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. 2011 Dec;4(6):243-251.
doi: 10.4021/gr379w. Epub 2011 Nov 20.

Proton Pump Inhibitors Interfere With Zinc Absorption and Zinc Body Stores

Free PMC article

Proton Pump Inhibitors Interfere With Zinc Absorption and Zinc Body Stores

Christopher P Farrell et al. Gastroenterology Res. .
Free PMC article


Background: Proton pump inhibitors (PPIs) cause a sharp elevation of gastro-duodenal luminal pH which in turn has resulted in reports of reduced absorption of magnesium and certain other nutrients.

Methods: Gastroesophageal reflux disease (GERD) patients on long-term PPI therapy (> 6 months) or healthy test subjects (not on any acid preventive or neutralizing medication) were administered oral doses of zinc gluconate (26.2 mg zinc, twice daily) for 14 days followed by 5 cc venous blood samples. Plasma was analyzed for total zinc content by atomic absorption spectrophotometry. Baseline plasma and red blood cell zinc levels were also measured in these two groups when not taking any zinc supplementation.

Results: Plasma zinc levels of healthy controls increased by 126% during the period of zinc supplementation compared to only a 37% increase for individuals on long-term PPI therapy. On their normal diet (with no zinc supplementation), PPI-users had a 28% lower plasma zinc level than healthy controls (P < 0.005).

Conclusions: PPI use dramatically reduces supplemental zinc uptake and can result in decreased zinc body stores. Certain individuals on long-term PPI therapy, such as infants being treated for colic, may be at risk for decreased systemic levels of trace metals needed for developmental, regenerative and immunological requirements.

Keywords: Acid; Colic; Intestine; Nutrition; Proton pump inhibitor; Stomach; Trace metal; Zinc; pH.


Figure 1
Figure 1
Elevation of plasma zinc after 14 days of 50 mg supplemental Zn per day. Results shown represent the mean ± standard error of the mean. A group of n = 10 healthy control, test subjects had a blood sample taken 12 hours after their final Zn dose. A second group (n = 5), also healthy controls, had their blood sample taken only 2 hours after their final Zn dose. *P < 0.005 (paired Student’s t test); **P < 0.01 against their own pre-zinc supplement plasma Zn values.
Figure 2
Figure 2
Lack of effect of Zn supplementation on plasma copper levels. A group of n = 10 healthy control, test subjects had their blood sample taken 12 hours after their final Zn dose. P = 0.35 (paired Student’s t). Not significant. Data shown represent mean ± standard error of the mean.
Figure 3
Figure 3
Effect of PPI use on percentage change in plasma zinc levels after zinc supplementation. The increase in plasma zinc levels after 14 days of 53.2 mg/day zinc supplementation was measured for n = 5 healthy control test subjects versus n = 5 reflux-disease patients on long-term PPI therapy. Data shown represent the mean percentage increase ± the standard error of the mean. P < 0.01 (paired Student’s t test).
Figure 4
Figure 4
The effect of chronic PPI use on plasma zinc levels. Plasma zinc levels (mcg/dL) were measured in a group of 10 test subjects on long-term PPI medication (as described in Methods) and a matched group of 10 healthy control test subjects not taking PPI, antacid or H2 blocker medication. For the healthy control group, the mean (±standard error of the mean) was 91 mcg/dL ± 3 and the mean for the PPI-group was 75 mcg/dL ± 3 (Paired Student’s t test, P = 0.004).

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