Vitamin B12 deficiency

Vitamin B12 deficiency

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Katie Stone - Naturopath

Written By:

Katie Stone - Naturopath
Kari Asadorian - BSN, RN

Medical Reviewer:

Kari Asadorian - BSN, RN
Jamie Hope - Methyl-Life® Founder

Edited By:

Jamie Hope - Methyl-Life® Founder

Updated On:

October 20, 2025

What is B12 deficiency?

Vitamin B12 deficiency develops when the body lacks enough of this essential nutrient to sustain normal function. B12 is required for numerous processes, including red blood cell production, nervous system health, neurotransmitter synthesis, and the metabolism of homocysteine.1


Chronic B12 deficiency can lead to serious health conditions such as megaloblastic anemia, fatigue, peripheral neuropathy, cognitive decline, and mood disorders.2

Symptoms of B12 deficiency

B12 deficiency can affect the gastrointestinal tract, blood, and nervous system. Symptoms may range from mild fatigue to anemia to severe neurological impairment.


Cutaneous signs of B12 deficiency

  • Nail hyperpigmentation (blue-black discoloration and dark streaks)
  • Hair changes (dull, sparse, or premature gray hair)
  • Skin hyperpigmentation
  • Glossitis (inflammation of the tongue)
  • Vitiligo


Gastrointestinal signs of B12 deficiency

  • Diarrhea
  • Weight loss


Hematological signs of B12 deficiency

  • Megaloblastic anemia
  • Macrocytic anemia
  • Fatigue 
  • Pallor
  • Jaundice (due to increased hemolysis caused by impaired red blood cell formation)
  • Decreased hemoglobin levels 
  • Pancytopenia


Neurological signs of B12 deficiency

  • Sensory changes (numbness, tingling, and pins and needles, especially in the hands and feet, due to myelin sheath damage).
  • Poor memory 
  • Mental health changes 
  • Peripheral neuropathy
  • Cognitive decline

Causes of B12 deficiency

Autoimmune
Pernicious anemia is an autoimmune condition in which the immune system attacks intrinsic factor, the protein required to break down B12. This means B12 cannot be absorbed by the ileum.3


Malabsorption
Impairment to intrinsic factor (IF) production or damage to the gastrointestinal system can result in malabsorption of B12. This can occur in cases such as:

  • Gastric bypass surgery (resulting in loss of IF production site)
  • Damage to the terminal ileum due to surgery or inflammatory bowel disorders (such as Crohn's disease).  Gastritis and other stomach conditions can also interfere with uptake.
  • Damage to the small intestine (due to inflammation from celiac disease or gastrointestinal infections) 
  • Other digestive conditions, including ulcerative colitis, Helicobacter pylori infection, and small intestinal bacterial overgrowth (SIBO)
  • Pancreatic insufficiency resulting in lack of pancreatic enzymes required to break down haptocorrin and release B12 so that it can bind with intrinsic factor


Genetic conditions
Inherited conditions such as Imerslund-Gräsbeck syndrome, intrinsic factor deficiency, and transcobalamin deficiency can also impair B12 absorption. These are generally rare.


Medications
Medications that reduce stomach acid or alter digestive function can affect uptake of B12. Common medications linked to impaired B12 absorption include metformin, proton pump inhibitors (PPIs), anticonvulsants and nitrous oxide.


Gynecological factors
Pregnancy increases the body’s demand for B12, which can then increase risk of deficiency. Oral contraceptives may also reduce B12 uptake.


Dietary insufficiency
People who follow a strict vegan or vegetarian diet may develop B12 deficiency as B12 is only present in animal foods.

