Alternatives to Proton Pump Inhibitors

I was going to address allergy supplements next, but because of the recent press on the increased risks of death with Proton Pump Inhibitors (PPI), I’m going to tackle this next!

Most likely you or someone you know has taken a PPI at some point in their life. I have (I wish I hadn’t), but as a college student in a traditional pharmacy program, I had no idea the implications it might have down the road. Currently proton pump inhibitors account for over $10 billion dollars in annual healthcare cost and are consistently within the top ten most prescribed medications. Common names for PPIs are below.

 

Prilosec® (Omeprazole)

Nexium® (Esomeprazole)

Prevacid® (Lansoprazole)

Protonix® (Pantoprazole)

Dexilant® (Dexlansoprazole)

Aciphex® (Rabeprazole)

 

What is a PPI? They are medications that reduce the secretion of acid in the stomach. And in many cases they may be needed to heal conditions such as erosive esophagitis (a condition where the lining of the throat is worn away) or peptic ulcers (small holes in the intestinal lining) and they may be needed long term for Barrett’s esophagus. Other conditions may be able to be treated with PPIs short term and then other methods likely can be used after healing has occurred.

The challenge with this is that our bodies are designed to have secretion of acid start the steps needed for proper digestion. So when we stop the initial acid trigger, we decrease production of digestive enzymes and other processes down the line. Then large food particles are undigested leading to a “leaky gut” which I will have another post on very soon by a guest (another pharmacist blogger!) Since we now know gut health is such an important underlying piece to a variety of health conditions, this may be why we see issues with the use of PPIs.

The most recent study8 was a longitudinal observational study in a Veterans Affairs population. The follow-up time frame was on average 5.71 years. Researchers compared patients on PPIs to patients on histamine H2 receptor antagonists (most commonly used drugs in this category are as Zantac (raniditine) and Pepcid (famotidine)), and patients without either medication. The results suggest excess risk of death among PPI users; risk is also increased among those without gastrointestinal conditions and with extended duration of use. The authors suggested limiting PPI use and duration to instances where it is medically indicated may be warranted. Other risks associated with PPIs are in the table below.

RiskRationale
Impaired Nutrient Absorption 9,10The long-term use of PPIs may impair the absorption of calcium, magnesium, iron, and vitamin B12 among other nutrients. These effects usually do not appear to be clinically relevant; however, there is speculation that some of these effects contribute to some of the other risks of PPIs.
Osteoporosis 11-14
PPIs have been linked to increased risk of fracture in several observational studies. This may be due to impaired calcium absorption; however, the exact mechanism has not been well-established.
Kidney Disease 15,16
PPIs have been implicated in both acute and chronic kidney disease. Again this is mostly observational data, but dose-response relationships have been demonstrated. PPIs appear to increase the risk of kidney disease; however, the mechanism for this is not well understood. There are some case reports of PPIs inducing acute interstitial nephritis, which may contribute.
Dementia and Functional Decline 17-19PPIs have been associated with increased risk of functional decline and loss of activities of daily living. PPIs have also been associated with an increased risk of dementia including Alzheimer’s disease. Both of these links are difficult to prove, and the evidence out there has bias and limitations. Still, studies have shown that patients using a PPI before diagnosis were 40% more likely to be diagnosed with dementia.
Pneumonia 20Observational evidence has shown a 50% increase in risk of developing community acquired pneumonia in patients taking a PPI. This risk may not be relevant after controlling for cofactors.
Clostridium Difficile 21,22There is evidence that PPIs may increase C Diff risk by 74%. This increases to 96% when PPIs are given along with antibiotics. H2RAs have been shown to have a lower risk compared to PPIs. There is also some evidence in mice that PPI use aggravates inflammation associated with C Diff infections.
Heart Attack 23PPI use has been shown to be associated with a 15% increase in risk of heart attack. This was observational data, and there is some argument that this increase in risk may be related to physicians mistaking dyspepsia for an MI.
Stroke 24A recent abstract from the American Heart Association’s 2016 meeting demonstrated a 21% increased risk in ischemic stroke for patients taking PPIs. The abstract also notes a dose-response relationship.

So the question is, I don’t have erosive disease, I’m just on this medication for heartburn/acid reflux.. how do I get off?

When patients discontinue a PPI, they may experience some rebound acid reflux. PPIs increase a hormone called gastrin, which would normally signal the production of acid; however, while patients are taking the PPI this effect is suppressed. Following the withdrawal of the PPI, the elevated gastrin can cause a rebound increased in acid secretion. The effects tend to last for one to two weeks.25,26

When discontinuing a PPI…

  • Talk with your healthcare provider to consider titrating it down; in other words slowly decreasing it.
  • Recognize that heartburn may return for the first week or two.
  • You could consider using OTC Antacids (like Tums) or H2RAs (like Ranitidine or Famotidine) for 1-2 weeks to help with the rebound effect.
  • Consider supplements and alternative options.

