Certain physical illnesses, toxins, or food intolerances appear to be able to increase the risk of ADHD (or other mental disorders) throughout life.
4.1. Breathing pauses during sleep¶
Breathing pauses in children’s sleep can trigger cognitive distress, causing symptoms that resemble ADHD.
It is open whether sleep breathing cessations can be such a stressor that they can contribute to ADHD through epigenetic changes, or whether they merely cause symptoms similar to those of ADHD. In the latter case, in people who did not have ADHD before, and who developed ADHD (similar) symptoms due to breathing pauses during sleep, these would have to disappear completely after elimination of the breathing pauses during sleep. So far, we are not aware of any studies on this.
4.2. Toxins¶
4.2.1. Parents smoking¶
Postnatal parental smoking correlates with a 1.3-fold risk (increased by 30%) for ADHD in the offspring.
This could be related to genetic factors, as ADHD sufferers smoke significantly more often. The comorbidity of smoking to ADHD is 40%. In contrast, of the total population, about 25% smoke less, namely 26.9% of women and 32.6% of men.
4.2.2. Polychlorinated biphenyls (PCBs) / Polychlorinated biphenyl ethers¶
Polychlorinated biphenyls and polychlorinated biphenyl ethers are suspected of causing ADHD.
Polychlorinated biphenyls inhibit dopamine synthesis as well as the storage of dopamine in the vesicles and its release, thus causing a too low dopamine level. PBCs also cause hyperactivity and impulsivity (in rats already at subtoxic doses).
There is weak evidence (= not proven) of relevance in ADHD.
PCBs have been banned in Germany since 1989.
4.2.3. Polyvenyl chloride (PVC)¶
One review describes a suspected correlation of PVC exposure and ADHD.
4.2.4. Pesticides¶
With regard to pesticides (especially organochlorine compounds, pyrethroids, organophosphates), there are indications (= not proven with certainty) of relevance in ADHD.
On pesticides in pregnancy and ADHD, see above.
4.2.4.1. Organochlorine compounds¶
A study of Greek school children with ADHD found no elevated blood serum levels of
- Dichlorodiphenyltrichloroethane (DDT) Metabolites
- Hexachlorocyclohexane (HCH) isomers
- Cyclodienes
- Methoxychlor
4.2.4.2. Organophosphates¶
Organophosphate pesticides have no effect according to two major studies, while other studies found a correlation of prenatal and postnatal exposure and ADHD((Marks, Harley, Bradman, Kogut, Barr, Johnson, Calderon, Eskenazi (2010): Organophosphate pesticide exposure and attention in young Mexican-American children: the CHAMACOS study. Environ Health Perspect. 2010 Dec;118(12):1768-74. doi: 10.1289/ehp.1002056. PMID: 21126939; PMCID: PMC3002198.)) or discussed a theoretically possible increase in ADHD risk. One source suggests an increased ADHD risk from organophosphates particularly when coinciding with a particular MAO-A gene variant that causes lower serotonin depletion.
A study in rats was able to induce ADHD-like behaviors in Wystar and SHR rats by organosphates and shows strong circumstantial evidence that these are mediated by decreases in fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) via the cannabinoid receptor.
Blood levels were measured in Egyptian adolescents, some of whom used pesticides, and parents were asked about ADHD symptoms in the adolescents:
No correlation to ADHD was found with respect to chlorpyrifos.
Measured were:
- Organophosphate
- Urinary trichloro-2-pyridinol (TCPy) as a specific metabolite biomarker for exposure to chlorpyrifos
4.2.5. Pyrethroids¶
Blood levels were measured in Egyptian adolescents, some of whom used pesticides, and parents were asked about ADHD symptoms in the adolescents:
A correlation to ADHD was found with respect to pyrethroid λCH by the Cis-DCCA reading (all subjects reported clinical ADHD symptoms).
Measured was:
- Pyrethroids
- urinary cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid (cis-DCCA) as a specific biomarker of exposure to αCM
- Lambda-cyhalothric acid (λCH-acid) as a specific biomarker for exposure to λCH
- urinary 3-phenoxybenzoic acid (3-PBA) as a general metabolite biomarker for exposure to pyrethroids
4.2.6. Mercury / Amalgam (Mercury)¶
There is weak evidence (= not proven) of relevance in ADHD.