How to test for B12 deficiency

Tests to determine B12 deficiency may include:

  • B12 and folate serum tests to directly measure the concentration of vitamin B12 in the blood
  • Complete blood count (CBC) which measures hemoglobin. Anemia appears as a decrease in both hemoglobin and hematocrit.
  • Peripheral blood smear to examine blood cells at microscopic level
  • Methylmalonic acid (MMA) testing. MMA is a metabolic byproduct that accumulates as B12 decreases, so the level of MMA in your blood can be a more sensitive indicator of B12 deficiency. 
  • Homocysteine testing. Elevated homocysteine levels can mean that your B12 is low, as B12 is required for recycling homocysteine.4

Risk factors and other health problems due to B12 deficiency

Hematological disorders:

  • Megaloblastic anemia (abnormally large red blood cells due to impaired DNA synthesis)
  • Cytopenia (reduction in numbers of mature blood cells) 
  • Hemolytic anemia (red blood cells are broken down faster than they are replaced) 
  • Hemolysis (reduced red blood cell lifespan, elevated bilirubin, elevated LDH)


Neurological disorders:

  • Myelopathy including subacute combined degeneration (SCD) due to impaired myelin synthesis5
  • Cerebellar ataxia (balance and coordination complications) 
  • Sensory deficits/paresthesia (numbness, tingling)


Neuropsychiatric disorders

  • Peripheral neuropathy6
  • Cognitive decline and some forms of dementia7
  • Depression8
  • Mental changes, including apathy, agitation, impaired concentration, insomnia, delusions9


Metabolic disorders

  • Hyperhomocysteinemia (elevated homocysteine)10


Reproductive issues

  • Infertility or difficulty conceiving11
  • Pregnancy complications (developmental anomalies, miscarriage, preeclampsia, low birth weight)12

Treatment for B12 deficiency

Pharmaceutical treatment for B12 deficiency

  • Severe deficiency is usually treated with intramuscular B12 injections, which bypass the digestive system to deliver the nutrient directly into the bloodstream. 
  • Oral B12 supplements (usually cyanocobalamin - even though research suggests the active forms are more effective) may also be prescribed at a dosage of 1000 mcg/day.  High doses are required for oral B12 because it must be broken down in the digestive tract, which involves both intrinsic factor and passive diffusion.13
  • Cyanocobalamin nasal spray provides 500 mcg B12 per spray. This is also an effective option for restoring B12 levels as it bypasses the digestive system. 

Natural treatment for B12 deficiency

Natural, active B12 supplements are available as methylcobalamin (MeCbl) and adenosylcobalamin (AdCbl). Hydroxocobalamin is the precursor of methylcobalamin and adenosylcobalamin. These forms are bioidentical to the B12 in the human body and in animal foods. Cyanocobalamin occurs only in trace amounts in the body.


Several studies show that supplementing with natural, active forms of B12 may be more efficient than cyanocobalamin.14 This is because cyanocobalamin must be processed and converted to its active form in the body before it can be used, whereas the natural forms are readily usable.15 For people with certain genetic or metabolic conditions that slow or impair B12 absorption, these bioavailable forms are considered preferable as they require no further conversion in the body.


B12 supplements that bypass the digestive tract - such as intramuscular injections, nasal spray, and sublingual supplements -  are generally more efficiently absorbed than tablets or capsules. Sublingual B12 supplements are particularly effective as they are absorbed via the mucous membranes under the tongue, bypassing digestive acids and the liver.


A 2024 meta-analysis found that sublingual methylcobalamin is as effective as intramuscular and sublingual cyanocobalamin for improving B12 levels.16 Other research suggests that sublingual B12 is often preferred by patients, especially those who are uncomfortable with injections, and/or require long-term supplementation.

Sublingual B12 is absorbed under the tongue and is shown to be as effective as injections. Sublingual B12 is convenient, well-tolerated, and generally preferred by patients who require long-term supplementation.17

B12 deficiency and vegan diet

Vegans and vegetarians are more likely to be deficient in B12 as the nutrient is only present in animal foods. Pregnant women and women of child-bearing age who eat a strictly plant-based diet are at even higher risk.18


Clinicians recommend that vegan and vegetarians supplement with B12 daily to prevent deficiency.

Vitamin B12 deficiency

Key takeaways

  • Icon Deficiency in B12 can occur as a result of pernicious anaemia, malabsorption, and/or dietary insufficiency
  • Icon Untreated B12 deficiency can lead to serious neurological and/or hematological health issues
  • Icon Treatment options may include B12 intramuscular injections, oral supplements, and sublingual supplements

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  • Methylcobalamin B12, Hydroxy B12 & Adenosylcobalamin
  • 3rd-Party Tested for Purity, Potency & Safety
  • 90 Vegan, Non-GMO, Chewable Mint Tablets

Frequently Asked Questions about vitamin B12 deficiency

What causes B12 deficiency?

