Children need EPA, DHA, GLA and Vitamin D to be healthy

In the first two years of life the omega-3 fatty acid Docosahexaenoic acid (DHA) is of crucial importance. DHA accumulates in human brain tissue at a rapid rate during the third trimester1,2 and at birth, DHA represents approximately 9% of total cortical fatty acid composition, and increases by an additional 6% over the following 20 years until adulthood3,4. Remarkably, after only the first year of life the brain has almost reached adult mass. Although DHA continues to be of importance after infancy and into childhood and adolescence, Eicosapentaenoic acid (EPA), another very important long chain polyunsaturated omega-3 fatty acid becomes much more important than it was during infancy due to its anti-inflammatory nature and its modulation of mood and well-being, atopy, asthma, ADHD and other diseases.

Summary Table

This table summarizes the health effects of EPA, DHA, GLA, and vitamin D and lists which omega-3 fatty acid (EPA, DHA or both) is most supported in the literature for specific health issues in infants and children.

Infant Health

DHA and infant visual development At birth, an infant’s visual system is poorly developed, but development occurs quickly during the first year of life5,6. Numerous studies have evaluated the effect of DHA status on the developing visual system and several have identified a significant positive correlation between visual acuity and milk DHA levels or infant DHA status7-12. Other studies have evaluated the effect of infant formula supplemented with omega-3 on visual development. Some studies used very low levels of DHA and found no statistically significant difference between formula groups13-15 but most studies like Uauy et al., (2006)16 demonstrated a significant positive association between DHA provided by supplement and higher visual acuity. DHA and infant cognitive development Research supports that in breastfed infants, higher DHA status at two months leads to better language production and comprehension at 14 and 18 months of age17,18. Similarly, children of lactating mothers that were given a daily DHA supplement had significantly better scores in psychomotor development19.  Additionally, infants given a formula supplemented with DHA and the omega-6 fatty acid arachidonic acid had improvements in cognitive function at 9-month of age.  Supplemented children had more intentional solutions (successful task completions) and higher intention scores (goal directed behaviors) than controls in a 2-step problem-solving task20. Childhood Health and Disease EPA+DHA for childhood cognition Omega-3 fatty acids from fish are beneficial to cognitive function21-25. In 10 thousand children, academic grades were higher in those who ate fish once a week compared with subjects whose fish consumption was less than once a week.  Grades were even higher in subjects with fish consumption of more than once per week21.  Supplementation with omega-3 fatty acids from fish oil is also able to modify and improve learning in children.   A 5:1 ratio of EPA to DHA fish oil (558 mg EPA, 174 mg DHA and 60 mg GLA) administered to 117 children between the ages of 5 and 12 led to three times the normal expected gain in reading skills and twice the normal gain in spelling competency22. Ryan et al. in 2008 [23] reported that 400mg of DHA improves vocabulary testing, listening comprehension and vocabulary acquisition in 4yrs old after just 4 months and in another study 480 mg DHA, 80mg EPA, 96mg GLA and 42mg AA improved reading speed in 13 of 17 dyslexic children24. Furthermore, DHA supplementation has been shown to increase sustained brain activity during tasks that require attention25. However, the relationship between DHA and learning improvements is not clear. 8 weeks of supplementation with 400 mg or even 1000 mg of DHA in healthy children had no effect on cognitive measures26Evidence therefore suggests that perhaps a higher ratio of EPA is needed for improvements in cognition but it still remains unclear whether DHA alone or combination of the two fatty acids is necessary. It is however clear that the use of omega-3 fatty acids for cognitive enhancement is certainly justified and should be encouraged for children. EPA for mood, well-being and depression in children Childhood depression, mania and disorders of mood are becoming more and more prevalent. It is important to ensure that a child has a healthy and positive mood and well-being in order to ensure proper mental and emotional development. High EPA fish oil produced a significant reduction in mania rating in bipolar children between the ages of 6 and 17 (375 mg EPA and 55 mg DHA)27. In another study, a high EPA fish oil (400mg EPA and 200mg DHA) significantly improved depression rating and score on a depression scale in depressed children aged 6 to 1228. EPA for skin allergy and inflammation in children Another disease that is highly prevalent in children is atopic dermatitis. Lower levels of EPA have been found in the plasma of atopic compared to non-atopic children but no difference was found between atopics and non-atopics for DHA29.  In atopic children, total omega-3 LC-PUFAs were lower and the ratio of total omega-6 to omega-3 was higher in allergic children than in controls30. Furthermore, lower levels of EPA were recorded in 11 of the allergic children with serum IgE levels above the median level as compared to 11 children with lower IgE levels30. EPA is the precursor to the anti-inflammatory leukotriene B5 and inhibits the formation of the inflammatory leukotriene B4 by competing for 5-lipoxygenation31. As leukotriene B4 enhances the production of IgE32,33, the low EPA levels in patients with elevated IgE levels suggests that EPA could contribute to the suppression of IgE antibody formation. Similarly, in 308 children aged 4-6 years total red blood cell omega-3 PUFA was lower in preschoolers with atopy than controls, while omega-6 PUFA and the ratio of n-6/n-3 PUFA were greater34. Gamma-linolenic acid (GLA) for childhood dermatitis

