MTHFR, Diabetes, Metformin, B12 and Methylation

December 31, 2023 11 mins to read

Most people are not aware of the full range of side effects for their medications, such as Metformin B12 deficiency; it turns out metformin can affect B12 absorption in the small intestine. More specifically they are not notified by their physicians of how these medications can interact with the body (the biological mechanisms) and affect nutrition, leading to various nutritional deficiencies (in this case B12) and another bundle of debilitating side effects.

But how does this tie in with our Genes? The MTHFR gene mutation affects how we methylate or processes certain nutrients, and it’s estimated to affect over 46% of the population (nearly half). A B12 deficiency only exacerbates the methylation issues in someone with an MTHFR mutation, creating a vicious cycle of negative health impacts which can potentially even worsen diabetic symptoms. This is not information you’ll typically get from your physician, because they simply lack the knowledge, or due to a general lack of concern for the wellbeing of their patients. So in this article I detail the relationship between MTHFR, methylation, Metformin and B12.

A Bit About Me

NutriGenomics has been another area of interest in my research addicted mind… or more specifically nutrigenetics – the relationship between our diets and genes; how our genes affect how we process what we eat and vice versa. I was introduced to the idea by Gary Brecka, a somewhat controversial figure with photographic memory…Then I began reading Dirty Genes by Dr. Ben Lynch. I began taking a Methylated Multivitamin and that’s when things changed drastically for me…my lifelong battle with insomnia – suddenly I was tired at 10:00pm and having deep restful sleeps. My memory and focus and consequently productivity improved 100% – suddenly I could work for 14+ hrs straight, which I hadn’t been able to do for years. I’ve been addicted to learning more about nutrigenetics ever since!

Most people are not notified by their doctor (or pharmacist) of the wide range of potential side affects for their medications. I’m confident if thy did, many people would seek natural remedies beforehand…Though in my professional practice I’ve come to learn that a lot of people would rather take a bill (despite the side effects), than change their diet and lifestyle. I don’t know if this is a fault of the individual, but often due to the mentality of western and modern medicine to look at health issues in a vacuum, rather than how we in holistic nutrition learn to look at all parts: diet, lifestyle, mental and spiritual and interconnected parts of the whole influencing each other.

Understanding Metformin B12 Deficiency Relationship

  • Metformin and B12 Absorption:
    • Reduced Absorption: Metformin has been associated with decreased absorption of vitamin B12 in the intestines.
    • Long-Term Use Concerns: Prolonged use of Metformin can increase the risk of B12 deficiency over time.
  • B12 Deficiency and Methylation:
    • Methylcobalamin: B12 is a vital in the methylation process, acting as a cofactor in the conversion of homocysteine to methionine.
    • Impaired Methylation: B12 deficiency can impair methylation processes, potentially leading to elevated homocysteine levels and compromised overall methylation efficiency.
  • Vicious Cycle with Diabetic Symptoms:
    • Methylation and Insulin Sensitivity: Methylation processes influence insulin sensitivity, and impaired methylation may contribute to insulin resistance.
    • Exacerbating Diabetic Symptoms: B12 deficiency and compromised methylation can potentially exacerbate diabetic symptoms, creating a cycle of negative health affects.
  • Importance of Monitoring B12 Levels:
    • Regular Check-Ups: Individuals on long-term Metformin should undergo regular B12 level monitoring.
    • Supplementation Consideration: Healthcare providers may recommend B12 supplementation to address deficiencies and support methylation processes.

Understanding MTHFR and Methylation

The MTHFR Enzyme

  • What It Is: The MTHFR gene produces an enzyme vital for converting homocysteine into methionine.
  • Why It Matters: This conversion is a cornerstone of the methylation process, affecting DNA synthesis and repair, as well as neurotransmitter production.

