How to Manage ADHD, Depression, and Heart Disease: What Are the Key Insights?

Many studies have found that a mutation in the MTHFR gene (which affects 10-15% of the entire population) can lead to many problems.

These problems often remain mysterious because almost no one prescribes a test to discover it.

Find out if you have it and what you can do to limit/block the possible damage.

Discover if you have this mutation with a simple saliva test.

The name is unpronounceable, namely “methylenetetrahydrofolate reductase (or MTHFR),” but it can really cause serious issues.

It involves an enzyme that breaks down the amino acids homocysteine and folates, a particular form of folic acid, a vitamin in the B group.

Indeed, if the MTHFR gene that codes for this enzyme is mutated, it can interfere with the enzyme’s ability to function normally or deactivate it completely.

And these MTHFR gene mutations occur in millions of people, approximately 25% of people of Hispanic origin and 10-15% of people of European origin.

There are millions of people who could potentially suffer more or less serious consequences due to this mutation.

Perhaps you too.

These mutations often lead to high levels of homocysteine in the blood, which can contribute to numerous health conditions, such as:

• birth defects
• cardiovascular disease
• glaucoma
• mental health disorders
• some types of cancer

People have two MTHFR genes, inheriting one from each of their parents.

The mutations can affect one (heterozygous) or both (homozygous) of these genes.

There are two common types or variants of MTHFR mutations: C677T and A1298C.

People inherit one copy of the MTHFR gene from each of their parents, which means everyone has two MTHFR genes. Mutations can occur in one or both genes.

Having a parent or close relative with an MTHFR gene mutation can increase a person’s risk of inheriting the same variant.

People who have two parents with mutations have a higher risk of having a homozygous MTHFR mutation.

To better understand the issues that can arise, I will examine MTHFR mutations in more detail, including related health conditions, how it is diagnosed, and treatment options.

MTHFR mutations can also affect pregnancy.

Conditions Linked to MTHFR Mutation

As I mentioned above, mutations in the MTHFR gene can affect the body’s ability to process amino acids—particularly homocysteine and folate—which can lead to negative health outcomes.

The conditions that researchers have associated with MTHFR gene mutations include:

• Homocystinuria (or hyperhomocysteinemia), which is the term for abnormally high levels of homocysteine in the blood or urine
• Ataxia, a neurological condition that affects coordination
• Peripheral neuropathy, a neurological condition that damages nerves
• Microcephaly, a condition present at birth where the head is smaller than usual
• Scoliosis, an abnormal curvature of the spine
• Anemia, which is a deficiency of healthy red blood cells
• Cardiovascular diseases, such as blood clots, strokes, and heart attacks
• Mental and behavioral disorders, such as depression and Attention Deficit Hyperactivity Disorder (ADHD)
• Autism
• Retinoblastoma (the most common eye tumor in pediatric age and affects almost exclusively children under the age of 4-5 years)
• Breast cancer and its recurrences
• Lymph node metastasis
• Premature coronary artery disease (CAD) and myocardial infarction (MI)
• Polycystic ovary syndrome (PCOS)

And many other issues that medical research has only begun to slowly uncover in recent years.

Possible Signs and Symptoms

Symptoms vary both among individuals and depending on the type of mutation. People usually do not know they have an MTHFR mutation unless they exhibit severe symptoms or undergo genetic testing.

Having one or two MTHFR mutations can increase the levels of homocysteine in the blood or urine, leading to homocystinuria.

Homocysteine is an amino acid (i.e., one of the ‘building blocks’ that make up proteins) that the body produces by breaking down dietary proteins.

In homocystinuria, the body is unable to break down certain proteins, particularly affecting an amino acid called methionine.

In healthy people, homocysteine is quickly transformed into other products thanks to the action of vitamins B6 and B12 and folates (folic acid).

If the diet does not provide sufficient amounts of these vitamins and folic acid, homocysteine accumulates in the blood and can cause damage to the nervous, cardiovascular, and skeletal systems.

Indeed, high levels of homocysteine have been linked to an increased risk of developing severe cardiovascular diseases, such as arteriosclerosis, myocardial infarction, cerebral stroke, and thrombosis.

Amino acids are essential human building blocks, so methionine is also crucial, for example, for the growth of children and also fundamental for adults as it regulates nitrogen in the body.

Nitrogen is important for human DNA because all amino acids contain this substance.

People with high levels of homocysteine tend to have low levels of vitamin B-12.

Several factors can influence the amount of homocysteine in the blood:

• environmental factors, such as smoking, alcohol, coffee, and physical inactivity
• physiological factors, such as age and gender (homocysteine levels are lower in women than in men. In women, an increase is observed after menopause, most likely due to a decrease in estrogen)
• diseases such as kidney failure and hypothyroidism
• drug use (oral contraceptives, antiepileptics)
• genetic factors (homocystinuria)

The symptoms of homocystinuria due to MTHFR mutations include:

• abnormal blood clotting
• developmental delays
• seizures
• microcephaly
• blood clots
• poor coordination
• numbness or tingling in the hands and feet
• Alzheimer’s and other dementias

Children with homocystinuria exhibit symptoms that range from mild to severe.

Infants with this disorder are healthy at birth. The first symptoms, including lens dislocation which causes a marked reduction in vision, usually appear after the age of three.

Most children present with skeletal abnormalities, such as osteoporosis.

Children are typically thin with a curved spine, chest deformities, elongated limbs, and arachnodactyly.

Beals syndrome, or congenital contractural arachnodactyly (CCA), is a connective tissue disorder characterized by multiple flexion contractures, arachnodactyly, severe kyphoscoliosis, abnormal ear shapes, and muscle hypoplasia.

In the absence of early diagnosis and treatment, behavioral and mental (psychiatric) disorders and intellectual deficits are common.

Homocystinuria increases the likelihood of spontaneous blood clotting, causing strokes, high blood pressure, and many other serious problems.

Neonatal Screening Test

Since 2008, nearly all U.S. states require screening of all newborns for homocystinuria with a blood test. The diagnosis is confirmed by a test that measures liver enzyme function and skin cell tests.

In Italy, almost no one checks for it, even in adults, so it is recommended to have this simple blood test done within the first 5 years of age or at the onset of these symptoms.

Normal homocysteine levels should be 3-10 μmol/L in plasma in boys up to 15 years old.

Effects on Pregnancy

Women who test positive for an MTHFR mutation may have an increased risk of preeclampsia (a potentially dangerous pregnancy complication for both the mother and the newborn), recurrent miscarriages, or giving birth to a child with congenital disabilities.

A 2015 meta-analysis revealed clear evidence suggesting that women with MTHFR C677T genotypes have a higher risk of preeclampsia.

According to researchers, this mutation was present 1,337 times more often among women with preeclampsia.

In a 2018 study, researchers found that miscarriages occurred more frequently in women with the MTHFR C677T mutation compared to those with the MTHFR A1298C mutation.

Researchers have also noted strong associations between MTHFR variants and the following pregnancy outcomes:

• children born with cleft lip or cleft palate (a congenital malformation of the palate, presenting as a more or less extended split in the front part)
• children born with cardiovascular abnormalities
• children born with urinary system abnormalities
• repeated miscarriages
• premature rupture of membranes (PPROM)
• placental abruption, which is when the placenta separates from the uterine lining before birth
• spina bifida, a malformation of the nervous system due to the failure of the neural tube to close in the early weeks of conception; in the most severe cases, the spinal cord protrudes from the spine.

The Genetic and Rare Diseases Information Center states that studies suggest women with two C677T gene variants may have an increased risk of giving birth to a child with a neural tube defect.

Neural tube defects refer to disabilities of the brain, spine, or spinal cord present at birth and usually develop during the first month of pregnancy.

Complications

The most severe complication of homocystinuria is blood clots, which can be potentially fatal and increase the risk of stroke.

Intellectual disability is also possible, but the risk can be reduced if homocystinuria is diagnosed early and treated successfully.

Dislocated eye lenses can damage vision. In fact, some individuals may require lens replacement surgery to assist them.

People with homocystinuria can lead a normal life if they are diagnosed early enough and their treatment is successful. However, blood clots can cause health problems and sometimes potentially fatal complications.

It is good to know that having an MTHFR mutation does not affect everyone in the same way.

People who have one or more MTHFR variants may have higher than normal levels of homocysteine in their blood or urine, but this does not necessarily mean that they will experience the problems listed above, while others might.

In short, each case is unique.

Therefore, delve deeper into the MTHFR/homocysteine issue especially these symptoms given by the lack of folates or vitamin B12, such as:

• fatigue
• shortness of breath
• constipation
• loss of appetite or involuntary weight loss
• muscle weakness
• numbness, tingling, or pain in the hands or feet
• dizziness or loss of balance
• mouth sores
• mood changes
• difficulty breathing
• headaches
• irregular heartbeat

High Homocysteine: Reference Values

Homocysteine levels are measured through a blood sample (i.e., blood analysis).

