Chemical Structures of Vitamin B12 and Folate

Can You Take Vitamin B12 and Folate Together? (11 Benefits Explained)

You can take vitamin B12 (cobalamin) and folate (folic acid or Vitamin B9) together. Though these two vitamins have distinct functions, they work together in synergy in several processes within the body.

In this article, we’ll explore the various benefits of taking vitamin B12 and folate together. Alongside their individual roles, we'll examine how their synergy enhances energy levels, supports heart health, aids in DNA synthesis, and promotes cognitive function. 

1. Enhances methylation cycle

Vitamin B12 and folate enhance the methylation cycle, which is essential for synthesizing DNA and RNA, producing neurotransmitters, and detoxifying harmful substances. 

The vitamins work together to contribute methyl groups necessary for methylation reactions and support the recycling of homocysteine back to methionine.

Folate (folic acid) serves as a precursor for the synthesis of 5-methyltetrahydrofolate (5-MTHF), which acts as a methyl donor. Then, vitamin B12 transfers a methyl group from 5-MTHF to homocysteine to generate methionine.

Methionine is easily converted to S-adenosylmethionine (SAM), the primary methyl donor in various methylation reactions, including DNA methylation and neurotransmitter synthesis.

Diagram of the Methylation Cycle Enhanced by Folate and Vitamin B12.

A review of B vitamins and one-carbon metabolism highlights the importance of vitamin B12 and folate in the methylation cycle to generate methyl groups for use in DNA synthesis, amino acid homeostasis, antioxidant generation, and epigenetic regulation.

So, folic acid or vitamin B12 deficiency can impair methylation processes, leading to disruptions in gene expression, neurotransmitter synthesis, and other cellular functions, potentially contributing to various health challenges. 

2. Supports cardiovascular health

Vitamin B12 and folate support cardiovascular health through their roles in homocysteine metabolism. Homocysteine is an amino acid the body produces when it breaks down protein. Thus, the amino acid shows up in your blood after eating proteinous food, especially animal foods (meat).

However, very little homocysteine remains in the blood. High levels of homocysteine generally cause cardiovascular diseases (such as stroke, heart attack, peripheral arterial disease, and coronary artery disease). 

Different studies have demonstrated that there’s a clear connection between high homocysteine levels and cardiovascular diseases (and related mortality).

Interestingly, homocysteine is an intermediate in the metabolism of methionine.

Folic acid and vitamin B12 work together to convert homocysteine to methionine. Folate is converted to 5-MTHF, and then vitamin B12 transfers a methyl group from this compound to homocysteine to generate methionine. 

Therefore, taking vitamin B12 and folate together helps lower the level of homocysteine in the blood. Since high serum homocysteine is a risk factor for cardiovascular disease, lowering homocysteine levels may reduce cardiovascular risks. 

A meta-analysis confirmed that administering folate, vitamin B12, and vitamin B6 can help decrease serum homocysteine levels.

Also read: Choosing the Right vitamin B12 Supplement: What You Need to Know.

3. Improves cognitive function

Vitamin B12 and folate help maintain cognitive function (such as memory, attention, and processing speed) through several mechanisms, including lowering homocysteine and synthesizing neurotransmitters.

The deficiencies of vitamin B12 and folate can cause blood homocysteine levels to rise. And high homocysteine levels are associated with incidences of cognitive impairment and dementia.

Remember that vitamin B12 and folate are involved in the conversion of homocysteine to methionine. This process reduces the accumulation of the amino acid homocysteine in the body, potentially protecting against cognitive decline.

Vitamin B12 and folate are involved in synthesizing neurotransmitters such as dopamine and norepinephrine, which play key roles in alertness, focus, concentration, memory, and decision-making.

In fact, stimulants and anti-depression medications that improve focus or concentration work by increasing the production of these neurotransmitters, particularly norepinephrine.

Thus, taking adequate levels of vitamin B12 and folate is necessary to produce and regulate essential neurotransmitters, thereby supporting optimal cognitive function.

A longitudinal study confirmed that homocysteine-lowering B Vitamins slow the rate of brain atrophy in old people with mild cognitive impairment. 

Studies have also shown that vitamin B12 and folate supplementation have a positive effect on the cognitive performance of Alzheimer’s disease patients.

4. Helps regulate mood

Vitamin B12 and folic acid help regulate mood by lowering homocysteine and synthesizing neurotransmitters. Researchers have found that there’s a connection between high levels of serum homocysteine and depression

Remember that a high serum homocysteine level indicates vitamin B12 and folate deficiency.

