Vitamin B12, Folate, and Homocysteine in Depression

27 January 2025
Dr Fahd Al Qureshah
Vitamin B12, Folate, and Homocysteine in Depression

This "Vitamin B12, Folate, and Homocysteine in Depression: The Rotterdam Study" investigates the relationship between vitamin B12, folate, and homocysteine levels and depression in an elderly population. The key findings and methodological details are summarized below.

Study Objective

The primary objective was to evaluate the associations between deficiencies in vitamin B12 and folate, elevated homocysteine levels, and depressive symptoms or disorders. These nutrients are vital for one-carbon metabolism, which plays a role in monoamine neurotransmitter synthesis, potentially influencing mood and depression.


Methodology

  • Population: The study involved community-dwelling elderly individuals aged 55 years and older in Rotterdam. Data were collected during the third survey of the Rotterdam Study (1997–1999).
  • Sample Size: Of 5,901 invited participants, 3,884 underwent depression screening, and 278 (7.0%) had depressive symptoms. Among these, 112 were clinically diagnosed with depressive disorders based on DSM-IV criteria.
  • Screening Tool: Depression was screened using the Center for Epidemiological Studies Depression Scale (CES-D), with scores ≥16 indicating depressive symptoms.
  • Biochemical Measures:
  • Vitamin B12 Deficiency: <258 pmol/L
  • Folate Deficiency: <11.4 nmol/L and homocysteine >13.9 µmol/L
  • Hyperhomocysteinemia: >15.0 µmol/L
  • Statistical Analysis: Associations were analyzed using logistic regression models, adjusting for age, gender, cardiovascular risk factors, and functional disability.


Results

Demographics and Characteristics

  • The mean age of participants was 72.9 years (SD = 7.1).
  • Women constituted a larger proportion of the depressed group (73% vs. 58%; p < 0.001).
  • Depressed individuals exhibited greater functional disability (mean score: 0.8 vs. 0.5; p < 0.001) and lower Mini-Mental State Examination (MMSE) scores (27 vs. 28; p < 0.001).

Nutritional and Biochemical Findings

Vitamin B12 Deficiency:

  • Depressed individuals were 70% more likely to have vitamin B12 deficiency (OR = 1.69; 95% CI: 1.10–2.56; p = 0.02).
  • This association remained significant even after adjusting for cardiovascular risk factors and functional disability (OR = 1.63; 95% CI: 1.03–2.56; p = 0.04).

Folate Deficiency:

  • A nonsignificant trend was observed between folate deficiency and depressive disorders after adjustments (OR = 0.97; 95% CI: 0.51–1.87; p = 0.98).

Hyperhomocysteinemia:

  • Individuals with depressive disorders had higher homocysteine levels (mean: 11.7 µmol/L vs. 10.6 µmol/L; p = 0.01).
  • The association weakened after adjusting for cardiovascular and functional factors (mean difference: 0.2 µmol/L; p = 0.66).

Loss of Appetite:

  • Hyperhomocysteinemia was significantly associated with self-reported loss of appetite (OR = 1.32; 95% CI: 1.03–1.70; p = 0.03), while vitamin B12 deficiency was not (p = 0.73).

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Discussion

Key Findings

  • Vitamin B12: There is strong evidence linking vitamin B12 deficiency to depressive disorders, suggesting a possible causal relationship. Unlike folate, this association appears to be independent of cardiovascular comorbidities and functional impairments.
  • Folate and Homocysteine: The relationships between folate deficiency, hyperhomocysteinemia, and depression are likely mediated by physical comorbidities and cardiovascular factors.
  • Mechanisms: While vitamin B12 may directly influence monoamine metabolism, folate's impact might be confounded by nutritional intake and comorbid conditions.

Strengths and Limitations

Strengths:

  • The study used a large, population-based sample and DSM-IV criteria for depression diagnosis.
  • Adjustments for confounders such as cardiovascular risks and functional status provided robust results.

Limitations:

  • The cross-sectional design precludes conclusions about causality.
  • Appetite loss, a symptom of depression, could confound associations with nutrient deficiencies.


Conclusion

The study highlights the potential importance of vitamin B12 in managing depression, particularly in elderly populations. Clinicians should consider screening for and addressing vitamin B12 deficiency in depressed patients, especially given the potential benefits of supplementation. Folate and homocysteine also merit attention but appear more closely tied to physical health and cardiovascular factors than directly to depression.

For full details, refer to the original article: https://pubmed.ncbi.nlm.nih.gov/26799654/