GLA has also been assessed as an oral treatment for children with atopic eczema. In treated children dramatic improvements in clinical condition were seen after 4 weeks of therapy, and these improvements were maintained over a 20 week treatment period35.  Similarly, in another study, 40 mg of GLA improved symptoms of dermatitis in children with atopic disease. There was a significant improvement in the overall severity of the clinical condition of treated children, independent of whether the children had manifestations of IgE-mediated allergy36. Finally, in children aged 1 to 14.5yrs, GLA levels were decreased with low IgE and with eczema, allergic rhinitis and asthma37

EPA and Asthma in Children

Asthma is one of the most common chronic inflammatory conditions and affects both children and adults.  Its prevalence has increased dramatically over the past few decades with the highest incidence occurring in children38.  The cause of airway inflammation can be multifactorial and inflammatory response is quite complex. Airway inflammation involves many cell types and inflammatory mediators.  Despite advances in research, asthma continues to increase in childhood39 and there has been a considerable interest in the potential therapeutic and protective value of dietary supplementation with omega-3 fatty acids due to their anti-inflammatory nature and inhibition of inflammatory molecules. In a recent study, omega-3 fatty acid levels were expressed in levels of exposure and wheeze, doctor visits for wheeze, bronchodilator use and nocturnal coughing were significantly reduced in children in the higher exposure to omega-3 fatty acids40.  In another study, 97 atopic children aged 4–6 years were compared to non-atopic controls.  Higher omega-6 and lower omega-3 were associated with increased risk for asthma41 and EPA and DHA were significantly lower in red blood cells of atopics42. Finally, in an intervention study, a high EPA fish oil (84 mg EPA & 36 mg DHA) significantly decreased asthma score in children (average age 10) with bronchial asthma43.

EPA and essential fatty acids in childhood ADHD

Perhaps one of the more prevalent disorders in children today is Attention deficit disorder with or without hyperactivity (ADD or ADHD). ADHD is primarily characterized by persistent inattention and/or hyperactivity-impulsivity, more frequently and severe than is typically observed44,45.  The American Psychiatric Association estimates that 3–5% of school aged children have ADHD (DSM-IV), while other sources report higher prevalence rates ranging from 5–13%46-49.  ADHD is the most common psychiatric disorder in children and there has been an increasing focus on the effects of diet on childhood hyperactivity. Researchers have reported that various aspects of a child's diet and fatty acid metabolism may have adverse effects on behaviour50. Interestingly, many of the behavioural and physical symptoms associated with essential fatty acid deficiency (i.e. a lack of omega-3) resemble the symptoms described in typical ADHD patients. It has therefore been suggested that perhaps a dietary deficiency of omega-3 fatty acids, or altered metabolic handling of these fatty acids, might contribute to ADHD50.  In support of this, higher physiological levels of omega-3 have been shown to be associated with decreased levels of inattention, hyperactivity, emotional problems, conduct difficulties and increased levels of prosocial behaviour51.

Several scientific research studies have been done to assess and confirm the hypothesis that omega-3 fatty acids EPA and DHA can treat and prevent ADHD. Studies suggest that a combination of long-chain omega-3 EPA/DHA with the omega-6 fatty acid GLA leads to a reduction in ADHD symptomology52. In 100 boys aged 6-12, an increased frequency of behavior problems (hyperactivity, impulsivity, conduct, anxiety, temper tantrums, and sleep problems) was found in children with lower levels of omega-3 fatty acids53.  A high EPA ratio fish oil significantly decreased in-attention and hyperactivity in children between the age of 4 and 1654and 360 mg of DHA alone led to no improvements in children age 6-12 with ADHD55. In another high EPA ratio (250mg EPA and 100mg DHA) study, supplementation led to reduced and maintained symptom control in a subgroup of children with ADHD [56]. A fish oil supplement with 153mg of EPA and 96 mg of DHA improved attention in children 8-13 years old with impaired visual sustained attention57. In another study, 500mg of just EPA was administered to children aged 7-12 with ADHD. EPA improved the inattention/cognitive subscale of Conners' Parent/Teacher Rating Scales (CTRS) and in oppositional children the total score on the CTRS improved in half of the children receiving EPA and only 9% for placebo58. High DHA supplementation in 41 children (8-12 yrs) with specific learning difficulties (mainly dyslexia) decreased the mean score for cognitive problems and general behavior problems63.  But, in another study done with high DHA, fatty acid specific effects determined that EPA was correlated with improvements in ADHD59.  Furthermore, another study found that supplementation with high DHA oil did not lead to any improvement in ADHD. Forty ADHD children took 3.6 g DHA/week for 2 months and there were no significant differences in attention deficit, hyperactivity, impulsivity, aggression, visual perception, visual and auditory short-term memory, and development of visual-motor integration or impatience60. Johnson et al (2008)61administered high EPA fish oil to children either between 8-12 years of age or 13-18 years of age. (558 mg EPA, 174 mg DHA, 60 mg GLA) and in some children there was as much as a 50% decrease in ADHD rating. In yet another study, 9 children who were supplemented with a high EPA ratio fish oil (10.8 g EPA and 5.4 g DHA) per day showed 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 scores62.    Finally, in the famous Oxford-Durham study22 580 mg of EPA, 174 mg of DHA and 60 mg of GLA was given to children with developmental coordination disorder (DCD) and significant improvements were seen in aggression and behavior. In conclusion, there is a large body of research that indicates EPA is responsible for improvements with in-attention, hyperactivity and behavioral problems. Although a few studies have been done with a high DHA supplement, DHA alone was of no benefit. It may also be possible that GLA offers some benefit as a few intervention studies used a combination of EPA, DHA and GLA.

