Heartburn and Proton Pump Inhibitors: A Case Study in Drug-Like Mentality

One of the big lessons I learned from studying medicinal plants is that, when a health concern isn’t an immediate emergency, it is better to focus on supporting the living human than trying to control one piece or another of the physiology.

So, for example, we use gentle infusions made with herbs like catnip and elderflower for children’s seasonal challenges instead of drugs that might reduce fever or suppress the secretion of mucus. It is often the case that over-the-counter and prescription medications, useful as they are, come at our bodies using a drug-like mentality: find the most obvious problem, and hit back at it hard. I can’t argue that this approach has been incredibly successful in a range of situations, notably acute infection, life-threatening autoimmune inflammation, shock, and acute cardiovascular events – but that doesn’t, by extension, mean that this drug-like mentality is the only approach, or that it should be the first approach in any given situation. In many cases, the herbalist’s approach of support over control makes a lot of sense.

Nowhere is this perhaps more clear than in the way we address occasional heartburn. There are a few options to choose from: regular antacids like Tums or bicarbonate, digestive bitters, H2 receptor blockers like Zantac, and proton pump inhibitors like Prilosec, to name just a few. The proton pump inhibitors are by far the most prescribed type of heartburn and acid reflux medication: in fact, these are the fourth top-selling prescription in the United States, with over 15 million monthly prescriptions.1 By some estimates, over 20% of the population is taking a proton pump inhibitor, up from about 15% ten years ago.2 This trend isn’t surprising: most research finds that well over 50% of the population in the United States experiences heartburn at least weekly.3 

The drug-like mentality looks at heartburn and correctly identifies that stomach acid is the cause of the painful burning sensations in the lower esophagus (usually perceived around the breastbone, but rising sometimes all the way up to the back of the throat).

If stomach acid is the cause of distress, then (so the argument goes) eliminating the acid is the solution: chemically neutralize it with antacids, block the signal for acid production with a H2 receptor blocker, or keep acid-producing cells from synthesizing and excreting acid with a proton pump inhibitor (PPI).

All of these approaches give some measure of relief: antacids are quickest, but also wear off quickly; H2 receptor blockers work fairly quickly and last longer, but are milder in their effects; PPIs take time to start working (a few hours) but are very effective and long-lasting. Doing something about the upward reflux of acid in heartburn is important: it’s not just a distressing symptom, it can also lead to changes in the cellular structure of the esophagus and, eventually, to esophageal cancer.4 For all these reasons, it’s no wonder that PPIs are the fourth top-selling prescription in the United States, and that heartburn drugs are the third top-selling over-the-counter remedy (after cold/flu products and painkillers).5

But what exactly is happening when we experience the first, occasional bouts of heartburn? There really seem to be four major components [FIGURE 1]:

As we’ve seen, stomach acid (hydrochloric acid, produced primarily to help digest protein and sterilize our food).6
The muscular valve at the bottom of the throat known as the lower esophageal sphincter, or LES (the purpose of which is to keep the acid in the stomach, where it belongs).7
Nerve mechanisms that help regulate movement of food, contraction of the LES, and secretion of acid, enzymes and fluid (notably mediated by the vagus nerve, part of our “rest-and-digest” nervous system, but also by gut-specific nerves).8
Hormonal mechanisms that synergize with the vagus nerve to regulate movement, tone in the valves, and secretions (an interesting counterbalance of two hormones, melatonin which seems to favor closing valves in the upper gut and serotonin which seems to favor increased movement and secretion in the lower gut).9

    It is interesting to note that acid is just one of the pieces here: we also have mechanical components (valves, muscles), and neuro-hormonal regulatory components that govern muscle tone and secretions (including secretion of acid).

    These other parts of the digestive system merit as much attention as the hydrochloric acid itself.10 So let’s take a closer look.

