This is a good rundown of the biochemistry of under- and overmethylation, and a discussion of some the genetic abnormalities that might play a role:
During the methylation process, neurotransmitters are created, giving rise to certain emotional states. If there is problems with the methylation process, it is speculated that a number of different psychiatric symptoms may arise. These speculative symptoms are thought to be specifically correlated with whether someone is considered to be stuck in a state of “overmethylation” vs. “undermethylation.”
Undermethylation vs. Overmethylation
There isn’t anything wrong with being overmethylated nor undermethylated, but it may cause some sort of mental distress. Too much methyl (overmethylation) results in a unique set of symptoms that are different than those resulting from too little methyl (undermethylation). While undermethylation is generally considered less problematic than overmethylation, you may want to consider “methylation” and its potential to cause mental illness.
Undermethylation (Histadelia): Too little methyl (a carbon group with three hydrogen atoms). Essentially they have low levels of SAM-e, which donates methyl. This can lead to perfectionism, high accomplishment, and high achievement. Now why would this be problematic? 15-20% of these people experience problems as a result of the undermethylation. This can lead to low levels of serotonin, making them susceptible to depression.
Overmethylation (Histapenia): Too much methyl (a carbon group with three hydrogen atoms). It is very active in the brain, and too much leads to “too much of a good thing.” This causes an overproduction of serotonin, norepinephrine, and dopamine in the brain. In many cases, high serotonin levels can cause psychological problems including reduced motivation, reduced libido, weight gain, and confusion.
MTHFR Gene Polymorphisms Causes Undermethylation or Overmethylation
There are a number of theories regarding the causes of overmethylation as well as undermethylation. The most obvious cause is that of MTHFR genetic polymorphisms. If you possess a polymorphism of the MTHFR gene, this may be directly associated with poor methylation or highly efficient methylation. Fortunately you can detect whether you have a mutation of the MTHFR gene by getting a simple blood test.
MTHFR is an acronym for “Methylenetetrahydrofolate Reductase.” MTHFR is an enzyme and the MTHFR gene is necessary for the creation of the enzyme which regulates the methyl cycle. When the gene is considered abnormal, the methyl cycle may function abnormally. There are a variety of possible mutations that may occur to the MTHFR gene as well as its nucleotides.
If the gene’s nucleotide is abnormal, it’s called a SNP (Single Nucleotide Polymorphism). With the MTHFR gene, there are a variety of nucleotide polymorphisms (SNPs) that may occur, some are considered heterozygous (on one strand of DNA) while others can be homozygous (on both strands of DNA). Upon diagnosis, a professional will be able to explain whether you have homozygous or heterozygous MTHFR and the specific SNP location.
Biochemistry of Undermethylation
The undermethylation can lead to a number of deficiencies in nutrients throughout the body. Some researchers believe that if a person is a poor methylator, they are likely to have high levels of histamine, reduced zinc, and a high basophil count.
- High histamine: It is thought that a metabolic imbalance occurs when a person isn’t capable of sufficient methylation, leading to abnormally high histamine (e.g. 70 ng/ml).
- Low zinc: Some individuals who are chronically undermethylated tend to have zinc deficiencies.
- Low copper: Those with poor methylation ability tend to have low levels of copper.
- High Basophil count: This is often detected in blood tests and is associated with infections and allergic reactions. If levels exceed 50 cells/cu mm, there’s a better chance of undermethylation.
- High homocysteine: The greater the degree of undermethylation, the higher you can expect your homocysteine levels.
- High heavy metals: Proper methylation is thought to help detoxify the body of heavy metals and toxins. If a person is undermethylated, some speculate that they may have increased build-up of heavy metals.
Undermethylation Symptoms
Keep in mind that if you are suffering from undermethylation, you may not experience every symptom on this list. There are different genetic polymorphisms of the MTHFR gene as well as other factors that may dictate your experience. Below is a collective list of symptoms that people with undermethylation tend to exhibit.
- Addictions: Those who are considered undermethylators may be more likely to battle addictions and/or have addictive personalities.
- Competitive: It is believed that many undermethylators are extremely competitive in sports, business, and other facets of life. Competition is a notable signal that a person may not have a sufficient methylation process.
- Concentrative endurance: Some individuals who are suffering from undermethylation may have a difficult time maintaining focus for prolonged periods of time. In other words, their concentration ability may wane quicker than average.
- Delusions: Certain individuals that fall into the undermethylation diagnosis may experience delusions or beliefs that aren’t based in reality. While these generally are not severe, then can interfere with the accuracy of a person’s perception of reality.
- Headaches: Some researchers believe that undermethylation may cause physical symptoms such as headaches.
- High achievement: One characteristic (rather than symptom) of people with low levels of methylation is that of accomplishment and achievement. Many individuals considered top athletes, CEOs, and professionals may be fueled in part by undermethylation.
- High libido: A person may be highly interested in sex and/or have a higher than average “drive” compared to others.
- Obsessive compulsive: Undermethylation may provoke symptoms of OCD or other obsessive tendencies. In fact, someone may actually get diagnosed with obsessive-compulsive disorder as a result of their methylation deficiency.
