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3. Unsaturated fatty acids, probiotics and more for ADHD

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3. Unsaturated fatty acids, probiotics and more for ADHD

3. Unsaturated fatty acids in ADHD

3.1. Monounsaturated fatty acids

A large study of 432 children found significantly lower serum levels of monounsaturated fatty acids (PUFAs) in children with ADHD.1 This correlated with an increased intake of nutrient-poor foods such as high-sugar and high-fat foods and a reduced intake of vegetables, fruit and protein-rich foods compared to healthy children.
It remains to be seen whether the change in diet is the cause, consequence or vicious circle of ADHD.

3.2. Polyunsaturated fatty acids (PUFAs)

One review came to the recommendation of a combination of EPA, DHA and GLA in a ratio of 9:3:1 for ADHD.2 The lead author is involved in a company that sells unsaturated fatty acids.

3.2.1. Omega-3 fatty acids

An administration of 635 mg eicosapentaenoic acid (EPA) and 195 mg docosahexaenoic acid (DHA) (unsaturated fatty acids) reduced serum CRP and IL-6 levels in children with ADHD and improved ADHD symptoms within 8 weeks in a double-blind placebo study.3

A combination of the triple unsaturated fatty acids EPA and DHA in rats in stress tests4

  • Prevented or compensated dendritic atrophy in the CA3 region of the hippocampus
  • Restored GABA release in the CA1 region of the hippocampus
  • Improved spatial memory.

A placebo-controlled double-blind study found improvements in attention in children with ADHD as well as in children not affected by omega-3 fatty acids.5
A study of healthy adolescents found a trend towards an improvement in sustained attention and ADHD symptoms in those participants who consumed nuts more consistently when consuming walnuts over 6 months.6 This could reflect the fact that young people who perceive a benefit (even unconsciously) from consuming nuts are more likely to continue doing so.

One RCT found no improvement in ADHD-RS intention score or inattention with omega-3/6 supplementation at either 6 or 12 months. There was a positive response of 46.3% in the omega-3/6 group and 45.6% in the placebo group. The study used two capsules per day, each containing 279 mg eicosapentaenoic acid [EPA], 87 mg docosahexaenoic acid [DHA], 30 mg gamma-linolenic acid [GLA].7

Omega-3 fatty acids are among others:

  • Eicosapentaenoic acid (EPA)
    • A Japanese study found significantly reduced EPA blood plasma levels in 24 people with ADHD under the age of 20.8
  • Docosahexaenoic acid (DHA)
    • A Japanese study found significantly reduced DHA blood plasma levels in 24 people with ADHD under the age of 20.8
    • A combination of the triple unsaturated fatty acids EPA and DHA in rats in stress tests4
      • Prevented or compensated dendritic atrophy in the hippocampus CA3 region
      • Restored GABA release in the hippocampus CA1 region
      • Improved spatial memory.
  • Roughanic acid
  • Alpha-linolenic acid
  • Stearidonic acid
  • Eicosatetraenoic acid
  • Heneicosapentaenoic acid
  • Docosapentaenoic acid
  • Tetracosapentaenoic acid
    (scoliodonic acid)
  • Tetracosahexaenoic acid
    (nisic acid)

3.2.2. Omega-6 fatty acids

One RCT found no improvement in ADHD-RS intention score or inattention with omega-3/6 supplementation at either 6 or 12 months. There was a positive response of 46.3% in the omega-3/6 group and 45.6% in the placebo group. The study used two capsules per day, each containing 279 mg eicosapentaenoic acid [EPA], 87 mg docosahexaenoic acid [DHA], 30 mg gamma-linolenic acid [GLA].7

Omega-6 fatty acids are among others:

  • Arachidonic acid (AA)
    • A Japanese study found significantly reduced AA blood plasma levels in 24 people with ADHD under the age of 20.8
  • Linoleic acid (LA)
  • Gamma-linolenic acid (GLA)
  • Dihomo-gamma-linolenic acid (DHGLA)

4. Treatment of the gut-brain axis in ADHD

4.1. Probiotics for ADHD

For background information on gut bacteria, gut-brain axis and their role in the development of ADHD, see Gut bacteria, gut-brain axis (gut-brain axis) In the article Age-independent physical stress as an environmental cause of ADHD in the chapter Development.

Various studies report positive effects of probiotics in children with ADHD.

