“Fire in the gut is fire in the brain — Dementia, Alzheimer’s. SUMMARY: A recent study found risk of dementia in PPI users aged 75 and over. Previous studies had found that Histamine H2 antagonists (H2RAs) also have adverse cognitive impact in the elderly but the mechanism differed… it was due to anticholinergic effects; I wrote about that here. Can the heartburn drugs, dementia, Alzheimer’s risk associations be extended to younger ages?
What may be possible mechanisms? This post lists the PubMed studies finding that heartburn drugs put fire in the gut; they
- Skew microbiome — PPIs microbiome skew is so severe it increases the risk of CDiff and HALF of users have small intestinal bowel overgrowth, aka SIBO. Regarding the H2RA impact on the microbiome, there is only a paucity of data though studies are now ongoing. However, given that it too is an acid reducer, microbiome impact is likely similar to PPI. And
- Both PPIs and H2RAs mug nutrients, especially B12 which is associated with cognition.
Both of these mechanisms are not age dependent. “Fire in the gut is fire in the brain”.
With dementia known to be associated with B12 deficiency, and if dementia is shown to be associated with microbiome skew in humans, (this mouse study also suggests such) are heartburn drugs (that skew microbiome and deplete B12), dementia, Alzheimer’s a risk for all ages? Can impaired cognition for Type 2 Diabetes (T2D) irrespective of age, many of whom also take acid reducers, be the canary in the coal mine suggesting YES? Read on; it may be time to re-think grandma, your dad, yourself, and your child on heartburn drugs.
Last, this post shows another mechanism for dementia for all ages — high blood sugar with or without diagnosed diabetes. Diet guidance (with links) that lowers blood sugar for all is provided.
Realize however, dementia and Alzheimer’s risks are multi-factorial. It is certainly worth reducing their risk by focusing on risk factor associations.
Some confounding factors for cognition risk includes exercise and here, cardiovascular, gut microbiome impact (mouse study) and diet this post details optimal microbiome diet learned thus far from American Gut though not specifically addressing brain health, or possibly even overgrowth of oral anaerobes in the brain. The later is challenging the entrenched dogma that organs are supposed to be sterile. For example, bacterial findings in the placenta and amniotic fluid is thought to likely be a natural part of in utero development with the hypothesis that exposure to harmless bacteria “trains” the developing immune system — however, bad things may happen to this taxa and overgrowth is one thought. For another example see the breast microbiome — cancer post). Actually, the greatest known risk factor for Alzheimer’s is the aging brain; it certainly makes sense to knock down all the risk factors that one can.
If gut microbiome is found to be associated with dementia, reducing/eliminating the acid reducer factor which is contributing to skewed microbiome, with physician guidance, knocks down a big contributor to microbiome skew. Check out Dr. Mark Hyman’s post here to begin to self educate yourself on reducing heartburn drugs.
We now know that acid reducers are associated with cognition impairment in the elderly.
The study: Association of Proton Pump Inhibitors With Risk of Dementia A Pharmacoepidemiological Claims Data Analysis, published Feb, 2016 in JAMA, reports on increased risk for dementia for PPIs in older patients. See also the associated MedScape article, Proton Pump Inhibitors Linked to Dementia. In the study, Regular PPI use was defined as at least 1 prescription per quarter for: omeprazole, pantoprazole, lansoprazole, esomeprazole, rabeprazole.
Results A total of 73 679 participants 75 years of age or older and free of dementia at baseline were analyzed. The patients receiving regular PPI medication (n = 2950; mean [SD] age, 83.8 [5.4] years; 77.9% female) had a significantly increased risk of incident dementia compared with the patients not receiving PPI medication (n = 70 729; mean [SD] age, 83.0 [5.6] years; 73.6% female) (hazard ratio, 1.44 [95% CI, 1.36-1.52]; P < .001). The association was slightly more pronounced in men than women (HR 1.52 versus HR 1.42), though both were statistically significant
Conclusions and Relevance: The avoidance of PPI medication may prevent the development of dementia. This finding is supported by recent pharmacoepidemiological analyses on primary data and is in line with mouse models in which the use of PPIs increased the levels of β-amyloid in the brains of mice. Randomized, prospective clinical trials are needed to examine this connection in more detail.
