I explain the need for personal health screening and promoting health assessments for the prevention of cardiometabolic disorders for those in the risk group

This research-based story does not include health advice. It is for information, inspiration, and awareness purposes.

Photo bySangharsh LohakareonUnsplash

My recent story highlighting the significance of vitamin B12 deficiency received over 2 million impressions on NewsBreak, accentuating the resonance of this topic and the recognition among experts of its status as a hidden epidemic.

What’s intriguing is not only the engagement from the average reader but also the keen interest from fellow scientists and caring clinicians who approached me privately and inspired me to cover unique and critical aspects of it to inform the public as they believe it is a significant public health concern.

Analyzing the comments and emails from collaborators, a striking revelation emerged. Some readers grappled with vitamin B12 deficiency due to genetic predisposition, a facet I aim to illuminate further in this short story.

It is a revelation that may catch many off guard; even those diligently consuming B12-rich foods or supplements can still find themselves deficient.

The root cause is MTHFR gene polymorphism or mutations. Definitions of mutation and polymorphism are blurred in the literature. Let me explain in simple words for those unfamiliar with them.

Polymorphism is a common variation in DNA among people, with some forms of a gene being more frequent than others. A mutation is a permanent change in the DNA that can cause different genetic outcomes, like single-letter changes or more significant alterations. These variations are natural and can be neutral, good, or harmful, contributing to the genetic differences we see in individuals.

The decision of whether to pursue testing for MTHFR gene polymorphism or mutations is multifaceted and should consider several factors. From my research, these include personal and familial medical backgrounds, existing symptoms, and the likelihood of conditions linked to MTHFR mutations like cardiovascular issues and neural tube defects.

Those with a family history of pertinent medical conditions or people experiencing symptoms associated with MTHFR mutations may find genetic testing valuable. Nevertheless, engaging in thorough discussions with healthcare professionals to evaluate personal risk profiles and receive personalized guidance aligning with specific health requirements is crucial.

By studying genetics and epigenetics in the context of cardiometabolic disorders at the postgraduate level, I have developed the skill to simplify intricate concepts and processes without resorting to overly technical language. I aim to give my readers a clear understanding of genetic anomalies, illuminating their impact without inundating them with scientific details.

Why is MTHFR polymorphism or mutation critical for health?

When reviewing MTHFR polymorphism, I found over 8000 medical reports and scientific papers on this genetic issue in Pubmed. To give you an idea of its significance, I will cite three important papers.

This 2015 literature review in the European Journal of Medical Genetics informs:

“The MTHFR polymorphism is linked to multiple diseases, including vascular issues, cancers, neurological conditions, diabetes, and psoriasis. Its prevalence varies based on geography and ethnicity. The MTHFR gene is located on chromosome 1 (1p36.6) and plays a crucial role in folate metabolism, which is essential for DNA, RNA, and protein methylation, key processes in cell metabolism.”

This 2020 cross-sectional study published in Brain Sciences found that:

Many people with NVAF cardiometabolic stroke have MTHFR gene mutations. Specifically, the C677T mutation was linked to more severe strokes and a higher occurrence of cardiovascular issues like hypertension, heart failure, dyslipidemia, and type II diabetes with high HbA1c levels, along with increased inflammation.

This 2016 meta-analysis in the journal Metabolic Brain Disease stated,

“The MTHFR enzyme is pivotal in this pathway, and the MTHFR C677T polymorphism has been identified as a potential risk factor for autism in numerous case-control studies. Despite some conflicting reports, the present meta-analysis strongly indicates a notable association between the MTHFR C677T polymorphism and autism.”

What Is MTHFR?

MTHFR, short for methylenetetrahydrofolate reductase, is a crucial enzyme in folate metabolism, pivotal in DNA synthesis, repair, and methylation processes. Folate (vitamin B9) is an essential B vitamin that is crucial to the prevention of genomic instability and hypomethylation of DNA.

By the way, some scientists call MTHFR protein in their papers, as enzymes are proteins that catalyze biochemical reactions in living organisms.

The enzyme’s function relies on the integrity of specific gene variants, notably the C677T and A1298C polymorphisms. The C677T variation entails a substitution of cytosine with thymine at position 677 of the MTHFR gene.

This alteration correlates with diminished enzyme activity, resulting in compromised conversion of homocysteine to methionine and disrupted methylation mechanisms.

Similarly, the A1298C polymorphism involves a substitution of adenine (A) with cytosine at position 1298 of the MTHFR gene. Like its counterpart, this variant is associated with reduced enzyme activity, affecting folate metabolism and methylation pathways.

Understanding these genetic nuances and mutations is pivotal in discerning people's susceptibilities and tailoring interventions for optimal health outcomes.

As documented in this NIH Book chapter on Madame Curie Bioscience Database:

“Severe mutations and mild gene variations at 677C→T can affect enzyme activity. Studies show that the valine allele of the 677C→T polymorphism can reduce enzyme activity by about 50%, both alone and when combined with severe mutations.

“Additionally, the 677 polymorphism contributes to MTHFR’s thermolability in patients with severe MTHFR deficiency. While initial reports attributed thermolability solely to deleterious mutations before the polymorphism identification, it’s now understood that mild gene variations can complicate genotype-phenotype analysis alongside known deleterious mutations.”

Compelling Reasons for Testing of MTHFR Polymorphisms or Mutations

Understanding our genetic predisposition to MTHFR polymorphisms or mutation can provide insights into their risk of elevated homocysteine levels, which are associated with cardiovascular disease, neural tube defects, pregnancy complications, and other health issues.

As documented in this paper on Circulation:

“Individuals with homocystinuria develop severe cardiovascular (affecting heart and blood vessels) disease in their teens and twenties, in addition to a variety of skeletal and neurological-developmental abnormalities and eye problems.”

Methylenetetrahydrofolate Reductase (MTHFR) Deficiency is the most common genetic cause of elevated levels of homocysteine in the plasma (hyperhomocysteinemia).

I introduced homocysteine in a previous Newbreak article titled:

Why High Homocysteine Levels Matter and How to Optimize Them. Homocysteine is a sulfur amino acid that exists in our bloodstream. It is a metabolite of methionine, which is another amino acid. Elevated plasma homocysteine is called hyperhomocysteinemia in the literature.

This amino acid is processed by folate, vitamin B6, and vitamin B12 to create other biochemicals in the bloodstream. In addition, energy production in mitochondria seems to cause the effects.

For example, as documented in this paper:

“Recent studies suggest that the interaction between homocysteine and mitochondria is complex, and reactive oxygen species are possible mediators of homocysteine effects.”

Testing MTHFR polymorphisms can also help tailor personalized treatment plans, including dietary interventions, supplementation with methyl folate (the active form of folate), and lifestyle modifications to optimize methylation processes.

People with MTHFR polymorphisms may have a reduced ability to metabolize folate and other nutrients critical for methylation, impacting various physiological processes.

The presence of MTHFR polymorphisms may increase susceptibility to certain health conditions, including cardiovascular disease, neural tube defects, depression, anxiety, and infertility.

Testing for MTHFR polymorphisms can guide healthcare providers in recommending appropriate interventions to mitigate the adverse effects associated with impaired folate metabolism.

The Impact of MTHFR Polymorphisms on Vitamin Deficiencies

The impact of MTHFR Polymorphisms on Vitamin Deficiencies MTHFR polymorphisms can indirectly contribute to vitamin B12 deficiency and other B vitamin deficiencies (B9 and B6) by influencing folate metabolism and methylation processes.

Impact on Folate Metabolism

MTHFR plays a critical role in converting dietary folate (vitamin B9) into its active form, methyl folate, which is vital for methylation reactions in the body. People with MTHFR polymorphisms, particularly the C677T variant, may experience diminished enzymatic activity, reducing methylfolate production. Consequently, this can impair folate metabolism and decrease the availability of methyl groups necessary for methylation reactions.

Impact on Vitamin B12 Metabolism

Methylfolate, a product of the folate cycle, is essential for converting homocysteine to methionine. Methionine serves as a precursor for synthesizing S-adenosylmethionine (SAMe), a methyl donor crucial for various methylation reactions, including the methylation of vitamin B12 to its active form, methylcobalamin. Diminished methyl folate availability due to MTHFR polymorphisms can disrupt vitamin B12 methylation, resulting in reduced levels of methylcobalamin and functional vitamin B12 deficiency.

