Boost your energy with folate and vitamin B12 for optimal health.

Understanding the Synergistic Effects of Vitamin B12 and Folate in Energy Metabolism

Vitamin B12 and folate (also called vitamin B9) are water-soluble essential vitamins that are crucial for various chemical reactions responsible for energy production. From DNA synthesis to red blood cell biosynthesis, they regulate your metabolism and fill you with energy.

The most interesting thing about them is how they work together. Vitamin B12 and folate complement each other perfectly to enhance their efficacy. Understanding this synergy at a molecular level will help you gain insight into how they work and how you can optimize your intake for better energy levels.

Overview of vitamin B12

A wooden frame and a stethoscope with the text "Vitamin B12".

Vitamin B12, or cobalamin, is a highly potent vitamin that has a central role in many of your body’s activities. It is required for DNA replication and the creation of red blood cells, and it supports your nervous system. 

What sets vitamin B12 apart is that it is a water-soluble vitamin, and that is why the human body can’t retain it for very long. However, unlike other water-soluble vitamins, vitamin B12 can be stored in the liver for several years.

Of all the B vitamins, vitamin B12 is special as it is almost exclusively found in animal products. This means that people who consume little or no animal products, such as vegetarians and vegans, are more prone to develop a deficiency. 

Vitamin B12 deficiency causes several health issues, such as fatigue, anemia, and neurological complications.

Best dietary sources of vitamin B12

Image showing the best vitamin B12 food sources such as cheese, milk, meat, salmon, mushrooms and more.

Incorporating certain foods into your diet is a great way to boost your vitamin B12 intake.

Here are some of the best dietary sources:

  • Meat: Beef, pork, and lamb are known to contain vitamin B12. The nutrient is also found in the liver and kidney. You can get 3.7 mcg of vitamin B12 from a single serving of 3 ounces of beef.
  • Fish and seafood: Some rich sources of vitamin B12 include salmon, trout, tuna, and shells such as clams and crabs. A 3-ounce cooked salmon contains enough vitamin B12 to meet your daily requirements.
  • Dairy products: vitamin B12 is also found in milk, cheese, and yogurt. You can get half of your daily allowance of vitamin B12 from a single cup of 2% milk.
  • Eggs: Eggs, especially the yolk part, contain moderate amounts of vitamin B12.
  • Fortified foods: For people on a vegan diet, most cereals, plant-based milk, and nutritional yeasts contain vitamin B12, making them the best options.

Consuming different types of these foods will help meet the body’s requirement of vitamin B12.

Recommended daily allowances for vitamin B12

Understanding how much vitamin B12 you should be taking will assist you in determining whether you are taking the right amount you need. RDAs of vitamin B12 also differ according to the age, gender, and stage in life you are in.

Here's a quick guide:

  • Infants (0-6 months): 0.4 micrograms (mcg)
  • Infants (7-12 months): 0.5 mcg
  • Children (1-3 years): 0.9 mcg
  • Children (4-8 years): 1.2 mcg
  • Children (9-13 years): 1.8 mcg
  • Teens (14-18 years): 2.4 mcg
  • Adults (19 years and older): 2.4 mcg
  • Pregnant women: 2.6 mcg
  • Breastfeeding women: 2.8 mcg

These values are merely guidelines that may help ensure you are taking adequate vitamin B12 for your body. Depending on your risk factors for deficiency or any other health conditions you may suffer from, your doctor may recommend a different dosage.

Symptoms of vitamin B12 deficiency

An elderly woman with symptoms of vitamin B12 deficiency: fatigue, weakness, and pale skin.

It is easy to overlook vitamin B12 deficiency because it gradually manifests before the symptoms become more prominent.

Here are some common symptoms to watch out for:

  • Fatigue: Chronic fatigue is one of the most evident symptoms of vitamin B12 deficiency. You feel tired without exerting your body, and apparently for no reason.
  • Anemia: Vitamin B12 is essential in the body since it plays a major role in synthesizing red blood cells. If you are deficient, you can suffer from anemia. Some early symptoms of the condition include pale skin, shortness of breath, and dizziness.
  • Neurological changes: Vitamin B12 is also responsible for neurological health, so its deficiency might cause neurological issues. Some neurological symptoms of vitamin B12 deficiency include a tingling or numb sensation in the hands and feet, problems with balance, and difficulty in concentration or remembering things.
  • Mood changes: Vitamin B12 is also key in regulating your mood and behavior. When you have less of this vitamin in your body, you may experience mood swings, bouts of depression, or feel irritable.
  • Glossitis and mouth ulcers: If you experience frequent mouth and tongue ulcers, you might be deficient in vitamin B12. Chronic deficiency of the vitamin causes persistent ulcers that are painful and difficult to heal.