Haenisch and colleagues noted, Medscape, PPIs May Hike Dementia Risk in Elderly, that their claims-based analysis could not exclude all potential confounders, and their data lacked specificity on specific dementia types and causes. Lewis Kuller, MD, DrPH editorial said, “further determinants of whether PPIs are causal for dementia requires validation in large cohorts and probably well-designed case-control studies with good measures of PPI use (especially long-term use), covariates, and especially methods to measure incidence of dementia.”
Cognitive Impairment Mechanism #1, Anticholinergic effects. For whatever reasons, hundreds have read the post, ALZHEIMER’S & DEMENTIA, COMMON MEDICATIONS INCREASE RISK in the last few days. That post discussed adverse cognitive effects for very common drugs — antihistamines antidepressants, and acid reducers — H2RAs , and named those drugs that are to be avoided in the elderly due to anticholinergic effects. While there is no evidence that anticholinergic drugs cause dementia, there is an association link, and H2RAs are listed as anticholinergic medications. Despite adverse cognition effects, alternatives to PPIs to treat gastrointestinal disorders in the elderly [in all ages actually] include H2RA, prostaglandins, and antacids. H2RA drug names include: cimetidine (Tagamet), ranitidine (Zantac or Pylorid), famotidine (Pepcid, Fluxid, Quamatel and Select), and nizatidine (Axid).
These drugs are also listed on the guideline called Beers tool which the American Geriatrics Society uses to assess elderly drug risk; they are listed there due to anticholinergic adverse cognitive effects. See this post for what is anticholinergic. See here for the guideline, American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults, and here for the pdf.
REAL EYE OPENER: the US Beers tool can not be used in the UK since approximately 50% of the Beers drugs are unavailable in European countries . see Potentially inappropriate prescribing among older people in the United Kingdom. Whoa… surprised?!?
Cognitive Impairment Mechanism #2: Many ages using PPI or H2RA have B12 deficiency (not just the elderly) which if left untreated can increase risk of dementia. Actually there many other nutrient deficiencies occurring for PPIs (Vit C, calcium, iron, magnesium); as well, 50% PPI users test positive for Small Intestine Bowel Overgrowth (SIBO). The studies:
- Long-term use of common heartburn and ulcer medications [PPI and H2RA] linked to vitamin B12 deficiency, see study PDF here, reported on a review of Kaiser Permanente records that found a link for PPIs or H2RA to B12 deficiency: Vitamin B12 deficiency left untreated, can increase the risk of dementia, nerve damage, anemia, and other medical complications, some of which may be irreversible. Gastric acid is required to cleave vitamin B12 from ingested dietary proteins for the essential vitamins to be absorbed; suppressing the acids can lead to the health-threatening vitamin deficiency.
Among the 25,956 patients [~33% were under age 60] who had vitamin B12 deficiency, 12% used PPIs for at least 2 years, compared with 7.2% of the control patients. The impact of taking any daily dosage of H2RA drugs was less pronounced but also significant: 4.2% of patients with B12 deficiency used these medications versus 3.2% of control patients. “Patients who took PPI medications for more than two years had a 65% increase in their risk of B12 deficiency,” said Douglas A. Corley, MD, PhD, a gastroenterologist and research scientist with the Kaiser Permanente Division of Research. “Higher doses also were associated with an increased risk, compared with lower doses.
- Cognitive impact after short-term exposure to different proton pump inhibitors: assessment using CANTAB software, Dec. 2015, evaluated 60 participants having overall age range 20–26 years and found for the first time that different PPIs have varying degrees of influence on different cognitive domains and have associations with Alzheimer’s… PPIs increase the brain burden of amyloid-beta (Aβ) and also create vitamin B12 deficiency… these two phenomena have deleterious effect on cognition and Alzheimer’s disease (AD). Importantly, these authors explain, “We do not firmly conclude that all patients receiving chronic PPI therapy will develop AD; rather, these patients may be at high risk of developing some sort of dementia when they are older. AD is a very slow, progressive dementia that takes many years to develop, and many other factors may contribute to its prognosis.” [Now isn’t that interesting… this post discusses Alzheimer biomarker predictors years ahead of diagnosis.]
