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Vitamin B12

Vitamin B12 and Mortality Risks: Analysis by Concentration Ranges

Introduction

Vitamin B12 (cobalamin) is an essential nutrient with critical roles in cellular metabolism, DNA synthesis, and neurological function. Recent research has revealed a complex relationship between serum vitamin B12 levels and mortality risk, with evidence suggesting both low and high levels may be associated with increased mortality under certain circumstances. This report examines the mortality risks associated with different vitamin B12 concentration ranges.

U-Shaped Relationship with Mortality

Current evidence demonstrates a U-shaped relationship between vitamin B12 levels and mortality risk, with both deficient and elevated levels associated with increased mortality compared to mid-range values:

  • For every 100 pmol/L increase in serum vitamin B12 concentration, there is a 4% higher risk of all-cause mortality in the general population and a 6% higher risk in older adults1
  • In MASLD (Metabolic dysfunction-associated steatotic liver disease) patients, serum vitamin B12 shows significant nonlinear associations with all-cause mortality, with risk decreasing as concentration increases from low levels, reaching lowest risk around the median level, and then leveling off2

Range-Specific Mortality Risks

Below 200 pg/mL (approximately <148 pmol/L)

Low vitamin B12 levels show mixed associations with mortality:

  • Serum B12 concentrations <140 pmol/L are associated with a moderate increase in all-cause mortality (HR 1.39, 95% CI 1.08–1.78) and cardiovascular mortality (HR 1.64, 95% CI 1.08–2.47)3
  • For vitamin B12 from supplements, concentrations less than 200 pg/ml may increase all-cause mortality, while dietary sources do not show the same effect1
  • In MASLD patients, low serum vitamin B12 levels are significantly associated with elevated risk of all-cause mortality compared to higher levels2

Clinical significance: Deficiency symptoms may occur even at levels considered within the lower reference range (>156 pmol/L)4, suggesting functional B12 deficiency may increase mortality risk even at "normal" lower values.

201-400 pg/mL (approximately 148-295 pmol/L)

This range appears to have lower mortality associations:

  • Serum B12 levels within 200-400 pmol/L did not show significant associations with increased mortality risk1
  • Research suggests that approximately 400 pmol/L is associated with optimal neurological function, particularly in older adults5

401-600 pg/mL (approximately 295-443 pmol/L)

Evidence suggests elevated risk in this range:

  • Concentrations ranging from 400-600 pmol/L are linked to a significantly higher risk of all-cause mortality1
  • However, for specific populations such as athletes, a B12 concentration range of 400-700 pg/mL may be beneficial for red blood cell parameters5

Above 601 pg/mL (approximately >443 pmol/L)

Higher concentrations show consistent associations with increased mortality:

  • Serum B12 concentrations exceeding 600 pmol/L show significantly higher mortality rates (adjusted HR 1.50, 95% CI 1.29-1.74)1
  • High serum B12 concentrations (>700 pmol/L) are associated with increased cardiovascular mortality (HR 1.45, 95% CI 1.01–2.06)3
  • In ICU settings, patients with B12 >1000 pmol/l had dramatically higher mortality rates (30-day: 32.7%, 90-day: 40.3%) compared to mid-range values (30-day: 14.6%, 90-day: 19.9%)6
  • Survival analysis showed increased mortality rates in patients with Vitamin B12 levels over 900 pg/ml7

Contextual Factors Affecting B12-Mortality Relationship

Several important contextual factors modify the relationship between B12 levels and mortality:

  1. Underlying Health Conditions: In ICU patients, elevated B12 levels were not a significant predictor of mortality when liver function was controlled for, suggesting B12 may be a proxy for liver dysfunction6
  2. Source of B12: For concentrations less than 200 pg/ml, vitamin B12 from supplements may increase all-cause mortality, while dietary sources do not show the same effect1
  3. Age: The association between elevated vitamin B12 and mortality is particularly pronounced in older adults1
  4. Specific Diseases: In MASLD patients, the risk of all-cause mortality was reduced by 42% and 28% in the third and fourth B12 quartile groups, respectively, compared with the lowest quartile group2

Conclusion

The relationship between vitamin B12 levels and mortality follows a U-shaped curve, with both deficient (<200 pg/mL) and excessive (>600 pg/mL) levels associated with increased mortality risk. The optimal range appears to be between 200-400 pg/mL for most populations, though this may vary by age, health status, and specific conditions.

For clinical practice, both high and low vitamin B12 levels should prompt further investigation, as they may indicate underlying health issues that contribute to increased mortality risk rather than direct causation from the B12 levels themselves.

Footnotes

  1. https://www.ajmc.com/view/analysis-says-excessive-vitamin-b12-concentration-can-increase-mortality-risk ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7

  2. https://pmc.ncbi.nlm.nih.gov/articles/PMC11655224/ ↩ ↩2 ↩3

  3. https://pmc.ncbi.nlm.nih.gov/articles/PMC7545540/ ↩ ↩2

  4. https://pmc.ncbi.nlm.nih.gov/articles/PMC2696961/ ↩

  5. https://consensus.app/questions/optimal-b12-levels/ ↩ ↩2

  6. https://pmc.ncbi.nlm.nih.gov/articles/PMC3961712/ ↩ ↩2

  7. https://pubmed.ncbi.nlm.nih.gov/21899932/ ↩