Category Archives for Genetic SNP’s

MTHFR Gene Mutation Defined for Your Health. What is MTHFR?

What if you could improve your health by knowing if you have an MTHFR gene mutation?

MTHFR is a gene encoding for Methylene-TetraHydroFolate Reductase (MTHFR). MTHFR is an enzyme found within the human body. Playing a vital role in how the body uses folate (vitamin B9). It converts the folate you eat, into folate your body can use (Folate → 5-methyltetrahydrofolate). The MTHFR gene has the information needed to make this important enzyme.

What Is An MTHFR Gene Mutation?

MTHFR gene mutations may contribute to serious health issues. Knowing you have one can help you start improving your health.

The MTHFR enzyme is a protein made up of amino acids. Each amino acid has a specific 3-letter code within your DNA. A mutation or single nucleotide polymorphism (SNP) changes one letter in the 3-letter code for a specific amino acid (or it could be a deletion).

An MTHFR gene mutation can replace one amino acid for another within the MTHFR enzyme, leading to a change in function. The MTHFR gene mutation alters the chain of amino acids that make up the MTHFR enzyme changing its overall shape. It’s important to understand that an enzyme’s shape gives rise to its function. So for example, the MTHFR C677T means that at place 677 on chromosome 1, the Cytosine has been changed to a Thymine. This change causes the amino acid sequence to change that makes the MTHFR enzyme.The result is a dysfunctional enzyme (it’s slower) and less 5-methylfolate production.

The overall shape of the MTHFR enzyme varies based on what MTHFR gene mutations are present. Each unique mutation has a different impact on how the MTHFR enzyme performs within the body. There are currently 34 different known MTHFR gene mutations. The two most researched mutations are C667T and A1298C, which are the mutations we focus on most.

Is There One Type Of MTHFR Gene Mutation?

Depending on the mutation you have the consequences are slightly different. Each mutation follows a similar trend towards less methylation within the body or less active folate production (5-MTHF). If a mutation is present, the enzyme can have a 20% to 70% loss of function.

Since everyone has two copies of each gene (one from each parent), loss of function depends on whether there are one or two copies of the MTHFR gene mutation present.

One copy of a gene = Heterozygous (C677T= ~40% loss, A1298C=~20% loss) (This means you have one copy from mom OR dad)

Two copies of a gene = Homozygous (C677T=~70% loss, A1298C=~40% loss) (This means you have one copy from both your mom AND dad)

One copy of both C667T and A129C = compound heterozygous = ~50% loss

(This means mom and dad each gave you one copy of C667T or A1298C)

In general, less methylation occurs in people who have two copies of an MTHFR gene mutation.

MTHFR Mutations = Less Methylation

Methylation is responsible for turning multiple processes within cells “on or off”.

Proper methylation (adding/removing methyl groups (CH3) from molecules) within the body ensures cells are doing their jobs.

Think of methylation as a master switch. Any biochemical product that ends in MT is a methyltransferase. Methyls act as a switch for methyltransferases, they make them stop and go. Methyltransferases have important biochemical roles in our bodies. For example:

  • The breaking down of toxic oestrogens through hormone production via COMT
  • The health of cellular membranes and energy through choline production via PEMT
  • For a more indepth understanding of the importance of methyltransferases click here (your methyltransferase article))

When methylation is not working or down regulated, the body is not able to produce correct responses to the environment, damaging the body. Certain process within cells will be turned on or off for too long, leading to an impaired ability to:

  • Get rid of toxins (detoxification)
  • Repair and rebuild DNA/RNA
  • Produce and process hormones
  • Build immune cells
  • Repair cell membranes
  • Turn the stress response on and off
  • Metabolize fat
  • Produce energy
  • Recycle and build neurotransmitters

When these vital cellular processes are not working correctly, adverse symptoms can arise such as: cardiovascular disease, impaired immunity, chronic inflammation, diabetes, anxiety, depression, chronic fatigue, cancer, fibromyalgia infertility and miscarriages. Problems with methylation will amplify the symptoms of existing autoimmune and psychiatric conditions. For a more in depth analysis about the symptoms of MTHFR mutations click here. (yes mthfr symptoms / conditions article

It is important to know if you have a mutation in the MTHFR gene.  Approximately 50-65% of the population has an MTHFR gene mutation.

However, if you have a mutation, this DOES NOT mean you have a problem with your health. Your environment plays a big role in determining the outcomes of mutations, which we will go over later in this article.

Testing For MTHFR Gene Mutations

Fortunately, there are  simple ways to find out if you test positive for a mutation in your MTHFR gene.

  • Through our MTHFR gene test. By ordering our simple blood spot test or buccal swab test you can find out if you are positive for an MTHFR mutation. The test is simple and you can do it in the privacy of your own home. Our test is available nationally and internationally.

Click here to order your testing kit and to learn more.

  • MTHFR buccal swab. This is a simple swab of the inside of the mouth. You swab your mouth and send it to us for analyses. This is an ideal option for children.

Click here to order your testing kit and to learn more.

    • Doctor/health practitioner. This method takes a bit longer than ordering our kit. You can make an appointment with your doctor or health care practitioner, who may give you a referral form to a pathology collection center. The pathologist will take a blood sample and the results are sent back to your doctor/health care practitioner for analyses. It is important to state you want to test for both of the most common MTHFR mutations (C677T and A1298C).

