Category Archives for "Gastrointestinal"

Probiotic FAQ: Part 2

It’s finally Spring in Ohio! Trees are blooming, and it’s warm enough for walking and playing outside. Our daughter learned to ride a bike without training wheels this week and she’s been non-stop asking to go outside. Balance bikes are amazing, she literally tried the real bike for 1 day before she got it after using the balance bike the last few years.

This is the final post in my Probiotic Series at least for now! If you haven’t checked out the other post, please do, it starts with Probiotics 101, then Probiotic FAQ: Part 1 . And now on to Part 2! I also have a post over on my friend Lindsey Elmore’s site you should read as well. Thanks again to my interns Vineeta Rao and Ruth Gunti who worked on this series with me.

I hope these post help explain some of the basics about probiotics and the answer your questions, if you have further questions. Don’t hesitate to reach out.

Dr. Hartzler

If I have histamine intolerance, should I avoid certain strains? If so which ones?

Histamine intolerance is a condition in which the body has imbalanced levels of histamine. In this state, through the body’s own metabolic processes or consumption of histamine-rich foods, the body has too much histamine and may react to certain food with allergic-like symptoms such as hives, skin rashes, and other digestive symptoms.1 Gut bacteria are involved in both producing and degrading histamine, and having too many histamine-producing bacteria or too little histamine-degrading bacteria may cause elevated histamine levels.2,3 Therefore, it is crucial to select a probiotic that contributes to the proper balance of histamine in the body.

If you have histamine intolerance, it is important to avoid certain species of histamine-producing bacteria when selecting a probiotic. Those that should be avoided are Lactobacillus casei, Lactobacillus Bulgaricus, Streptococcus thermophilus, Lactobacillus delbrueckii, Lactobacillus helveticus.3
In contrast, certain probiotics appear to aid in relieving the imbalances found with histamine intolerance. Lactobacillus rhamnosus strains GG and c705 have been observed to inhibit the effect of histamine in the body.4 Additionally, in vitro studies suggest that bifidobacterium lactis and lactobacillus plantarum species promote histamine breakdown. 5,6

Should I take a probiotic while also taking an antibiotic? If so which one, and for how long?

Although clinicians have generally supported using probiotics with an antibiotic course, this is an area of controversy as new studies suggest that probiotics may interrupt the body’s natural process of restoring the bacterial balance in the gut. There are many studies that support using probiotics to prevent antibiotic-associated diarrhea, and among the tested species S. boulardii has specifically been shown to be effective.7 Studies have also shown that Lactobacillus rhamnosus GG, the strain contained in the Culturelle probiotic, appears and effective to prevent antibiotic associated diarrhea (AAD) in an outpatient setting.8 The recommended  dose is 107 to 1010 colony-forming units (CFU) per capsule (taken one to 3 times daily) as that is what has been studied; duration of therapy can be 1-3 weeks or the entire length of time that the patient is on antibiotics.9 For reference, Metagenics “UltraFlora LGG” and Culturelle “Digestive Health” products contains 1010 CFU per dose, and Culturelle “Kids” product contains 109 CFU per dose, making these products good choices for AAD.10 It is generally recommended to take probiotics for a couple months after therapy and consuming fermented foods. Overall it is said that “probiotics appear to be effective in preventing and treating AAD in children and adults receiving a wide variety of antibiotics.” 8-10

However, there is emerging research that suggests that probiotics may actually delay spontaneous recovery of the microorganisms in the gut, or the “gut microbiome.” A recent study compared spontaneous gut recovery to probiotic use in humans receiving a broad-spectrum antibiotic course. By performing endoscopies and examining the stool from the patients before and after receiving antibiotics, normal genetic expression of bacteria in the gut was delayed by up to 5 months in the probiotic group versus a matter of weeks in the group allowed to spontaneously recover.11,12 The in vitro portion of the study suggested that Lactobacillus acidophilus may inhibit the native gut microbiome.11 While this study cautions against the preventative use of probiotics with an antibiotic course, further studies to shed light on the benefit or harm of probiotics are needed to come to a clear conclusion.12

In the meantime, it may be wise to avoid probiotics with Lactobacillus acidophilus when taking an antibiotic course. One of the challenges as a provider recommending probiotics is that this was just 1-2 studies in the midst of all the literature and didn’t not look at saccharomyces boulardii and its effect, therefore it really just raises questions for future research and gives us a pause to our practice of using blanket probiotics for everyone on antibiotics habit.

If I have dysbiosis or Small intestinal bacterial Overgrowth, should I avoid pre-biotics or certain probiotic strains?

Small Intestinal Bacterial Overgrowth (SIBO) typically refers to a form of dysbiosis (imbalance of bacteria on the body) attributed to an excessive overgrowth or changes in types of bacteria in the small-intestine.13,,14 While the small intestine is not sterile, it has far fewer bacteria than the large intestine. Thus, SIBO may result from the specific bacteria that normally grows in the large intestine growing inappropriately in the small intestine.13,14 Other causes of SIBO include multiple courses of antibiotics and impaired defense mechanisms such as low stomach acid, which may be caused by use of Proton Pump Inhibitors (PPIs). While the definition is constantly changing and expanding to include other forms of dysbiosis, SIBO is typically characterized by non-specific gastrointestinal symptoms such as bloating, abdominal discomfort, diarrhea, fatigue, and weakness and might be treated with an antibiotic course.13,14

There are several studies that actually support the use of probiotics for this disorder.15  However, at the moment there is little consensus across the studies as to which probiotics species and strains will provide benefit for SIBO. Regardless of the species, the theoretical concern with using probiotics in SIBO even if the bacteria added to the gut is “good” bacteria, too much bacteria often produces symptoms of bloating and gas, which would worsen symptoms. In SIBO, patients often have an overgrowth of D-lactate-producing bacteria, so it may be best to avoid probiotics that also produce D-lactate such as Lactobacillus acidophilus.16

