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One nutritional imbalance related to depression is Cobalamin, also known as Vitamin B12, is one of the most important water-soluble vitamins. The primary functions of Vitamin B12 are appropriate red blood cell formation, neurological functioning, and DNA synthesis [1]. Deficiency of Vitamin B12 can result in hematological changes, neurological and psychiatric problems, which can manifest as irritability, changes in personality, depression, and memory loss [2]. It is also known to worsen depression by excitotoxic reactions caused by the accumulation of homocysteine [3].


Higher homocysteine levels are associated with a phenomenon called "methionine loading." A deficiency of Vitamin B12 along with B6 and folate usually prevents the conversion of homocysteine to methionine, increasing the levels of homocysteine. Hyperhomocysteinemia can also occur in patients with renal disorders or genetic alterations of methyl-tetrahydro-folate reductase (MTHFR) or cystathionine beta-synthetase (CBS), which are required for the metabolism of homocysteine [4,5]. Higher levels of homocysteine affect the DNA formation and overall turnover of red blood cells (RBCs), causing the development of megaloblastic or pernicious anemia, ultimately affecting the cognitive ability and mood of the patient [6].


Vitamin B12 deficiency is reportedly known to cause mental disturbances. Cobalamin is one of the essential elements for monoamine neurotransmitter synthesis in the brain. A study published in 2011 in the Academy of Psychosomatic Medicine included supplementation of Vitamin B12 and folate, which resulted in improved cognitive functioning among patients participating in the study. A borderline Vitamin B12 level of 75-95 pg/mL, as well as up to a normal level of 307 pg/mL, is known to cause neuropsychiatric symptoms in patients, and such symptoms may start manifesting even with such borderline deficiencies or low normal levels of Vitamin B12 [7].

Figure 1 gives an overview of the various neurochemical pathways affected by Vitamin B12 levels, which ultimately leads to some form of depressive disorder or episode (8).



Although other vitamins like Vitamin B6 and folate are known to have an impact on depression, we have presented information on Vitamin B12 to give you an overview of how a single nutrient imbalance can contribute to depression. 


1. Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. Morris MS, Jacques PF, Rosenberg IH, Selhub J. Am J Clin Nutr. 2007;85:193–200. 

2. Vitamin B12 deficiency. Oh R, Brown DL. Am Fam Physician. 2003;67:979–986. 

3. Clinical spectrum and diagnosis of cobalamin deficiency. Stabler SP, Allen RH, Savage DG, Lindenbaum J. Blood. 1990;76:871–881.

4. Homocysteine, renal function, and risk of cardiovascular disease. Clarke R, Lewington S, Landray M. Kidney Int Suppl. 2003;63:131.

5. The kidney and homocysteine metabolism. Friedman AN, Bostom AG, Selhub J, Levey AS, Rosenberg IH. J Am Soc Nephrol. 2001;12:2181–2189. 

6. Folic acid with or without vitamin B12 for cognition and dementia. Malouf M, Grimley EJ, Areosa SA. Cochrane Database Syst Rev. 2003. 

7. Acute psychotic depression as a sole manifestation of vitamin B12 deficiency. Bar-Shai M, Gott D, Marmor S. Psychosomatics. 2011;52:384–386.

8. Vitamin B12 Supplementation: Preventing Onset and Improving Prognosis of Depression. Sangle P, Sandhu O, Aflab Z, Anthony A, Khan S. Cereus. 2020:12:10

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