If you experience any of these symptoms, you should visit your doctor to get your vitamin B12 levels checked. If you are deficient, your doctor will suggest a supplement.

Always ensure that the supplement you take is bioavailable and contains the right dosage of the active vitamin. Why Not Natural’s Organic Vitamin B12 Liquid is perfect for boosting energy and improving memory. 

Overview of folate

Image showing folate structure.

Folate, or vitamin B9, is another B-complex vitamin essential to many bodily processes. It is involved in DNA synthesis, repair, and methylation and consequently plays a central role in cell division and growth. 

This is especially important during pregnancy and childhood when your body is rapidly growing. Folate is also responsible for red blood cell production and preventing anemia, which causes fatigue and weakness.

One of the most important roles of folate is to convert an amino acid called homocysteine into methionine. The conversion is essential for regulating protein synthesis and glucose metabolism. Folate is also important for maintaining the cardiovascular system as it reduces the levels of homocysteine and odd-chain fatty acids, exerting a cardioprotective effect.

Folate is the natural form of vitamin B9 that you get from your diet, while folic acid is the synthetic derivative used in nutritional supplements and fortified foods. 

Both of them are effective in the body, but it is easier for the body to absorb folic acid than the naturally occurring folate. It is, therefore, important to have adequate knowledge of folate and its relation to food to take the necessary measures to improve human health.

Best dietary sources of folate

Folate-rich foods: spinach, lentils, avocado, broccoli, asparagus, citrus fruits, beans, and fortified cereals.

Folate is present naturally in many foods. Adding these foods to your diet will help prevent folate deficiency. Here are some of the best dietary sources of folate:

  • Leafy greens: Folate is abundant in spinach, kale, and romaine lettuce. One cup of raw spinach contains approximately 58 mcg of folate. Try to add these green leafy veggies to your everyday diet.
  • Legumes: Some of the best folate-rich foods include beans, lentils, and peas. For instance, a cooked cup of lentils contains approximately 358 mcg of folate, almost 80% of your daily dietary reference intake.
  • Citrus fruits: All citrus fruits, like oranges and grapefruits, are rich in easily absorbable forms of folate. There is 55 mcg of folate in one large orange alone. Try to avoid processed juices, however. Stick to the whole fruits as they will provide you with the much-needed fiber as well.
  • Avocado: Avocado is known for its creamy and rich texture and folate content. You can get as much as 82 mcg of folate from just half an avocado. Add it to your salads for a healthy dose of folate and healthy fats.
  • Broccoli: Whether steamed, roasted, or raw, broccoli is a healthy vegetable that provides about 104 mcg of folate per cup when cooked.
  • Nuts and seeds: Among nuts and seeds, sunflower seeds and peanuts contain rich amounts of folate. A quarter cup of roasted sunflower seeds contains about 82 mcg of folate. That said, these seeds also contain a lot of fat, so make sure you are not over-consuming them if you have elevated fat levels.
  • Fortified foods: Synthetic folate is added to many grains, cereal products, and breads. These can be a great source of folate, particularly for those who can’t get adequate amounts of folate from natural products.

Including some of these foods in your diet can assist you to meet your daily recommended amount of folate and live a healthy life.

Recommended daily allowances for folate

The RDAs for folate vary according to age, sex, and life stage. The recommended amount of folate is usually expressed in terms of Dietary Folate Equivalents (DFE). 

DFE is a term used to account for the difference in bioavailability between natural folate and synthetic folic acid. For instance, one microgram of dietary folate equals 1 microgram of DFE, but one microgram of folic acid from fortified foods or supplements equals 1.7 mcg of DFE if the product is consumed with food.