Alternative Options

ProductDirectionsRationale
Apple Cider Vinegar 27Take 1-2 teaspoons in a glass of water before meals. (drink with a straw to avoid erosion to teeth)Some theories for how heartburn develops suggest that heartburn can happen as a result of not having enough stomach acid to properly digest food. Adding a small amount of the acidic apple cider vinegar may help reduce symptoms.
Probiotics 27Aim for at least 10 to 20 billion CFUs per day.Heartburn symptoms could be due to an imbalance of GI bacteria. Probiotics can help restore the balance of GI flora and improve digestion. Various bacteria play different roles in digestion.
Digestive Enzymes 28Take 1 capsule with meals.Poor digestion may make heartburn symptoms worse. Adding digestive enzymes can aid digestion and prevent symptoms.
DGL 29-31Take 1 capsule once daily with a meal.Soothes gut lining, stimulates proper digestion.
GI Revive 29-35
(Contains DGL and other ingredients)
Take 7 capsules daily; These can be spaced out however the patient tolerates them. It may be beneficial to take them with meals.GI Revive can help heal the gut if damage or “leaky gut” is suspected. The theory is that since most of the immune system lies in the gut, if there is damage and large inflammatory particles get through, patients will experience inflammation and GI symptoms.
DGL by OrthoMolecular 29-31, 36-401-2 tablets per daySoothes gut lining, stimulates proper digestion. Marshmallow root has a long history of providing a soothing property to mucous membranes. Slippery elm bark also helps protect the GI tract and promotes a healthy cycle of inflammation. Aloe Vera has studies that show it helps balance gastric acid secretion and at low doses protects the membranes from excess acid.
Heartburn Essentials 29-31, 36-371 capsule with each mealHas DGL, marshmallow root, slippery elm, artichoke, and turmeric plus digestive enzymes.

In our practice we typically use GI Revive for patients with suspected leaky gut and inflammation in the gut because it has good nutrients for helping to restore tissues such as zinc carnosine, l-glutamine, and N-Acetyl Glucosamine. As well as some anti-inflammatory supplements like MSM and Quercetin. Then it also has some of the similar ingredients to other products above such as DGL, slippery elm, and marshmallow root, etc. I typically do it for 1-2 months then move on to something a bit less expensive for maintenance if needed. Again this is for patients with inflammation present and you may not know that unless you work with a provider who can do some functional medicine testing.

For most patients with occasional heart burn and reflux without other symptoms of “leaky gut” starting with DGL may be enough. I like the Orthomolecular product that also includes slippery elm bark, marshmallow root, and aloe vera. There is a similar product called Heartburn Essentials by Pure Encapsulations noted in the table as well.

If you aren’t taking the GI Revive, it may be worth considering adding Zinc Carnosine.  It is a great nutrient for helping re-build the mucosal lining. It also has anti-ulcerative properties.

In summary for most patients trying to get off a PPI (without evidence of erosive disease)

I would recommend discussing the following with your health-care provider.

  1. A quality probiotic like OrthoBiotic from OrthoMolecular (I like that this doesn’t need to be in the fridge and includes Saccharomyces Boulardii) or Ther-Biotic Complete Klaire Labs
  2. Digestive Enzymes take your pick of products, I have some of my favorites listed in my Full Script store. If you have symptoms that include a “burning sensation” at this time, you likely want to avoid a product with HCL until soothing nutrients have allowed the mucous membranes to heal.
  3. Deglycyrrhizinated licorice (DGL) (The Orthomolecular product or plain DGL) OR the Heartburn Essentials (Pure Encapsulations).

Also consider

  1. Zinc carnosine  if not taking GI Revive
  2. Ox Bile if your heartburn is worse after fatty meals and you have trouble digesting those, you could add  Ox bile 125 mg with fatty meals. The OrthoDigestzyme product has this in it already but also has HCL.

You can find these in my FullScript Supplement store under the “GastroIntestinal Health” category.

Additional things to consider would be acupuncture, chiropractic care, or osteopathic manipulation with a DO physician. The human body never ceases to amaze me, that God created each part of us to work together, to balance our bodies. If one area is out of whack, it often affects other processes in the body. I have found all three to be helpful at different points in my life. Lastly in the list below, there are some other ideas that are non-medication or non-supplement related steps reducing heartburn as well.

