See This Study....Evidence that PPIs are necessary in most indications is VERY WEAK (Even for Cirrhotic patients)!

I realize this post is long, but please at least take the time to scroll to the bottom and look at the studies (and what's been highlighted) and you'll see why I'm NOT a fan of PPIs.

--------------------------

I finally got around to researching more about: Why DO doctors give PPIs to patients? I mean, why do they really give them? When it comes to medications, it's clear why patients take almost all the different medications. We know the lactulose is to help a person go to the bathroom and keep bacteria (and therefore, ammonia) from building up, and causing encephalopathy. We know diuretics are to reduce swelling and fluid buildup in the body and abdomen. We know antibiotics are to prevent an infection.

To me, it was never entirely clear why Proton Pump Inhibitors are prescribed for almost all cirrhosis patients. And to be honest sometimes I even wonder if doctors fully understand why they're being given to their patients. 

The general vibe you get from doctors is that PPIs are given because doctors believe they reduce a person's risk of bleeding from their esophagus or stomach. I get it. Bleeding to death would be a very bad thing. But I really do question how much the PPIs help most cirrhotics in this regard, and studies show not everyone is at risk (particularly if you haven't had surgery). 

Yes, you DO have to weigh the risks vs. the side effects. It's easy for doctors to prescribe things for people across the board, when they have an extreme fear, and nothing sounds scarier than bleeding to death. But how much do the PPIs really prevent this? Especially when PPIs can cause MORE scar tissue and make a person's cirrhosis WORSE?

When you google the term: "does gastric acid cause bleeding"? this is what you get: 


Stomach acid that returns, or "refluxes," back into the esophagus from the stomach can cause irritation and inflammation of the esophagus (esophagitis) that may lead to bleeding.

In my opinion, it is the irritation and inflammation that are the root of the problem. If you can find a way to fix THAT issue, then in my opinion, you will be at a lower risk for the bleeding.  I truly believe that, the fact that my husband was drinking George's aloe vera juice while he was in the hospital in 2013, is the reason why his esophagus looked good during his endoscopy (despite the fact that things were so bad, he had 21 liters of fluid drained that same week). There was no bleeding. And aloe vera juice is known (among other things) to reduce inflammation. I can't tell you what to do, but you really should do your own research on this. 

In my opinion, proton pump inhibitors are like loan sharks. They might help you in the short term, but there's a good chance you're going to pay a VERY high price later on.

Please read the study, further down the page, and draw your own conclusions about PPIs (Proton Pump Inhibitors). In my strong opinion, they do more harm than good, for people with cirrhosis. 

If you want to see more about why I am NOT a fan of PPIs, please read THIS POST (and click on the links for the other posts on that page, and have a look at my husband's cracked tongue). This photo might surprise you, like it surprised me. 

 


I understand that doctors like to give that whole "well, you have to outweigh the benefits vs. the negative side effects" but so far I haven't seen the benefits.... just the side effects. Maybe their use would be justified in the case for someone who's had surgery, but my husband didn't have surgery, so in my opinion, their use was never really justified.


Please have a look at this study (pasted below).

Source: Sreedharan A, Martin J, Leontiadis GI, Dorward S, Howden CW, Forman D, Moayyedi P. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database Syst Rev. 2010 Jul 7;7:CD005415. Review. PubMed PMID: 20614440.

Efficacy Endpoints: Major Endpoints: Mortality, Re-bleeding, Need for surgical intervention.
Minor Endpoints: Need for endoscopic hemostasis, Blood transfusion, Decrease in Hospital Days.

Harm Endpoints: Delaying definitive diagnosis and treatment, direct cost to patient, indirect cost (change in level of care, nursing care, emergency department flow, etc.)