Here’s a detailed guide to help you understand how much folate you need:

  • Infants (0-6 months): 65 micrograms (mcg) of Dietary Folate Equivalents (DFE)
  • Infants (7-12 months): 80 mcg DFE
  • Children (1-3 years): 150 mcg DFE
  • Children (4-8 years): 200 mcg DFE
  • Children (9-13 years): 300 mcg DFE
  • Teens (14-18 years): 400 mcg DFE
  • Adults (19 years and older): 400 mcg DFE
  • Pregnant women: 600 mcg DFE
  • Breastfeeding women: 500 mcg DFE

There is a need to point out that the folate requirement increases during pregnancy. You need significantly more folate to support the growth of your baby and produce milk during lactation. Women of childbearing age are also urged to take adequate folate to prevent fetal neural tube defects when they get pregnant.

Symptoms of folate deficiency

Female with palpitations and shortness of breath with signs of folate deficiency.

If you are deficient in folate, you might experience serious health issues, including metabolic disorders. Some of the most common folate deficiency signs and symptoms include:

  • Fatigue and weakness: One of the earliest signs of folate deficiency is persistent tiredness and general weakness. This is due to its role in red blood cell production; without enough folate, you may develop anemia.
  • Mouth sores and swollen tongue: A lack of folate can cause painful sores inside your mouth and a swollen, red tongue, known as glossitis.
  • Cognitive difficulties: Folate is crucial for brain function, so a deficiency can lead to difficulty concentrating, memory problems, and even mood changes such as irritability or depression.
  • Digestive issues: Folate deficiency causes a range of GI symptoms, like nausea, diarrhea, and a loss of appetite.
  • Heart palpitations and shortness of breath: Folate regulates red blood cell production and oxygen transport, so a folate deficiency can lead to heart palpitations and shortness of breath.
  • Neural tube defects in babies: For pregnant women, a deficiency in folate increases the possibility of neural tube defects in the developing fetus. Incidences of defects such as spina bifida and anencephaly might increase.
  • Elevated levels of homocysteine: Without enough folate, homocysteine levels can rise, increasing the risk of cardiovascular disease.

If you are experiencing any of the symptoms above, please visit your doctor and get your folate levels checked. You might need folic acid supplementation to reverse some of these symptoms.

Biochemical relationship between vitamin B12 and folate

Vitamin B12 and folate or vitamin B9 are two micronutrients that work in tandem in the body. They are a perfect example of how some vitamins work synergistically to carry out important bodily functions. 

Vitamin B12 and folate work together in DNA synthesis, red blood cell production, and maintainance of the nervous system. 

A number of studies have been conducted regarding the biochemical interaction between vitamin B12 and folate.

A paper in the American Journal of Clinical Nutrition examined the impact of folate and vitamin B12 on homocysteine concentrations. This study also revealed that while folate supplementation lowered homocysteine levels by a large margin, combining folate and vitamin B12 had a much stronger impact. 

This shows that these vitamins work in combination with the metabolism of amino acids like homocysteine.

Another study on elderly Koreans examined the effect of these B vitamins on brain function. The researchers' data indicated that the participants with the highest levels of folate and vitamin B12 scored better on the cognitive tests than the control group, indicating that adequate intake of both folate and vitamin B12 is necessary for proper cognitive health.

Let’s take a closer look at the biochemistry of the two and see why it is so crucial for human health:

The folate cycle and one-carbon metabolism

Illustration showing the process of the folate cycle and one-carbon metabolism.

The folate cycle is a biochemical chain reaction in your body in which folate gets converted to different forms that transfer one-carbon units. Popularly called the one-carbon metabolism, this cycle is required for the production of purines and pyrimidines, which are the building blocks of your DNA and RNA.

5-methyltetrahydrofolate (5-methyl THF) is one of the most important forms of folate because it transfers a methyl group to homocysteine to form methionine, an amino acid that is used in the methionine cycle.

Vitamin B12 helps activate the enzyme methionine synthase, which converts homocysteine to methionine. This reaction needs the participation of 5-methyl THF to donate its methyl group. If vitamin B12 is not present, methionine synthase is not active, homocysteine accumulates, and methionine is deficient. 

This process highlights the critical dependency of folate on vitamin B12 to regulate energy metabolism.

The methyl trap hypothesis

A fairly recent idea that helps to explain the connection between these vitamins is the so-called “methyl trap” hypothesis. If there is insufficient vitamin B12, 5-methyl THF can’t be converted back to THF, which is the active form required for the synthesis of DNA.

This means that folate is locked up as 5-methylTHF and can’t be used for other functions; therefore, people develop folate deficiency symptoms even if they are consuming folate in their diet. The phenomenon is an example of how a lack of one vitamin leads to the functional deficiency of the other, even when present in adequate amounts.

Practical implications on human health

Understanding the biochemical relationship between vitamin B12 and folate has significant practical implications. For instance, it explains why certain populations, such as vegetarians and the elderly, are at higher risk for deficiencies. 

Vegetarians may not get enough vitamin B12 from their diet, leading to a functional folate deficiency. Similarly, as people age, their ability to absorb vitamin B12 decreases, making supplementation or dietary intake adjustments crucial.

It is also important for pregnant women to take adequate amounts of both folate and vitamin B12. It is a fact that folate is very effective in avoiding the occurrence of neural tube defects, but it can’t work effectively when it is not combined with vitamin B12. This is why prenatal vitamin supplementation typically contains both nutrients.

Also read: Can You Take Vitamin B12 and Folate Together? (11 Benefits Explained).

What are the synergistic effects of vitamin B12 and folate in energy metabolism?

Before we discuss how vitamin B12 and folate interrelate, it is essential to define energy metabolism. Energy metabolism is the mechanism by which the human body utilizes nutrients to generate energy. This energy is accumulated through adenosine triphosphate (ATP), the energy currency for the cells involved in various functions, ranging from muscle contraction to brain activity.

Folic acid and energy metabolism

Folate is involved in the folate cycle, catalyzing the conversion of homocysteine to methionine, another amino acid. It is a precursor to S-adenosylmethionine (SAMe). SAMe is essential in methylation processes that control the expression of genes and proteins.

A study published in the Cleveland Clinic Journal of Medicine noted that folate deficiency damages the creation of new cells and causes diseases like megaloblastic anemia, which causes fatigue and weakness. The study's evidence shows that folate is essential in maintaining energy levels, as the red blood cells in the body must be produced adequately to transport oxygen within the body.

Another study revealed that supplementation with folate reduced body weight gain and significantly decreased the levels of branched-chain amino acids in animal models. The study indicates that folate might play a role in fatty acid synthesis by altering the composition of the gut microbiota.

Vitamin B12 and energy metabolism

Vitamin B12 plays the role of a cofactor for an enzyme called methionine synthase, which is involved in converting homocysteine to methionine, thus allowing the folate cycle to proceed. When vitamin B12 is not available in sufficient quantities, this process halts, homocysteine accumulates, and methionine and SAMe are deficient.

A study in the American Journal of Clinical Nutrition revealed that vitamin B12 deficiency may cause high homocysteine levels. Elevated homocysteine is associated with an increased risk of cardiovascular diseases and neurological complications. 

Also, B12 is crucial in maintaining the myelin sheath, which encases the nerves and transmits nerve impulses. B12 directly influences the body's mental health and energy levels.

You may also like: Supplements or Vitamins to Boost Your Energy? (Answered)

The synergistic interaction

Now, let’s analyze the interaction of these two vitamins. vitamin B12 and folate are good examples of synergistic nutrients. Their effects are enhanced when taken together.

The folate and methionine cycles are interrelated. 5-methyltetrahydrofolate (5-methyl THF), the form of folate, transfers a methyl group to homocysteine using the methionine synthase enzyme, which requires vitamin B12.

If there is a lack of vitamin B12 or folate, this process is interrupted, and a range of metabolic problems occur. If there is a deficiency of vitamin B12, folate is bound in its 5-methyl THF form, creating what is referred to as the ‘‘methyl trap.'' It leads to limited folate availability for DNA synthesis and energy-producing processes related to cell division.

Scientific evidence of synergy

Many studies have revealed the possibility of vitamin B12 and folate synergy in the human body. For example, research published in the New England Journal of Medicine showed that folate and vitamin B12 supplements could lower homocysteine levels in patients better than when each nutrient was used singly. 

It means that the two supplements, when taken together, may be useful in preventing cardiovascular diseases associated with high homocysteine.

Another study conducted to examine the impact of B vitamins on cognitive health was published in The Lancet among the elderly with mild cognitive impairment. The researchers discovered improved cognitive function and reduced brain atrophy in the group that received vitamin B12 and folate compared to the group that did not receive the supplements.

