Should You Use Prokinetic Drugs for Gastrointestinal Issues?

Understanding How Prokinetic Drugs Work and When to Use Them

If you have been struggling with gastrointestinal problems such as chronic constipation and stomach pain for a long time, it can be frustrating to feel like you’re not getting better. 

It has been increasingly common, including in the functional medicine space, for people to turn to prokinetics to treat chronic constipation and/or SIBO (small intestinal bacterial overgrowth) or constipation-predominant IBS (irritable bowel syndrome). Prokinetics are pharmaceutical or natural agents that help to increase gastrointestinal motility – in other words, to get food to move through the digestive tract better.  

Prokinetics can certainly be helpful for some people, but widespread use of prokinetic agents is probably not necessary for most people with these conditions. In this article, we will look at what prokinetic drugs are, how they work, when to use them, and the best way to resolve the root causes of constipation. 

Prokinetic drugs: woman with extreme abdominal pain sitting on her couch

What Are Prokinetic Drugs?

Prokinetic drugs support healthy motility throughout your stomach and intestines. Motility refers to the way food moves through your intestinal tract. Slow motility most often shows up as constipation. Good motility is important for gut health, as it keeps the intestinal system in balance. And without good motility, stagnant food in the digestive tract can foster excessive bacterial growth in the gut, which can lead to gut dysbiosis.   

Prokinetic agents are most often used in gastroenterology for treating gastroesophageal reflux (GERD). They are also becoming more widely used to treat constipation and other common symptoms of IBS and SIBO, because in some cases these conditions may be caused by low gastrointestinal motility.

There are both pharmaceutical prokinetic drugs and natural options. Some of the pharmaceutical agents are cisapride, metoclopramide, domperidone, and erythromycin. Natural agents with similar effects may include peppermint oil, magnesium, and ginger. 

Understanding Motility

Should You Use Prokinetic Drugs for Gastrointestinal Issues? - Gut Motility %26 Peristalsis Landscape L

Gastrointestinal motility is a complex system. Understanding how it works will help you understand how and why different prokinetic agents work. 

Motility requires good communication between different cells, including enteric (intestinal) neurons, interstitial cells of Cajal (ICC), and smooth muscle cells. Together, these create peristalsis, which is the contraction and relaxation of the intestinal muscles that moves food through the GI tract. The ICC are important in this process. They are located in many parts of the body, including the esophagus, stomach, large and small intestine, urinary tract, and even heart muscles [1 Trusted SourcePubMedGo to source].

The gut-brain connection is central to motility, as neurotransmitters (chemical messengers that help signals travel from neurons in the brain to other cells throughout the body, including in the gut) help to regulate peristalsis. 

Without proper communication and peristalsis, motility slows down. This is where prokinetics can be useful, as they help to stimulate peristalsis and motility. 

Pharmaceutical Prokinetic Drugs

Should You Use Prokinetic Drugs for Gastrointestinal Issues? - What Are Prokinetics Landscape L

Prokinetic drugs generally work by either stimulating or suppressing neurotransmitters in order to encourage peristalsis and improve motility. 

Let’s take a look at the various classes of pharmaceutical prokinetic drugs and their effectiveness. The table below shows how most of these drugs work in the central nervous system (CNS), how they affect neurotransmitters, and their benefits. 

ClassProkinetic NamesProkinetic Effects
Serotonin receptor agonists: Acts on serotonin receptors in the intestine to stimulate peristaltic contractions. Prucalopride (Motegrity, Resolor)

Mosapride

Tegaserod & Cisapride* 
• Prucalopride reduced bouts of reflux and length of time of reflux, increased gastric emptying [2 Trusted SourcePubMedGo to source].
• Both prucalopride and mosapride were found to improve IBS-C, constipation predominant irritable bowel syndrome [3 Trusted SourcePubMedGo to source].
•*Both tegaserod and cisapride have side effects of cardiac arrhythmia. Cisapride was removed from the market [4 Trusted SourcePubMedGo to source].
Macrolides: Antibiotics that are also motilin agonists (motilin is a gastrointestinal hormone) [4 Trusted SourcePubMedGo to source]Erythromycin

Azithromycin
• For patients with SIBO and IBS, erythromycin led to about five months of symptom improvement, but not long-lasting results [5 Trusted SourcePubMedGo to source].  
Dopamine antagonist: Blocks dopamine receptors.Levosulpiride

