How Serious is MTHFR C677T Heterozygous Mutation?

DNA Mutation

Last Updated on 21 June 2024

The heterozygous mutation of MTHFR C677T gene affects less than 50% of Europeans, and even though it is classified as a normal genetic polymorphism, namely an unharmful condition, it is believed to cause several symptoms, along with a few, severe, modern diseases.

But how serious is this genetic mutation? Can it have an impact on your health?

The answers are not so easy to give, because there is still an open debate among doctors and scientists who consider MTHFR C677T heterozygous mutation a physiological evolution of human genes, while others affirm the contrary. This article tried to shed a light on the truth related to this controversial, genetic condition.

What is MTHFR C677T heterozygous mutation?

To clearly understand the matter, you need to know what MTHFR C677T heterozygous mutation is.

MTHFR or methylenetetrahydrofolate reductase is both an enzyme and a gene. The latter provides the enzyme with instructions to process amino acids, build proteins and convert folates, especially vitamin B9, from methylenetetrahydrofolate to 5-methyltetrahydrofolate.

Acid Folic Molecular Structure

This is the form of vitamin B9 that is in the bloodstream and is responsible to turn homocysteine into another amino acid, called methionine. This compound, in turn, is involved in many bodily processes that build proteins and other vital molecules.

If you have MTHFR C677T heterozygous mutation, it means that you have only a copy of the defective gene, while the other copy is normal.

Usually, indeed, we receive two copies of the gene: one from the mother and one from the father.

If you have two copies of the defective gene, you have a homozygous mutation.

There is also to say that Mthfr mutation can involve other parts of DNA, usually indicated with a sequence of numbers and letters. In a normal sequence, letters follow letters, and numbers follow numbers. Hence, a correct DNA sequence should be 677CT, for example.

If you have, for instance, the variant of MTHFR A1298C, your body will have normal levels of homocysteine and folates; while, if you have the MTHFR C677T variant, you could have some abnormality, such as high homocysteine which may give rise to cardiovascular diseases.

Generally, MTHFR C677T heterozygous mutation does not cause high levels of homocysteine, this condition is, in fact, present in the C677T homozygous mutation.

However, even people with MTHFR C677T heterozygous mutation may experience serious symptoms and ailments.

Indeed, I have been diagnosed with MTHFR C677T heterozygous mutation in September 2022, to discover the hidden roots of my several health disorders.

MTHFR C677T heterozygous mutation symptoms

What are the symptoms of MTHFR C677T heterozygous mutation?

In his blog, naturopathic doctor Michael Ruscio affirms that research can be misleading, sometimes, and that symptoms such as anxiety, brain fog, depression, chronic fatigue may be linked to gut disorders and inflammation, rather than to MTHFR C677T heterozygous mutation.

For its part, instead, Research focuses the attention on the cancer risk tied to this genetic condition.

The one published in the national Library of Medicine, for example, says that: “The C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with a decreased risk of colon cancer while it may increase the risk of breast cancer.” But the related clinical trial dates back to 2009-2010.

Very interesting is instead the pdf document of 14 pages published in Italian by the European Network and Registry for Homocystinuria and Methylation Defects.

According to this document, MTHFR C677T heterozygous mutation is included in the defects mentioned above.

This genetic polymorphism, in fact, would have an impact on the way in which the body processes two important vitamins, B12 (cobalamin) and B9 (folic acid).

The induced deficits of this condition go from mild to severe, with a wide range of symptoms. These vary from person to person and may occur in different stages of life, during the adolescence or in adulthood.

The severe MTHFR deficit mainly affects eyes, brain, cardiovascular system and kidneys.

Another pdf document in Italian published by Italianutrizione.it reveals that the heterozygous polymorphism of MTHFR C677T is the most relevant under the profile of thrombotic risk, because it entails a diminished enzymatic activity of 50%.

Symptoms and conditions associated with this mutation are:

high homocysteine, cardiovascular diseases (thromboembolism, atherosclerosis, heart attack), stroke, dementia and loss of memory, depression and irritability, hypertension, increased risk of breast cancer in women over 55 years of age), neural tube defects (and other in the unborn child), problems with the vascularization of the placenta, peripheral neuropathy, loss of lean fat and increase in fat mass, autism and schizophrenia.

A poor diet and nutrient deficiencies may alone cause high homocysteine, and consequently, many symptoms and diseases could not depend on MTHFR C677T heterozygous mutation.

Tested with this mutation, I follow, for example, a healthy diet, and have normal homocysteine, but I have Hashimoto’s thyroiditis, with all of the resulting symptoms of anxiety, mood swings, depression, irritable bowel syndrome and more.

Moreover, it has been discovered that homocysteine is always normal in MTHFR C677T heterozygous mutation, while it is likely that a methylation defect may be present with it, such as the difficulty to adsorb and metabolize folates. L-methylfolate, for instance, is the purest version of folic acid or vitamin B9, the only one capable of crossing the blood-brain barrier to help the brain produce neurotransmitters that regulate mood and immune system.

This defect might explain because people tested with MTHFR C677T heterozygous mutation may experience mood disorders and autoimmune thyroiditis.

According to the data collected by Dr. Isabella Wenz, the utmost expert of thyroid disorders, MTHFR C677T heterozygous mutation may be the root for Hashimoto’s disease, but scientists at the Cleveland Clinic affirm that the impact of this mutation is minimal in the onset of specific diseases and modern auto immunities.

As you can see, the matter is fairly controversial and still distant from being clarified. It is possible that a few genetic mutations make us more vulnerable to particular disorders under specific circumstances, such as bad lifestyle, pollution, alcohol, smoke, stress, poor nutrition and infections.

On this last aspect, a serious study published in 2021 in the Journal of Clinical Laboratory Analysis, showed a correlation between MTHFR C677T prevalence and COVID-19 incidence and mortality rates in the Latino population (50%). In this ethnic group, with MTHFR C677T homozygous mutation, the fatality rate of Covid19 infection was 85%.

It always remains unclear the severity of the heterozygous variant.

The same study reveals that: “Homocysteine has been under a lot of speculation since its discovery in 1932. It is known that a high plasma level of homocysteine significantly increases the incidence of vascular damage in both small and large vessels. Hyperhomocysteinemia has neurotoxic, neuroinflammatory, neurodegenerative, proatherogenic, prothrombotic, and prooxidative effects. Homocysteine concentration above 90% is associated with increased risk of degenerative and atherosclerotic processes in the coronary, cerebral and peripheral circulatory system.”

As always, research takes into account only conditions associated with high homocysteine in MTHFR C677T homozygous mutation, while heterozygotes are not minimally considered.

Only a study of February 2023 revealed that a patient with a double heterozygous mutation MTHFR C677T and A1298C has experienced acute macular neuroretinopathy (AMN) due to Covid19 disease.

And so? Is MTHFR C677T heterozygous mutation really serious or not?

The True Answer on the Severity of MTHFR C677T Heterozygous Mutation

Maybe you don’t know that the news on the severity of MTHFR C677T heterozygous mutation derives from a fake news spread prior to the pandemic.

It is an article by The Atlantic to reveal that.

MTHFR Gene Mutation

The article explains that the interest in MTHFR gene dates back to 2008, and, later, in 2016, when a vaccine skeptical doctor published his own research which linked this gene to the adverse reactions of smallpox vaccines. In the study, the doctor invited his colleagues to use DNA tests before administering vaccines, because the adverse reactions in those who had a MTHFR gene mutation included autism, as well.

This theory was never cited in the scientific literature, while the doctor was cited in a court case in 2019. Moreover, at the time, smallpox was already eradicated and the related vaccine was no longer administered.

Unfortunately, this fake research spread worldwide and many parents started denying any type of vaccine to their children, putting them at risk to get deadly infections.

Ever since, MTHFR C677T heterozygous mutation has circulated in the global healthcare systems, becoming viral, just like other fake news boosted by social media.

But there is no study which proves that the symptoms you have depend on this genetic mutation. Nowadays, indeed, MTHFR C677T heterozygous mutation is classified as a polymorphism, that means it is a common variant of a genetic sequence, such as, for example, the one of the eye colors.

However, people who have it complain of suffering from autoimmune thyroiditis, irritable bowel syndrome, depression, anxiety, fatigue, insomnia, and bipolar disorder.

But, without scientific evidence, it is impossible ascribing these disorders to MTHFR C677T heterozygous mutation.

MTHFR C677T Heterozygous Mutation Treatment

MTHFR C677T heterozygous mutation is written in your DNA, and unless scientists discover how to replace it, there is no treatment for this mutation.

A helpful cure may be the one to treat the symptoms individually, in order to soothe them. But a valid therapy must always be prescribed by your practitioner.

MTHFR enzyme must be taken only if you have been tested with methylation defects. If your vitamins B and homocysteine are normal, it means that you don’t have methylation disorders.