PPIs increase Aβ, not only in cell cultures but also in mouse brain . Another reason was that during AD accumulation of Aβ in the parietal cortex is associated with impaired visuospatial skill, executive function, and attention. Furthermore, impaired visual and verbal memory are due to accumulation of Aβ in the medial temporal lobe of the human brain [44–47].
Another aspect of how PPI consumption influences cognitive function is rather elusive. It has been suggested that chronic PPI consumption results in malabsorption of vitamin B12, leading to cognitive decline [17, 27,28]. Although this phenomenon is unlikely to occur in healthy people who follow a normal diet, it might be of significant importance for elderly patients who are relatively malnourished and receiving chronic PPI therapy . [Note however, B12 marginal depletion (serum 148–221 pmol/L) was more common and occurred in ≈14–16% of those aged 20–59 y and >20% of those >60 and vegetarians are at particular risk of B12 deficiency: 62% among pregnant women, between 25% and almost 86% among children, 21-41% among adolescents, and 11-90% among the elderly) [Note: there are many other nutrient deficiencies occurring for PPIs (Vit C, calcium, iron, magnesium), as well, 50% PPI users tested positive for SIBO. See details below my signature.]
[Interesting… the placebo control group received a hard gelatin shell capsule containing husk of isabgol — psyllium seed husk which is a prebiotic that helps modulate the microbiome, and that helps optimize the gut/brain axis.]
Gut microbiome changes includes systemic consequences such as cognition.
The microbiome has a gut/brain axis connection: Strong evidence suggests that gut microbiota has an important role in bidirectional interactions between the gut and the nervous system. It interacts with central nervous system by regulating brain chemistry and influencing neuro-endocrine systems associated with stress response, anxiety and memory function.
This mouse study showed that C. butyricum treatments could modulate the gut microbiota, and a relation was observed between improvement of brain function and changes in the microbiota composition. The authors hypothesized that the rise of butyrate in the brains is due to the changes in the microbiota composition, and the butyrate travels from the intestinal tract to the brains to exert neuroprotective effects. Butyrate can cross the blood-brain barrier to modulate CNS functions including brain development and behavior [17, 43]. Butyrate might play an important role in the CNS [24, 44].
PPIs mess up the microbiome with huge consequences. The mechanism is NOT age dependent and should be the same for H2RA: improperly digested food exits the stomach and has downstream ramifications for the microbiome.
Microbiome adverse skew occurs for PPIs; PPI microbiome diversity is so decreased and skewed that users have increased risk, independent of age, of: CDiff infection (recall… FMT restores the desert CDiff microbiome.), half of PPI users have SIBO, vitamin/mineral deficiencies occur (B12, C, calcium, iron, magnesium), IgE food allergies to common food occurs (milk, potato, celery, carrots, apple, orange, and wheat and rye flour occurs, chronic kidney disease, and heart attack risks increase 16-21%. Add now to that list, cognition impairment for the elderly as discussed above. I was surprised to see Table 3, PPI ranitidine make the list of top drugs prescribed to kids; especially concerning given antibiotics carpet bombing microbiome are there too. Details and links to the above studies can be found below my signature at the end of this post.
Sidebar rant: What’s up with dispensing PPIs that severely adversely alters the microbiome to kids? Isn’t it enough that the antibiotics carpet bomb their microbiome? You’d think patient consent following full PPI risk disclosure would be required for all. Elevated CDiff risk alone should require patient consent given the epidemic antibiotic resistance now associated with CDiff and other antibiotic resistant infections. “C. diff is very much the poster child for how we’ve messed things up by interfering with the microbiota. And it is just the most obvious problem [antibiotic resistance].” -Dr. Emma Allen-Vercoe, a key microbiome researcher I follow. It affects more than just the drug user. Scientists are concerned the microbiota is becoming more impoverished with each successive generation. From Sonnenburg Lab at Stanford University, “It appears that this ecosystem is also fragile and that dietary decisions made by one generation could affect the microbial ecosystem that future generations carry around inside them. While we all accept that we pass our genome [human genes] onto our children, we now must appreciate that we also bequeath our microbiome. How we have cared for this community is not only important for our health, but also that of future generations.” See posts on microbiome acquisition during birth here, and here. Rant over.
