Tyrosine for ADHD

Tyrosine is a precursor in the synthesis of dopamine. Although the rate-limiting enzyme of catecholamine synthesis is not tyrosine but tyrosine hydroxylase, an increase in tyrosine levels in the brain stimulates catecholamine production, but only in actively firing neurons ¹²

More on this under Tyrosine In the article Dopamine formation and storage

1. Tyrosine increases dopamine and noradrenaline
2. Protein-rich food increases tyrosine
3. Competing amino acids reduce tyrosine and thus dopamine

1. Tyrosine increases dopamine and noradrenaline

Tyrosine administration increased extracellular dopamine in the striatum and nucleus accumbens in rats.³ Another source also reported this for the striatum, but only if the animals had previously received a dopamine receptor antagonist (halperidol).⁴ Tyrosine administration also significantly increased (in light only) the conversion of tyrosine to L-dopa (part of the dopamine synthesis pathway) in the retina of rats⁵ and subsequently increased dopamine in the retina.⁶ Since dopamine suppresses melatonin, this pathway could influence the circadian rhythm. More on this at Melatonin and dopamine and the circadian rhythm in the article Melatonin in ADHD
In rats, the tyrosine level in the hypothalamus varies linearly with a range of protein content in the diet between 2 and 10 %. At 20 %, the tyrosine level in the hypothalamus barely increased further.¹

A type input in humans

improved impulse control in a stop signal task one hour after ingestion.⁷
increased cognitive flexibility / facilitated task switching⁸
in DRD2 gene C957T (rs6277) T/T homozygous carriers (associated with lower striatal DA levels) produced greater improvements in a stop signal task and working memory updating in an N-back task than C/C homozygous carriers (associated with higher striatal DA levels). Thus, tyrosine worked better at low striatal dopamine than at higher levels.⁹
improved cognitive performance in stressful or demanding situations with reduced dopamine / noradrenaline levels¹⁰¹¹¹²¹³
reduced temporal discounting and reduced arousal, shorter response times with the same response qualityl¹⁴
deteriorated task switching under high cognitive load¹⁵
- in our opinion, this could possibly be explained if the high cognitive load already caused stress-related increased dopamine and noradrenline levels, which were then further increased by tyrosine administration and thus moved even further away from the optimal level (inverted-U effect for catecholamines).

Rats given glutamate in the striatum showed increased dopamine synthesis from tyrosine and only moderate changes in dopamine release.¹⁶¹⁷

2. Protein-rich food increases tyrosine

Protein-rich food increases the tyrosine level in the brain. Theoretically, a protein-rich diet could therefore improve a dopamine deficiency and improve ADHD symptoms if these arise due to dopamine synthesis problems caused by tyrosine deficiency. Although this is probably only rarely the case, we believe it is conceivable that this could be one of the many pathways leading to ADHD and could therefore help people with ADHD.
A few people with ADHD reported an improvement in ADHD symptoms with a ketogenic diet or tyrosine intake. More on this under Ketogenic diet In the article Nutrition and diet for ADHD
In SHR, the most widely used animal model for ADHD, which also serves as an animal model for hypertension, tyrosine caused a reduction in blood pressure and an increase in extracellular noradrenaline levels.¹⁸ Like the inhibition of prolactin release caused by tyrosine in rats pre-treated with reserpine, this is thought to be due to a stimulation of dopamine and noradrenaline synthesis¹
Tyrosine is also said to improve working memory in humans under cold stress conditions.¹⁹
Administration of L-tyrosine to rats increased extracellular dopamine in the mPFC and striatum²⁰²¹ and norepinephrine release in the hippocampus.²²

3. Competing amino acids reduce tyrosine and thus dopamine

The amount of tyrosine available in the brain is also influenced by other large neutral amino acids that compete with tyrosine for the same transporter across the blood-brain barrier, e.g:¹²³

