height="516" />

Nutrient Solutions to Complement the 5R Protocol: A Comprehensive Approach to Maintaining Gut
Health

The Institute for Functional Medicine developed the 5R Program, a framework for addressing leaky gut and other
gastrointestinal concerns. This program focuses on five areas of health that can be individualized based on a
patient’s unique symptoms and health needs: Remove, Replace, Reinoculate, Repair and Rebalance.

The cornerstone of any plan of care incorporates a healthy diet and lifestyle changes. Removing triggering or
offensive foods is a hallmark of the 5R protocol, and the practitioner needs to advise the patient about what
foods they can and should eat.  The focus should be on whole foods, phytonutrient-rich fruits and vegetables,
fiber, and quality fats, choosing organic when possible.  A variety of diets exist that can be tailored to a
patient’s individual nutritional needs and health goals.  Three of the most popular include:

• The Low FODMAP diet


• The Mediterranean diet


• The Paleo or Autoimmune Paleo Diet

Evaluating a patient's nutritional status, symptoms, and dietary history can assist in identifying the most
beneficial diet. Considering the diverse food restrictions and allowances inherent in these diets, a patient's
commitment and capacity to comply can influence their overall success.

LOW FODMAP DIET

FODMAP stands for Fermentable, Oligo-Di and Mono-saccharides and Polyhydric Alcohols. FODMAPS encompass foods
that can interact with gut microbiota, and through fermentation, can provoke symptoms of discomfort, flatulence
and altered bowel habits. Included in this category of foods are lactose, fructose, fructans and other poorly
absorbed carbohydrates.

Overall, symptom improvement has been seen in some patients adhering to a Low FODMAP diet, with reductions in
abdominal pain frequency and severity, bloating, and improved satisfaction with bowel habits and quality of
life, compared to a standard diet consisting of high FODMAP foods.^{1, 2}

MEDITERRANEAN DIET

The Mediterranean Diet is rooted in whole foods and is abundant in essential fatty acids, with plenty of olive
oil, nuts and seeds.  Low in red meat, it emphasizes fresh seafood, dairy, eggs, fruits, vegetables, whole
grains, herbs and spices. In an explorative analysis of 68 women from the LIBRE-1 study, researchers observed
that the women who adhered to a Mediterranean Diet (n=33) had greater plasma levels of n-3 essential
fatty acids and decreased plasma Lipopolysaccharide Binding Protein and decreased fecal zonulin levels, compared
to controls.³

PALEO DIET OR AUTOIMMUNE PALEO DIET

This diet emphasizes eating the way our hunter-gatherer ancestors may have eaten. It avoids refined sugars,
dairy, processed foods, grains, legumes, soy and peanuts and focuses on all meats, fish, poultry, fruits and
vegetables, eggs, nuts, seeds, herbs and spices and healthy fats.  This way of eating can be therapeutic for
people who need to remove a wide variety of offensive foods for a period to allow the gut to heal. A
meta-analysis of the Paleo diet showed that it can reduce insulin resistance, cholesterol markers, blood
pressure and C-reactive protein, making it worth exploring in patients with metabolic concerns.⁴

THE 5R PROGRAM & PURE ENCAPSULATIONS® NUTRIENT SOLUTIONS

Pure Encapsulations provides products for all areas of gut health that can support your patient in every area of
the 5R protocol.

REMOVE

In this phase, the removal of processed foods, poor-quality fats, refined sugars, artificial sweeteners, alcohol
and possible sources of food sensitivities, like gluten, dairy and carbohydrate intolerances are recommended.
The focus should also be on removing stressors, environmental toxins and non-beneficial microorganisms.
Supplemental support can include microbial balance, motility support and nutrients that promote liver
detoxification.^‡

Pure Encapsulations Nutrient Solutions

• MotilPro contains ginger
  extract, 5 hydroxytryptophan, pyridoxal-5 phosphate, and acetyl-l carnitine that provide support for
  gastrointestinal motility, GI comfort and stimulation of gut-signaling neurons.^‡ Suggested use: 2
  capsules, 1-2 times daily between meals.


• MicroDefense
  w/ Oregano is comprised of a combination of olive leaf, artemisia and clove extracts to
  promote healthy gastrointestinal tract function and microbial balance and supports immune function and
  respiratory tract balance^‡. Suggested use: 1 capsule, 1-3 times daily, just before a meal, with
  6-8 oz water for 2-3 months.


• Liver-G.I. Detox contains a nutrient-rich matrix that includes vitamins, minerals, protein,
  carotenoids and botanical support like chlorella, broccoli and artichoke extracts, along with turmeric and
  milk thistle to provide dual support for liver and gastrointestinal detoxification. It enhances phase II
  detoxification enzymes and helps maintain healthy intestinal integrity and proper nutrient
  utilization.^‡ Suggested use: 2 capsules daily with a meal.

REPLACE

The focus should be on replacing processed and poor-quality foods with whole foods and phytonutrients by
consuming a wide variety of colorful fruits and vegetables. Hydrochloric acid, bile salts and digestive enzyme
support are recommended to support optimal digestion.  Exploring ways to support the patient’s sleep quality,
exercise, stress management and work/life balance should also be addressed.

Pure Encapsulations Nutrient Solutions

• Betaine HCl
  contains Betaine HCl and pepsin to support healthy gastric function and promote the absorption of protein,
  vitamin B₁₂ and calcium.^‡ Suggested use: 1 capsule, 3 times daily, with each meal.
  


• Digestive
  Enzymes Ultra contains an extensive profile of vegetarian digestive enzymes to
  support protein, carbohydrate, fat, fiber, and dairy digestion and promote enhanced nutrient bioavailability
  and absorption.^‡ Suggested use: 2 capsules with each meal.

REINOCULATE

This area explores the use of probiotics and prebiotics to repopulate the gut with beneficial microbes and their
metabolites. Cultured and fermented foods may also be used to feed the microbiome, depending on the patient’s
tolerance.

Pure Encapsulations Nutrient Solutions

• Probiotic
  G.I. provides 10 billion CFU per capsule of the beneficial bacteria
  Lactobacillus acidophilus, Lactobacillus salivarius, Lactobacillus casei, Bifidobacterium bifidum,
  Bifidobacterium lactis and Streptococcus thermophilus to promote healthy immune balance
  within the G.I. tract and help maintain the integrity of the intestinal mucosa.^‡ Suggested use: 1
  capsule, 1-2 times daily, with or between meals.
  


• Poly-Prebiotic
  Powder is a unique powdered blend of researched prebiotic fibers and polyphenols to
  support gastrointestinal, cellular and immune function by boosting bifidobacteria and microbiome
  diversity.^‡ Suggested use: 1 scoop, 1-2 times daily, mixed with a beverage or into food.

REPAIR

This area of the program focuses on foods that are easy to digest, provide nourishment and support gut integrity,
like bone broths, soups and stews, teas and well-cooked versus raw foods. Medical foods may also be employed
during repair.  Supplement recommendations should include nutrients that soothe the GI tract and support the gut
mucosa.^‡

Pure Encapsulations Nutrient Solutions

• Peptic-Care^‡ contains
  a patented 1:1 chelate of zinc and l-carnosine, providing synergistic GI mucosal protection and supports the
  stomach’s mucosal defenses, buffers gastric acid, maintains healthy cytokine release and provides
  antioxidant support for the GI tract.^‡ Suggested use: 1 capsule, 1-2 times daily with meals.


• Epi-Integrity Powder
  promotes healthy modulation of mucosal immune responses to support GI integrity.^‡ Suggested use:
  1 scoop, 1-2 times daily. Add 1 serving to 8 oz of water or juice.


• L-Glutamine
  delivers 850 mg of L-glutamine to support the mucosal lining and healthy functioning of the gastrointestinal
  tract; it may help to maintain lean muscle mass.^‡ Suggested use: 1 capsule, 1-3 times daily,
  between meals. Also available in powder.


• SunButyrate^TM-TG
  Liquid provides 875 mg of short-chain fatty-acid butyric acid in one teaspoon to
  promote gut-barrier integrity, cytokine balance in the GI tract, abdominal comfort and bowel motility.^‡
  Suggested use: 1 teaspoon, 1-3 times daily, with meals.


• DGL
  Plus^® contains a synergistic combination of
  deglycyrrhizinated licorice extract, aloe vera extract, slippery elm and marshmallow root extract to help
  stimulate the quality and production of stomach mucus, provide nutritional support to the gastrointestinal
  tract and support the body’s natural defense mechanisms.^‡ Suggested use: 1 capsule daily before a
  meal.

REBALANCE

In this stage, the patient should have experienced improvements in their health and the focus is on continued
implementation of approaches to reduce stress, maintain sleep quality and support healthy gut function.
Reassessing nutrient needs and supplement dosages is recommended, as well as reintroducing some previously
eliminated foods to assess tolerance.

SUMMARY

Supporting a patient’s gut health requires a multi-layered approach. Following the 5R Framework partnered with
Pure Encapsulations premium products can be foundational in a patient’s digestive system balance and improving
their overall health.^‡

Pure Encapsulations® provides uniquely formulated products made with high-quality, pure ingredients backed by
verifiable science to complement your plan of care.

REFERENCES

1. Varjú P, Farkas N, Hegyi P, et al. PLoS One. 2017;12(8):e0182942. Published 2017 Aug 14.
   doi:10.1371/journal.pone.0182942


2. Halmos EP et al.  JGGastroenterology. 2014;146(1):67-75.e5. doi:10.1053/j.gastro.2013.09.046


3. Seethaler B et al. Eur J Nutr. 2023;62(7):2779-2791. doi:10.1007/s00394-023-03172-2


4. Sohouli MH, Fatahi S, Lari A, et al. Crit Rev Food Sci Nutr. 2022;62(17):4551-4562.
   doi:10.1080/10408398.2021.1876625

Is It a Leaky Gut? Defining What Lurks Beneath a Patient’s Symptoms

TABLE OF CONTENTS

1. The First Line of Defense

2. Structure and Function of the Intestinal Barrier

• 3.1. The Chemical Barrier


• 3.2. The Physical Barrier


• 3.3. The Immune Barrier

3. What Can Go Wrong?

4. Underlying Causes of a Leaky Gut

5. Potential Health Consequences Associated with a Leaky Gut

6. Assessments for Leaky Gut

• 6.1. Urine
  
  
  
  • Lactulose Mannitol
  
  
  
  


• 6.2. Serum
  
  
  
  • Lipopolysaccharide
  
  
  
  
  
  
  • Zonulin or Zonulin/Occludin
  
  
  
  
  
  
  • Citrulline
  
  
  
  
  
  
  • Intestinal Fatty Acid Binding Protein
  
  
  
  


• 6.3. Fecal
  
  
  
  • Secretory IgA
  
  
  
  

7. Exploring Nutrients to Support Healthy Gut Function^‡

• Glutamine


• Botanicals


• Probiotics & Prebiotics


• Zinc Carnosine


• Deglycyrrhizinated Licorice (DGL), Marshmallow Root & Slippery Elm

8. Pure Encapsulations® Nutrient Solutions

• Betaine HCl


• Digestive Enzymes Ultra


• MotilPro


• MicroDefense w/ Oregano


• Probiotic G.I.