EPA+DHA and Autism

Autistic spectrum disorder is characterized by a marked impairment in social interaction, restricted patterns of behavior and delayed language.  In addition to these core symptoms, autistic children frequently display behavioral disturbances, such as aggression, injurious behavior towards themselves and tantrums.  These behavioral problems usually compromise education and development64. In an observational study, parents of children with autism who supplemented their children with omega-3 rich fish oils reported improvements in general health, cognitive and motor skills, sleeping patterns, eye contact, sociability, concentration and reductions in irritability, aggression and hyperactivity65. Both EPA and DHA levels are reduced in the plasma of autistic children and total omega-3 PUFA levels are reduced by 20%66.  In an intervention study, a high ratio EPA fish oil administered to 13 children with autism (age 5-17yrs) and severe tantrums, aggression, or self-injurious behavior showed that omega-3 supplement improved hyperactivity and stereotypy, each with a large effect size64. Omega-3 fatty acid supplementation has also led to reduced anxiety in autism patients67. In 33 children with high-functioning autism spectrum disorder the delivery of omega-3 treatment and behavioural group therapy led to significant reductions in parental reports of anxiety symptoms compared to controls. High DHA ratio oil also led to improvements in autism68.  60 mg DHA, 12 mg of GLA, 13 mg EPA and 5 mg of AA improved score on the childhood autism rating scale in 20 of 30 Egyptian autistic children aged 3-11 years.

EPA and childhood Crohn’s disease

In 232 children and adolescents, consumption of EPA and DHA was negatively associated with Crohn’s disease and a higher ratio of long chain omega-3/omega-6 fatty acids was significantly associated with lower risk for Crohn’s disease69. Similarly, children aged 5-16 years, in remission from Crohn’s, were give a high ratio EPA to DHA fish oil and amino-salicylic-acid or amino-salicylic-acid alone. Children were randomized and treated for 12 months. The number of patients who relapsed at 1 year was significantly lower in those given omega-3 then those given only amino-salicylic-acid70.

Omega-3 fatty acids and childhood diabetes

In children, consumption of omega-3 fatty acids reduces the risk of diabetes. In fifty-eight children; after adjusting for family history of type 1 diabetes, caloric intake, and omega-6 fatty acid intake, omega-3 fatty acid intake was inversely associated with risk of islet autoimmunity71 and in 545 cases of childhood-onset type 1 diabetes and 1668 population control subjects a questionnaire on the frequency of supplement use was administered; use of omega-3 supplements in the first year of life was associated with a significantly lower risk of type 1 diabetes72.

EPA+DHA and childhood obesity

Overweight adolescents not only have higher circulating levels of inflammatory markers, but they also have higher plasma-saturated fatty acids and lower levels of omega-3. Omega-3 fatty acids are also able to modulate the intensity of obesity in children73. Similarly, plasma levels of omega-3 fatty acids are associated with the degree of obesity. In obese children aged 8-12 years and normal weight children matched for age/sex a low amount of omega-3 fatty acids and a low ratio of omega-3 to omega-6 fatty acids were associated with a higher BMI z-score. In was concluded that in obese children, plasma fatty acid profile may be associated with the degree of obesity74.

Vitamin D for Childhood Health and Disease


Vitamin D deficiency is highly prevalent among children and adolescents worldwide. The high rates of vitamin D deficiency during childhood are of major concern given the growing evidence that vitamin D deficiency may play a role in many chronic diseases beyond rickets including: Autoimmune conditions, cardiovascular disease and cancer. Identifying treating, or preventing vitamin D deficiency in children could therefore have a profound effect on their health throughout their life span75.  Vitamin D deficiency has been reported in many healthy children worldwide and within several populations76-81.  A recent cross-sectional study done in a clinic setting with 307 healthy children (age 11-18) reported that 52% of the children assessed were vitamin D deficient76. Furthermore, Sullivan et al observed that at the end of winter and summer 48% and 17%, respectively, of white girls (9-11 years of age) in Maine were deficient77.  In another study 34% of children aged 2-16 were vitamin D deficient [78]. Even in sunny countries such as Lebanon, vitamin D inadequacy is common in school children79.