- Oppositional defiance: Another common finding is that those displaying signs of oppositional defiant disorder (ODD) tend to also have undermethylation. While this isn’t a very common diagnosis, it is thought to be related to undermethylation.
- Inner tension: While a person who is an undermethylator may appear to exhibit a calm demeanor, they may be filled with inner tension.
- Low pain tolerance: Individuals with undermethylation tend to have a poor tolerance to any sort of pain.
- Perfectionism: Another trait of undermethylators is that of perfectionism. They aren’t satisfied unless tasks are completed in accordance to their specific methodology. They may be intolerant to less-than-perfect outcomes.
- Phobias: Certain phobias or irrational fears may be caused in part by undermethylation.
- Ritualistic behavior: Those who are undermethylated may engaged in ritualistic behavior with rigid schedules. They may have specific daily rituals to which they must adhere.
- Seasonal allergies: It has also been suggested that allergies may be stronger among undermethylators, particularly during seasonal transitions. This may be related to naturally elevated levels of histamine, leading to more pronounced reactions.
- Self-motivated: A person who is undermethylated may be highly self-motivated in both school and work functions. They may not need any outside inspiration or encouragement to complete their work, they are fuelled internally by themselves.
- Social isolation: Some individuals with undermethylation may isolate themselves from others and prefer to be left alone, especially during the completion of work.
- Strong willed: Another characteristic that is found among those who are undermethylated is that of a strong will.
Undermethylation and Serotonin: Researchers speculate that undermethylation is associated with abnormally low levels of serotonin in the brain. While the mainstream media has lead most people to believe that low serotonin is always bad, clearly not all outcomes are poor. However, the fact that undermethylators tend to have low serotonin, it can make some of these individuals more prone to developing depression. It is estimated that 15% to 20% of people dealing with undermethylation tend to find it problematic; likely as a result of serotonergic deficits.
Undermethylation Treatment
Assuming you are suffering from undermethylation, there are numerous supplements you can consider for treatment. Generally treatment doesn’t yield drastic improvement overnight, and in some cases it can take 8 to 12 months before a person feels noticeably better. However, it is also important to realize that nutritional intervention can be highly effective and successful over the long-term.
Since undermethylation results in low levels of calcium, magnesium, methionine, and Vitamin B6 – it’s important to consider these for supplementation. Additionally it may be important to avoid folic acid as levels may be abnormally high throughout neurons. Correcting nutritional imbalances is considered an important step towards improving undermethylation symptoms.
Supplements for Undermethylation
Most people aren’t fans of taking pharmaceutical medications once they have pinpointed the problem of undermethylation. If you know for a fact that undermethylation is the problem, taking a targeted nutritional approach is your best bet. Work with a professional to determine what quantities of vitamins and/or “stack” you should be taking.
- Choline
- Calcium
- Magnesium
- Methionine
- Omega-3 fatty acids
- SAM-e
- Vitamin B12
- Vitamin C
Medication Outcomes
If you plan on taking a medication, some researchers have noted that outcomes among individuals with undermethylation are considered specific based on the type of drug utilized.
- Antihistamines: Since those with undermethylation tend to have high levels of histamine, using an antihistamine may result in favorable effects.
- Benzodiazepines: People taking benzodiazepines like Xanax tend to have unfavorable responses if they are suffering from undermethylation.
- SSRIs: Those dealing with undermethylation tend to respond well to selective-serotonin reuptake inhibitors. These are antidepressant drugs that specifically increase the amount of extracellular serotonin. These are considered helpful among undermethylators because they have low levels of serotonin.
- Vitamin B Complex: Those taking Vitamin B Complex may experience adverse effects. This is because the person already has high levels of folic acid (Vitamin B9) and the complex serves to further elevate it.
Biochemistry of Overmethylation
Overmethylation is the polar opposite of undermethylation. If you are overmethylated, you will likely have elevated levels of serotonin, low levels of histamine, and likely a low count of absolute basophils. Additionally you may discover high levels of copper, but low presence of zinc and histamine throughout the body.
- High copper: Abnormally high levels of copper are generally present among those who exhibit overmethylation.
- Low basophil count: In cases of overmethylation, basophil count tends to be depressed, meaning theres less likelihood of an allergic reaction.
- Low histamine: Overmethylation results in the reduction of histamine, making it completely unnecessary to use an over-the-counter antihistamine.
- Low zinc: Another common finding among those who are overmethylators is low levels of zinc.
Overmethylation Symptoms
Below is a list of possible symptoms that you may experience during overmethylation. Understand that overmethylation will not necessarily cause every single symptom on the list and that severity of each symptom is highly subject to individual variation.
- ADHD: Those who are overmethylators may have attention deficits and may have been previously diagnosed with ADHD.
- Anxiety: In some cases, the overmethylation can lead to increased levels of anxiety and susceptibility to panic attacks.
- Artistic: Some sources have suggested a link between artistic and musical pursuits and overmethylation. Whether this is accurate is subject to debate.