Vitamin B12 and folate are also involved in converting homocysteine to methionine. Thus, taking a vitamin B12 and folic acid supplement can help reduce homocysteine levels, helping to mitigate the potential effects of this amino acid on mood.

Remember also that vitamin B12 and folic acid help synthesize neurotransmitters like dopamine and norepinephrine. These neurotransmitters do not only enhance cognitive function, but they also boost mood and overall mental health. 

That is why dopamine is called the “happy hormone” or “feel-good hormone.” Its presence in the body leads to feelings of happiness.

So, vitamin B12 and folate deficiency can result in imbalances in neurotransmitter levels, which may contribute to mood disorders like depression and anxiety. Conversely, adequate levels of vitamin B12 and folic acid help synthesize the neurotransmitters necessary for regulating and maintaining emotional well-being.

A meta-analysis of randomized controlled trials in the Journal of Psychopharmacology found that using folate dietary supplements as an adjunct therapy increased serum folate and significantly reduced depression ratings.

5. Helps with optimal energy production

Vitamin B12 and folate are key to energy metabolism. When taken together, these vitamins can help you fight fatigue and weakness. All the B Vitamins (including B12 and folic acid) help the body convert food into usable energy. 

The B vitamins are essential precursors of coenzymes that play essential roles in energy metabolism. B12, folic acid, and other B vitamins help form the helper molecules that bind to and activate enzymes involved in energy release and storage. 

Without these helper molecules (coenzymes), the enzymes will not work properly (or may not work at all) to catalyze reactions that lead to energy production.

Deficiency in B12 or folate may result in poor energy metabolism, causing weakness or fatigue.

Studies investigating the effect of vitamin B12 (cobalamin) and folic acid supplementation in boosting energy and fighting fatigue are promising. For example, a 2015 study found that patients with chronic fatigue syndrome responded favorably to vitamin B12 injections in combination with folic acid supplements.

You may also like: 5 Top Vitamins for an Energy Boost: Essential Nutrients for Boosting Your Energy Levels.

6. Aids DNA synthesis

Folate and vitamin B12 work together to synthesize DNA effectively, ensuring accurate cell division and minimizing the risks of mutations.

Folate is converted to its active form (tetrahydrofolate) in the body, and this compound is a carrier of one-carbon units necessary for synthesizing purines and pyrimidines (nucleotides), which are the building blocks of DNA. 

Adequate levels of folate ensure the availability of nucleotides for DNA synthesis, which supports cell replication and division.

Folate and vitamin B12 also combine to produce methionine, a precursor for DNA methylation, which is critical in regulating gene expression and maintaining genomic stability.

Given the crucial roles of folate and vitamin B12 in DNA synthesis, deficiencies of these vitamins can lead to impaired DNA synthesis, which may contribute to disruptions in cell proliferation, differentiation, and function.

One study investigating the role of nutrition in DNA replication, DNA damage prevention, and DNA repair confirmed that folate and vitamin B12 are required for nucleotide synthesis and DNA replication, as well as the maintenance of DNA methylation and chromosome stability.

The study added that deficiency in these micronutrients increases DNA replication stress and genomic instability, exacerbating susceptibility to DNA damage.

Another study found that vitamin supplementation may help prevent DNA damage by aiding DNA replication and transcription.

7. Forms red blood cells

Vitamin B12 and folate play crucial roles in red blood cell production, ensuring adequate oxygen delivery to tissues and preventing anemia. These vitamins help in red blood cell production by supporting DNA.

During red blood cell production, hematopoietic stem cells (HSCs) undergo several rounds of cell division and differentiation to produce mature red blood cells. DNA synthesis is essential for these processes, as it provides the genetic material necessary for cell division and differentiation.

Deficiencies in vitamin B12 and folate will affect DNA synthesis and, by extension, cell division. When red blood cells do not divide properly, an individual can have macrocytic anemia—a condition where the red blood cells are unusually large and, as a result, are fewer and less efficient at carrying oxygen to cells.

Red blood cell division: Adequate folate ensures efficient division, while folate deficiency leads to improper division, causing macrocytic anemia.

Thus, vitamin B12 and/or folate deficiencies can result in lower hemoglobin levels, causing anemia. In one retrospective analysis of anemia in pregnancy, researchers compared pregnant women who were taking “high vitamin B12, high folic acid food” with those who were taking standard prenatal food with “low vitamin B12, low folic acid.” 

