Written by Lee stevenson, sorry there will be a lot of typos I am not the best editor.
This is not medical advice , if you are ill please seek the help of someone qualified. I am writing this for educational purposes. By knowing these things it can better guide you to knowing whether the professional you seek knows what they are doing or whether they do not.
COMT MAO enzymes
Our hormones and neurotransmitters regulate how we think, how we feel emotionally, and it also regulates our energy levels in our bodies. Though men usually have fast COMT and fast MAO and women usually have slow I would not assume that is the case. I have seen many women with fast COMT and fast MAO and men with slow COMT and slow MAO. When there is excess amounts of hormones for too long it starts to desensitize the receptor and a person will need more and more of the hormone until the receptors stop functioning entirely. This is why it is better to correct the problem instead of treating it with medications or herbs. Herbs can help to alleviate symptoms as you work to correct the problems. If you have slow MAO you will do poorly when you consume things that have catechols such as green tea, coffee, bananas, citrus fruit, chocolate it will cause anxiety, inability to relax, aggressiveness if MAO is slow, If MAO is high it those will make you feel better.
COMT ( catechol-o-methyltransferase) and MAO (monoamine oxidase) help to regulate neurotransmitters and hormones. I have found people can switch between fast and slow COMT and fast and slow MAO activity but it seems the switching between MAO high and slow expression happens much less often in most people. Something COMT needs whether fast or slow is glutathion, magnesium and vitamin C. There are many toxins that inhibit COMT but mercury is the most common because it is used in some vaccines. Nutrients even determine if things are fast or slow. When stressed based on the nutrient levels at the time a person could be effected either way. So I don’t assume someone is fast or slow I pay attention to what their symptoms are.
COMT effects MAO because it regulates hormone levels and neurotransmitters. Hormones effect MAO , testosterone and androgen inhibits MAO causing lower neuropeptide levels. Estrogen and progesterone decrease MAO causing higher neuropeptide levels. COMT breaks down hormones , dopamine, epinephrine and norepinephine adrenal hormones. Because women have lower catechols and adrenal hormones they are much more sensitive to things that would cause fear such as getting in a fight, or dealing with a dangerous situation. But they can handle stress better then men. Because men have low levels they can they are less prone to fear but cannot handle as much stress. Mean can get overwhelmed by stress much more easily. Now this does not hold true for those who experienced trauma as a child especially sexual abuse because it damages many areas of the brain making those areas none receptive to certain stimuli while other areas of the brain are over activated. Those ones need a therapist who knows how to use nutrients, to heal the brain and how to use therapy to heal the brain. Studies have shown those areas can heal but when the areas start working again the victim will start remembering things they had not remembered and start feeling things they never felt before which can be overwhelming and confusing for them.
Slow COMT slows down the ability to break do neurotransmitters such as dopamine, estrogen and adrenal hormones such as epinephrin and norepinephrin. Meaning adrenal hormones and sex hormone levels could become too high. Stress slows down COMT. Slow COMT are the warriors or problem solvers, because of the high dopamine and adrenal hormone levels. When these people get stressed many areas of the brain can shut down from the increased dopamine and adrenal hormones. It can cause them to be worriers, experience head pain, get annoyed easily and have difficulty falling asleep. Odd these people will not back down from a fight but when stressed they collapse. I am one of them. But I almost have it corrected. People with slow COMT tend to over react to stress, and pressure because it increases dopamine and adrenal hormone levels which are already high. This causes many areas of the brain to shut down. Estrogen has a calming effect when broken down by COMT because it produces calming metabolites but in high levels makes a woman anxious, she cannot calm down or relax because it slows down MAO. Too little estrogen will cause excessive crying and depression. Fast COMT is why men tend to be grumpier.
Slow COMT causes high estrogen and progesterone which speeds up MAO activity. This can cause low hormone levels low dopamine and low serotonin levels. COMT and MAO have to be addressed along with balancing hormones when this occurs. Stress slows COMT and MAO. Men already have low levels so when they are decreased more they could get involved in risky and dangerous behavior to try and increase them. They will be more prone to being angry and getting violent when levels are low. Men’s hormones are a bit more resistant to change. There is a form of COMT that can alternate between fast and slow expression.
MAO deficiency can cause aggressive behavior, low impulse control. Hyper activeness, ADHD, autism, if severe skin flushing sweating, diarrhea and headaches. It can also cause violent behavior. Those with low MAO enzymes will be aggressive, experience weight gain, and can be violent. People think those with certain gene mutations experience high and low. That is not true life , diet, and toxins can effect these enzymes. Even our microbiome can effect our COMT and MAO because they effect our hormones and catechols.
