Evidence-Based Nutrient Recommendations

Overt B12 Deficiency: Nerve Damage and Anemia


Ways to Get B12 Deficiency

The two main ways people get vitamin B12 deficiency are inadequate dietary intake and inadequate absorption from loss of intrinsic factor or lack of stomach acid.

Please note that the symptoms listed below are found in overt vitamin B12 deficiency. You can be B12 deficient, increasing your risk of disease because of elevated homocysteine without suffering any noticeable symptoms.

Early, Noticeable Symptoms of Overt B12 Deficiency (1)

  • Unusual fatigue
  • Faulty digestion
  • No appetite
  • Nausea
  • Loss of menstruation

Other Symptoms of Overt B12 Deficiency

  • Numbness and tingling of the hands and feet (1)
  • Lingual linear lesions of the tongue (15)
  • Nervousness (1)
  • Diarrhea (2)
  • Mild depression (1)
  • Striking behavioral changes (1)
  • Paranoia (1)
  • Hyperactive reflexes (1)
  • Fever (3)
  • Frequent upper respiratory infections (4)
  • Impotence (5)
  • Impaired memory (5)
  • Infertility (6)
  • Sore tongue (2)
  • Macrocytic anemia
  • Low platelet count (3, 7) and increased bleeding (3)
  • Neutropenia (3)
  • Skin hyperpigmentation (dark skin with even darker spots) (13)

Neurological Symptoms

Neurological symptoms, often referred to as subacute combined degeneration (SCD), are the biggest concern regarding B12 deficiency. The damage can be irreversible if not caught early enough. SCD affects peripheral nerves and the spinal cord, and is normally different in children than adults (8).

Optic Neuropathy

Vitamin B12 deficiency may trigger the onset of optic neuropathies such as Leber’s hereditary optic neuropathy (LHON) (14). People who suspect or are diagnosed with optic neuropathy should make sure they have adequate levels of B12.

Theories of How B12 Deficiency Causes Nerve Damage

There are 3 main theories as to how B12 deficiency causes nerve damage:

1. B12 deficiency produces a lack of methionine for conversion into S-adenosylmethionine (SAM) (9). SAM is required for the production of phosphatidylcholine (10) which is part of the myelin (the fatty material that insulates many nerves) (10). See Figure: Vitamin B12 Cycle.

2. The inability to convert methylmalonyl-CoA (a 3-carbon molecule) to succinyl-CoA (a 4-carbon molecule) results in an accumulation of propionyl-CoA (a 3-carbon molecule). Fatty acids are normally made by adding 2 carbons at a time to an even numbered carbon molecule. In an overabundance of 3 carbon molecules, large amounts of unusual 15-carbon and 17-carbon fatty acids may be produced and incorporated into nerve sheets, causing altered nerve function (11).

3. Nerves are damaged by different hormone-like molecules (cytokines, tumor necrosis factor, and epidermal growth factor) which become unbalanced in the nerve tissue in B12 deficiency (8).

When Is It Time to Call a Doctor?

There are some serious diseases that have similarities to B12 deficiency, including Guillian-Barre syndrome, Lyme neuropathy, heavy metal intoxication, and lupus myelopathy (12). Anyone who develops symptoms of nerve damage should see a doctor immediately for treatment.

Neural Tube Defects in Infants

A neural tube defect (NTD) is when the spinal cord or brain fails to form properly in a developing fetus; spina bifida and anencephaly are the two most common NTDs. Folic acid is the vitamin most often associated with NTDs, but poor B12 status has also been implicated. We discuss this more in Pregnancy, Infants, and Children.


1. Crane MG, Sample C, Pathcett S, Register UD. “Vitamin B12 studies in total vegetarians (vegans). Journal of Nutritional Medicine 1994;4:419-430.

2. Lindenbaum J, Healton EB, Savage DG, Brust JC, Garrett TJ, Podell ER, Marcell PD, Stabler SP, Allen RH. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med. 1988 Jun 30;318(26):1720-8.

3. Sarode R, Garewal G, Marwaha N, Marwaha RK, Varma S, Ghosh K, Mohanty D, Das KC. Pancytopenia in nutritional megaloblastic anaemia. A study from northwest India. Trop Geogr Med. 1989 Oct;41(4):331-6.

4. Crane MG, Register UD, Lukens RH, Gregory R. Cobalamin (CBL) studies on two total vegetarian (vegan) families. Vegetarian Nutrition. 1998; 2(3):87-92.

5. Ho C, Kauwell GP, Bailey LB. Practitioners’ guide to meeting the vitamin B-12 recommended dietary allowance for people aged 51 years and older. J Am Diet Assoc .1999 Jun;99(6):725-7.

6. Kuhne T, Bubl R, Baumgartner R. Maternal vegan diet causing a serious infantile neurological disorder due to vitamin B12 deficiency. Eur J Pediatr. 1991 Jan;150(3):205-8.

7. Refsum H, Yajnik CS, Gadkari M, Schneede J, Vollset SE, Orning L, Guttormsen AB, Joglekar A, Sayyad MG, Ulvik A, Ueland PM. Hyperhomocysteinemia and elevated methylmalonic acid indicate a high prevalence of cobalamin deficiency in Asian Indians. Am J Clin Nutr. 2001 Aug;74(2):233-41.

8. Scalabrino G. Subacute combined degeneration one century later. The neurotrophic action of cobalamin (vitamin B12) revisited. J Neuropathol Exp Neurol. 2001 Feb;60(2):109-20.

9. Groff J, Gropper S. Advanced Nutrition and Human Metabolism, 3rd ed. Wadsworth: 2000.

10. Grattan-Smith PJ, Wilcken B, Procopis PG, Wise GA. The neurological syndrome of infantile cobalamin deficiency: developmental regression and involuntary movements. Mov Disord. 1997 Jan;12(1):39-46.

11. von Schenck U, Bender-Gotze C, Koletzko B. Persistence of neurological damage induced by dietary vitamin B-12 deficiency in infancy. Arch Dis Child. 1997 Aug;77(2):137-9.

12. Licht DJ, Berry GT, Brooks DG, Younkin DP. Reversible subacute combined degeneration of the spinal cord in a 14-year-old due to a strict vegan diet. Clin Pediatr. (Phila). 2001 Jul;40(7):413-5.

13. Cherqaoui R, Husain M, Madduri S, Okolie P, Nunlee-Bland G, Williams J. A reversible cause of skin hyperpigmentation and postural hypotension. Case Rep Hematol. 2013;2013:680459. doi: 10.1155/2013/680459. Epub 2013 Jun 11.

14. Pott JW, Wong KH. Leber’s hereditary optic neuropathy and vitamin B12 deficiency. Graefes Arch Clin Exp Ophthalmol. 2006;244(10):1357-1359.

15. Bao ZX, Yang XW, Fang DD. Lingual Linear Lesions: A Clinical Sign Strongly Suggestive of Severe Vitamin B12 Deficiency. Nutr Clin Pract. 2021 Oct;36(5):1041-1048. (Abstract)

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