MTHFR – Over or Under Methylated?

Please note: The content of this post is my own, unless the technical terms is too hard to explain, then the content is copy and pasted. I am not a medical professional and thus the post is my point of view. But the content is science-based and credible. Just because it is a new science, does not necessarily make it quackery. 

Say What?

Is it not enough that you are not methylating properly, now you need to worry about under or over methylating? What does that mean? But there is more. What about Copper overload, Pyrrole Disorder, Glucose dyscontrol and Malabsorption?

Before running to the pharmacy to pick up a B-vitamins supplement, you have to understand that if you have the MTHFR mutation that you can be either over or under methylated and the B-vitamins supplement will not help you much.

OVER methylation

Overmethylation (Histapenia): Too much methyl (a carbon group with three hydrogen atoms). 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. If you are overmethylated you might also have 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.

Overmethylation Characteristics

Below is a list of possible characteristics 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.
Supplements for 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) or Folinic acid
  • Niacinamide (Vitamin B3)
  • 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.
  • Many persons who are over methylated might have adverse reaction to serotonin-enhancing substances such as Prozac, Paxil, Zoloft, St. John’s Wort, methionine.
Under Methylation

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? This can lead to low levels of serotonin, making them susceptible to depression.

The undermethylation can lead to a number of deficiencies in nutrients throughout the body: High histamine, low zinc, low copper, high Basophil count, high homocysteine and high heavy metals.

Undermethylation characteristic

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 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

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 (methyl 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.
  • These undermethylated persons may benefit nicely from Paxil, Zoloft, and other serotonin-enhancing medications, although nasty side effects are common.  A more natural approach is to directly correct the underlying problem using SAMe, methionine, calcium, magnesium, amongst others.  Although most undermethylated patients thrive on folates, supplements of folates must be avoided for patients whose problems are dominated by low activity at serotonin receptors.  Folic acid, folinic acid, and methylfolate all reduce serotonin/dopamine neurotransmission by an epigenetic mechanism, and this effect overwhelms the folate benefits of improved methylation and serotonin synthesis.
Enzyme polymorphisms (genes)
  • MTHFR
  • COMPT

For a more comprehensive list of Over and under methylation characteristics click here.

Click on the link for more on Methylation: https://www.youtube.com/watch?v=W14kkO61Ano&t=2741s

 

MTHFR part 4: Folate Cycle

Please note: The content of this post is my own, unless the technical terms is too hard to explain, then the content is copy and pasted. I am not a medical professional and thus the post is my point of view. But the content is science-based and credible. Just because it is a new science, does not necessarily make it quackery. 

Found this really cool picture on livewello.com that explains what the Methylation Cycle does:

But we want to look at the Folate Cycle – MTHFR C667T and A1298C:

Fitting this picture, the explanation of the Folate cycle is described as:

“The Folate Cycle is the “Organic Farming Region” where everything is homegrown. This Region grows “organic” work tags (methyl groups) and is instrumental in the front-line production of new RNA and DNA. Still, this plantation is a bit old fashioned, employing a chain gang (homocysteine) to help them get the work done. Though rarely considered in everyday life, RNA & DNA are essential to making you unique, as well as directing health and longevity. Despite this, there must be balance between available work tags and crafting new genetic code. ” (http://resqua.com/702188759/what-is-the-folate-cycle)

So lets look at Alex’s results for MTHFR C667T and A1298C:

From a previous post you would remember that the clear markers mean there were no effect from this gene, but as you can see his C667T is not looking too good with 3 blue markers and the double T (TT). What does that mean?

Firstly the “T” is called allele. An Allele is one of two or more alternative forms of a gene that arise by mutation and are found at the same place on a chromosome. An TT allele lowers the activity of the MTHFR enzyme and increase the homocynsteine levels. Secondly, this means that there is less DNA repair and an increase in DNA adducts. An Adduct is a segment of DNA connected to a cancer-causing chemical. The TT results means that your MTHFR enzyme function is only at 40%. Thirdly,  an T allele carrier have increased folate, B2, B6 and B12 requirements.

To keep this whole process going B2 must be present in high enough amounts in the body to allow other B vitamins including B6 and folic acid to properly do their jobs.

The Folate cycle is huge and has many other steps involved. It produce Serine, Sarcosine and Glycine. And continue into the MAO & COMT and Urea Cycle. From the COMT cycle you have Neurotransmitter Metabolism (melatonin, Serotonin, Dopamine and Adrenaline) and Hystamine Metabolism. The Urea Cycle are responsible for Purines, Oxalate production and Nitric Oxide Production. The Urea/ Citric acid cycle also have Vit B3 (Niacin) involved.

Vitamin B3

The body uses vitamin B3 in the process of releasing energy from carbohydrates. Vitamin B3 comes in two basic forms- niacin (also called nicotinic acid) and niacinamide (also called nicotinamide). Niacin is involved in the production of NAD, required for redox reactions in glycolysis and in Krebs cycle during oxidative phosphorylation.

Vitamin D and VDR receptors

And somewhere in there Vitamin D plays a big roll.

Virtually every tissue type in your body has receptors for vitamin D, meaning that they all require vitamin D for adequate functioning. The very presence of specific receptors define vitamin D as a hormone, rather than a vitamin. It interacts with receptors throughout the body and has a number of different effects.

It’s becoming evident that higher doses of vitamin D are required to support its other activities in tissues such as heart muscle, brain cells, and fat tissue, to name just a few. Additionally, vitamin D regulates genes that control cell growth and development, immune function, and metabolic control.

Studies have now shown that vitamin D deficiency is associated with increased risk of numerous chronic disorders, including type II diabetes, cancer, infections, and cardiovascular, autoimmune, and neurological diseases.

While humans can make some vitamin D in their bodies, most of us require additional amounts from our diet, the sun, or from supplements in order to maintain adequate levels.

Once vitamin D has been ingested in the diet or produced in the skin, the liver and kidneys convert it to its active form, called 1,25-dihydroxyvitamin D, or vitamin D3.

According to mainstream medical standards, there are three levels of vitamin D status: sufficient, insufficient, and deficient.

  • People who are considered vitamin D “sufficient” have blood levels of at least 30 ng/mL. However, optimal vitamin D status is achieved with a minimum of 50 ng/mL.
  • Those considered “insufficient” (meaning their bodies aren’t at optimal vitamin D capacity) have levels between 21 and 29 ng/mL.
  • And those who are “deficient” are defined as having levels at or below 20 ng/mL.

To make reading pleasant, I will mention more about MAO & COMT and the Urea Cycle in a following post…