Because COMT breaks down dopamine it’s over expression can cause anxiety, impusliveness, obsessive behavior that can lead to addiction to drugs , alcohol or even behavior that is dangerous, ADHD, irritability, hyperactivity, poor sleep quality. These are what they call type A personalities. They feel pressured to perform. They usually will be people pleasers.
In woman during pregnancy MAO activity decreases, shortly after child birth it increases. This is why many women experience depression after pregnancy. Those who experience this usually get depressed in the winter.
Slow MAO activity causes high dopamine and high serotonin levels. Estrogen and Progesterone slow down MAO. So women have higher dopamine and adrenal hormone levels then men, making them more prone to the negative effects of stress. So this means women are more prone to the mental effects of stress. Low MAO activity. can cause hypomania, depression, anxiety, hypertension, and a stiff neck. Low MAO activity causes loss of impulse control , extreme agitation, nausea, muscle twitching, and straight forwardness. Low MAO is what can cause people to get stuck in fight or flight mode. Slow MAO causes a person to worry more and and experience anxiety. Because women have slow MAO they are more prone to worrying and experiencing anxiety. When MOA and COMT are slow and we get xenoestrogens a toxin produced by man, into our bodies or some phytoestrogen it can cause dopamine levels to get too high. This causes excess anxiety, insomnia, chronic pain. A woman with this problem will have a very low tolerance to stress and trauma. Excess estrogen will slow down many methylation pathways. This makes me wonder about the men now days who are showing to have high estrogen levels from the toxins in our food and many farm chemicals in our food.
Slow MAO causes high tyramine levels which acts just like histamines. So they think they have high histamines so they take an antihistimine. This causes them to experience difficulty sleeping, increased sexual drive but unable to achieve and orgasm, weight gain, dry mouth, sleepiness and POTS.
I see this all the time people post they are having histamine issues when it is actually tyramine. The foods they name are high in tyramine. People with high tyramine levels from inhibited MAO will react to aged or fermented foods, oranges, bananas that are too ripe, beers and wines, Avocado’s , fava beans and lima beans because they are high in tyramine. Inhibited mitochondrial beta oxidation also causes high tyramine. At the end of this article you will see the importance of this.
Slow MAO can also experience a burning tongue, nausea , hiccups, muscle twitching, restlessness, restless leg syndrome, nervousness, hyperactivity, hyper sexuality, mania, OCD, hypertension, sweating especially at night, heart palpitations, hypertension, skin may get pale, fatigue, weight gain, anxiety, bloating, headaches, moody, breast tenderness, irritable and easy to anger. When very severe they can experience difficulty breathing, asthma, many heart issues, disorientation, autism, aspbergers, dementia, adrenal fatigue, glucose imbalance, low luteinizing hormone, low growth hormone, High T4 and low T3 from low conversion of thyroid hormones. Women need to get their estrogen and progesterone levels balanced if they are slow MAO. Slow COMT tend to be more lean and cannot gain weight.
Estrogen decreases COMT activity. Even though COMT breaks down estrogen it is inhibited 30% by estrogen. The hormones produced from estrogen have a calming effect. I have watched some women’s hormone levels jump up and down meaning their COMT and MAO levels are also fluctuating. When COMT or MAO is fast it will show up on OATS test with high homovanillic acid. There are other enzymes that break down dopamine which I will try to discuss. So it stands to reason if COMT or MAO is slow then dopamine will be high and homovanillic acid levels will be low. It takes two weeks for the body to replace MAO when they have been completely inhibited by a drug.
Usually if someone is having issues with slow MAO it will effect their CBS and BH4 pathways. If BH4 levels are low dopamine will get low. When BH4 activity is low it puts more of a burden on the CBS pathway. These ones will have high hydrogen sulfide, and high ammonia levels and will react to foods high in glutamine, and phenylalanine. They will also get ill when they eat meat or cruciferous vegetables , onions or garlic because of the high sulfur content. Normally phenylalanine and tyrosine would increase alertness and arousal but if someone has slow MAO the tyrosine will increase tryptamine causing and allergy like reaction. Phenylalanine will increase ammonia causing high glutamate levels. Glutamate is an excitotoxin in high levels it damages the brain. If levels get high enough a person will get headaches so severe they will think their head is going to split open.