The Impact of MTHFR Mutation

  • The Change: Mutations in the MTHFR gene can reduce this enzyme’s efficiency at converting homocysteine to methionine.
  • The Result: Potential elevation in homocysteine levels and reduced methionine, leading to a cascade of health affects and negatively impacts overall health. For example elevated homocysteine can deplete glutathione levels. Glutathione is our ‘master detoxifier‘ so you can imagine how that impacts our cells and over-all our bodies ability to detox.

The Methylation Cycle and Its Importance

Methylation’s Role

  • A Biochemical Process: Methylation involves transferring methyl groups to different substances in the body; occurring millions to billions of times per second.
  • Why It’s Important: It’s key for gene expression, detoxification, and maintaining DNA integrity.

A Note About Methylation and Detox

I want to highlight the importance of methylation for detoxing…in this modern age of chemicals and electronics we are exposed to toxins everywhere: air we breath, clothes we wear, food we eat (pesticides, herbicides, chemicals, additives) and even products we use in our homes (cleaning products) and on our bodies (cosmetics, shampoo/conditioner, lotion, etc). Combined often with a lack of adequate exercise, hydration and/or sleep. If our bodies aren’t methylating effectively it can cripple our ability to detox all of these pollutants were exposed to on a daily basis, potentially even turning ‘dirty genes’ related to diseases (like cancer) and illness.

This is why I highly recommend you get a methylation panel (test for MTHFR and other gene mutation). It’s a once in a lifetime test that can set you up for a life-long health, through applying precision (genetic) nutrition tailored to your unique genetics.

How MTHFR Mutation Affects Health

Elevated Homocysteine Levels | Health Impacts

The Risk: Increased cardiovascular risk and potential neurological issues due to high homocysteine.

  • Increased Cardiovascular Risk:
    • Atherosclerosis: Elevated homocysteine is associated with the development of atherosclerosis, (a condition) where arteries become narrowed and hardened.
    • Blood Clot Formation: High homocysteine levels can contribute to blood clot formation, increasing the risk of heart attacks and strokes.
  • Potential Neurological Issues:
    • Neuronal (Brain) Damage: Elevated homocysteine is linked to neuronal damage and impaired cognitive (brain) function; if you want good memory and brain function, keeping homocysteine levels in check is key!
    • Neurodegenerative Diseases: There’s evidence suggesting a connection between high homocysteine levels and an increased risk of neurodegenerative diseases, such as Alzheimer’s; and you wonder why these diseases are on the rise.
  • Impact on Mental Health:
    • Mood Disorders: Elevated homocysteine is associated with an increased risk of mood disorders, including depression and anxiety; a global epidemic!
  • Pregnancy Complications:
    • Increased Risk of Birth Defects: Elevated homocysteine levels during pregnancy are linked to an increased risk of certain birth defects; if you want a healthy baby, address this before-hand!
  • Bone Health:
    • Bone Density Reduction: High homocysteine levels can contribute to reduced bone density, potentially increasing the risk of fractures, especially in the elderly.
  • Inflammation and Oxidative Stress:
    • Inflammatory Response: Elevated homocysteine can contribute to inflammation in the body, a primary driving force behind disease, and which plays a big role in severity of many disease symptoms.
    • Oxidative Stress: Homocysteine is associated with increased oxidative stress, which can impact overall cellular health; another primary driver behind disease, especially in the face of inadequate anti-oxidant intake to counter this.

Reduced Methionine | Health Impacts

The Consequences: Affects critical bodily functions, including detoxification and mood regulation.