In the past it has also been generally recommended that one avoid the use of prebiotics until SIBO symptoms under control. Currently, studies that challenge this notion are frequently emerging, and in time, we may see a demonstrable benefit of certain probiotics and prebiotics in SIBO.16 However, until studies show which species and strains relieve rather than aggravate SIBO symptoms, it is likely best to avoid prebiotics and probiotics that produce D-lactate. In general, I recommend treating the overgrowth before working on replacing the flora with probiotics. Once those probiotics are tolerated, consider adding prebiotics to support healthy growth of gut flora along with other measures to prevent SIBO recurrence. Specifically, Partially Hydrolyzed Guar Gum (PHGG) is a prebiotic that has been shown to treat SIBO when administered alongside the antibiotic rifaximin better than rifaximin alone.17 Thus, this product could be a good option for encouraging healthy gut flora growth.

That’s a wrap. As always you can find great probiotic options on my FullScript Store or at YoungLiving. Feel free to message me if you have specific questions. We have so much science but we are still not quite a place were we absolutely know which probiotic product is going to work for each person. We are moving closer to that each day.

References:

  1. Maintz L,  Novak N.Histamine and histamine intolerance.Am J Clin Nutr. 2007;85(5):1185-96.
  2. Pugin B, Barcik W, Westermann P, et al. A wide diversity of bacteria from the human gut produces and degrades biogenic amines. Microb Ecol Health Dis. 2017;28(1):1353881.
  3. What causes Histamine Intolerance. Facts vs Fitness. https://factvsfitness.com/probiotics-histamine-intolerance/. Updated July 27, 2017. Accessed January 23, 2019.
  4. Oksaharju A, Kankainen M, Kekkonen RA, et al. Probiotic Lactobacillus rhamnosus downregulates FCER1 and HRH4 expression in human mast cells. World J Gastroenterol. 2011;17(6):750-9.
  5. Mokhtar S., Mostafa G, Taha R. et al. Effect of different starter cultures on the biogenic amines production as a critical control point in fresh fermented sausages. Eur Food Res Technol. 2012;235(3): 527-535.
  6. Capozzi V, Russo P, Ladero V, et al. Biogenic Amines Degradation by Lactobacillus plantarum: Toward a Potential Application in Wine. Front Microbiol. 2012; 3: 122.
  7. Mcfarland LV. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J Gastroenterol. 2010;16(18):2202-22.
  8. Blaabjerg S, Artzi DM, Aabenhus R. Probiotics for the Prevention of
    Antibiotic-Associated Diarrhea in Outpatients-A Systematic Review and Meta-Analysis. Antibiotics (Basel). 2017 Oct 12;6(4).
  9. Rodgers B, Kirley K, Mounsey A. PURLs: prescribing an antibiotic? Pair it with probiotics. J Fam Pract. 2013;62(3):148-50.
  10. Antibiotic Use & Associated Diarrhoea Prevention. Probiotic Advisor. https://www.probioticadvisor.com/ Accessed February 9, 2019.
  11. Suez J, Zmora N, Zilberman-Schapira G, et al. Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT. Cell. 2018;174(6):1406-1423.
  12. Kresser C. RHR: What the Latest Research Says about Probiotics, with Lucy Mailing. https://chriskresser.com/what-the-latest-research-says-about-probiotics-with-lucy-mailing/ Updated November 4, 2018. Accessed February 9, 2019.
  13. Drake LE, Guilliams TG. Small intestinal bacterial overgrowth (SIBO): diagnostic challenges and functional solutions. Point Institute. 2018;14(2)1-15.
  14. Kresser C. What Causes SIBO (Small Intestinal Bacterial Overgrowth) and Why It’s So Hard To Treat. https://chriskresser.com/sibo-what-causes-it-and-why-its-so-hard-to-treat/ Updated November 4, 2014. Accessed February 9, 2019.
  15. Chen WC, Quigley EM. Probiotics, prebiotics & synbiotics in small intestinal bacterial overgrowth: opening up a new therapeutic horizon!. Indian J Med Res. 2014;140(5):582-4.
  16. Kresser C. RHR: Treating SIBO, Cold Thermogenesis, and When to Take Probiotics. https://chriskresser.com/treating-sibo-cold-thermogenisis-and-when-to-take-probiotics/. Updated March 12, 2013. Accessed February 9, 2019.
  17. Furnari M, Parodi A, Gemignani L, et al. Clinical trial: the combination
    of rifaximin with partially hydrolysed guar gum is more effective than rifaximin alone in eradicating small intestinal bacterial overgrowth. Aliment Pharmacy Ther. 2010;32(8):1000-6.



1 Probiotic FAQ: Part 1

Hope you all had a great weekend! Our family was visiting my husband’s parents. On Friday my daughter and I had appointments for acupressure allergy treatments which went very well. I’ve been struggling with a lot of sinus headaches recently and I’m hopefully that these will help those calm down. One of the foods I was reacting to was chocolate 😔, but thankfully the treatment should allow me to put it back in my diet occasionally. 😊 I think I’m going to try to abstain for a little while before re-introducing. Our daughter is doing so well from where she was as a baby, hopefully these will help her be able to continue to expand her food choices. We had a lot of success with them in the past and calming down her eczema.

We enjoyed a relaxing Saturday with his family and today are celebrating his mom’s birthday before we head home. Hopefully this week we also get to meet our newest nephew who is due to arrive any day now!

Probiotics are a hot topic, and I don’t have all the answers but this post and my post next week will help address some of the most common questions I receive about them. We aren’t at a place yet where we can say you have this issue and you need this particular product 100%, but we have good data and is helping us guide recommendations. The microbiome is complex and everyone’s is different which makes it challenging. A lot of probiotic treatment is trial and error but sometimes what we try the first few times works! If you missed the first post Probiotic 101, make sure to check it out. As with the last post, two of my interns Vineeta Rao and Ruth Gunti worked hard on this! Thank you!

