Nutrient Deficiency Linked to Acid Reflux Medications

When you’re suffering from reflux, shutting down acid production in your stomach may seem like the best way to neutralize your symptoms. While this can provide some short-term relief, over the long-term, you can deplete your body of much needed nutrients.

There are three types of medications that are used to treat reflux by suppressing the production of acid in the stomach: Proton Pump Inhibitors or PPIs (ex. Nexium, Prilosec), H2 blockers (ex. Pepcid, Tagamet) and antacids (ex. Tums, Maalox). [For more information on each of these drug types, see a previous post titled “Reflux 101 (Part II): How Acid Reflux Medications Work”.] These medications are available both over-the-counter and with a prescription from your doctor.

With acid production in the off position, the pH balance in your stomach changes and heads towards the neutral zone. As a refresher, pH is a measure of the acidity or alkalinity of a solution with a scale ranging from zero to fourteen: the more acidic a solution, the lower the number and the more alkaline or base, the higher the number with seven being neutral.

According to Dr. Keith Halperin, the pH of our stomach is vital to the digestion of many nutrients and acts as the first line of defense against harmful bacteria and viruses. He explains in his article “Stomach Acid, pH and Health” that the stomach is a reservoir of strong acid, requiring a very acidic pH of 1.5 to 2.5 to maintain digestive health. He goes onto explain how a lack of hydrochloric acid, the acid which determines stomach pH, affects the digestion of iron, folate, B12, calcium and protein.

You may recall back in March 2011, the FDA issued a drug safety communication regarding the use of PPI drugs due to low magnesium levels occurring when taken for long periods, typically a year or more. Not only was the nutrient deficiency brought to light, but also of concern was the finding that, in a quarter of the cases, supplementing with magnesium did not improve low serum levels.

Since then, more articles have surfaced about the impact of pH levels in the stomach on nutrient absorption. Author Susan Cohen, a licensed pharmacist for over twenty years who is nationally known for her syndicated health column, has written an article specifically about acid reflux medications and the potential side effects of nutrient depletion. She asserts the possibility of getting diagnosed with a new disease when deprived of certain nutrients for too long. Here is a list of the possibilities she has recently outlined:

Folate

In order for vitamin B9 (folate) to be absorbed from your intestine, the pH in your gut must be between 5.5 and 6.0. [1,2] So it makes sense that depletion with H2 antagonists happens because pH increases in the gut. A deficiency of folate in the body may cause or exacerbate atherosclerosis, confusion, depression, irritability, pale skin, and megaloblastic anemia.

Iron

Iron deficiency has been noted with cimetidine (an H2 antagonist). The reduction ranges from 28 to 65 percent with single doses of 300 to 900 mg and depletion occurs because gut pH increases. [3, 4] You may think “no big deal,” but iron deficiency can lead to chronic fatigue, shortness of breath, paleness, heart palpitations, dizziness, anxiety, symptoms that might be labeled as obsessive-compulsive, hair loss and muscle twitching.

Vitamin B12

B12 is glued to protein, and your gastric acid is needed to release B12 from the protein so you can absorb it from the gut. B12 deficiency can cause fatigue, weakness, confusion, depression and neuropathy. [5, 6, 7, 8, 9, 10, 11] It may cause psychiatric and dementia-like symptoms. Just remember, stomach acid is needed to unglue the vitamin B12 from the protein molecule in order for it to be fully absorbed. [28, 29, 30, 31] Reduced secretion of gastric acid and pepsin, which occurs with H2 blocker usage, can reduce absorption of protein-bound (dietary) vitamin B12 but not supplemental vitamin B12. [34-41] Simply put, acid blockers prevent you from getting B12 out of your food.

Magnesium

Reports of hypomagnesemia have occurred with long-term PPI use (greater than 1 year); these drugs block the active transport of magnesium in the intestine, causing low magnesium and resulting in serious pathophysiology including cardiac arrhythmia, muscle spasms, tetany, hypocalcemia, epileptic convulsions (seizures), hypoparathyroidism, depression. [See references 8-19 below, 12-23] There’s a blood test available to determine your red blood cell (RBC) levels of magnesium.