    Secretions like stomach acid are crucial in breaking down the food we eat into “building blocks” that we can absorb and use. The digestive system regulates these secretions pretty closely, as you can imagine, releasing just what is needed in response to cues it gets from sensory organs like taste and smell receptors. For example, we start salivating right away when we smell a delicious meal! But this trend continues all throughout the gut. High protein meals lead to more hydrochloric acid and pepsin production in the stomach, to jump-start the breakdown of protein. Next, the pancreas releases bicarbonate to neutralize the hydrochloric acid in the food leaving the stomach, along with a range of specific enzymes depending on the relative amounts of protein, fats and carbs we’ve eaten. The liver releases bile to help with the absorption of fats. And further down, in the colon, the secretion and absorption of water is finely tuned to make sure that the stool is the right consistency – not too dry, not too loose.

    But we can’t forget the action of muscles that line the whole gut: taken as a whole, they govern motility and peristalsis, physically timing the movement of food and pushing bulk material (like the stool) on down the pike. Motility is important for things like regular bowel habits, complete digestion of food, and yes, the prevention of occasional heartburn: after all, secretions don’t matter much if the food we eat isn’t in the right place at the right time. Finally, in a few special areas along the gut, there are concentrations of tighter bands of muscle that act as valves to isolate different gut compartments. The internal and external anal sphincters are examples: imagine if we didn’t have the ability to keep our stool contained for 12-24 hours! But the LES at the bottom of our throat is another example – and in heartburn, this valve stays loose and can’t keep stomach contents where they belong.11

    The coordination of secretion and motility is accomplished using both nerves and hormones [FIGURE 2]. This dance is incredibly complex and beautiful, laced with feedback loops and connected to our immunity, moods, and more. It is essential for the proper absorption of all the nutrients we consume. And altering any one part of this dance can affect the whole in (sometimes unpredictable) ways. At the hub of all this activity is a network of nerves, the enteric nervous system (also referred to as the “brain of the gut”, or even “second brain”). It is connected to specialized cells that both sense the contents of the food we consume, and also secrete hormones into the bloodstream that coordinate action with the enteric nervous system. In the upper GI tract – the mouth, esophagus, and stomach – these cells are known as enteroendocrine cells.12 They secrete hormones that regulate secretions and motility, and also affect appetite and feeding behavior: this is where we see, for example, the secretion of melatonin that contributes to a greater level of tone to the LES (and consequently less upward reflux of stomach content). The action of the upper GI enteroendocrine cells also help explain appetite regulation: if motility is reduced, we tend to feel full more quickly; additionally, hormones such as polypeptide YY from enteroendocrine cells seem to make us feel full and satisfied. On the gut side, enteroendocrine cells can sense the presence of fats and protein, and also strongly bitter-tasting substances (via bitter taste receptors).

    Further down, in the intestinal/absorptive side of the gut, we find more hormone-secreting cells known as enterochromaffin cells. They secrete hormones such as serotonin into the local area and into the general circulation, too: here, serotonin seems able to relax the gut, balance water absorption and secretion, and regulate bowel motility.13 Remarkably, enterochromaffin cells have receptors on their surface that are very similar to the odor receptors in our noses: they sense the presence of volatile molecules from plants, and increase serotonin secretion in response.14

    When you look at an herbal bitters formula (typically a balanced blend of bitter-tasting plants like gentian or artichoke, coupled with aromatic plants from the citrus family, mint, ginger or more exotic spices like cardamom and allspice) [FIGURE 3] you start to see that these traditional preparations are well-tuned to interfacing with the entire dance of neuro-hormonal activity in the gut: first off, via action on enteroendocrine cells and stimulation of the enteric nervous system, bitter-tasting plants can help close the LES and reduce upper gastric motility,15 all while improving digestive secretions.16 Further down, the aromatic volatile molecules in herbal bitters interface with enterochromaffin cells and help balance movement and moisture in the intestines and bowel. Crucially, bitters don’t actually provide anything digestive: they aren’t hydrochloric acid, nor chemical neutralizers of acid; they don’t contain enzymes, or bile, or have any stimulant laxative action; they don’t (usually) coat, or soothe, or directly inhibit GI tract inflammation. However, by a deep and intimate connection to the complex neuro-hormonal dance of the GI tract, and via the taste and olfaction receptors found throughout the gut, they are able to help restore the correct operating environment, the cues and signals that the GI tract needs to secrete the right hormones, fire the right nerves, and bathe our food in the right secretions for optimal digestion.17

    You will see right away that this is a very different approach from the drug-like mentality that advocates for PPIs and for blocking acid as a way forward in managing heartburn. For occasional symptoms, a traditional digestive bitter is a better choice because it trains the body to work properly, prevents overeating and increased abdominal pressure so often a trigger for heartburn, and does so by engaging all the players in the digestive dance.