Metoclopramide
• Levosulpiride increases motility and is an antiemetic (anti-vomiting agent.) It may also be used as an antidepressant and antipsychotic [6].
• When used with PPIs (proton pump inhibitors) as a treatment for reflux disease, levosulpiride may decrease the risk of SIBO (small intestinal bacterial overgrowth) associated with long-term PPI use [7 Trusted SourcePubMedGo to source].
• This class of drugs has been shown to stimulate peristalsis because they are cholinergic, meaning they act on the nerve cells that affect the neurotransmitter acetylcholine [8 Trusted SourcePubMedGo to source].
Opioid receptor antagonist: Blocks opioid receptors. Naltrexone• Low dose naltrexone has shown efficacy in helping with gastrointestinal disorders such as IBS with or without SIBO and chronic constipation. Some report adverse effects such as neurological issues and additional GI distress, but most people find it tolerable and helpful [9 Trusted SourcePubMedGo to source].

Natural Prokinetic Agents

There are a few natural prokinetic agents that have also shown promise in improving motility disorders. There are a few products that have been studied for use as natural prokinetics, such as iberogast, motilpro, and prodigest. These products all contain natural prokinetic agents, and we are going to talk about the research behind these agents below. 

Iberogast (STW 5) is an herbal compound made from five different plant extracts [10 Trusted SourcePubMedGo to source]. It has been found to be safe and as effective at treating functional dyspepsia (indigestion) and IBS as metoclopramide and cisapride, but with fewer adverse effects [11 Trusted SourcePubMedGo to source, 12 Trusted SourcePubMedGo to source, 13 Trusted SourcePubMedGo to source, 14 Trusted SourcePubMedGo to source].

Ginger has been widely studied to help with stomach upset and other gi issues. In relation to improving constipation, one study showed that eating ginger after soup accelerated gastric emptying and stimulated stomach contractions [15 Trusted SourcePubMedGo to source]. There is another study, though, that indicates ginger is no more effective at changing the rate of gastric emptying than placebo in clinical trials [14 Trusted SourcePubMedGo to source].

Artichoke and ginger have been studied under the label of prodigest, which is a combination of 100mg of artichoke and 20 mg of ginger extracts. It was found to be 24% better than placebo at improving motility after a meal [16 Trusted SourcePubMedGo to source]. 

Peppermint oil is another natural prokinetic many people have been using for centuries to help an upset stomach. Peppermint oil has been shown to help the gut by decreasing inflammation, improving motility, and improving the balance of the gut microbiome [17 Trusted SourcePubMedGo to source, 18 Trusted SourcePubMedGo to source, 19 Trusted SourcePubMedGo to source].

Guar gum is a fiber made from guar beans that you may see on the back of your coconut or other nut milk containers, as it is also used as a thickener. Guar gum has also been used to increase motility. One study involving SIBO patients found that the combination of the medication rifaximin with partially hydrolysed guar gum was better at eradicating SIBO than rifaximin alone [20 Trusted SourcePubMedGo to source]. However, some people experience bloating and diarrhea when consuming foods with guar gum [20 Trusted SourcePubMedGo to source, 21 Trusted SourcePubMedGo to source].

Probiotics are live, beneficial bacteria. While they may not be used strictly as prokinetics, probiotics have been shown to help resolve constipation, significantly improve symptoms of SIBO and IBS, and improve overall gut health. 

For example, probiotics have been shown to improve mild to moderate delays in gastric emptying [22 Trusted SourcePubMedGo to source]. 

We go more in depth on probiotics later in this article, but probiotics have also been shown to improve many of the underlying causes of SIBO and constipation, making them a well-rounded treatment option. In fact, a meta-analysis of 18 clinical trials concluded that probiotics were an effective treatment for SIBO. They reduced bacterial overgrowths and hydrogen concentrations, as well as improved symptoms [23 Trusted SourcePubMedGo to source].  

Prokinetic drugs: ginger root and ginger powder in a bowl

Why Prokinetic Drugs Are An Incomplete Solution 

While prokinetics can be effective in some cases, slow motility may really be a symptom of an underlying gut issue, which is why just using prokinetics to improve constipation is an incomplete solution. If we keep treating the symptom, the root cause will never be resolved and we will continue to chase symptoms. We want to focus on healing rather than symptom management. 

Many things can contribute to poor gut motility, and those are the issues that we should look to resolve in treatment for constipation, SIBO, and other gastrointestinal concerns.