Bone Health

Vitamin D is very important for bone health. It stimulates matrix formation and bone maturation, stimulates osteoclast activity and can influence bone cell differentiation. It helps to regulate calcium and phosphorus metabolism and promotes calcium absorption. Some studies suggest that calcium absorption is increased by 30–40% with adequate vitamin D status compared with a lower 10–15% absorption rate without adequate vitamin D82.  Research suggests that mild vitamin D insufficiency can have a negative effect on bone mineral mass in adolescent females82 and children83,84.  Studies also suggest that insufficient vitamin D has an impact on bone turnover in healthy children85. In 171 healthy Finnish girls aged 9–15 years of age, those with severely low levels of vitamin D had 4% lower bone mineral densities. The adjusted change in lumbar spine BMD was 27% higher in the highest vitamin D intake group compared with those subjects in the lowest vitamin D intake group86.  Vitamin D supplementation is also able to modify BMD.   The effect of vitamin D supplementation on bone mineral accretion was examined in 212 adolescent girls (mean age 11.4 years). 200 or 400 IU/day of vitamin D was compared with placebo and results showed that bone mineral augmentation at the femur was 14.3% and 17.2% higher, respectively, in the groups receiving the vitamin D supplementation when compared to controls87.

Childhood Diabetes

Low vitamin D increases the risk of child diabetes88.  A cohort study involving 10,366 children conducted in Finland showed that higher dietary vitamin D supplementation was associated with reduced risk of type 1 diabetes mellitus. Children who regularly took the recommended supplemental dose of 2000 IU/d of vitamin D during their first year of life had a much lower risk for type 1 diabetes compared with those who regularly received less than 2000 IU/d89. In another study, an association was found between low sun exposure and high incidence rates of type I childhood diabetes after controlling for per capita health expenditure90.  Levels of 25-hydroxyvitamin D (the circulating form of vitamin D) have also been found to be lower in children with type1 diabetes91.

Childhood Asthma

In children there is an association between nutritional rickets (due to vitamin D deficiency) and respiratory disease92. Furthermore, recent epidemiologic studies have clearly demonstrated that there is a link between vitamin D deficiency and incidence of respiratory infections and infants and children seem more susceptible to viral infections in the face of vitamin D deficiency. In a recent study 616 children with asthma were assessed for vitamin D status and 28% of the children had insufficient levels of vitamin D93.  Similarly, an increase in vitamin D levels was associated with reduced odds of any hospitalization in the previous year, any use of anti-inflammatory medications in the previous year, and increased airway responsiveness93.


DHA is extremely important during pregnancy and infancy and contributes to healthy neurological development. Research suggests that DHA is of continued importance after infancy however the physiological need for EPA and the omega-6 GLA increases during childhood and adolescence and provide benefit for a broad range of conditions; modulates mood, well-being, mania and depression; atopic dermatitis and skin allergies; asthma and ADHD.  Vitamin D supplementation is also recommended in children. Deficiencies in this important vitamin is widespread has been documented in many population types and geographic regions. Adequate levels of vitamin D help prevent and reduce low bone mineral density, ensure proper calcium absorption and reduce the incidence of atopic dermatitis, diabetes and asthma.

1. Chance GW. Intrauterine fatty acid accretion rates in human brain: implications for fatty acid requirements, Early Hum. Dev. 1980; 4:121–129.

2. Martinez M. Tissue levels of polyunsaturated fatty acids during early human development, J. Pediatr. 1992;120 : S129–S138.

3. Carver JD, Benford VJ, Han B, Cantor AB, The relationship between age and the fatty acid composition of cerebral cortex and erythrocytes in human subjects.   Brain Res. Bull. 2001; 56: 79–85.

4. Macnamara RK and Carlson SE. Role of omega-3 fatty acids in brain development and function: Potential implications for the pathogenesis and prevention of psychopathology. Prostaglandins, Leukotrienes and Essential Fatty Acids. 2006 ;75: 329–349

5. SanGiovanni JP, Berkey CS, Dwyer JT, Colditz GA. Dietary essential fatty acids, long-chain polyunsaturated fatty acids and visual resolution acuity in healthy full term infants: a systematic review. Early Human Develop. 2000; 57:165-88.

6. Uauy R, Hoffman DR, Mena P, Llanos A, Birch EE. Term infant studies of DHA and ARA supplementation on neurodevelopment: results of randomized controlled trials. J Pediatr. 2003;143:S17.

7. Malcolm CA, McCulloch DL, Montgomery C, Shepherd A, Weaver LT. Maternal docosahexaenoic acid supplementation during pregnancy and visual evoked potential development in term infants; a double blind prospective, randomized trial. Arch Dis Child Fetal Neonatal Ed. 2003; 88:F383.

8. Dunstan JA, Mori TA, Barden A, Beilin JT, Taylor AL, Holt PG, et al. Fish oil supplementation in pregnancy modifies neonatal allergen specific immune responses and clinical outcomes in infants at high risk of atopy: a randomized, controlled trial. J Allergy Clin Immunol. 2003;112:1178-84.

9. Innis SM, Gilley J, Werker J. Are human-milk long-chain polyunsaturated fatty acids related to visual and neural development in breast-fed infants? J Pediatr. 2001;39:532.

10. Jorgensen MH, Hernell O, Hughes EL, Michaelsen KF. Is there a relation between docosahexaenoic acid concentration in mothers’ milk and visual development in term infants? J Pediatr Gastro Nutr. 2001;32:293.