  • L. rhamnosus GG
    • Administration during the first 6 months of life reduced the risk of later ADHD9
    • Giving children improved ADHD symptoms in the parent rating, but not in the teacher rating10
  • B. bifidum Bf-688
    • Administration to children improved inattention, hyperactivity/impulsivity, increased weight11
      • Firmicutes reduced
      • Ratio of Firmicutes to Bacteroidetes (F/B ratio) reduced
      • Proteobacteria increased
    • B. subtilis, B. bifidum, B. breve, B. infantis, B. longum, L. acidophilus, L. delbrueckii, L. casei, L. plantarum L. lactis, L. salivarius, S. thermophiles
      • Administration in addition to MPH improved ADHD symptoms in children compared to placebo12
    • L. reuteri, L. acidophilus, L. fermentum, B. bifidum
      • Administration improved ADHD symptoms RS in children compared to placebo. In addition, serum high-sensitivity C-reactive protein (hs-CRP) decreased and total antioxidant plasma volume (TAC) increased compared to placebo. CDI and other metabolic characteristics unchanged.13
  • L. mesenteroides, L. paracasei, L. plantarum, B-glucan, inulin
    • ADHD symptoms in children and adults improved to the same extent in the treatment group and placebo group, ASD symptoms remained unchanged14

A meta-analysis found no improvement with probiotics in ADHD.15

4.2. Fecal transplantation for ADHD

To date, the studies needed to assess whether fecal transplants are a treatment option for ADHD are lacking.

One study found that mice whose guts were contaminated with gut bacteria from people with ADHD had structural changes in the brain (white matter, gray matter, hippocampus, internal capsule), decreased connectivity between motor and visual cortices right in the resting state, and higher anxiety than mice in which gut bacteria from people without ADHD were used.16
A single case study reported an improvement in ADHD symptoms in a young woman with gut bacteria replacement related to a recurrent Clostridioides difficile infection.17

5. Other substances for ADHD

5.1. Homocysteine

Homocysteine is not a vitamin, but an amino acid
A deficiency of folic acid, vitamin B2, B6 and/or B12 can cause an excess of homocysteine.18 Elevated homocysteine levels can have a neurotoxic effect.

One study found elevated homocysteine levels in ADHD correlated with increased hyperactivity/impulsivity 19
In contrast, a smaller study found evidence of homocysteine deficiency in children with ADHD.20

5.2. Polyphenols

Polyphenols are aromatic compounds with two or more hydroxyl groups directly bound to an aromatic ring. Polyphenols are formed from phenylalanine, which in turn is formed from shikimic acid.

Natural polyphenols (of which there are said to be over 8,000) are often contained in plants as bioactive substances (colorants, flavorings, tannins), e.g.

  • Flavonoids (colorants)
    • Flavonoids appear to have a glutamate-antagonistic and GABA-agonistic effect.21
  • Anthocyanins (colorants)
  • Procyanidins
  • Benzoic acid derivatives, e.g.
    • Vanillic acid
    • Gallic acid
    • Protocatechuic acid
  • Cinnamic acid derivatives, e.g.
    • Caffeic acid
    • Coumaric acid
  • Style derivatives, e.g.
    • Resveratrol
      • Component of red wine

Certain polyphenols are said to be able to influence neurophysiological changes caused by early childhood stress:22 e.g:

  • Reduction of depressive symptoms through
    • Xanthohumol
    • Quercetin
    • Phlorotannins
  • Reduction of anxiety symptoms through
    • Quercetin
    • Phlorotannins
  • Elimination of the BDNF reduction by
    • Xanthohumol
  • No correction of the dopamine and serotonin level changes in the brain stem triggered by early stress
  • Reduction of the cortisol stress response to acute stress through
    • Xanthohumol

One study found a correlation of increased polyphenol intake with reduced risk of ADHD in preschool children.23

5.3. Phosphatidylserine

Phosphatidylserine is not a vitamin, but a phospholipid.

Source: Bieger.24


  1. Wang, Yu, Fu, Yeh, Hsu, Yang, Yang, Huang, Wei, Chen, Chiang, Pan (2019): Dietary Profiles, Nutritional Biochemistry Status, and Attention-Deficit/Hyperactivity Disorder: Path Analysis for a Case-Control Study. J Clin Med. 2019 May 18;8(5). pii: E709. doi: 10.3390/jcm8050709. n = 432

  2. D’Helft, Caccialanza, Derbyshire, Maes (2022): Relevance of ω-6 GLA Added to ω-3 PUFAs Supplements for ADHD: A Narrative Review. Nutrients. 2022 Aug 10;14(16):3273. doi: 10.3390/nu14163273. PMID: 36014778.