• Poly-Prebiotic Powder


• Peptic-Care^‡


• Epi-Integrity Powder


• L-Glutamine


• SunButyrate^TM-TG liquid


• DGL Plus^®

9. Conclusion

10. Resources

This small intestinal barrier is the first line of defense when it comes to living organisms. It is not only
responsible for absorbing nutrients from the diet but also serves a pivotal role as the body’s first line of
defense against ingested harmful substances. Only a single layer of cells protects the body from the external
world, and it exists in this barrier. A healthy and properly functioning intestinal barrier protects from
non-beneficial microorganisms, undigested food particles and toxins from entering the bloodstream. When the
integrity of the intestinal barrier is disrupted, it can become hyperpermeable.

Intestinal hyperpermeability, also known as Leaky Gut, allows non-beneficial microorganisms, toxins and
undigested food particles to “leak” through the barrier and into circulation, where they can impact other organs
and systems.

Homeostasis of the intestinal barrier relies on three interdependent layers: a chemical barrier, a physical
barrier and an immune barrier.

CHEMICAL BARRIER

The chemical barrier consists of the microbiota-rich mucus layer. In direct contact with the contents of the
lumen, it’s the body’s first line of defense and provides a protective coating over epithelial cells.
Surrounding cells secrete glycoproteins, mucin, and peptides to support the health of the mucus layer and
prevent bacteria, toxins and antigens from penetrating the epithelial layer. Secretory IgA is also found in the
mucus, as it helps prevent bacteria from adhering to the epithelial cells.

The mucus layer is also home to the microbiota of the gut. The microbiota participates in many important roles
that regulate barrier function and overall health, including harvesting nutrients from the diet, synthesizing
vitamins and metabolites like short-chain fatty acids, preventing the proliferation of non-beneficial bacteria
and engaging in crosstalk with other organs and systems. Aberration of the gut microbiota and its metabolites
can lead to downstream consequences and alterations of the intestinal barrier.¹

PHYSICAL BARRIER

Beneath the mucosa exist multiple cell types, including enterocytes, goblet cells, enteroendocrine cells, Paneth
cells and intestinal stem cells. These cells are responsible for assisting with the absorption of nutrients and
interacting with immune cells, the mucus layer and the microbiota to support homeostasis. Collectively, these
cells form the one-cell-thick, semipermeable physical barrier known as the epithelial intestinal barrier. The
epithelial cells tightly regulate the space between cells (paracellular) and through cell (transcellular)
permeability. The integrity of the epithelial barrier is maintained by tight junctions, which are key structures
that seal and provide tight connections between the adjacent cells and regulate paracellular trafficking of
macromolecules through the intestinal barrier. The overlapping of proteins like zonulin, occludin, clauden and
cadherin provides stability of tight junctions. Changes to the structure or function of these proteins are
implicated in leaky gut.^{2, 3, 4}

IMMUNE BARRIER

Beneath the epithelial barrier is the lamina propria, comprised of innate and adaptive immune cells, making up
the immune barrier. Also residing here are components of the mucosal- associated lymphoid tissue (MALT) and
gut-associated lymphoid tissue (GALT) and include Peyer’s Patches, which support IgA’s production and transport
between the interdependent layers. Macrophages, dendritic cells, T cells, B cells and mast cells also colonize
the immune barrier.

Interferences in the structure and functions of this cellular barrier, or its chemical and immune components, can
lead to increased permeability. Intestinal hyperpermeability, also known as leaky gut, allows non-beneficial
microorganisms, toxins and undigested food particles to “leak” through the barrier and into circulation, where
they can impact other organs and systems.

Patients with gut barrier concerns and intestinal hyperpermeability may present uniquely different symptoms. This
occurs because individuals may encounter a variety of factors throughout their lifetime that can lead to leaky
gut, including:

• Food sensitivities³


• Stress⁵


• Mast cell activation^{6, 7}


• Poor diet or alcohol intake^{8, 9}


• Inadequate zinc or Vitamin D^{10, 11}


• Certain medications^{12, 13}


• Non-beneficial microorganisms,¹⁴


• Environmental contaminants


• Altered microbiome²


• Low digestive enzymes or HCl

Optimizing the function and integrity of the intestinal barrier can be one of the most important things a
practitioner can do for their patient. The consequences of a leaky gut can extend far beyond the gut and impact
many areas of health, including cardiovascular,¹⁵ metabolic,^{16, 17} mental,^18,
19 neurological,²⁰ skin,²¹ immune²² and reproductive health.

URINE

Lactulose Mannitol: One of the initial non-invasive laboratory tests, the lactulose mannitol
test uses sugar molecules to assess intestinal permeability. The patient is given an oral dose of both lactulose
and mannitol. the smaller monosaccharide, freely passes through the epithelial barrier and into the bloodstream.
Lactulose, a larger disaccharide, is typically prevented from paracellular travel through the tight junctions.
The presence of these two sugar molecules in the urine is expressed as a ratio of the percentage of the ingested
doses, known as the LMR or lactulose mannitol ratio. This ratio can reflect increased intestinal
permeability.²⁴

SERUM

Lipopolysaccharide: Lipopolysaccharide, or LPS, is an endotoxin found in the cell wall of
Gram-negative organisms that is naturally present in the gastrointestinal, respiratory and genitourinal tracts.
When the organism’s outer membrane is shed or ruptured, LPS is expressed. The detection of LPS and LPS IgA, IgG
and IgM antibodies in the serum can indicate intestinal permeability.²³ Because other factors can
cause LPS to be present in the serum, LPS testing is often used alongside other biomarkers for leaky gut.

Zonulin or Zonulin/Occludin: These proteins contribute to the stability of tight junctions and
epithelial cells and their presence in the serum can be clinically relevant when assessing intestinal
permeability.²⁴

Citrulline: Citrulline is an amino acid synthesized by enterocytes from glutamine or arginine.
Traditionally used as a marker for decreased enterocyte mass with immune-related conditions of the GI tract, low
plasma citrulline can also be a significant biomarker of intestinal barrier permeability.

Intestinal Fatty Acid Binding Protein (I-FABP): Plasma I-FABP is another useful biomarker for
assessing intestinal permeability. Expressed by the enterocytes, I-FABP belongs to a family of fatty
acid-binding proteins responsible for binding to and transporting fatty acids.²⁴ Like other markers
for leaky gut, I-FABP is detected in the serum when it has breached the intestinal barrier due to
hyperpermeability.²⁴ In a case-control study by Linsalata et al., higher serum levels of I-FABP were
detected in patients with Functional GI Concerns with occasional diarrhea, concurrent with altered
lactulose-mannitol ratio and increased intestinal permeability.²⁵

FECAL

Secretory IgA: Found throughout the mucosa of the intestinal barrier, sIgA supports the mucosa's
health by preventing bacteria adhesion to the epithelial cells and coordinating immune responses.²⁴
Secretory IgA found in the stool can suggest hyperpermeability. Also detected in saliva and serum, sIgA
testing is often interpreted alongside other biomarkers for leaky gut.
According to a survey conducted in
2022 by the American Gastroenterological Association, 1 in 4 people in the US experience occasional
uncomfortable gut symptoms over the last year.²⁶ As the list of health conditions associated with
leaky gut continues to grow, optimizing a patient’s gut function to maintain their overall health should take
center stage. Just as leaky gut has no single cause, there is no single cookie-cutter approach. Many
practitioners find that their patients with leaky gut benefit from a customized plan, using the 5R Program as a
guide.

Along with dietary and lifestyle changes, nutrients that support GI motility, gut barrier integrity and microbial
balance can help support patient outcomes.

Glutamine: The most abundant amino acid in the body is a primary energy source for intestinal
epithelial cells and is utilized by the body for tissue repair and gastrointestinal support.^{27, 28,
29} Glutamine plays a large role in maintaining healthy intestinal integrity by enhancing the
intestine’s protective mucosal lining.^‡

Botanicals: Some patients may benefit from artemisia, olive leaf extract, oregano, clove or
berberine sulfate, which can help promote healthy microbial balance.^{30, 31, 32, 33, 34‡}

Probiotics & Prebiotics: Probiotics have been shown to be efficacious in all subtypes of
Functional GI Concerns, although specific strains should be considered for each subtype and symptoms presented.
Overall, meta-analyses have shown that probiotics may significantly improve stool consistency, regulate stool
frequency and gut transit time.^{35, 36, 37‡}
Prebiotic fibers, like Arabinogalactan, are
nondigestible food components that modulate and support the gut microbiota. They perform beneficial metabolic,
trophic and protective functions within the gut, leading to overall cellular, immune and metabolic
support.³⁸ Arabinogalactan may increase the concentration of beneficial bacteria, such as
Bacteroidetes and Faecalibacterium prausnitzii.^39‡

Zinc carnosine: Zinc and carnosine provide synergistic antioxidant protection, support the
stomach's mucosal defenses, buffer gastric acid and maintain healthy cytokine release.⁴⁰ Studies
suggest that this combination is more effective in maintaining the integrity of the gastric lining than either
ingredient alone.^41‡

Deglycyrrhizinated licorice (DGL), Marshmallow Root & Slippery Elm: Deglycyrrhizinated
licorice (DGL), marshmallow root and slippery elm bark are demulcent herbs that are traditionally recognized for
their value in soothing the gastrointestinal tract and maintaining the integrity of the mucosal lining.^{42,
43, 44‡}

Pure Encapsulations® provides products designed to complement your care plans for patients needing digestive and
GI support. You’ll find Pure Encapsulations offers nutrients individually and in combination to meet all your
patient’s unique needs. Pure Encapsulations® products are also highly suitable for use with the 5R Program, a
functional medicine model.

DIGESTIVE ENZYMES

• Betaine HCl
  contains betaine HCl and pepsin to support healthy gastric function and promote absorption of protein,
  vitamin B₁₂, and calcium.^‡ Suggested use: 1 capsule, 3 times daily, with each meal.
  


• Digestive Enzymes
  Ultra contains an extensive profile of vegetarian digestive enzymes to support protein,
  carbohydrate, fat, fiber, and dairy digestion and promote enhanced nutrient bioavailability and
  absorption.^‡ Suggested use: 2 capsules with each meal.

MOTILITY

• MotilPro contains ginger
  extract, 5 hydroxytryptophan, pyridoxal-5 phosphate, and acetyl-l-carnitine that provides support for
  gastrointestinal motility, GI comfort and stimulation of gut-signaling neurons.^‡ Suggested use: 2
  capsules, 1-2 times daily between meals.