B12 deficiency can have multiple causes, including insufficient dietary intake (due to vegan or vegetarianism), malabsorption due to pernicious anemia, gastrointestinal damage or surgery, medications, poor pancreatic function, and/or genetic disorders affecting intrinsic factor or B12 receptors.

Can Vitamin B12 deficiency be a sign of cancer?

B12 deficiency is not necessarily a sign of cancer, but some research suggests that insufficient intake of B12 may have a role in carcinogenesis due to the critical role B12 plays in regulating DNA synthesis and DNA methylation. While further research is pending, it has been suggested that deficiency in B12 affects methylation patterns, leading to genomic instability and abnormal gene expression.19

What are the symptoms of a low B12 level?

Possible signs of low B12 may include fatigue, shortness of breath, muscle weakness, paleness, numbness or tingling in the hands or feet, low mood, irritability, memory difficulties, and a sore tongue or mouth.

How do you fix a B12 deficiency?

You can restore your B12 levels with intramuscular injections or oral B12 supplements. Active forms of B12 in the form of sublinguals are available without prescription and are shown to be as effective as intramuscular supplementation.20

References

  1. Aimee Rachel Mathew, Giacomo Di Matteo, Piergiorgio La Rosa, Saviana Antonella Barbati, Luisa Mannina, Sandra Moreno, Ada Maria Tata, Virve Cavallucci, Marco Fidaleo; "Vitamin B12 Deficiency and the Nervous System: Beyond Metabolic Decompensation-Comparing Biological Models and Gaining New Insights into Molecular and Cellular Mechanisms"; International journal of molecular sciences; 2024 Jan

    https://pubmed.ncbi.nlm.nih.gov/38203763/

  2. Milind Umekar, Tanvi Premchandani, Amol Tatode, Mohammad Qutub, Neha Raut, Jayshree Taksande, Ujban Md. Hussain; "Vitamin B12 deficiency and cognitive impairment: A comprehensive review of neurological impact"; Brain Disorders; 2025 Jun

    https://www.sciencedirect.com/science/article/pii/S266645932500040X

  3. Sarosh Vaqar, Karen B. Shackelford; "Pernicious Anemia"; StatPearls [Internet]; 2023 May

    https://www.ncbi.nlm.nih.gov/books/NBK540989/

  4. Sae-Mi Lee, Jongwon Oh, Mi-Ryung Chun, Soo-Youn Lee; "Methylmalonic Acid and Homocysteine as Indicators of Vitamin B12 Deficiency in Patients with Gastric Cancer after Gastrectomy"; Nutrients; 2019 Feb

    https://pmc.ncbi.nlm.nih.gov/articles/PMC6412945/

  5. Shambaditya Das, Souvik Dubey, Alak Pandit, Biman Kanti Ray; "Myeloradiculoneuropathy due to vitamin B12 deficiency: an unusual clinical and radiological presentation"; BMJ case reports; 2021 Jan

    https://pmc.ncbi.nlm.nih.gov/articles/PMC7839883/

  6. Ahmed Badar; "Neuropsychiatric Disorders Associated With Vitamin B12 Deficiency: An Autobiographical Case Report"; Cureus; 2022 Jan

    https://pmc.ncbi.nlm.nih.gov/articles/PMC8858590/

  7. Shazia Jatoi, Abdul Hafeez, Syeda Urooj Riaz, Aijaz Ali, Muhammad Ishaq Ghauri, Maham Zehra; "Low Vitamin B12 Levels: An Underestimated Cause Of Minimal Cognitive Impairment And Dementia"; Cureus; 2020 Feb

    https://pmc.ncbi.nlm.nih.gov/articles/PMC7077099/

  8. Prerna Sangle, Osama Sandhu, Zarmeena Aftab, Adarsh Thomas Anthony, Safeera Khan; "Vitamin B12 Supplementation: Preventing Onset and Improving Prognosis of Depression"; Cureus; 2020 Oct