Tips to leverage the synergy between folate and B12

The knowledge of the interaction between vitamin B12 and folate has applied value when it comes to foods and supplements. Here are some tips to leverage the synergy between the two nutrients:

  • Take a balanced diet: You should always consume enough foods with a high folate content to meet your daily requirements. For vitamin B12, include foods of animal origin, such as meat, fish, eggs, and dairy products. If you are vegan or vegetarian, go for fortified foods or supplements. Pair the foods rich in folate with foods rich in vitamin B12 to get the most out of your diet.
  • Monitor your intake: The Recommended Dietary Allowance (RDA) for adults is 400 micrograms (mcg) of folate and 2.4 mcg of vitamin B12 daily. Pregnant and breastfeeding women require higher amounts to support fetal and infant development.
  • Supplement wisely: Taking a supplement containing folate and vitamin B12 is the best way to ensure you get the most benefit. Why Not Natural's Vitamin B12 + Folate Liquid contains both folate and vitamin B12 in a highly absorbable formulation. The formula is 100% organic without additives, fillers, or preservatives.
  • Get regular check-ups: Blood tests should be done periodically to ensure that your vitamin B12 and folate levels are as they should be, especially if you are in a high-risk group. If the deficiency is detected and treated early, the effects on energy metabolism and health can be avoided.


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

Are vitamin B12 and folate interdependent for their activation?

Yes, in a way, vitamin B12 and folate depend on each other because vitamin B12 is necessary for converting folic acid to its active form. Vitamin B12 is also essential for reactivating the active forms of folate, 5-methyltetrahydrofolate, and tetrahydrofolate (THF), which are involved in DNA synthesis and cell division. When B12 levels are low, folate can’t work as it is locked in an inactive state.

How do I diagnose vitamin B12 deficiency?

Vitamin B12 deficiency is diagnosed through blood tests, which include Serum B12 level, Methyl Malonyl Acid (MMA), and Homocysteine level. High MMA and homocysteine and a low B12 indicate deficiency. A complete blood count (CBC) could also show anemia with large red blood cells (megaloblastic anemia), pointing to B12 deficiency.

Do older adults require increased amounts of vitamin B-12?

Yes, elderly people need more water-soluble vitamins, especially vitamin B12, than other members of society. Older people are less able to absorb B12 from food because stomach acid diminishes with age, and other changes in the digestive tract occur. They may require higher amounts of nutrients in their diets or dietary supplements to receive adequate nutrition.

What role does vitamin B12 play?

B12 is important for synthesizing nucleic acids, red blood cell formation, and maintaining nervous system health. It is involved in the homocysteine metabolism to methionine with the help of methionine synthase as a cofactor. It is required for the methylation reactions involved in gene expression and protein function.

How does folate work in the body?

Folate functions through the folate cycle, which donates one-carbon groups required for DNA replication, repair, and methylation. It plays a role in synthesizing red blood cells and amino acids through its active form, THF.

What are the three forms of folate?

You might encounter three types of folate: dietary folate, dihydrofolate (DHF), and tetrahydrofolate (THF). Folate naturally occurs in foods and is also known as dietary folate. DHF is an intermediate in the folate cycle, while THF is the form that is used in DNA synthesis and methylation.

What hinders the absorption of folate?

Conditions affecting the GI tract, like celiac disease and Crohn’s disease, might hinder your folate absorption. Furthermore, the use of certain drugs, including anticonvulsant drugs, methotrexate, and alcohol, also diminishes your body’s ability to absorb folate. Other nutrient deficiencies, particularly vitamin B12, while not directly affecting folate absorption, may limit folate utilization.

Takeaway: Energize your life with vitamin B12 and folate

Vitamin B12 and folate are essential to your nutrient profile and key to overall health. The combined action of vitamin B12 and folate is crucial for proper energy production, DNA synthesis, red blood cell formation, and proper nervous functioning.

They enable your body to metabolize food into energy, effectively preventing fatigue and promoting vitality. Incorporating B12-rich foods like meat and dairy and folate-rich foods like leafy greens and legumes into your diet or considering supplementation if necessary will help optimize your energy levels and enhance your overall health.

Get the Why Not Natural Vitamin B12 + Folate Liquid to harness the full potential of vitamin B12 and folate. Our sublingual formulation has high bioavailability with no added fillers, preservatives, or additives.

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