Next steps…. if no improvement you may want to consider doing a stool test with Genova Diagnostics. This will discover if you have inflammation in the gut, an imbalance in bacteria, yeast or an invader like a parasite contributing to symptoms. It also shows you if you have undigested proteins and fats in the stool.  You can find providers in your area at this site. Or come find me in Enon/Fairborn, Ohio! You can also search for functional medicine providers in your area here.

I hope you find this helpful! A HUGE thank you to a past student of mine Dr. Trevor Stump for compiling a lot of this information. He shared with our team of local providers earlier this year.

Dr. Hartzler

Non-Pharmacological Recommendations for Heartburn

  • Weight Loss
  • Smoking Cessation (Quitting Smoking)
  • Avoiding Spicy or Fatty Foods
  • Eating Smaller Meals
  • Avoiding Tight Clothing
  • Elevating the Head of the Bed at Night
  • Avoiding Meals within 3 Hours of Bedtime
  • Yoga or Meditation (Stress Relief)
  • Eating More Slowly

*this post contains affiliate links to products I recommend, all the supplements recommended in this post can be found in my FullScript Store You do have to set-up a quick account to use.  Thanks for supporting the blog, remember 10% goes to support various ministries! Check out My Favorite Things for more details. Reminder that this information is general and personal specific health decisions should be made between you and your medical provider. Remember supplements can interact with certain medications, so make sure to include a pharmacist knowledgeable in this area in your decisions as well.

References:

  1. Gawron AJ, Feinglass J, Pandolfino JE, Tan BK, Bove MJ, Shintani-smith S. Brand name and generic proton pump inhibitor prescriptions in the United States: insights from the national ambulatory medical care survey (2006-2010). Gastroenterol Res Pract. 2015;2015:689531.
  2. Forgacs I, Loganayagam A. Overprescribing proton pump inhibitors. BMJ. 2008;336(7634):2-3.
  3. Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013;108(3):308-28.
  4. Heidelbaugh JJ, Kim AH, Chang R, Walker PC. Overutilization of proton-pump inhibitors: what the clinician needs to know. Therap Adv Gastroenterol. 2012;5(4):219-32.
  5. Masclee GM, Sturkenboom MC, Kuipers EJ. A benefit-risk assessment of the use of proton pump inhibitors in the elderly. Drugs Aging. 2014;31(4):263-82.
  6. Scarpignato C, Gatta L, Zullo A, Blandizzi C. Effective and safe proton pump inhibitor therapy in acid-related diseases – A position paper addressing benefits and potential harms of acid suppression. BMC Med. 2016;14(1):179.
  7. Benmassaoud A, Mcdonald EG, Lee TC. Potential harms of proton pump inhibitor therapy: rare adverse effects of commonly used drugs. CMAJ. 2016;188(9):657-62.
  8. Xie Y, Bowe B, Li T, et al Risk of death among users of Proton Pump Inhibitors: a longitudinal observational cohort study of United States veterans BMJ Open 2017;7:e015735. doi: 10.1136/bmjopen-2016-015735
  9. Aronson JK. Inhibiting the proton pump: mechanisms, benefits, harms, and questions. BMC Med. 2016;14(1):172.
  10. Jung SB, Nagaraja V, Kapur A, Eslick GD. Association between vitamin B12 deficiency and long-term use of acid-lowering agents: a systematic review and meta-analysis. Intern Med J. 2015;45(4):409-16.
  11. Zhou B, Huang Y, Li H, Sun W, Liu J. Proton-pump inhibitors and risk of fractures: an update meta-analysis. Osteoporos Int. 2016;27(1):339-47.
  12. Thaler HW, Sterke CS, Van der cammen TJ. Association of Proton Pump Inhibitor Use with Recurrent Falls and Risk of Fractures in Older Women: A Study of Medication Use in Older Fallers. J Nutr Health Aging. 2016;20(1):77-81.
  13. Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA 2006;296:2947-53.
  14. Corley, D.A., Kubo, A., Zhao, W., Quesenberry, C., Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients, Gastroenterology (2009), doi:10.1053/j.gastro.2010.03.055.
  15. Lazarus B, Chen Y, Wilson FP, et al. Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease. JAMA Intern Med. 2016;176(2):238-46.
  16. Arora P, Gupta A, Golzy M, et al. Proton pump inhibitors are associated with increased risk of development of chronic kidney disease. BMC Nephrol. 2016;17(1):112.
  17. Haenisch B, Von holt K, Wiese B, et al. Risk of dementia in elderly patients with the use of proton pump inhibitors. Eur Arch Psychiatry Clin Neurosci. 2015;265(5):419-28.
  18. Batchelor R, Gilmartin JF, Kemp W, Hopper I, Liew D. Dementia, cognitive impairment and proton pump inhibitor therapy – a systematic review. J Gastroenterol Hepatol. 2017; e-pub ahead of print.
  19. Corsonello A, Maggio M, Fusco S, et al. Proton pump inhibitors and functional decline in older adults discharged from acute care hospitals. J Am Geriatr Soc. 2014;62(6):1110-5.
  20. Lambert AA, Lam JO, Paik JJ, Ugarte-gil C, Drummond MB, Crowell TA. Risk of community-acquired pneumonia with outpatient proton-pump inhibitor therapy: a systematic review and meta-analysis. PLoS ONE. 2015;10(6):e0128004.
  21. Kwok CS, Arthur AK, Anibueze CI, Singh S, Cavallazzi R, Loke YK. Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. Am J Gastroenterol. 2012;107(7):1011-9.
  22. Hung YP, Ko WC, Chou PH, et al. Proton-Pump Inhibitor Exposure Aggravates Clostridium difficile-Associated Colitis: Evidence From a Mouse Model. J Infect Dis. 2015;212(4):654-63.
  23. Shah NH, Lependu P, Bauer-mehren A, et al. Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population. PLoS ONE. 2015;10(6):e0124653.
  24. Sehested TSG, Fosbol EL, Hansen PW, Charlot MG, Torp-Pedersen C, Gislason GH. Abstract 765. Proton pump inhibitor use increases the associated risk of first-time ischemic stroke. A nationwide cohort study. Presented at: the 2016 American Heart Association Scientific Sessions. November 12-16, 2016; New Orleans, LA.
  25. Reimer C, Søndergaard B, Hilsted L, Bytzer P. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology. 2009;137(1):80-7, 87.e1.
  26. Niklasson A, Lindström L, Simrén M, Lindberg G, Björnsson E. Dyspeptic symptom development after discontinuation of a proton pump inhibitor: a double-blind placebo-controlled trial. Am J Gastroenterol. 2010;105(7):1531-7.
  27. Kines K, Krupczak T. Nutritional Interventions for Gastroesophageal Reflux, Irritable Bowel Syndrome, and Hypochlorhydria: A Case Report. Integr Med (Encinitas). 2016;15(4):49-53.
  28. National Enzyme Company, TNO Nutrition and Food Research. The First Quantitative Evidence Proving The Efficacy Of Supplemental Enzymes. National Enzyme Company. 2004. http://www.enzymeessentials.com/TNO_Research_Web.pdf.
  29. Aly AM, Al-alousi L, Salem HA. Licorice: a possible anti-inflammatory and anti-ulcer drug. AAPS PharmSciTech. 2005;6(1):E74-82.
  30. Momeni A, Rahimian G, Kiasi A, Amiri M, Kheiri S. Effect of licorice versus bismuth on eradication of Helicobacter pylori in patients with peptic ulcer disease. Pharmacognosy Res. 2014;6(4):341-4.
  31. Brogden RN, Speight TM, Avery GS. Deglycyrrhizinised liquorice: a report of its pharmacological properties and therapeutic efficacy in peptic ulcer. Drugs. 1974;8(5):330-9.
  32. Mahmood A, Fitzgerald AJ, Marchbank T, et al. Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes. Gut. 2007;56(2):168-75.
  33. Klimberg, V. Suzanne, M.D., et al. Prophylactic Glutamine protects the intestinal mucosa from radiation injury. Cancer 1990, July 1;66(1):62-68.
  34. Hickson R, et al. Glutamine prevents downregulation of myosin heavy chain synthesis and muscle atrophy from glucocorticoids. Am J Physiol 1995 Apr;268(4 Pt 1):E730-E734.
  35. Noyer CM, Simon D, Borczuk A, Brandt LJ, Lee MJ, Nehra V. A double-blind placebo-controlled pilot study of glutamine therapy for abnormal intestinal permeability in patients with AIDS. Am J Gastroenterol 1998;93(6):972-5.
  36. Engels, G. Marshmallow. HerbalGram. 2007;(75):1-5.
  37. From: https://umm.edu/health/medical/altmed/herb/slippery-elm. Accessed 3-3-14. (Slippery Elm reference)
  38. Blitz, J.J., Smith, J.W. et al. Aloe vera gel in peptic ulcer therapy: preliminary report. J Am Osteopath Assoc. 1963;62:731-735.
  39. Rajendran A, Sobiya G et al. Study on the Effective Supplemenation of Aloe vera Gel Antacid to Peptic Ulcer Res J Medicine & Med Sci. 2008; 3(2):132-134.
  40. Gawron-Gzella, A., Witkowska-Banaszczak, E. et al. [Herbs and herbal preparations applied in the treatment of gastric hyperacidity, gastric and duodenal ulcer in cigarette smokers]. Przegl Lek. 2005; 62(10):1185-1187.

 

Leave a Reply 0 comments

Leave a Reply: