Unravelling MTHFR Gene Mutations: A Nutritional Perspective

Dr Pennie Taylor PhD MND BHlthSc

Introduction: Human genetics is one of the greatest areas of complexity and interest where the methylenetetrahydrofolate reductase (MTHFR) gene takes centre stage, linking its influence through the delicate threads of our health. As we explore into the basics of MTHFR gene mutations, we uncover a fascinating story of how nutrition can play a vital role in shaping our overall health and well-being.

Understanding MTHFR Gene Mutations: Currently in Australia, genetic testing for 2 common polymorphisms in the MTHFR gene, C677T and A 1298C are being accessed by general practitioners (GPs) when indicated.  MTHFR holds the key to an essential process known as methylation. This biochemical pathway is critical in various functions in the body, including DNA synthesis, repair, and detoxification. MTHFR gene mutations, marked by variations in the gene sequence and can impact the efficiency of the MTHFR enzyme, influencing an individual's susceptibility to certain health conditions.

There are 2 common mutations, C677T and A1298C which have been identified in the MTHFR gene, with up to 70% of the population predicted to have at least one of these variants. These variations can alter the methylation cycle, setting the stage for potential health challenges.  

The C677T mutation results in the substitute of the amino acid Alanine for Valine and can result in mild homocystinuria. Whilst the A1298C does not cause homocystinuria.  However, studies exist associating these MTHFR polymorphisms with multiple conditions including Cardiovascular Disease, Infertility however more research is still warranted for stronger indicators for health care and management.  For now, while not everyone with these mutations will experience health issues, understanding their implications opens the door to personalised approaches for better health.

Nutritional Implications: Nutrition emerges as a powerful ally in the quest for better health and wellbeing, particularly for individuals with MTHFR gene mutations. The interplay between genetics and nutrition is complex and understanding the nuances through seeking support from an accredited practising dietitian can pave the way for a healthier lifestyle.

Folate and Its Forms: At the heart of the matter is folate, a B-vitamin with a starring role in the methylation process. For individuals with MTHFR mutations, the form of folate matters. While folic acid, the synthetic form, is commonly found in fortified foods and supplements, its conversion into the active form, 5-MTHF (5-methyltetrahydrofolate), may be impaired in individuals with MTHFR mutations. Choosing foods rich in natural folate and opting for supplements containing 5-MTHF can be a game-changer, including at least a 3 of following each day: Dark green leavy vegetables (spinach, romaine lettuce, broccoli, brussels sprouts, green beans or asparagus) , peanuts, sunflower seeds, fresh whole fruits, edamame, lentils and avocado.

B Vitamins: The supporting cast in this nutritional drama includes B vitamins – riboflavin (B2), pyridoxine (B6), and cobalamin (B12). These vitamins act as essential cofactors in various methylation reactions. Ensuring an adequate intake of B vitamins through a balanced diet or supplementation can help optimize the methylation pathway, offering a lifeline for individuals with MTHFR mutations. Foods to include daily are, salmon, tuna, chickpeas, poultry, some fruits and vegetables (See folate)

Methyl Donors: Certain nutrients act as methyl donors, contributing methyl groups crucial for methylation reactions. Betaine, choline, and methionine, found in foods like beets, spinach, and poultry, serve as valuable methyl donors. Including these foods in the diet can provide the necessary support for individuals with MTHFR mutations, aiding in the maintenance of optimal methylation processes.

Steering Clear of Synthetic Folate: While fortification has been a public health success in addressing folate deficiency, individuals with MTHFR mutations need to navigate this landscape carefully. Synthetic folic acid, commonly added to fortified foods, may not be efficiently converted into the active form in individuals with MTHFR mutations. Selecting supplements containing the bioactive 5-MTHF ensures a direct and effective route for folate utilization. These foods are commonly highly processed including some breads, cereals and pasta. Speak to you local dietitian for more information.

Genetic Testing and Personalised Nutrition: The advent of genetic testing has ushered in a new era of personalized medicine. Understanding one's MTHFR gene status provides a roadmap for tailoring nutritional interventions. Personalized nutrition plans, crafted based on individual genetic makeup, empower individuals to make informed choices, optimizing their health outcomes.

Navigating Research: The journey through the world of MTHFR gene mutations and nutrition is guided by a sea of research. Studies such as those by Frosst et al. (1995), unravel the genetic underpinnings of vascular diseases, shedding light on the importance of the MTHFR gene. Stover (2004) delves into the physiological intricacies of folate and vitamin B12, providing a foundation for understanding their roles in health. Czeizel et al. (1992) contribute insights into the prevention of neural tube defects, emphasizing the significance of periconceptional vitamin supplementation.

Conclusion: This exploration of MTHFR gene mutations and their relationship with nutrition identifies clear picture highlighting that nutrition is a potent tool for optimizing health within a personalised nutrition framework, particularly for those with genetic variations. By taking on the power of natural folate, B vitamins, and methyl donors, individuals can navigate the complexities of their genetics towards improving well-being. With genetic testing guiding the way, personalised nutrition becomes the sign of hope for the drive towards healthier, more vibrant life.