Vitamin A

Beta carotene forms vitamin A in the body, but beta carotene itself is not absorbed from the gastrointestinal tract very well in the presence of omeprazole (a PPI drug) because of the higher pH. [24] Supplementation with natural beta carotene or plain vitamin A may be necessary especially if you have: dry eyes, color blindness, peeling nails, dry hair, dry skin, grey spots in the eyes (Bitot’s spots), night blindness and impaired immunity.

Calcium and Zinc

These minerals have to be solubilized in water in order to be fully absorbed, and the solubility of minerals is dependent on having an acidic pH in the stomach. A reduction of calcium or zinc can have profound effects on the body, increasing risk of osteoporosis. There is a higher risk of fractures among takers of certain acid blockers. [42]

Probiotics (Lactobacillus)

Gastric ulcer patients show bacterial overgrowth in the jejunum and fat malabsorption after omeprazole treatment. [26] The bacterial over-growth included anaerobes and aerobes and is more than likely associated with a drug-induced shift to neutral pH. Also, probiotics protect against bacterial adhesion of Helicobactor pylori, the organism known to cause ulceration. [27] Having poor gut integrity due to low probiotic status can affect immunity, levels of energy and weight. Signs that you may not have enough of these friendly organisms in your mucosal barrier include urinary tract infections, mouth sores/ulcers, gas, constipation/diarrhea, digestive pain, inflammatory bowels and food sensitivities.

Vitamin D

Activation of vitamin D occurs partly in the stomach, and then in the liver. If the acid is reduced in the stomach, complete activation does not occur. Data suggests that cimetidine treatment affects vitamin D levels because one month after cessation of therapy, D levels rose significantly. [32, 33] Vitamin D is important for a happy mood and to prevent infections.

While it’s important to be aware of the effects on your body when taking medications, you should always consult your doctor before making any changes to your regimen. If you’re taking acid blockers and have some of the symptoms noted above, talk to your doctor to see if one of the vitamins and minerals may make sense. You can also learn more about drug-nutrient depletion in Susan Cohen’s book, Drug Muggers, Which Medications are Robbing Your Body of Essential Nutrients, and Natural Ways to Restore Them.

Finally, it’s always safe to supplement your treatments with lifestyle changes. Avoiding trigger foods, eating smaller meals and sleeping with MedCline can help neutralize reflux while maintaining the proper acidic levels for optimal digestive health.

Susan Cohen References

1. Russell RM, Golner BB, Krasinski SD, et al. Effect of antacid and H2 receptor antagonists on the intestinal absorption of folic acid. J Lab Clin Med 1988;112:458-63.

2. Russell RM, Golner BB, Krasinski SD, Sadowski JA, Suter PM, Braun CL. Effect of antacid and H2 receptor antagonists on the intestinal absorption of folic acid. J. Lab Clin Med 1988 Oct;112(4):458-63.

3. Skikne BS, Lynch SR, Cook JD. Role of gastric acid in food iron absorption. Gastroenterology 1981;81:1068-71.

4. Sturniolo GC, Montino MC, Rossetto L, et al. Inhibition of gastric acid secretion reduces zinc absorption in man. J Am Coll Nutr 1991;10:372.

5. Termanini B, Gibril F, Sutliff VE, et al. Effect of long-term gastric acid suppressive therapy on serum vitamin B12 levels in patients with Zollinger-Ellison syndrome. Am J Med 1998;104:422-30.

6. Bellou A, Aimone-Gastin I, De Korwin JD, et al. Cobalamin deficiency with megaloblastic anaemia in one patient under long-term omeprazole therapy. J Intern Med 1996;240:161-4.\

7. Saltzman JR, Kemp JA, Golner BB, et al. Effect of hypochlorhydria due to omeprazole treatment or atrophic gastritis on protein-bound vitamin B12 absorption. J Am Coll Nutr 1994;13:584-91.

