Research indicates omeprazole affects calcium and iron levels in adult rats — Evidence Review
Published in ACS Omega, by researchers from Federal University of São Paulo (UNIFESP), ABC Medical School (FMABC)
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Table of Contents
Researchers in Brazil found that extended use of proton pump inhibitors (PPIs) in rats led to disruptions in mineral absorption, raising concerns about potential risks for anemia and bone health. Most related studies generally support the association between long-term PPI use and altered nutrient absorption or bone effects, though findings on the mechanisms and clinical significance are mixed. The full study is available in the journal ACS Omega.
- Several studies agree that PPIs such as omeprazole can reduce iron absorption and affect calcium metabolism, potentially increasing the risk for anemia and bone loss, particularly during prolonged use or in populations with pre-existing deficiencies 7 9 11 12 13.
- Some research suggests that while PPI-induced reduction in stomach acid can impair mineral absorption, short-term or low-dose use may have minimal effects in healthy individuals, highlighting the importance of duration and underlying health status 6 8 14.
- Mechanistic studies further indicate that PPIs may alter bone metabolism through both direct effects on bone cells and indirect effects via nutrient absorption, with recent evidence identifying genetic targets involved in PPI-induced osteoporosis 5.
Study Overview and Key Findings
Proton pump inhibitors are widely used to treat gastrointestinal disorders, but their long-term safety profile—especially concerning nutrient absorption and bone health—has become a topic of increased scrutiny. The recent study from researchers at the Federal University of São Paulo (UNIFESP) and ABC Medical School (FMABC) provides new insights by examining how prolonged omeprazole use affects the distribution and absorption of key minerals in rats. This work is particularly timely given policy changes in Brazil that have increased over-the-counter access to PPIs, potentially leading to wider and less supervised use.
| Property | Value |
|---|---|
| Organization | Federal University of São Paulo (UNIFESP), ABC Medical School (FMABC) |
| Journal Name | ACS Omega |
| Authors | Angerson Nogueira do Nascimento, Fernando Fonseca, Andréa Santana de Brito |
| Population | Adult rats |
| Methods | Animal Study |
| Outcome | Mineral absorption, nutrient deficiencies, immune system alterations |
| Results | Omeprazole caused higher calcium and lower iron levels in rats. |
Literature Review: Related Studies
To place these findings in context, we searched the Consensus database, which includes over 200 million research papers. The following search queries were used to identify relevant studies:
- omeprazole anemia bone loss
- acid reflux medication effects on calcium
- iron levels omeprazole rat studies
Related Studies by Key Topic
| Topic | Key Findings |
|---|---|
| How does long-term PPI use affect bone health and mineral metabolism? | • Long-term PPI therapy is associated with decreased bone mineral density and possible increased risk of fractures, particularly in vulnerable populations 2 3 4 5 7 9. • Mechanistic studies suggest PPIs can alter bone remodeling, both by reducing calcium absorption and by direct effects on bone cells 1 4 5. |
| What is the impact of PPI therapy on iron absorption and anemia risk? | • Chronic PPI use can impair non-heme iron absorption, especially in the context of iron deficiency or long-term therapy, increasing the risk of anemia 11 12 13 7. • Short-term PPI administration in healthy individuals may not significantly affect iron absorption 14. |
| Does reduced stomach acid from PPIs always result in nutritional deficiencies? | • Studies in healthy volunteers suggest that short-term or moderate PPI use does not consistently reduce calcium or iron absorption 6 8 14. • The risk of deficiencies appears to increase with duration, higher dosage, or pre-existing risk factors 7 9 13. |
| What molecular mechanisms underlie the effects of PPIs on bone and mineral metabolism? | • PPIs may impact bone metabolism by interacting with genes and pathways crucial for bone formation and resorption, such as EGFR, ESR1, and SRC 5. • Suppression of gastric acid may lead to compensatory hormonal and metabolic changes affecting bone and mineral homeostasis 9 12. |
How does long-term PPI use affect bone health and mineral metabolism?
Long-term use of PPIs has been linked to reduced bone mineral density and increased risk of fractures, with both animal and human studies supporting these associations. The new rat study echoes these findings by showing mineral imbalances—specifically, increased blood calcium and decreased iron—after prolonged omeprazole administration. Notably, related research suggests that PPIs may affect bone health not only by impeding calcium absorption but also through direct effects on bone cell function and remodeling.
- Multiple studies report decreased bone mineral density and altered bone structure in both animal models and specific patient populations exposed to long-term PPI therapy 2 3 4.
- Mechanistic work identifies direct inhibition of bone resorption and changes in bone turnover markers following PPI use 1 4 5.
