Should Hydrochloric acid (HCl) and pepsin, rather than salivary gland enzymes, liberate vitamin B12 from animal-derived proteins?

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Last updated: June 15, 2025View editorial policy

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From the Guidelines

Yes, hydrochloric acid (HCl) and pepsin should liberate vitamin B12 from animal-derived proteins rather than salivary gland enzymes. This process is supported by the espen micronutrient guideline study published in 2022 in the Clinical Nutrition journal 1. According to this study, cobalamin absorption consists of several steps, starting with its release from proteins under the action of gastric acid and pepsin. The study highlights that edible plants and mushrooms rarely contain a considerable amount of cobalamin, making humans dependent on animal sources or fortification 1.

The role of HCl and pepsin in liberating vitamin B12 is crucial as it occurs in the stomach, where parietal cells secrete HCl, creating an acidic environment necessary for pepsin activation. When consuming animal products containing B12, the vitamin is bound to proteins, and the stomach acid denatures these proteins while pepsin breaks the peptide bonds, freeing the B12 molecules.

Key points to consider:

  • The espen micronutrient guideline study emphasizes the importance of gastric acid and pepsin in the initial steps of cobalamin absorption 1.
  • Conditions affecting stomach acid production, such as atrophic gastritis or long-term use of proton pump inhibitors, can lead to B12 deficiency despite adequate dietary intake, as the crucial first step of liberating B12 from food proteins is compromised.
  • Salivary enzymes like amylase primarily digest carbohydrates and lack the protein-digesting capabilities and acidic environment required for B12 release.
  • After liberation in the stomach, B12 binds to R-proteins, then to intrinsic factor in the duodenum, enabling absorption in the ileum, as outlined in the study 1.

From the Research

Liberation of Vitamin B12 from Animal-Derived Proteins

  • The process of liberating vitamin B12 from animal-derived proteins involves several steps and components, including gastric intrinsic factor, pancreatic proteases, and specific receptors in the ileum 2, 3.
  • In the stomach, vitamin B12 is released from food carrier proteins and binds to haptocorrin (HC), which is then degraded by pancreatic proteases, triggering the transfer of B12 to intrinsic factor (IF) in the duodenum 2.
  • The role of hydrochloric acid (HCl) and pepsin in this process is crucial, as they help to break down the protein-bound vitamin B12 in the stomach, making it available for binding to HC and subsequent absorption 2, 3.
  • Salivary gland enzymes do not play a significant role in the liberation of vitamin B12 from animal-derived proteins, as this process occurs primarily in the stomach and small intestine 2, 3.

Mechanisms of Vitamin B12 Absorption

  • Vitamin B12 absorption is a complex process involving multiple transport proteins, receptors, and enzymes, including intrinsic factor, haptocorrin, transcobalamin, and cubilin 2, 3, 4.
  • The absorption of vitamin B12 occurs primarily in the distal ileum, where the vitamin is taken up by a specific receptor complex composed of cubilin and amnionless 2, 3.
  • Impaired absorption of vitamin B12 can lead to deficiency, which can have significant health consequences, including hematological and neurological disorders 2, 3, 4, 5.

Importance of Vitamin B12

  • Vitamin B12 is an essential nutrient that plays a critical role in cellular metabolism, including DNA synthesis, methylation, and mitochondrial metabolism 4, 5, 6.
  • Vitamin B12 deficiency is a significant public health concern, particularly in populations with limited access to animal-derived foods, such as vegans and vegetarians 4, 5.
  • The diagnosis and management of vitamin B12 deficiency require a comprehensive approach, including dietary assessment, biomarker measurement, and supplementation or fortification strategies 4, 5, 6.

References

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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