Narrative: Acute upper gastrointestinal bleeding is a potentially life threatening condition that can demand aggressive intervention from the emergency physicians. Although bleeding can originate in any area above the ligament of Treitz, the majority of bleeding is from a peptic ulcer1,2. Proton pump inhibitors (PPIs) work by reducing gastric acid secretion, neutralizing gastric pH, increasing clot formation3 and decreasing clot lysis4. Intravenous proton pump inhibitors have traditionally been used after endoscopic hemostasis and are believed to prevent re-bleeding and decrease the need for surgery5. Patients with undifferentiated upper GI bleed, however, are often also placed on continuous PPI therapy prior to endoscopy6. This practice can delay definitive diagnosis and endoscopic treatment. Since 37-45% of undifferentiated upper GI bleed is not from a peptic ulcer1,2 patients can be subject to unnecessary medications and cost.

Four randomized control trials comprising of almost 1500 patients were included in the analysis. In this systematic review, PPIs failed to reduce death, re-bleeding rates, or the need for surgery. They did reduce the incidence of high risk lesions found during endoscopic evaluation. There was not sufficient evidence to assess for amount of blood transfused or decrease in hospitalized days, though one trial in the review and one recent trial (citation) showed that there was no difference in either.

Caveats: There were a relatively small number of patients in the PPI group (about 760) and there is a male preponderance in most of the studies. Though studies were conducted in both Asia and Europe, the relatively low numbers might limit generalizability. Also, a decrease in high risk stigmata on endoscopic evaluation may represent a clinically useful outcome if it reduced the need for hemostatic intervention. A study by Lau1 showed that there was a 14% reduction in endoscopic hemostasis in the PPI group, with a number needed to treat to prevent one intervention of 7.

Author: Koustav Mukherjee, MD

Published/Updated: January 7, 2010

--------------------
Please note the term "high risk lesions" (underlined above). In my opinion, if a person has an endoscopy, and they do not find any high risk lesions, then IN MY OPINION the side effects negate the benefits of taking this medication. My husband had an endoscopy and there was no sign of bleeding or high risk lesions. I saw the pictures with my own eyes. In my opinion he should never have been given the PPIs, and certainly not for NINE MONTHS STRAIGHT. 

My OPINION is that, if a person doesn't have bulging varices, or isn't having a surgical procedure in their throat or stomach, then the risks outweigh the benefits. And I even question their safety if a person DOES have a surgical procedure, but that's up to each person to do their own research and decide for themselves.

It also concerns me that doctors NEVER seem to warn patients that, if they suddenly stop taking PPIs cold turkey, they could get a big SURGE of gastric acid and acid reflux, which could make their condition worse! So, for this reason, I'd never recommend that someone just suddenly stop taking PPIs, cold turkey. If a person is going to get off them, they'd need to do so, gradually (there are videos on youtube about this).  

I talked to someone in Amsterdam who told me that his Dad's doctor says they give an "extra layer of protection" in the stomach. Doctors are very vague about why they're giving PPIs to cirrhotic patients. Yeah, it sounds good, to give "an extra layer of protection in the stomach." Who wouldn't want that? So most people never question the PPIs further. To me it's just a confusing blanket statement that's easily given to patients, that tends to make it easier to give them assurance (and keep em quiet). It's only when you start doing your own research, that you start to realize how horrible the side effects can be, ESPECIALLY for a person with cirrhosis.

When you use strong cleaners like household bleach, every day, to kill pathogens in your kitchen, you're giving your family "an extra layer of protection" against bacteria.... while you're also exposing them to toxic poisons that are likely to make them sick in the long run. You can call sh** a rose.... but that doesn't take away the stink.

According to this study (and what I've seen in my own experience with cirrhosis), it seems like they are just way over-prescribed out of habit. Doctors do get kickbacks for prescribing certain medications, and I can't help but believe they get kickbacks for prescribing PPIs, given how commonly they are over-prescribed.

Acid in the stomach is NECESSARY for nutrient absorption, and a person with cirrhosis is EXTREMELY, CRITICALLY deficient in nutrients, so in my opinion, doing anything to make nutrient absorption even worse, could have very detrimental effects for a cirrhosis patient. 

