Prokinetic Agents – A Scientific Review

Why is Gastrointestinal Motility Important?

GI motility is defined as the movements of the muscles of the digestive organs, which include the esophagus, stomach, small and large intestines. GI motility allows the content of the digestive tract to move through each stage of digestion ¹.

When the nerves and/or muscles of these organs do not function properly, people can suffer from common symptoms associated with impaired GI motility, ¹ such as:

• Severe constipation
• Acid reflux disease
• Recurrent vomiting
• Recurrent obstructions
• Bloating

Below are the GI disorders that are associated with motility issues by specific organs ².

Migrating Motor Complex: A Critical Motility Promoter

The migrating motor complex (MMC) is a cyclic and recurring pattern of motility that occurs in the stomach and small intestine during periods of fasting and is interrupted following food consumption ³.

Many species, including humans, have the MMC, which is further subdivided into four main phases that repeat every 1.5 to 2 hours in normal and healthy individuals.

Phases of MMC

1. 45-60 minute period of smooth muscle inactivity in the GI system. Muscle contraction during this state of motility is rare.
2. 30 minute period in which peristalsis, or muscle contractions of the GI system beginning in the stomach and continuing through the small intestine, occur and progressively increase in their frequency.
3. 5-15 minute period in which rapid and evenly spaced peristaltic contractions occur. During this phase, the pylorus of the stomach remains open to allow for any indigestible materials to continue through the small intestine.
4. Short transition period between the contractions of phase 3 into the inactivity of phase 13.

The MMC appears to be controlled by the nervous system, which includes the brain, spinal cord, and its nerve extensions, as well as by the secretion of the enteric hormone, motilin.

Motilin is produced by endocrine cells in the beginning part of the small intestine and plays an important role in the regulation of MMC, as the levels of this hormone are directly related to the different phases of MMC ⁴.

GI contraction can be measured by analyzing the concentration of motilin in the blood plasma, as these levels will fluctuate every 90-120 minutes as we fast (reaching a peak during phase 3 of the MMC), and will almost disappear once you eat.

MMC and SIBO

SIBO, which is defined as an excessive bacterial growth greater than 10⁵ colony-forming units per milliliter (ml) in the small intestine, is often diagnosed by a glucose or lactulose breath test, or by cultures obtained from the small intestine ³.

Intestinal dysmotility plays a crucial role in the severity of the most common symptoms of SIBO such as bloating, diarrhea, and abdominal pain. Researchers have shown through a number of animal studies that any disruption to the MMC significantly increases the risk of bacterial overgrowth.

Therefore, MMC, in addition to controlling motility, is also an important mechanism for controlling the bacterial flora of the small intestine and is known as the “intestinal housekeeper”³. This is because the MMC promotes motility of the small intestine, allowing the bacteria to migrate towards the large intestine, effectively stopping the accumulation of bacteria in the small intestine and the associated symptoms of SIBO.

What are Prokinetic Agents?

When you break down the word ‘prokinetic,’ ‘pro’ means to promote or give rise to something, whereas ‘kinetics’ means movement or activation of something.

Prokinetic agents, therefore, are a class of drugs that promote motility within the gastrointestinal (GI) tract and manage the following symptoms:

• Impaired motility
• Gastroesophageal reflux (acid reflux, occasionally)
• Gastroparesis (paralysis of the stomach muscles so that food is stuck)
• Intestinal pseudo-obstruction
• Colonic inertia (motility disorder of the large intestine) ⁵

Pharmaceutical Prokinetic Drugs

Pros and Cons of Pharmaceutical Prokinetic Drugs

People who suffer from altered motility or chronic constipation, whether due to a known GI disorder or no known reason at all, often suffer from a plethora of symptoms including bloating, vomiting, nausea, and early feeling of fullness or upper abdominal pain after eating.

The use of prokinetic agents can provide patients with chronic constipation with some relief.

Overall, the use of prokinetic drugs can improve the absorption of food, especially following extended periods of dysmotility that have affected our body’s natural ability to absorb important nutrients.

However, these drugs affect other parts of the body apart from the gut, leading to many side effects. For example, many of the drugs act on chemicals that are important for regulating memory, mood, and behavior. It is important for you to have all the information to make the most informed decision possible before taking a pharmaceutical prokinetic drug.

Below is a table listing the benefits and possible side effects of specific pharmaceutical prokinetic drugs.

Natural Prokinetic Agents

As you can see from the numerous side effects associated with pharmaceutical drugs, many individuals suffering from motility issues look towards more natural remedies.

While several herbal remedies have been used for a long time to promote GI motility, there is a lack of sufficient scientific studies currently available to investigate whether these drugs are truly useful for treating constipation and motility disorders.

Below is a table listing some of the natural prokinetic drugs and how they work to reduce constipation and improve motility disorders.

Pros and Cons of Natural Prokinetic Drugs

One of the biggest benefits of using natural prokinetic drugs is that they often have fewer adverse effects compared to pharmaceutical prokinetic agents. Since most pharmaceutical prokinetics either directly promote or antagonize chemicals involved in important brain processes, they are often nonspecific and cause several types of effects outside of the GI tract.

It is important to realize that most natural and herbal medications are not regulated by the FDA, therefore the benefits (and purity of ingredients) posted on the labels may not be completely accurate. IT is crucial to equip yourself with all the available information before trying a natural remedy.

Also, keep in mind that to get the medicinal benefits it is important to buy quality herbal products made with organic or wildcrafted herbs.

While herbal formulas are generally safe, you should make sure you are using the correct dosage and buying quality herbs. Also, if you take prescribed medications, know that herbal supplements (especially in large doses) sometimes interact with your prescriptions causing other side effects.

When Should Prokinetics be Used?

Individuals with GI disorders, such as IBS and SIBO, often have nerve damage or bacterial overgrowth, which causes a very slow transit of food through the gut. Subsequently, they will often suffer from constipation and a plethora of associated symptoms.

Once an individual has completed primary treatment for the disorder, it is helpful to follow up with prokinetics to stimulate the MMC and to prevent relapse.

It is also helpful to take the prokinetic agents immediately before going to sleep since we go through many detoxifying and repairing processes during sleep and also have the most number of MMCs as we are fasting.

Prokinetics for SIBO

Pharmaceutical Remedies:

A number of different types of pharmaceutical prokinetics are indicated for the treatment of SIBO. These, along with their rationale for SIBO treatment, include:

• 50 mg/day Erythromycin: Low rate of side effects at this dose

• 2-6 mg/day Tegaserod: Can only be used outside of the U.S., useful for gastroparesis

• 0.5-1 mg/day Prucalopride: Can only be used outside of the U.S., strong prokinetic agent which stimulates MMC

• Low-dose Naltrexone (LDN): This drug may help to decrease the overactivity of the immune system and, at low doses, can act as a prokinetic since it reduces inflammation and pain. (Note: this is an off-label use of the medicine)

Remember that it may be best to take these medications at night before bed.

Natural Remedies:

As far as natural remedies are concerned, triphala, ginger, and Iberogast are safe prokinetics that can be used for extended periods of time without causing any harmful effects that are associated with the use of common pharmaceutical drugs.

To learn more about SIBO treatment and how prokinetics can work in conjunction see this review: https://sibosurvivor.com/sibo-treatment/

Conclusion 

In conclusion, prokinetics can be a very important part of SIBO treatment where there is a motility disorder involved. A prokinetic can play a supercritical role in preventing bacterial overgrowth from occurring and also allow the bowels to start moving and functioning better.

There are a number of good natural options to try as well as pharmaceutical drugs if the natural remedies are not strong enough.