Hope you enjoy this first FAQ and stay tuned for more next week.

Dr. Hartzler

If I have a milk or other food allergy, can I take probiotics?

Yes. A  randomized controlled-trial found that supplementation with a probiotic helped infants allergic to cow’s milk develop a tolerance at a higher rate.1  Severe milk allergy patients should avoid probiotics made from milk. Dairy free probiotics are recommended for those with severe intolerance or allergy, where as dairy free would not be necessary for lactose intolerant patients. Additionally, a recent study that followed peanut allergic children found that a combination of probiotics (Lactobacillus rhamnosus) and peanut oral immunotherapy produced a sustained non-allergic response in children even four years after initial treatment indicating potential future use of probiotics in immunotherapy for the treatment of food allergies.2

If I have lactose intolerance, can I take probiotics?

Yes. In fact, probiotics are being used to help those with lactose intolerance. In a review article examining the relationship between probiotics and their use in those with lactose intolerance it was found that there was an overall positive relationship. The species of bacteria that were most common among the reviews studied were lactobacillus acidophilus, lactobacillus bulgaricus, and streptococcus thermophilus all of which demonstrated some level activity. 3

The World Gastroenterology Organisation Global Guidelines on probiotics states that “Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus improve lactose digestion and reduce symptoms related to lactose intolerance.”3

Should I take my probiotic with or without food?

A study looking at four species of bacteria found that survival through the GI tract was most preserved when given with a meal or 30 minutes before the meal.4   This may be due to the changes in acidity of the stomach during the fed and fasting states. During the fasting state, the stomach environment is more acidic, making it is more difficult for the bacteria to survive. Upon eating, however, the stomach environment becomes less acidic, thus providing a more favorable environment for bacteria to thrive. 4,5 In this study, probiotic survival was greater when taken with foods high fat content than with carbohydrates, apple juice, or water alone. Fat content appears to help “coat” the bacteria to protect against stomach acid. Thus, it is best to take your probiotic with a higher fat meal or snack to help the bacteria survive transit through the acidic stomach environment.4

What is the safety profile of probiotics?

Studies have found that probiotics have minimal to no side effects. Side effects that are observed are most commonly bloating and flatulence, but the symptoms are mild and subside with continued use of the probiotic. Constipation and increased thirst have also been rarely associated with the species S. boulardii.6 The extreme side effects that have been found are in patients whose immune system have already been compromised.

Why might my probiotic cause diarrhea or constipation?

Diarrhea or constipation can occur with probiotics especially at the start of therapy due to multiple factors. Likely, it depends on the degree to which the gut is imbalanced to begin with, and as the gut is being rebalanced, bacteria can release by-products through fermentation that influence how fast the bowels move. Also, since the brain and gut appear to influence each other, lifestyle factors such as stress may influence the gut’s movement. While we do not know how each of these factors specifically affect the gut, there are multiple neurological influences by different types of bacteria which may contribute to the speed in which transit happens.7

That is a wrap for today’s FAQ.. more to come next week! Next week I will address probiotics with antibiotics, histamine intolerance, and Small Intestinal Bacterial Overgrowth (SIBO). Don’t miss it! If you are looking for a quality probiotic feel free to check out my FullScript Store or send me an email if you need help!

References:

  1. Probiotic formula reverses cow’s milk allergies by changing gut bacteria of infants. The University of Chicago Medicine. https://www.uchicagomedicine.org/biological-sciences-articles/probiotic-formula-reverses-cows-milk-allergies-by-changing-gut-bacteria-of-infants. Updated September 22, 2015. Accessed February 9, 2019.
  2. Hsiao KC, Ponsonby AL, Axelrad C, Pitkin S, Tang MLK. Long-term clinical and immunological effects of probiotic and peanut oral immunotherapy after treatment cessation: 4-year follow-up of a randomised, double-blind, placebo-controlled trial. Lancet Child Adolesc Health. 2017;1(2):97-105.
  3. Oak SJ, Jha R. The effects of probiotics in lactose intolerance: A systematic review. Crit Rev Food Sci Nutr. 2018;9:1-9.
  4. Tompkins TA, Mainville I, Arcand Y. The impact of meals on a probiotic during transit through a model of the human upper gastrointestinal tract. Benef Microbes. 2011;2(4):295-303.
  5. Zembroski R. Why taking probiotics on an empty stomach is a bad idea. REBUILD. https://www.drzembroski.com/why-taking-probiotics-on-an-empty-stomach-is-a-bad-idea/. Accessed February 9, 2019.
  6. Williams NT. Probiotics. Am J Health Syst Pharm. 2010;67(6):449-58.
  7. Conlon MA, Bird AR. The impact of diet and lifestyle on gut microbiota and human health. Nutrients. 2014;7(1):17-44.

3 Probiotics 101

It’s been a whirlwind the last few months. I’m teaching my last lecture in Endocrine tomorrow.. I’m excited it’s on functional medicine approach to pre-diabetes and obesity! The best part about teaching part-time is getting to teach what I’m passionate about. After this, I just have lots of grading and course coordination items. But the course ends next week then I’m off to Seattle, WA to speak on diabetes cardiovascular outcomes trials. It’s the same presentation from December in Anaheim showcased at a different meeting. It’s nice when you spend a lot of time on something, to be able to do it twice! For this blog post, I had a lot of help from two students working on this probiotic series, so thank you to Vineeta Rao and Ruth Gunti for your hard work. Soon they will be my colleagues! Enjoy!

Dr. Hartzler


Welcome to probiotics 101, a guide to all your FAQs!

What are probiotics?