I cannot tell any person to stop taking PPI's.  I can tell you that I, personally, wouldn't take them. I can tell you my husband won't take them. But you'll have to make that decision for yourself. Please read the articles and studies below, to see why I feel so strongly that people need to be warned about PPIs.

 Check out this study:

Proton pump inhibitors in cirrhosis: Tradition or evidence based practice?  

Francesca Lodato, Francesco Azzaroli, Maria Di Girolamo, Valentina Feletti, Paolo Cecinato, Andrea Lisotti, Davide Festi, Enrico Roda, and Giuseppe Mazzella

Author information ► Article notes ► Copyright and License information ►

This article has been cited by other articles in PMC.

Go to:

INTRODUCTION

Proton Pump Inhibitors (PPI) are extensively used in different acid related diseases. Their efficacy in inhibiting acid secretion is well known[1–4], and the use of this class of drugs has increased worldwide. They act through inhibition of the H+/K+ ATPase of parietal cells producing the so called “inhibitory complex” and blocking HCl secretion[5]. They are metabolized in the liver by the CYP450 cytochrome[6].

PPI are also often used in patients with liver cirrhosis sometimes in the absence of a specific acid related disease, with the aim of preventing peptic complications in patients with variceal or hypertensive gastropathic bleeding receiving multidrug treatment.

The aim of this editorial is to revise the efficacy and safety profile of PPI in patients with liver cirrhosis.

Go to:

GASTRIC ACID SECRETION AND LIVER CIRRHOSIS

The role of gastric secretion in cirrhosis is controversial. Some studies report reduced acid production[7–10] while others reported normal production[11–15]. The evaluation of 24-h acidity by gastric ph-metry in 49 patients with cirrhosis showed a marked hypoacidity in patients with cirrhosis compared to controls, mainly during the night hours[16]. This may depend on hemodynamic alterations consequent to portal hypertension and is supported by experimental studies showing reduced gastric acid secretion in animals with portal hypertension[17,18]. These observations rule out the relevance of gastric acid in the pathogenesis of ulcers in cirrhotics.

Gastrin, the gastric hormone whose secretion is regulated by intragastric pH, and that regulates the production of HCl and pepsin, is partially metabolized by the liver and mainly by the kidneys. Gastrin is elevated in serum of patients with Helicobacter pylori (H pylori) infection or atrophic gastritis. Few studies have evaluated gastrin levels in cirrhosis, and their contribution towards understanding the pathophysiology of gastric acid secretion is very limited. Avgerinos et al[19] evaluated the urinary gastrin output in patients with cirrhosis with and without hepato-renal syndrome. Serum gastrin levels were higher in cirrhotics compared to controls; and in cirrhotics with hepato-renal syndrome the difference was greater suggesting that impaired urinary gastrin secretion may contribute to their hypergastrinemia. The same results were found by Lo et al[11] who also showed a significantly lower maximal pepsin output in cirrhotics compared to controls.

Progastrin and gastrin serum levels have been reported to be significantly higher in patients with cirrhosis of any Child-Pugh class compared to controls while there are no differences between controls and patients with chronic hepatitis B or C[20]. Indeed, it is important to note that in this study, the prevalence of H pylori infection in cirrhotic patients was 83% versus 50% in controls. Therefore, it is not clear whether the difference in progastrin and gastrin level was due to reduced liver metabolism, to H pylori infection, or both. In summary, gastrin increase in patients with liver cirrhosis could be related to: (1) impaired hepatic gastrin catabolism; (2) impaired renal function, at least in those with HRS; (3) gastric mucosal alteration due to gastropathy-related cirrhosis.