MICROBIAL BALANCE

• MicroDefense w/
  Oregano is comprised of a combination of olive leaf, artemisia and clove extracts to
  promotes healthy gastrointestinal tract function and microbial balance^‡ and supports immune
  function and respiratory tract balance.^‡ Suggested use: 1 capsule, 1-3 times daily, just before a
  meal, with 6-8 oz water for 2-3 months.

PROBIOTICS & PREBIOTICS

• Probiotic G.I.
  provides 10 billion CFU per capsule of the beneficial bacteria Lactobacillus acidophilus, Lactobacillus
  salivarius, Lactobacillus casei, Bifidobacterium bifidum, Bifidobacterium lactis and
  Streptococcus thermophilus to promote healthy immune balance within the G.I. tract and help
  maintain the integrity of the intestinal mucosa.^‡ Suggested use: 1 capsule, 1-2 times daily, with
  or between meals.


• Poly-Prebiotic
  Powder is a unique powdered blend of researched prebiotic fibers and polyphenols to
  support gastrointestinal, cellular and immune function by boosting Bifidobacteria and microbiome
  diversity.^‡ Suggested use: 1 scoop, 1-2 times daily, mixed with a beverage or into food.

GUT BARRIER INTEGRITY

• 
  

  Peptic-Care^‡
  contains a patented 1:1 chelate of zinc and l-carnosine, providing synergistic GI mucosal protection and
  supports the stomach’s mucosal defenses, buffers gastric acid, maintains healthy cytokine release and
  provides antioxidant support for the GI tract.^‡ Suggested use: Take 1 capsule, 1-2 times
  daily with meals.

  
  


• 
  

  Epi-Integrity
  Powder promotes healthy modulation of mucosal immune responses to support GI
  integrity.^‡ Suggested use: 1 scoop, 1-2 times daily. Add 1 serving to 8 oz of water or juice
  and shake or stir until dissolved.

  
  


• 
  

  L-Glutamine delivers
  850 mg of L-glutamine to support the mucosal lining and healthy functioning of the gastrointestinal
  tract; it may help to maintain lean muscle mass.^‡ Suggested use: 1 capsule, 1-3 times daily,
  between meals. Also available in powder.

  
  


• 
  

  SunButyrate^TM
  - TG liquid provides 875 mg of short-chain fatty-acid butyric acid in one teaspoon
  to promote gut-barrier integrity, cytokine balance in the GI tract, abdominal comfort and bowel
  motility.^‡ Suggested use: 1 teaspoon, 1-3 times daily, with meals.

  
  


• 
  

  DGL Plus^®
  contains a synergistic combination of deglycyrrhizinated licorice extract, aloe vera extract, slippery
  elm and marshmallow root extract to help stimulate the quality and production of stomach mucus, provide
  nutritional support to the gastrointestinal tract and support the body’s natural defense
  mechanisms.^‡ Suggested use: Take 1 capsule daily before a meal.

  
  

With the gut being the chief portal for entry of nutrients, antigens and non-beneficial microorganisms into the
body, a healthy intestinal barrier is key to maintaining a healthy gut and overall health. A patient-centered
approach with nutrient and lifestyle solutions tailored to an individual’s unique clinical presentation and
nutrient needs can have a profound effect not just in the gut but at a systemic level.

With Pure Encapsulations, you have the promise of premium sourced ingredients backed by verifiable science, so
you can be confident you are recommending products with quality, purity and potency.

A
Comprehensive Approach to Maintaining Normal Gut Health: Offers guidance and product suggestions for the
5R Program to address Leaky Gut Factors and other GI conditions, developed by the Institute for Functional
Medicine.

Drug-Nutrient Interactions
Checker | DNI Calculator: Offers scientifically supported, clinically relevant information
that’s easy to understand with product suggestions based on verifiable science.

You can also explore Pure Encapsulations® to
find On-Demand Learning,
Clinical
Protocols and other resources developed with our medical and scientific advisors.

REFERENCES

1. Su Q, Tun HM, Liu Q, et al. Gut Microbes. 2023;15(1):2157697. doi:10.1080/19490976.2022.2157697


2. Vita AA, Zwickey H, Bradley R. Front Nutr. 2022;9:962093. Published 2022 Sep 6. doi:10.3389/fnut.2022.962093
   


3. Awad K, Barmeyer C, Bojarski C, et al. Cells. 2023;12(2):236. Published 2023 Jan 5.
   doi:10.3390/cells12020236


4. Zhou Q, Zhang B, Verne GN. Pain. 2009;146(1-2):41-46. doi:10.1016/j.pain.2009.06.017


5. Vanuytsel T et al. Gut. 2014;63(8):1293-1299. doi:10.1136/gutjnl-2013-305690


6. Bashashati M et al. Neurogastroenterol Motil. 2018;30(1):10.1111/nmo.13192. doi:10.1111/nmo.13192


7. Lee H et al. J Neurogastroenterol Motil. 2013;19(2):244-250. doi:10.5056/jnm.2013.19.2.244


8. Saffouri GB et al. Nat Commun. 2019;10(1):2012. Published 2019 May 1. doi:10.1038/s41467-019-09964-7


9. Bhonchal S et al. J Gastroenterol Hepatol. 2008;23(7 Pt 2):e43-e48. doi:10.1111/j.1440-1746.2007.05080.x
   


10. Wessells KR et al. J Pediatr Gastroenterol Nutr. 2013;57(3):348-355. doi:10.1097/MPG.0b013e31829b4e9e


11. Linsalata M et al. Nutrients. 2021;13(3):1011. Published 2021 Mar 21. doi:10.3390/nu13031011


12. Duan H et al. Crit Rev Food Sci Nutr. 2022;62(6):1427-1452. doi:10.1080/10408398.2020.1843396


13. Matsui H. et al. J Clin Biochem Nutr. 2011;48(2):107-111. doi:10.3164/jcbn.10-79


14. Fukuda, Y et al. Digestion, 63(1), 93–96. doi:10.1159/000051918


15. Kavanagh K, Hsu FC, Davis AT, Kritchevsky SB, Rejeski WJ, Kim S. Geroscience. 2019;41(6):923-933.
    doi:10.1007/s11357-019-00112-z


16. De Munck TJI, Xu P, Verwijs HJA, et al. Liver Int. 2020;40(12):2906-2916. doi:10.1111/liv..14696


17. Damms-Machado A, Louis S, Schnitzer A, et al. Am J Clin Nutr. 2017;105(1):127-135.
    doi:10.3945/ajcn.116.131110


18. Asbjornsdottir B, Snorradottir H, Andresdottir E, et al. Nutrients. 2020;12(7):1982. Published 2020 Jul 3.
    doi:10.3390/nu12071982


19. Maes M, Kubera M, Leunis JC. Neuro Endocrinol Lett. 2008;29(1):117-124.


20. Clairembault T, Leclair-Visonneau L, Coron E, et al. Acta Neuropathol Commun. 2015;3:12. Published 2015 Mar
    10. doi:10.1186/s40478-015-0196-0


21. Nam B, Kim SA, Park SD, et al. PLoS One. 2020;15(4):e0231268. Published 2020 Apr 10.
    doi:10.1371/journal.pone.0231268


22. Zheng Y, Zhang Z, Tang P, et al. Front Immunol. 2023;14:1143548. Published 2023 Apr 24.
    doi:10.3389/fimmu.2023.1143548


23. Nendl A, Raju SC, Broch K, et al. Front Cardiovasc Med. 2023;10:1160030. Published 2023 Jun 2.
    doi:10.3389/fcvm.2023.1160030


24. Linsalata M, Riezzo G, D'Attoma B, Clemente C, Orlando A, Russo F. BMC Gastroenterol. 2018;18(1):167.
    Published 2018 Nov 6. doi:10.1186/s12876-018-0888-6


25. American Gastroenterological Association. Accessed January 22, 2024.


26. Rastgoo S, Ebrahimi-Daryani N, Agah S, et al. Front Nutr. 2021;8:746703. Published 2021 Dec 16.
    doi:10.3389/fnut.2021.746703


27. Sasaki E, et al. Luminescence. 2013 Jul- Aug;28(4):442- 9.


28. Song QH, et al. Int J Clin Pharmacol Ther. 2015 May;53(5):372-6


29. Oguche S, et. al. Am J Trop Med Hyg. 2014 Nov;91(5):925-35


30. Takeda R, et. al. Phytomedicine. 2013 Jul 15;20(10):861-4.


31. Force M, et al. Phytother. Res. 2000: 14, 213–214.


32. Bansal V, et. al. Niger Med J. Nov-Dec 2019;60(6):285- 289.


33. Khin-Maung-U, et. al. Br Med J (Clin Res Ed). 1985 Dec 7;291(6509):1601-5.


34. Yong Wen, Jun Li, Qing Long, Chao-chi Yue, Bing He, Xue-gui Tang,


35. International Journal of Surgery, 2020. Volume 79. pp 111-19.


36. Sun JR, Kong CF, Qu XK, Deng C, Lou YN, Jia LQ Saudi J Gastroenterol. 2020;26(2):66-77.
    doi:10.4103/sjg.SJG_384_19


37. Shang X, E FF, Guo KL, et al. Nutrients. 2022;14(12):2482. Published 2022 Jun 15. doi:10.3390/nu14122482
    


38. Natalia S, et al. Nutrients. 2018 May; 10(5): 576.


39. Riede L, et. al. Curr Med Res Opin. 2013 Mar;29(3):251-8.


40. Shimada T, et al. J Pharmacol Exp Ther. 1999 Oct;291(1):345-52.


41. Sakae K, et al. Nutr Clin Pract. 2013 Oct;28(5):609-16.


42. Das SK, et al. J Assoc Physicians India. 1989 Oct;37(10):647.


43. Deters A, et al. J Ethnopharmacol. 2010 Jan 8;127(1):62-9.


44. Marakis G, et al. Phytomedicine. 2002 Dec;9(8):694-9.

Extinguishing the Flames: Putting Out the Fire of Occasional Heartburn

TABLE OF CONTENTS

1. Introduction: The Upper Digestive Tract and Symptoms of Occasional Heartburn

2. Lifestyle Factors Contributing to Occasional Heartburn

• 2.1. Stress and Mood Concerns


• 2.2. Medications


• 2.3. Excess Weight


• 2.4. Smoking


• 2.5. Diet

3. Underlying Causes of Occasional Heartburn

• 3.1. Low Stomach Acid


• 3.2. Altered Motility


• 3.3. Food Sensitivities


• 3.4. Balance of the Gut Microbiome


• 3.5. Mast Cell Activation


• 3.6. H. pylori


• 3.7. Hiatal Hernia

4. Assessments for Occasional Heartburn

• 4.1. Betaine HCl Challenge


• 4.2. Esophagogastroduodenoscopy (EGD)


• 4.3. Esophageal pH Monitoring


• 4.4. IgG Food Sensitivity Testing


• 4.5. Elimination Diet


• 4.6. 3-Hour Breath Test


• 4.7. Biopsies with CD117 Staining


• 4.8. H. pylori Stool Testing


• 4.9. Barium Swallow

5. Exploring Nutrients to Support Occasional Heartburn^‡

• 5.1. Betaine HCl and Digestive Enzymes


• 5.2. Deglycyrrhizinated Licorice (DGL), Marshmallow Root & Slippery Elm


• 5.3. Microbial Balance


• 5.4. Probiotics


• 5.5. Ginger Root Extract


• 5.6. Zinc Carnosine

6. Key Takeaways

• 6.1. Lifestyle Factors
  
  
  
  • 6.1a. Stress Management
  
  
  • 6.1b. Maintaining a Healthy Weight
  
  
  • 6.1c. Smoking Cessation
  
  
  
  


• 6.2. Diet & Nutrition
  
  
  
  • 6.2a. Avoiding Trigger Foods
  
  
  • 6.2b. Low FODMAP
  
  
  • 6.2c. Fiber
  
  
  
  

7. Pure Encapsulations® Nutrient Solutions

• 7.1. Betaine HCl


• 7.2. Heartburn Essentials^‡


• 7.3. Digestive Enzymes Ultra


• 7.4. MicroDefense w/ Oregano


• 7.5. DGL Plus^®


• 7.6. Probiotic G.I.