  3. Hariri, Djazayery, Djalali, Saedisomeolia, Rahimi, Abdolahian (2012): Effect of n-3 supplementation on hyperactivity, oxidative stress and inflammatory mediators in children with attention-deficit-hyperactivity disorder. Malays J Nutr. 2012 Dec;18(3):329-35. n = 103

  4. Pérez, Peñaloza-Sancho, Ahumada, Fuenzalida, Dagnino-Subiabre (2018): n-3 Polyunsaturated fatty acid supplementation restored impaired memory and GABAergic synaptic efficacy in the hippocampus of stressed rats. Nutr Neurosci. 2018 Oct;21(8):556-569. doi: 10.1080/1028415X.2017.1323609.

  5. Bos, Oranje, Veerhoek, Van Diepen, Weusten, Demmelmair, Koletzko, de Sain-van der Velden, Eilander, Hoeksma, Durston (2015): Reduced Symptoms of Inattention after Dietary Omega-3 Fatty Acid Supplementation in Boys with and without Attention Deficit/Hyperactivity Disorder. Neuropsychopharmacology. 2015 Sep;40(10):2298-306. doi: 10.1038/npp.2015.73. PMID: 25790022; PMCID: PMC4538345. n = 79

  6. Pinar-Martí A, Gignac F, Fernández-Barrés S, Romaguera D, Sala-Vila A, Lázaro I, Ranzani OT, Persavento C, Delgado A, Carol A, Torrent J, Gonzalez J, Roso E, Barrera-Gómez J, López-Vicente M, Boucher O, Nieuwenhuijsen M, Turner MC, Burgaleta M, Canals J, Arija V, Basagaña X, Ros E, Salas-Salvadó J, Sunyer J, Julvez J (2023): Effect of walnut consumption on neuropsychological development in healthy adolescents: a multi-school randomised controlled trial. EClinicalMedicine. 2023 Apr 6;59:101954. doi: 10.1016/j.eclinm.2023.101954. PMID: 37096186; PMCID: PMC10121389. RCT

  7. Carucci, Romaniello, Demuru, Curatolo, Grelloni, Masi, Liboni, Mereu, Contu, Lamberti, Gagliano, Zuddas (2022): Omega-3/6 supplementation for mild to moderate inattentive ADHD: a randomised, double-blind, placebo-controlled efficacy study in Italian children. Eur Arch Psychiatry Clin Neurosci. 2022 Jun 7. doi: 10.1007/s00406-022-01428-2. PMID: 35672606. RCT, n = 160

  8. Yonezawa, Nonaka, Iwakura, Kusano, Funamoto, Kanchi, Yamaguchi, Kusumoto, Imamura, Ozawa (2018): Investigation into the plasma concentration of ω3 polyunsaturated fatty acids in Japanese attention-deficit hyperactivity disorder patients. J Neural Transm (Vienna). 2018 Jun 20. doi: 10.1007/s00702-018-1895-z.; n = 24

  9. Pärtty A, Kalliomäki M, Wacklin P, Salminen S, Isolauri E (2015): A possible link between early probiotic intervention and the risk of neuropsychiatric disorders later in childhood: a randomized trial. Pediatr Res. 2015 Jun;77(6):823-8. doi: 10.1038/pr.2015.51. PMID: 25760553., n = 132

  10. Kumperscak HG, Gricar A, Ülen I, Micetic-Turk D (2020): A Pilot Randomized Control Trial With the Probiotic Strain Lactobacillus rhamnosus GG (LGG) in ADHD: Children and Adolescents Report Better Health-Related Quality of Life. Front Psychiatry. 2020 Mar 17;11:181. doi: 10.3389/fpsyt.2020.00181. PMID: 32256407; PMCID: PMC7092625. RCT, n = 35

  11. Wang LJ, Yang CY, Kuo HC, Chou WJ, Tsai CS, Lee SY (2022): Effect of Bifidobacterium bifidum on Clinical Characteristics and Gut Microbiota in Attention-Deficit/Hyperactivity Disorder. J Pers Med. 2022 Feb 7;12(2):227. doi: 10.3390/jpm12020227. PMID: 35207715; PMCID: PMC8877879. n = 30

  12. Ghanaatgar M, Taherzadeh S, Ariyanfar S, Razeghi Jahromi S, Martami F, Mahmoudi Gharaei J, Teimourpour A,Shahrivar Z (2023): Probiotic supplement as an adjunctive therapy with Ritalin for treatment of attention-deficit hyperactivity disorder symptoms in children: a double-blind placebo-controlled randomized clinical trial“, Nutrition & Food Science, Vol. 53 No. 1, pp. 19-34. doi.org/10.1108/NFS-12-2021-0388, RCT, n = 38