H2RA impact to microbiome has a paucity of data available. Seems microbiome ramifications would be similar to PPIs as the mechanism, improperly digested food exiting the stomach, is the same and NOT age dependent. H2RA microbiome studies are starting. The clinical trial, Effect of Acid Suppression Medication on Pediatric Microbiome is currently recruiting children with GERD, but otherwise healthy, for microbiome studies to determine whether acid suppression with these meds affects the microbiome. The MedPage article, Do Antacids Pose Infection Risk in Kids? addresses H2RA and associated adverse microbiome ramifications. These authors note the lack of evidence supporting safety of H2RA in children. This study found H2RA use in Crohn’s doubled the risk of hospitalisation/surgery; PPI use was associated with medication change in UC.
What is the risk of dementia, Alzheimer’s, for those with and those without diagnosed diabetes?
Look over the below slides. Seems to be an uncomfortably high risk for ALL having high blood sugar. Recall there is a huge amount of folks, 27.8%, with diabetes yet undiagnosed; they at already at higher cognitive risk… they just don’t know it. Dr. Andreas Eenfeldt notes in his post having the first pic below, the ideal average blood sugar level is maintained around 90 mg/dl (5 mmol/l) – and less beneficial is if the average is above 108 mg/dl (6 mmol/l).
The stats for having eventually an Alzheimer’s diagnosis is shocking; from an interview of Dr. Thomas Wisniewski, @ time 25:30: “Brains – The Latest Research 7/01/2013 — 1 in 8 by age 64 will have Alzheimer’s. It doubles every 5 years. So… By age 70, Alzheimer’s will affect 1 in 4; by age 75, 1 in 2. Alzheimer’s affected 4.7 million in 2010, and is projected to be about 7 million by age 85 or older in 2050. From “Dementia, Alzheimer’s and Aging Brain,” interview of Steven Ferris, 07/02/2015 — The single greatest risk for dementia is brain aging. Slowing brain aging reduces the likelihood to brain aging. Stats at time 14:45, cite a greater than 30% risk of Alzheimer’s for over age 85.” To keep the brain healthy, Ferris noted: don’t smoke, exercise the body, exercise the brain with intellectual challenge (body exercise has greater beneficial effect on high mental health), eat right (Mediterranean or variations, lots of fruit and vegetables rich in antioxidants, low saturated fats). Cardiovascular risk factors ends up being Alzheimer’s risk factors. What is good for the heart is good for the brain to reduce risk of Alzheimer’s.”
Can impaired cognition for T2D (many of whom also take acid reducers) be the canary in the coal mine suggesting heartburn drugs is contributing to that risk?
First, why did I pick the T2D population? Because T2D affects a lot of folks, and there is huge population that are undiagnosed and don’t even know they have the disease. From WHO: In 2014, 9% of adults 18 years and older had diabetes, 90% of those are T2D, and diabetes will be the 7th leading cause of death in 2030. Even more astounding, the CDC reports that 27.8% of people with diabetes are undiagnosed.
Diabetes mellitus is associated with cognitive dysfunction and abnormalities that can be seen with brain imaging.
- T2D monotherapy with either metformin, an H2RA, or a PPI can deplete vitamin B12 which left untreated increases risk for dementia. – See Metformin With Either Histamine H2-Receptor Antagonists or Proton Pump Inhibitors: A Polypharmacy Recipe for Neuropathy via Vitamin B12 Depletion.
