Contributors: Rachael T., Doreen M., Dr. Jeffrey Phillips,
Compiled by: Sarah Camp, December 2020
Nocturnal Acid Dump
Click here for a PDF file that you can download/print: Nocturnal Acid Breakthrough In Patients With GERD, by Kay Shaver, Pharm.D
What is the Nighttime/Nocturnal Acid Dump?
Nocturnal/Nighttime Acid Dump/Breakthrough refers to the period of time from about 2 A.M. through 7 A.M. in which the stomach goes into overdrive producing more acid.
Nocturnal acid breakthrough is defined as the presence of intragastric pH < 4 during the overnight period for at least 60 continuous minutes in patients taking a proton-pump inhibitor (PPI). Nocturnal acid breakthrough occurs in more than 70% of Helicobacter pylori-negative patients on PPI therapy and has clinical consequences in particular in patients with complicated gastroesophageal reflux disease (GERD), Barrett’s esophagus, and esophageal motility abnormalities. [Source]
Some have hypothesized that this may be connected to histamine peaks overnight as well. [Source]
Both of these factors combined can cause some very rough nights for Gerdlings, but that isn’t to say that nothing can be done to help! By now you may have already learned that PPIs are the best longterm choice for treating GERD. However, not all PPIs are created equal. Learn about the different choices here.
Why are Delayed Release (DR) PPIs Unfavorable for Covering the Nocturnal Acid Dump?
DR PPIs should not be given after 5:30 P.M. unless a baby will be eating throughout the night. It boils down to a few reasons:
The PPIs have a short half-life (regardless of how they are given, delayed release – DR; or immediate release – IR). This means that the PPI will be in the bloodstream for ~2 to 2.5 hrs. So, when using a delayed release PPI the amount of proton pumps that are active during that time will depend on how well the feeding was timed with the dose and how efficient the feeding is at turning on the acid pumps (a feeding is generally okay at stimulating some proton pumps) as compared to a immediate release PPI with buffer where the buffer turns on many of the proton pumps (highly efficient) and then blocks them as well. Things are further complicated because the enteric coated PPIs are absorbed only when they get into the duodenum (which of course takes time) – this is why the enteric coated PPIs must be given 1/2 hr before feeding so that the drug (PPI) will be in the blood as the meal stimulates the pumps to come “on.
So the difference is that an evening dose of an IR PPI will turn on pumps that would have come on later in the early morning hours thru till ~5 am and then also block those pumps. The DR PPI dosed at 5pm or so (timed with a feeding) will block some pumps but others will come on starting around midnight till 5 am (and since there is no PPI in the bloodstream at that time) those pumps will make acid. All of this was learned in studies of Zegerid which produced excellent nighttime control as compared to the other PPIs (all delayed release) that had poor nighttime control of acid.
PPI medicines require that acid pumps (called proton pumps) be in the mode of trying to make acid. When they are in this mode (and only when they are in this mode) the pumps can be shut down. If the pumps are not “on” they cannot be turned off, kind of like lights in your house. (Try to turn off a light if it is already off – it doesn’t work). Anyway, in real life – food is the major stimulator of the acid pumps coming on. So for example throughout the day there is a meal or formula or milk stimulus from early in the day till later in the afternoon till around 6pm or so. Then typically, the feeding stops and hence the acid secretion goes way down (because the pumps are not “on”). So if you try to give a dose of PPI during this period evening thru to 5am there will be little effect. However, antacids are good stimulators of acid pumps coming on, especially sodium bicarb, calcium carbonate and magnesium hydroxide.
Why are Immediate Release (IR) PPIs Better for Treating the Nocturnal Acid Dump?
We also have our own recipes for immediate release that you can make yourself at home! Check out Home Compounding 101 to learn all about it!
Immediate release has its own acid pump activator (buffer). See explanation below:
The following was posted by Rachel T., from Facebook:
SoluTabs and any of the delayed release PPIs do not work at nighttime very well. Let me [PharmD Researcher] clarify, from 9 pm till about 2 am there is very little acid production (this is because of ancient genetic encoding; ancient people ate their evening meal while it was day light, at about 6pm or so, then they’d go to sleep and their bodies’ acid would ‘kicks-in’ in the early am (~2 am to 6 am), to kill any bacteria that were ingested). This remnant genetic predisposition is still with us. What do PPIs require to work??? (Answer: actively secreting acid pumps). How long is the PPI in your baby’s system? (for approx. 120 minutes after you give it). If the acid pumps (proton pumps) are not on during that time period then acid will not be blocked. Immediate release PPIs (such as Zegerid) have a buffer in them and that turns on the acid pumps (in addition to protecting the PPI from acid degradation). So Immediate acting PPIs can be given without regard to meals (or even in the bottle).
Delayed release PPI such as Prevacid OTC need to have active acid secreting cells (“pumping”) in order to block the pumps. The body shuts down pumps after 7 pm to ~3am. If you give the delayed release Prevacid, then it will be in the baby’s body for 3.5 to 4 hrs after administration, then it will be gone. SO, if you give the PPI after 5:30 it will have no effect because no pumps will be on while the Prevacid is in the bloodstream. It is simple really, PPI drugs (such as SoluTab) can only block pumps that are in place and ready to make acid.
Well it is really quite interesting. The acid pumps are finite (meaning there are only so many available in a 24 hr period). When you use a buffer and immediate release PPI – the buffer hits the stomach and raises the pH. This makes the stomach lining send a signal to the acid secreting cells (parietal cells) to wake the pumps and get some of them making acid just a the PPI part hit the pumps and shuts them down. When you use a buffer, a lot of these pumps get used up. Therefore, by giving a dose around 8 or 9pm, or thereabouts, the pumps are exhausted and there aren’t any to come on in the 2am period – so then there is no acid dump.
