Carolyn Mercer, B.Sc., N.D.

08 Jul 2021


They are the biggest selling and most over prescribed Rx drugs since the late 1980’s.


Some evidence has suggested that PPI use has been associated with decreased magnesium levels.  There have been about 30 cases documented in the literature, where 61% of those having received PPI therapy for 5 or more years had a magnesium deficiency.  Another study looking at hospitalized patients over the age of 50 on PPI’s, showed an increased risk of hypomagnesemia.
Not all people experience hypomagnesemia on PPI’s. But if people already have any signs of magnesium deficiency including paresthesia’s, seizures, cardiac arrhythmias, cramping, headaches or gastrointestinal symptoms, like constipation, they should consider not to take a PPI, since it can further lower magnesium levels.2


Magnesium levels should be monitored in at-risk patients.  With PPI use, magnesium supplementation can sometimes even be insufficient in correcting magnesium deficiency caused by the proton pump inhibitors3 and in some cases, magnesium levels only increased after being off the PPIs.4


Vitamin B12 requires gastric acid to be absorbed and this affects 30% of the elderly.4   Vitamin B12 absorption involves the use of peptic enzymes to cleave dietary B12 from protein; this is done by pepsin in the stomach.2
Omeprazole, which is a PPI, suppresses the conversion of pepsinogen to pepsin.  
Further, after cleavage of the B12 in the stomach, it then binds with “intrinsic factor” so it can be absorbed from the small intestine into the blood.5
Absorption of B12 will not happen if the initial cleavage with pepsin is not done in the stomach. 
Vitamin B12 deficiency over long periods of time can result in memory issues, brain fog, tingling and numbness in the extremities.6


Vitamin C is secreted in human gastric juice, and PPI’s lower the concentration of active Vitamin C in gastric juice.7
Humans are unable to synthesize Vitamin C and rely solely on obtaining adequate amounts of the water-soluble vitamin from dietary intake.  PPI’s affect its bioavailability by lowering acid concentration in gastric juices.2
Symptoms of a Vitamin C deficiency include dry hair and nails, easy bruising, frequent nosebleeds, fatigue, and weakness.8


PPI’s alter the secretion of Vitamin C by gastric cells that is needed to facilitate iron absorption. 
In one study with 50 anemic patients, in those that used 40 mg of omeprazole daily, the response to oral ferrous sulphate was suboptimal. 
Taking Iron and Vitamin C on alternate days of a PPI could be an alternative to help with absorption.8


PPI’s affect Zinc absorption.  One study looked at zinc levels in healthy individuals versus those on PPI Therapy.  Zinc supplementation in healthy individuals increased by 126% compared to only 37% in those with PPI therapy.  On a normal diet, PPI users had a 28% lower plasma zinc level than healthy controls.9


Interestingly, it has also been shown that zinc can be effective at lowering gastric acid levels and a potential alternative to PPIs.  Zinc has been shown to lower the compound histamine which triggers stomach acid secretion.10

Elevated homocysteine levels have been shown to correlate with long-term PPI use.11
High homocysteine levels in the blood can damage the lining of the arteries, promoting plaque formation. High levels may also make the blood clot more easily which can increase the risk of blood vessel blockages


The enzyme required for the synthesis of methionine from homocysteine requires folate12 in its active form, Methyltetrahydrofolate, L-5 MTHF (see Figure 1).13 




In summary, PPI’s have been associated with an increased risk of vitamin and mineral deficiencies, impacting Vitamin B12, Vitamin C, iron, zinc, and magnesium bioavailability.
Reducing inflammatory foods and the use of alkalinizing agents could be an alternative to the use of PPI’s, which would minimize the risk of vitamin and mineral deficiencies.2


Reference List

  1. com, May 2018: Proton Pump Inhibitors. June 25, 2021).
  2. Heidelbaugh, J. 2013. “Proton pump inhibitors and risk of vitamin and mineral deficiency: evidence and clinical implications,” Therapeutic Advances in Drug Safety 4(3) (June), (accessed June 25, 2021).
  3. Emerson, David. 2016. Proton Pump Inhibitors for GERD Cause Magnesium Deficiency. People Beating Cancer. (accessed June 26, 2021).
  4. Proton Pump Inhibitors Cause Low Magnesium. (accessed June 26, 2021).
  5. Busti, Anthony J. 2015. “The Mechanism for Omeprazole Induced Vitamin B12 Deficiency and Risk of Developing Macrocytic Anemia, Hyperhomocysteinemia, and/or Neuropathy,” Evidence- Based Medicine Consult,” (accessed June 29, 2021).
  6. Life Spa, February 2016. Proton Pump Inhibitors Block this Vital Nutrient. (accessed June 27, 2021).
  7. Acid Blockers and Vitamin and Mineral Depletion Blog. (accessed June 28, 2021).
  8. Tran-Duy, N.J. et al. 2018. “Use of proton pump inhibitors and risk of iron deficiency: a population-based case-control study,” Journal of International Medicine 285 (2) (August), (accessed June 29, 2021).
  9. Mullin, James M et al. 2011. “Proton Pump Inhibitors Interfere With Zinc Absorption and Zinc Body Stores,” Gastroenterology Research 4(6) (December), June 28, 2021).
  10. Stomach acid zapped by a single dose of zinc. (accessed June 28, 2021).
  11. Zharkova, A et al. 2012. “Correlation between long-term proton pump inhibitor use, homocysteine and lipoproteins serum concentrations in patients with comorbidity of ischemic heart disease and acid peptic disease.” 213. Abstract in Georgian Medical News.
  12. Oregon State University, June 2015: Vitamin B12. (accessed June 30, 2021).
  13. Termanini, B et al. 1998. “Effect of long-term gastric acid suppressive therapy on serum vitamin B12 levels in patients with Zollinger-Ellison syndrome,” 104(5). Abstract in The American Jounal of Medicine.


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