 

Managing MTHFR Gene Mutations

Knowing if you are positive for an MTHFR gene mutation is important because it may affect your biochemistry to the point that your energy, hormones, mood and detoxification systems are affected. It’s important to remember, just because you have a mutation in this gene, it may not mean you have any issues. What plays the biggest part in MTHFR mutations causing problems is your environment. What you eat, the amount of sleep you get, the stress you are under, the toxins you are exposed to, all play a role in the way your genes are expressed. Your genes are always feeding off of the environment to determine which how much a gene should be expressed and what genes to turn on/off. Working to create a stress free environment is a simple way to begin managing MTHFR gene mutations.

Over the past couple of decades science has been uncovering vast amounts of information in the field of nutritional and biochemical sciences There are some basic guidelines to managing MTHFR mutations through diet and lifestyle. These guidelines revolve around consuming foods that are easy for your body to digest, do not cause inflammation and avoiding toxins overloading the body’s detoxification systems. It is recommended that you:

  • Avoid cereal grains (because they are fortified with folic acid (not the right form of folate we want – see our folic vs 5-MTHF article
  • Avoid dairy products (they put extra stress on our immune system)
  • Avoid processed foods (they lack nutrients and folic acid is often added)
  • Lower alcohol consumption (it depletes all our B Vitamins)
  • Quit smoking (puts too many harmful chemicals into our body)
  • Reduce/modulate stress (stress responses consume the most methyl groups)
  • Reduce environmental toxins (MTHFR mutations impair the ability to detoxify, placing extra stress on the liver)
  • Increase vegetable consumption (especially dark leafy greens)
  • Maintain a healthy weight

Diet and lifestyle is individual. What is right for you, may not be right for the person next to you. But basic guidelines are here.  Our detailed diet and lifestyle guide for MTHFR gene mutations can be found here.

Key Considerations If You Have An MTHFR Mutation

I like to think of this as exciting news! It means you have a roadmap to improving your health and stopping the progression of health issues that plague many people in later life. The earlier you address your health, the easier it is to bring the body back into balance.

Cheers,

Carolyn.

P.S. If you are looking for a more in depth explanation and management of MTHFR before pregnancy, be sure to check out our Flagship course “MTHFR and Preconception”. This 4 to 8 module course will guide you through the ins and outs of preparation your body will need to have a healthy and thriving pregnancy. Modules include what tests to expect, how to analyze the results and steps to take to prepare mentally, physically and emotionally for your pregnancy.

What Is Glyphosate And How Can It Affect Our Health

Roundup is a popular brand of herbicide by Monsanto and has been making rounds not because of how great a product it is but because of its active ingredient: Glyphosate, a compound declared carcinogenic by the International Agency for Research on Cancer or IARC.

It’s household popularity is not just what makes it dangerous. It made headlines when people found out Roundup was being used on GMOs (Genetically Modified crops). Research has also linked it to antibiotic resistance and hormone disruption. Because of this, many governments are considering banning or at least restricting the use of the substance particularly in public places such as school districts.

Glyphosate use

Monsanto introduced Glyphosate in the US in 1974 and was originally used to kill weeds by blocking proteins essential to plant growth. It’s now a common herbicide in more than 160 countries with a reported use of at least 1.4 billion lbs. (635 million kg) annually. While this is mostly sold for home use, it’s mostly applied by the agricultural sector on corn, soy, and cotton crops, especially in the US.

Its use skyrocketed after seeds were genetically engineered to tolerate the chemical. Because these seeds produce plants that are not killed by glyphosate, farmers can apply the weed killer to entire fields without worrying about destroying crops.

The effect of Glyphosate to our health

Glyphosate has been linked to the following diseases/conditions:

1. Gastrointestinal disease

  • The action of glyphosate as an antibiotic may alter the gastrointestinal microbiome in vertebrates, which could favor the proliferation of pathogenic microbes in humans, farm animals, pets and other exposed vertebrates. Basically, by destroying the Shikamate pathway in plants (and we eat these plants, and animals feed on them) our gut microbiota is affected and we are seeing a reduction in Lactobacillus among other things.
  • Glyphosate-contaminated soybean feeds used in the pork industry have also been associated with elevated rates of gastrointestinal-health problems and birth defects in young pigs. Related impacts have been observed in poultry.

2. Obesity

  • It has been proposed that the exponential increase in the production of synthetic organic and inorganic chemicals may be causal in the current worldwide obesity epidemic, due to alterations in body chemistry that promote weight gain.
  • The shikimate pathway is the route for aromatic amino acids phenylalanine, tyrosine and tryptophan. Tryptophan is an essential amino acid, meaning that mammalian cells cannot synthesize it. Serum tryptophan depletion leads to serotonin and melatonin depletion in the brain. Since serotonin (derived from tryptophan) is a potent appetite suppressant, it follows that serotonin deficiency would lead to overeating and obesity.
  • As we have seen, tryptophan supplies could be depleted both in plant-based food sources and through impaired tryptophan synthesis by gut bacteria as direct effects of glyphosate. The observed 20-fold increase in the synthesis of tryptophan-derived polyphenolic flavonoids in the context of glyphosate provides strong evidence of impaired tryptophan synthesis.