‘Probiotics are defined as live microorganisms, which when administered in adequate amounts, confer a health benefit on the host.’ 1 The microorganisms are bacteria of different strains that process our food into nutrients that benefit our health. Probiotics come from the Latin preposition pro (“for”) and the Greek adjective (biōtikos) meaning “fit for life, lively.” Put together this means that probiotics are for life.

Why use probiotics?

Using probiotics enhances the gut microbiota to better do its job.  The gut microbiota/microbiome is the conglomerate of bacteria that live in your gut and work together to bolster the immune system, to fight against potential infections, and to make nutrients such as vitamins, fats and other molecules that are needed by the body to function. 1  Furthermore facets of our modern day western lifestyle, such as diet, stress, geography, as well as sleep and travel patterns can negatively affect our gut microbiome meaning we don’t have a healthy gut to begin with. 2 In addition to the poor lifestyle factors, the increasingly prevalent use proton pump inhibitors is correlated with and probably contributes to “decreased bacterial richness” of  gut microbiome, an increased amount of oral bacteria that is potentially pathogenic present in the gut, and an overall greater “microbial alterations” in the gut than those on antibiotics. 3

How do probiotics work?

While probiotics are most commonly associated with replacing flora or colonizing the gut, modifications made to the gut microbiota are not likely permanent and reflect only one of many actions that probiotics have in the body. Among these actions are immune modulation, anti-inflammatory activity, pathogen antagonism, production of short chain fatty acids, repairing and strengthening of the intestinal barrier, metabolism of gut cholesterol, and enhanced antibody secretion.4 While not all probiotics encompass all of these features, depending on the strain, a given probiotic may provide one or several of these protective benefits.5

What is genus, species, and strain?

Bacteria are usually classified to the public by three names much like people who have first, middle and last names. Therefore the first name is a broad name termed genus, followed by a more specific name called a species finally followed by a strain number that is further specifies the exact kind of bacteria.  A labeled example is below!

What is the evidence for probiotic use?

Numerous review studies indicate that probiotics are beneficial overall, especially for gut health.6 However, evidence for treating or preventing specific conditions through probiotics is best established through clinical trials that demonstrate how probiotics produce a specific effect. While the number of controlled trials demonstrating specific effects in humans is still growing, probiotics have also been evaluated in animal experiments and or other in vitro studies that demonstrate efficacy and safety in terms of their use. 1  Fermented foods with probiotics in them have been consumed for centuries for health benefits. Additionally, the modern diet lacks prebiotic fiber that contributes to a diverse gut microbiome.7

What is the difference between Bifidobacterium and Lactobacillus genus of bacteria?

Lactobacillus bacteria is a type of bacteria that produces lactic acid as an end-product of its metabolism. Bifidobacterium bacteria on the other hand produce lactic acid and acetic acid; both these substances are important for the maintenance of the gut microbiome. 8,9

Here are some of the bacteria in each genus considered to be probiotics.8

Microorganisms
 considered as probiotics
Lactobacillus speciesBifidobacterium species
L. acidophilus
L. casei
L. crispatus
L. gallinarum
 L. gasseri
L. johnsonii
L. paracasei
L. plantarum
L. reuteri
L. rhamnosus
B. adolescentis
B. animalis
B. bifidum
B. breve
B. infantis
B. lactis
 B. longum

How to know you are getting a good product?

There are many overarching reviews that conclude that probiotics as a whole class are effective, suggesting that many strains share the similar levels of effectiveness. Additionally, there are number of factors that contribute to how probiotics act in our bodies such as genetics, diet and host microbiome that makes it difficult to isolate the effects of one strain over another. However, it is important that the product contains the live bacteria in large doses that will survive the harsh environments of the stomach.6

How much does the specific strain matter when ensuring that you have a good product? As more studies for probiotic use emerge, there is an ongoing controversy about the importance of the strain. On one side of the debate, larger studies that examine multiple clinical trials suggest that probiotics have benefit even when grouping similar strains together in one class. The theory behind this position is that similar strains of probiotics will have actions causing similar effects in the body.6 One the other side of the debate, some clinicians compare strain selection to choosing a particular antibiotic to attack a specific disease-causing microbe.4 Advocates of this position point to the fact that Lactobacillus plantarum DSM 9843 reduces irritable bowel syndrome while Lactobacillus plantarum MF 1298 aggravates the condition and thus conclude that when supporting a specific condition, one should only use a strain that has demonstrated efficacy for that specific condition.10-12

In summary, data for use of probiotics is exploding on a daily basis. Probiotics are useful to promote healthy gut transit and repair and for a myriad of immune benefits.  In addition, data suggests significant changes to the gut microbiome is most easily stimulated by ingestion of prebiotics, which are non-digestible foods that promote and stimulate the growth of bacteria in the gut.13 Prebiotics are often combined with probiotic supplements.  Sometimes they may not be well tolerated by certain individuals especially those that have an imbalance in bacteria. Certain non-gas producing prebiotics may be helpful for some patients. We will talk more about these situations in my next post!

If you are looking for quality probiotics. Please check out my Fullscript store and click on the probiotics category! I’m happy to help with simple questions on products via email or if you are interested in a 1:1 personal GI health consults with my team, please let me know. We are launching tele-health services soon!