Go to:

PEPTIC ULCERS AND LIVER CIRRHOSIS

Many authors reported an increased prevalence of peptic ulcers in patients with cirrhosis[21,22] and it was shown that cirrhotics have an increased risk of developing gastric or duodenal ulcers during an interval of one year compared to non cirrhotics[23]. The prevalence of peptic ulcers ranges between 4.6% and 21% in patients with cirrhosis[21,22,24–26,39] (Table (Table1).1). However, the pathogenesis of this finding is far from being elucidated and different factors have been proposed in relation to increased ulcer prevalence in patients with cirrhosis.  Furthermore the prevalence of duodenal and gastric ulcers in patients with liver cirrhosis increases with disease progression[27] (Table (Table2).2). Several theories have been postulated. It has been demonstrated that the gastric mucosa in rats with portal hypertension is more susceptible to aggressive agents such as bile acids, aspirin and alcohol[28]. Some investigators have attributed to portal hypertension itself the increased risk of peptic ulcer[29], nevertheless no study has clarified the pathogenesis of peptic ulceration in cirrhosis.

Table 1

Prevalence of peptic ulcer in patients with liver cirrhosis

Table 2

Gastric and duodenal ulcer in patients with liver cirrhosis according to the severity of portal hypertension (from Wu et al 1995)

Go to:

H PYLORI IN PATIENTS WITH LIVER CIRRHOSIS

The prevalence of H pylori in patients with cirrhosis has been investigated in many epidemiological studies with values ranging from 27% to 89%[24,27,30–33]. This large variability may be due to the test used to evaluate H pylori infection. In the study with the largest prevalence of H pylori infection, values were been obtained by titration of serum IgG, against H pylori. The tests usually used for evaluating the presence of H pylori should be revised since haemodynamic alterations in cirrhosis could impair the results of urea 13C BT, and hypergammaglobulinemia typical of cirrhosis, might produce a false positive test[34–38]. Italian studies generally and sometimes significantly showed a higher prevalence than in non cirrhotic patients, while studies from Taiwan failed to show a similar trend. When evaluating the prevalence of H pyloriinfection in cirrhotics there seems to be no relationship between the aetiology of cirrhosis and the prevalence of H pylori evaluated by determination of serum IgG[24]. The role of H pylori in determining peptic ulceration in cirrhosis is controversial: some authors conclude that the increased risk of gastroduodenal ulcer is not related to H pylori infection, whilst others conclude that peptic disease and non-ulcer dyspepsia are firmly linked to H pylori infection[32,39–41]. A meta-analysis showed an increased risk of ulcers developing in patients with H pylori infection and cirrhosis[42].

If H pylori infection were an etiopathological factor implicated in digestive bleeding in cirrhosis, eradication of infection would decrease the risk of ulcer recurrence. However a study aiming to investigate the role of H pylori eradication in cirrhotics demonstrated a similar recurrence rate between cirrhotics with successful H pylori eradication and those with active H pylori infection[43]. In conclusion, the role of H pylori infection in the occurrence of gastric or duodenal ulcers or in determining digestive bleeding in the setting of liver cirrhosis is still unclear.

Go to:

ESOPHAGEAL DISORDERS AND LIVER CIRRHOSIS

It has been postulated in the past, that gastro-esophageal reflux may contribute to oesophagitis and variceal bleeding in cirrhotic patients[44], and acid reflux could be exacerbated by the presence of ascites and water retention[45]. More recent papers do not confirm these hypotheses[46,47] and report a high incidence of gastro-esophageal reflux only in patients with alcoholic cirrhosis, though the presence of reflux did not correlate with disease severity or bleeding episodes[48]. Functional studies showed decreased lower esophageal sphincter function with low amplitude of primary peristalsis and acid clearance in patients with large varices[49–51]. These phenomenon could also be due to a mechanical effect of the presence of varices. In conclusion, it is unclear whether the presence of cirrhosis itself could predispose to the onset of gastroesophageal reflux. It seems that the presence of varices is related to reflux episodes, although it is not clear whether these might contribute to bleeding from varices.