Normal levels for adults aged 15 to 65 range between 5 and 15 micromoles per liter (micromoles are the unit of measurement for smaller molecules).

Above these levels, high homocysteine is noted, but it has various degrees of severity:

• Above 15-30 micromoles per liter: mild/moderate
• 30-100 micromoles per liter: moderate
• Greater than 100 per liter: severe
• Over 65 years old, the values should be within 3-20 micromoles
• 3-10 micromoles in boys up to 15 years old.
• Some scholars consider the presence of homocystinuria when the value exceeds 12 micromoles.

Severe homocystinuria is rare, while the moderate form is present in 5-7 percent of the general population.

It is considered one of the most important cardiovascular risk factors since levels above 12% of normal values coincide with a threefold greater risk of stroke or heart attack.

Homocystinuria is particularly common in patients with coronary artery diseases (about 30 percent) and those with cerebrovascular diseases (42 percent).

As can be seen from this table, the mortality from cardiovascular diseases in various populations is correlated with the average amount of homocysteine in the blood.

Therefore, the higher the value of this substance, the greater the likelihood of death from heart attacks and strokes.

It is interesting to note that the population of Northern Ireland has very high levels of homocysteine and therefore, unfortunately, high cardiovascular mortality.

Coincidentally, the MTHFR mutation in this nation is among the most frequent compared to the rest of the world, as we will also see later in the epidemiological data.

Prevalence

High blood homocysteine levels are very dangerous for health and are present in about 7-12% of the general population.

In Italy, homocystinuria affects one newborn in every 1,200,000/1,400,000, while in the USA it is believed to have an incidence of about 1 in every 200,000 to 300,000 children and is more common among whites in New England who are of Irish descent. In this group, the condition affects one in 50,000 newborns.

Worldwide, the most common type of homocystinuria affects 1 in 200,000 to 335,000 people and appears to be more prevalent in certain countries, including Germany, Norway, Ireland, and Qatar.

What to do to find out if you have mutated MTHFR genes and/or high homocysteine levels

• For MTHFR, a simple genetic test using a swab to collect a saliva sample (similar to those seen on CSI) is sufficient.
• For homocysteine, request the specific measurement with a standard blood draw.
• Also check the levels of folates, vitamin B6, and vitamin B12.

Here are the 4 things you absolutely must do if you find out you have mutated MTHFR and/or high homocysteine:

1. Dietary Considerations

The MTHFR gene regulates how the body processes folate, an amino acid from animal proteins, and other B-group vitamins.

Eating foods rich in folates can help reduce symptoms due to MTHFR mutations and thus also the dangerous increase in homocysteine.

The GeoPaleoDiet is recommended, therefore excluding grains/dairy/legumes and focusing on consuming these folate-rich foods:

Animal and plant proteins, such as beef and eggs

Vegetables, including spinach, asparagus, Brussels sprouts, and broccoli

Fruits like banana, melon, papaya, and avocado

2. Physical Activity

Include regular weight training, according to a study from the University of Virginia (USA).

American researchers subjected two homogeneous groups of people aged 60 to 72, both normal weight and obese; one group practiced weight lifting for 6 months, while the control group remained sedentary.

At the end of the study, homocysteine levels in the blood were lower in the group that had trained with weights, both those of normal weight and the obese.

Not only that, but levels of lipid peroxidation, a process that leads to damaging our cells and accelerating aging, were lower in the group that had trained with weights.

The researchers concluded that:

“To our knowledge, these data are the first to indicate that weight training reduces oxidative stress induced by exercise and homocysteine levels. These data suggest that weights may provide some protection against cardiovascular risk factors, especially for elderly subjects, both obese and not.”

3. Get Plenty of Sun and/or Vitamin D Supplements

A study published in Plos One in 2016, conducted on 4475 Canadians, found that both higher baseline serum vitamin D concentrations and greater temporal improvements in blood levels of this vitamin through sunlight and/or supplements were associated with a reduced risk of high homocysteine.

Researchers thus concluded that, consequently, more sun, more vitamin D (even as supplements) means less risk of cardiovascular diseases.

4. Supplements

In case of MTHFR mutation/s and/or high homocysteine (for some above 8 micromoles per liter can already be problematic) take a supplement containing:

• ACTIVATED folic acid 5-methyltetrahydrofolate (normal folic acid can even be harmful)
• Vitamin B2
• Vitamin B6
• Vitamin B12
• Zinc