    https://pmc.ncbi.nlm.nih.gov/articles/PMC7688056/

  9. Prashant Sahu, Harish Thippeswamy, Santosh K Chaturvedi; "Neuropsychiatric manifestations in vitamin B12 deficiency"; Vitamins and hormones; 2022

    https://pubmed.ncbi.nlm.nih.gov/35337631/

  10. Dhipak Arthur, Deepa John, Jude Joseph Fleming, Grace Rebekah, Mahasampath Gowri, Sheeja Susan John; "Role of hyperhomocysteinemia and Vitamin B12 deficiency in central and hemi-central retinal vein occlusion: A case–control study"; Oman journal of ophthalmology; 2022 Mar

    https://pmc.ncbi.nlm.nih.gov/articles/PMC8979380/

  11. Audrey J Gaskins, Yu-Han Chiu, Paige L Williams, Jennifer B Ford, Thomas L Toth, Russ Hauser, Jorge E Chavarro, for the EARTH Study Team; "Association between serum folate and vitamin B-12 and outcomes of assisted reproductive technologies"; The American journal of clinical nutrition; 2015 Sep

    https://pmc.ncbi.nlm.nih.gov/articles/PMC4588741/

  12. Julia L Finkelstein, Alexander J Layden, Patrick J Stover; "Vitamin B-12 and Perinatal Health"; Advances in nutrition; 2015 Sep

    https://pmc.ncbi.nlm.nih.gov/articles/PMC4561829

  13. Hans Berlin, Ragnar Berlin, Gunnar Brante; "ORAL TREATMENT OF PERNICIOUS ANEMIA WITH HIGH DOSES OF VITAMIN B12 WITHOUT INTRINSIC FACTOR"; Journal of Internal Medicine; 1968

    https://onlinelibrary.wiley.com/doi/10.1111/j.0954-6820.1968.tb02452.x

  14. 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; 2017 Feb

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

  15. A S M Al Amin, Vikas Gupta; "Vitamin B12 (Cobalamin)"; StatPearls [Internet]; 2023 Jul

    https://www.ncbi.nlm.nih.gov/books/NBK559132/

  16. Omar Ahmed Abdelwahab, Ahmed Abdelaziz, Sherein Diab, Ali khazragy, Toka Elboraay, Taha Fayad, Rehab Adel Diab, Ahmed Negida; "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; 2024 Jan

    https://link.springer.com/article/10.1007/s11845-023-03602-4

  17. Omar Ahmed Abdelwahab, Ahmed Abdelaziz, Sherein Diab, Ali khazragy, Toka Elboraay, Taha Fayad, Rehab Adel Diab, Ahmed Negida; "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; 2024 Jan

    https://pmc.ncbi.nlm.nih.gov/articles/PMC11128391/

  18. Ali Niklewicz, A David Smith, Alison Smith, Andre Holzer, Andrew Klein, Andrew McCaddon, Anne M Molloy, Bruce H R Wolffenbuttel, Ebba Nexo, Helene McNulty, Helga Refsum, Jean-Louis Gueant, Marie-Joe Dib, Mary Ward, Michelle Murphy, Ralph Green, Kourosh R Ahmadi, Luciana Hannibal, Martin J Warren, P Julian Owen, on behalf of CluB-12; "The importance of vitamin B12 for individuals choosing plant-based diets"; European journal of nutrition; 2022 Dec

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10030528/

  19. Alexandra K Loedin, Dave Speijer; "Is There a Carcinogenic Risk Attached to Vitamin B12 Deficient Diets and What Should We Do About It? Reviewing the Facts"; Molecular nutrition & food research; 2021 Feb

    https://pmc.ncbi.nlm.nih.gov/articles/PMC8126961/

  20. Omar Ahmed Abdelwahab, Ahmed Abdelaziz, Sherein Diab, Ali khazragy, Toka Elboraay, Taha Fayad, Rehab Adel Diab, Ahmed Negida; "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; 2024 Jan

    https://link.springer.com/article/10.1007/s11845-023-03602-4

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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