Here are a few of the underlying causes that may be leading to constipation:

  • Inflammation from any number of factors such as an inflammatory diet, leaky gut, use of antibiotics, and even lifestyle factors such as chronic stress or poor sleep can lead to constipation [24 Trusted SourcePubMedGo to source, 25 Trusted SourcePubMedGo to source].
  • Food poisoning contributes to constipation, as it can damage the gut microbiome and even lead to the development of antibodies that damage motility [26 Trusted SourcePubMedGo to source]. That damage and resulting decreased motility can lead to SIBO because stagnant food creates a microbiome imbalance. However, this does not mean prokinetics treat SIBO. In fact, people with IBS-C often do not test positive for these antibodies, so the antibodies are not always an indicator of constipation [27 Trusted SourcePubMedGo to source, 28 Trusted SourcePubMedGo to source]. 
  • Gut dysbiosis (an imbalance of the bacteria in the gut) leads to constipation in many people. Gut dysbiosis can be due to many facts, such as inflammation and food poisoning mentioned above [24 Trusted SourcePubMedGo to source, 29 Trusted SourcePubMedGo to source].  
  • Damage to the ICC (interstitial cells of Cajal), either from autoimmune issues or other reasons such as the damage from food poisoning mentioned above may lead to constipation [28 Trusted SourcePubMedGo to source]. 
Woman with her hands near her stomach

Resolving Gut Issues

Improving the underlying causes of slow gut motility doesn’t have to be complicated. For most people, we can use three interventions: an anti-inflammatory diet, probiotics, and (if needed) herbal antimicrobials, to create better gut health. 

Anti-inflammatory Diet

I suggest most of my patients start with a Paleo diet in order to decrease inflammation and improve gut health. The Paleo diet removes foods that create an immune response such as grains, gluten, legumes, and dairy [30 Trusted SourcePubMedGo to source]. The paleo diet also improves the gut microbiome, which as we noted earlier, is important when it comes to treating SIBO, IBS, and other digestive concerns [31 Trusted SourcePubMedGo to source, 32 Trusted SourcePubMedGo to source].

If a Paleo diet doesn’t provide sufficient relief, it’s worth trying a low FODMAP diet next. The low-FODMAP diet has also been shown to be effective for inflammation and an imbalanced gut microbiome that may be leading to IBS or SIBO. A low-FODMAP diet restricts bacteria-feeding carbs, or, fermentable oligo-, di-, mono-saccharides and polyols such as wheat, onion, legumes, dairy, and fructose which can ferment in the gut and cause gut issues, including constipation [33 Trusted SourcePubMedGo to source, 34 Trusted SourcePubMedGo to source, 35 Trusted SourcePubMedGo to source]. 

Probiotics

Probiotics are incredibly important for overall gut health and should be part of the plan for any dysfunction of the gut. 

Probiotics have consistently been shown to be helpful in treating IBS, SIBO, and constipation. 

Not only have probiotics been shown to improve the symptom of constipation, but probiotics can resolve many of the underlying causes of constipation. 

Antimicrobials

If trying an anti-inflammatory diet and probiotics do not resolve your symptoms, you may want to try herbal antimicrobials. These can help to remove unwanted gut microbes that may be contributing to dysbiosis and dysmotility. SIBO treatment often includes the use of prescription antibiotics, which have been shown to eliminate SIBO for 67% of patients [47 Trusted SourcePubMedGo to source]. 

Herbal antimicrobials work in the same way as antibacterials and have also been shown to be effective in resolving SIBO [48 Trusted SourcePubMedGo to source49 Trusted SourcePubMedGo to source].

When to Use Prokinetics

Prokinetics have been shown to help with constipation. You and your healthcare professional may choose to use them for a short period of time. However, there are risk factors with some of the pharmaceutical prokinetics, and they may not resolve the underlying issue causing the dysmotility.

This is why I find it best to work on improving the gut through an anti-inflammatory diet, probiotics, and antimicrobials as needed. If those interventions do not work well enough, and constipation or other SIBO symptoms are getting in the way of your daily functioning, then you may want to look at using prokinetics while your gut improves. 

You will want to work with your healthcare provider, especially if you will be using pharmaceutical prokinetics, as you will need a prescription and will want to monitor any adverse side effects. 

A functional medicine provider will probably lean towards one of the natural prokinetics first, as they have been shown to often be as effective as pharmaceutical prokinetics with fewer side effects. 

Putting It All Together

There can be a time and place for prokinetics, but we generally do not want them to be our first step when dealing with slow gut motility. For your long-term health, focus on resolving the root cause of poor gut motility, such as inflammation and gut dysbiosis. My book, Healthy Gut, Healthy You, can give you more information on gut health and inflammation as well as more details on using an anti-inflammatory diet, probiotics, and antimicrobials. If you would like more personalized help, you can visit our functional medicine center virtually or in person.

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