SOURCES:

  1. Fijan S. Microorganisms with claimed probiotic properties: an overview of recent literature. Int J Environ Res Public Health. 2014;11(5):4745-67.
  2. Conlon MA, Bird AR. The impact of diet and lifestyle on gut microbiota and human health. Nutrients. 2014;7(1):17-44.
  3. Imhann F, Bonder MJ, Vich vila A, et al. Proton pump inhibitors affect the gut microbiome. Gut. 2016;65(5):740-8.
  4. Probiotic Advisor. The Importance of Strain. https://www.probioticadvisor.com/probiotic-essentials-1/the-importance-of-strain/#.XC-EEPZFxPZ. Accessed January 21, 2019.
  5. Hill, C., et al., Expert consensus document: The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol, 2014. 11(8): p. 506-514.
  6. California Dairy Research Foundation. Is it time to consider generic probiotic effects? http://cdrf.org/2013/03/01/is-it-time-to-consider-generic-probiotic-effects/. Updated March 1, 2013. Accessed August 20, 2018.
  7. Holscher HD. Dietary fiber and prebiotics and the gastrointestinal microbiota. Gut Microbes. 2017;8(2):172-184.
  8. Kechagia M, Basoulis D, Konstantopoulou S, et al. Health benefits of probiotics: a review. ISRN Nutr. 2013;2013:481651.
  9. Bifidobacteria Institute. Difference between bifidobacteria and lactobacillus. http://bb536.jp/english/basic/basic03.html. Accessed August 20, 2018.
  10. Ducrotte, P., P. Sawant, and V. Jayanthi, Clinical trial: Lactobacillus plantarum 299v (DSM 9843) improves symptoms of irritable bowel syndrome. World J Gastroenterol, 2012. 18(30): p. 4012-8.
  11. Niedzielin, K., H. Kordecki, and B. Birkenfeld, A controlled, double-blind, randomized study on the efficacy of Lactobacillus plantarum 299V in patients with irritable bowel syndrome. Eur J Gastroenterol Hepatol, 2001. 13: p. 1143-1147.
  12. Ligaarden, S.C., et al., A candidate probiotic with unfavourable effects in subjects with irritable bowel syndrome: a randomised controlled trial. BMC Gastroenterol, 2010. 10: p. 16.
  13. Cashman K. Prebiotics and calcium bioavailability. Curr Issues Intest
    Microbiol. 2003 Mar;4(1):21-32. Review.

1 Intro to “leaky gut” – what it is and why you should care

Today’s post is brought to you by Dr. Alexandra Perreiter, PharmD of HealthyLifeExplained.com. She is also a clinical pharmacist who I recently connected with. I hope you enjoy her post and check out her site!

Even though all health care professionals have taken the Hippocratic Oath of “First do no harm,” little did we learn in our professional schools regarding Hippocrates’s philosophy on treating and preventing disease, including his famous quote “Let food be thy medicine and medicine be thy food.” This is unfortunate because while conventional medicine is superb in diagnosing disease, little attention is being placed on identifying and targeting the actual root causes of these diseases to prevent them from occurring in the first place.

Currently the prevailing theory regarding the cause of many chronic diseases is genetics. Unfortunately, this theory alone appears insufficient to explain our susceptibility towards disease, especially because it is undeniable that many chronic diseases, such as autoimmune diseases and chronic pain syndromes are much more prevalent in the developed world than the undeveloped world. Take, for example, Japanese women who come to live in the United States. While their risk of developing breast cancer is quite low when they live in Japan, once they move to the United States their risk increases dramatically.[i] Why? It is definitely not because their genes have changed. Instead it is because their gene expression has changed, which is largely dictated by the environment (a field referred to as epigenetics).[ii],[iii] Thus, if we can understand what environmental factors turn on and off gene expression, we might be able to prevent disease and/or restore health.

And this is where we are starting to comprehend what Hippocrates had already eluded to many centuries ago, namely that “all disease begins in the gut.”[iv]

But why just is our gut so important?

Mainly because everything we take in from the external environment passes through our gut and, thus, our gut needs to finely regulate what actually passes from our gastrointestinal (GI) tract into our blood stream and from there into our organs, tissues and cells.

This is why our body has created a very finely tuned “gut-blood barrier” that determines what will or will not enter our body. We need this barrier (aka the “intestinal epithelial lining”) to function properly, only allowing “good things” (like nutrients) to enter and “bad things” (like disease causing bacteria) to stay out.[iii]This is, for example, one reason why ~70-80% of our immune system lies in our gut (referred to as the gut-associated lymphoid tissue (GALT), which houses plasma cells, mainly Immunoglobulin A (IgA), which provide first line defense to foreign invaders).[v]

So what then affects this “intestinal permeability”? The long answer is many things, including antibiotics, toxins, stress and infections.[iv]However, the two major factors that appear to be the most commonly cited and perhaps most modifiable are: 1) food and 2) the bacteria that live in our gut (aka “microbiome”).[iv],[vi],[vii] And these two factors are interrelated in that the food we eat can help or hinder bacteria to live in our gut and, vice versa, bacteria in our gut can give us “food cravings” that can then promote certain bacteria to thrive and others to die. We now know that roughly 39 trillion bacteria (400 different species!) live in our body – which is about the equivalent to all human cells in our body combined![iv],[viii],[ix] Thus, it is important that we understand that our gut bacteria play a crucial role in our overall health and look at food not only in its relationship to micro- and macronutrients, but also in its relationship to cause this excessive “intestinal permeability”, also referred to as “leaky gut”.

One of the major proteins known to increase the “holes” in our gut lining is zonulin.[iii],[vii],[x] It does so by causing a dysregulation of our “tight junctions”, thereby allowing things to enter our body that were never intended to be present. We now have pretty good evidence to suggest that overexpression of zonulin seems to be associated with autoimmune diseases (like rheumatoid arthritis and multiple sclerosis), neurodegenerative diseases (like dementia and Alzheimer’s disease), psychiatric diseases as well as cancer development and inflammatory diseases (such as Type 2 diabetes)![iii],[xi],[xii],[xiii] Overexpression of zonulin has been specifically associated with certain types of foods, such as gluten.[vii] However, enteral infections can also contribute as can other things that change our microbiota (such as medications that can alter the pH of our stomach, etc.)[iv]

