The Complete Guide to Methylated & Active B Vitamins

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The Pure TheraPro Team

The Pure TheraPro Education Team is comprised of researchers from diverse backgrounds including nutrition, functional medicine, fitness, supplement formulation & food science. All articles have been reviewed for content, accuracy, and compliance by a holistic integrative nutritionist certified by an accredited institution.
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In the intricate world of nutrition, understanding the specific roles and benefits of B vitamins—particularly in their activated forms—can be a game-changer for personal health. This guide explores the importance of methylated and activated B vitamins, and offers practical advice on whether these supplements might be right for you.

What Are Activated B Vitamins?

Activated B vitamins are pre-converted, bioavailable forms of B-complex vitamins that your body can use immediately. These forms bypass the usual metabolic conversion in your liver, making them particularly effective. Examples include methylcobalamin for B12, pyridoxal-5-phosphate for B6, and methylfolate for B9. This activation, often involving a process called methylation, enhances the vitamins' absorption and efficacy.

In the image below, you’ll find the 8 different B vitamins, the name of their active form, and the benefits of this activated form.

B Vitamin Active Form Benefits of the Active Form
B1 (Thiamin) Benfotiamine This form bypasses the liver and is directly usable by the body, ensuring better support for your energy levels and overall health.
B2 (Riboflavin) Riboflavin 5'-Phosphate Sodium Immediate availability for energy production and antioxidant defense.
B3 (Niacin) Niacinamide & Niacin Niacinamide is better tolerated and does not cause flushing, whereas niacin effectively supports cholesterol levels.
B5 (Pantothenic Acid) D-Calcium Pantothenate Directly used by the body to make coenzyme A, vital for metabolizing fats and maintaining healthy skin.
B6 (Pyridoxine) Pyridoxal 5'-Phosphate Immediately available to help the body process proteins and support overall metabolism.
B7 (Biotin) Biotin Supports healthy skin, hair, and nails, and is crucial in fat and sugar metabolism.
B9 (Folate) Methylfolate Directly usable by the body, essential for DNA creation and repair, and crucial during pregnancy.
B12 (Cobalamin) Methylcobalamin Supports nerve health, brain function, and energy levels right away without needing conversion.


Benefits of Methylated and Activated B Vitamins

Not all B-Complex supplements include the methylated and activated forms. In fact, most do not! As you can see in the table graphic above, it’s crucial for you to ensure the formula you’re taking includes these forms in order to decrease side effects and maximize absorption, bioavailability & benefits. 

The primary advantages of using methylated and activated B vitamins include:

Immediate Bioavailability

They are ready for immediate use by the body, which can be crucial for individuals with specific genetic makeups or dietary restrictions. Those eating a vegetarian or vegan diet may not obtain sufficient amounts of certain B vitamins, such as Vitamin B12, which is primarily found in animal products.

Enhanced Metabolic Support

These vitamins play vital roles in energy production, DNA synthesis, and the regulation of neurotransmitters, contributing to overall mental and physical well-being.

Optimal Support for Genetic Variations

Individuals with genetic variations like MTHFR mutations, which affect how the body processes folic acid, can particularly benefit from methylated forms of B vitamins. It's estimated that up to 25% of people of Hispanic descent and 10-15% of Caucasian descent in the U.S. carry at least one variant of the MTHFR gene mutation. Other populations, including approximately 1-2% of African Americans, also carry this mutation, but at lower frequencies.

Differences Between Activated vs Inactivated B Vitamins

Activated B vitamins differ from their inactivated counterparts in that they are readily absorbed and utilized by the body without the need for conversion. In contrast, inactivated B vitamins require conversion by the liver, which can be inefficient or insufficient due to genetic variations or health conditions.

While all methylated vitamins are active, not all active vitamins are necessarily methylated. Methylated vitamins specifically include a methyl group that makes them ready for use in the body's methylation cycles, particularly important in genetic cases where individuals do not methylate efficiently. On the other hand, active vitamins may be formulated in ways other than methylation to be readily usable by the body. 