3. Cobalamin deficiency

  • Species of Lactobacillus and Bifidobacterium have the capability to biosynthesize folate, so their disruption by glyphosate could contribute to folate deficiency. Either cobalamin (B12) or folate deficiency leads directly to impaired methionine synthesis from homocysteine, because these two vitamins are both required for the reaction to take place. This induces hyperhomocysteinemia (high homocysteine). Because a deficiency in cobalamin can generate a large pool of methyl-tetrahydrofolate that is unable to undergo reactions, cobalamin deficiency will often mimic folate deficiency.
  • We depend on our gut bacteria to produce cobalamin, and impaired cobalt supply would obviously lead to reduced synthesis of this critical molecule. Glyphosate is known to chelate or bind to metals like iron, copper, cobalt, molybdenum, zinc, and magnesium. It has also been proposed that chelation by glyphosate of both cobalt and magnesium contributes to the impaired synthesis of aromatic amino acids in Escherichia coli bacteria. Thus, it is plausible that glyphosate similarly impairs cobalamin function in humans by chelating cobalt. In addition is severely affecting our zinc, molybdenum, iron, copper, manganese, and calcium in foods and the body.

4. Cancer

  • Despite most studies saying it’s generally not cancerous, one study on breast cancer conducted by Thongprakaisang S et. al. confirms at least one connection.
  • Glyphosate exerts proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer. The proliferative concentrations of glyphosate that induced the activation of estrogen response element transcription activity were 5-13 fold of control in T47D-KBluc cells.
  • This activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. This indicates both low and environmentally relevant concentrations of glyphosate possessed estrogenic activity.
  • Recently Stephanie Seneff (the world’s most significant researcher of Glyphosate) released a paper discussing the link between glyphosate and cancer. In this paper she says “glyphosate has a large number of tumorigenic effects on biological systems, including direct damage to DNA in sensitive cells” she goes on to say that “epidemiological evidence supports strong temporal correlations between glyphosate usage on crops and a multitude of cancers that are reaching epidemic proportions, including breast cancer, pancreatic cancer, kidney cancer, thyroid cancer, liver cancer, bladder cancer and myeloid leukaemia”

5. Infertility

  • Glyphosate has been described as an endocrine disruptor affecting the male reproductive system.
  • Glyphosate toxicity was proposed to implicate CA(+2) overload, cell signaling misregulation, stress response of the endoplasmic reticulum, and/or depleted antioxidant defenses, could contribute to Sertoli cell disruption in spermatogenesis that could have an impact on male fertility.

6. Kidney disease

  • The strong association of the consumption of hard water and occurrence of chronic kidney disease has been subjected to many discussions among investigators, but none of the available theories could explain this relationship coherently.
  • Glyphosate is metabolized via the glyoxalate pathway. When this pathway is inundated more oxalate is formed and this is a direct cause of kidney disease. Oxalates are naturally occurring substances found in a wide variety of foods and although they play a supportive role in the metabolism of many plants and animals when they over accumulate inside our body, they can form stones in the kidney. They bind to calcium and can also interfere with calcium metabolism.

What now?

The EPA is reviewing its approved uses of glyphosate while countries such as Sri Lanka has banned it. Brazil is considering a similar move. Mexico and the Netherlands have imposed new restrictions, and Canada has just begun a process to consider new rules.

As for Australia, it may take a while for our government to follow suit .

So what can we do?

  1. Avoid genetically modified foods
  2. Eat as organically as you can
  3. Avoid canola oil
  4. Avoid processed foods
  5. Regularly check key nutrients that may be depleted by glyphosate – copper, zinc, iron, manganese, magnesium, cobalt (B12) and sulfur
  6. If you have a family history of kidney stones or gall bladder issues consult someone who knows about oxalates and glyphosate to get yourself assessed.
  7. If you have a family history of thyroid disease, you may have oxalate issues
  8. If you have gut issues, particularly low lactobacillus you may have oxalate/glyphosate issues.
  9. If you have recurrent diarrhea you may have oxalate issues.
  10. If you are juicing lots of high oxalate foods like spinach, beetroot, carrot, and celery these may disturb kidney function. My motto is ‘if you can’t eat it on a plate then don’t juice it. That means that if the amount you juiceis too much for you to sit down and eat at the one meal, you are having too much.
  11. I suspect those with chronic iron issues may have an oxalate/glyphosate problem. Because oxalates will bind to iron making it unavailable.
  12. DEFINITELY DON’T USE ROUNDUP AT HOME!!!!!

If you are preparing your body for a healthy and thriving pregnancy, we have a free pregnancy checklist of the “10 most important things you need to do before you become pregnant” 

 

References

MYERS JP, ANTONIOU MN, BLUMBERG B, ET AL. CONCERNS OVER USE OF GLYPHOSATE-BASED HERBICIDES AND RISKS ASSOCIATED WITH EXPOSURES: A CONSENSUS STATEMENT. ENVIRON HEALTH. 2016;15:19.
BAILLIE-HAMILTON PF. CHEMICAL TOXINS: A HYPOTHESIS TO EXPLAIN THE GLOBAL OBESITY EPIDEMIC. J ALTERN COMPLEMENT MED. 2002;8(2):185-92.
BREISCH ST, ZEMLAN FP, HOEBEL BG. HYPERPHAGIA AND OBESITY FOLLOWING SEROTONIN DEPLETION BY INTRAVENTRICULAR P-CHLOROPHENYLALANINE. SCIENCE. 1976;192(4237):382-5.
ZHAO J, WILLIAMS CC, LAST RL. INDUCTION OF ARABIDOPSIS TRYPTOPHAN PATHWAY ENZYMES AND CAMALEXIN BY AMINO ACID STARVATION, OXIDATIVE STRESS, AND AN ABIOTIC ELICITOR. PLANT CELL. 1998;10(3):359-70.
ROSSI M, AMARETTI A, RAIMONDI S. FOLATE PRODUCTION BY PROBIOTIC BACTERIA. NUTRIENTS. 2011;3(1):118-34.
THONGPRAKAISANG S, THIANTANAWAT A, RANGKADILOK N, SURIYO T, SATAYAVIVAD J. GLYPHOSATE INDUCES HUMAN BREAST CANCER CELLS GROWTH VIA ESTROGEN RECEPTORS. FOOD CHEM TOXICOL. 2013;59:129-36.
JAYASUMANA C, GUNATILAKE S, SENANAYAKE P. GLYPHOSATE, HARD WATER AND NEPHROTOXIC METALS: ARE THEY THE CULPRITS BEHIND THE EPIDEMIC OF CHRONIC KIDNEY DISEASE OF UNKNOWN ETIOLOGY IN SRI LANKA?. INT J ENVIRON RES PUBLIC HEALTH. 2014;11(2):2125-47.
SAMSEL, A., & SENEFF, S. (2015). GLYPHOSATE, PATHWAYS TO MODERN DISEASES IV: CANCER AND RELATED PATHOLOGIES. JBPC JOURNAL OF BIOLOGICAL PHYSICS AND CHEMISTRY, 15(3), 121-159. DOI:10.4024/11SA15R.JBPC.15.03