- Depression: Those with overmethylation may become depressed as a result of high levels of serotonin, lack of motivation, and accomplishment.
- Dry skin: It has also been speculated that in those who are overmethylated tend to be more susceptible to bouts of dry skin.
- Food sensitivities: If you are an overmethylator, you may notice that you are highly sensitive to certain foods and/or chemicals.
- Frustration: Another sign among overmethylators is rampant frustration or becoming easily frustrated in seemingly benign situations.
- High pain threshold: Unlike those who are poor methylators, overmethylation is associated with a higher pain tolerance.
- Low libido: Another symptom of overmethylation is that of a decreased sex drive. They may be considerably less interested in sex than average.
- Low motivation: The general tendency among overmethylators is that of deficient achievement in workplace or competitive settings. This is often a direct result of the motivational deficit that may be a byproduct of overmethylation.
- Nervousness: This ties into the generalized anxiety that a person may experience as a result of the overmethylation.
- Obsessions: Some have suggested that individuals with overmethylation may demonstrate clear obsessions, but they aren’t usually accompanied by compulsions.
- Overweight: Those who are overmethylated may be more likely to pack on weight in part due to motivational deficits and depression.
- Paranoia: Among those who are strongly affected by overmethylation, paranoid thoughts, and possibly auditory hallucinations may emerge.
- Restless legs: Another possible symptom that you may experience if you’re dealing with too much methylation is restless legs.
- Self-imposed isolation: Those who isolate themselves from others may do so in part as a result of depression and or anxiety from overmethylation.
- Self-harm: Researchers believe that among those who commit acts of self-harm and mutilation, overmethylation tends to occur.
- Sleep disorders: Those with sleep problems may be more likely to have overmethylation.
Overmethylation Treatment
If you are dealing with overmethylation, many experts will recommend a specific supplement regimen over the course of 3 to 6 months. Some believe that it is easier to offset the effects of overmethylation than undermethylation. While you probably won’t notice major benefit overnight, you may start to feel gradually better over the course of several months.
To properly cope with overmethylation, it is recommended to work with a professional to construct a specific regimen of supplements. These supplements work to correct nutritional imbalances and should improve symptoms of the condition.
Supplements for Overmethylation
Working with a professional will help you come up with a supplement regimen that effectively offsets the overmethylation. The goal is to gradually reduce the amount of methylation that occurs with targeted nutritional interventions. Below are some supplements that someone may take if they are overmethylated.
- DMAE
- Folic Acid (Folate)
- Niacinamide
- Omega-3 fatty acids
- Vitamin B6
- Vitamin C
- Vitamin E
- Zinc
Medication Outcomes
If you are taking a medication and have a mutation of MTHFR that leads to overmethylation, below are some likely reactions.
- Antihistamines: Since you already have low levels of histamine, you are going to respond poorly to any antihistamine drug. People who are overmethylated tend to have less allergic responses than usual as a result of the low endogenous histamine.
- Benzodiazepines: Favorable responses have been noted among those with overmethylation to taking benzodiazepines.
- Lithium: The mood stabilizing agent Lithium has also been thought to yield noticeable improvement among those who are overmethylated.
- Oestrogen therapy: Should you engage in oestrogen therapy as an overmethylator, you are likely to experience an adverse reaction.
- SAM-e: This supplement should be avoided by any individual that is dealing with overmethylation. Adverse reactions are likely to occur as this will further increase methylation.
- SSRIs: In general, people who are overmethylated already have high levels of serotonin and don’t require an SSRI. Further increasing serotonin levels may be problematic and may yield unwanted side effects or adverse reactions.
Does treating undermethylation or overmethylation cure mental illness?
Assuming you are a person who has a polymorphism of the MTHFR gene that is causing undermethylation or overmethylation, balancing the methylation process could drastically improve your mood or psychiatric symptoms. While many people preach that treating “over” or “under” methylation with supplement stacks will “cure” you of your psychitric illness, it is important to realize that this isn’t often the case.
Addressing the methylation imbalances could significantly improve your symptoms and/or overall health. However, it does NOT mean that you will be eventually cured of your severe anxiety or depression. A considerable number of people do improve once they address their MTHFR mutations with nutritional-based therapy, but don’t isolate methylation as the sole cause of your mental illness. Your condition may be a result of a collective number of other genetic and environmental factors.
Are you suffering from overmethylation or undermethylation?
It is important to avoid assuming that you are an overmethylator or undermethylator based on the symptoms listed above. While you may be one or the other, self-diagnosing based off of information you’ve read online may end up doing more harm than good. If you are serious about learning whether you truly have a methylation problem, get the MTHFR gene tested and have the results analyzed.
Determining whether you have an MTHFR mutation is the best way for you to get proof that supports your hypothesis of being an overmethylator or undermethylator. Using a treatment protocol for overmethylation or undermethylation when you have no actual methylation dysfunction may be more problematic than beneficial.
I don't see social anxiety listed as one of the symptoms of either under or over methylation. However, you shouldn't operate on guesswork. Have had your MTHFR gene tested to know if you have a genetically-caused methylation dysfunction.