B Vitamin Inactive Form Pitfalls of the Inactive Form
Vitamin B1 (Thiamine) Thiamine mononitrate or thiamine hydrochloride Less bioavailable and not as easily absorbed, particularly for individuals with genetic variations or digestive issues.
Vitamin B2 (Riboflavin) Riboflavin Riboflavin is relatively stable, but its active form is more readily utilized by the body for energy production and antioxidant activity. Without conversion to the active form, riboflavin can’t exert its full benefits.
Vitamin B3 (Niacin) Nicotinic acid or nicotinamide Too much nicotinic acid can cause uncomfortable flushing, and nicotinamide may not have the same cardiovascular benefits as niacin in its active form.
Vitamin B5 (Pantothenic Acid) Calcium pantothenate Calcium pantothenate is stable, but its bioavailability may be lower compared to the active form of pantothenic acid.
Vitamin B6 (Pyridoxine) Pyridoxine hydrochloride This requires conversion to its active form in your body. Some individuals have impaired ability to convert pyridoxine to its active form, leading to potential deficiencies despite supplementation.
Vitamin B7 (Biotin) D-Biotin While biotin is generally well-absorbed, excessive intake of D-biotin supplements may interfere with the metabolism of L-biotin, the natural form found in foods.
Vitamin B9 (Folate) Folic acid Folic acid requires enzymatic conversion to its active forms, in order to be utilized. Individuals with genetic variations (MTHFR) may have difficulty converting it to its active forms, leading to potential health risks.
Vitamin B12 (Cobalamin) Cyanocobalamin This is the most common form of B12 in supplements, and it must be converted to its active forms, in order to be utilized. It also contains cyanide, a toxic poison.


Why Methylation Matters?

Methylation is a fundamental biochemical process that occurs in every cell and tissue in our body and plays a crucial role in maintaining health and proper biological functions. It involves the transfer of a methyl group (one carbon atom and three hydrogen atoms) onto amino acids, DNA, RNA, and other molecules. This seemingly simple process is vital for a wide range of critical functions in the body.

Methylation’s broad impact on so many critical functions makes it a key player in maintaining health and preventing disease. Problems in the methylation process can lead to a wide range of health issues, including cardiovascular diseases, neurological disorders, and birth defects. The efficiency of methylation processes can be influenced by genetics, diet, lifestyle, and environmental factors.

Ensuring optimal methylation function is important, and this can often be supported through diet, supplements (like B vitamins that support methylation), and lifestyle changes aimed at enhancing the body's natural processes. Understanding methylation and how it affects your health can be a significant step towards maintaining or improving your overall well-being.

Key Functions of Methylation

  • Detoxification:
    Methylation helps to detoxify toxins and heavy metals, making them easier for the body to eliminate. This process reduces the risk of accumulation and the potential harm these substances could cause.
  • Synthesis of DNA and RNA:
    Methylation is directly involved in the synthesis and repair of DNA and RNA, which are essential for the growth, development, and functioning of all cells.
  • Nerve Protection:
    It contributes to the production and function of myelin, the protective sheath around nerves, which is essential for the proper functioning of the nervous system.
  • Fat Metabolism:
    Methylation aids in the processing of fats in the body. It helps to burn fat for energy and is essential for maintaining healthy weight and overall metabolism.
  • Liver Support:
    The liver is central to detoxifying the body, and methylation supports many of the liver's processes, including breaking down excess hormones and helping in the detox pathways.
  • Immune System Support:
    Methylation is involved in creating and regulating immune cells, which are crucial for defending the body against infections and disease.
  • Hormone Metabolism:
    It helps in the metabolism of hormones and assists in keeping hormonal levels balanced within the body.
  • Energy Production:
    Methylation plays a role in the energy production processes of cells, ensuring that the body has enough energy to perform its functions.
  • Neurotransmitter Production:
    It is crucial for the synthesis of neurotransmitters, such as serotonin and dopamine, which play significant roles in mood regulation and brain function.
  • Gene Regulation:
    Perhaps one of the most crucial roles of methylation is its ability to turn genes on and off. This gene expression regulation is essential for responding to environmental changes and controlling the development of diseases.

