Associations of atrophic gastritis and proton-pump inhibitor drug use with vitamin B12 status, and the impact of fortified foods, in older adults

Kirsty Porter, L. Hoey, Catherine Hughes, M Ward, Michelle Clements, JJ Strain, Conal Cunningham, Miriam Casey, Fergal Tracey, Maurice O'Kane, K. Pentieva, LB McAnena, Kevin McCarroll, Eamon Laird, Anne M. Molloy, H McNulty

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Background: Atrophic gastritis (AG) and use of proton pump inhibitors (PPIs) result in gastric acid suppression that can impair the absorption of vitamin B-12 from foods. The crystalline vitamin B-12 form, found in fortified foods, does not require gastric acid for its absorption and could thus be beneficial for older adults with hypochlorhydria, but evidence is lacking. Objectives: To investigate associations of AG and PPI use with vitamin B-12 status, and the potential protective role of fortified foods, in older adults. Methods: Eligible participants (n = 3299) not using vitamin B-12 supplements were drawn from the Trinity-Ulster and Department of Agriculture cohort, a study of noninstitutionalized adults aged ≥60 y and recruited in 2008-2012. Vitamin B-12 status was measured using 4 biomarkers, and vitamin B-12 deficiency was defined as a combined indicator value < -0.5. A pepsinogen I:II ratio <3 was considered indicative of AG. Results: AG was identified in 15% of participants and associated with significantly lower serum total vitamin B-12 (P < 0.001) and plasma holotranscobalamin (holoTC; P < 0.001), and higher prevalence of vitamin B-12 deficiency (38%), compared with PPI users (21%) and controls (without AG and nonusers of PPIs; 15%; P < 0.001). PPI drugs were used (≥6 mo) by 37% of participants and were associated with lower holoTC concentrations, but only in participants taking higher doses (≥30 mg/d). Regular, compared with nonregular, consumption of fortified foods (i.e., ≥5 and 0-4 portions/wk, respectively) was associated with higher vitamin B-12 biomarkers in all participants, but inadequate to restore normal vitamin B-12 status in those with AG. Conclusions: Older adults who have AG and/or use higher doses of PPIs are more likely to have indicators of vitamin B-12 deficiency. Fortified foods, if consumed regularly, were associated with enhanced vitamin B-12 status, but higher levels of added vitamin B-12 than currently provided could be warranted to optimize status in people with AG.

Original languageEnglish
Article numbernqab193
Pages (from-to)1286-1294
Number of pages9
JournalThe American Journal of Clinical Nutrition
Issue number4
Early online date16 Jun 2021
Publication statusPublished (in print/issue) - 1 Oct 2021

Bibliographical note

Funding Information:
Supported by governmental funding from the Irish Department of Agriculture, Food and the Marine and Health Research Board (under the Food Institutional Research Measure initiative) and the Northern Ireland Department for Employment and Learning (under its Strengthening the All- Island Research Base initiative).

Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.


  • Vitamin B12 biomarkers
  • atrophic gastritis
  • proton pump inhibitor drugs
  • fortified foods
  • food-bound malabsorption
  • hypochlorhydria
  • older adults
  • vitamin B-12 biomarkers


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