- T2D B12 deficiency has increased risk of cognitive decline. Up to 30% of patients taking metformin may be deficient in B12, and this is thought to be due to an interaction between metformin and a receptor in the distal ileum, leading to some inhibition in the uptake of the vitamin. The researcher, Dr. Moore told Medscape Medical News that she recommends clinicians and patients with diabetes should “aim to maintain good, rather than adequate, serum vitamin-B12 levels” of greater than 300 pmol/L to reduce the risk of cognitive decline later in life.” See study, Increased Risk of Cognitive Impairment in Patients With Diabetes Is Associated With Metformin and this Medscape article, Diabetes Drug Metformin May Impair Cognition, Study Finds. Participants were aged 51 to 99 years (mean, 74 years), and 59.5% were female. Scores on the Mini-Mental State Examination (MMSE), a measure of cognitive ability, were normal (28–30) in about half (50%), minimally impaired (24–27) in 22%, mildly impaired (18–23) in 18%, and most impaired (less than 18) in 10%. After adjustment for age, sex, education, and depression, the subjects with type 2 diabetes had worse cognitive performance (MMSE of <28) than did those without diabetes, with an adjusted odds ratio of 1.51 (P = .033).And in the diabetes group, cognitive performance was significantly worse among those who were taking metformin, Scores on the MMSE were 22.8 [this is mildly impaired] in those on metformin vs 24.7 [this is the lower threshold for minimally impaired, mildly impaired is 23-18] for those with diabetes not taking metformin.Also among the participants with diabetes, MMSE scores were lower among those who had serum vitamin-B12 levels less than 250 pmol/L compared with those who had higher vitamin-B12levels (MMSE 22.9 vs 25.0, respectively).
- A brief review of the mechanisms potentially linking T2D with cognitive impairment (as of 2012) is here, Type 2 diabetes and cognitive impairment: linking mechanisms. A follow-up study, Inflammation -associated declines in cerebral vasoreactivity and cognition in type 2 diabetes, see full study text here, found relationships between inflammation, cerebral vasoregulation, and cognitive decline in T2D treated for over 5 years, over a 2-year span.
Findings: Impaired vasoreactivity is a marker of microangiopathy in T2DM (25) and is linked to impaired cognitive function in the aging diabetic brain (3) and Alzheimer disease. (22) After 2 years of follow-up, participants with T2DM had diminished global and regional cerebral vasoreactivity (>50%, see table 2) and a decline in multiple cognitive tasks compared with baseline. In the T2DM group, lower cerebral vasoreactivity was associated with a greater decrease in daily living activities score , and lower global vasodilation was associated with a greater decline in executive function. Higher serum soluble intercellular and vascular adhesion molecules, higher cortisol, and higher C-reactive protein levels at baseline were associated with greater decreases in cerebral vasoreactivity and vasodilation only in the T2DM group, independent of diabetes control and 24-hour blood pressure. Higher glycated hemoglobin A1c levels were associated with a greater increase in vasoconstriction in the T2DM group.
CONCLUSIONS: Inflammation may further impair cerebral vasoregulation, which consequently accelerates decline in executive function and daily activities performance in older people with T2DM.
- This paper discussed B12 induced deficiencies found with Metformin and concomitant GERD meds create a positive feedback loop with increasing neuropathy, Metformin With Either Histamine H2-Receptor Antagonists or Proton Pump Inhibitors: A Polypharmacy Recipe for Neuropathy via Vitamin B12 Depletion:
The study explains: Both metformin and acid-suppressing medications have been demonstrated to deplete B12 independently and to have additive effects when used concomitantly. The potential for neuropathy to develop is a result of this likely polypharmacy scenario. What is generally thought of as “diabetic” neuropathy may be, at least in part, B12 deficiency–induced neuropathy resulting from the concomitant use of these medications.Both H2RAs and PPIs have been documented to interfere with B12 absorption (43–47). Discontinuation of the H2RAs stopped B12 depletion (48,53). In 1980, Steinberg et al. (48) found that, while undergoing treatment with H2RAs, patients were able to absorb unbound B12 (i.e., B12 from a vitamin supplement) but not protein-bound B12 (i.e., B12 from food sources). Numerous subsequent articles have also reported H2RA-induced B12 depletion (49–51). When protein-bound B12 absorption was assessed before and after H2RA therapy, a 53% drop in absorption was noted (from 5.3% before treatment to 2.5% after treatment) (49). When protein-bound B12 absorption was assessed before and after ranitidine therapy, an 89% drop in absorption was noted (from 7.66% before treatment to 0.84% after treatment) (52). Other studies analyzing ranitidine have also noted decreases in B12 (53). In addition to H2RAs, studies have noted an inverse correlation between duration of PPI therapy & B12 levels (54–57).