Signs your B-Complex isn’t Cutting It

If you’re already taking a B-Complex and wondering if it’s meeting the needs of your body, there are a few tell-tale signs you can look for. These signs don’t necessarily mean your B-Complex isn’t an ideal solution for you, but they are a good place to start when determining if you should stick with your current supplement, or seek out an alternative version. 

  • Lackluster Energy Levels:
    Despite getting enough sleep and eating well, you still find yourself feeling fatigued and sluggish.
  • Brain Fog:
    Difficulty concentrating, forgetfulness, and mental fog can be signs of inadequate B-vitamin levels.
  • Mood Swings:
    B-vitamins play a crucial role in neurotransmitter synthesis, so low levels can contribute to mood swings, irritability, and even depression.
  • Poor Hair, Skin, and Nails:
    B-vitamin deficiency can manifest in various ways, including brittle nails, dull hair, and dry skin.
  • Digestive Issues:
    Since B-vitamins are crucial for proper digestion and nutrient absorption, digestive problems like bloating, constipation, or diarrhea could signal a deficiency.

If you're experiencing any of these symptoms, it might be time to reassess your B-vitamin supplement and explore alternative options to better support your wellness journey.

Should I Take Activated B Vitamins?

Certain groups of people can particularly benefit from methylated B vitamins:

Individuals with MTHFR Gene Mutation

The MTHFR gene mutation affects how individuals process folate. Methylated folate is essential for those with this mutation to bypass the faulty metabolic pathway.

People with Homocysteinemia

Elevated homocysteine levels are linked to cardiovascular disease and other health issues. Active forms of B vitamins, particularly B12, B6, and folate, help to properly metabolize homocysteine.

Elderly Population

As the body ages, it becomes less efficient at converting vitamins to their active forms. This can be exacerbated by factors such as reduced stomach acid production and changes in digestive function. The elderly can benefit from methylated B vitamins to help maintain cognitive function and energy levels.

Individuals with Digestive and Absorption Disorders

Conditions such as Crohn's disease, celiac disease, or gastric bypass surgery can impair the absorption of vitamins in their inactive forms.

Individuals with Elevated Alcohol Consumption

Excessive alcohol intake can interfere with the absorption and utilization of several B-vitamins, including B1 (thiamine), B9 (folate), and B12 (cobalamin).

People Consistently Eating Processed Foods

Diets high in processed foods often lack essential nutrients, including B-vitamins. Additionally, certain food processing techniques can destroy or reduce the availability of these vitamins. You’ll often see processed foods being fortified to add back in vitamins and minerals that are destroyed and stripped from the ingredients during the processing. That said, the vitamins and minerals they’re adding to these foods is almost always low quality and not the methylated or activated forms.

Individuals Taking Prescription or Over-the-Counter Medications

Some medications, such as antacids, proton pump inhibitors, and certain antibiotics, can interfere with B-vitamin absorption or increase the body's need for these nutrients.

Those Experiencing Frequent Stress

Chronic stress can deplete B-vitamin stores in the body and increase the body's need for these nutrients. Incorporating stress-management techniques into your routine can help support optimal B-vitamin levels.

Vegetarians and Vegans

Plant-based diets can be lower in certain B-vitamins, particularly B12, which is primarily found in animal products. It's important for vegetarians and vegans to include supplements in their diet to ensure adequate intake of these nutrients, since fortified foods often don’t include the activated or methylated forms.

How to Choose the Best B-Vitamin Supplement

Not all B-complexes are created equal, so it's essential to choose a high-quality supplement that meets your body's needs. Here's what to look for:

  • Methylated Forms:
    Opt for supplements that contain methylated forms of B-vitamins, such as methylcobalamin (B12) and methylfolate (B9). These forms are more bioavailable and suitable for individuals with MTHFR gene mutations.
  • Balanced Formulation:
    Look for a B-complex that provides a balanced blend of all eight B-vitamins (B1, B2, B3, B5, B6, B7, B9, and B12) in optimal doses.
  • Third-Party Testing:
    Choose supplements from reputable brands that undergo third-party testing for potency, purity, and safety. Ideally, the company will also share their third-party testing results on their website via a Certificate of Authenticity, or will provide you access to the CoA when asked. 
  • Added Nutrients:
    Some B-complex supplements include additional nutrients and/or cofactors like Trimethylglycine (TMG), Choline Dihydrogen Citrate, which can further enhance absorption, while also supporting energy production and overall well-being.