Another more studied point is the fact that endoscopic treatment for variceal bleeding or prevention of bleeding varices, may produce oesophageal motility dysfunction. Several studies evaluated the effect of endoscopic variceal sclerotherapy (EVS) on gastro-oesophageal reflux. Some authors suggest that endoscopic treatment produces an acute impairment of oesophageal motility which is partially restored after days or weeks[52–54], others suggest that sclerotherapy produce a chemical esophagitis that impairs oesophageal motility and in turn may favour acid related reflux esophagitis[55]. It seems that endoscopic variceal ligation (EVL) is safer in terms of oesophageal dysmotility induction when compared to EVS[56–59]. The reason for this finding is unclear. Autoptical studies after EVS show the presence of obliteration of the submucosal vascular channels, fibrosis and oesophagitis[60] reflecting the necrosis induced by the sclerosing agent. The inflammation caused by EVS may justify motor dysfunctions and acid reflux. Avgerinos et al[61] showed that EVL produces a higher early increase in lower oesophageal sphincter pressure, and this might prevent gastro-oesophageal reflux.

Apart from the pathogenesis of motor dysfunction following EVS and EVL, these procedures are related to local complications such as oesophageal ulcerations, strictures and perforations[62,63]; although from this point of view, EVL seem to be safer than EVS[64,65]. Uncontrolled non randomized studies, showed that PPI may have a role in the prevention and healing of post-EVS ulcerations[66–69] although this was not confirmed by other authors[70]. With regard to post EVL ulcers, the incidence is between 2% to 5%[71,72]. Pantoprazole has been shown to reduce the size of ulcers in patients undergoing elective band ligation, but not the rate of occurrence or the symptoms[73]. Given the relatively benign nature of the intervention, the authors conclude that PPI treatment is advisable in patients undergoing elective EVL.

In summary, expert opinion based on evidence of scarce value, advise PPI use in cirrhotic patients undergoing endoscopic treatment for varices, especially when treatment is performed by EVS, to prevent gastroesophageal reflux which may worsen the procedure-related inflammation or ulceration.

(Note from Ellie - please note, the paragraph above is basically stating that the surgical procedure can be the cause of inflammation or ulceration). If you're not having this elective procedure, you may want to question whether PPIs are something you want to take in the long term. I can't say if you should or shouldn't. I can't say what's best for you. I'm saying, you should do as much research as possible, on this. It's your body and your life.

Go to:

PPI SAFETY IN CIRRHOTIC PATIENTS

Acute hepatitis due to PPI use is described in the literature for most PPIs available on the market[74–79]. All PPIs are metabolized in the liver by cytochrome CYP450; two isoenzymes are involved in PPI metabolism (CYP2C19 and CYP3A4)[6]. CYP2C19 is the main metabolic pathway while CYP3A4 is activated only when the other enzyme is saturated[80]. Nevertheless, the affinity of each isoenzyme for different PPIs is different and rabeprazole is metabolized mainly by a non enzymatic pathway. There are two CYP2C19 phenotypes: extensive and poor metabolisers[81–83]. The poor phenotype is present in 2%-6% of Caucasians and 20% of the Asian population. Poor metabolisers have higher plasma levels of PPI, which could lead to higher efficacy but also to potential adverse events. The effects of these genotypes varies according to the specific PPI used and in general is greater when using omeprazole decreasing progressively to lansoprazole, esomeprazole, pantoprazole and finally rabeprazole[6,83].

PPI are metabolized in the liver and secreted by the kidney. Renal impairment has minimal effect on PPI clearance, and therefore there is no need to reduce PPI dosage in patients with renal diseases[80,84]. This is not the case for liver impairment in which the Area under the Curve (AUC) of PPIs increases and their half-life becomes 4 h to 8 h greater[80] with increasing risk of accumulation. This effect was also seen with rabeprazole[85] although a dose reduction seems to be unnecessary with a 20 mg, once daily dose in patients with mild to moderate liver cirrhosis. When using other PPIs or rabeprazole at 40 mg/d dose, dose reduction in patients with cirrhosis is advisable.