11. Gibson RA, Makrides M, Hawkes JS, Neumann MA, Euler AR. A randomized trial of arachidonic acid dose in for mulas containing docosahexaenoic acid in term infants. In: Riemersma RA, et al., editors. Essential fatty acids and eicosanoids: invited papers from the Fourth International Congress. Champaign, IL: AOCS Press; 1998. pp. 147– 153.

12. Lauritzen L, Jorgensen MH, Mickelsen TB, Skovgaard IM, Straarup E, Olsen SF, et al. Maternal fish oil supplementation in lactation: effect on visual acuity and n-3 fatty acid content of infant erythrocytes. Lipids. 2004;39:195-206.

13. Fleith M, Clandinin MT. Dietary PUFA for preterm and term infants: review of clinical studies. Crit Rev Food Sci and Nutr. 2005;45: 205-29.

14. SanGiovanni JP, Berkey CS, Dwyer JT, Colditz GA. Dietary essential fatty acids, long-chain polyunsaturated fatty acids and visual resolution acuity in healthy full term infants: a systematic review. Early Human Develop. 2000; 57:165–88.

15. Simmer K. Long chain polyunsaturated fatty acid supplementation in infants form at term. The Cochrane Library. 2004;3:1.

16. Uauy R, Hoffman DR, Mena P, Llanos A, Birch EE. Term infant studies of DHA and ARA supplementation on neurodevelopment: results of randomized controlled trials, J. Pediatr. 2003;143:S17–S25.

17. Innis SM, Gilley J, Werker J. Are human-milk long-chain polyunsaturated fatty acids related to visual and neural development in breast-fed infants? J Pediatr. 2001;39:532.

18. Innis SM, Gilley J, Werker J. N-3 docosahexaenoic acid is related to measures of visual and neural development in breast-fed infants to 14 months of age. Am J Clin Nutr. 2002;75:406S.

19.Jensen DL, Voig t RG, Prager TC, Zou YL, Fraley JK, Rozelle JC, et al. Effects of maternal docosahexaenoic acid intake on visual function and neurodevelopment in breastfed term infants. Am J Clin Nutr. 2005;82:125–32.

20.Drover J, Hoffman DR, Castañeda YS, Morale SE, Birch EE. Three randomized controlled trials of early long-chain polyunsaturated Fatty Acid supplementation on means-end problem solving in 9-month-olds. Child Dev. 2009 Sep-Oct;80(5):1376-84.

21. Kim JL, Winkvist A, Aberg MA, Aberg N, Sundberg R, Torén K, Brisman J. Fish consumption and school grades in Swedish adolescents: a study of the large general population. Acta Paediatr. 2010 Jan;99(1):72-7.

22. Richardson AJ, Montgomery P. The Oxford-Durham Study: a randomized, controlled trial of dietary supplementation with fatty acids in children with developmental coordination disorder. Pediatrics 2005;115:1360-1366.

23.Ryan &Nelson 2008. Assessing the Effect of DHA on Cognitive Functions in Healthy, Preschool Children. Clinical Paramedics. 2008;47: 355-362.

24. Lindmark L and Clough P. A 5-Month Open study with Long-Chain Polyunsaturated Fatty Acids in Dyslexia. Journal of Medicinal Food. 2007; 10:662-666.

25. McNamara RK, Able J, Jandacek R, Rider T, Tso P, Eliassen JC, Alfieri D, Weber W, Jarvis K, DelBello MP, Strakowski SM, Adler CM. Docosahexaenoic acid supplementation increases prefrontal cortex activation during sustained attention in healthy boys: a placebo-controlled, dose-ranging, functional magnetic resonance imaging study. Am J Clin Nutr. 2010 Apr;91(4):1060-7.

26. Kennedy DO, Jackson PA, Elliott JM, Scholey AB, Robertson BC, Greer J, Tiplady B, Buchanan T, Haskell CF. Cognitive and mood effects of 8 weeks' supplementation with 400 mg or 1000 mg of the omega-3 essential fatty acid docosahexaenoic acid (DHA) in healthy children aged 10-12 years. Nutr Neurosci. 2009;12:48-56

27. Wozniak J, Biederman J, Mick E, Waxmonsky J, Hantsoo L, Best C, Cluette-Brown JE, Laposata M. Omega-3 fatty acid monotherapy for pediatric bipolar disorder: a prospective open-label trial. Eur Neuropsychopharmacol. 2007 May-Jun;17(6-7):440-7

28. Nemets H, Nemets B, Apter A, Bracha Z, Belmaker RH. Omega-3 treatment of childhood depression: a controlled, double-blind pilot study. Am J Psychiatry. 2006 Jun;163(6):1098-100.

29. Byberg K , Oymar K , Aksnes L. Fatty acids in cord blood plasma, the relation to soluble CD23 and subsequent atopy Prostaglandins Leukotrienes and Essential Fatty Acids. 2008: 78; 61-65

30. Yu G, Bjorksten B. Polyunsaturated fatty acids in school children in relation to allergy and serum IgE levels: Pediatric Allergy and Immunology. 1998; 9: 133-138

31. Lee TH, Hoover RL, Williams JD, et al. Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. N Engl J Med 1985: 312:

32. Snijdewint FGM, Kalinski P, Wieringa EA, Bos JD, Kapsenberg ML. Prostaglandin E2 differentially modulates cytokine secretion profiles of human T-helper lymphocytes. J Immunol 1993: 150: 5321-9.

