symptoms.



http://www.ncbi.nlm.nih.gov/pubmed/18622940

Z Kinder Jugendpsychiatr Psychother. 2008 Mar;36(2):109-16.
The treatment of Attention-Deficit/Hyperactivity Disorders with polyunsaturated fatty acids - an effective treatment alternative?
[Article in German]
Frölich J, Döpfner M.
Klinik und Poliklinik für Psychiatrie und Psychotherapie des Kindes- und Jugendalters der Universität zu Köln. Praxis-dr-froelich@t-online.de
Abstract
OBJECTIVES: Both omega-3 and omega-6 long-chain polyunsaturated fatty acids (PUFA) have a substantial impact on human brain development and function. However, in western industrial countries omega-3 LC-PUFA in particular are often lacking in diets. Increasing evidence indicates that LC-PUFA imbalance or deficiencies may be associated with Attention Deficit/Hyperactivity Disorder (ADHD) through involvement in the dopaminergic corico-striatal metabolism. Preliminary study result suggest that dietary supplementation with LC-PUFA might be effective in the treatment of ADHD. METHODS: This review summarizes the knowledge in terms of a hypothesized pathogenetic relationship between fatty acid metabolism and ADHD and discusses the possible clinical benefit of a primary or combined treatment with LC-PUFA. RESULTS: Actually it is unclear whether a deficit in intake or metabolism of LC-PUFA may play a major role in the pathogenesis of ADHD. Moreover treatment studies yielded conflicting results. A combination of Omega-3 and Omega-6 - fatty acids might attenuate the symptoms of ADHD significantly, thus making this dietary intake useful. CONCLUSIONS: Considerable research has to be done in the future to identify ideal therapeutic combinations and dosages of various fatty acids, and to develop reliable ways of defining those individuals to benefit from this treatment access.


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