So, how then does this “leaky gut” ultimately lead to chronic disease? In essence what happens is that things (in particular large protein particles) start entering our body that were never meant to get out of our intestine. These things are registered as foreign by our body, so our body goes on defense mode and starts mounting an immune response to protect ourselves from the “bad guys”. Unfortunately, the leakier our gut, the more “bad guys” are coming in and the harder our immune system fights. Even worse, the “bad guys” that our immune system should have never seen (had we had a better gut barrier) look so similar to our own cells that as the assault continues, our body starts attacking our own cells thinking they are “bad guys”. This confusion is called “molecular mimickry“ and may be the root cause of many chronic diseases that are on the rise. But this isn’t where it stops.[xiv]

On a normal day and in a normal person, a small percentage of our cells die off and get replaced with new ones. To do so our body generates a small amount of autoantibodies (aka “antibodies against self”) that help get rid of the damage. However, when we have a large amount of cellular damage on a consistent basis as a result of molecular mimickry, we end up developing more and more autoantibodies to get rid of all the cellular damage and then, after a while, our autoantibodies get so overwhelmed and confused that they autoperpetuate, resulting in more and more inflammation and damage that ultimately results in us developing a chronic disease.[xiv]

Thus, in essence, so the theory goes, most chronic diseases are caused by mis-regulation of our immune system that in one way or the other is misguided by environmental triggers. While leaky gut may not be the only reason why these diseases develop, many do believe it to be the main contributor and that fixing our “leaky gut” and restoring normal intestinal permeability will prevent and may even reverse such chronic diseases and cause disease remission.[xv]

So, what can we do? While research is ongoing into ways to restore and maintain a healthy gut-blood barrier, here are some things that health care professionals are already doing[iv] (Note: The below is not to be misconstrued as medical advice. You should be under medical supervision before you try any of the below mentioned options, including, but not limited to, the supplements listed. As with any lifestyle changes, you should always consult your healthcare provider before undergoing them and be monitored throughout the process.):

  • An Elimination diet.[iv],[xiv] Elimination diets usually consist of avoidance of all of the potential food causes, such as gluten, dairy, legumes, etc., for 14 – 30 days, followed by reintroduction of the food groups one after the other to determine which ones may affect you. This can be a very challenging process, but it can also be extremely rewarding because symptoms one has been having for years may suddenly disappear.
  • Strict whole food diet, with complete elimination of processed foods, including highly refined carbohydrates and vegetable oils as well as artificial coloring, sweeteners and preservatives.[iv],[xiv]
  • Supplementation with a probiotic with at least 50+ billion colony-forming units and containing Lactobacillus and Bifidobacterium[xvi] Quality brands include OrthoMolecular, Klaire Labs, and Pure Encapsulations.*
  • Bone brothiv and other glycine rich containing foods. (Thrive Market has a variety of options including Kettle & Fire (my favorite), or you can make your own, and/or supplement with Collagen Protein like Vital Proteins)
  • Colostrum[xvii](OrthMolecular’s IGG Protect or Tegricel Colostrum by Designs for Health are good options*)
  • Glutamine[vi](Thorne Research, PureEncapsulations and others have glutamine, it’s also an ingredient in GI Revive by Designs for Health as well as GI Repair Powder by Vital Nutrients*)
  • Stress management[iv] (including plenty of sleep!)

*You can find these supplements on Full Script under Gut Health.

Dr. Perreiter

**this post contains affiliate links to products Dr. Hartzler recommends, all the supplements recommended in this post can be found in my FullScript Store You do have to set-up a quick account to use.  Thanks for supporting the blog, remember 10% goes to support various ministries! Check out My Favorite Things for more details. Reminder that this information is general and personal specific health decisions should be made between you and your medical provider. Remember supplements can interact with certain medications, so make sure to include a pharmacist knowledgeable in this area in your decisions as well.

[i] Dunn JE. Breast cancer among American Japanese in the San Francisco Bay area. Natl Cancer Inst Monogr. 1977 Dec;47:157-60.

[ii] What is Epigenetics (2017, July 23). Epigenetics: Fundamentals. Retrieved from https://www.whatisepigenetics.com/fundamentals/

[iii] Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011 Jan;91(1):151-75.

[iv] Kresser, C. (2011, February 24). 9 Steps to Perfect Health – #5: Heal Your Gut. Retrieved from https://chriskresser.com/9-steps-to-perfect-health-5-heal-your-gut/.

[v] Vighi G, Marcucci F, Sensi L, Di Cara G, Frati F. Allergy and the gastrointestinal system. Clin Exp Immunol. 2008 Sep; 153(Suppl 1): 3–6.

[vi] Rapin JR, Wiernsperger N. Possible links between intestinal permeability and food processing: a potential therapeutic niche for glutamine. Clinics (Sao Paulo). 2010 Jun;65(6):635-43.

[vii] Hollon J, Puppa EL, Greenwald B, et al. Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non-celiac gluten sensitivity. Nutrients. 2015 Feb 27;7(3):1565-76.

[viii] Gill H.S., Guarner F. Probiotics and human health: A clinical perspective. Postgrad Med J. 2004;80:516–526.

[ix] Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol 2016 Aug:14(8):  e1002533.

[x] Fasano, A. Intestinal Permeability and its Regulation by Zonulin: Diagnostic and Therapeutic Implications. Clin Gastroenterol Hepatol. 2012 Oct;10(10):1096-1100.

[xi] Kelly JR, Kennedy PJ, Cryan JF, et al. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front Cell Neurosci. 2015; 9: 392.

[xii] Galland L. The gut microbiome and the brain. J Med Food. 2014 Dec 1; 17(12): 1261–1272.

[xiii] Mu Q, Kirby J, Reilly CM, et al. Leaky gut as a danger signal for autoimmune diseases. Front Immunol. 2017; 8: 598.

[xiv] O’Bryan T. (2016). The Autoimmune Fix. New York, NY: Rodale Inc.