33. Gold KN, Weyand CM, Goronzy JJ. Modulation of helper T-cell function by prostaglandins. Arthritis Rheum 121 7-24. 1994: 37: 925-33.

34. Hwang I, Cha A, Lee H, Yoon H, Yoon T, Cho B, Lee S, Park Y. N-3 polyunsaturated fatty acids and atopy in Korean preschoolers. Lipids. 2007;42:345-9.

35. Biagi PL, Bordoni A, Masi M, Ricci G, Fanelli C, Patrizi A, Ceccolini E. A long-term study on the use of evening primrose oil (Efamol) in atopic children. Drugs Exp Clin Res. 1988;14:285-90

36. Biagi et al. The effect of GLA on clinical status, red cell fatty acid composition and membrane microviscosity in infants with atopic dermatitis. Drugs Exp Clin Res. 1994;20:77-84.

37. Focke M, Sesztak-Greinecker G, Brannath W, Gotz M, Jarisch R, Hemmer W. Plasma levels of polyunsaturated fatty acids in children with atopic dermatitis and in atopic and non-atopic controls. Weiner Klinische Wochrndchrift. 2005; 117 : 485-491

38.McKeever TM, Britton J. Diet and asthma. Am J Respir Crit Care Med 2004; 170: 725–9.

39.National Institute of Health, National Heart, Lung and Blood Institute. National asthma education & prevention program: expert panel report3: guidelines for diagnosis and management of asthma. Washington, DC, NIH, 2007. Available [Accessed].

40. Mihrshahi S, Peat JK, Webb K, Oddy W, Marks GB, Mellis CM Effect of omega-3 fatty acid concentrations in plasma on symptoms of asthma at 18 months of age. Pediatr Allergy Immunol. 2004;15:517-22.

41. Marks GB, Mihrshahi S, Kemp AS, Tovey ER , Webb K, Almqvist C, Ampon RD, Crisafulli D, Belousova EG, Mellis CM, Peat JK, Leeder SR . Prevention of asthma during the first 5 years of life: A randomized controlled trial. Journal of Allergy and Clinical Immunology. 2006;118: 53-61

42. Oddy WH, de Klerk NH, Kendall GE, Mihrshahi S, Peat JK. Ratio of omega-6 to omega-3 fatty acids and childhood asthma Journal of Asthma. 2004; 4: 319-326

43. Nagakura T, Matsuda S, Shichijyo K, Sugimoto H, Hata K. Dietary supplementation with fish oil rich in omega-3 polyunsaturated fatty acids in children with bronchial asthma. Eur Respir J. 2000;16:861-5.

44. Association AP: Attention deficit hyperactivity disorder. In Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) Arlington, VA, American Psychiatric Association; 2000.

45. Harding KL, Judah RD, Gant C: Outcome-based comparison of Ritalin versus food-supplement treated children with AD/ HD. Altern Med Rev 2003, 8:319-330.

46. Scahill L, Schwab-Stone M: Epidemiology of ADHD in school-age children. Child Adolesc Psychiatr Clin N Am 2000, 9:541-55.

47. Boyle MH, Offord DR, Racine Y, Sanford M, Szatmari P, Fleming JE: Evaluation of the original Ontario Child Health Study scales. Can J Psychiatry 1993, 38:397-405.

48. Breton JJ, Bergeron L, Valla JP, Berthiaume C, Gaudet N, Lambert J, St Georges M, Houde L, Lepine S: Quebec child mental health survey: prevalence of DSM-III-R mental health disorders. J Child Psychol Psychiatry 1999; 40:375-384.

49. Rowland AS, Lesesne CA, Abramowitz AJ: The epidemiology of attention-deficit/hyperactivity disorder (ADHD): a public health view. Ment Retard Dev Disabil Res Rev 2002, 8:162-170.

50. Richardson AJ, Puri BK: The potential role of fatty acids in attention-deficit/hyperactivity. Essent Fatty Acids 2000, 63:79-87.

51. Kirby A, Woodward A, Jackson S, Wang Y, Crawford MA. Childrens' learning and behaviour and the association with cheek cell polyunsaturated fatty acid levels. Res Dev Disabil. 2010 May-Jun;31(3):731-42.

52. Transler C, Eilander A, Mitchell S, van de Meer N. The Impact of Polyunsaturated Fatty Acids in Reducing Child Attention Deficit and Hyperactivity Disorders. J Atten Disord. 2010 Apr 27. [Epub ahead of print]

53. Stevens LJ, Zentall SS, Abate ML, Kuczek T AND Burgess JR. Omega-3 Fatty Acids in Boys With Behavior, Learning, and Health Problems Physiology & Behavior. 1996; 59:915-920

54. Germano M, Domenico M, Montorfano G, Adorni L, Negroni M, Berra B, Rizzo AM. Plasma, red blood cells phospholipids and clinical evaluation after long chain omega-3 supplementation in children with attention deficit hyperactivity disorder (ADHD). Nutritional Neuroscience. 2007;10: 1–9

55. Voigt, R.G., Llorente, A.M., Jensen, C.L., Fraley, J.K., Berretta, M.C., and Heird, W.C. A Randomized, Double-Blind, Placebo-Controlled Trial of Docosahexaenoic Acid Supplementation in Children with Attention Deficit /Hyperactivity Disorder, J. Pediatr. 2001;139: 189–196.

