Methylated B vitamins (B9&B12)- Strengths and Limitations of Methylated Vitamins

Methylated B vitamins (B9&B12)- Strengths and Limitations of Methylated Vitamins

Katie Stone - Naturopath

Written By:

Katie Stone - Naturopath
Dr. Nare Simonyan - PhD Pharmaceutical Science

Medical Reviewer:

Dr. Nare Simonyan - PhD Pharmaceutical Science
Kari Asadorian - Bachelor of Science in Nursing

Edited By:

Kari Asadorian - Bachelor of Science in Nursing

Updated On:

February 24, 2025

Table of Contents

    Methylated B vitamins and why you need them

    You probably know that getting your daily dose of B vitamins is crucial for healthy mental and physical function. But that doesn’t mean you can grab any old B-complex off the shelf.


    There are eight important B vitamins that play many crucial roles in the body. Along with producing energy and supporting your mood, they’re required for red blood cell formation, immune system maintenance, and much more. Deficiency in any of the Bs - especially folate or B12 - can have severe implications for your health.


    The most effective way to restore a deficiency and maintain healthy levels of B vitamins in the body is by supplementing with a methylated B vitamin product.


    Let’s explain why. 

    What are the B vitamins?

    The eight types of B vitamins1 include Vitamin B1 (thiamin), Vitamin B2 (riboflavin), Vitamin B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B7 (biotin), B9 (folate), and B12 (cobalamin). While the B vitamins all have a similar molecular structure, they each have very different roles within the body. 


    When working together, these nutrients create energy by breaking down glucose from the food you eat into the form of Adenosine triphosphate (ATP) molecules. Without ATP, crucial organs such as your heart and brain would not be able to function.


    Folate (also known as folate B vitamin 92) alone is required for numerous functions of the brain and nervous system, including proper methylation and the making and repairing of DNA. Folate is also a key player in breaking down homocysteine, a potentially harmful amino acid. It’s involved in creating serotonin, dopamine, and norepinephrine: important neurotransmitters that regulate mood. It’s also required for proper immune cell function and the formation of myelin. During pregnancy, folate is crucial for normal fetal growth and development.


    Vitamin B12 also has numerous crucial roles in the body, including DNA and amino acid synthesis, fatty acid metabolism, cognitive function, healthy myelin formation, and nervous system maintenance. 

    How folate and vitamin B12 work together

    Folate and cobalamin (vitamin B12) both play essential roles in one-carbon metabolism.


    The methylation cycle allows the body to transfer a methyl group so that it can attach to specific molecules and perform different cellular functions, such as activating DNA, detoxifying hormones, converting homocysteine, and so on.


    In the methylation cycle, folate and B12 work together to pass a methyl group from homocysteine into methionine. This process is essential for clearing homocysteine. Homocysteine is an amino acid produced in the human body as a result of methionine metabolism, a process required for the methylation of a wide range of substances, including DNA. High levels of homocysteine are associated with low levels of monoamine neurotransmitters and depression.


    The remethylation of homocysteine to methionine is essential not only for reducing levels of homocysteine in the body but for the proper synthesis of S-adenosylmethionine (SAMe). SAMe is a methyl donor that plays a key role in the synthesis and function of neurotransmitters, including noradrenaline, adrenaline, dopamine, serotonin, and histamine. These neurotransmitters are essential for healthy mood and motivation, and have potential antidepressant effects. SAMe deficiency has been reported in major depression as well as other neuropsychiatric conditions. 

    The benefits of taking folate and vitamin B12

    Deficiency or low levels of folate and/or B12 can be caused by genetics, certain diseases, medications, or by not obtaining enough folate from your food. Folate deficiency can lead to anemia (decreased red blood cell count) or hyperhomocysteinemia (high levels of homocysteine) in the blood.

    For this reason, supplementing with folate and vitamin B12 in their active, methylated forms has many health benefits.

    Support for the immune system

    Low levels of folate and B12 affects production of nucleic acid, protein synthesis, the activity of immune cells, and interfere with metabolic processes, including methylation. Inefficient methylation can lead to hyperhomocysteinemia and subsequent inflammation, increasing the risk of many diseases.


    Folate supports T cell proliferation and functions while also promoting the survival and suppressive function of regulatory T cells3. Vitamin B12 also acts as an immunomodulator for cellular immunity, especially regarding T cells and the natural killer cell system4. Methionine synthase uses methylcobalamin as a cofactor and is essential for the synthesis of purines and pyrimidines in all cells, including immune cells.

    May help protect against the risk of cancer

    Low or deficient folate status is associated with increased risk of many cancers.


    Some research shows that higher folate intake is associated with decreased risk for some types of cancer, including a decrease of nearly 50% for squamous cell carcinoma of the head and neck, 41% reduced risk for esophageal cancer, and a 34% reduction in pancreatic cancer5. However, it should be noted that high intake of folic acid (which is not the same thing as methylfolate) has also been associated with an increased risk of certain cancers6. Researchers  have noted that B vitamins “may” provide protection from developing cancer but may also play a detrimental role in patients diagnosed with cancer. 7

    Support for cognitive function

    Folate and B12 are necessary for the production of monoamine neurotransmitters, phospholipids and nucleotides in the brain, which contribute to healthy cognitive function and mood. Low levels of these B vitamins have been associated with increased homocysteine, which is known to have a direct neurotoxic effect on the brain. Both folate and B12 deficiency are shown to increase the likelihood of cognitive decline, dementia, and reduced neurological function. 8


    However, maintaining adequate levels of folate, vitamin B6, and vitamin B12 is shown to support cognitive performance and protect against oxidative stress and inflammation. 