Go to:

CONCLUSION

PPI drugs are extensively used in clinical practice in cirrhotic patients. Besides habit, the evidence that PPI are necessary in most indications is very weak. First of all, there is convincing evidence that acid secretion is reduced in patients with liver cirrhosis. This is mainly due to the presence of hypertensive gastropathy for which there is no evidence of any efficacy of PPI. With regard to H pylori infection, its prevalence in patients with cirrhosis is largely variable among different studies, probably as a result of different diagnostic tests used. We believe that the condition of hypochloridemia of cirrhotics makes it more probable that its prevalence is lower than in the general population. Nevertheless, it seems that H pylori eradication does not prevent from gastroduodenal ulcer formation and bleeding.

It is probable that the main reason for PPI use in cirrhosis might be the prevention and treatment of oesophageal complications after banding or sclerotherapy of oesophageal varices. However even in this case evidence for a protective role of PPI are scarce. When using PPI in cirrhotic patients, the dose should be reduced in consideration of the increased half-life of these drugs in this group of patients. Dose adjustment does not seem necessary when using rabeprazole at a 20 mg, once daily dose. The use of this class of drugs seems more habit-related than evidence- based, eventually leading to an increase in health costs.

Peer reviewer: Katja Breitkopf, Dr, Department of Medicine II, University Hospital Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Germany

S- Editor Zhong XY L- Editor Lalor PF E- Editor Lu W

The Dangers of Proton Pump Inhibitors

on JUNE 14, 2016 by CHRIS KRESSER 

https://chriskresser.com/the-dangers-of-proton-pump-inhibitors/

Proton pump inhibitors rank among the top 10 prescribed classes of drugs and are commonly used to treat acid reflux, indigestion, and peptic ulcers. Although generally assumed to be safe, recent studies have shown that they have numerous side effects, from an altered gut environment and impaired nutrient absorption to an increased risk for cardiovascular events, kidney disease, and dementia.  

istock.com/Roel Smart

PPIs have become one of the most commonly prescribed classes of drugs in the industrialized world, despite increasingly frequent warnings by researchers about potential risks and complications.

A 2010 study found that of 946 patients receiving PPI therapy in a hospital setting, only 35 percent were prescribed PPIs for an appropriate upper GI diagnosis (1). In 2014, Americans filled more than 170 million prescriptions for acid blockers, falling only behind statins in total cost expenditure worldwide (2). PPIs are the most common of the acid blockers. They go by a variety of names but typically end in the suffix “-prazole” (omeprazole, pantoprazole, esomeprazole, etc.).

The purpose of this article is to provide an update to these earlier articles on heartburn and antacids, focusing on a number of scientific studies published in just the last few years. If you haven’t already, be sure to check out these previous blog posts.

The many roles of proton pumps in the body

Before we get into the potential harmful effects associated with PPIs, it’s important to understand what they do in the body. PPIs are inhibitors of proton pumps, specifically the proton/potassium pump of parietal cells in the stomach. The theory is that heartburn is caused by excess production of stomach acid by these cells, so inhibiting this proton pump will reduce the acidity of the stomach and prevent the burning sensation of acid reflux or the formation of peptic ulcers.

But proton pumps aren’t limited to the stomach; they are present in just about every cell in your body. All of your cells, with the exception of red blood cells, have mitochondria that allow your body to metabolize carbohydrates and fat to produce energy. They do this by pumping protons across the membrane to generate a source of electric potential that can be harnessed to form ATP, the body’s main storage form of energy. Without an efficient proton-pumping system, the body must rely on anaerobic systems for energy production, leading to rapid fatigue.

Proton pumps are also important in the transport of various substances in the body, as we will see in detail in later sections. And while proton pump inhibitors are designed to interact specifically with the hydrogen/potassium pump in parietal cells of the stomach, research suggests that they likely have nonspecific binding capabilities (3). In other words, their chemical structure enables them to bind to other proton pumps as well. Though PPIs don’t stay in the blood for very long, their binding to proton pumps is essentially irreversible—they will continue to inhibit the proton pump until the master antioxidant glutathione is able to facilitate dissociation (4).

(Note from Ellie: Glutathione is drastically reduced in patients with cirrhosis!!)