56. Bélanger SA, Vanasse M, Spahis S, Sylvestre MP, Lippé S, L'heureux F, Ghadirian P, Vanasse CM, Levy E. Omega-3 fatty acid treatment of children with attention-deficit hyperactivity disorder: A randomized, double-blind, placebo controlled study. Paediatr Child Health. 2009;14:89-98.

57. Vaisman N, Kaysar N, Zaruk-Adasha Y, Pelled D, Brichon G, Zwingelstein G, Bodennec JCorrelation between changes in blood fatty acid composition and visual sustained attention performance in children with inattention: effect of dietary n-3 fatty acids containing phospholipids. Am J Clin Nutr. 2008;87:1170-80.

58. Gustafsson PA, Birberg-Thornberg U, Duchén K, Landgren M, Malmberg K, Pelling H, Strandvik B, Karlsson T. EPA supplementation improves teacher rated behaviour and oppositional symptoms in children with ADHD. Acta Paediatr. 2010 May 19. [Epub ahead of print]

59. Stevens L, Zhang W, Peck L, Kuczek T, Grevstad N, Mahon A, Zentall SS, Arnold LE, Burgess JR. EFA supplementation in children with inattention, hyperactivity, and other disruptive behaviors. Lipids. 2003;38:1007-21.

60. Hirayama S, Hamazaki T, Terasawa K. Effect of docosahexaenoic acid-containing food administration on symptoms of attention-deficit/hyperactivity disorder - a placebo-controlled double-blind study. Eur J Clin Nutr. 2004 Mar;58(3):467-73.

61.Johnson M, Ostlund S, Fransson G, Kadesjö B, Gillberg C. Omega-3/omega-6 fatty acids for attention deficit hyperactivity disorder: a randomized placebo-controlled trial in children and adolescents. J Atten Disord. 2009;12:394-401.

62. Sorgi PJ, Hallowell EM, Hutchins HL, Sears B. 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. Nutr J. 2007 J;6:16.

63. Richardsona AJ, Basant Puri K .A randomized double-blind, placebo controlled study of the effects of supplementation with highly unsaturated fatty acids on ADHD-related symptoms in children with specific learning difficulties. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 202;26:233-23

64. Amminger GP, Berger GE, Schäfer MR, Klier C, Friedrich MH, Feucht M.Omega-3 Fatty Acids Supplementation in Childrem with Autism: A Double-blind Randomized, Placebo-controlled Pilot Study. Biol Psychiatry. 2007;61:551-3.

65. Bell JG, MacKinlay EE, Dick JR, MacDonald DJ, Boyle RM, Glen AC. Essential fatty acids and phospholipase A2 in autistic spectrum disorders. Prostaglandins Leukot Essent Fatty Acids. 2004; 71:201–204.

66. Vancassel S, Durand G. Barthelemy C, Lejeune B, Martineau J, Guilloteau D, Andre's C, Chalon S. Plasma fatty acid levels in autistic children. Prost Leukotrienes and Essential Fatty Acids. 2001;65:1-7

67. Reaven et al. Cognitive-Behavioral Group Treatment for Anxiety Symptoms in Children With High-Functioning Autism Spectrum Disorders A Pilot Study Focus on Autism and Other Developmental Disabilities. 2009;24:27-37

68. Meguid NA, Atta HM, Gouda AS, Khalil RO. Role of polyunsaturated fatty acids in the management of Egyptian children with autism. Clin Biochem. 2008;41:1044-8.

69. Amre DK, D'Souza S, Morgan K, Seidman G, Lambrette P, Grimard G, Israel D, Mack D, Ghadirian P, Deslandres C, Chotard V, Budai B, Law L, Levy E, Seidman EG.Imbalances in dietary consumption of fatty acids, vegetables, and fruits are associated with risk for Crohn's disease in children. Am J Gastroenterol. 2007;102:2016-25

70. Romano C, Cucchiara S, Barabino A, Annese V, Sferlazzas C.Usefulness of omega-3 fatty acid supplementation in addition to mesalazine in maintaining remission in pediatric Crohn's disease: a double-blind, randomized, placebo-controlled study.World J Gastroenterol. 2005;11:7118-21.

71. Norris JM, Yin X, Lamb MM, Barriga K, Seifert J, Hoffman M, Orton HD, Barón AE, Clare-Salzler M, Chase HP, Szabo NJ, Erlich H, Eisenbarth GS, Rewers M.    Omega-3 polyunsaturated fatty acid intake and islet autoimmunity in children at increased risk for type 1 diabetes. JAMA. 2007 Sep 26;298(12):1420-8.