5 Common MTHFR Symptoms and How to Manage Your Gene Mutation

MTHFR Symptoms are brought on by MTHFR gene mutations and commonly underlie many health problems.

With a few simple changes and some professional advice, you may be able to alleviate some symptoms laid out in this article. MTHFR is often overlooked. New research is showing how important it really is. You may be shocked to find out how many symptoms are linked to MTHFR gene mutations.

MTHFR gene mutations may lead to less methylation in your body. Less methylation means that a variety of complex biochemical changes can change over time, leading to health problems. Since everyone is unique, (for example family history, lifestyle, diet etc..) symptoms arising from MTHFR mutations vary from person to person.

Fortunately, depending on how your MTHFR mutation is affecting you, you can see vast improvements in your health by treating MTHFR mutations and restoring methylation. Knowing you have a gene mutation is the first step to treating MTHFR symptoms associated.

5 Common MTHFR Symptoms Linked To MTHFR Gene Mutations

  • Cardiovascular Conditions

      • MTHFR mutation may be adding fuel to the fire of cardiovascular problems. The following is a list of cardiovascular conditions where MTHFR combined with an elevated homocysteine could be playing a role:
        • High blood pressure
        • Stroke
        • Heart attack
        • Deep vein thrombosis

  • Multiple Miscarriages and troubles falling pregnant.

    • Pregnancy is one of the most beautiful and complicated biological processes on earth. Due to the complex nature of pregnancy, the most important nutrients required for the baby’s growth and development and good DNA from Mum and Dad is active folate.Ensuring your active folate production is in tip-top shape during preconception and pregnancy is critical for a healthy and successful pregnancy.
    • Problems arising from MTHFR mutation during pregnancy include:
      • Miscarriage
      • Down syndrome
      • Neural tube defects (Cleft lip/palate and spina bifida)
      • Elevated blood pressure
      • Anencephaly, encephalocele

  • Oestrogen Dominance

    • Methylation plays a crucial role in the production/regulation of hormones within the human body. In some cases, problems with methylation are the underlying factor behind Oestrogen dominance, which can produce the following symptoms:
      • Fibrocystic ovaries and breasts
      • Tenderness and swelling of breasts
      • Mood swings
      • Irregular menstruation cycle
      • Food cravings
      • Thyroid dysfunction
      • Heavy periods
      • Painful Periods
      • Endometriosis (overgrowth of tissue lining the uterus, this is often painful)
      • Fibroids

  • Mental Health Problems

    • Mental health problems can be influenced by imbalances in hormones and neurotransmitters caused by a lack of methylation. Remember that SAMe is essential for our brain chemicals and your active folate helps you build SAMe levels. Receiving treatment for your faulty MTHFR gene may aid in improving/relieving the following symptoms:
      • Depression
      • Anxiety
      • Bipolar
      • Migraines
      • ADD/ADHD
      • Brain fog (difficulty concentrating)

  • General MTHFR Symptoms and Conditions Of MTHFR Gene Mutations Include:

    • Chronic inflammation
    • Chronic fatigue
    • Dizziness
    • Hives
    • Allergies
    • Eczema
    • Asthma
    • Heightened reaction to allergens
    • Elevated liver enzymes
    • Increased red blood cell folate
    • Decreased white cell levels
    • Decreased immune function
    • High Homocysteine levels
    • Low B12

Common Medications That Reduce Methylation

Common medications may be reducing your ability to methylate by lowering B12 or overall folate levels. If less B12 and/or folate is available to use in your body, symptoms may become worse. Medications that could be interfering with your B12 and folate levels include:

  • Antacids
  • Cholestyramine
  • Nitrous oxide – your dentist will often use this. Its known as laughing gas.
  • Methotrexate
  • Niacin (at high doses) – because Niacin uses methyl groups in its metabolism
  • Theophylline
  • Cyclosporin
  • Metformin
  • Phenytoin
  • Bactrim – an antibiotic
  • Sulfasalazine
  • Triamterene
  • Trimethoprim
  • Ethanol
  • Oral Contraceptive Pill
  • Antimalarials

Conditions of Hypomethylation (Under Methylation)

MTHFR mutations cause widespread undermethylation throughout the body. Undermethylation is responsible for an enormous amount of health conditions that prevent you from living life to its fullest. Below you can find a comprehensive list (organized categorically) of conditions associated with undermethylation:

General Physiological Malfunctions

  • Allergic conditions
  • Aging
  • Alzheimer’s Disease
  • Asthma
  • Autoimmune Disease
  • Cancer
  • Chronic degenerative diseases
  • Cardiovascular disease
  • Chronic fatigue
  • Diabetes
  • Poor detoxification
  • Fibromyalgia
  • Headaches
  • Joint pain, stiffness, and swelling
  • Muscle pain
  • Low neurotransmitter levels
  • Obesity
  • Increased pain
  • Thyroid dysfunction

Mental Health

  • ADD/ADHD
  • Addictive behaviors
  • Anorexia
  • Anxiety
  • Bipolar
  • Bulimia
  • Delusions
  • Depression
  • Autism
  • Insomnia
  • Obsessive-compulsive disorder (OCD)
  • Oppositional defiant disorder (ODD)
  • Phobias
  • Psychosis
  • Schizophrenia

Pregnancy/Development

  • Spina bifida
  • Anencephaly
  • Encephalocele
  • Iniencephaly
  • Down syndrome
  • Infertility
  • Polycystic ovary syndrome
  • Recurrent pregnancy loss/miscarriage

Improving Your Health With An MTHFR Mutation

If you want to take back control of your methylation cycle right away, supplementing is a great way to fight back against your MTHFR gene mutation. Care must be taken when supplementing to ensure symptoms do not worsen. To get started now, you can take a look at our “How to get started with MTHFR supplements” video below, or, download our guide on how to start supplementing MTHFR products.

P.S. Carolyn has also prepared a full overview of the MTHFR Gene Mutation and Management. Grab a good spot to listen and take some time to educate yourself with this Patient Webinar, exclusive to our audience. In this video, Carolyn gives you a thorough overview of MTHFR and symptoms related.

The Importance Of Methyltransferases

The Importance Of Methyltransferases

The Importance Of Methyltransferases

Without them, life would not be possible. Put simply, methyltransferases are enzymes responsible for adding and/or removing methyl groups from molecules within the body.

A methyltransferase is similar to a light switch. If you want to turn the lights on or off in a room, you flip the light switch. You flip the switch up, you get light. You flip the switch down, the light turns off.

Methyltransferases function the same way in the body as a light switch. They add a methyl group to a molecule, to activate or deactivate its function. The addition of a methyl group turns on or off the lights so to speak. But what carries the signal from the switch to the light bulb? The answer is S-adenosyl methionine (SAM).

S-Adenosyl Methionine (SAM)

If methyltransferase is the switch to turn on and off processes in the body, what carries the signal from the switch to the light bulb? SAM. SAM is responsible for physically passing off or donating the methyl group to another molecule. SAM does this by working alongside methyltransferases as a cosubstrate (SAM forms a complex with the methyltransferase enzyme). SAM donates the methyl group to the molecule, protein or DNA/RNA targeted by the methyltransferase, undergoing the following reaction:

S-adenosyl methionine (SAM) → S-adenosyl homocysteine (SAH)

SAH then feeds back into the SAM-e cycle and is made into homocysteine. From here homocysteine is converted back to SAM by the MTHFR enzyme. 5-MTHF donates its methyl group to homocysteine making it become methionine and 5-MTHF becomes tetrahydrofolate (THF).

Primary Functions Of Methyltransferases

Genomic Regulation

Genome methylation (regulation) is the main source of gene expression control. Methylation plays a role in determining which genes are put to use and which genes remain inactive. DNA methylation is crucial for survival. Methylation on the level of the genome, allows the body to respond quickly to its environment.

Of course, the body can deal with stresses in a variety of ways. Ensuring your body handles stress efficiently is the job of methylation. The body always wants to use the least amount of energy to get the job done. Regulating the genome through methylation helps processes within the body stay efficient. You do not always want your body making something from your DNA that is not useful to have all the time. Every methylation process in the body involves adding or removing a methyl group. Problems arise when the body is unable to utilize methyl groups by adding/removing them from molecules and enzymes, playing a large role in some human diseases.

Methylation activates and deactivates DNA when needed by altering the structure of the genome through adding or removing methyl groups. Over time sections of DNA become methylated and gene expression changes. The study of changes in gene expression over time due to methylation is a field of genetics called epigenetics.
Protein Regulation

Methyltransferases play a role in activating and deactivating proteins within the body. If some proteins were active all the time, the body would pay a high cost. The human body is quite resilient but things can get thrown off balance quickly and become problematic. Protein regulation through methyltransferases makes sure the complex biochemistry within cells remains stable.

Methyltransferases regulate proteins beyond activation/deactivation. When a protein becomes methylated it can gain a new function and/or start working with another protein. Allowing proteins to have multiple functions. Methylating proteins increases their range of possibilities making them more flexible, dynamic and ready to respond to changing conditions.

Take Aways

Methyltransferases are miracle workers within the body, they keep it functioning and not functioning at the right times. Keeping your methyltransferases healthy by making sure they have the right vitamin cofactors to work with will go a long way towards the journey of better health and successful pregnancy.

Have more questions on methyltransferases? Post below and let’s have a discussion!

High homocysteine – it can affect your brain, your heart and your pregnancy.

High homocysteine – it can affect your brain, your heart and your pregnancy.

Hyperhomocysteinemia, the condition of having high homocysteine in the blood, causes numerous health issues within the body. This article will cover health and pregnancy-related aspects of high homocysteine. If you do not know what homocysteine is or want to know more about homocysteine before reading this article check out “What’s All The Fuss About Homocysteine?”

High homocysteine levels cause hyperhomocysteinemia — a condition that results in fertility issues, mental health disorders, and cardiovascular problems. Since individual genes are responsible for metabolizing homocysteine, people with MTHFR mutations and mutations in genes involved in vitamin B and folate metabolism are at risk of developing high homocysteine levels.