By prioritizing quality and choosing a B-vitamin supplement that's tailored to your individual needs, you can ensure that you're getting the support you need to thrive.

Our Favorite Active B Vitamin Supplement

Pure Thera’s Methyl Active  B™ is a super B complex with a potent combination of 2 methylated B vitamins, 6 active B vitamins & 2 essential co-factors in water-soluble forms.

For those considering an active B vitamin supplement, our top recommendation includes a comprehensive blend:

Methylated B Vitamins included:

  • Quatrefolic® Folate (Patented Methylated Vitamin B9)
  • MecobalActive® Methylcobalamin (Patented Methylated Vitamin B12)

Active-Form B Vitamins Include:

  • Thiamine & BenfoPure® Benfotiamine (Patented & Active Forms of Vitamin B1)
  • Riboflavin 5'-Phosphate Sodium (Active Form of Vitamin B2)
  • Niacin & Niacinamide (2 Active Forms of Vitamin B3)
  • D-Calcium Pantothenic Acid (Active form of Vitamin B5)
  • Pyridoxal 5'-Phosphate (Active Co-Enzyme Form of Vitamin B6)
  • Biotin (Active Form of Vitamin B7)

The B vitamins included in Methyl Active B are essential to support whole-body health, and are particularly implicated in supporting energy production, brain & nervous system, heart & vascular system, liver & detoxification, and hair, skin & nails.

The most complete pharmaceutical-grade active B complex vitamins for women and men alike! Our formula contains the complete spectrum of B vitamins in their Methylated AND Active forms! This Methylated Vitamin B complex provides essential B vitamins to support MTHFR and methylation processes. Featuring MethylFolate as Quatrefolic® for increased bioactivity, Trimethylglycine (TMG), and Vitamins B12 (Methylcobalamin and Adenosylcobalamin), BenforPure® Benfotiamine® & and much more.


Lachner, C., Steinle, N. I., & Regenold, W. T. (2012). The neuropsychiatry of vitamin B12 deficiency in elderly patients. Journal of Neuropsychiatry and Clinical Neurosciences, 24(1), 5-15.

Smith, A. D., & Refsum, H. (2016). Homocysteine, B vitamins, and cognitive impairment. Annual Review of Nutrition, 36, 211-239.

Fenech, M. (2012). Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 733(1-2), 21-33.

Bailey, L. B., & Stover, P. J. (2015). Folate and vitamin B12 recommended intakes and status in the United States. Nutrition Reviews, 73(4), 258-272.

Pawlak, R., Lester, S. E., & Babatunde, T. (2014). The prevalence of cobalamin deficiency among vegetarians assessed by serum vitamin B12: a review of literature. European Journal of Clinical Nutrition, 68(5), 541-548.

Green, R., Allen, L. H., Bjørke-Monsen, A.-L., Brito, A., Guéant, J.-L., Miller, J. W., Molloy, A. M., Nexo, E., Stabler, S., Toh, B.-H., Ueland, P. M., & Yajnik, C. (2017). Vitamin B12 deficiency. Nature Reviews Disease Primers, 3, 17040.

Watkins, D., & Rosenblatt, D. S. (2012). Update on cobalamin, folate, and homocysteine. Hematology, 2012(1), 62-81.

Spector, R., & Johanson, C. E. (2007). Vitamin transport and homeostasis in mammalian brain: focus on Vitamins B and E. Journal of Neurochemistry, 103(2), 425-438.

Selhub, J., Morris, M. S., & Jacques, P. F. (2009). In vitamin B12 deficiency, higher serum folate is associated with increased total homocysteine and methylmalonic acid concentrations. Proceedings of the National Academy of Sciences, 106(50), 21528-21533.

Gueant, J.-L., Caillerez-Ferrer, L., & Perrin, A. E. (2018). The role of genetic polymorphisms in folate metabolism on the interplay between methylation and folate levels and their effect on psychiatric disease susceptibility. Molecular Psychiatry, 23(9), 1924-1931.