3. Unsaturated fatty acids, probiotics and more for ADHD
- 3. Unsaturated fatty acids in ADHD
- 4. Treatment of the gut-brain axis in ADHD
- 5. Other substances 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)
Omega-3 PUFAs are not synthesized in the human organism and must be taken in with food. If the diet is unbalanced, they must be supplemented. Foods with a high omega-3 PUFA content are linseed oil, linseed, chia seeds, walnut oil, walnuts, rapeseed oil, tuna, herring, salmon and mackerel.
The need for omega-3 PUFA is particularly high during growth phases (first years of life and puberty).
Omega-3 PUFAs are important for the anatomical and functional brain development of the brain. They influence the maturation and function of neurons and the processes of neurogenesis, migration, synaptogenesis and neurotransmission. They are substrates for the synthesis of bioactive compounds and are involved in the control of acute and chronic inflammation and the regulation of immune cells.9
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
- B. bifidum Bf-688
- Administration to children improved inattention, hyperactivity/impulsivity, increased weight12
- 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 placebo13
- 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.14
- Administration to children improved inattention, hyperactivity/impulsivity, increased weight12
- 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 unchanged15
A meta-analysis found no improvement with probiotics in ADHD.16
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.17
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.18
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.19 Elevated homocysteine levels can have a neurotoxic effect.
One study found elevated homocysteine levels in ADHD correlated with increased hyperactivity/impulsivity 20
In contrast, a smaller study found evidence of homocysteine deficiency in children with ADHD.21
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.22
- 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
- Resveratrol
Certain polyphenols are said to be able to influence neurophysiological changes caused by early childhood stress:23 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.24
5.3. Phosphatidylserine
Phosphatidylserine is not a vitamin, but a phospholipid.
Source: Bieger.25
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 ↥
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. ↥
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 ↥
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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 ↥
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 ↥
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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 ↥ ↥ ↥
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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 ↥
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 ↥
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 ↥
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 ↥
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