• 7.7. Peptic-Care^‡


• 7.8. MotilPro

8. Conclusion

9. Resources

The regular movement of food through the digestive tract begins with food traveling from the mouth to the stomach via peristalsis through the esophagus. At the distal end of the esophagus, the lower esophageal sphincter (LES) serves as the anatomical gatekeeper between the esophagus and the fundi, or upper stomach. The LES relaxes after swallowing to allow food to pass into the stomach and then contracts and remains contracted between meals. This way, it prevents food and acid from backing up into the esophagus.

Transient LES relaxation can cause brief episodes of stomach contents refluxing back into the esophagus, which is normal and may resolve without symptoms. LES relaxation, however, can expose the esophagus to gastric acid, digestive enzymes and bile salts, leading to irritation of the esophagus and more bothersome symptoms like occasional heartburn.

Most people are affected by occasional heartburn and can be supported by maintaining a healthy gastrointestinal tract.¹

While a burning sensation in the chest and reflux of food and gastric acid into the esophagus are the cardinal symptoms associated with occasional heartburn, patients may also describe accompanying GI and extraintestinal complications, including:

• Regurgitation


• Sour stomach


• Chest tightness


• Bloating


• Sensitivity to certain foods and beverages


• Trouble sleeping


• Nausea


• Fullness after eating


• Hoarseness


• Cough

Conventional interventions of occasional heartburn involve pharmacological options to suppress, neutralize or buffer stomach acid. Since up to half of patients experience inadequate relief with these options, optimizing lifestyle factors that contribute to occasional heartburn and other underlying causes can be important in improving patient outcomes.^{2, 3}

STRESS AND MOOD CONCERNS

Patients with occasional heartburn commonly note stress.^{4, 5} A 2022 meta-analysis of nine observational studies with over one million participants examined the co-occurrence of occasional heartburn and occasional nervous tension or low mood. In studies that used heartburn and accompanying symptoms as outcomes, individuals with occasional nervous tension or low mood had a greater than two-fold increase in occasional heartburn and associated reflux symptoms than healthy controls. What’s more, occasional nervous tension or low mood as outcomes, individuals with heartburn and associated reflux symptoms had a 3.43-fold (95% CI) greater risk of occasional nervous tension and a 2.6-fold (95% CI) greater risk of low mood than healthy controls.⁶

MEDICATIONS

Certain medications can contribute to or worsen occasional heartburn and accompanying symptoms by irritating the esophagus, lowering LES pressure or delaying gastric emptying,^{1, 7} including:

• Nonsteroidal anti-inflammatory drugs (NSAIDs)


• Calcium channel blockers


• Benzodiazepines


• Asthma medications


• Tricyclic anti-depressants


• Anticholinergics


• Estrogen

EXCESS WEIGHT

Being overweight has been shown to increase the risk of occasional heartburn and accompanying symptoms up to 3-fold³, with a dose-dependent relationship between increasing BMI and frequency of symptoms. ⁸

SMOKING

Smoking is an independent risk factor for occasional heartburn.⁹ People who smoke may experience reduced LES pressure, prolonged acid clearance and decreased bicarbonate in their saliva compared to non-smokers.⁹

DIET

Alcohol: Several observational studies have found a significant association between alcohol consumption and the risk of occasional heartburn,¹⁰ observing a dose-response relationship between alcohol consumption and occasional heartburn risk. Individuals who drank more than 3-5 times or days per week had a greater risk of occasional heartburn and associated symptoms. These studies also propose that the hyperosmotic properties of alcohol may contribute to esophageal sensitivity by disrupting the integrity of tight junctions in the esophageal epithelial layer, allowing penetration of gastric acid and stimulation of sensory nerves.¹⁰

Food Triggers: Patients experiencing occasional heartburn may describe dietary triggers,^{1, 7} including:

• High-fat foods


• Acidic foods like tomatoes and citrus


• Chocolate


• Mint


• Coffee and caffeine


• Spicy foods


• Carbonated beverages

The National Institutes of Health have reports that occasional heartburn and its accompanying symptoms are the most frequent digestive concerns seen at ambulatory care visits.¹² Causes of occasional heartburn can be multifactorial and can include existing health conditions as well as contributors like low stomach acid, altered motility, diet and an altered microbiome.

LOW STOMACH ACID

Insufficient stomach acid can inhibit proper digestion and absorption. This can lead to altered motility, altered microbial balance, fermentation by microbes, symptoms of gastric distension and occasional discomfort accompanying occasional heartburn.^{13, 14} Gastric distension can stimulate LES relaxation and cause stomach contents to wash back into the esophagus.¹⁵

ALTERED MOTILITY

Delayed gastric emptying increases the time acidic food remains in the stomach and raises intragastric pressure. Increased intragastric pressure causes a relaxation of the LES, allowing the regurgitation of stomach contents back into the esophagus and contributing to occasional heartburn symptoms. Some patients may also experience altered esophageal motility, resulting in impacted esophageal peristalsis.¹⁶

FOOD SENSITIVITIES

IgG-mediated food sensitivities can have a role in Functional GI concerns and trigger occasional heartburn and accompanying symptoms.¹⁷ Patients often report that dietary factors bring on their symptoms. Aside from the apparent trigger foods known to promote occasional heartburn, patients may have difficulty isolating other offending foods related to IgG-mediated sensitivity.

BALANCE OF THE GUT MICROBIOME

The gut microbiota and its metabolites can impact the integrity of the intestinal barrier and its secretions, affect the gut-brain axis and contribute to altered motility, promoting the development of occasional heartburn and accompanying symptoms.¹⁸ The fermentation of carbohydrates by gut microbiota can produce various gases like hydrogen and methane, contributing to abdominal distension and bloating. the effect of changes in intragastric pressure on the LES, overlapping symptoms seen between those that may accompany occasional heartburn, altered microbial balance and Functional GI concerns should be considered.

MAST CELL ACTIVATION

Mast cells (MCs) are found throughout the gastrointestinal tract and are associated with other Functional GI concerns where altered motility is a factor. Mast cells generate histamine and serotonin, which promote enteric smooth muscle contraction.¹⁹ Activation of mast cells and their mediators can lead to irritation of the gastric lining and altered motility, causing symptoms like abdominal pain, upset stomach, bloating and change in bowel habits and occasional heartburn.¹⁸

H. PYLORI

Heliobactor pylori is a bacteria that can survive stomach acid and lead to chronic irritation of the gastric lining. However, the discussion on the role of H. pylori in occasional heartburn symptoms is not without controversy. It has been argued that the presence of H. pylori may be protective against occasional heartburn and that its eradication may increase the risk of occasional heartburn and accompanying symptoms.^{21, 22} Conversely, it has also been argued that treating H. pylori has a beneficial effect on occasional heartburn.²³ Although there is no unified consensus on the role of H. pylori and occasional heartburn, a patient’s history, individual response to pharmacological agents used during treatment and the level of irritation in the stomach lining require consideration in a personalized treatment plan.²¹

HIATAL HERNIA

A hiatal hernia can be present in up to 43% of patients experiencing occasional heartburn, and a linear relationship exists between the size of a hiatal hernia and the severity of a patient’s symptoms.¹⁵ The protrusion of the upper stomach into the esophageal hiatus can displace the crural diaphragm from the LES and increase the frequency of transient relaxation of the LES. The size and location of the hiatal hernia may also cause it to act as a basin, trapping gastric acid and impeding esophageal clearance.¹⁵

BETAINE HCl CHALLENGE

Long-term use of acid-suppressing agents and poor diet can lead to reduced hydrochloric acid production. Challenge with Betaine HCl, dosed to tolerance with meals containing protein, can be used when hypochlorhydria is a concern. This assessment method is contraindicated in patients with irritated esophagus, stomach lining or duodenum.

ESOPHAGOGASTRODUODENOSCOPY

An esophagogastroduodenoscopy (EGD), or upper endoscopy, is used to observe the lining of the esophagus, stomach and duodenum to investigate and assess concerns related to occasional heartburn. Biopsies of the esophageal tissue may also be performed.¹

ESOPHAGEAL pH MONITORING

Esophageal pH monitoring detects stomach acid in the esophagus. Stomach acid can be detected by a catheter inserted through the nose and into the esophagus or with a capsule placed in the esophagus lining. Patients also wear a monitor that receives information from the catheter or capsule about their diet, sleep and symptoms. Esophageal pH monitoring may also be used to assess the effectiveness of treatment.

IgG FOOD SENSITIVITY TESTING

Because food sensitivities may trigger symptoms that overlap with occasional heartburn and other symptoms associated with Functional GI concerns, IgG Food Sensitivity Testing can assist with making personalized dietary recommendations for patients.

ELIMINATION DIET

In multiple clinical trials where food exclusion diets were implemented based on foods identified as having IgG antibodies with ELISA testing, patients found significant improvement in symptoms that often lead to or accompany occasional heartburn, including abdominal distension, bowel regularity and stress.^{24, 25, 26}

3-HOUR BREATH TEST

Breath tests involving ingestion of a lactulose solution are a noninvasive way to measure exhaled hydrogen and methane gases and are used to determine altered microbiota, which may be an underlying cause for heartburn and related GI symptoms.