Note: Relative to the B12 and diabetic neuropathy association, a conflicting study showing non-association, published March 2016, Diabetic neuropathy is not associated with homocysteine, folate, vitamin B12 levels, and MTHFR C677T mutation in type 2 diabetic outpatients taking metformin.
Are T2D folks using PPI and/or H2RAs?
This study showed that the prevalence for GERD in T2D is the same as the general population, so the short answer is YES; there was no differences between diabetics and non-diabetics concerning the use of proton pump inhibitors and pro-kinetics (59/65 [90.8%] vs. 118/130 [90.8%]. Other studies find increased GERD in diabetes (so acid reducers may be prescribed more than the general population). See prevalence of GERD symptoms in diabetics is 40.7% and that percent increases with neuropathy symptoms to 59%. The paper, Metformin With Either Histamine H2-Receptor Antagonists or Proton Pump Inhibitors: A Polypharmacy Recipe for Neuropathy via Vitamin B12 Depletion further explains that 70% of T2D with GERD use oral antidiabetic medications. Thus, it is likely that millions of individuals are managing blood glucose and GERD concomitantly with oral medications (1,7) Therefore, it is important to assess the drug interactions and clinical sequelae that may occur with this particular polypharmacy scenario.
Recent findings of adverse cognition risks for T2D may be moving the needle for acid reducing drugs, H2RA and PPI, associations to cognitive impairment to include non-elderly.
Defining the hearburn meds.
What are PPIs and how many use them? Harvard Health Letter, Proton-pump inhibitors: Prescriptions are sometimes needed for: omeprazole (Prilosec, Omesec, Zegerid, and Select), lansoprazole (Prevacid, Select, and Rugby), esomeprazole (Nexium) whereas prescriptions are required for: pantoprazole (Protonix), pantoprazole (Protonix), dexlansoprazole (Dexilant), and rabeprazole (AcipHex). These medications are consistently in the top 10 meds prescribed and sales lists (see full list of top 100 here). From April 2014 through March 2015, PPIs esomeprazole (Nexium, AstraZeneca) ranked third in number of prescriptions written having ~18.2 million. Population-based studies have demonstrated that 44% and 20% of the US adult population reported GERD-related symptoms (heartburn and acid regurgitation) at least once a month and once a week, respectively.1 Many use PPIs without indication based evidence including nearly half of nursing home patients.
How often are PPI users dosing and with what? 42% supplement PPIs with H2RAs! Treatment patterns and symptom control in patients with GERD: US community-based survey found for 617 PPI users: 71.0% used PPIs once a day, 22.2% used twice a day and 6.8% more than twice a day or on an as-needed basis. About 42.1% of all patients supplemented their prescription PPIs with other GERD medications, including over-the-counter medications and H(2)-receptor antagonists. Despite this, 25% were not completely satisfied with their PPI treatment. Importantly, it has been estimated that nearly 30% of GERD patients are treated with a double-dose PPI.44
What are the PEARLs diet wise, to minimize risk of dementia, Alzheimer’s?
For everyone, more blood sugar increases risk of dementia. If you want to avoid dementia as you get older, then perhaps use caution with foods that raise blood sugar. Move your diet to that which lowers blood sugar.
Ironically, for many, moving to this diet reduces, if not eliminates, the need for acid reducers which are linked to dementia and Alzheimer’s in the elderly. These conditions are thought to start much earlier which makes sense given adverse microbiome skew from PPIs (H2RA still needs confirmed).
T2D and the acid reducer and dementia associations may be the canary in the coal mine suggesting acid reducers contribute to cognitive impairment for many.