8. Marcuard SP, Albernaz L, Khazaine PG. Omeprazole therapy causes malabsorption of cyanocobalamin. Ann Intern Med 1994;120:211-5.

9. Carpentier JL, Bury J, Luyckx A, et al. Vitamin B12 and folic acid serum levels in diabetics under various therapeutic regimens. Diabete Metab 1976;2:187-90.

10. Ruscin JM, Page RL, Valuck RJ. Vitamin B12 deficiency associated with histamine-2-receptor antagonists and a proton-pump inhibitor. Ann Pharmacother 2002;36:812-6.

11. Force RW, Meeker AD, Cady PS, et al. Increased vitamin B12 requirement associated with chronic acid suppression therapy. Ann Pharmacother 2003;37:490-3.

12. Safety Alert. Proton Pump Inhibitor drugs (PPIs): Drug Safety Communication – Low Magnesium Levels Can Be Associated With Long-Term Use. U.S. Food and Drug Administration, March 2, 2011. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformati... SafetyAlertsforHumanMedicalProducts/ucm245275.htm

13. Mackay JD, Bladon PT. Hypomagnesaemia due to proton-pump inhibitor therapy: a linical case series. QJM 2010;103:387-95.

14. Kuipers MT, Thang HD, Arntzenius AB. Hypomagnesaemia due to use of proton pump inhibitors–a review. Neth J Med 2009;67:169-72.c

15. Cundy T, Dissanayake A. Severe hypomagnesaemia in long-term users of proton-pump inhibitors. Clin Endocrinol (Oxf) 2008;69:338-41.

16. Doornebal J, Bijlsma R, Brouwer RM. [An unknown but potentially serious side effect of proton pump inhibitors: hypomagnesaemia]. Ned Tijdschr Geneeskd 2009;153:A711.

17. Epstein M, McGrath S, Law F. Proton-pump inhibitors and hypomagnesemic hypoparathyroidism. N Engl J Med 2006;355:1834-6.

18. François M, Lévy-Bohbot N, Caron J, Durlach V. [Chronic use of proton-pump inhibitors associated with giardiasis: A rare cause of hypomagnesemic hypoparathyroidism?]. Ann Endocrinol (Paris) 2008;69:446-8.

19. Broeren MA, Geerdink EA, Vader HL, van den Wall Bake AW. Hypomagnesemia induced by several proton-pump inhibitors. Ann Intern Med 2009;151:755-6.

20. Hoorn EJ, van der Hoek J, de Man RA, et al. A case series of proton pump inhibitor-induced hypomagnesemia. Am J Kidney Dis 2010;56:112-6.

21. Regolisti G, Cabassi A, Parenti E, et al. Severe hypomagnesemia during long-term treatment with a proton pump inhibitor. Am J Kidney Dis 2010;56:168-74.

22. Cundy T, Mackay J. Proton pump inhibitors and severe hypomagnesaemia. Curr Opin Gastroenterol 2011;27:180-5

23. Fernández-Fernández FJ, Sesma P, Caínzos-Romero T, Ferreira-González L. Intermittent use of pantoprazole and famotidine in severe hypomagnesaemia due to omeprazole. Neth J Med 2010;68:329-30.

24. Tang G, Serfaty-Lacrosniere C, Camilo ME, Russell RM. Gastric acidity influences the blood response to a beta-carotene dose in humans. Am J Clin Nutr. 1996 Oct;64(4):622-6.

25. Sturniolo GC, Montino MC, Rossetto L, et al. Inhibition of gastric acid secretion reduces zinc absorption in man. J Am Coll Nutr 1991;10:372.

26. Shindo K, Machida M, Fukumura M, Koide K, Yamazaki R. Omeprazole induces altered bile acid metabolism. Gut. 1998 Feb;42(2):266-71.