The 3-hour profile is a useful tool for those patients who also experience occasional constipation and for pinpointing the possible presence of hydrogen sulfide gas, indicated by a flat line at the 3-hour mark.

BIOPSIES WITH CD117 STAINING

Patients with occasional heartburn may also have dyspeptic symptoms induced by mast cells and their mediators. A jejunal biopsy with CD117 staining can be utilized to determine mast cell numbers and activity in the mucosa of the proximal small intestine.³⁴

H. PYLORI STOOL TESTING

Two different stool tests exist as a noninvasive way to assess the presence of H. pylori. The Stool Antigen Test (SAT) detects proteins related to H. pylori. The PCR test, although more expensive, can detect H. pylori and identify other factors that could impact methods of intervention.

BARIUM SWALLOW

The Barium Swallow is a contrast-enhanced x-ray used to examine aberrations in the esophagus and stomach. It can identify strictures, perforations and motility concerns of the esophagus and identify the presence of a hiatal hernia. These physiological factors and assessments may be indicative of or identify a more serious issue than occasional heartburn alone. Such diagnoses should come from a qualified healthcare professional.

Betaine HCL & Digestive Enzymes: In addition to being an underlying contributor to occasional heartburn, hypochlorhydria or achlorhydria and reduced digestive enzyme production can lead to malabsorption of nutrients, inadequate digestion, increased risk of food hypersensitivity, bacterial overgrowth and digestive discomfort and bloating.^{13, 275} In patients where either of these are suspected, Betaine HCl may be used at mealtime to support optimal gastric pH and enhance digestion of protein and other nutrients to support daily wellness and neurotransmitter synthesis.^{28, 29} The use of digestive enzymes can also support the digestion and absorption of proteins, carbohydrates, fats and fibers not acted upon by the gastric environment.^‡

Deglycyrrhizinated Licorice (DGL), Marshmallow Root & Slippery Elm: Deglycyrrhizinated licorice (DGL), marshmallow root and slippery elm bark are demulcent herbs that are traditionally recognized for their value in soothing the gastrointestinal tract and maintaining the integrity of the mucosal lining.^{30, 31, 32‡}

Microbial Balance: With the commonality of symptoms that exist between heartburn and microbiota imbalance in the GI tract, employing strategies to mitigate growth of non-beneficial bacteria may be warranted in some patients. Botanicals like artemisia, olive leaf extract, oregano, clove and berberine sulfate can help promote healthy microbial balance^{33, 34, 35, 36, 37‡}

Probiotics: Probiotics are believed to support healthy gut-associated lymphoid tissue (GALT) composition and support barrier function, G.I. epithelial cell health and T cell function within the G.I. tract.³⁸ Some probiotic strains may also modulate local production of cytokines and other immune mediators in the G.I. epithelium.^39‡

Ginger Root Extract: Ginger helps to stimulate digestive enzymes and the production and secretion of bile from the liver and gallbladder.⁴⁰ More recent evidence shows that ginger's volatile oil components (gingerols and shogaols) modulate intestinal serotonin receptors that regulate motility and secretions.⁴¹ Ginger also maintains healthy eicosanoid balance in the GI tract, joints and the cardiovascular system.^{42, 43‡}

Zinc Carnosine: Zinc and carnosine provide synergistic antioxidant protection, support the stomach's mucosal defenses, buffer gastric acid and maintain healthy cytokine release.⁴⁴ Studies suggest that this combination is more effective in maintaining the integrity of the gastric lining than either ingredient alone.^45‡

LIFESTYLE FACTORS

Stress Management: Stress is the most common lifestyle factor described by patients with occasional heartburn.^{4, 46} In a post-hoc analysis of over 12,000 patients from the LEGEND study, addressing lifestyle factors that contributed to stress had a significant effect on patient’s heartburn and accompanying symptoms.⁴ Patients who receive advice on stress management techniques have reported improvement in GI symptoms and quality of life.⁴⁷

Maintaining a Healthy Weight: Excess weight, particularly in the midsection, increases the gastroesophageal pressure gradient.⁴⁸ The higher intragastric pressure correlates to lower LES pressure and increased frequency of transient relaxation of the LES.¹⁴ Encouraging patients to make lifestyle changes to initiate weight loss of 10-15 lbs. can be a successful strategy to reduce occasional heartburn.⁸

Smoking Cessation: A prospective study by Kohata et al. examined the long-term effects of smoking cessation on heartburn and accompanying symptoms and health-related quality of life in 191 patients. Those patients who successfully achieved smoking cessation (n=141) experienced a significant (43.9%) improvement in symptoms compared to those who were unsuccessful at quitting smoking (n=50, 18.2%). Significant improvement in health-related quality of life was only seen in the success group.⁹

DIET & NUTRITION

There are multiple dietary approaches that can be explored for individuals with occasional heartburn. In addition to providing education about foods that can relax the LES, the practitioner should also consider a patient’s possible food sensitivities and dietary patterns, as some patients may benefit from trial elimination of difficult-to-digest carbohydrates.

Avoiding Trigger Foods: First-line treatment of occasional heartburn often involves avoidance of foods that commonly trigger occasional heartburn. Advising patients to eat smaller meals and to avoid eating too close to bedtime may also be supportive.

Low FODMAP Diet: FODMAP stands for Fermentable, Oligo-Di and Mono-saccharides and Polyhydric Alcohols. FODMAPS encompass foods that can interact with gut microbiota, and through fermentation can provoke symptoms of GI discomfort often seen with occasional heartburn.
In a small, randomized crossover study, patients with occasional heartburn and Functional GI concerns were provided either a high FODMAP meal or a low FODMAP meal for breakfast and lunch to evaluate the effects of each meal on postprandial transient relaxation of the LES, intestinal gas production and occasional heartburn and accompanying GI symptoms. The results indicated that the high FODMAP meal induced a higher frequency of transient LES relaxation, greater heartburn and higher upper GI symptom scores than the low FODMAP meals.⁴⁹

Fiber: Contrary to a Low FODMAP diet, a cross-sectional study of nearly 4000 adults found that those individuals with the highest intake of fruits and vegetables had a 33% lower risk of occasional heartburn.⁵⁰
Low dietary fiber intake has been associated with altered motility, delayed gastric emptying and increased intragastric pressure.⁵¹ In some patients, a fiber-rich diet may support an increase in LES pressure and decrease frequency of occasional heartburn.⁵⁰
Just as multiple mechanisms can contribute to heartburn and accompanying GI symptoms, multiple factors can contribute to an individual’s response to different foods, illuminating the merits of individualized dietary advice and nutrient support for patients.

While there is some value in pharmacological agents to counter acid production, patients can develop a reliance on them, leaving underlying causes of occasional heartburn unaddressed. Long-term acid suppression can also affect a patient’s absorption of multiple micronutrients including B₁₂, calcium, iron and magnesium.⁵²

Pure Encapsulations has products to help you provide individualized dietary supplement recommendations to attend to your patients’ nutrient needs and extinguish the flames of occasional heartburn, by supporting their gastric function, promoting motility and microbial balance, maintaining the mucosa, and soothing irritation.^‡

Certain medications may be appropriate and should be used under the recommendation of healthcare professional for managing chronic, long-term, and/or more serious cases of acid reflux and heartburn. Dietary supplements are not intended to replace the use of such medications.

However, if looking for a way to potentially manage occasional and/or minor heartburn, the following supplement recommendations may be appropriate for you, along with other dietary and lifestyle changes.

DIGESTION/DIGESTIVE ENZYME SUPPORT

• Betaine HClcontains betaine HCl and pepsin to supports healthy gastric function and promote absorption of protein, vitamin B₁₂, and calcium.^‡ Suggested use: 1 capsule, 3 times daily, with each meal.


• Digestive Enzymes Ultra contains an extensive profile of vegetarian digestive enzymes to support protein, carbohydrate, fat, fiber, and dairy digestion and promote enhanced nutrient bioavailability and absorption.^‡ Suggested use: 2 capsules with each meal.

MUCOSAL SUPPORT

• Heartburn Essentials^‡ contains a unique blend of Gamma oryzanol, deglycyrrhizinated licorice extract, marshmallow root extract, slippery elm extract, artichoke extract, turmeric extract along with amylase, lipase and cellulase to support comfort and relief from occasional heartburn, and occasional gas and bloating, promote healthy gastric secretion and support the integrity of the mucosal lining.^‡ Suggested use: 1 capsule at the start of each meal.


• DGL Plus^® contains a synergistic combination of deglycyrrhizinated licorice extract, aloe vera extract, slippery elm and marshmallow root extract to help stimulate the quality and production of stomach mucus, provide nutritional support to the gastrointestinal tract and support the body’s natural defense mechanisms.^‡ Suggested use: 1 capsule daily before a meal.


• Peptic-Care^‡ contains a patented 1:1 chelate of zinc and l-carnosine provides synergistic G.I. mucosal protection, and supports the stomach’s mucosal defenses, buffers gastric acid, maintains healthy cytokine release and provides antioxidant support for the GI tract.^‡ Suggested use: 1 capsule, 1-2 times daily, with meals.

MICROBIAL BALANCE

• MicroDefense w/ Oregano is comprised of a combination of olive leaf, artemisia and clove extracts to promotes healthy gastrointestinal tract function and microbial balance^‡ and supports immune function and respiratory tract balance.^‡ Suggested use: 1 capsule, 1-3 times daily, just before a meal, with 6-8 oz water for 2-3 months.

PROBIOTICS/PREBIOTICS

• Probiotic G.I. provides 10 billion CFU per capsule of the beneficial bacteria Lactobacillus acidophilus, Lactobacillus salivarius, Lactobacillus casei, Bifidobacterium bifidum, Bifidobacterium lactis and Streptococcus thermophilus to promote healthy immune balance within the G.I. tract and help maintain the integrity of the intestinal mucosa.^‡ Suggested use: 1 capsule, 1-2 times daily, with or between meals.

MOTILITY

• MotilPro contains ginger extract, 5 hydroxytryptophan, pyridoxal-5 phosphate, and acetyl-l carnitine that provide support for gastrointestinal motility, GI comfort and stimulation of gut-signaling neurons.^‡ Suggested use: 2 capsules, 1-2 times daily, between meals.

Diet and lifestyle play significant roles in gastrointestinal health. Addressing occasional heartburn requires a comprehensive approach to not just alleviate symptoms but to also investigate underlying causes, assess the patient’s nutrient needs and support their digestive function.

With Pure Encapsulations, you have the promise of premium-sourced ingredients backed by verifiable science, so you can be confident you are recommending products with quality, purity and potency to meet your patients’ needs.

Heartburn Support Protocol: This protocol offers focused interventions to support gastrointestinal health in patients with occasional heartburn.

Drug-Nutrient Interactions Checker: Offers scientifically supported, clinically relevant information that’s easy to understand with product suggestions based on verifiable science.