High homocysteine can be treated with a combination of nutrients like folate, B12, B6 and trimethylglycine. It’s important to work with a practitioner because levels can drop quickly and the formula may need to be changed frequently to avoid homocysteine levels dropping too low.

Homocysteine and Cardiovascular Disease

High homocysteine concentrations increase one’s risk for cardiovascular disease. Arteries harden and narrow due to hyperhomocysteinemia, ultimately resulting in cardiovascular disease – which occur in coronary, cerebral and peripheral blood vessels. People with a familial history of, or current, cardiovascular disease should get tested frequently and seek medical advice.

Homocysteine and Mental Illness

According to studies, the nervous system can be severely harmed by high levels of homocysteine in the body. Homocysteine functions to maintain blood vessels, is a vital intermediate molecule in the creation of primary methyl donors. High levels of homocysteine results in numerous biochemical imbalances in the body, and in the brain, which causes irreparable damage to our bodies and mental health.

A study has shown that patients with depression also had hyperhomocysteinemia, metabolic disorders involving folate metabolism, and neurotransmitter metabolic issues. It proved that 20-30% of patients suffering from hyperhomocysteinemia and depression showed more severe symptoms. It is therefore evident that hyperhomocysteinemia does not affect everyone in the same manner. A specific supplementation program is essential to determine whether your hyperhomocysteinemia is affected by depression. However, depression is not the only condition related to mental health that could show exacerbated symptoms due to high levels of homocysteine. Homocysteine levels are known to increase as we age. Dementia and Alzheimer’s are also potential resultant effects from such increased cellular concentrations.

Homocysteine and Pregnancy

Homocysteine levels during pregnancy are relatively inconsistent as they continuously fluctuate. However, high amounts of homocysteine during pregnancy can result in adverse outcomes to both mother and child. Additionally, some people may experience changes due to insufficient vitamin cofactors or have impaired functionality of methionine synthase.

Methionine is an enzyme which converts homocysteine to methionine. This process is called transsulfuration or remethylation. When transsulfuration is not working or inactive, it can lead to myelin deficiency during pregnancy (Mills, 1995).  Myelin is a fatty material, white in appearance which forms a sheath around the neurons within the central nervous system. The purpose of myelin is to increase the speed of neural transmission and is crucial for the proper function of the nervous system. Multiple Sclerosis (MS), is an autoimmune disease that attacks and destroys the myelin surrounding neurons. This damage can lead to a wide variety of symptoms associated with MS that include:

  • cognitive impairment
  • depression
  • dizziness
  • optic neuritis
  • pain
  • fatigue
  • tinnitus
  • muscle weakness
  • numbness/tingling
  • tremors
  • twitching

 

Neural tube defects or NTD’s, which are birth defects of the brain, spine or spinal cord, can arise when there is not enough myelin production in a fast-growing fetus during pregnancy.  The most significant development of myelination occurs during the third trimester of fetal development and progresses rapidly during the first few years of a child’s life. Environmental input supportive of myelination during pregnancy does not only help prevent neural tube defects but also helps to develop a functional and healthy nervous system for your child to inherit.

Pre-eclampsia

When there is too much homocysteine in the blood it can cause damage to the vascular system, which in turn may lead to increases in blood pressure, vascular abnormalities in the mother and fetus, and ultimately preeclampsia. Although the cause of preeclampsia remains largely unknown., it appears to be caused by oxidative stress during pregnancy from high levels of homocysteine.

Research surrounding preeclampsia and homocysteine shows evidence supporting the harmful role hyperhomocysteinemia plays in the development of preeclampsia. A study done by Dekker et al., 1995, found that 2% of pregnant women have pregnancies that develop pre-eclampsia, and 17.7% of these women have hyperhomocysteinemia. A follow-up study done by Leeda et al., in 1998, confirmed the finding of Dekker and his team – showing the association between preeclampsia and hyperhomocysteinemia.

Placental Abruption

Placental abruption (Abruptio placentae) occurs when the placental lining detaches from the uterus (after week 20 and before birth), causing internal bleeding. Depending on the severity, the mother and the fetus could face death or serious injury. Placental abruptions occur, on average, 1 in 200 pregnancies and are a major contributor to maternal deaths around the world.

In a study done by Goddijin-Wessel et al., in 1996 found 31% of pregnant patients who have placental abruptions have hyperhomocysteinemia after a methionine loading test, compared to 9% of the control group. Methionine loading tests provide insight into how efficiently the body is utilizing homocysteine.  This study concluded that higher levels of homocysteine result in higher chances of having placental abruptions.

Another study was done by Vries et al., in 1998 found that 26% of people with placental abruptions without preeclampsia had hyperhomocysteinemia 3 months after their pregnancy. This study concluded that having a placental abruption or preeclampsia during pregnancy can be an indicator of hyperhomocysteinemia. In such a case, you should get your homocysteine levels checked if you experience these complications during pregnancy.

Thromboembolic Events

Hyperhomocysteinemia is a subcategory of a broader set of congenital conditions called thrombophilias. Thrombophilias occur when the body has an abnormal tendency of blood to clot. This results in higher chances of thromboembolic events occurring, namely, heart attacks, strokes and pulmonary embolisms. Unfortunately, hyperhomocysteinemia is more likely to cause thromboembolic events in women compared to men. Women are 3.8 times more likely to have a thromboembolic event compared to men having a 1.8 times higher chance.