27. Lam EK, Yu L, Wong HP, Wu WK, Shin VY, Tai EK, So WH, Woo PC, Cho CH.Probiotic Lactobacillus rhamnosus GG enhances gastric ulcer healing in rats. Eur J Pharmacol. 2007 Jun 22;565(1-3):171-9.

28. Salom IL, Silvis SE, Doscherholmen A. Effect of cimetidine on the absorption of vitamin B12. Scand J Gastroenterol 1982;17:129-31.

29. Ruscin JM, Page RL, Valuck RJ. Vitamin B12 deficiency associated with histamine-2-receptor antagonists and a proton-pump inhibitor. Ann Pharmacother 2002;36:812-6.

30. Force RW, Nahata MC. Effect of histamine H2 receptor antagonists on vitamin B12 absorption. Ann Pharmacother 1992;26:1283-6.

31. Force RW, Meeker AD, Cady PS, et al. Increased vitamin B12 requirement associated with chronic acid suppression therapy. Ann Pharmacother 2003;37:490-3.

32. Odes HS, Fraser GM, Krugliak P, Lamprecht SA, Shany S. Effect of cimetidine on hepatic vitamin D metabolism in humans. Digestion. 1990;46(2):61-4. PubMed PMID: 2253823.

33. Bengoa JM, Bolt MJ, Rosenberg IH. Hepatic vitamin D 25-hydroxylase inhibition by cimetidine and isoniazid. J Lab Clin Med. 1984 Oct;104(4):546-52. PubMed PMID: 6481217.

34. Ruscin JM, Page RL, Valuck RJ. Vitamin B12 deficiency associated with histamine-2-receptor antagonists and a proton-pump inhibitor. Ann Pharmacother 2002;36:812-6.

35. Force RW, Nahata MC. Effect of histamine H2 receptor antagonists on vitamin B12 absorption. Ann Pharmacother 1992;26:1283-6.

36. Force RW, Meeker AD, Cady PS, et al. Increased vitamin B12 requirement associated with chronic acid suppression therapy. Ann Pharmacother 2003;37:490-3.

37. Aymard JP, Aymard B, Netter P, et al. Haematological adverse effects of histamine H2-receptor antagonists. Med Toxicol Adverse Drug Exp 1988;3:430-48.

38. Belaiche J, Zittoun J, Marquet J, et al. Effect of ranitidine on secretion of gastric intrinsic factor and absorption of vitamin B12. Gastroenterol Clin Biol 1983;7:381-4.

39. Salom IL, Silvis SE, Doscherholmen A. Effect of cimetidine on the absorption of vitamin B12. Scand J Gastroenterol 1982;17:129-31.

40. Force RW, Meeker AD, Cady PS, et al. Increased vitamin B12 requirement associated with chronic acid suppression therapy. Ann Pharmacother 2003;37:490-3.

41. Termanini B, Gibril F, Sutliff VE, et al. Effect of long-term gastric acid suppressive therapy on serum vitamin B12 levels in patients with Zollinger-Ellison syndrome. Am J Med 1998;104:422-30

42. “Possible Increased Risk of Bone Fractures With Certain Antacid Drugs”. U S Food and Drug Administration. 25 May 2010. Retrieved 26 May 2010.

References:

1. Halperin, Keith, DC. Stomach Acid, pH, and Health. www.keithhalperin.com

2. Safety Alert. Proton Pump Inhibitor drugs (PPIs): Drug Safety Communication – Low Magnesium Levels Can B 

Associated With Long-Term Use. U.S. Food and Drug Administration, March 2, 2011. http://www.fda.gov/Drugs/DrugSafety/ucm245011.htm#Safety_Announcement.

3. Cohen, Susan. R. Ph. “Acid Reflux Medications Are Big Drug Muggers Causing Many Side Effects”. January 28, 2013. http://www.huffingtonpost.com/suzy-cohen-rph/acid...