  13. Sepehrmanesh Z, Shahzeidi A, Mansournia M, Ghaderi A, Ahmadvand A (2021): Clinical and Metabolic Reaction to Probiotic Supplement in Children Suffering Attention-Deficit Hyperactivity Disorder. A Randomized, Double-Blind, Placebo-Controlled Experiment. International Archives of Health Sciences 8(2):p 90-96, Apr–Jun 2021. | DOI: 10.4103/iahs.iahs_112_20. RCT, n = 34

  14. Skott E, Yang LL, Stiernborg M, Söderström Å, Rȕegg J, Schalling M, Forsell Y, Giacobini M, Lavebratt C. Effects of a synbiotic on symptoms, and daily functioning in attention deficit hyperactivity disorder - A double-blind randomized controlled trial. Brain Behav Immun. 2020 Oct;89:9-19. doi: 10.1016/j.bbi.2020.05.056. PMID: 32497779., RCT, n = 182

  15. Liang SC, Sun CK, Chang CH, Cheng YS, Tzang RF, Chiu HJ, Wang MY, Cheng YC, Hung KC (2024): Therapeutic efficacy of probiotics for symptoms of attention-deficit hyperactivity disorder in children and adolescents: meta-analysis. BJPsych Open. 2024 Jan 25;10(1):e36. doi: 10.1192/bjo.2023.645. PMID: 38268113.

  16. Tengeler, Dam, Wiesmann, Naaijen, van Bodegom, Belzer, Dederen, Verweij, Franke, Kozicz, Arias Vasquez, Kiliaan (2020): Gut microbiota from persons with attention-deficit/hyperactivity disorder affects the brain in mice. Microbiome. 2020 Apr 1;8(1):44. doi: 10.1186/s40168-020-00816-x. PMID: 32238191; PMCID: PMC7114819.

  17. Hooi, Dwiyanto, Rasiti, Toh, Wong RKM, Lee JWJ (2022): A case report of improvement on ADHD symptoms after fecal microbiota transplantation with gut microbiome profiling pre- and post-procedure. Curr Med Res Opin. 2022 Sep 26:1-13. doi: 10.1080/03007995.2022.2129232. PMID: 36164761.

  18. Bieger (2011): Neurostress Guide, Seite 12

  19. Yektaş, Alpay, Tufan (2019): Comparison of serum B12, folate and homocysteine concentrations in children with autism spectrum disorder or attention deficit hyperactivity disorder and healthy controls. Neuropsychiatr Dis Treat. 2019 Aug 6;15:2213-2219. doi: 10.2147/NDT.S212361. eCollection 2019. n = 118

  20. Altun, Şahin, Belge Kurutaş, Güngör (2018): Homocysteine, Pyridoxine, Folate and Vitamin B12 Levels in Children with Attention Deficit Hyperactivity Disorder. Psychiatr Danub. 2018 Sep;30(3):310-316. doi: 10.24869/psyd.2018.310. n = 60

  21. Citraro, Navarra, Leo, Donato Di Paola, Santangelo, Lippiello, Aiello, Russo, De Sarro (2016): The Anticonvulsant Activity of a Flavonoid-Rich Extract from Orange Juice Involves both NMDA and GABA-Benzodiazepine Receptor Complexes. Molecules. 2016 Sep 21;21(9). pii: E1261.

  22. Donoso, Egerton, Bastiaanssen, Fitzgerald, Gite, Fouhy, Ross, Stanton, Dinan, Cryan (2020): Polyphenols selectively reverse early-life stress-induced behavioural, neurochemical and microbiota changes in the rat. Psychoneuroendocrinology. 2020 Jun;116:104673. doi: 10.1016/j.psyneuen.2020.104673. PMID: 32334345.

  23. Darzi M, Abbasi K, Ghiasvand R, Akhavan Tabib M, Rouhani MH (2022): The association between dietary polyphenol intake and attention-deficit hyperactivity disorder: a case-control study. BMC Pediatr. 2022 Dec 6;22(1):700. doi: 10.1186/s12887-022-03768-3. PMID: 36474220; PMCID: PMC9724259. n = 400

  24. Bieger (2006): Neuroscience Guide – Ein innovatives, diagnostisches und therapeutisches Stufenprogramm bei Neurotransmitter-Störungen, Seite 19

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