Tryptophan
Phenylalanine
L-methionine
Histidine
Threonine
L-glycine
- different²⁴
L-lysine
L-arginine
L-leucine
L-isoleucine
L-valine
DOPA²⁴
Cysteine²⁴
Histidine²⁴
Glutamine²⁴
Asparagine²⁴
Serine²⁴
but not
- Alanine¹⁸²⁴
- Proline²⁴
- Glycine²⁴

Therefore, administration of a combination of these large neutral amino acids (without tyrosine and without phenylalanine, as phenylalanine is immediately metabolized to tyrosine in the liver) can reduce brain tyrosine levels in the hypothalamus and retina within 2 hours.²³ Consequences are that the dopamine level in the brain also decreases, but not in the PFC.¹²⁵
In other brain regions, only the tyrosine level decreased within 2 hours after administration of the competing amino acids, but not the dopamine or noradrenaline level²⁶

Cortex (tyrosine reduced by 50 %, dopa reduced by 20 to 24 %)
Hippocampus (tyrosine reduced by 50 %)
Striatum (tyrosine reduced by 50 %, dopa reduced by 44 %)
Nucleus accumbens (dopa reduced by 34 %)

The tyrosine level recovered completely after 6 hours²⁶

Insofar as the studies were carried out on people without ADHD, an even more significant effect can be expected in people with ADHD due to the ADHD-related dopamine and noradrenaline deficits. Non-affected persons showed a few hours after taking the competing amino acids:

neurophysiological changes
- Dopamine levels
  - in the striatum
    - reduces²⁷ by 6 %²⁸
    - unchanged²⁶
  - in the hypothalamus is reduced (indicated by an increase in prolactin)²⁹³⁰³¹
  - cerebral reduced³²
- Reduced activity in the putamen³³
  - Putamen and SMA mediate the storage of temporal information in working memory
- Reduced activity in the supplementary motor area (SMA)³³
  - Putamen and SMA mediate the storage of temporal information in working memory
frontostriatal connectivity impaired³⁴
reduced deactivation in areas that are suppressed during attention-demanding tasks, including:³⁴
- mPFC
- posterior cingulate cortex
- Hippocampus
Behavioral changes
- spatial working memory
  - deteriorated²⁹³⁵³⁶
  - worsens in women only on low-fat/low-sugar diets, not on high-fat/high-sugar diets³⁷
  - unchanged³⁸ but associated ERP showed neurophysiological deterioration³⁹
- episodic memory unchanged, but associated ERP showed neurophysiological deterioration³⁹
- State of mind / mood
  - deteriorates²⁹⁴⁰ , at least slightly³¹⁴¹
  - worsened pain assessment³²
  - deteriorated mood after stress⁴²
  - unchanged³⁵⁴³⁴⁴
- Pain and temperature sensation unchanged⁴¹³²
- other planning and memory skills
  - unchanged³⁸
  - Go/no-go task: increased number of errors in healthy adults³¹
  - Simon Task: Results unchanged, but N-40 changed⁴⁵
  - Timing impaired³³
  - Time perception changes depending on the tyrosine base value⁴⁶
  - Reward response (delay discounting and working memory)
    - Effect only dependent on COMT gene type; increased elective impulsivity with COMT val/val (which causes increased dopamine degradation in the PFC)⁴⁷
  - Habitual control (only in women) stronger than goal-directed control when goal-directed and habitual systems competed for control in the slips-of-action test⁴⁸, also for tryptophan depletion⁴⁹
- Learning from positive and negative reinforcement (probabilistic selection task) improved in women with low-fat/low-sugar diets as with high-fat/high-sugar diets³⁷
- directed attention deteriorates with simultaneous serotonin depletion⁵⁰
- Reaction time unchanged with divided attention⁵¹

For comparison: tryptophan depletion, executive functions and impulsivity

Similarly, depletion of tryptophan, which is a precursor in the formation of serotonin, results in a reduction of serotonin in the brain and effects on executive functions and impulsivity:

Go/NoGo task⁵²
- unchanged (3 studies)
- improved accuracy and response times (1 study)
- increased number of errors (1 study)
Continuous Performance Test⁵²
- Increased impulsivity (4 studies)
- unchanged (1 study)
Four-choice Serial reaction time task⁵²
- Increased impulsivity (1 study)
Wisconsin card sorting test⁵²
- unchanged (2 studies)
Tower of London⁵²
- increased response time (1 study)
- unchanged (2 studies)
Stroop Test⁵²
- improved (focused) attention (3 studies)
- unchanged (1 study)
Probabilistic reversal learning⁵²
- unchanged (2 studies)

The reduction of tryptophan by a tryptophan-free amino acid mix could be prevented by blocking protein formation. Apparently, the tryptophan reduction is mediated by the formation of proteins (from tryptophan).⁵³ It is possible that this prevents tryptophan degradation⁵⁴

We think it is worth considering whether tyrosine depletion (at the appropriate dosage) could be a helpful or even supportive treatment for disorders based on elevated dopamine levels (such as autism or schizophrenia and the rare cases of ADHD, which (according to the DAT-KO model) are based on elevated dopamine levels) or elevated noradrenaline levels, such as PTSD.
One study reports an improvement in manic symptoms in people with ADHD.⁵⁵ A case study reports a cure (!) of a person with ADHD through a gluten- and casein-free diet.⁵⁶ However, studies that systematically compared gluten-free and casein-free diets in relation to autism found no relevant influence.⁵⁷⁵⁸
Products that contain a lot of casein also contain a lot of tyrosine. A study on children with ASD found reduced tyrosine blood levels.⁵⁹ In our view, it is at least theoretically conceivable that reduced tyrosine blood levels may not be a contributory cause of ASD, but the consequence of a diet that people with ADHD have unconsciously perceived as helpful in reducing their symptoms.
Even if the background is interesting, it would be completely illusory to regard a diet low in tyrosine and phenylalanine as a cure for autism. An individual case is not proof of treatment for an entire disorder.
The major risk is that there are other (possibly previously unknown) amino acids or other substances that are absorbed into the brain via the same transporters through the blood-brain barrier. Long-term intake of an amino acid mixture that occupies the blood-brain barrier transporters would cause deficiency states of these amino acids/substances, which could cause considerable damage.
In view of the possibility of significant side effects, we therefore strongly advise against experiments that are not supported by a doctor.

Theoretically, we also thought it was conceivable that taking tyrosine-depleting amino acids 2 hours before going to bed could help with sleep.
This option has not yet been discussed medically and should therefore be considered with particular caution. Even if these substances are available over the counter, they should never be taken without consulting a doctor.

As shown above, tyrosine intake can increase dopamine and noradrenaline and tyrosine depletion can decrease dopamine and noradrenaline.
However, a lower noradrenaline level is helpful to calm down.
A combined intake of the amino acids that compete with tyrosine for the same transporters across the blood-brain barrier may help to reduce dopamine and noradrenaline.
Taking a combination of the amino acids mentioned (without tyrosine and phenylalanine) could therefore possibly help people with ADHD with increased arousal to calm down.
To avoid disadvantages during the day, this should be combined with a morning intake of tyrosine and phenylalanine.

Conversely, the administration of tyrosine to reduce sleep problems caused by certain forms of stress, which are associated with reduced noradrenaline levels, has been discussed.⁶⁰ Similarly, a study of unaffected individuals found that tyrosine reduced arousal.¹⁴

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Tyrosine for ADHD

1. Tyrosine increases dopamine and noradrenaline¶

2. Protein-rich food increases tyrosine¶

3. Competing amino acids reduce tyrosine and thus dopamine¶

1. Tyrosine increases dopamine and noradrenaline

2. Protein-rich food increases tyrosine

3. Competing amino acids reduce tyrosine and thus dopamine