[xv] Fasano A, Shea-Donohue T. Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nat Clin Pract Gastroenterol Hepatol. 2005 Sep;2(9):416-22.

[xvi] Chutkan, R. (2015).The Microbiome Solution. New York, NY: Penguin Random House LLC.

[xvii] Hałasa M, Maciejewska D, Baśkiewicz-Hałasa M, et al. Oral supplementation with bovine colostrum decreases intestinal permeability and stool concentrations of zonulin in athletes. Nutrients. 2017 Apr; 9(4): 370.

Alternatives to Proton Pump Inhibitors

I was going to address allergy supplements next, but because of the recent press on the increased risks of death with Proton Pump Inhibitors (PPI), I’m going to tackle this next!

Most likely you or someone you know has taken a PPI at some point in their life. I have (I wish I hadn’t), but as a college student in a traditional pharmacy program, I had no idea the implications it might have down the road. Currently proton pump inhibitors account for over $10 billion dollars in annual healthcare cost and are consistently within the top ten most prescribed medications. Common names for PPIs are below.

 

Prilosec® (Omeprazole)

Nexium® (Esomeprazole)

Prevacid® (Lansoprazole)

Protonix® (Pantoprazole)

Dexilant® (Dexlansoprazole)

Aciphex® (Rabeprazole)

 

What is a PPI? They are medications that reduce the secretion of acid in the stomach. And in many cases they may be needed to heal conditions such as erosive esophagitis (a condition where the lining of the throat is worn away) or peptic ulcers (small holes in the intestinal lining) and they may be needed long term for Barrett’s esophagus. Other conditions may be able to be treated with PPIs short term and then other methods likely can be used after healing has occurred.

The challenge with this is that our bodies are designed to have secretion of acid start the steps needed for proper digestion. So when we stop the initial acid trigger, we decrease production of digestive enzymes and other processes down the line. Then large food particles are undigested leading to a “leaky gut” which I will have another post on very soon by a guest (another pharmacist blogger!) Since we now know gut health is such an important underlying piece to a variety of health conditions, this may be why we see issues with the use of PPIs.

The most recent study8 was a longitudinal observational study in a Veterans Affairs population. The follow-up time frame was on average 5.71 years. Researchers compared patients on PPIs to patients on histamine H2 receptor antagonists (most commonly used drugs in this category are as Zantac (raniditine) and Pepcid (famotidine)), and patients without either medication. The results suggest excess risk of death among PPI users; risk is also increased among those without gastrointestinal conditions and with extended duration of use. The authors suggested limiting PPI use and duration to instances where it is medically indicated may be warranted. Other risks associated with PPIs are in the table below.

RiskRationale
Impaired Nutrient Absorption 9,10The long-term use of PPIs may impair the absorption of calcium, magnesium, iron, and vitamin B12 among other nutrients. These effects usually do not appear to be clinically relevant; however, there is speculation that some of these effects contribute to some of the other risks of PPIs.
Osteoporosis 11-14
PPIs have been linked to increased risk of fracture in several observational studies. This may be due to impaired calcium absorption; however, the exact mechanism has not been well-established.
Kidney Disease 15,16
PPIs have been implicated in both acute and chronic kidney disease. Again this is mostly observational data, but dose-response relationships have been demonstrated. PPIs appear to increase the risk of kidney disease; however, the mechanism for this is not well understood. There are some case reports of PPIs inducing acute interstitial nephritis, which may contribute.
Dementia and Functional Decline 17-19PPIs have been associated with increased risk of functional decline and loss of activities of daily living. PPIs have also been associated with an increased risk of dementia including Alzheimer’s disease. Both of these links are difficult to prove, and the evidence out there has bias and limitations. Still, studies have shown that patients using a PPI before diagnosis were 40% more likely to be diagnosed with dementia.
Pneumonia 20Observational evidence has shown a 50% increase in risk of developing community acquired pneumonia in patients taking a PPI. This risk may not be relevant after controlling for cofactors.
Clostridium Difficile 21,22There is evidence that PPIs may increase C Diff risk by 74%. This increases to 96% when PPIs are given along with antibiotics. H2RAs have been shown to have a lower risk compared to PPIs. There is also some evidence in mice that PPI use aggravates inflammation associated with C Diff infections.
Heart Attack 23PPI use has been shown to be associated with a 15% increase in risk of heart attack. This was observational data, and there is some argument that this increase in risk may be related to physicians mistaking dyspepsia for an MI.
Stroke 24A recent abstract from the American Heart Association’s 2016 meeting demonstrated a 21% increased risk in ischemic stroke for patients taking PPIs. The abstract also notes a dose-response relationship.

So the question is, I don’t have erosive disease, I’m just on this medication for heartburn/acid reflux.. how do I get off?

When patients discontinue a PPI, they may experience some rebound acid reflux. PPIs increase a hormone called gastrin, which would normally signal the production of acid; however, while patients are taking the PPI this effect is suppressed. Following the withdrawal of the PPI, the elevated gastrin can cause a rebound increased in acid secretion. The effects tend to last for one to two weeks.25,26

When discontinuing a PPI…

  • Talk with your healthcare provider to consider titrating it down; in other words slowly decreasing it.
  • Recognize that heartburn may return for the first week or two.
  • You could consider using OTC Antacids (like Tums) or H2RAs (like Ranitidine or Famotidine) for 1-2 weeks to help with the rebound effect.
  • Consider supplements and alternative options.

