B12 for energy – here’s why it matters

Vitamin B12 is a powerhouse when it comes to supporting our overall health. As an essential water-soluble vitamin, it plays a critical role in many key processes, from DNA synthesis to maintaining a healthy nervous system. One of its most principal functions though is its involvement in converting the food we eat into usable energy. Despite its importance, many of us have insufficient levels, and a ‘sub-clinical’ category of B12 deficiency is on the rise.

With the Christmas period behind us, many of us are left feeling sluggish and drained and the remaining winter months can often bring a sense of fatigue, both mentally and physically. In this week’s blog, we’ll explore how B12 plays an important role in supporting and maintaining our energy levels. We’ll also examine the factors that can lead to poor absorption and insufficiency and why ensuring an optimal status is key to feeling your best. 

B12’s role in energy

Converts food into energy[i]

Vitamin B12 is crucial for the enzymatic reactions and biochemical pathways, such as the Citric Acid (Krebs) Cycle, that convert macronutrients into ATP (adenosine triphosphate). ATP is the energy currency of our cells and powers all cellular activities, from muscle contraction to brain function.[ii]

• Fatty Acid Metabolism: B12 acts as a cofactor for the enzyme methylmalonyl-CoA mutase, which catalyses the conversion to succinyl-CoA. Succinyl-CoA then enters the Krebs cycle, assisting the efficient utilisation of fatty acids for energy production.[iii]
• Carbohydrate Conversion: B12 supports the metabolism of carbohydrates by aiding the conversion of glucose into ATP.
• Protein Metabolism: B12 is essential for converting homocysteine to methionine via the enzyme – methionine synthase. Methionine is then converted to S-adenosylmethionine (SAMe), a methyl group donor involved in many methylation reactions, including those required for energy [iv]

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 B12 & red blood cell formation

B12 is vital for the production of healthy red blood cells, which transport oxygen around the body. Oxygen is a critical substrate for oxidative phosphorylation in the mitochondria, where it is used in the electron transport chain to generate ATP. A sufficient oxygen supply to organs, tissues, and muscles is vital for optimal energy production. 

DNA synthesis

B12 is involved in the synthesis of DNA, which is essential for the production of new cells. With healthy DNA and cell regeneration, the mitochondria can also function optimally.[v]

 B12 and neurological health

B12 is vital for nervous system health, as it protects the myelin sheath around nerve fibres, ensuring effective nerve signalling. Healthy nerves are crucial for muscle coordination and physical activity. Without adequate B12, myelin can deteriorate, leading to nerve damage and impaired function. B12 also supports focus, mental clarity, and cognitive function by aiding neurotransmitter production, helping sustain energy, boost motivation, and counteract fatigue. 

Homocysteine regulation

B12 helps convert homocysteine into methionine, which is important for various metabolic pathways. The negative effects of high homocysteine include impaired mitochondrial function and reduced ATP. 

Symptoms of B12 deficiency

B12 is so fundamental to cellular health, that suboptimal levels can lead to widespread signs and symptoms, including (but not limited to):

• Fatigue: Feeling unusually tired or weak.
• Hormonal or mood imbalances: Depression, irritability, or mood swings.
• Pain and inflammation of the mouth or tongue: Ulcers, or a sore, red tongue, glossitis.
• Cognitive impairment: Memory loss, confusion, brain fog or difficulty concentrating.
• Shortness of breath/dizziness: Especially noticeable during exercise.
• Nerve issues: Tingling or numbness in the hands and feet.
• Pale or jaundiced skin: Skin appears pale or slightly yellow.
• Digestive disturbances: Constipation, diarrhoea or gas.
• Balance/visual: Difficulty maintaining balance or impaired vision.

B12-rich diet

Incorporating vitamin B12-rich foods into your diet is key to ensuring you maintain healthy levels. B12 is concentrated in animal tissues and therefore is found in foods of animal origin.[vi]

For those that do consume animal-based foods, high-quality sources include seafood, as well as liver, beef, poultry, and pork. Dairy products also provide good sources, as do eggs, especially the yolks.

For those adhering to plant-based diets, achieving sufficient B12 intake can be more challenging due to the absence of naturally occurring B12 in plants. However, fortified foods such as plant-based milks, breakfast cereals, and nutritional yeast can contribute to requirements.

In one recent meta-analysis groups following a vegan or vegetarian diet did not demonstrate increased risk of vitamin B12 deficiency due to the widespread consumption of fortified foods and supplementation.[vii]

However, even with adequate dietary intake, some individuals may experience suboptimal B12 status due to a range of factors outlined below. 