That’s why many diabetics eat the low carbohydrate high fat (LCHF) diet. See the leading LCHF anti-sugar increased healthy fat MD crusader advocates: cardiologist, Dr. Aseem Malhotra, Dr. Andreas Eenfeldt and/or Dr. Peter Attia. Attia expains, “This diet, for health and weight management/loss, is low in sugar and refined carbohydrates. It is especially for people who are insulin resistant which is true for about 70% of people who are overweight. If you must make a change immediately, though, here are a few of the changes you should choose from, probably in this order [see the pic below]. As you go down the list, the improvements get incrementally greater.” A cancer radiologist that I respect, Dr. Colin Champ, eats this way for health, shares My Meals in a Week (included below — but go to the link if not readable). I included this as it is an eye opener for what types and amounts of food is consumed).
Another way to think about diet. It is an alternative to PPIs and H2RA — that lowers blood sugar to avoid cognitive impairment. It is an anti-inflammatory, low toxin, nutrient dense diet and lifestyle. Non-diabetics do not need to be as carb limited, but they still need to exercise caution and avoid carb loads in excess of energy output. Obviously, the carbs are not refined and processed.
Motivation turns many to diet and lifestyle rethinking their plate; the collage below walks you through the nuts and bolts (understanding what are the healthy non-insulin spiking microbiome building macronutrients and loads for such, for carbs, healthy fats, and quality sourced proteins). The LCHF diet (links above) would modify or tweak that below. You should recognize the associated posts, but read this post for practical ideas for diet transition that supports digestion. Note: Some folks are so compromised they need to include digestive enzyme support at the start.
In acid reducing PPI/H2RA cognition impairment conclusion:
As Dr. Kelly Brogan so eloquently explains, “This tends to be my major concern with regard to pharmaceutical interventions – there’s just no free lunch with medication treatment, and a risk/benefit analysis is very difficult to do if we don’t know what environmental and genetic risks an individual is bringing to the table. If there is a treatment option that presents minimal to no appreciable risks and some degree of evidence-based benefit, this, to me would represent the kinder, gentler road to health.”
It is becoming clearer that what the drugged microbiome looks like for any drug you are prescribed is crucially important for your overall health and wellness including systemic implications like cognition.
Realizing the systemic hit to cognition is real for certain drugs, you have a choice & can decide if the risks to your microbiome makes the drug’s claimed benefits worth it knowing that you can always try healing diet and lifestyle modifications to increase microbiome diversity and immunity first.
I’d like to see you keep your brain! Please, don’t lose it!!!
Last updated: January 19, 2017 at 8:47 am
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How may PPIs be increasing the risk for dementia, Alzheimer’s in older patients? Some of the mechanisms of action are not just limited to the elderly.
They need to look beyond the brain, and look at the gut.
PPIs impact to the microbiome was discussed on the post, DO MICROBIOMES ON DRUGS LOOK HEALTHY? BIOLOGICS & PPI, which is excerpted below for continuity and convenience.
PPI physiology & consequent health ramifications due to improper digestion — upstream/downstream ramifications
Normal gastrointestinal acidity provides:
Acidity within the human gastrointestinal tract varies by anatomic location and is part of essential physiologic processes including digestion and nutrient absorption.2 In the stomach, lumenal pH can approach 1.0; gastric acid plays a role in breakdown of food particles, and the pH-dependent separation of intrinsic factor from R-protein.3 Outside of the stomach, lumenal pH is often discussed in the context of optimizing drug delivery. In general, pH tends to rise gradually from 6.5 in the small bowel to a high of 7.5, drop in the cecum (to as low as 5.5), and again rise gradually in the left colon to a high of 6.5 – 7.0.4 Local pH partially determines the absorption of biotin and folate in the small bowel,5,6vitamin B12 in the distal ileum,7 and calcium and other electrolytes in the colon.8 Thus, in addition to the influence that pH exerts on the microbiome, gastrointestinal acidity is important and tightly regulated.
PPIs interfere with the digestive function of the stomach and train wreck the gut microbiome.
