Can vitamin deficiencies, such as vitamin B12 (cobalamin) and vitamin D, contribute to mood swings in an adult patient?

Vitamin Deficiencies and Mood Swings

Yes, vitamin deficiencies—particularly vitamin B12, folate (B9), and vitamin D—can directly cause mood swings and other psychiatric symptoms including depression, and should be screened for in patients presenting with mood disturbances.

Evidence Linking Vitamin Deficiencies to Mood Disturbances

Vitamin B12 Deficiency and Mood

• Vitamin B12 deficiency causes an extensive range of neuropsychiatric symptoms, including mood disturbances and depression, which often appear before macrocytic anemia develops 1
• B12 is essential for preserving the myelin sheath around neurons and serves as a cofactor for methionine synthase, which is crucial for brain metabolism and neurotransmitter production 2
• In a 2025 cross-sectional study of 1003 patients with severe mental illnesses, B12 deficiency was linked to greater psychiatric symptom severity and metabolic disturbances 3
• Low vitamin B12 status has been found in multiple studies of depressive patients, and an association between depression and low B12 levels is consistently found in general population studies 4
• B vitamins (particularly B1, B3, B6, B9, and B12) are essential for neuronal function, monoamine oxidase production, and DNA synthesis—deficiencies have been directly linked to depression 5

Vitamin D Deficiency and Mood

• Vitamin D deficiency was significantly associated with worse psychiatric outcomes, including increased depressive symptoms (adjusted OR = 1.89, p = 0.018) and lower Global Assessment of Functioning scores (adjusted OR = -0.18, p < 0.001) 3
• In children and adolescents with depression, vitamin D levels were clearly low compared to controls (p < 0.001), with a negative correlation between depression severity and vitamin D levels 6
• Seasonal Affective Disorder (SAD) is associated with insufficient sunlight exposure and vitamin D deficiency, though supplementation studies show inconsistent results due to methodological variations 7

Folate (Vitamin B9) Deficiency and Mood

• Low plasma and red cell folate have been found in studies of depressive patients, with low folate levels linked to poor response to antidepressants 4
• Folate deficiency was linked to greater psychiatric symptom severity in patients with severe mental illnesses 3
• Treatment with folic acid (800 mcg daily) is shown to improve response to antidepressants 4

Biochemical Mechanisms

One-Carbon Metabolism Pathway

• Folate and vitamin B12 are major determinants of one-carbon metabolism, in which S-adenosylmethionine (SAM) is formed—SAM donates methyl groups that are crucial for neurological function and neurotransmitter synthesis 4
• B12 deficiency impairs one-carbon metabolism, which is crucial for DNA synthesis and repair in neuronal cells, and leads to functional folate deficiency, creating a "methyl trap" 2
• Increased plasma homocysteine (a functional marker of both folate and B12 deficiency) is found in depressive patients and is associated with increased risk of depression 4

Neurological Impact

• B12 deficiency leads to elevated homocysteine levels (hyperhomocysteinemia), which has been associated with cognitive decline and is considered a potential mechanism in the development of dementia and mood disorders 2
• The vitamin is essential for mitochondrial metabolism in brain cells, which is necessary for energy production in neurons 2

Clinical Screening Recommendations

Who Should Be Screened

• Patients presenting with mood swings, depression, or other psychiatric symptoms should be tested for vitamin B12, folate, and vitamin D deficiencies 1, 6
• High-risk populations include: adults >75 years, patients on metformin >4 months, PPI or H2 blocker use >12 months, vegetarians/vegans, patients with autoimmune thyroid disease, and those with malabsorptive conditions 1

Diagnostic Algorithm

1. Initial testing should include serum total vitamin B12, folate, and 25-OH vitamin D levels 1, 6
2. For B12 interpretation:
   • <180 pg/mL confirms deficiency
   • 180-350 pg/mL is indeterminate—measure methylmalonic acid (MMA) to confirm functional deficiency

   • 350 pg/mL makes deficiency unlikely 1

3. MMA >271 nmol/L confirms functional B12 deficiency with 98.4% sensitivity 1
4. Homocysteine >15 μmol/L supports B12 or folate deficiency diagnosis, though it is less specific than MMA 1

Treatment Recommendations

Vitamin B12 Deficiency

• Oral vitamin B12 1000-2000 mcg daily is as effective as intramuscular administration for most patients, including those with malabsorption 1
• For patients with neurological involvement, hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement, then maintenance of 1 mg IM every 2 months for life 1
• Treatment with high-dose B12 (1 mg daily) orally or parenterally can effectively correct biochemical deficiency and improve cognition in patients with pre-existing B12 deficiency 8

Folate Supplementation

• Oral doses of folic acid (800 mcg daily) should be tried to improve treatment outcome in depression 4
• Never administer folic acid before treating B12 deficiency, as it may mask anemia while allowing irreversible neurological damage to progress 1

Vitamin D Supplementation

• While vitamin D deficiency is associated with depression, supplementation studies show variable results 7
• Correction of documented vitamin D deficiency is reasonable given the association with mood symptoms 3

Critical Clinical Pitfalls

• Standard serum B12 testing misses functional deficiency in up to 50% of cases—the Framingham Study found that while 12% had low serum B12, an additional 50% had elevated MMA indicating metabolic deficiency despite "normal" serum levels 1
• Neurological and psychiatric symptoms often appear before hematologic changes (macrocytic anemia) develop, so normal blood counts do not rule out B12 deficiency 1
• Low folate levels are linked to poor response to antidepressants, making screening particularly important before initiating psychiatric treatment 4
• In children and adolescents with depression, there was a positive correlation between depression severity and homocysteine, and negative correlations with vitamin B12 and vitamin D 6