Fast MAO is usually found in men because androgen and testosterone causes Fast MAO expression which rapidly break down dopamine and serotonin which can cause anxiety, impulsiveness, obsessive behavior which can lead to drug addiction or even addiction to doing dangerous things. It can also cause ADHD, irritability, hyperactivity, poor sleep quality, these are the type A personality people who can be people pleasers because they feel pressure to perform. Foods high in catechols help. Because men have lower catechol levels they can tolerate more in their diet. I have seen woman with fast COMT and fast MAO and they show many of the traits a man would with a few differences. They tend to be more disassociative and more unforgiving when they have fast COMT and fast MAO. that is just my observation.
Testosterone and androgen increase COMT and MAO. Since some woman have low estrogen and progesterone , and high androgen now days I would not doubt of many of them are now fast COMT and fast MAO.
Slow MAO can be caused by adrenal fatigue. The body tries to preserve the adrenal hormones by slowing MAO. It is very important for those with slow MAO to manage stress and learn stress management techniques.
Fast MAO can be caused by inflammation and oxidative stress. Fast MAO can cause Crohn’s usually MAO inhibitors helps with Chron’s Fast MAO causes processed sugar and processed carbohydrate cravings. These ones will wake in the middle of the night hungry. Fast MAO causes low dopamine and adrenal hormones. Because men have fast MAO they are more prone to having social anxiety especially if they have been stressed.
Fast MAO causes a craving for processed sugar and processed carbohydrates. Eating them makes it worse. From the low serotonin they will be prone to constipation. Those with low MAO get depressed during the winter. They experience insomnia, low tolerance to pain, low self esteem, OCD, panic, many with PTSD have fast MAO. They also have poor dream recall, have aggressive behavior, and can be violent very quickly and unpredictably. Very impulsive and often times do not think their decision’s through.
Symptoms of fast MAO depression, lack of motivation, lack of sex drive, no desire to live, chest pain, stiff neck, nausea, loss of libido,
Whether someone has fast or slow MAO they should reduce inflammation and oxidative stress so the body can balance things out. They should pay attention to how their COMT and MAO are working so they can make the adjustments in their protocols.
Nutrients needed for low MAO:
Iron, zinc picolinate, copper and riboflavin, glutathione, folate (make certain it is not folic acid), vitamin B12, vitamin B2, SAMe, vitamin C
Herbs for the adrenals. Such as eleuthero, ashwangha, passion flower, lemon balm, valerian
Nutrients and foods to avoid: Pay attention to high phenol foods those with low MAO can react to phenols.
Foods high in tryptophan and phenylalanine, phytoestrogens,
Fermented and aged foods.
MAO inhibitors: need to be avoided by those with slow MAO activity. Those with slow MAO may react to methy donors so should try to get non methylated forms of vitamins. I reacted to methyl groups but once I healed I was fine. For example Hydroxy B12 my be a better option for those with low MAO. Those with low nitric oxide should not take hydroxy B12.
Things that contain apigenin, luteolin,
Virodhamine and endogenous cannabinoid.
Nutrients and supplements for low MAO:
Riboflavin phosphate increases MAO this helps reduce aggressiveness.
Magnesium malate or magnesium glycinate. Especially needed if you take SAMe.
Things that increase MAO: Increasing MAO will reduce neurotransmitters preventing excess neurotransmitters.
Fulvi acid increases MAO it is high in organic, non sulfured black strap molasses, calcium.
Indian snake root
St Jon’s wort
Things a person with low MAO should avoid: MAO inhibition can cause high levels of neurotansmitters. Drugs that inhibit MAO can cause serotonin syndrome.
These should be avoided until they are healed are tyrosine, tryptophan, soy sauce, chocolate, alcohol, raisins, curcumin, passion flower , nutmeg, kava, calcium , riboflavin.
Andrographin, angelica, bayberry, bilberry, celery, coffee, curcumin, echinacea, coriander , evening primrose, St John’s wort, Uva Ursa and other things with berberine.
Nutrients needed for fast MAO: be aware of any foods you are sensitive to and avoid them as much as possible.
High protein, lots of fiber, complex carbohydrates, glutathione, tryptophan,
Fermented foods and aged foods.
Some things that help with fast MAO:
Foods high in Querciten
Things to avoid with fast MAO:
Eating process sugar and processed carbs will make things worse so fight the cravings when possible.