You can also explore Pure Encapsulations® to find On-Demand Learning, Clinical Protocols and other resources developed with our medical and scientific advisors.

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    Koyyada A. Therapie. 2021;76(1):13-21. doi:10.1016/j.therap.2020.06.
    

Unraveling the Complexity of Functional GI Concerns: Understanding Types, Causes and Solutions

TABLE OF CONTENTS

1. Symptoms, Prevalence, and Subtypes of Functional GI Concerns

2. Underlying Causes of Functional GI Concerns

• 2.1. Food Sensitivity/Leaky Gut


• 2.2. Microbial Balance in the GI Tract


• 2.3. Spoiled Food


• 2.4. Mast Cell Activation


• 2.5. Low Stomach Acid and Digestive Enzymes


• 2.6. Genetic Factors


• 2.7. Gut-Brain Connection

3. Assessments for Functional GI Concerns

• 3.1. IgG Food Sensitivity Testing


• 3.2. 3-Hour Breath Test


• 3.3. Auto Antibody Testing


• 3.4. Biopsies with CD117 Staining

4. Nutrients to Support Functional GI Concerns

• 4.1. Glutamine


• 4.2. Herbal Ingredients


• 4.3. Betaine HCl & Digestive Enzymes


• 4.4. Probiotics


• 4.5. Fiber


• 4.6. Butyrate

5. Key Takeaways

• 5a. Lifestyle
  
  
  
  • Stress Management
  
  
  • Exercise
  
  
  
  


• 5b. Diet & Nutrition
  
  
  
  • Low FODMAP Diet
  
  
  • High-Fiber Foods
  
  
  
  

6. Pure Encapsulations® Nutrient Solutions

• 6.1. Probiotic G.I.


• 6.2. PureGG 25B


• 6.3. PureBi*Ome^TM Intensive


• 6.4. Poly-Prebiotic Powder


• 6.5. Epi-Integrity Powder


• 6.6. SunButyrate^TM-TG liquid


• 6.7. Digestive Enzymes Ultra with Betaine HCl


• 6.8. Digestive Enzymes Ultra


• 6.9. Betaine HCl


• 6.10. MicroDefense w/ Oregano

Symptoms that involve abdominal discomfort, bloating, flatulence and occasional diarrhea or constipation are functional GI concerns that have an estimated worldwide prevalence of up to 1 in 10 individuals,¹ making them the most common functional bowel concerns worldwide. Impacting approximately three times as many women as men,² functional GI concerns can occur at any age, with 50% of patients experiencing symptom onset before 35 years.³

Functional GI concerns are characterized by abdominal discomfort coupled with altered bowel habits and are also associated with visceral hypersensitivity, altered motility, immunomodulation, altered gut microbiota and dysregulation of the gut-brain axis. Functional GI concerns can be differentiated into subtypes determined by an individual’s predominant clinical manifestation: occasional diarrhea, occasional constipation, or mixed symptoms - primarily constipation with intermittent episodes of diarrhea.

Due to the heterogeneous nature of functional GI concerns, symptoms and severity can vary within each subtype and from individual to individual, negatively impacting a person’s quality of life. An individual with functional GI concerns will often describe uncertainty about what foods trigger their symptoms, state the difficulties of eating out and express fear of experiencing symptoms in social situations.

Although no single causative factor has been isolated for functional GI concerns, several etiologies have come to the forefront of investigations.

FOOD SENSITIVITY/LEAKY GUT

The intestinal barrier serves an important function of being a selectively permeable barrier between environmental exposures and systemic circulation. Intercellular tight junctions are the key structures that regulate paracellular trafficking of macromolecules through the intestinal barrier. Disturbance of this barrier, also popularly termed as “leaky gut,” allows antigens in the form of Lipopolysaccharides and bacterial components, which would otherwise be restricted to the gut, to gain access to the mucosa and systemic circulation, triggering immune activation and cytokine release.^{4, 5} Proteins that contribute to the stability of tight junctions and barrier function, like occludin, claudin, cadherin and zonulin, are a factor in leaky gut and have been implicated in functional GI concerns.^4-6 This may in turn contribute to higher stool frequency, visceral sensitivity and an increase of symptoms in patients, especially those with occasional diarrhea.^{6, 7}

It has been suggested that IgG-mediated food sensitivities have a role in functional GI concerns.^{8, 9, 10}

The intestinal permeability biomarkers, anti-lipopolysaccharide (LPS) and anti-occludin IgG and IgA antibodies have been significantly and positively associated with IgG-mediated food sensitivities, and a higher prevalence of food sensitivity has been found in patients with functional GI concerns. In a randomized, controlled trial and two studies utilizing exclusion diets, researchers observed greater numbers of food-specific IgG antibodies in individuals with functional GI concerns vs. controls.^8-10 Serum zonulin, another biomarker for leaky gut, has also been observed to be increased in patients with occasional diarrhea or mixed symptoms compared to healthy controls.^{7, 11}

MICROBIAL BALANCE IN THE GI TRACT OR SMALL INTESTINE

A study published by Su and colleagues in 2023 examining the functional composition of gut microbiota of 942 subjects with varying subtypes of functional GI concerns who were enrolled in the American Gut Project determined that bacterial diversity of patients with functional GI concerns was lower than that of healthy controls, with all subtypes showing a deficiency of beneficial bacteria and enrichment of non-beneficial microorganisms.¹²

A reduction in Bifidobacteria and Lactobacillus,has been observed in patients with functional GI concerns and in patients with occasional diarrhea and mixed symptoms, along with a reduction in butyrate-producing microorganisms.^{13, 14}

Aberration of the gut microbiota and its metabolites can disrupt the integrity of the intestinal barrier and its secretions can affect the gut-brain axis, contribute to visceral sensitivity, altered motility, and promote the development of symptoms related to functional GI concerns.¹²

Disturbance of microbial balance in the GI tract or small intestine is a prominent contributor to functional GI concerns, with one meta-analysis finding a 31% prevalence compared to controls.¹⁵ The strongest association is seen in diarrhea, with some investigations revealing the presence of a microbial imbalance in more than 80% of patients with occasional diarrhea.¹⁶

The fermentation of carbohydrates by gut microbiota can produce gases like hydrogen and methane, contributing to the overlapping symptoms of occasional abdominal discomfort, distension, occasional diarrhea and bloating, as seen between microbial imbalance and functional GI concerns.

A positive association and significant prevalence have been established between methane positivity on lactulose breath tests and occasional constipation.^{17, 18}

FOOD QUALITY AND FUNCTIONAL GI CONCERNS

Every year, 1 in 6 U.S. adults is affected by food quality issues according to the CDC.¹⁹

Spoiled food exposure affecting the digestive tract are among the greatest risk factors for developing functional GI concerns, with affected individuals having a four times higher risk of functional GI concerns than nonexposed individuals.²⁰ Women and individuals with psychological distress at the time of an episode are at an increased risk of developing functional GI concerns post-exposure.²⁰

MAST CELL ACTIVATION

Abundant in the intestinal landscape, mast cells and their mediators have been implicated in the study of functional GI concerns and can be provoked by exposure of non-beneficial microorganisms, food antigens, cytokines and even psychological stress.²¹

When activated, they release various mediators, including histamine, serotonin, protease, leukotrienes, prostaglandins, cytokines, TNF and platelet-activating factors.

An increased number of mast cells in the colon and mucosa of the small intestine has been observed both in patients with occasional diarrhea or occasional constipation vs. controls.^{21, 22} Owing to their proximity to enteric and pain transmitting afferent nerves, individuals with an increased activity of these mast cells can experience visceral hypersensitivity, along with altered motility, immune activation and increased barrier permeability.^{21, 22}

LOW DIGESTIVE ENZYMES AND STOMACH ACID

Gut microbiota can quickly overpopulate given the right environment. Insufficient stomach acid or digestive enzyme production can create an environment that prevents proper digestion and absorption.^{23, 24} Adequate stomach acid is required to absorb multiple micronutrients, including calcium, magnesium, iron and several B vitamins.²³ Inadequate digestion can lead to altered motility, altered microbiota, fermentation by microbes and symptoms of bloating and discomfort seen in functional GI concerns discussed here, and in other overlapping gastrointestinal conditions.^{24, 25}

GENETIC FACTORS

Case-control and prospective studies have shown that patients with functional GI concerns frequently report a positive family history of functional GI concerns.^{26, 27, 28}

Genome-wide association studies have investigated possible genetic variations in signaling pathways that could increase susceptibility to functional GI concerns. One such pathway, the serotonergic pathway, has received significant attention. Polymorphisms in the 5-HT3 receptor family and disrupted serotonergic function have been linked to a greater degree of visceral hypersensitivity and increased susceptibility to functional GI concerns, especially in women.²

With greater than 90% of the body’s production taking place in the gut, serotonin or 5-HT, regulates motility, secretion and visceral sensation. It also performs as a neurotransmitter, paracrine factor, endocrine hormone and growth factor, and interacts with the vagus nerve. Serotonin’s interaction with the vagus nerve influences emotional processing, behavior and the immune and nervous system. Variants in the 5-HT3 receptor family have been associated with concerns related to mood because they are co-occurringwith functional GI concerns.²

GUT-BRAIN CONNECTION

The significance of the gut-brain axis in functional GI concerns has been well established. This bidirectional relationship influences the onset and course of functional GI concerns and partly accounts for the great amount of co-occurring psychological concerns. The risk of occasional nervous tension and mood concerns in patients with functional GI concerns is threefold compared to healthy controls²⁹ and at least 50% of patients with functional GI concerns describe occasional nervous tension or mood concerns.³⁰

Compared to healthy controls, patients with functional GI concerns have a greater reactivity to stress,^{15, 30} which induces alterations in:

• gastric motility


• autonomic tone


• HPA axis response


• visceral perception


• microbial composition

The existence of stress and mood concerns have also been linked to onset of symptoms after an episode of non-beneficial microorganism exposure affecting the digestive system, with mixed symptoms of occasional constipation and occasional diarrhea being the greatest risk following exposure.

IgG FOOD SENSITIVITY TESTING

Two-thirds of patients with functional GI concerns report that dietary factors trigger their symptoms¹² and there is increasing evidence suggesting that IgG hyperreactivity plays a role in functional GI concerns.

In numerous clinical trials where food exclusion diets were implemented based on foods identified as having IgG antibodies with ELISA testing, symptom improvement was seen in patients with functional GI concerns.^{8-11, 31} Significant improvements most often seen were:

• bloating


• diarrhea frequency


• abdominal discomfort


• feelings of distress


• stool shape/consistency

Patients experiencing functional GI concerns often cannot predict what foods may trigger them or when their symptoms will be aggravated, which can limit their social activity. Incorporating food sensitivity testing may lessen this burden and assist patients with personalizing their diet and nutrient needs.