Reference List:

  1. Calderón-Larrañaga A, Saadeh M, Hooshmand B, Refsum H, Smith AD, Marengoni A, Vetrano DL. (2020) Association of Homocysteine, Methionine, and MTHFR 677C>T Polymorphism With Rate of Cardiovascular Multimorbidity Development in Older Adults in Sweden. JAMA Netw Open. 2020 May 1;3(5):e205316.
  2. Chang HL, Chen GR, Hsiao PJ, Chiu CC, Tai MC, Kao CC, Tsai DJ, Su H, Chen YH, Chen WT, Su SL. (2020)  Decisive evidence corroborates a null relationship between MTHFR C677T and chronic kidney disease: A case-control study and a meta-analysis. Medicine (Baltimore). 2020 Jul 17;99(29):e21045.
  3. Czeizel, A. E., Dudas, I., & Vereczkey, A. (1992). Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. New England Journal of Medicine, 327(26), 1832-1835.
  4. Frosst, P., Blom, H. J., Milos, R., Goyette, P., Sheppard, C. A., Matthews, R. G., ... & Rozen, R. (1995). A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nature genetics, 10(1), 111-113.
  5. Somayeh-Sadat, T. Ghaemimanesh, F. Zarei, S. Reihani-Sabet, F. Pahlevanzadeh, Z. Modarresi, MH. And Jeddi-Tehraini, M. (2015) Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms in Male Partners of Recurrent Miscarriage Couple. J Reprod Infertility,  16 (4): 193-194.
  6. Stover, P. J. (2004). Physiology of folate and vitamin B12 in health and disease. Nutrition reviews, 62(suppl_1), S3-S12.
  7. Wu X, Liu K, Zhao X, Zhang X, Guo H, Jiang H, Chang J, Lv X, Gao X, Zhi X, Ren C, Chen Q, Liang Y, Li Y. (2022)  Correlation Between the MTHFR C677T Genotype and Coronary Heart Disease in Populations from Gansu, China. DNA Cell Biol. 2022 Nov;41(11):981-986. 

 

TOPIC - Understanding MTHFR Gene Mutations - Summary

“Supporting summary.

MTHFR Gene Mutations

  1. C677T Mutation:
    • This mutation involves a cytosine-to-thymine substitution at position 677 of the MTHFR gene.
    • Homozygous (TT) individuals often exhibit reduced enzyme activity, impacting the conversion of folate to 5-MTHF.
    • Heterozygous (CT) individuals may also experience decreased enzyme efficiency, though to a lesser extent.
  2. A1298C Mutation:
    • This mutation involves an adenine-to-cytosine substitution at position 1298 of the MTHFR gene.
    • The impact of this mutation on enzyme function is less clear compared to the C677T mutation.
    • Some studies suggest that the A1298C mutation may affect MTHFR enzyme activity, albeit to a milder degree.

Relationship with Health Conditions

  1. Association with Neural Tube Defects:
    • MTHFR gene mutations, particularly the C677T variant, have been associated with an increased risk of neural tube defects during foetal development.
    • Adequate folate intake, especially in the form of 5-MTHF, is crucial for preventing these birth defects.
  2. MTHFR and Cardiovascular Health:
    • Some studies have explored the potential link between MTHFR mutations and cardiovascular diseases.
    • The association between MTHFR mutations and cardiovascular risk factors is complex and may vary among different populations.
  3. MTHFR and Mental Health:
    • There is ongoing research on the connection between MTHFR gene mutations and mental health disorders, including depression and anxiety.
    • Methylation processes influenced by MTHFR mutations play a role in neurotransmitter synthesis, potentially impacting mental health.

Nutritional Considerations

  1. Folate Intake:
    • Adequate folate intake is crucial for individuals with MTHFR mutations, as they may have reduced enzymatic activity.
    • Dietary sources of folate include leafy green vegetables, legumes, and fortified foods.
    • Supplementation with 5-MTHF, the active form of folate, may be beneficial for those with MTHFR mutations.
  2. B Vitamins:
    • Vitamin B12 is closely linked to folate metabolism, and deficiencies in either can disrupt methylation processes.
    • Vitamin B6 is another key player in the methylation pathway, and its adequate intake is essential for optimal function.
  3. Methylation Support:
    • Nutrients such as choline, betaine, and trimethylglycine can support methylation processes and may be beneficial for individuals with MTHFR mutations.

Challenges in Research and Clinical Interpretation

  1. Heterogeneity in Study Findings:
    • Research findings on the impact of MTHFR gene mutations on health outcomes are mixed.
    • Variability in study populations, methodologies, and genetic backgrounds contribute to discrepancies in results.
  2. Individualized Approach:
    • The effects of MTHFR mutations can vary among individuals, emphasizing the importance of personalized healthcare.
    • Genetic testing can provide valuable information for tailoring nutrition and supplementation recommendations.

 

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