72. Stene LC, Joner G; Norwegian. Use of cod liver oil during the first year of life is associated with lower risk of childhood-onset type 1 diabetes: a large, population-based, case-control study. Am J Clin Nutr. 2003;78:1128-34.

73. Scaglioni et al. Plasma long-chain fatty acids and the degree of obesity in Italian children. Acta Paediatr.2006;95:964-9.

74.Klein-Platat C, Drai J, Oujaa M, Schlienger J-L, Simon C. Plasma fatty acid composition is associated with the metabolic syndrome and low-grade inflammation in overweight adolescents. Am J Clin Nutr. 2005;82:1178-1184.

75. Huh S.Y. and Gordon C.M. Vitamin D deficiency in children and adolescents: Epidemiology, impact and treatment. Reviews in Endocrine and Metabolic Disorders 2008; 9:161-170

76. CM, DePeter KC, Feldman HA, Grace E, Emans SJ. Prevalence of vitamin D deficiency among healthy adolescents. Arch Pediatr Adolesc Med. 2004;158:531-537.

77. Sullivan SS, Rosen CJ, Halteman WA, Chen TC, Holick MF. Adolescent girls in Maine are at risk for vitamin D insufficiency. J Am Diet Assoc. 2005;105:971-97

78. Roth D.E., Martz P., Yeo R., Prosser C., Bell M. and Jones A.B. Are national vitamin D guidelines sufficient to maintain adequate blood levels in children? Canadian Journal of Public Health 2005; 96:443-449

79. El-Hajj Fuleihan G, Nabulsi M, Choucair M, et al. Hypovitaminosis D in healthy schoolchildrren. Pediatrics. 2001;107:E53.

80. Glendenning P, Fraser WD. 25-OH-vitamin D assays [letter]. J Clin Endocrinol Metab. 2005;90:3129.

81. Looker AC, Dawson-Hughes B, Calvo MS, Gunter EW, Sahyoun NR. Serum 25-hydroxyvitamin D status of adolescents and adults in two seasonal subpopulations from NHANES III. Bone. 2002;30:771-777.

82. Outila TA, Karkkainen MU, Lamberg-Allardt CJ. Vitamin D status affects serum parathyroid hormone concentrations during winter in female adolescents: associations with forearm bone mineral density. Am J Clin Nutr. 2001;74:206-210

83. Lehtonen-Veromaa M, Möttönen T, Leino A, Heinonen OJ, Rautava E, Viikari J. Prospective study on food fortification with vitamin D among adolescent females in Finland: minor effects. Br J Nutr. 2008;100:418-23.

84. Cheng S, Tylavsky F, Kröger H, Kärkkäinen M, Lyytikäinen A, Koistinen A, Mahonen A, Alen M, Halleen J, Väänänen K, Lamberg-Allardt C. Association of low 25-hydroxyvitamin D concentrations with elevated parathyroid hormone concentrations and low cortical bone density in early pubertal and prepubertal Finnish girls. Am J Clin Nutr. 2003;78:485-92.

85. Fares JE, Choucair M, Nabulsi M, Salamoun M, Shahine CH, Fuleihan Gel-H. Effect of gender, puberty, and vitamin D status on biochemical markers of bone remodedeling. Bone. 2003;33:242-7.

86. Lehtonen-Veromaa MK, Möttönen TT, Nuotio IO, Irjala KM, Leino AE, Viikari JS.Vitamin D and attainment of peak bone mass among peripubertal Finnish girls: a 3-y prospective study. Am J Clin Nutr. 2002;76:1446-53.

87. Viljakainen HT, Palssa A, Kärkkäinen M, Jakobsen J, Cashman KD, Mølgaard C, Lamberg-Allardt C. A seasonal variation of calcitropic hormones, bone turnover and bone mineral density in early and mid-puberty girls - a cross-sectional study. Br J Nutr. 2006;96:124-30.

88. Borkar VV, Verma S, Bhalla A. Low levels of vitamin D in North Indian children with newly diagnosed type 1 diabetes. Pediatr Diabetes. 2009 Nov 9. [Epub ahead of print]

89. Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet. 2001; 358:1500-1503

90. Mohr SB Garland CF, Gorham ED, Garland FC . The association between ultraviolet B irradiance, vitamin D status and incidence rates of type 1 diabetes in 51 regions worldwide. Diabetologia. 2008; 51: 1391-1398

91. Munns C, Zacharin MR, Rodda CP, et al. Prevention and treatment of infant and childhood vitamin D deficiency in Australia and New Zealand: a consensus statement. Med J Aust 2006; 185: 268-272.

92. Walker VP , Modlin RL. The Vitamin D Connection to Pediatric Infections and Immune Function. Pediatric Research. 2009;65: 106R-113R

93. Brehm JM, Celedón JC, Soto-Quiros ME, Avila L, Hunninghake GM, Forno E, Laskey D, Sylvia JS, Hollis BW, Weiss ST, Litonjua AA. Serum vitamin D levels and markers of severity of childhood asthma in Costa Rica. Am J Respir Crit Care Med. 2009;179:765-71.