A large study with n = 2073 participants could not find any association between amalgam and ADHD.
4.2.7. Manganese or formaldehyde¶
There is weak evidence of relevance in ADHD, with elevated levels of manganese found only in hair but not in blood levels in ADHD sufferers.
4.2.8. Lead (Lead)¶
Elevated blood lead levels lead to an increased risk of ADHD. A blood lead level of ≥ 5 μg/dl was found to increase the risk of ADHD by 1.33 (OR 2.33).
A connection between ADHD and lead is said to exist in particular if affected individuals possess the DRD2 gene variant rs1800497r. A connection to certain MAO-A gene variants is also mentioned, which causes a lower serotonin degradation. A study in rats suggests interactions of lead exposure and early stress on the dopaminergic system.
One long-term study found no immediate increased ADHD risk in people with past lead exposure, but increased externalizing behaviors and increased addiction risks.
Lead disposition during pregnancy may increase ADHD risk. See above.
Even a lead content in drinking water below the limit values is said to be problematic.
Increased lead absorption can occur from old water pipes. In principle, lead water pipes pose little risk in areas with calcareous water, since lime forms a reliably protective layer in the pipes. However, if a water softening system is installed, this protective lime layer can be lost. If old lead pipes are still present, this can lead to increased lead absorption.
Lead is hardly relevant as a toxin in Central Europe. In less developed countries, however, lead can be a serious problem.
Lead increases dopaminergic activity and has been linked to attention deficits, Alzheimer’s disease, and increased drug sensitivity.
4.2.9. Bisphenol A¶
Bisphenol A is suspected of increasing the risk of ADHD. A connection with certain MAO-A gene variants, which cause lower serotonin degradation and an influence on thyroid balance is discussed.
A meta-study found a clear link between bisphenol exposure and ADS(H)S.
4.2.10. Perfluoroalkyl compounds¶
Elevated levels of perfluoroalkyl compounds have been observed in ADHD.
4.2.11. Fluoridated drinking water¶
In Canada, a study found that a 1 mg/liter increase in fluoride in drinking water increased the risk of ADHD by 6.1 times in 6- to 17-year-olds. Among 14-year-olds living in areas where fluoride was added to drinking water, a 2.8-fold risk of an ADHD diagnosis was found compared with 14-year-olds in areas without fluoridated drinking water. Older children responded with a higher risk. In contrast, fluorine urine levels did not correlate with ADHD (1,877 subjects).
In Germany, 90% of drinking water has a fluoride content of 0.3 mg/liter. Drinking water is not fluoridated in Germany.
4.2.12. Benzene, toluene, ethylbenzene, xylene/xylene (BTEX)¶
Higher exposure to these airborne substances correlated with a 1.54-fold increased risk of ADHD in kindergarten-age children.
4.2.13. Phthalates¶
Higher phthalate metabolites in children’s urine correlated with increased likelihood of ADHD by 3 to 9-fold.
4.2.14. Inorganic arsenic¶
Those children in the 20% with the highest urinary arsenic levels were found to have a doubled risk of ADHD (OR 2.02).
4.2.15. Synergistic effects of neurotoxins¶
The synergistic effects of neurotoxins should be noted:
- Formaldehyde enhances the toxicity of mercury.
- Amalgam increases the toxicity of PCBs and formaldehyde.
- Mercury and PCBs potentiate each other’s effects.
4.3. Food intolerances, allergies¶
It is certain that ADHD is not caused by single, specific foods, phosphates or additives.
However, individual food intolerances or allergies are just as much stressors as diseases, toxins or psychological stress and can therefore worsen the stress situation of affected individuals to such an extent that symptoms develop. This is not an ADHD-specific finding. For example, in a group of children with schizophrenia problems, dietary treatment of an existing gluten intolerance eliminated the schizophrenia symptoms in the children affected. The same was found in patients with non-affective psychosis.
To detect rarely occurring food intolerances (which, unlike allergies, cannot be detected by blood tests), an elimination diet may be helpful. However, such a diet is very difficult to implement and maintain, and is unlikely to be adhered to, especially in younger children. In particular, any advantages must be weighed against the sometimes serious social consequences.