  • Detoxification Processes:
    • Glutathione Production: Methionine is a precursor to glutathione known as the ‘master detoxifier’, largely the most powerful antioxidant crucial for detoxifying harmful substances in the body.
    • Phase II Liver Detoxification: Methionine supports phase II liver detoxification, which plays a key role in breaking down toxins for elimination.
  • Mood Regulation and Neurotransmitters:
    • Serotonin Production: Methionine contributes to the serotonin synthesis, a neurotransmitter connected with mood regulation.
    • Dopamine and Norepinephrine Synthesis: Methionine is involved in the production of dopamine and norepinephrine, neurotransmitters influencing mood and alertness; if you have deficient dopamine and norepinephrine it’s a serious problem for your mental health!
  • Protein Synthesis:
    • Essential Amino Acid: Methionine is an essential amino acid, meaning it’s necessary for the synthesis of proteins in the body.
  • DNA Synthesis and Repair:
    • Methyl Donor for DNA Methylation: Methionine provides methyl groups essential for DNA methylation, a crucial process for DNA synthesis and repair.
  • Homocysteine Regulation:
    • Conversion of Homocysteine: Methionine is involved in the conversion of homocysteine to cysteine, which means it helps regulate homocysteine levels.
  • Collagen Formation:
    • Sulfur Amino Acid: Methionine is a sulfur-containing amino acid, contributing to the formation of sulfur-containing compounds like cysteine, important for collagen synthesis; skin, joints, tendons, etc all can be affected.

MTHFR Testing

The test I use with my clients is an MTHFR panel from MaxGen Labs that covers roughly 90 Genes. It’s an at-home test that uses a simple cheek swab, which you mail back to the laboratory. It provides a full report from their team of genetic experts on diet and supplement recommendations. There are many other options available as well. Feel free to contact me or book an appointment for help by a nutrition professional developing a nutrition plan, once you have your methylation panel results.

Lifestyle and Dietary Considerations

Nutritional Factors

  • Folate-Rich Foods: Emphasizing natural folate sources like leafy greens and legumes.
  • B Vitamin Supplement: Ensuring adequate B vitamin intake, particularly B12 and B6. If supplementing B12 look for methylcobalamin (the methylated form of B12).

Lifestyle Factors

  • Regular Exercise: Supports overall methylation processes and has a wide range of physical and cognitive benefits.
  • Stress Management: Reduces the body’s demand for methyl groups. Our minds learn to adapt to stress but it still can have a massive negative impact on our health, often without us realizing it. I’m a big fan of recommending everyone see a life coach, counselor or therapist to acquire tools to better manage stress.

Final Thoughts | Conclusion

When you consider that likely over 46% of the population has an MTHFR mutation, and that diabetes is a rapidly growing problem, it’s clear that understanding the relationship between metforming, B12 deficiency and methylation is key to improving and maintaining good health. While it might seem daunting, with small incremental (sustained) informed changes to our diet and lifestyle, we can improve our health and create a positive feedback loop where we have more energy and motivation to further implement health and life improving habits. Help from a nutrition professional is only a video call away.

To learn more about NutriGenetics (and the relationship between genes and diet) be sure to follow my socials and subscribe to my newsletter


  • “Dirty Genes: A Breakthrough Program to Treat the Root Cause of Illness and Optimize Your Health” by Dr. Ben Lynch. This book offers a comprehensive look into how genes like MTHFR can impact our health and provides strategies to manage these genetic predispositions.
  • “Genetic Bypass: Using Nutrition to Bypass Genetic Mutations” by Dr. Amy Yasko. Dr. Yasko’s work focuses on the role of nutrition in managing genetic mutations, including MTHFR, and how dietary changes can significantly impact overall health.
  • “The Methylation Miracle: Unleashing Your Body’s Natural Source of SAM-e” by Paul Frankel. Frankel’s book delves into the science of methylation and its importance in bodily functions, offering insights into how to support this critical process.
  • “MTHFR Gene Therapy Demystified: Crack Your Genetic Code to Better Health” by Robin Terranella. This book provides a detailed understanding of the MTHFR gene and its mutations, offering practical advice on managing its health implications.
  • “Nutrient Power: Heal Your Biochemistry and Heal Your Brain” by Dr. William J. Walsh. Dr. Walsh explores the connection between biochemistry, including methylation processes, and brain health, offering a unique perspective on treating mental health issues through nutritional therapy.


The information provided in this article is for educational and informational purposes only and is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of any health care agency or government entity in Canada or the United States.

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