PPIs can harm your heart, brain, kidneys, and gut. There are other alternatives.

PPIs alter the gut

The composition of microbes that inhabit your gut is incredibly sensitive to changes in the local environment. pH, a measure of the acidity of an environment, is an important facet of gut health and a particularly potent regulator of microbial communities (5). PPI use reduces the amount of acid produced in the stomach, and ultimately the amount of stomach acid that reaches the gut. This causes a significant shift in the pH of the intestines.

Indeed, several recent studies have shown that PPI alters the gut microbiota by reducing its overall diversity (6,7). Opportunistic pathogens, including Enterococcus, Streptococcus, Staphylococcus, and E. coli, tended to be more prevalent in the guts of PPI users.

As stomach pH becomes less acidic, many ingested microorganisms that would normally be destroyed are able to make their way into the gut (8). Imhann and colleagues found that oral bacteria, such as the genus Rothia, were over-represented in the gut microbiota of PPI users (7). Those who used acid blockers also had an increased chance of acquiring Clostridium difficile, Campylobacter, Salmonella, Shigella, Listeria, and community-acquired pneumonia than those using other medications (9,10).

Another note from Ellie: a person with cirrhosis is already at risk for a bacterial infection. Once a patient with ascites develops Spontaneous Bacterial Peritonitis, the chance of survival is POOR.   You can see an article about that, here:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2621420/

A 2013 study also found a significantly increased percentage of individuals with small intestinal bacterial overgrowth (SIBO) among PPI users (11). Together, these studies point to the vital importance of sufficient stomach acid for protecting against bacterial influx into the GI tract and maintaining an intestinal pH that supports GI health.

PPIs impair nutrient absorption

Another consequence of long-term PPI use is impaired nutrient absorption, which I discussed extensively in a previous article. Stomach acid is essential for the absorption of many macro- and micronutrients. PPI users have been shown to have an increased risk of vitamin and mineral deficiencies, including vitamin B12, vitamin C, calcium, iron, and magnesium (12,13). Achlorhydria (a lack of stomach acid) and atrophic gastritis (stomach inflammation) allow for the overgrowth of bacteria, which compete with the host for consumption of micronutrients like vitamin B12 (14).

These micronutrients are particularly important for bone health. Studies have found an association between PPI use and total bone fractures in the elderly (15). While the association was modest, the findings were significant enough that the FDA felt it necessary to issue a news release in 2010 warning of the possible increased fracture risk (16). Since then, a more recent study has shown a similar association in young adult PPI users (17).

The effects of PPIs on bone health may be more nuanced than simply causing nutrient deficiency. Osteoclasts, the bone cells responsible for the resorption of calcium, also possess proton pumps, and their activity is thought to be directly affected by PPIs (18,19).

PPIs increase the risk of cardiovascular events

Several recent studies have also shed light on PPIs and the cardiovascular system. PPI users have been shown to have a significantly greater risk of heart attack than those on other antacid medication (20, 21). PPIs also reduce production of nitric oxide, a natural substance that promotes the dilation of blood vessels and improves blood flow (22).

PPIs may also damage blood vessel cells, as shown by a study published in May 2016. When researchers exposed cultured human blood vessel endothelial cells to esomeprazole, the cells seemed to age much more quickly, losing their ability to split into new cells. PPIs, which are designed to work especially well in acidic environments, seemed to inhibit an acidic compartment of the cell called the lysosome, which can be thought of as the cell’s “garbage disposal.” Without the ability to break down old proteins and other waste products of metabolism in lysosomes, “garbage” built up in the cells and inhibited their function (23).

PPIs harm the kidneys

The kidneys are also affected by PPIs. A study published in 2016 compared patients using PPIs to patients using H2 blockers, another common antacid drug. They showed that over the course of five years, those in the PPI group were 28 percent more likely to develop chronic kidney disease and 96 percent more likely to develop end-stage renal disease (24).