    Drugs isolate one component to a system – in this case, stomach acid – and attempt to control it. Many of our most beloved herbal formulas, on the other hand, touch many pieces of the living system, supporting function rather than trying to control a part of it.

    The differences between herbal bitters and a PPI are a great example of these contrasting approaches.

    In the case of heartburn, knowing what we now know, it makes little sense to use acid blockers for prolonged periods of time. First off, drugs such as Nexium and Prilosec (PPIs) aren’t meant to be used for more than eight weeks at a time.18 But additionally, even when used for only eight weeks, these drugs only address a small piece of the puzzle: we’ve known for over 50 years that the tone of the LES is an essential part of how we keep heartburn at bay.19 So why are we only looking at acid production? In a fascinating study from 2010, researchers compared heartburn sufferers to those with no symptoms of reflux pain.20 At baseline, those with heartburn had a LES tone value around 10, whereas those without measured around 22. Some folks with heartburn got placebo, others got a PPI, and a third group got melatonin: the hypothesis was that you can address heartburn by giving an acid blocker or a hormone that increases LES tone, and both might be helpful. After 8 weeks, both the PPI and the melatonin groups reported much improvement – but while the PPI group’s LES tone remained at around 10, the melatonin group’s was closer to 20. One approach turns off secretions, the other restores normal muscle tone. Which would you prefer?

    I submit that there is a third option, neither an inhibitory drug nor an exogenous hormone: bitter and aromatic plants, blended into traditional digestive bitters, interface with all the pieces of the digestive dance and help regulate all its components. So, while melatonin may help with LES tone, it does little to support the liver’s bile production, or the bowel’s rhythm.

    While a PPI may help with the burning sensations of heartburn, it also leads to decreased iron, B12, magnesium and calcium absorption21 and a worsening of bone density,22 and may also increase the risk of heart attack (in some cases doubling the risk).23

    In a recent report that looked at over 3 million US veterans, PPIs were found to significantly increase the risk of death.24 And while melatonin is much more benign than omeprazole (the most common PPI), its use still comes from a drug-like mentality: this hormone increases LES tone, and we need more LES tone in heartburn, so let’s take more hormone to control the valve’s tone.

    Bitters are totally different: they support the organic processes of secretion, motility, and neurohormonal communication in the gut. As such, they are a great example of what herbal medicine has to offer—

    a truly nurturing and supportive approach, one that trusts and works with the complex processes of human physiology while at the same time increasing the diversity and richness of our human experience. Try a good quality herbal bitter formula for occasional heartburn symptoms. You won’t be disappointed.


    Guido Masé RH(AHG)is a clinician and educator in the Western herbal tradition. He spent his childhood in Italy and has been living in Vermont since 1996. His practice interweaves clinical experience, mythology, and science.
    He is chief herbalist at Urban Moonshine, clinician at the Burlington Herb Clinic, faculty member and clinical supervisor at the Vermont Center for Integrative Herbalism, teacher in herbal medicine at the University of Vermont, and author of The Wild Medicine Solution and DIY Bitters. He is developing the integrative phytotherapy department at Wasso Hospital in Loliondo, Tanzania.


    1. 100 Best-Selling, Most Prescribed Branded Drugs Through March – Medscape – May 06, 2015

    2. Qato, Dima M., et al. “Changes in prescription and over-the-counter medication and dietary supplement use among older adults in the United States, 2005 vs 2011.” JAMA internal medicine 176.4 (2016): 473-482.