3-HOUR BREATH TEST

Breath tests involving ingestion of a lactulose solution are a noninvasive way to measure exhaled hydrogen and methane gases and are used to determine disruption of the balance of microbiota.

For those patients with occasional constipation or slower transit time, the 3-hour assessment can discern gas levels over a more extended period. The 3-hour profile is also useful in pinpointing the possible presence of hydrogen sulfide gas, indicated by a flat line at the 3-hour mark.

AUTO ANTIBODY TESTING

Non-beneficial bacteria that are often elevated in patients with occasional diarrhea or mixed symptoms: anti-CdtB and anti-vinculin.  An auto antibody test can detect elevated levels of these biomarkers and determine subtypes within functional GI concerns.^{32, 33}

BIOPSIES WITH CD117 STAINING

Patients with functional GI concerns commonly experience occasional dyspeptic symptoms. A jejunal biopsy with CD117 staining can be utilized to determine mast cell numbers and activity in the mucosa of the proximal small intestine.³⁴

Glutamine: Glutamine, the most abundant amino acid in the body, is a primary energy source for intestinal epithelial cells and is utilized by the body for tissue repair and gastrointestinal support.^{35, 36, 37} Glutamine plays a large role in maintaining healthy intestinal integrity by enhancing the intestine’s protective mucosal lining.^38‡

Herbal Ingredients: With the high prevalence of microbiota imbalance in the GI tract and small intestine seen in functional GI concerns, employing strategies to shift this balance may be warranted in some patients. Botanicals like artemisia, olive leaf extract, oregano, clove and berberine sulfate can help promote healthy microbial balance.^{39, 40, 41, 42, 43‡}

Betaine HCL & Digestive Enzymes: Hypochlorhydria or achlorhydria and reduced digestive enzyme production can lead to malabsorption of nutrients, inadequate digestion, potential food sensitivities, altered microbiota and digestive discomfort and bloating.^{24, 25} In patients where either of these are a factor, Betaine HCl may be used at mealtime to support optimal gastric pH, enhance digestion of protein and other nutrients to support daily wellness and neurotransmitter synthesis.^{44, 45} The use of digestive enzymes can also support the digestion and absorption of proteins, carbohydrates, fats and fibers not acted upon by the gastric environment.^‡

Probiotics: Probiotics are efficacious in all subtypes of functional GI concerns, although specific strains should be considered for each subtype and symptoms presented. Overall, meta-analyses have shown that probiotics may support stool consistency, regulate stool frequency and gut transit time, and support symptoms related to functional GI concerns.^{46, 47, 48‡}

Fiber: Owing to contradictory outcomes in clinical studies and the multifactorial nature of functional GI concerns, using fiber has experienced a pendulum effect. While fiber intake is typically deficient in individuals with functional GI concerns, and both soluble and insoluble fiber can aggravate symptoms, studies examined by meta-analyses seem to favor using soluble fiber.^{49, 50‡}


Psyllium husk, a valued source of soluble fiber, helps promote larger and softer stools for healthy bowel movement frequency. It is fermented in the intestines, producing short-chain fatty acids (SCFAs) that provide an energy source for the colon to maintain healthy colon cell function and promote beneficial microflora.^51‡

Prebiotic fibers, like arabinogalactan, are nondigestible food components that modulate and support the gut microbiota. They perform beneficial metabolic, trophic and protective functions within the gut, leading to overall cellular, immune and metabolic support.⁵² Arabinogalactan may increase the concentration of beneficial bacteria, such as Bacteroidetes and Faecalibacterium prausnitzii.^53‡


When recommending a fiber supplement to patients with functional GI concerns, practitioners should consider the fiber type and symptoms. It’s advisable to start “low and slow” with fiber supplementation, adding small amounts of fiber gradually over several weeks, monitoring symptoms and ensuring adequate hydration. Some patients respond better to increased fiber when they are in the later stages of gut healing.^‡

Butyrate: Butyrate is one of the three most abundant short-chain fatty acids (SCFAs) produced by anaerobic bacterial fermentation of polysaccharides/fiber in the colon, where it serves as an energy source for epithelial cells.⁵⁴ Butyrate plays a major role in intestinal physiology, supporting both physical and biochemical protective barrier function, bowel motility, nutrient absorption and immune activity of intestinal cells.⁵⁵ It also promotes the proliferation, differentiation and renewal process of the colonocytes. This trophic property of butyrate and other SCFAs support tight-junction assembly, healthy mucus production and a healthy intestinal barrier.^56‡

SUMMARY

The heterogeneity of functional GI concerns requires that patients receive a comprehensive, individualized approach, accounting for symptom type and fluctuation, co-occurring conditions and nutrient needs. Therapeutic options should include personalized dietary changes, supplemental support and lifestyle modifications.

LIFESTYLE

Stress Management: Patients with functional GI concerns who have stress compared to those not exposed to stressful events should make stress management a vital component of their support plan.⁵⁷

Patients receiving advice on stress management techniques as part of a stress management program have reported support for symptoms and quality of life.⁵⁷

Given the high prevalence of stress and mood concerns in patients with functional GI concerns, certain therapies may also provide a benefit for these patients. One option is cognitive behavioral therapy (CBT). CBT can improve cognitive flexibility and may support symptom severity, especially abdominal discomfort, particularly in patients with functional GI concerns.

Regular Exercise: The benefits of regular exercise go beyond just improving physical health. Regular exercise can evoke feelings of well-being, enhance cognition, reduce stress and support mental health by improving symptoms of occasional nervous tension and low mood.

In a pilot study and two randomized, controlled studies examining physical activity for functional GI concerns, both regular engagements in low-impact and high-intensity exercise had beneficial effects on symptoms and feelings of well-being in individuals with functional GI concerns compared to controls.^{59, 60, 61} Individuals with functional GI concerns experienced increased quality of life, reduced mood concerns and occasional nervous tension.^59-61 Regular exercise in these studies ranged from yoga and walking to cycling, aerobics and swimming.

These outcomes support the benefits of regular physical activity in patients with functional GI concerns and underpin the argument that physical activity recommendations can meet patients “where they are” in terms of fitness level, motivation and ability.

DIET & NUTRITION

Low FODMAP Diet: The low FODMAP Diet has gained increasing popularity among patients with functional GI concerns and some healthcare practitioners.

FODMAP stands for Fermentable, Oligo-,Di, Monosaccharides And Polyhydric alcohols. FODMAPS encompass foods that can interact with gut microbiota and through fermentation, can provoke symptoms of discomfort, flatulence and dysregulated bowel habits like those seen in functional GI concerns. This category of food includes lactose, fructose, fructans and other poorly absorbed carbohydrates.

Overall, symptom improvement has been seen in some patients adhering to a Low FODMAP diet, with reductions in abdominal discomfort frequency and severity, bloating, and improved satisfaction with bowel habits and quality of life, compared to a standard diet consisting of high FODMAP foods.^62,63

When recommending a Low FODMAP diet, a few things should be considered. One is the effect on the gut microbiome. FODMAPS are a food source for colonic microbiota, which degrade them into short-chain fatty acids. Deprivation of these carbohydrates can affect the production of SCFAs and reduce bacterial counts like Bifidobacteria, consequently affecting the integrity of the mucosal barrier.⁶⁴

Additionally, the Low FODMAP diet is quite restrictive and long-term adherence may affect nutrient status and prove expensive, difficult and frustrating for the patient. Utilizing a Low FODMAP diet as a therapeutic option should be undertaken in three distinct stages: elimination, reintroduction, and personalization. Once Low FODMAP foods have been eliminated and patients see symptom improvement, they should be guided on how to reintroduce individual FODMAP foods back into their diet gradually, and the patient’s tolerance or reaction to that food should be assessed. It’s important to remember that different FODMAP foods affect different functional GI concerns and their subtypes differently. Taking the time to assist the patient through the reintroduction phase provides an opportunity to personalize their diet and for a greater variety of tolerable foods to be added to their diet over time.

High Fiber Foods: To echo Lucretius from De Rerum Natura: “What is food to one, is to others bitter poison.”

Fiber may pose the same challenge in patients with functional GI concerns. While it is recommended that men and women consume 38g and 25g of fiber daily, most patients with functional GI concerns have suboptimal fiber intakes.

As seen with fiber supplementation, dietary soluble fiber is more beneficial for patients with functional GI concerns. When incorporating more dietary fiber, the type, amount and method of preparation are important.

• Type: Foods high in soluble fiber and low in insoluble fiber are less aggravating to symptoms


• Amount: Fiber with adequate hydration should be introduced in small amounts over several weeks.


• Preparation: Patients may find high-fiber foods are less tolerable when eaten raw and more tolerable when cooked or pureed.

PROBIOTICS/PREBIOTICS

• Probiotic G.I. is shelf stable and provides 10 billion CFU per capsule of beneficial bacterial strains in thre Lactobacillus and Bifidobacteria genuses. This probiotic supports GI barrier function and helps to maintain the integrity of the intestinal mucosa.^‡ Suggested use: 1 capsule, 1-2 times daily, with or between meals.


• PureGG 25B contains shelf-stable, highly researched Lactobacillus rhamnosus that supports immune, GI and overall health.^‡ Suggested use: 1 capsule daily, with or between meals.


• PureBi*Ome^TM Intensive is a high-potency, 4-strain, clinically researched proprietary probiotic blend combined with Saccharomyces boulardii to support intestinal microbial balance and help lessen the occurrence of occasional diarrhea.^‡ Suggested use: 1 capsule daily, with a meal.


• Poly-Prebiotic Powder is a unique powdered blend of researched prebiotic fibers and polyphenols to support gastrointestinal, cellular and immune function by boosting bifidobacteria and microbiome diversity.^‡ Suggested use: 1 scoop, 1-2 times daily, mixed with a beverage or into food.

GUT BARRIER INTEGRITY

• Epi-Integrity Powder promotes healthy modulation of mucosal immune responses to support GI integrity.^‡ Suggested use: 1 scoop, 1-2 times daily. Add 1 serving to 8 oz of water or juice.


• SunButyrate^TM-TG liquid provides 875 mg of short-chain fatty-acid butyric acid in one teaspoon to promote gut-barrier integrity, cytokine balance in the GI tract, abdominal comfort and bowel motility.^‡ Suggested use: 1 teaspoon, 1-3 times daily, with meals.


• L-Glutamine delivers 850 mg of L-glutamine to support the mucosal lining and healthy functioning of the gastrointestinal tract; it may help to maintain lean muscle mass.^‡ Suggested use: 1 capsule, 1-3 times daily, between meals. Also available in powder.

DIGESTIVE ENZYMES

• Digestive Enzymes Ultra with Betaine HCl helps maintain optimal gastric pH and delivers a comprehensive blend of vegetarian digestive enzymes to support protein, carbohydrate, fat, fiber and dairy digestion.^‡ Suggested use: 2 capsules with each meal.