- Network toxicology and molecular docking studies highlight specific genes (e.g., EGFR, ESR1, SRC) that PPIs may target to influence bone metabolism 5.
- The risk of bone loss appears to be higher with longer duration of therapy, higher potency PPIs, and in populations with other risk factors for osteoporosis 2 3 9.
What is the impact of PPI therapy on iron absorption and anemia risk?
The evidence indicates that PPIs can impair iron absorption, particularly with chronic use or when underlying iron deficiency exists. The animal study from UNIFESP and FMABC found decreased iron levels in rats treated with omeprazole, consistent with previous rat, mouse, and cell culture studies. However, short-term or low-dose PPI use in healthy individuals does not always result in significant changes in iron absorption.
- Animal studies demonstrate that omeprazole reduces iron absorption, especially in the context of pre-existing iron deficiency 11 13.
- Molecular research shows that PPIs can upregulate hepcidin, a hormone that limits iron absorption, providing a plausible mechanism for PPI-induced anemia 12.
- Clinical and epidemiological studies report increased risk of iron-deficiency anemia in chronic PPI users 7 12.
- Short-term PPI use in healthy volunteers generally does not significantly affect iron uptake 14.
Does reduced stomach acid from PPIs always result in nutritional deficiencies?
Not all studies find that PPIs cause significant nutrient deficiencies in all users. Several clinical trials and observational studies show that healthy individuals using PPIs for short periods do not experience major declines in calcium or iron absorption. The risk of deficiency appears to be more notable among those with prolonged use, higher doses, or additional risk factors.
- Randomized controlled trials in healthy adults show no significant reduction in calcium absorption after 30 days of PPI therapy 6 8.
- Short-term administration of omeprazole does not impair iron absorption in healthy subjects 14.
- Animal studies and clinical observations suggest that the risk of deficiency increases with therapy duration and in those with underlying health conditions or nutritional vulnerabilities 7 9 11 13.
- Supplementation can mitigate deficiency in certain contexts, as iron supplementation prevented anemia in omeprazole-treated rats 13.
What molecular mechanisms underlie the effects of PPIs on bone and mineral metabolism?
Recent research has begun to elucidate the genetic and molecular pathways through which PPIs affect bone and mineral metabolism. The inhibition of gastric acid leads to changes in calcium bioavailability, while PPIs may also interact with key genes involved in bone remodeling. Moreover, changes in hormone levels (e.g., hepcidin, parathyroid hormone) and cytokines have been observed, indicating complex systemic effects.
- Network toxicology and molecular modeling have identified EGFR, ESR1, and SRC as key gene targets of PPIs related to osteoporosis risk 5.
- PPIs can induce hypergastrinemia and secondary increases in parathyroid hormone, potentially leading to increased bone turnover and loss 9.
- Animal studies demonstrate that PPIs affect both bone formation and resorption, potentially through suppression of pro-inflammatory cytokines and direct action on bone cells 4.
- PPIs stimulate hepcidin production, which reduces iron absorption and may contribute to anemia 12.
Future Research Questions
Further research is needed to clarify the long-term clinical significance of PPI-induced nutrient alterations and to determine which populations are most at risk. Understanding the precise mechanisms and identifying strategies to mitigate adverse effects will be important as PPIs remain widely used worldwide.
| Research Question | Relevance |
|---|---|
| What are the long-term effects of chronic PPI use on bone health and fracture risk? | Long-term PPI use is associated with decreased bone mineral density and potential fracture risk, but the magnitude and clinical impact over years are not fully established, especially in diverse populations 2 3 9. |
| How does PPI therapy affect iron absorption and risk of anemia in different populations? | The risk of iron deficiency and anemia due to PPI use may vary by age, baseline nutritional status, and comorbidities, but vulnerable groups are not well-defined and mechanisms need further clarification 11 12 13. |
| Can nutritional supplementation effectively prevent PPI-induced mineral deficiencies in long-term users? | Supplementation with iron or calcium could mitigate deficiencies during prolonged PPI therapy, but optimal strategies and target populations for intervention remain to be determined 13 7. |
| What are the molecular mechanisms by which PPIs affect bone metabolism? | Recent studies implicate genetic pathways and hormonal changes, but the specific molecular interactions and their relevance to clinical outcomes are not fully understood 5 9 12. |
| Are there differences in nutrient absorption effects between different PPIs (e.g. omeprazole, pantoprazole, esomeprazole)? | Potency and duration of action vary among PPIs, which may influence their impact on nutrient absorption and side effect profiles; comparative studies are needed to inform safer prescribing practices 5 4. |