Kyurenine maintains brain health. Kyurenine pathway produces serotonin from tryptophan. It is not the Kyrenine pathway itself that is the problem but the way I worded this it may seem to be. The problem is when it becomes dysfunctional and is producing high levels of quinolinic acid. It metabolizes tryptophan and produces metabolites that are very healing to the body reduces inflammation and oxidative stress when functioning properly. It produces Quinolinic acid which is involved in many psychiatric disorders, and neurodegenerative processes in the brain. Quinolinic acid is an excitotoxin. Quinolinic acid affects neurons located mainly in the hippocampus, striatum, and neocortex, due to the selectivity toward quinolinic acid by the specific NMDA receptors residing in those regions. Quinolinic acid causes excess cell death. When it is dysfunctional serotonin levels can become decreased. Those with Lyme disease have extremely high levels of quinolinic acid. High ammonia levels can also cause high quinolinic acid levels.
High quinolinic acid levels will resemble high glutamate levels because glutamate increases, and it causes glutamate to be released, but you also may only you may sleep a lot, have brain fog and get very severe headaches and severe depression, loss of the ability to focus, loss of the ability to learn, severe forgetfulness.
kyurenine pathway when functioning properly will produce beneficial metabolites from tryptophan. It produces toxic metabolites when there is excess Inflammation, oxidative stress, infection, high glyphosate, or if someone has taken antibiotics such as fluoroquinolones which can cause it to dysfunction producing too much quinolinic acid, which causes brain swelling and brain fog, and brain cell death. KYNA inhibits the convulsive and excitotoxic effects of too much glutamate transmission. This occurs because it has to be used to neutralize excess glutamate. High levels of kynurenic acid have been identified in patients suffering from tick-borne encephalitis, schizophrenia and HIV-related illnesses. Notice all conditions that involve confusion and psychotic symptoms. Kynurenic acid acts in the brain as NMDAr antagonist, key in glutamatergic neurotransmission system, which is thought to be involved in the pathophysiology and pathogenesis of schizophrenia. So even though it is involved in producing ATP it’s upregulation can cause many problems in the brain. So it is very important to get rid of any infections causing it’s upregulation, inflammation and oxidative stress. It’s upregulation causes a pyridoxine 5-posphate deficiency which effects many metabolic and mitochondria functions negatively.
Reducing KYNA increases glutamatergic function in the hippocampus and enhances cognitive abilities and synaptic plasticity. Hippocampus has been found to be dysfunctional in those who suffered child hood abuse, experienced chronic stress or who have PTSD. By reducing it, it would increase a persons desire to experience life spatial recognition, passive avoidance, and spatial discrimination. So they would become more enthused about life, be more aware of their surroundings and be able to identify bad situations and avoid them. Their ability to learn from mistakes they have made that could have endangered them or caused them harm improves. Those who have hippocampal damage will constantly make bad decisions that endanger them, bring them pain whether physically or emotionally. They cannot remember those experiences when the hippocampus is not functioning so they will continually put themselves in bad situations that can damage their lives, relationships and the effects often times are completely life changing bringing more trauma on themselves. It is not good to inhibit this pathway because inhibiting it can cause MAO to be inhibited. KYNA also damages the amydala which is also damaged in those who experienced childhood trauma, chronic stress and who have PTSD. Stress also activates KYNA pathway so stress management technique learning is important to reduces it’s activation. You do not want to inhibit it because it is involved in helping us overcome social defeat. Low kynurenine levels have been implicated in aggression, depression, and headaches. So it should never be inhibited. If you experience any of those symptoms then tryptophan can help alleviate the feelings of social defeat, aggressiveness , depression and headaches.
kynurenic acid exerts its neuroprotective effect by acting as an antagonist of the glutamate receptor, N-methyl-d-aspartate (NMDA), quinolinic acid exerts its neurotoxic effect by acting as an agonist of the NMDA receptor. So you can see it is not so much KYNA that is the problem but when inflammation, toxins, stress, trauma has caused it to start producing quinolinic acid in higher amounts then kynurenic acid. The reason it does this is to produce more ATP in the body because when injured , or when you have an infection the body needs more ATP. Also if you have a metabolic issue slowing the production of ATP found in obesity then KYNA pathway will compensate and more quinlolinc acid is produced.
The headaches caused by high quinolinic acid is because it prevents glutamate from being uptaken into cells causing high levels of glutamate in the brain which is an excitotoxin when levels are high.
caffeine and regular black tea consumption can elevate quinolinic acid levels so should be avoided if KYNA is upregulated.