How PPIs wreck your gut microbiome:
Generally, PPIs increase stomach pH to above 5.0 (within 5 days for omeprazole). However, protein digestion requires pH of 1.8-3.2 for the activation of pepsinogens. The stomach’s gate keeping protective function to mitigate bacterial infection is almost totally abolished due to the reduced stomach acid. Gastric acid suppression by PPIs exerts a downstream effect on small intestinal bacterial composition. Normal breakdown of food antigens is inhibited; intact food proteins persist in the small intestine having consequence:
- Increased risk for infections like CDiff and pneumonia due to decreased diversity of microbiome gut bacteria at both low and high dosages of omeprazole, after both 1 week and 1 month. These researchers found that at the end of the 28-day treatment period, the observed OTU counts were similar to those from patients with a first CDiff infection episode indicating the potential for PPIs to negatively influence the robustness of the host microbial ecology and increase the susceptibility to CDiff infection. The microbiome skew was only partly reversed after a 1 month recovery period. The authors suggest that with the elimination of nutrient competitors, PPI use may directly affect gene expression across metabolic pathways in favor of CDiff growth. –Prolonged use of a proton pump inhibitor reduces microbial diversity: implications for Clostridium difficile susceptibility and Proton pump inhibitors decrease diversity in gut microbiome, increase risk for complications and Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case–control studies: Almost 50% of the patients receiving antibiotics in our cohort study were prescribed PPIs, with another 10% receiving H2 blockers. In the majority of the patients in the case–control study, we could not ascertain from the chart review why the patients were prescribed a proton pump inhibitor. A recent report suggested that acid suppressive therapy is overused in hospital patients and demonstrated that 46% of the patients in whom they determined the prescription unnecessary were still taking the medications 3 months after discharge.29
- Common food allergies develop. 10% had a boost of pre-existing IgE antibodies and 15% had de novo IgE formation to milk, potato, celery, carrots, apple, orange, and wheat and rye flour. –Anti-ulcer drugs promote IgE formation toward dietary antigens in adult patients and Adverse Effects of Proton Pump Inhibitor Drugs: Clues and Conclusions.
- Vitamin and mineral deficiencies including 44% increased risk of hip fracture. B12 (since stomach acid cannot separate vitamin from the protein it is attached), C, calcium, iron, magnesium. B12 deficiency risk is 65% for PPI and 25% for Histamine users. NIH estimates up to 15% of US population has a B12 deficiency. B12 is your body’s master anti-oxidant. –Proton pump inhibitors and risk of vitamin and mineral deficiency: evidence and clinical implications and Proton Pump Inhibitor and Histamine 2 Receptor Antagonist Use and Vitamin B12 Deficiency and Effect of proton pump inhibitors on vitamins and iron.
- SIBO was detected in 50% of patients using PPIs, prevalence increased after 1 year treatment, assessed by glucose hydrogen breath test (GHBT), compared to patients with N=200, IBS off PPIs for at least 3 years (24.5%) or N=50 control subjects off PPIs for at least 10 years (6%). High dose therapy with rifaximin eradicated 87%-91% of cases of SIBO in patients who continued PPI therapy. Note: no mention about SIBO relapse. Increased incidence of small intestinal bacterial overgrowth during proton pump inhibitor therapy and The impact of proton pump inhibitors on the human gastrointestinal microbiome. This meta analysis looked at SIBO testing (GHBT versus a highly accurate testing modality — duodenal/jejunal aspirate culture). A statistically significant association between PPI use and SIBO was found only when the diagnosis was made by duodenal/jejunal aspirate culture. Conclusion: Both clinicians and patients should be judicious in the use of PPI and consider dose-tapering whenever possible. In addition, a high level of suspicion should be raised when evaluating PPI users presenting with symptoms or signs suggestive of SIBO. -Proton Pump Inhibitor Use and the Risk of Small Intestinal Bacterial Overgrowth: A Meta-analysis
- 16 to 21% increased risk of heart attack, see Common heartburn medications linked to greater risk of heart attack
- Also note, it is hard to wean off PPIs due to habit forming and rebound effects.
Another PPI synopsis can be read at: Proton Pump Inhibitors – A Risky Experiment?