Genetics

COMT, MAOA, DRD2

COMT, MAO-A and DRD2 Phenotypes at your worst and best

Genetics, neurotransmitters / /

The combination of COMT and MAO-A variants can affect mood regulation and neurotransmitter balance. Add in a DRD2 variant and you have very different phenotypes. Definition of phenotype: the expression (set of symptoms) of your genes as influenced by your epigenetic factors such as your diet, lifestyle and environment. You can change your phenotype by changing your epigenetics as this will in turn change the expression of your genes. Here is a quick breakdown of these different phenotypes. I have also included a fictional character for each one to help you see how this could play out, especially with regards to risks, predispositions , mental and physical symptoms that might present. Keep in mind, though, that the effects of these enzyme activities are also influenced by other genetic factors and environmental stressors. Personal history, stress, diet, sleep, and overall health can influence how these enzymes  impact mood and behavior. So while someone with a specific genotype could tend to lean towards a certain phenotype, it would ultimately depend on a combination of their genetic make-up, and other internal and external epigenetic factors.   When I am doing a feedback report for a genetic test, I take a look at this in connection with the client. This can be of benefit when it comes to making recommendations in how they can adjust their diet, certain lifestyle choices and habits and clean these up to help their genes express better. This also will determine what supplements will and won’t work for them. Sometimes we are not even aware of how the small choices we make each day impact our physical and mental health.   Slow COMT / Fast MAO-A / DRD2 (Wired but tired phenotype) With this phenotype, you’re likely to experience higher dopamine levels especially in the prefrontal cortex due to slow COMT. You will likely be quite good at problem solving and have better attention and focus and memory (slow COMT) but on the other hand you will probably struggle with mood stability due to low serotonin (Fast MAO-A)  The Reward factor is low, and there may be an increased risk of addictive behaviors and mood swings due to DRD2.   Fast COMT / Slow MAO-A / DRD2: ( ) You may struggle with cognitive issues like poor focus, attention and lack of motivation due to rapid dopamine depletion (fast COMT) but may find that you have greater emotional stability thanks to higher serotonin (slow MAO-A) which means you are able to cope better when under stressful situations. The Reward factor remains low, and the addiction tendency remains the same due to the DRD2.   Let’s break it down a bit further.   COMT -fast or slow The slow COMT variant (Met/Met, AA) leads to a slower breakdown of the neurotransmitters dopamine, norepinephrine and epinephrine. This can lead to higher levels in the brain, particularly the prefrontal cortex and basal ganglia,  that stick around for longer than what they should. When this happens it can lead to increased anxiety, mood swings and irritability. The fast COMT variant (val/val, GG) leads to an accelerated breakdown of the neurotransmitters dopamine, norepinephrine and epinephrine, which can lead to lower levels in the brain. This affects executive functioning like working memory, focus and attention. (also seen in inattentive ADHD)   MAO-A- fast or slow A fast MAO-A variant leads to an accelerated breakdown of the neurotransmitters serotonin, metatonin, dopamine,epinephrine and norepinephrine in the brain. Which results in lower levels of these affecting  mood, and potentially leading to anxiety, and reduced motivation and impacting sleep. A slow MAO-A variants leads to a reduced breakdown of the neurotransmitters serotonin, dopamine, and norepinephrine in the brain. Which results in higher serotonin availability. This can provide a buffer against emotional volatility and protect against anxiety or depression.   DRD2 DRD2 is a dopamine receptor located in the stratum, hippocampus, amygdala and cerebral cortex. The DRD2 gene codes the dopamine receptor DRD2.  The variant causes a reduced number of dopamine binding sites in the brain, resulting in reduced dopamine signaling which means that individuals with mutations are less sensitive to the activation of dopamine- based reward system and this makes them more likely to be predisposed to addictive behaviour. A simple example would be while some people may feel satisfied after one block of chocolate, it may require a whole slab for someone with a variant in DRD2 to feel the same sense of satisfaction which is why they often are led to overeating. They need stronger stimuli to experience the same level of reward as individuals with a normal receptor density, which is what often leads to addictive behaviors or seeking out more intense experiences.  Shopping, gaming, spending money, seeking out new experiences, trying new hobbies, or over eating are often part of the reward seeking. The DRD2 receptors play an important role in addiction and eating behaviour as they are involved in the dopamine based reward circuitry. This receptor has been associated with Parkinson’s Disease, alcohol addiction, opioid addiction, ADHD with hyperactivity and impulsivity, and binge-eating, affecting working memory.     Slow COMT / Fast MAO-A / DRD2 (Wired but tired phenotype) Greg (fictional character) has this combination. He works really hard and loves his job. In fact, he finds it hard to stop working! Greg is quite meticulous when it comes to detail and work ethic, paying close attention to small details. He can sit for long periods of time, focusing on his work without any problems. He likes things to be “just right”, perhaps even bordering on some perfectionist tendencies. However, when things don’t go his way, he finds himself reacting with annoyance and anger. Small things often annoy him, like spelling and grammatical errors. Greg finds it hard to switch off and relax. He feels the constant need to keep going. Others would describe him as a workaholic. When he isn’t working, he likes to participate in sports, go to the gym or do fun and exciting activities on the weekend like go-cart