Pregnancy itself is a risk factor for thromboembolic events, further increasing the risk in addition to hyperhomocysteinemia. With the right precautions, the risk of having a thromboembolic event during pregnancy can be mitigated. Pregnancy and hyperhomocysteinemia are not the only risk factors for thromboembolic events. All factors should be taken into consideration while developing a plan to decrease or prevent chances of thromboembolic events before, during and after pregnancy.

Fetal Death in Utero

The conditions leading to fetal death are complex and come from many sources. Often a combination of embryonic processes go wrong, many of which are outlined in this article. Preventing fetal death requires a multifaceted approach which can be overwhelming if taken on alone. If you are worried, had previous issues, or are at risk, then reach out for professional support who will conduct proper examinations through regular check-ups and give advice during every step of your pregnancy.

Intrauterine Growth Retardation (IUGR)

Only a few studies have been done around the world into IUGR and hyperhomocysteinemia. The results of these studies obtained are somewhat contradictory. Researchers hypothesize that hyperhomocysteinemia increases the likelihood of IUGR and their studies both support and reject their hypothesis. More research is needed to clear up the contradictory scientific evidence gathered so far. It is too soon to jump to any conclusions about the relationship between hyperhomocysteinemia and IUGR and larger prospective studies are needed in this field.

Recurrent Pregnancy Loss

The main hypothesis surrounding homocysteine and recurrent pregnancy loss is that high levels of homocysteine interfere with the implementation of the embryo into the endometrial wall of the uterus. This interference occurs due to premature damage to the capillaries that supply the endometrial uterine wall. The capillaries are less functional due to excessive amounts of homocysteine being present, making them unable to support the new embryo and leading to miscarriages. In animal models, using rats and chickens, homocysteine levels higher than 15 ɥmol/l cause 75% of pregnancies to abort due to developmental abnormalities.

There are significant links between recurrent pregnancy loss and hyperhomocysteinemia, 14% of women who have primary repeated miscarriages have hyperhomocysteinemia and 33% of women who have secondary repeated miscarriages have hyperhomocysteinemia. If you have had miscarriages in the past, or are worried about having miscarriages in the future, make sure to get your cellular homocysteine concentrations to the correct levels.

Take Aways

There is overwhelming scientific evidence suggesting high homocysteine (hyperhomocysteinemia) increases fertility complications, cardiovascular disease and mental health issues. The most pressing and immediate concerns of hyperhomocysteinemia are its effects on pregnancy. If you are considering pregnancy, make sure you check homocysteine levels before, during and after pregancy, especially if you have the MTHFR gene mutation as this increases the risk of having high homocysteine levels. Creating a strategy with a trained professional is an even better idea because pregnancy is an extremely complicated process with a lot of moving parts. Ensuring you have professional support during pregnancy is in you and your child’s best interest. High homocysteine levels are not the only problem, you could be experiencing health problems from low homocysteine levels.

 

References

(1) Aubard, Y., Darodes, N., & Cantaloube, M. (2000). Hyperhomocysteinemia and pregnancy—review of our present understanding and therapeutic implications. European Journal of Obstetrics & Gynecology and Reproductive Biology, 93(2), 157-165.

(2) Dekker, G. A., De Vries, J. I. P., Doelitzsch, P. M., Huijgens, P. C., Von Blomberg, B. M. E., Jakobs, C., & Van Geijn, H. P. (1995). Underlying disorders associated with severe early-onset preeclampsia. American journal of obstetrics and gynecology, 173(4), 1042-1048.

(3) Den Heijer, M., Koster, T., Blom, H. J., Bos, G. M., Briët, E., Reitsma, P. H., … & Rosendaal, F. R. (1996). Hyperhomocysteinemia as a risk factor for deep-vein thrombosis. New England Journal of Medicine, 334(12), 759-762.

(4) Goddijn-Wessel, T. A., Wouters, M. G., vd Molen, E. F., Spuijbroek, M. D., Steegers-Theunissen, R. P., Blom, H. J., … & Eskes, T. K. (1996). Hyperhomocysteinemia: a risk factor for placental abruption or infarction. European Journal of Obstetrics & Gynecology and Reproductive Biology, 66(1), 23-29.

(5) Hague, W. M. (2003). Homocysteine and pregnancy. Best practice & research Clinical obstetrics & gynaecology, 17(3), 459-469.

(6) Leeda, M., Riyazi, N., de Vries, J. I., Jakobs, C., van Geijn, H. P., & Dekker, G. A. (1998). Effects of folic acid and vitamin B 6 supplementation on women with hyperhomocysteinemia and a history of preeclampsia or fetal growth restriction. American journal of obstetrics and gynecology, 179(1), 135-139.

(7) Mills, J. L., Lee, Y. J., Conley, M. R., Kirke, P. N., McPartlin, J. M., Weir, D. G., & Scott, J. M. (1995). Homocysteine metabolism in pregnancies complicated by neural-tube defects. The Lancet, 345(8943), 149-151.

(8) Refsum, MD, H., Ueland, MD, P. M., Nygård, MD, O., & Vollset, MD, Dr. PH, S. E. (1998). Homocysteine and cardiovascular disease. Annual review of medicine, 49(1), 31-62.

(9) Reynolds, E. H. (2002). Folic acid, ageing, depression, and dementia. British Medical Journal, 324(7352), 1512.

(10)Rosenquist, T. H., Ratashak, S. A., & Selhub, J. (1996). Homocysteine induces congenital defects of the heart and neural tube: effect of folic acid. Proceedings of the National Academy of Sciences, 93(26), 15227-15232.