    Support for cardiovascular health

    Homocysteine is a chemical in the blood formed when the amino acid methionine is metabolized. Vitamins B12, B69, and folate are required to recycle homocysteine back into methionine so it can be used to build other proteins.


    Elevated homocysteine can severely damage the lining of the arteries, increasing the risk of cardiovascular issues such as atherosclerosis (hardening of the arteries) and development of blood clots in the arteries and veins.

    Why take a methylated vitamin B complex? And what does methylated mean?

    There are many reasons to take a methylated vitamin B instead of a non-methylated form. Methylated B vitamins are in their biologically active form and can be directly and immediately utilized by the body. Non-methylated B-vitamins must first be converted to their methylated form through specific enzymatic processes in the body. Although both forms can be effective, the methylated forms are much more efficient.


    Most importantly, methylfolate is absorbed more efficiently than folic acid. Folic acid is a synthetic form of folate that must be converted to active folate by the enzyme methylenetetrahydrofolate reductase (MTHFR) - and for many people, this process is hindered by genetics, medications, or malabsorption in the gut.


    Methyl-Life® has created a methyl B complex specifically for this reason. 


    Methyl-Life’s® B-Methylated-II is a chewable methylated b-complex and multivitamin made with bioactive folate and vitamin B12. It’s designed for maximum absorption and bioavailability to support healthy brain, heart and nerve function, as well as assisting with mood and homocysteine maintenance.


    It contains methylfolate and methylcobalamin, which makes it ideal for people with MTHFR. Those with a MTHFR mutation are also likely to be low in B12. Methylfolate and methylcobalamin are the natural and active forms that require little to no conversion in the body.


    One of the best methylated b complex products is Methyl-Life® Methylfolate 7.5+. This contains a moderate dose (7.5 mg) of L-Methylfolate and 2.5 mg of Active B12 (as Hydroxocobalamin).


    These methylated forms have been shown to improve folate10 and B12 levels11 more effectively than synthetic folic acid and cyanocobalamin. 


    Remember, each person’s dosage of b complex12 vitamins will vary, so it’s a good idea to talk to a health practitioner before starting a new supplement regime. 

    The takeaway

    Supplementation with methylated B vitamins may help to fill in any gaps in the diet and assist with metabolic dysfunctions (such as MTHFR insufficiency) that may contribute to nutritional deficiencies.


    A multivitamin that contains methylated folate, methyl B12 and other bioavailable nutrients is highly recommended. These vitamins are essential for proper support of the methylation cycle, DNA repair, nervous system maintenance, and many other vital functions. 

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    References

    1. Berry, J; "A complete guide to B vitamins"; Medical News Today; 2024 Feb

      https://www.medicalnewstoday.com/articles/325292

    2. Aparicio-Ugarriza, R., Palacios, G., Alder, M., González-Gross, M., González-Gross, M.; "Dietary sources and intakes of folates and vitamin B12 in the Spanish population: Findings from the ANIBES study"; PLoS One; 2017 Dec

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731688/

    3. Henry Kurniawan, Takumi Kobayashi, Dirk Brenner; "The emerging role of one-carbon metabolism in T cells"; Current Opinion in Biotechnology, Vol. 68, Pg. 193-201; 2021 Apr

      https://www.sciencedirect.com/science/article/pii/S0958166920301841?via%3Dihub

    4. Tamura, J., Kubota, K., Murakami, H., Sawamura, M., Matsushima, T., Tamura, T., Saitoh, T., Kurabayshi, H., Naruse, T.; "Immunomodulation by vitamin B12: augmentation of CD8+ T lymphocytes and natural killer (NK) cell activity in vitamin B12-deficient patients by methyl-B12 treatment"; Clinical and Experimental Immunology; 1999 Apr

      https://pubmed.ncbi.nlm.nih.gov/10209501/

    5. Kim, Y.-I.; "Folate and Its Impact on Cancer Risk"; Current Nutrition Reports; 2018 Sep

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132377/

    6. Vollset, S. E., Clarke, R., Lewington, S., Ebbing, M., Halsey, J., Løken, E. B., Bønaa, K. H.; "Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials": A Meta-Analysis; The Lancet; 2013.

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278486/

    7. Peterson, C. T., Rodionov, D. A., Osterman, A. L., Peterson, S. N.; "B Vitamins and Their Role in Immune Regulation and Cancer"; Nutrients; November 2020 Nov

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693142/

    8. Anat Rotstein, Arad Kodesh, Yair Goldberg, Abraham Reichenberg, Stephen Z Levine; "Serum folate deficiency and the risks of dementia and all-cause mortality: a national study of old age"; BMJ Mental Health: Vol. 25 Iss. 2, Old age psychiatry Original research; 2021

      https://ebmh.bmj.com/content/25/2/63

    9. Peterson, C. T., Rodionov, D. A., Osterman, A. L., Peterson, S. N.; "B Vitamins and Their Role in Immune Regulation and Cancer"; Nutrients; 2020 Nov

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551072/

    10. Papakostas GI, Shelton RC, Zajecka JM; "L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials"; The American Journal of Psychiatry; 2012 Dec

      https://pubmed.ncbi.nlm.nih.gov/23212058/

    11. Cristiana Paul, David M Brady; "Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms"; Integrative Medicine: A Clinician's Journal; 2017 Feb

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312744/

    12. David O Kennedy; "B Vitamins and the Brain: Mechanisms, Dose and Efficacy - A Review"; Nutrients; 2016 Jan

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772032/

    13. Banner Image Designed by Freepik

      https://www.freepik.com/

    Katie Stone - Naturopath

    About the Author

    Katie is a qualified Naturopath (BNatMed) and freelance writer from New Zealand. She specializes in all things health and wellness, particularly dietary supplements and nutrition. Katie is also a dedicated runner and has completed more half-marathons than she can count!

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