The women in the vitamins-enriched prenatal balanced diet group had significantly higher hemoglobin levels at delivery than those in the standard prenatal food group.

A study investigating the role of vitamins in the prevention and control of anemia has also shown that vitamin B12 and folate supplementation are effective in preventing and treating anemia

8. Supports the immune system

Vitamin B12 and folate play roles in cellular proliferation and differentiation, making them essential for a properly functioning immune system that helps the body fight infection and illnesses.

Remember that adequate levels of vitamin B12 and folate are required for DNA synthesis, which is essential for cell division and differentiation during immune responses. 

Immune cells, including lymphocytes (like T cells and B cells) and myeloid cells (like macrophages, dendritic cells, and granulocytes), require these B vitamins for proliferation and differentiation. 

Vitamin B12 and folate also have antioxidant properties that help protect immune cells from oxidative stress and damage caused by reactive oxygen species. The role of the B vitamins in neutralizing ROS and maintaining redox balance supports immune cell function and enhances immune responses to infections.

So, inadequate levels of vitamin B12 and folic acid can drastically alter immune responses and increase susceptibility to infections. These B vitamin deficiencies inhibit the activity of immune cells by interfering with methylation and other metabolic processes. 

Inadequate methylation can cause systemic and vascular inflammation that contributes to the pathogenesis of many diseases.

9. Supports neurological health

Vitamin B12 and folate are crucial for maintaining the myelin sheath, protecting nerve cells from damage, and ensuring efficient nerve signaling.

Vitamin B12, in particular, is a co-factor in myelin formation. The myelin sheath insulates nerve fibers. This protects them from damage caused by mechanical damage. The insulation also increases the speed at which electrical impulses travel along nerve fibers. 

By supporting myelin formation, vitamin B12 ensures the nervous system functions properly and supports various sensory, motor, and cognitive processes. 

Thus, deficiencies in the vitamin can contribute to demyelinating diseases such as neuromyelitis optica (NMO), acute‐disseminated encephalomyelitis, and multiple sclerosis. These diseases are characterized by damage to the myelin sheath. 

They impair the transmission of nerve impulses, resulting in neurological symptoms like numbness, tingling numbness, and coordination difficulties. Therefore, adequate vitamin B12 intake helps reduce the chances of neurological diseases.  

Folate’s involvement in DNA repair, methylation reactions, and glutathione synthesis means it indirectly contributes to the body’s antioxidant defense mechanism. It prevents oxidative damage that can lead to neurodegenerative diseases. So, taking vitamin B12 and folate together enhances the vitamins’ neurological function. 

10. Regulates hormones

The role of vitamin B12 and folate in methylation reactions makes these vitamins crucial to hormone metabolism and regulation. Methylation reactions are involved in the synthesis, activation, inactivation, and degradation of various hormones (including estrogen, testosterone, thyroid hormones, and adrenal hormones).

For example, in estrogen metabolism and regulation, the primary forms of estrogen are converted to various metabolites. Methylation reactions then convert these estrogen metabolites into methylated forms that are less reactive and can be excreted from the body. 

Interestingly, the methylation reactions are catalyzed by enzymes requiring vitamin B12 and folate as co-factors.

So, without these vitamins, enzymes remain inactive and cannot catalyze specific methylation reactions for the synthesis, activation, or degradation of hormones. 

11. Supports fetal development

Vitamin B12 and folic acid work together during pregnancy to support the baby’s spinal cord and brain development. Thus, maintaining adequate levels of vitamin B12 and folate levels during pregnancy can reduce the risk of birth complications, such as neural tube defects and spina bifida.

The American Pregnancy Association says folate is one of the most important B vitamins to take during pregnancy.

Remember that pregnancy is a time of rapid cell growth and differentiation for the mother and fetus. So, folate’s role in cell division and differentiation makes it crucial to fetal development.

Folate deficiency during pregnancy increases the likelihood of birthing babies with spina bifida, a neural birth defect occurring when a baby’s spinal cord does not develop properly, causing a gap in the spine.

Image of spina bifida showing that the spine does not completely enclose the spinal cord.

Folate enhances cell growth, and the highly proliferating cells help the neural spine close properly. Therefore, adequate folate intake before and during pregnancy (especially during early pregnancy when the neural tube is still forming) helps prevent neural tube defects in the brain and spinal cord.

The benefits of taking folate with vitamin B12 extend beyond preventing neural tube defects. The vitamins’ role in methylation reactions makes them essential in reducing pregnancy complications.