Dr. Isabella Wentz, instead, suggests taking lithium orotate if you have depression caused by Hashimoto’s thyroiditis related to the MTHFR gene.  According to the data collected by Dr. Wentz, it also seems that lithium orotate is able to relieve the symptoms ascribed to MTHFR C677T heterozygous mutation, thanks to its strong antioxidant activity.

On its side, the Australian MTHFR support suggests a dietary therapy made of leafy greens, vegetables, vitamin C, D, E rich organic food, fish oil, curcumin and exercise.

Conclusion

As you can see, MTHFR C677T heterozygous mutation may be severe when you experience symptoms, disorders and discomfort. A certain vulnerability caused by this gene mutation can be avoided with a healthy lifestyle and diet.

It is important to care for mood and gut with MTHFR C677T heterozygous mutation. If you balance these two essential systems, many symptoms linked to this genetic condition will disappear. For the rest, the alleged severity of MTHFR C677T heterozygous mutation is the result of a fake news built internationally around vaccines. No more, no less.

References and Bibliography

  1. MTHFR gene methylenetetrahydrofolate reductase – National Library of Medicine https://medlineplus.gov/genetics/gene/mthfr/
  2. Numerical Characterization of DNA Sequence Based on Dinucleotides – The Scientific World Journal –  Research Article | Open Access – Volume 2012 | Article ID 104269 | https://doi.org/10.1100/2012/104269                  
  3. What’s Really Causing Your ‘MTHFR Gene Mutation’ Symptoms – Dr. Michael Ruscio – March,16,2021 – https://drruscio.com/mthfr-gene-mutation-symptoms/
  4. Sohn, K. J., Jang, H., Campan, M., Weisenberger, D. J., Dickhout, J., Wang, Y. C., Cho, R. C., Yates, Z., Lucock, M., Chiang, E. P., Austin, R. C., Choi, S. W., Laird, P. W., & Kim, Y. I. (2009). The methylenetetrahydrofolate reductase C677T mutation induces cell-specific changes in genomic DNA methylation and uracil misincorporation: a possible molecular basis for the site-specific cancer risk modification. International journal of cancer, 124(9), 1999–2005. https://doi.org/10.1002/ijc.24003
  5. Disturbi della Rimetilazione – European Network and Registry for Homocystinuria and Methylation Defects – http://www.cblc.it/remethylation.pdf
  6. Giovanni Ponti, Lorenza Pastorino, Marco Manfredini, Tomris Ozben, Gabriella Oliva, Shaniko Kaleci, Raffaele Iannella, Aldo Tomasi – COVID-19 spreading across world correlates with C677T allele of the methylenetetrahydrofolate reductase (MTHFR) gene prevalence, June, 1, 2021 – Journal of Clinical Laboratory Analysis – https://onlinelibrary.wiley.com/doi/10.1002/jcla.23798
  7. Christina Karakosta, Evgenia Kontou, Tina Xirou, Stamatina A. Kabanarou – Acute Macular Neuroretinopathy Associated With COVID-19 Infection: Is Double Heterozygous Methylenetetrahydrofolate Reductase (MTHFR) Mutation an Underlying Risk Factor? – February 11, 2023 – Cureus –  https://www.cureus.com/articles/136877-acute-macular-neuroretinopathy-associated-with-covid-19-infection-is-double-heterozygous-methylenetetrahydrofolate-reductase-mthfr-mutation-an-underlying-risk-factor#!/
  8. Could Nutritional Lithium Benefit or Hurt Hashimoto’s? –  Dr. Isabella Wentz, Pharm.D., FASCP – December 10, 2021 – The Thyroid Pharmacist – https://thyroidpharmacist.com/articles/lithium-and-hashimotos/
  9. What you need to eat and avoid for mthfr – MTHFR Support – August, 2020 – https://mthfrsupport.com.au/2020/08/what-you-need-to-eat-and-avoid-for-mthfr/
Author: Rosalba Mancuso
Rosalba Mancuso is a medical journalist, an international content writer credited at the University of Washington and a blogger born in Sicily. She is internationally appreciated for founding a network of four websites in English. On Modernhealthinfo.com, Rosalba writes well researched and detailed health articles backed by her experience as a medical writer for pharma companies and as a PR assistant for a clinical analysis laboratory. She is also a member of the AHCJ, American Association of Health Care Journalists and Center for Excellence in Health Journalism. Her health magazine survives thanks to spontaneous donations, and sponsorships with brands and clinical organizations.