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Estrogen Dominance : risk for cancer

detoxification, Genetic Testing, Genetics, Hormones / /

Estrogen dominance affects many women in ways they might not realize. For example, did you know that PMS is a form of estrogen dominance? What is estrogen dominance? How does it happen? How is estrogen metabolized? How does too much estrogen lead to cancer? These are all questions this article will cover.   What is Estrogen Dominance/imbalance? Estrogen is known as the female hormone, although men have it too, just in smaller amounts with higher testosterone. It is is involved in reproduction and daily functioning, affecting mood, cognitive health, our skin, bone health and so much more. Sometimes estrogen becomes imbalanced. We might have too much estrogen compared to progesterone. Estrogen dominance happens when it starts to take the dominant role. Other factors influence this too: our genes our diet, lifestyle and environment our liver function You might not even know you have estrogen dominance, because it is not necessarily about having high levels of estrogen. It could simply be that you don’t have enough counterbalancing hormones like progesterone to mitigate the effect of estrogen in your body.   How Estrogen dominance happens Estrogen needs to be broken down and metabolized by certain enzymes in the liver and the gut before it can be safely excreted naturally. There are three pathways in which this happens. Each pathway determines whether estrogen will be converted into a good or a bad metabolite. The 2-OH is the good pathway, allowing good estrogen metabolites that support  a healthy mood, libido, and reproductive health. This is the pathway we want to encourage our body to use and has the least associated health risks. The 4-OH and 16 OH pathways are considered bad pathways because they produce estrogen metabolites that can cause cancer, low mood, PMS, PMDD and more. We are exposed to synthetic estrogens on a daily basis, called xenoestrogens. These are fake estrogens that mimic real estrogen. Your body does not know how to tell the difference.  These are found in our diet (hormones and antibiotics that animals are given; preservatives and food dyes; pestisides and fungicides on food; caffeine, alchohol) our lifestyle (certain medications, HRT, birth control pills) environment ( plastics, chemicals, pollution, skin and body products, household cleaning products, perfumes, sprays, sunscreen) These xenoestrogens are often stored in fat cells. The more fat you have, the more estrogen you are likely to have. Especially the fat on your midsection and thighs. Fat loves to absorb estrogen and elevated estrogen levels encourage your body to make more fat cells which leads to vicious cycle. When the body can’t metabolize estrogen, it gets stored in fat cells where it can recirculate and cause estrogen dominant symptoms (Such as estrogen related cancers, endometriosis, fibrocystic breasts, fibroids, PMS)   Genetic variants involved in Phase 1 and 2 of estrogen metabolism As I mentioned, estrogen is broken down in the liver and the gut by various enzymes. Methylation: COMT and MTHFR COMT stands for catechol-O-methyltransferase. It breaks down certain neurotransmitters and estrogen. When the activity of COMT is slow, it means you are likely to have higher levels of estrogen in your body, which is great if it stays balanced. Estrogen gives you glowing skin, it increases dopamine and thus helps you to feel motivation and pleasure and it acts as natural anti-depressant.  The problem lies in our diet and lifestyle and our exposure to those xenoestrogens. The more you take those in, the more they build up and the slower this enzyme works. The result? Estrogen dominance. Estrogen dominance can make you feel irritable, annoyed, aggressive and argumentative and anxious.   MTHFR MTHFR decresed activity has been associated with long duration of estrogen exposure. Someone with this enzyme can end up with two different kinds of estrogen and their metabolites circulating in their bloodstream. This is seen in an increased risk for premenopausal breast cancer. CYP450 enzymes These gene variants are involved in phase 1 liver detoxification that identify and convert fat soluble compounds coming in through our diet, lifestyle and environment into water soluble so that they can be excreted safely. However when there is altered activity in these enzymes, it can lead to the estrogen getting metabolized down a harmful pathway, which can cause health issues. (everything you eat, breath in and put on your body needs to go through this process) Oxidative Stress enzymes This is known as your intermediate phase, Once the enzymes in phase 1 have identified and converted the compounds, they wait to be processed by phase 2 enzymes, but during this waiting period they are potentially harmful and cause oxidative stress. Oxidative stress means free radicals are generated . Free radicals are a potentially harmful by product that can damage cells and cause illness and accelerate aging. We need the help of antioxidants from nutrients to neutralize them.  GST enzymes These enzymes are involved in phase 2 detoxification where they neutralize the potentially harmful compounds and get them ready for excretion. There are a few different processes that make this happen and one of them is using glutathione which is a powerful antioxidant to neutralize free radicals.   Phase 3: elimination Phase 3 is the last phase that relies on the gallbladder, intestines. Your liver packages waste products into bile, stores them in the gallbladder, and releases them into the intestines upon fat consumption, eventually exiting the body through stool. Waste is also removed by sweat and urine. Your body does not rely on enzymes alone to do this.  It needs the right nutrients coming in through your diet (antioxidants). If you you are exposed to many xenoestrogens through diet, lifestyle and environment, if you have genetic mutations and if you have a poor diet, this will all affect your body’s ability to detox estrogen properly, which means estrogen dominance.   Take Action As you can see this is an important part of a woman’s health that needs attention. If you are struggling with being overweight, poor sleep, diet, stress and you noticed from this article that you could

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