A study investigating the effect of folate and cobalamin deficiency during pregnancy found that deficiencies of these vitamins cause recurrent spontaneous abortion, preterm delivery, fetal malformations, low birth weight, stillbirth, and abruption of the placenta. So, taking these vitamins together during pregnancy can help reduce these risks.

Also read: The Benefits of Liquid B Complex Over Tablets: A Comprehensive Guide.


Here are the answers to some frequently asked questions about folate and vitamin B12. 

Why are folate and vitamin B12 important for pregnancy?

Folate and vitamin B12 promote cell division and differentiation during pregnancy, which is essential for optimal development of the developing fetus and reducing the risk of pregnancy and birth complications.

Why take vitamin B12 before folate?

Folate can mask the symptoms of vitamin B12 deficiency. Consider the case of megaloblastic anemia where vitamin B deficiency causes the production of unusually big and inefficient red blood cells. Taking folic before vitamin B12 can support red blood cell production and alleviate symptoms of anemia without addressing neurological complications associated with vitamin B12 deficiency.

What vitamins should not be taken together with B12?

When taking vitamin B12, you should avoid taking vitamin C. This is because vitamin C converts B12 into a more readily excreted form, reducing its absorption availability. If you must take vitamin C when taking vitamin B12, space the timing of the two vitamins intake by several hours.

What vitamins should not be taken together with folate?

While vitamin B12 and folate can be taken together, you should not take too much folate when taking vitamin B12. This is because too much folic acid masks the symptoms of vitamin B12 deficiency.

What are the causes of vitamin B12 or folate deficiency?

The main cause of vitamin B12 or folate deficiency is poor dietary intake of the vitamin (not taking adequate levels of the vitamins from food).

The main sources of vitamin B12 are animal-based foods such as meat, fish, eggs, and dairy products. So, a vegan diet increases susceptibility to vitamin B12 deficiency. The main sources of folate are leafy green vegetables, citrus fruits, whole grains, and beans. 

Can excess B12 damage kidneys?

Vitamin B12 is generally considered safe and non-toxic, even at high doses, because it is water-soluble. As a water-soluble vitamin, excess amounts are excreted through urine.

However, some studies suggest that people with kidney function loss may experience quicker kidney deterioration with very high doses of vitamin B12.

Does vitamin B12 have side effects?

Vitamin B12 is generally safe for most people, even in high doses. However, it may cause side effects in some people, especially when taken in high doses. These side effects include:

  • Nausea
  • vomiting, 
  • Diarrhea
  • Headache
  • Tingling sensation in the hands and feet.

Is it safe to take B12 every day?

Yes, it is safe to take vitamin B12 every day. In fact, your body needs a specific amount of vitamin B12 each day for proper functioning. The daily recommended amount of vitamin B12 depends on age as follows:

  • 0 to 6 months - 0.4 mcg
  • 7 to 12 months - 0.5 mcg
  • 1 - 3 years - 0.9 mcg
  • 4 - 8 years - 1.2 mcg
  • 9 - 13 years - 1.8 mcg
  • 14 and above - 2.4 mcg (Pregnant women - 2.6 mcg; breastfeeding women - 2.8 mcg).

How do I check my vitamin B12 levels? 

You can check your vitamin B12 levels using a routine blood test called the vitamin B12 level test. The blood test checks the amount of vitamin B12 in your blood. Normal levels range from 200 to 900 picograms per mL. You’ll be diagnosed with vitamin B12 deficiency if the level of B12 in your blood is less than 150 picograms per mL.

Takeaway: Maintain adequate vitamin B12 and folate levels with Why Not Natural supplements

WhyNotNatural Dietary Supplement: B-12 Methyl + Folate, unflavored.

Vitamin B12 and folate are essential B vitamins critical to many physiological processes in the body. Though they have distinct functions, they play complementary roles in many processes. As such, you can take them together. 

There are no adverse drug interactions between vitamin B12 and folate. Instead, taking them together enhances their functions, which include supporting heart rate, improving cognition, and regulating mood.

Our vitamin B12 + folate supplement features the most bioavailable forms of B12 and folate—methylcobalamin and folinic acid. This makes them more readily absorbed by the body to give you all their nutritional goodness.

Also, the Why Not Natural vitamin B12 + folate supplement is pure. It contains no toxic cyanide or synthetic folic acid like other inferior vitamin supplements. It doesn’t even contain fillers and preservatives. 

Start your journey to better health today! Get the vitamin B12 + folate dietary supplement!

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