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Genetic Testing and Gastrointestinal Medication (PPI) Effectiveness
Genetic Testing and Gastrointestinal Medication (PPI) Effectiveness
Genetic Insights on Proton Pump Inhibitor (PPI) Effectiveness
What Proton Pump Inhibitors (PPIs) Do & When They're Prescribed
Proton Pump Inhibitors (or PPIs) are a class of medications that reduce production of acid pumped into your stomach. Though stomach acid production is a normal bodily process needed to help digest food, reducing the extent of this process is sometimes necessary to help treat certain circumstances. Cases where PPIs may be prescribed include:
- When acid is overproduced and causes disruptive symptoms (like heartburn,
regurgitation, or worsened asthma) due to GERD or otherwise - When the body cannot contain stomach acid and it spills into the esophagus
to protect existing stomach ulcers from worsening due to the normal presence of stomach acid, including cases caused by the bacteria H. pylori - To prevent stomach ulcers from forming in at-risk individuals (e.g., advanced age, use of anti-inflammatories)
Common PPI Side Effects
PPIs are often taken without noticeable side effects. However, some individuals do
experience side effects shortly after starting use. These may include headache, nausea or diarrhea.
Long-term use, however, is associated with some notable concerns, but these too may not always be obvious. Or, they may be one contributing factor in the development of a new concern. These effects are linked to how these medications work.
The first example is increased risk and development of a certain type of infection in the gastrointestinal tract called C. difficile. It is not fully clear why this risk arises, but it is possible that it is related to its therapeutic effect (i.e., lowering stomach acid production) in those that are exposed to the bacteria. Other factors, like use of certain antibiotics, can also contribute.
The second example is a broader grouping of nutritional deficiencies. This is due to reduced absorption of these nutrients from food and supplements in the stomach. Notable examples are the mineral magnesium, and vitamin B12. Specific nutrient deficiencies, if unaddressed, can lead to the development of specific conditions.
Other potential long-term effects have been explored, though many are still not confirmed.
Why Some People Don’t Get Full Relief from PPIs
Not everyone experiences full relief from PPIs. This could be due to a variety of reasons.
In some cases, the diagnosis may have been incorrect. Since a diagnosis often points to specific causative factor(s), a mismatch between what PPIs do (lower stomach acid) and what is needed can lead to treatment failure.
In other cases, the diagnosis may be correct, but PPIs don't meaningfully address the
underlying cause but are prescribed anyways.
Oftentimes the diagnosis is correct, and PPIs are prescribed in circumstances where they are known to work. Full relief may not come, however. This could be due to how the medication is actually taken (i.e., skipped doses, or not taken 30-60 minutes before meals) or even natural limitations of the PPI effectiveness even in ideal circumstances.
Sometimes, it is simply the dose or specific PPI that is the issue. This can be due to
interactions with other medications, or someone’s genetics.
How CYP2C19 and Other Genes Impact PPI Response
PPIs are metabolized, at least in part, by an enzyme called CYP2C19. This enzyme is found, in particular, in the liver and also helps metabolize a number of other medications.
The "version" of CYP2C19 found in your liver is highly dependent on your DNA. In short, variations in the responsible gene (also referred to as CYP2C19) influence how your body metabolizes certain PPIs. Depending on how "slow" or "fast" your version is, your ability to benefit from standard doses of the medication can differ greatly from the next person. This could be the reason why a PPI has not been working for gastritis, for example.
The relationship could be referred to as a genetic CYP2C19 PPI interaction, or, more
specifically, drug-gene interaction with the specific PPIs, respectively (e.g., pantoprazole CYP2C19).
Differences Between Pantoprazole, Esomeprazole & Lansoprazole
The PPIs dexlansoprazole, lansoprazole, omeprazole and pantoprazole are significantly impacted by CYP2C19. This can mean that "faster" (and even "normal") metabolizers process usual doses of these medications at a rate that doesn't allow the medication to build up and lower stomach acid meaningfully. Depending on the specific DNA variations and which of these four PPIs is being taken, a higher prescribed dose may be needed, and may be the reason, for example, why pantoprazole is not working. Those that are "slower" metabolizers, on the other hand may respond favourably to usual doses. It should be noted, however, that specific doses may only be needed for a limited amount of time before the dose is lowered or the medication is stopped by the prescriber.
The PPIs rabeprazole and esomeprazole are also impacted by CYP2C19, but to a lesser extent. This impact is notable in very slow or "poor" metabolizers' blood concentrations of these medications. However, there is no proof that this changes their effectiveness, side effect risk or dosing strategies. In fact, these medications could be used based on standard prescribing guidance in situations where the previous four PPIs (dexlansoprazole, lansoprazole, omeprazole and pantoprazole) required genetically informed dosing to produce sufficient benefit. So, say you and your doctor are deciding on esomeprazole vs. lansoprazole, this is something that could be explored further.
Though risks of PPI side effects may be altered by genetic variations in CYP2C19, there isn't much clarity in the scientific evidence that is the case. Side effect considerations are important for anyone taking PPIs, regardless of their genetics. PPIs should only be taken as prescribed for the length of time determined by the health care provider, and use should be re-evaluated periodically.
When to Consider Genetic Testing for Digestive Issues
Genetic testing for PPIs can be helpful in many circumstances, though a few in particular are notable. These include:
- When the outcome of the treatment is of particularly high importance (e.g.,
resolution of stomach ulcers, healing of the esophagus from stomach acid exposure) - Multiple PPI trials without sufficient relief
- Repeated dosing adjustments without sufficient relief
- Prior to starting a PPI when life circumstances could make trial-and-error particularly difficult
Note that when prescribers advise to start PPI treatment without delay but PPI genetic test results are not yet known, treatment can be adjusted by prescribers once results are available.
How Inagene Helps Personalize PPI Treatment
Pharmacogenetic testing provides actionable insights that can support health care providers in their medication treatment decisions. The results help identify which medications or dosing strategies are more compatible with a person’s genetic profile, helping to improve symptoms and health outcomes. Practically speaking, this may mean that some individuals may have specific dosing requirements depending on the specific PPI. These insights can help health care professionals better tailor their approach to the individual being treated.