KYNA production of quinolinic acid activates an inflammatory response, and increases oxidative stress in the body and brain. Once inflammation and oxidative stress has activated it, these will need addressed. Remember oxidative stress and inflammation is what caused the production of quinolinic acid, so a cycle is created that needs to be broken. Major depression and bipolar depression contain increased quinolinic acid. High quinolinic acid levels causes a person to be less caring towards others. It can cause amyotropic lateral sclerosis, Alzheimer’s, restricted blood flow to the brain, Huntington’s disease, Parkinson’s disease. Quinolinic acid also causes low acetylcholine levels which causes brain fog, lack in the ability to concentrate, hindered ability to learn, inability to focus, poor memory recall, and low energy levels or enthusiasm. Sulfation issues need corrected , because it is involved in regulating KYNA. The excess glutamate causes restlessness, anxiety, inability to focus, increased pain throughout the body. If levels get high enough a person can get ringing or strange sounds in their ears and splitting headaches.
Exercise helps to reduce KYNA, learning to manage stress and reduce it reduces KYNA.
Things that help to decrease the production of quinolinic acid are melatonin, selenium, L-theanine, green tea, curcumin combine with black pepper, niacin, Pyridoxal 5-phosphate, cruciferous vegetables, astanxanthan from natural sources, man made astaxanthan is toxic to the body, glutathione, riboflavin, Vitamin E which is found in COD liver oil and extra virgin olive oil. Zinc picolinate can help but in high dose it can do the opposite, grape seed extract, and pine bark extract. Amino acids leucine, isoleucine, phenylalanine, and methionine reduce quinolinic acid production. Chromium, lipoic acid and vanadium help to get out of ketosis if beta oxidation is inhibited.
These should be avoided if quinolinic acid levels are high because they will increase it more arginine, tryptophan, and glutamine. Quinolinic acid causes Pellagra (niacin deficienty) which causes excess weight loss, scaly skin lesions, delusions and confusion. Magnesium can actually increase quinolinic acid so those with high quinolinic acid levels will react to magnesium. You will also react to carbohydrates because they increase tryptophan levels which get converted to quinolinic acid when KYNA is dysfunctional.
N,N-dimethyltryptamine (DMT) melatonin and serotonin are needed to produce it. Very healing to the brain but can cause hallucinations.Holding your breath (hypoxia) Yoga increases DMT. Fast MAO causes low levels. Slow MAO have increased levels.
DMT acts on Sig1R it can interact with other neurotransmitter receptors and change their function by forming complexes with them. When it’s inside the cell, it binds anti-stress proteins and aids them in performing their functions. In the nucleus, it recruits other proteins that bind to DNA and activate or deactivate different genes via epigenetic mechanisms. Other compounds bind to it as well, including cocaine and the sex hormone progesterone. It protects the brain from cell death even during oxygen deprivation. DMT is shown to lead to the production of cyclic adenosine monophosphate. (cAMP), a secondary receptor messenger. Forskolin can increase cAMP. Low cAMP levels causes depression by increasing cAMP it would improve mood. Also many hormones and neurotransmitters are regulated by cAMP. DMT also 5-hydroxytryptamine 2A receptor or the trace amine–associated receptor to cause its psychedelic effect.
DMT is found in many hallucinogenic plants and mushrooms that are being used to heal injury to the brain. DMT prevents anxiety and depression. DMT has been found to restore inflammatory and immune homeostasis.
DMT improves HPA function which helps to reduce fatigue and improve tolerance to stress. DMT improves brain plasticity and has been found to help those who’s brains have been damaged by trauma, chronic stress, and PTSD. It improves the health of tissue throughout the body.
DMT is produced from tryptamine by certain enzymes. MAO breaks it down so fast MAO would have low levels and slow MAO would have higher levels. This may be way fermented and aged foods make some feel better because they are high in tryptamine. It inhibits MAO for a very short amount of time. L-amino acid decarboxylase converts tryptamine to DMT. L-amino acid decarboxylase needs pyridoxal 5-phosphate to form DMT. The enzymes that produce it need oil soluble vitamins such as vitamin A, vitamin E, and Vitamin D most of those can be acquired from cod liver oil and olive oil, omega 3 oils increases DMT. L-amino acid decarboxylase that is involved in DMT production are also involved in serotonin and dopamine production. Ironically it’s expression is increased by cAMP. L-amino acid decarboxylase other biogenic amines. So if this enzyme is slow a person would have issues when consuming fermented foods. Lack of sufficient P5P is the main cause of it being slow. Those with Slow MAO will react to tryptamine an biogenic amines so be they could try this they would need to address issues with MAO. Also those who’s beta oxidation in their mitochondria is inhibited would need to address their mitochondrial issues because it causes high tyramine. So if they have mitochondrial issues and slow MAO it is going to cause them a lot of problems.