Impact on Vitamin B6 Metabolism

The methylation cycle, where MTHFR is involved, interacts with other B vitamins like vitamin B6. Impaired methylation reactions can hamper the conversion of pyridoxine (vitamin B6) to its active form, pyridoxal-5-phosphate, which is essential for numerous enzymatic reactions in the body. Understanding these intricate metabolic pathways can illuminate the complexities underlying vitamin deficiencies associated with MTHFR polymorphisms.

How are MTHFR Polymorphisms and Mutations tested?

As documented in MedlinePlus, a MTHFR gene test uses a sample of your blood to look for two very common changes in a gene called MTHFR. A change in this gene is also called an MTHFR variant or MTHFR mutation.

We have two copies of the MTHFR gene, one from each parent. The genes provide instructions for making the MTHFR protein. This protein helps our bodies use folate. The body needs folate and other B vitamins to break down an amino acid called homocysteine.

The MTHFR test serves two primary purposes: firstly, it helps identify if a common gene mutation is contributing to elevated homocysteine levels in the blood, although treatment remains consistent regardless of the mutation.

Secondly, it assists in estimating the risk of developing blood clots or early cardiovascular diseases. While some medical experts advise against using MTHFR testing for this purpose due to uncertainties about homocysteine’s role, others see it as a valuable tool for risk assessment. You need to find a trustworthy health consultant who best informs you.

I got mine tested years ago, and it cost me $300, and my private health insurance covered 70% of it. Now, some online places offer $89 for two gene mutation test kits, including C677T and A1298C Analysis, if your healthcare provider does not cover it. You can search for them on Google, as I don’t recommend products and services in my articles.

What do test results mean?

The results of an MTHFR gene test determine whether you carry one or both of the most common changes in the gene. Test outcomes are typically categorized as positive or negative.

A positive result indicates the presence of an MTHFR gene change in one or both genes. Having a single gene change usually doesn’t pose health issues. If your homocysteine levels are elevated and your test reveals:

• Two copies of the C677T gene change or one copy each of C677T and A1298C. These mutations likely contribute to high homocysteine levels.
• Two copies of the A1298C gene change, these mutations are unlikely to be the cause. A negative result means neither common MTHFR gene change was detected.

Elevated homocysteine levels may stem from other factors like vitamin deficiencies, medications, age, thyroid issues, kidney problems, or other health conditions.

Conclusions and Takeaway Points

Testing for MTHFR polymorphisms can provide valuable information for risk assessment, personalized treatment planning, and preventive care, ultimately contributing to improved health outcomes and quality of life for individuals with these genetic variations.

While MTHFR polymorphisms or mutations are prevalent, their clinical significance and impact on health outcomes can vary widely among individuals. Genetic testing for MTHFR polymorphisms should be interpreted regarding an individual’s overall health, family history, and lifestyle factors.

Addressing MTHFR-related issues involves a multifaceted approach. This may include supplementation with methyl folate and other methyl donors, optimizing dietary intake of B vitamins, and addressing factors that affect methylation pathways and nutrient metabolism.

Treatment strategies for individuals with MTHFR polymorphisms may also involve optimizing dietary folate intake, supplementation with methyl folate, vitamin B12, and other methyl donors like choline, betaine (TMG), methionine, and SAMe, as well as addressing modifiable risk factors such as smoking, alcohol consumption, and stress.

A few years ago, I wrote an article titled "Here’s How TMG Supplementation Might Improve Four Health Conditions." You may find it via a Google search. I will write one for NewsBreak soon as it is a valuable nutrient from my experience.

Collaboration between patients, healthcare providers, and genetic counselors is crucial in developing personalized management plans that address the unique needs and challenges associated with MTHFR polymorphisms and mutations.

Thank you for reading my perspectives. I wish you a healthy and happy life.

If you found this story helpful, you may also check out my other articles on NewsBreak. As a postdoctoral researcher and executive consultant, I write about important life lessons based on my decades of research and experience in cognitive, metabolic, and mental health.

To inform my new readers, I wrote multiple articles that might inform and inspire you. My topics include brain and cognitive function, significant health conditions, longevity, nutrition/food, valuable nutrients, ketogenic lifestyle, self-healing, weight management, science, technology, business, and humor.