The SoluTab contains Prevacid in enteric-coated granules (inside the SoluTab). The medicine (Lansoprazole) is absorbed in 1.5 hrs and the amount of time it is in the system is 120 minutes. So approx. 3.5 hrs after a dose there is no drug in the system to block the acid pumps (called proton pumps). The nighttime acid begins at 2am and continues till 7 am (roughly). So, if you give a dose at 5:30pm then it is gone at 9pm (way before the acid pumps start making the nighttime acid).
Immediate Release PPIs (such as Zegerid) have a buffer that stimulates those pumps to come on (that would have come on from 2 am till ~7am) and then blocks them while they are on.
You have a period of acid dump from 2 am till about 7am. That is the period of maximal acid dump at night. So, if the drug is in the bloodstream for a maximum of ~2hrs (remember the absorption occurs after ~1.5hrs so, from the 1.5hr mark forward for ~2 hrs you have coverage for any acid being made. So let’s say you time it perfectly and give the dose at 1/2 hr after midnight so that the drug would be in the blood stream at 2 am (it takes 1.5 hrs to get absorbed) Then at 2 am you would have drug present for 2 hrs – till 4am. Then no drug – but body still making loads of acid (nocturnal acid). From 4 am on there would be no protection from acid.
The acid pumps (called proton pumps) are in the acid making cells (called parietal cells). They make acid when signaled to do so. They are signaled to make acid after you begin eating (mainly by food or milk which raises the pH in the stomach). After your evening meal they go dormant till approx 2am, then they come on and make a large amt of acid. This is because long ago we did not cook things well (no stoves existed, hardly any fire existed) and the large meal of the day was at night then you went to sleep. During the night your body would make a lot of acid to kill the bacteria you ingested (that is how you lived through the night-in essence). So we still have that 2 am to 7 am acid dump.
The other thing you have to know is a little PPI pharmacology – PPIs can only turn off acid pumps that are already on. So if the pumps are not on (in the resting phase) and you take a PPI (that does not have a buffer) then the PPI will get absorbed and when the PPI gets to the parietal cell it will find no acid pumps that are on and it will not be able to shut off any pumps and the PPI will be removed from the body (just as all drugs are removed from the body) through metabolism and elimination. If you take the PPI in an immediate release form with a buffer, then the buffer will turn on a large quantity of acid pumps and they will all get shut off by the PPI. Then later in the early morning hours when the body tries to make the nighttime acid dump (there will be no acid pumps remaining) – so no acid dump. The studies were performed (not by me) but over hundred’s of studies who look at the baseline pH (before treatment) and then after treatment. So all this baseline data exists and in the observation of these baseline data. And it was observed (quite obvious) that there was all this nighttime acid.”
Quoting Doreen: “If they do not eat at night there is nothing to turn the pumps on to get the medication going. If they eat at night then the pump, acids and meds can do their little dance.”
Dr. Phillips wrote: There are a couple ways to make an immediate release compounded version. TCMax is one that I invented when I was at The Univ of Missouri School of Medicine. It was made specifically for infants. I did the original studies on Zegerid (which I had called SOS, for simplified omeprazole suspension). My original work was in critically ill adults who were in the ICU and had high risk of stomach bleeding from something known as “stress ulcers”. Anyway, needless to say, these patients are on the mechanical ventilator and have other risk factors for stress ulcer bleeding (e.g. head injury, burns, major surgery, and others). They have a tube (nasogastric) in their stomachs since they have no ability to swallow on their own. So, my initial goal was to make a liquid formulation of omeprazole (since the small granules in the capsule would cause the nasogastric tube to clog. Anyway, in the process of doing the research I found that the acid control was much faster and better (higher pH was obtained) with the SOS. So I worked on flavorings for SOS and started research in infants who had reflux. We found that once again the acid control was immediate and the pH obtained was higher than with the pellets (or granules) of omeprazole. This was then repeated in clinical trials in adults. Here is an excerpt from a recent review of Treatments for GERD. First a few abbreviations: drPPI = delayed release PPI (this is any form other than Zegerid) and irPPI = immediate release PPI (Zegerid). Recent developments in gastroesophageal reflux disease and Barrett’s esophagus. Author: Tytgat GN. Published 2012 Journal of Digestive Diseases 2012; 13; 291–295. All drPPIs have a relatively slow onset of pharmacological action and may require several doses to achieve maximum acid suppression. The time of dosing and ingestion of meals may also influence the pharmaco- kinetics of drPPIs. Moreover, they fail to provide full 24-h suppression of gastric acid production because they all allow nocturnal acid recovery, defined as a drop of intragastric pH under 4 for more than 1 h even with twice-daily dose. IR omeprazole consists of pure, non-enteric-coated omeprazole powder along with sodium bicarbonate. The antisecretory effect of IR omeprazole is quicker than that of drPPI. The rapid increase of intragastric pH is likely due to the neutralizing effect of sodium bicarbonate, which may also accelerate and enhance the absorption of omeprazole, whose increased bio-availability may translate in more profound acid suppression. The rapid rise of intragastric pH may also facilitate gastrin release, enhancing the activation of proton pumps available for inhibition. This new formulation provides sustained control of intragastric pH at steady state, and dosed at bedtime may be effective in improving the control of nocturnal pH and, therefore, useful in treating night-time acid reflux.
Are There Any Other Solutions for the Nocturnal Acid Breakthrough?
Yes. If you are unable to use an immediate release PPI, or are still having severe reflux at night, adding in an H2 blocker such as Pepcid (famotidine) may help. These must be spaced 3-4 hours from a PPI dose each way. This article explains the reasons for spacing. Where you see Zantac, substitute it for Pepcid; this article was written prior to the recall of Zantac.