In other cases, such a diet can help alleviate the symptoms of existing intolerances.
When assessing the effectiveness of diets (and other “desirable” therapeutic avenues), parents often come up with assessments that far exceed what tests or teacher evaluations can confirm.
See ⇒ for more details Nutrition and diet in ADHD.
4.4. Gut bacteria, Gut-brain-axis (gut-brain-axis)¶
The primary functions of the microbiota include:
- Protection against pathogens by increasing mucus production and thus stabilizing the intestinal-blood barrier
- Immune system support
- Vitamins production
- Production of short-chain fatty acids (SCFAs) from indigestible carbohydrates
Short-chain fatty acids are:
|
|
|
|
|
|
C1:0 (no SCFA) |
formic acid |
methanoic acid |
formates |
methanoates |
HCOOH |
C2:0 |
Acetic acid |
Ethanoic acid |
Acetates |
Ethanoates |
CH3COOH |
C3:0 |
propionic acid |
propanoic acid |
propionates |
propanoates |
CH3CH2COOH |
C4:0 |
Butyric acid |
Butanoic acid |
Butyrate |
Butanoate |
CH3(CH2)2COOH |
C4:0 |
isobutyric acid |
2-methylpropanoic acid |
isobutyrate]] |
2-methylpropanoate |
(CH3)2CHCOOH |
C5:0 |
valeric acid |
pentanoic acid |
valerate |
pentanoate |
CH3(CH2)3COOH |
C5:0 |
isovaleric acid |
3-methylbutanoic acid |
isovalerate |
3-methylbutanoate |
(CH3)2CHCH2COOH |
C6:0 |
caproic acid |
hexanoic acid |
capronate |
hexanoate |
CH3(CH2)4COOH |
A study on short-chain fatty acids in blood serum in ADHD compared to healthy family members found:
- Adults with ADHD
- Formic acid reduces
- Acetic acid reduced
- Propionic acid reduces
- Succinic acid reduced (C4H6O, an aliphatic dicarboxylic acid; food additive number E 363)
- Children with ADHD
- Formic acid lower than adults
- Propionic acid lower than adults
- Isovaleric acid lower than in adults
- Antibiotic medications in the last 2 years caused
- Formic acid reduces
- Propionic acid reduces
- Succinic acid reduced
- current stimulant use in children caused
- Acetic acid reduced
- Propionic acid reduces
Research found abnormalities in gut flora in children with ADHD
ADHD correlated with leaky gut, neuroinflammation, and overactivated microglial cells. The colon microbiota exhibit a pro-inflammatory shift and harbor more gram-negative bacteria that contain immune-triggering lipopolysaccharides in their cell walls.
Adults with ADHD had lower plasma concentrations of formic, acetic, propionic, and succinic acids than their healthy family members. Adjusting ADHD patients for SCFA-affecting factors, children had lower concentrations of formic, propionic, and isovaleric acid than adults, and those who had taken more antibiotic medications in the past two years had lower concentrations of formic, propionic, and succinic acid. Adjusting for antibiotic medication, we found that among children, those currently taking stimulant medications had lower acetic and propionic acid concentrations, and adults with ADHD had lower formic and propionic acid concentrations than adult healthy family members.
Early disruption of the developing gut microbiota can affect neurological development and potentially lead to adverse mental health outcomes later in life.
Decreased were:
- Bacteroides coprocola (B. coprocola)
- Enterococcus
- Faecalibacterium prausnitzii
- Faecalibacterium
- Lachnospiraceae bacterium
- Ruminococcus gnavus
- Bifidobacterium
- Coprococcus
- Eucbacterium
- Eubacterium rectale
- Lactobacillus
- Prevotella
- Roseburia
Increased were
- Bacteroides uniformis (B. uniformis)
- Bacteroides ovatus (B. ovatus)
- Increase correlated with ADHD symptoms
- Sutterella stercoricanis (S. stercoricanis)
- Increase correlated with intake of dairy products, nuts, seeds, legumes, iron, magnesium
- Increase correlated with ADHD symptoms
- Veillonellaceae
- Bacteroides caccae
- Odoribacter splanchnicus
- Paraprevotella xylaniphila
- Veillonella parvula
- Bifidobacterium
- A slight increase in Bifidobacterium in the gut is thought to be associated with increased production of cyclohexadienyl dehydratase, which is a precursor to phenylanaline, which is a precursor to dopamine. At the same time, the increase in Bifidobacterium is thought to be associated with decreased reward anticipation, which is likely to suggest decreased levels of dopamine in the striatum. How these two seemingly contradictory pathways fit together is not explained to us at this time.