Alternative Options

ProductDirectionsRationale
Apple Cider Vinegar 27Take 1-2 teaspoons in a glass of water before meals. (drink with a straw to avoid erosion to teeth)Some theories for how heartburn develops suggest that heartburn can happen as a result of not having enough stomach acid to properly digest food. Adding a small amount of the acidic apple cider vinegar may help reduce symptoms.
Probiotics 27Aim for at least 10 to 20 billion CFUs per day.Heartburn symptoms could be due to an imbalance of GI bacteria. Probiotics can help restore the balance of GI flora and improve digestion. Various bacteria play different roles in digestion.
Digestive Enzymes 28Take 1 capsule with meals.Poor digestion may make heartburn symptoms worse. Adding digestive enzymes can aid digestion and prevent symptoms.
DGL 29-31Take 1 capsule once daily with a meal.Soothes gut lining, stimulates proper digestion.
GI Revive 29-35
(Contains DGL and other ingredients)
Take 7 capsules daily; These can be spaced out however the patient tolerates them. It may be beneficial to take them with meals.GI Revive can help heal the gut if damage or “leaky gut” is suspected. The theory is that since most of the immune system lies in the gut, if there is damage and large inflammatory particles get through, patients will experience inflammation and GI symptoms.
DGL by OrthoMolecular 29-31, 36-401-2 tablets per daySoothes gut lining, stimulates proper digestion. Marshmallow root has a long history of providing a soothing property to mucous membranes. Slippery elm bark also helps protect the GI tract and promotes a healthy cycle of inflammation. Aloe Vera has studies that show it helps balance gastric acid secretion and at low doses protects the membranes from excess acid.
Heartburn Essentials 29-31, 36-371 capsule with each mealHas DGL, marshmallow root, slippery elm, artichoke, and turmeric plus digestive enzymes.

In our practice we typically use GI Revive for patients with suspected leaky gut and inflammation in the gut because it has good nutrients for helping to restore tissues such as zinc carnosine, l-glutamine, and N-Acetyl Glucosamine. As well as some anti-inflammatory supplements like MSM and Quercetin. Then it also has some of the similar ingredients to other products above such as DGL, slippery elm, and marshmallow root, etc. I typically do it for 1-2 months then move on to something a bit less expensive for maintenance if needed. Again this is for patients with inflammation present and you may not know that unless you work with a provider who can do some functional medicine testing.

For most patients with occasional heart burn and reflux without other symptoms of “leaky gut” starting with DGL may be enough. I like the Orthomolecular product that also includes slippery elm bark, marshmallow root, and aloe vera. There is a similar product called Heartburn Essentials by Pure Encapsulations noted in the table as well.

If you aren’t taking the GI Revive, it may be worth considering adding Zinc Carnosine.  It is a great nutrient for helping re-build the mucosal lining. It also has anti-ulcerative properties.

In summary for most patients trying to get off a PPI (without evidence of erosive disease)

I would recommend discussing the following with your health-care provider.

  1. A quality probiotic like OrthoBiotic from OrthoMolecular (I like that this doesn’t need to be in the fridge and includes Saccharomyces Boulardii) or Ther-Biotic Complete Klaire Labs
  2. Digestive Enzymes take your pick of products, I have some of my favorites listed in my Full Script store. If you have symptoms that include a “burning sensation” at this time, you likely want to avoid a product with HCL until soothing nutrients have allowed the mucous membranes to heal.
  3. Deglycyrrhizinated licorice (DGL) (The Orthomolecular product or plain DGL) OR the Heartburn Essentials (Pure Encapsulations).

Also consider

  1. Zinc carnosine  if not taking GI Revive
  2. Ox Bile if your heartburn is worse after fatty meals and you have trouble digesting those, you could add  Ox bile 125 mg with fatty meals. The OrthoDigestzyme product has this in it already but also has HCL.

You can find these in my FullScript Supplement store under the “GastroIntestinal Health” category.

Additional things to consider would be acupuncture, chiropractic care, or osteopathic manipulation with a DO physician. The human body never ceases to amaze me, that God created each part of us to work together, to balance our bodies. If one area is out of whack, it often affects other processes in the body. I have found all three to be helpful at different points in my life. Lastly in the list below, there are some other ideas that are non-medication or non-supplement related steps reducing heartburn as well.

Next steps…. if no improvement you may want to consider doing a stool test with Genova Diagnostics. This will discover if you have inflammation in the gut, an imbalance in bacteria, yeast or an invader like a parasite contributing to symptoms. It also shows you if you have undigested proteins and fats in the stool.  You can find providers in your area at this site. Or come find me in Enon/Fairborn, Ohio! You can also search for functional medicine providers in your area here.

I hope you find this helpful! A HUGE thank you to a past student of mine Dr. Trevor Stump for compiling a lot of this information. He shared with our team of local providers earlier this year.

Dr. Hartzler

Non-Pharmacological Recommendations for Heartburn

  • Weight Loss
  • Smoking Cessation (Quitting Smoking)
  • Avoiding Spicy or Fatty Foods
  • Eating Smaller Meals
  • Avoiding Tight Clothing
  • Elevating the Head of the Bed at Night
  • Avoiding Meals within 3 Hours of Bedtime
  • Yoga or Meditation (Stress Relief)
  • Eating More Slowly

*this post contains affiliate links to products I recommend, all the supplements recommended in this post can be found in my FullScript Store You do have to set-up a quick account to use.  Thanks for supporting the blog, remember 10% goes to support various ministries! Check out My Favorite Things for more details. Reminder that this information is general and personal specific health decisions should be made between you and your medical provider. Remember supplements can interact with certain medications, so make sure to include a pharmacist knowledgeable in this area in your decisions as well.

References:

  1. Gawron AJ, Feinglass J, Pandolfino JE, Tan BK, Bove MJ, Shintani-smith S. Brand name and generic proton pump inhibitor prescriptions in the United States: insights from the national ambulatory medical care survey (2006-2010). Gastroenterol Res Pract. 2015;2015:689531.
  2. Forgacs I, Loganayagam A. Overprescribing proton pump inhibitors. BMJ. 2008;336(7634):2-3.
  3. Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013;108(3):308-28.
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