While the mechanism by which this occurs is unclear, we do know that proton pumps are present in the intercalated cells of the kidney. These proton pumps are responsible for moving protons into the urine, creating a gradient that allows for bicarbonate reabsorption into the blood (25). Bicarbonate is vitally important to maintaining proper blood pH.

PPIs negatively affect cognitive function

PPIs also impair cognitive function. A 2016 study found that regular PPI users had a 44 percent increased risk of dementia compared with those not using the drugs (26). A different study published in 2015 that assessed cognitive function in PPI users versus controls found statistically significant impairment in visual memory, attention, executive function, and working and planning function among PPI users (27).

Several commonly prescribed PPIs, such as lansoprazole and omeprazole, have been reported to cross the blood-brain barrier. In mice, PPIs were observed to affect β- and γ-secretase enzymes, resulting in increased levels of amyloid β, a protein fragment that forms the plaques characteristic of Alzheimer’s disease (28).

Furthermore, communication between brain cells requires the action of proton pumps. Simplistically, neuron cells contain small vesicles, or pockets, of neurotransmitters. When a neuron is stimulated, the vesicle releases these neurotransmitters into the synaptic space, where they can then interact with receptors on other nearby neurons, transmitting the signal down the line. The neurotransmitters must then be taken back up by the neuron so that they can be released again in response to the next stimulus. The energy required for this reuptake process is driven by proton pumps (29). If PPIs bind to these proton pumps, cognitive abilities would certainly be impaired.

PPI withdrawal can lead to rebound reflux

Your body is acutely sensitive changes in your physiology and is constantly trying to maintain a stable equilibrium, often termed homeostasis. In the case of PPIs, when it senses reduced stomach acid production, your body produces the hormone gastrin to try to compensate. Gastrin normally stimulates gastric (stomach) acid production.

Excess gastrin has in turn been shown to lead to an expansion of enterochromaffin-like cells (ECLs) (30). ECLs are found in the mucosa of the stomach in close proximity to parietal cells. A greater number of ECLs results in a greater amount of ECL hormones released that can interact with parietal cells. Parietal cells, as you may recall, are the cells responsible for stomach acid production via proton pumps. These parietal cells undergo hypertrophy, or an expansion in the size of each cell (31).

Larger parietal cells have more proton pumps and can produce larger amounts of stomach acid. This is termed “rebound hypersecretion,” or an overproduction of stomach acid after taking PPIs (32). This is why getting off PPI therapy is so difficult, because long-term use fundamentally changes the physiology of stomach cells. It also points to yet another instance where simply treating the symptoms of a condition fails to recognize and treat the underlying root cause.

Luckily, parietal cells are constantly undergoing renewal, with an average lifespan of only 54 days (33). So just because you took PPIs does not necessarily mean you are destined to rebound hypersecretion forever, as after a few months your stomach cells should have largely turned over. However, the repair mechanisms after PPI discontinuation have not been widely studied, and it is entirely possible that there are lasting effects.

Alternatives to PPIs

Collectively, these and many other studies suggest that PPIs are not as safe as they are made out to be. Frankly, it’s bordering on criminal that the FDA continues to allow these drugs to be prescribed as frequently as they are, and for durations of years or even decades in some cases, given the overwhelmingly large body of evidence documenting the potential harms associated with long-term PPI use.

Accusations in Lawsuits Against Heartburn Drug Manufacturers

https://www.drugwatch.com/proton-pump-inhibitors/lawsuit/

Lawsuits over kidney-related complications claim that Prilosec manufacturer AstraZeneca knew of possible kidney risks as early as 2004, but never warned patients about the danger. PPI labels did not warn of AIN risks until the FDA required that labels include it starting in 2014.

PPI MANUFACTURERS ARE ACCUSED OF:

• Negligence
• Misbranding
• Deceptive advertising
• Negligent misrepresentation
• Fraud
• Failure to warn of PPI side effects
• Accepting kickbacks
• Designing, manufacturing and selling defective products

 

Sounds like it's mostly about money! In my opinion, anyway.