Vitamin B12 absorption and utilisation

Of all the vitamins and minerals, B12 has perhaps the most complex absorption and utilisation mechanisms. Let’s take a look below at this multi-step process:

1. Release from food: Vitamin B12 is bound to protein in food and must be released before it is absorbed. This process starts in the mouth when food is mixed with saliva. The freed vitamin B12 then binds with haptocorrin, a cobalamin-binding protein in the saliva.[viii] In the stomach, hydrochloric acid and gastric protease help further break down the protein-B12 complex.
2. Binding to intrinsic factor: In the duodenum, digestive enzymes free the vitamin B12 from haptocorrin, and this freed vitamin B12 combines with intrinsic factor (a transport and delivery binding protein secreted by the stomach’s parietal cells). Without intrinsic factor, B12 cannot be effectively absorbed by the intestines.
3. Transport to the small intestine: The B12-IF complex travels to the ileum of the small intestine, where specialised receptors help it bind to intestinal cells.
4. Absorption: B12 is absorbed into the bloodstream and transported to the liver and other tissues.
5. Storage and utilisation: Generally, around 50% of active B12 is delivered directly to the liver for storage, while the rest is circulated for use in the body tissues.

This process relies on adequate stomach acid, intrinsic factor, and small intestine function. Any disruption to these can impair absorption and contribute to low B12 status. (It is worth noting that in supplement form, B12 is already in free form and therefore does not require the separation step.)

Factors that impact absorption and contribute to low B12 status 

Gastrointestinal disorders

Conditions such as gastritis, acid reflux, and Helicobacter pylori infection can contribute to low stomach acid, impairing B12 release from food. Issues with intrinsic factor, such as in pernicious anaemia (an autoimmune attack against the parietal cells in the stomach) prevent B12 absorption in the small intestine. Diseases including Crohn’s, ulcerative colitis and coeliac disease can also damage the small intestine, affecting the area where B12 is absorbed, while small intestinal bacterial overgrowth (SIBO) can consume B12 before absorption and damage the cells that produce intrinsic factor.

Stress

Stress affects us all at times and when it is prolonged, it can take a significant toll on both our physical and mental health. Chronic stress affects appetite, disrupts digestion, reduces digestive efficiency, and can cause inflammation of the gut, impairing B12 absorption. It may also lead to poor dietary choices and increased nutrient demand, exacerbating a deficiency. Meditation, regular gentle exercise, yoga and adequate sleep are effective strategies to counteract stress.

Diet

B12 is found in animal-based foods meaning that vegetarians and vegans are at higher risk of deficiency, since plant-based foods lack B12.

Age

B12 deficiency is common in older adults, affecting up to 20% of those over 60. Reduced stomach acid, medication use, and poor appetite contribute to the increased risk in this age group.

Medications

Proton Pump Inhibitors and H2 Blockers for acid reflux and ulcers reduce stomach acid, necessary for B12 absorption.[ix] Metformin, commonly used to treat type II diabetes, can decrease B12 absorption in the gut, especially with long-term use.[x] Long-term deficiency of B12 can lead to serious conditions such as neuropathy and anaemia, so it’s important for those taking medications to monitor their B12 levels and consider supplementation if necessary.

Genetics

Specific genetic variations can affect the production or function of proteins involved in absorption and metabolism of B12. For example, mutations in the TCN2 gene, which encodes for transcobalamin II (a protein that helps transport B12 in the bloodstream), can impair B12 delivery to tissues. Similarly, variations in the IF gene, which codes for intrinsic factor, can reduce the efficiency of B12 uptake. Additionally, genetic differences can impact the enzymes involved in converting B12 into its active forms.

Pregnancy and breastfeeding

During pregnancy, the body’s need for vitamin B12 increases to support the developing foetus. However, various factors can affect B12 levels during this time. Hormonal and digestive changes may make it more challenging for the body to absorb B12, while changes in appetite and cravings can impact dietary intake. Ensuring sufficient B12 levels throughout pregnancy however, is essential, as a deficiency can lead to complications such as anaemia in the mother and neural tube defects in the baby.[xi] 

B12 supplementation: the different forms available and their benefits

The factors above are examples in which B12 supplementation may be necessary, even alongside a B12-rich diet. Vitamin B12 is available in various forms, each suited to different needs based on individual requirements. In a recent systematic review and meta-analysis, all routes of administration of B12 (oral, sublingual, intramuscular) were found to be effective.[xii] Below, we will review the different forms of B12 supplements and when each might be most appropriate:

Cyanocobalamin

• Synthetic form of B12: Cyanocobalamin is commonly used in supplements because it is stable and inexpensive – it is not present in nature.
• Inactive form: This form of B12 is not immediately usable by the body. It requires four metabolic steps to convert into the active forms.
• Conversion challenges: Some individuals, especially those with genetic mutations or health conditions affecting absorption, may find it difficult to efficiently convert into active forms.
• Cyanide content: While this amount is typically harmless, it can pose issues for people with compromised liver or kidney function, or for smokers. The presence of cyanide can make absorption more difficult as a methyl donor is required to detoxify the cyanide from the body.