• Digestive Enzymes Ultra offers a comprehensive blend of vegetarian digestive enzymes to support protein, carbohydrate, fat, fiber and dairy digestion.^‡ Suggested use: 2 capsules with each meal.


• Betaine HCl supports healthy gastric function, promoting the absorption of protein, vitamin B12, calcium and iron from food sources.^‡ Suggested use: 1 capsule, 3 times daily, with each meal.

MICROBIAL BALANCE

• MicroDefense w/ Oregano is a combination of plant extracts designed to support healthy gastrointestinal tract function and microbial balance.^‡ Suggested use: 1 capsule, 1-3 times daily, just before a meal, with 6-8oz water for 2-3 months.

RESOURCES

Functional GI Protocol: This protocol supports abdominal comfort, bloating, occasional diarrhea, constipation or a mix of both.

Drug Nutrient Interactions Checker | DNI Calculator: Offers scientifically supported, clinically relevant information that’s easy to understand with product suggestions based on verifiable science.

You can also explore Pure Encapsulations® to find On-Demand Learning, Clinical Protocols and other resources developed with our medical and scientific advisors.

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58. Lackner JM, Jaccard J, Keefer L, et al. Gastroenterology. 2018;155(1):47-57. doi:10.1053/j.gastro.2018.03.063


59. Johannesson E, Simrén M, Strid H, Bajor A, Sadik R. Am J Gastroenterol. 2011;106(5):915-922. doi:10.1038/ajg.2010.480


60. Johannesson E, Simrén M, Strid H, Bajor A, Sadik R. Am J Gastroenterol. 2011;106(5):915-922. doi:10.1038/ajg.2010.480


61. Shahabi L, Naliboff BD, Shapiro D. Psychol Health Med. 2016;21(2):176-188. doi:10.1080/13548506.2015.1051557


62. Varjú P, Farkas N, Hegyi P, et al. PLoS One. 2017;12(8):e0182942. Published 2017 Aug 14. doi:10.1371/journal.pone.0182942


63. Halmos EP, Power VA, Shepherd SJ, Gibson PR, Muir JG. Gastroenterology. 2014;146(1):67-75.e5. doi:10.1053/j.gastro.2013.09.046


64. So D, Loughman A, Staudacher HM. Am J Clin Nutr. 2022;116(4):943-952. doi:10.1093/ajcn/nqac176

Supporting Your Gut Health: The Essential Guide to Gut Supplements^‡

Written by Heidi Harris, RD-N, CD-N, LD-N

What You’ll Learn: We discuss the different nutrients and probiotics that build and promote a natural and healthy gut. In this blog, we will briefly outline the supplements needed to help support healthy GI function, microbiome health and the nutrients needed to support the mucosal lining of the G.I. tract.^‡

Have you ever wondered what natural steps you can take to help support your gut health? Gut health refers to the overall health of the digestive health system. The digestive system begins in the mouth and ends in the rectum. It includes organs such as the stomach, small intestine, large intestine and even the colon.¹ Gut health considers a healthy balance and diversity of bacteria and microorganisms that make up the microbiome. The microbiome helps aid the digestion of macronutrients such as carbohydrates, fats and proteins found in food and aids in the absorption of nutrients for use in the body.¹

Gut health isn’t just a passing trend. Gut health is essential to overall physical wellness because the gut plays a role in various bodily functions. From immune and skin health to gut signaling for mental health, a well-supported gut helps support your overall health.

Let’s dive deeper into this guide on essential nutrients to support your gut health.^1‡

PROBIOTICS FOR GUT HEALTH

We refer to living organisms such as bacteria, yeast, viruses, fungi, archaea and protozoa in the GI tract as the microbiome. To help support your gut health, you need to nourish healthy bacteria and keep them thriving.^2‡

A healthy microbiome balance in your gut is also important to support the immune system. Not to mention, the microbial balance is also susceptible to emotional and physical stress. The role of probiotics is to benefit and replenish the microbes typically found in your GI tract.^‡

Now, let’s discuss common types of bacterial probiotics and some key characteristics surrounding probiotics.²

LACTOBACILLUS

Lactobacillus is a group of rod-shaped, non-spore-forming bacteria. There are many different types of strains of Lactobacillus, such as the popular Lactobacillus acidophilus, which helps support the immune system and healthy bacterial strains in the GI tract.³ The Lactobacillus genus is also home to Lactobacillus salivarius, which has been found to help maintain healthy immune mediator balance.^{4, 5, 6} Lactobacillus is also home to my favorite strain, Lactobacillus rhamnosus, which supports healthy GI colonization, GI function and immune function with a special focus on skin and respiratory health.⁷ Our PureGG 25B provides 25 billion colony-forming units of Lactobacillus rhamnosus.^‡

WHAT ARE COLONY-FORMING UNITS?

Another aspect to consider when discovering which probiotics are helpful with gut health is how many colony-forming units are offered per serving. Colony-Forming Units (CFUs) are a unit of measurement that estimates the concentration of live microbial cells in a probiotic.⁸

BIFIDOBACTERIUM

Bifidobacterium is another type of beneficial probiotic. It is a genus or type of branched rod-shaped bacteria, and like Lactobacillus, there are multiple species and strains. Our Probiotic G.I. provides Bifidobacterium in the strains of Bifidobacterium bifidum and Bifidobacterium lactis. These beneficial microflora support the gut’s own immune system. The strains in this probiotic are also believed to help support barrier function, G.I. cell health and T cell function within the G.I. tract.^10‡

PREBIOTICS

Let’s switch gears and focus on prebiotics and their role in maintaining gut health. Prebiotics are essentially the healthy food source for probiotics. They are composed of food like complex carbohydrates and fibers. Prebiotics work to support the balance of microorganisms in the GI tract.^11‡

Prebiotics are non-digestible food components that modulate and support the gut microbiota. Research suggests that they play an even more significant role than probiotics, performing beneficial protective functions within the gut, leading to overall cellular, immune and metabolic support.¹¹ I mentioned Bifidobacterium a little earlier, but prebiotics promote Bifidobacterium (the predominant intestinal bacterial genus during the first year of life) and is associated with healthy immune development and cytokine balance in infants and later in life.^12‡

Pure Encapsulations® Poly-Prebiotic capsules provides the proprietary PreticX^TM and cranberry to help support microbiome and GI health. If you want a larger serving, we offer our Poly-Prebiotic Powder, which provides 4.6 grams of prebiotics to support microbiome diversity.^‡

POSTBIOTICS

We’ve discussed prebiotics and some specific probiotic strains. Now, let’s shift gears and discuss postbiotics. Postbiotics are bioactive compounds resulting from when probiotics feed on prebiotics.¹³ While postbiotics technically are considered microbial “waste” products, they offer many health benefits to support gut health.^‡

Some types of postbiotics include short-chain fatty acids, lipopolysaccharides and even some enzymes. Pure Encapsulations® offers the short-chain-fatty-acid butyric acid in our SunButyrate Liquid to promote gut barrier integrity, cytokine balance, abdominal comfort and even bowel motility. ^‡

GLUTAMINE AND GUT HEALTH

Another important concept to consider when discussing gut health is gut permeability, commonly called leaky gut. “Leaky gut” isn’t a recognized medical condition but rather a way to refer to increased gut permeability.¹⁴

The function of digestion ultimately relies on the GI tract being semi-permeable. It’s the responsibility of the mucosal lining of the intestines to absorb water and nutrients from our food and into our bloodstream. Gut permeability refers to the mucosal lining letting more than just water and nutrients through, meaning the gut lining “leaks.”^14‡

Maintaining a healthy mucosal lining is another way to help support your immune system. Our L-Glutamine provides glutamine, the most abundant amino acid in the body for tissue repair and GI support. Glutamine works by playing a large role in maintaining the intestine’s mucosal protective lining.^{15, 16, 17}

GUIDE TO GUT HEALTH SUPPLEMENTS

Pre and probiotics are significant in gut health, immunity support and bowel motility. What makes Pure Encapsulations® pre and probiotics different is that we provide scientifically backed strains for both general and specific health applications.^‡

REFERENCES

1. Smith, R. P. et al. (2019). Gut microbiome diversity is associated with sleep physiology in humans. PLoS ONE, 14(10). https://doi.org/10.1371/journal.pone.0222394


2. Digestive Health Team. (2018, November 9). How to Pick the Best Probiotic for You. Health Essentials from Cleveland Clinic; Health Essentials from Cleveland Clinic. https://health.clevelandclinic.org/how-to-pick-the-best-probiotic-for-you/


3. Rogers, K. (2019). Lactobacillus | bacteria | Britannica. In Encyclopedia Britannica. https://www.britannica.com/science/Lactobacillus


4. Foligne B, et al. World J Gastroenterol.2007 Jan 14; 13(2): 236(1)43.


5. Paineau D, et al. FEMS Immunol Med Microbiol.2008 Jun;53(1):107-13.


6. Claes IJ, et al. Mol Nutr Food Res.2011 Oct;55(10):1441-53.


7. Hojsak et al. Clin Nutr2010; 29, 312-6.


8. Hartline, R. (2022, January 15). 15: Determination of Bacterial Numbers. Biology LibreTexts. https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_Laboratory_Manual_(Hartline)


9. Seminario-Amez, M., Lopez-Lopez, J., Estrugo-Devesa, A., Ayuso-Montero, R., & Jane-Salas, E. (2017). Probiotics and oral health: A systematic review. Medicina Oral Patología Oral Y Cirugia Bucal, 22(3). https://doi.org/10.4317/medoral.21494


10. Iweala OI, Nagler CR. 2019 Apr 26;37:377-403.


11. Natalia S, et al. 2018 May; 10(5): 576.


12. Childs CE, et al. Br J Nutr.2014 Jun 14;111(11):1945-56.


13. Żółkiewicz, J., et al. (2020). Postbiotics—A Step Beyond Pre- and Probiotics. Nutrients, 12(8). https://doi.org/10.3390/nu12082189


14. Cleveland Clinic. (2022, April 6). Leaky gut syndrome. Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/22724-leaky-gut-syndrome


15. Sasaki E, et al. Luminescence. 2013 Jul-Aug;28(4):442-9.


16. Song QH, et al. Int J Clin Pharmacol Ther. 2015 May;53(5):372-6.


17. Lima AA, et al. Clinics (Sao Paulo). 2014;69(4):225-33.

"padding-right:16px">Heidi Harris, RD-N, CD-N, LD-N is a Registered Dietitian, Certified Group Exercise Instructor and Certified Strength Train Coach. She has a wealth of clinical knowledge in community management, social engagements, and nutritional science, and is here to help answer questions and educate you on the most up-to-date nutritional information.