    3. Cohen, Erica, et al. “GERD symptoms in the general population: prevalence and severity versus care-seeking patients.” Digestive diseases and sciences 59.10 (2014): 2488.

    4. Shaheen, Nicholas, and David F. Ransohoff. “Gastroesophageal reflux, barrett esophagus, and esophageal cancer: scientific review.” Jama 287.15 (2002): 1972-1981.

    5. Consumer Health Products Association statistics: https://www.chpa.org/OTCsCategory.aspx

    6. Wikipedia: https://en.wikipedia.org/wiki/Gastric_acid 

    7. Wikipedia: https://en.wikipedia.org/wiki/Esophagus#Sphincters

    8. Wikipedia: https://en.wikipedia.org/wiki/Enteric_nervous_system

    9. Wikipedia: https://en.wikipedia.org/wiki/Enteroendocrine_cell and regarding melatonin: Konturek, S. J., et al. “Role of melatonin in upper gastrointestinal tract.” Journal of physiology and pharmacology 58.6 (2007): 23-52.

    10. Miller, Larry, et al. “Physiology of the upper segment, body, and lower segment of the esophagus.” Annals of the New York Academy of Sciences 1300.1 (2013): 261-277.

    11. Katzka, David A., and A. J. DiMarino. “Pathophysiology of gastroesophageal reflux disease: LES incompetence and esophageal clearance.” The esophagus. Boston: Little, Brown (1992): 449-55.

    12. Sternini, Catia, Laura Anselmi, and Enrique Rozengurt. “Enteroendocrine cells: a site of ‘taste’ in gastrointestinal chemosensing.” Current opinion in endocrinology, diabetes, and obesity 15.1 (2008): 73.

    13. Baig, M. K., et al. “Variability in serotonin and enterochromaffin cells in patients with colonic inertia and idiopathic diarrhoea as compared to normal controls.” Colorectal Disease 4.5 (2002): 348-354.

    14. Braun, Thomas, et al. “Enterochromaffin cells of the human gut: sensors for spices and odorants.” Gastroenterology 132.5 (2007): 1890-1901.

    15. Chen, Monica C., et al. “Bitter stimuli induce Ca 2+ signaling and CCK release in enteroendocrine STC-1 cells: role of L-type voltage-sensitive Ca 2+ channels.” American Journal of Physiology-Cell Physiology 291.4 (2006): C726-C739.

    16. Drewnowski, Adam, and Carmen Gomez-Carneros. “Bitter taste, phytonutrients, and the consumer: a review.” The American journal of clinical nutrition 72.6 (2000): 1424-1435.

    17. Rozengurt E. Taste receptors in the gastrointestinal tract. I. Bitter taste receptors and -gustducin in the mammalian gut. Am J Physiol Gastrointest Liver Physiol 291: G171–G177, 2006.

    18. FDA: prescribing information for Prilosec (omeprazole) https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019810s096lbl.pdf

    19. Maclaurin, Campbell. “The intrinsic sphincter in the prevention of gastro-oesophageal reflux.” The Lancet 282.7312 (1963): 801-805.

    20. Kandil, Tharwat S., et al. “The potential therapeutic effect of melatonin in gastro-esophageal reflux disease.” BMC gastroenterology 10.1 (2010): 7.

    21. Ito, Tetsuhide, and Robert T. Jensen. “Association of long-term proton pump inhibitor therapy with bone fractures and effects on absorption of calcium, vitamin B12, iron, and magnesium.” Current gastroenterology reports 12.6 (2010): 448-457.

    22. Ozdil, Kamil, et al. “Bone density in proton pump inhibitors users: a prospective study.” Rheumatology international 33.9 (2013): 2255-2260.

    23. Shah, Nigam H., et al. “Proton pump inhibitor usage and the risk of myocardial infarction in the general population.” PLoS One 10.6 (2015): e0124653.

    24. Xie, Yan, et al. “Risk of death among users of Proton Pump Inhibitors: a longitudinal observational cohort study of United States veterans.” BMJ Open7.6 (2017): e015735.


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