Hydroxocobalamin

• Natural form: One of the natural forms of B12. It still needs three steps to be converted into active forms.
• Longer half-life: This form stays in the body longer compared to cyanocobalamin and has a very good sustained release making it effective for restoring B12 levels over a longer period.
• Broad use: Hydroxocobalamin is often used for long-term B12 supplementation and treatment of severe deficiencies. It is commonly administered via injection. Non-methylated form, making it suitable for individuals who experience adverse reactions to methyl groups.
• Detoxification: Does not contain cyanide. In fact, it helps the body excrete cyanide through the urine, making it ideal for severe deficiencies, injectable therapy, and detoxification scenarios. 

Methylcobalamin

• Active form: One of the two active forms, meaning it can be directly used by the body without needing conversion.
• Role in methylation: Plays a crucial role in methylation reactions, which are essential for producing neurotransmitters and maintaining proper nerve function and regeneration.
• Neurological health: Due to its direct involvement in nerve function, methylcobalamin is often preferred for supporting neurological health.
• Better absorption: Particularly beneficial for those who have difficulty converting inactive forms of B12. It can be absorbed more effectively, especially when taken sublingually.

Adenosylcobalamin

• Active form: The other active form of B12, primarily involved in mitochondrial function and energy production.
• Energy Production: This form supports energy production at the cellular level, making it particularly useful for individuals with fatigue-related conditions or those needing mitochondrial support.
• Combination use: Often used in combination with methylcobalamin to ensure optimal B12 activity in the body.

Summary

Ensuring sufficient vitamin B12 intake is key to sustaining optimal energy levels, supporting cognitive function, and promoting overall well-being.

While a well-balanced diet may provide many people with adequate B12, its complex absorption and utilisation processes mean that individuals should be mindful of the factors that can impact B12 status and supplementation may be necessary for many individuals.

A deficiency in vitamin B12 is normally established by a blood test and this is an important step to consider, particularly in certain instances outlined above or if experiencing symptoms.  Medical professionals are aware of the importance of vitamin B12 and frequent tests for this nutrient are becoming increasingly common.

With a broader understanding of the factors that can contribute to low B12 and with knowledge of the wide range of symptoms that can arise from deficiency, we can take proactive measures to support our diet, health and lifestyle.

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References

[i] Tardy, A. L., Pouteau, E., Marquez, D., Yilmaz, C., & Scholey, A. (2020). Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence. Nutrients, 12(1), 228.

[ii] Dunn J, Grider MH. Physiology, Adenosine Triphosphate. [Updated 2023 Feb 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK553175/

[iii] Allen L. H. (2012). Vitamin B-12. Advances in nutrition (Bethesda, Md.), 3(1), 54–55.

[iv] Allen L. H. (2012). Vitamin B-12. Advances in nutrition (Bethesda, Md.), 3(1), 54–55.

[v] Halczuk, K., Kaźmierczak-Barańska, J., Karwowski, B. T., Karmańska, A., & Cieślak, M. (2023). Vitamin B12-Multifaceted In Vivo Functions and In Vitro Applications. Nutrients, 15(12), 2734.

[vi] O’Leary, F., & Samman, S. (2010). Vitamin B12 in health and disease. Nutrients, 2(3), 299–316.

[vii] Janko, R. K., Haussmann, I., & Patel, A. (2025). Vitamin B12 Status in Vegan and Vegetarian Seventh-Day Adventists: A Systematic Review and Meta-Analysis of Serum Levels and Dietary Intake. American journal of health promotion : AJHP, 39(1), 162–171.

[viii] https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/

[ix] Mumtaz, H., Ghafoor, B., Saghir, H., Tariq, M., Dahar, K., Ali, S. H., Waheed, S. T., & Syed, A. A. (2022). Association of Vitamin B12 deficiency with long-term PPIs use: A cohort study. Annals of medicine and surgery (2012), 82, 104762.

[x] Sayedali, E., Yalin, A. E., & Yalin, S. (2023). Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes. World journal of diabetes, 14(5), 585–593.

[xi] Molloy, A. M., Kirke, P. N., Troendle, J. F., Burke, H., Sutton, M., Brody, L. C., Scott, J. M., & Mills, J. L. (2009). Maternal vitamin B12 status and risk of neural tube defects in a population with high neural tube defect prevalence and no folic Acid fortification. Pediatrics, 123(3), 917–923.

[xii] Abdelwahab, O. A., Abdelaziz, A., Diab, S., Khazragy, A., Elboraay, T., Fayad, T., Diab, R. A., & Negida, A. (2024). Efficacy of different routes of vitamin B12 supplementation for the treatment of patients with vitamin B12 deficiency: A systematic review and network meta-analysis. Irish journal of medical science, 193(3), 1621–1639

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nutrition@cytoplan.co.uk
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Further reading: B12 Deficiency: An issue of widespread concern

Last updated on 30th January 2025 by cytoffice