115+ Ways To Increase Tyrosine Hydroxylase (And What Decreases It)

Tyrosine hydroxylase is a necessary enzyme to create neurotransmitters and protect the body against oxidative stress.

In this post, we will discuss its benefits, downsides, and ways to increase its activity. 

Tyrosine Hydroxylase (TH) starts the conversion of L-tyrosine into L-Dopa, and thus is the rate-limiting step in the creation of catecholamines, particularly dopamine. R

It is expressed in both neurons (neurotransmitters) and endocrine (hormonal) cells. R

TH is also dependent on tetrahydrobiopterin (BH4), which is biosynthesized by GTP cyclohydrolase I (GTPCHI). R

Low Activity Of Tyrosine Hydroxylase:

• Alzheimer's Disease R

• Autoimmunity R

• Chronic Stress R

• Depression R

• Diabetes R

• Endotoxemia R R

• Eye Problems (such as ptosis and miosis) R

• Huntington's Disease R

• Impaired Learning/Cognition R

• Low Blood Pressure R

• Low Libido/Sexual Inactivity R R

• Nerve Degeneration R

• Parkinson's Disease (including Lewy Bodies and alpha-synuclien) R R R R

• Pitx3 deficiency R

• Reduced Spacial Memory R

• Scurvy R

• Tyrosine hydroxylase deficiency R

• Withdrawal R

High Activity Of Tyrosine Hydroxylase:

• Acute Stress R

• Arthritis (acutely) R

• Atrial Fibrillation R

• Brain Cancer R

• High Blood Pressure R

• Hypoxia R R

• Iron Deficiency R

• Sleep Deprivation R

• Stronger Reactions to Stimulants R

• Traumatic Brain Injury (delayed increase) R

1. May Help With Arthritis And Inflammation

Tyrosine hydroxylase (TH) activity increases in times of (acute) inflammation and stress as one of the body's mechanisms as an antioxidant. R

For example, TH activity may help with arthritis as increasing TH can reduce levels of TH17 inflammatory cytokines and possibly promote the upregulation of T-regulatory helper cells (Tregs). R

Tregs are strong promotors of TH activity. R

2. Promotes Dopamine And Norepinephrine Synthesis 

Increasing TH function can help with the synthesis of dopamine and norepinephrine.

It helps with those who genetically have tyrosine hydroxylase deficiency. R

3. Improves Symptoms Of Parkinson's Disease

Loss of TH function is extremely common in Parkinson's Disease (PD). R

Increasing TH can help with Bradykinesia (shaking seen in PD). R

TH also has neuroprotective effects on dopaminergic neurons and GABAergic neurons. R R

One reason for this is because TH activation can increase dopamine levels in the substantia nigra and striatum. R

Another reason is that TH (along with NR4A2 activation) can increase stem cell activity in the hippocampus. R

4. Promotes Skin And Eye Pigmentation

TH activation is necessary for the production of melanin in the skin and eyes. R

It does this by activating the enzyme tyrosinase. R

5. May Help With Depression And Stress

TH may help with depression by regulating levels of Brain Derived Neurotrophic Factor (BDNF) in the brain. R

It may also help with depression by increasing catecholamine levels. R

TH expression is lowered by chronic stress and increasing TH expression may help with stress. R

For example, licorice is able to improve spatial learning/memory and reduce stress-induced anxiety by increasing TH activity in animal models. R

6. Helps With TBI And Stroke

Increasing TH activity may help restore dopaminergic function after traumatic brain injuries by altering the HPA axis. R

Increase TH activity can enhance the swallowing reflex, which is useful in preventing pneumonia in chronic stages of stroke. R

7. May Improve Pain And Touch

Nerve injuries (ranging from peripheral nerve injury to vagus nerve dysfunction) decreases TH activity. R

TH activity plays a role in "emotional touch" sensations. R

In the dorsal root ganglion (DRG), TH activity plays a role in visceral pain. R

8. Helps Fight Addictions

TH activity may help with addiction and withdrawal from stimulants such as sugar, cocaine, and amphetamines. R R

1. May Increase Blood Pressure

Tyrosine hydroxylase (TH) by acting on DA and NE may increase blood pressure. R

For example, in animals models unable to produce TH, they were resistant to age-associated blood pressure elevation. R

2. May Play A Role In Schizophrenia

Although TH activity doesn't necessarily induce schizophrenia, it may influence suicide in schizophrenics. R

TH also plays a role in IQ levels in those with schizophrenia. R

3. May Increase Headaches And Migraines

Increased TH activity, as well as increased dopamine, norepinephrine and tryptamine are associated with cluster headaches and cluster migraines. R

My Top 5 Ways To Increase TH

1. Bright Light Device (or I'll use Sunlight and Blue Light)

2. Butyrate R

3. Exercise R

4. Music - this is what I listen to R

5. Uridine + Eating Fish (or fish oil) R

Diet / Lifestyle / Devices:

• Avoid Chronic Stress R

• Black Pepper R

• Bright Light (increases TH in eye and hypothalamus, but decreases TH-neurons) R R R

• Caffeinated Teas (Green, Black, or Oolong) and Coffee (Super Coffee would stabilize TH) R R

• Caloric Restriction (increases in substantia nigra, but reduces it in striatal area) R R

• Chronic Hypoxia R

• Cold Exposure (showers, baths, gear) R

• Electroshock Therapy R

• Enriched Environments R

• Exercise R R

• Fish Oil or Krill Oil (specifically DHA) R R

• Garlic R

• High Protein Diet (specifically high in Tyrosine) R

• Music (possibly) R

• Nerve Stimulation (use Nervana) R

• Photobiomodulation (infrared LLLT) R

• Spirulina R R

Supplements:

• An-Jun-Ning R

• Bacopa R

• Baicalein/Skullcap (protects TH neurons from oxidative-stress induced death) R

• Beta-caryophyllene R

• Bupleurum + Angelica (Dong Qui) + Paeonia suffruticosa R

• Butyrate R

• Caffeine R

• Cistanche R

• Copper (low) R

• Cordyceps R

• Creatine R R

• Da Bu Yin Wan R

• Eucommia ulmoides (Du Zhong) R

• Ferulic Acid (in striatum) R

• Forskolin R

• Gastrodin R R R

• Geng Nian (Tian Gui aka Menoplease) R

• Ginkgo Biloba (increases TH neurons) R

• Hepad (strong - combo of Cang Zhu, Cnidium, Paeonia japonica, Fu Ling, Gastrodin, and Jujube) R

• Horny Goat Weed (Icaarin) R

• Inositol R

• Iron (low) R

• Jiaogulan (Gynostemma protects TH neurons from oxidative-stress induced death) R

• Licorice (stabilizes TH during stress) R

• Limonene (increases TH) R

• Lion's Mane (prevents TH reduction from oxidative stress, but doesn't increase TH) R

• Lithium (increases TH in brain but reduces it in adrenals) R R

• Milk Thistle (prevents TH reduction from oxidative stress, but doesn't increase TH) R

• Mucuna pruriens + Ashwaganda (they work on TH independently, but the combo is stronger) R R R R

• Mulberry (prevents TH reduction from oxidative stress, but doesn't increase TH) R

• N-acetylcysteine (NAC - strong) R

• Narigenin R

• Nobiletin R

• Olive Leaf Extract (protective of TH neurons) R

• Quercetin R

• Retinol (strong) R

• Rhodiola (salidrosides balance TH levels, whereas tyrosol decreases TH, see below) R

• Safflower R

• Selenium (low doses) R

• Stephania (tetrandra) R

• Tangerine (Rikkunshito) R

• Tauroursodeoxycholic acid (TUDCA) R

• Thunder God Vine (Triptolide protects TH neurons from neuroinflammation) R R

• Toki To (TKT) R

• Uridine R

• Vitamin B6 (P5P) R

• Vitamin C R

• Xiao Yao San R

• Yin Yang Huo R

Hormones:

• Insulin R

• Melatonin (increases it in ventral mesencephalon but not in the hypothalamus) R R

• Oxytocin (coexpressed in the hypothalamus) R

• Vitamin D (D3) R R R

Drugs/Chemicals:

• Alcohol (acutely and decreases with alcohol tolerance) R R

• Amphetamines R

• BH4 (tetrahydrobiopterin) R

• Bradykinin R

• Bromantane (Lodastan) R R R

• Carbachol R

• Ceftriaxone R

• Cilostazol R

• Cocaine (decreases w/ tolerance) R

• Deferoxamine R R

• Dexamethasone R

• Fluoxetine R R

• Hydrocortisone R

• Intranasal Testosterone Propionate R

• Nicotine R

• Nomifensine R

• Perindopril R

Pathways:

• Acetylcholine R

• α-Synuclein inhibition R

• BDNF R R

• cAMP (PKA) R R

• CB1 (increases TH activity) R

• CB2 (protects TH neurons) R

• CDNF R R

• EGF R

• ERK R

• FoxO1 inhibition (activation lowers activity) R

• GDNF (dose dependent) R

• HIF1alpha R

• Hsc70 R

• Increase Tregs cells R

• Laminin R

• MANF R

• M1 mAChR R

• nAChR R

• NGF R R

• Nitric Oxide R

• Noggin R

• NRF2 (protective of TH neurons) R

• NR4A2 (downstream increases TH, VMAT2, and DAT) R

• PARK7/DJ-1 R

• PDE2 inhibition R

• PPAR-γ R

• ser40 R

• TGF-B1 R

Other:

• Butterfly Bush R

• Silver (during pregnancy may increase TH in offspring) R

Lifestyle:

• Intermittent hypoxia training R

• Oxidative Stresss (ie N2O, OONO) R

• Sleep Deprivation R

Devices:

• Deep Brain Stimulation (reduced activity in the PFC) R

Supplements:

• Acetyl-L-Carnitine (ALCAR) R

• Ginger R

• Ginseng R R

• Glutamine R

• Glutathione (in cancer) R

• Manganese R

• Nicotinamide (may increase TH in adrenals) R R

• Pine Bark R

• Propolis R

• Rhodiola (tyrosol, not salidroside, inhibits tyrosinase thus inhibiting melanin production) R

• SAMe R

• Selenium (chronic high doses) R

• Theanine R

Hormones:

• Estrogen (E2, but ER-alpha increases TH during pregnancy/lactation) R R

• Prolactin R

Drugs/Chemicals:

• Alpha-methyl-p-tyrosine (AMPT) and and iodotyrosines R

• Ketamine R

• PrPC R

• Rhynchophylline R

Pathways:

• Amyloid Beta R

• GABA (in eye) R

• GSK-3β R

• Negative feedback - Dopamine , L Dopa, Norepinephrine, Phenylalanine, AMPT (above) R R

Simple:

• Increases Dopamine R

• Increases GPX R

• Increases GR R

• Increases L-Dopa R

• Increases Norepinephrine R

• Reduces IL-17 R

• Reduces TATR

Advanced:

• TH activity can be regulated by 2 mechanisms primarily - medium- to long-term regulation of gene expression, or short-term regulation of enzyme activity [cAMP-dependent responsive element (CRE), AP-1, ATF-2, and Nurr1]. R

• TH is mainly produced in the adrenals, gut and brain and regulated by iron. R R R R

• It can pass the BBB and TH activity is site specific, for example, the ser40 phosphorylation increases TH activity, but so can the site of ser31 and ser19 in different parts of the striatum and substantia nigra. R

• You can see different activators targeting these different areas, such as GDNF particularly acts on ser31 phosphorylation. R

• TH activity can be regulated by glucocoritcoid receptors in times of stress. R

• In the striatum, striatal TH interneurons do not release DA, but instead work on inhibition via GABA. R

• In the retina, glutamatergic and GABAergic inputs may stimulate and inhibit dopamine release via TH. R

• In the immune system TH in actively increased by Tregs, and in a feedback loop, catecholamines downregulate Tregs (as well as TGF-b1 and IL-10). R

TH

• rs10770141 (I'm GG)

  • T allele - predictive of elevated levels of dopamine and norepinephrine had lower scores of novelty seeking than those without this allele R

  • C-824T - common variation in the proximal TH promoter is functional, giving rise to changes in autonomic function and consequently cardiovascular risk R

  • C-824T - possibly associated with chronic fatigue syndrome (CFS) R

• rs1470750 (I'm GG)

  • No strong evidence was found for the associations between personality and TH or DDC in overall tests for suicide R

  • TH variants were not associated with suicide R

• rs2070762 (I'm GA)

  • G allele - increased risk of migraines R

  • G allele - increased risk of hypertension R

• rs25531

  • G allele - almost always in phase with the long (L) allele of the 5-HTTLPR and may be associated with lower levels of serotonin R

  • G allele - may have a tendency to be optimists and to be more resilient to stress R

  • A allele - females may be at increased risk for side effects (e.g. headaches) from escitalopram R

  • Less active 5-HTTLPR genotypes - were nominally significantly associated with increased blushing propensity in patients with social anxiety disorder, and association remained significant even when statistically controlled for he influence of depression R

• rs3842727 (I'm TT)

  • No allele - associated with selective attention variability factor R

• rs6356 (I'm TC)

  • No observation for nicotine dependence R

  • A/G allele - associated with schizophrenia with COMT mutation R

  • T allele - increased risk of migraines R

• rs689

  • Association with Type 1 Diabetes R

  • Association of the vitamin D metabolism R

• rs80338892

  • 291delC relation to tyrosine hydroxylase deficiency R

• rs998850 (I'm CC)

  • Not associated with suicide R

  • Association of serotonin system to autism R

• Mutations in NR4A2 also contribute to TH deficiency. R