- Eggerthella
- Odoribacter
- Differently a study according to which Odoribacter were reduced
- Alistipes
- Flavonifractor
No significant difference was found in the alpha diversity of the intestinal bacteria.
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 and higher anxiety than mice in which gut bacteria from people without ADHD were used.
A single-case study reported improvement in ADHD symptoms in a young woman with intestinal bacterial exchange that occurred in relation to a recurrent Clostridioides difficile infection.
4.5. Polycystic ovary syndrome (PCOS)¶
Women with polycystic ovary syndrome (PCOS) appear to have an increased risk of mental disorders, primarily anxiety disorders and depression, but also ADHD.
4.6. (Untreated) type 1 diabetes¶
A study among diabetes sufferers with and without treatment using an insulin pump found a 2.45-fold increased risk of ADHD in those with type 1 diabetes who were not treated, with ADHD considered a risk factor for inconsistent diabetes treatment.
4.7. Phenlylketonuria (PKU)¶
Phenylketonuria (Følling disease, phenylpyruvic acid oligophrenia) is a genetically caused metabolic disorder by which the amino acid phenylalanine cannot be broken down to tyrosine due to the lack of the enzyme phenylalanine hydroxylase (PAH). Tyrosine, in turn, is required for the synthesis of dopamine, so dopamine deficiency is a consequence of PKU. PKU has a prevalence of 1 in 8000 people.
One study found an ADHD rate of 38% in phenlylketonuria despite adequate treatment.
ADHD is also associated with dopamine deficiency.
4.8. Anabolic androgenic steroids (AAS)¶
Power athletes who take anabolic androgenic steroids are significantly more likely to have ADHD than power athletes who do not.
4.9. Viral infections¶
4.9.1. Enteroviruses in general¶
(Non-polio) enteroviruses cause a good half of all cases of aseptic meningitis, making them among the most important known causes. In addition to encephaltitis, (non-polio) enteroviruses also frequently cause febrile illness, hand-foot-and-mouth disease, herpangina, aseptic meningitis, and encephalitis, as well as sometimes severe and threatening infections such as myocarditis or neonatal sepsis.
A previous study found an increased risk of ADHD from mild enterovirus infections (16%) and severe enterovirus infections (182%).((Chou IC, Lin CC, Kao CH (2015): Enterovirus Encephalitis Increases the Risk of Attention Deficit Hyperactivity Disorder: A Taiwanese Population-based Case-control Study. Medicine (Baltimore). 2015 Apr;94(16):e707. doi: 10.1097/MD.00000000000707. PMID: 25906098; PMCID: PMC4602682.))
4.9.2. Enterovirus A71 (EV-A71)¶
A longitudinal study of 43 adolescents who had a central nervous system infection with enterovirus A71 (EV-A71) between the ages of 6 and 18 years found ADHD in 34.9%. This more than triples the risk of ADHD. In addition, increased autistic symptoms were found. Other psychiatric diagnoses were not elevated. Another study found ADHD particularly prevalent when A71 infection was associated with cardiopulmonary failure.
EV-A71 often shows weakness, limb atrophy, seizures, hand-foot-mouth disease, encephalitis, and decreased intelligence.
4.9.3. HIV¶
A study of children and adolescents with HIV in stable health found ADHD symptoms in 20%.
4.9.4. Zoster encephalitis¶
In an isolated case, ADHD was mentioned in association with zoster encephalitis.
4.10. Bacterial infections¶
Periodontal disease is a bacterial inflammation of the gums caused by the bacterium P. gingivalis, which secretes toxins. Periodontal disease and is described as a risk factor for ADHD.