(11)Vanaerts, L. A., Blom, H. J., Deabreu, R. A., Trijbels, F. J., Eskes, T. K., Peereboom‐Stegeman, J. H., & Noordhoek, J. (1994). Prevention of neural tube defects by and toxicity of L‐homocysteine in cultured postimplantation rat embryos. Teratology, 50(5), 348-360.

(12)Vries, J. D., Dekker, G. A., Huijgensb, P. C., Jakobs, C., Blomberg, B. M. E., & Geijn, H. V. (1997). Hyperhomocysteinaemia and protein S deficiency in complicated pregnancies. BJOG: An International Journal of Obstetrics & Gynaecology, 104(11), 1248-1254.

(13)Wouters, M. G., Boers, G. H., Blom, H. J., Trijbels, F. J., Thomas, C. M., Borm, G. F., … & Eskes, T. K. (1993). Hyperhomocysteinemia: a risk factor in women with unexplained recurrent early pregnancy loss. Fertility and sterility, 60(5), 820-825.

Introduction To MTHFR Mutations

If you have heard of MTHFR mutations before but didn’t know where to start. This article is for you! It will give you a foundational understanding of biology while introducing you to MTHFR and fertility.

What Are Genes?

Genes are the deoxyribonucleic acid (DNA) sequences responsible for making proteins and enzymes. Gene expression is the process of the body actually using the gene to produce a protein or enzyme. Many factors contribute to gene expression and gene expression changes throughout life. For example, gene expression is different before puberty and after puberty, or before menopause and after menopause. Gene expression also changes due to psychological, environmental and dietary factors.

What Are Genetic Mutations?

DNA is made up of four building blocks: adenine (A), thymine (T), guanine (G) and cytosine (C).  Genetic mutations are changes within a sequence of DNA. For example, an “A” might change to a “C”, or a “T” might be removed/added to a DNA sequence. There are multiple forms of genetic mutations that are beyond the scope of this article. It is important to know that genetic mutations mostly have negative consequences on the performance of their products (i.e enzymes).

What Are Enzymes and Why Are They So Important?

Enzymes are proteins that help build, break down, and/or speed up biochemical reactions within the body. Some chemical reactions would take days, weeks, or months to happen, but enzymes make these reactions happen much faster. Without enzymes, life as we know it would not be possible. Chemical reactions would be too slow within the body, and we would not have the capacity to produce the necessary chemicals for survival.   

What Is MTHFR?

MTHFR stands for Methylenetetrahydrofolate reductase. The MTHFR enzyme is made from the MTHFR gene. The MTHFR gene contains the genetic information required to make the MTHFR enzyme. It is the enzyme responsible for the final step in the folate cycle. When the MTHFR enzyme is not functioning properly, there is a shortage of important biochemical substances and a build-up of harmful substances within the body. MTHFR gene mutations impair the body’s ability to perform many crucial tasks.

How Common are MTHFR  Mutations?

Some people, approximately 30-50% but some research shows possibly 70-75%, have genetic mutations in their MTHFR gene (3). As more people have their genomes sequenced around the world, we will get a better understanding of how prevalent MTHFR mutations are around the world.  Different populations of people around the world have different frequencies of MTHFR mutations, for example, the highest concentration of  MTHFR C667T mutations in the world are found in Italy (1). These mutations affect the ability of the MTHFR enzyme to complete the final step in the folate cycle. MTHFR mutations lead to a complex cascade of biochemical reactions that cause a wide variety of health and fertility issues.

Consequences Of The MTHFR Mutations On Health And Fertility

According to a new scientific review published in July 2017, in the Journal of Genes and Genomics, MTHFR mutations play a role in the following multifactorial diseases (2):

  • Cardio-cerebrovascular
  • Neurodegenerative disorders
  • Autoimmune diseases
  • Diabetes
  • Neuropsychiatric disorders
  • Renal diseases
  • Cancer
  • Birth defects

The health consequences of MTHFR are so far-reaching because the MTHFR enzyme is crucial to basic functions within our bodies. If you are wondering how one gene/enzyme can have such a wide variety of consequences, without getting too involved in the science, you need to gain a basic understanding of how MTHFR mutations actually create health and fertility problems.

Understanding MTHFR Mutations

There is not just one kind of MTHFR mutations there are several (MTHFR C667T and A129C are most common). Each mutation lowers the functionality of the MTHFR enzyme to varying degrees. Having an MTHFR mutation is like your body building a single lane bridge in the middle of a busy city when the bridge should be at least four lanes wide. It significantly reduces the number of cars (i.e biochemical reactions) that can use the bridge at one time and creates a traffic jam on both sides (i.e build up of biochemical products).

Take Aways

Hopefully, you now have a basic understanding of MTHFR. If you are looking for more information on MTHFR, there are multiple articles surrounding how MTHFR Mutations affects your overall health and fertility that can be found below:

 

References

  1. Botto, L. D., & Yang, Q. (2000). 5, 10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. American journal of epidemiology, 151(9), 862-877.
  2. Cristalli, C. P., Zannini, C., Comai, G., Baraldi, O., Cuna, V., Cappuccilli, M., … & La Manna, G. (2017). Methylenetetrahydrofolate reductase, MTHFR, polymorphisms and predisposition to different multifactorial disorders. Genes & Genomics, 1-11.
  3. De Mattia, E., & Toffoli, G. (2009). C677T and A1298C MTHFR polymorphisms, a challenge for antifolate and fluoropyrimidine-based therapy personalisation. European Journal of Cancer, 45(8), 1333-1351.