aor digestive healthvol 4 issue 3

8/13/2019 Aor Digestive HealthVol 4 Issue 3

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VOLUME 4 ISSUE 3

Digestive Health What your gut is telling you

Health Problems ofDigestive OriginThe Digestive Connection toInammatory Bowel Disease,Acid Reux and Autism

Supplement Supportfor Digestive SystemProblemsBotanicals, Nutrients and Enzymes toSupport Healthy Digestive Function

vances

I N O R T H O M O L E C U L A R R E S E A R C H

RESEARCH-DRIVEN BOTANICAL INTEGRATIVE ORTHOMOLECULAR


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Advances in Orthomolecular Researchis published and distributed through integrativephysicians, health care practitioners, and progressivehealth ood retailers.

Te content o this magazine is provided orin ormational purposes only, and is not intendedas medical advice or individuals, which can onlybe provided by a healthcare pro essional. Contentsand design 2013 AOR. Any reproduction in whole

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Published in Canada by Advanced Orthomolecular Research Inc.

Publisher/Editor-in-Chief Jaime Tomas, BSc

Research & Writing Dr. raj Nibber, PHD Dr. Colin OBrien, ND Dr. Cameron McIntyre, ND

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Graphic Design/Art Production Neil Bromley

Alvin Cha email: [email protected]

Volume 4 Issue 3

Digital versions o this magazine and back issues areavailable online at www.AOR.ca ADVANCED

ORTHOMOLECULAR RESEARCH

4 Te Gut-Brain Connection8 Autoimmunity and the Gut: aking

a Closer look at the Immune SystemFunction and Celiac & IBD

11 Te Ups and Downs o Heartburn

14 Te World o Probiotics: Good Bugs vs.Bad Bugs

17 Botanical Supplement Support or theDigestive System

21 Nutrient Supplements or the Digestive System26 Te Breakdown on Digestive Enzymes

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4 Advances

Have you ever experienced butteries in the stomach be orean important meeting? Does attempting to cure the blueswith Ben and Jerrys sound amiliar? I so, then you are alreadyacquainted with the existence o a connection between ourmoods and our gut. Indeed, the brain and the digestivesystem are linked by complex pathways where in ormationows back and orth on a continual basis: certain eelings andthoughts can stimulate an exaggerated gut response, whilesensitized nerves in the gut can trigger changes in the brain.

Te Nervous System and the Second BrainTe nervous system is a complex network o nerves and cellsthat carry messages to and rom the brain and spinal cord to various parts o the body, through the relaying o in ormationby chemical messengers called neurotransmitters. Tehuman nervous system consists o two main parts: the centralnervous system (CNS) and the peripheral nervous system(PNS). Te brain and the spinal cord belong to the CNS,while the PNS consists mainly o nerves connecting the CNSto every other part o the body. Te PNS is comprised o thesomatic nervous system (SNS) and the autonomic nervous

system (ANS). Te enteric nervous system (ENS) is a semi-independent part o the ANS whose unction is to control thegastrointestinal (GI) system.

Te ENS comes complete with a network o more than100 million neurons, neurotransmitters and proteins,combined with a complex neuronal circuitry that enablesit to control the bowel and produce gut eelings separate

rom the brains impulses. In each situation, the gut mustassess conditions such as: progress o digestion, presence o

nutrients and acidity level, among others and then decide ona course o action and initiate a reex. Tis amazing piece owork continues to unction even when the vagus nerve - theprimary neural conduit between the gut and the brain - issevered!1 Its location in the GI tract, right next to the systemsthat it controls, makes per ect sense rom an evolutionarystandpoint.

Te ENS was rst described by Dr. John Newport Langleyin 1921 and it was coined the second brain by Dr. MichaelD. Gershon in 1996 in re erence to the complexity o its

unctions. When Gershon, who has been called the ather

The Gut-Brain Connection

Health Problems of Digestive Origin


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o neurogastroenterology, suggestedthat the gut might in act be using someo the same neurotransmitters as thebrain, his theory was widely ridiculed.Since the early 80s however, theconcept o the enteric nervous systemand the role o neurotransmitters in thegut have been accepted by the scienticcommunity. Te connection betweenthe two brains is accountable or thedirect relationship between emotionalstress and physical distress. It explainswhy conditions such as anxiety,depression, irritable bowel syndrome,ulcers and Parkinsons disease mani estsymptoms both at the brain and at thegut level.Psychology or Physiology, Which OneComes First?

Psychology clearly plays an importantrole in gut disorders. According to Dr.Emeran Mayer, pro essor o medicine,physiology and psychiatry at U.C.L.A.,the majority o patients with anxietyand depression present alterationso their GI unction. Dr. Mayer alsoreports that up to 70 percent o thepatients he treats or chronic gut disorders had experiencedearly childhood traumas. Tis observation is corroboratedby recent studies in animal models which demonstrate thatearly li e stress is associated with chronic GI diseases.

Stress affects the gut in several ways. In response to aperceived stressor, the brain triggers a response along twomajor bodily paths: the hypothalamic-pituatary-adrenal axisand the autonomic nervous system. Te resulting increasedsecretion o cortisol, adrenaline and noradrenaline directlyaffects the ENS. Corticotropin-releasing- actor (CRF), apeptide ound in both the brain and the gut, is anothersubstance which appears to have major signicance inthe stress response. CRF increases anxiety-like behavior,abdominal pain, colon secretions, muscle contractions(motility) and increased permeability within the liningo the bowel. CRF also stimulates a type o immune cellcalled mast cells. Another interesting experiment on rodents

demonstrates what most clinicians have already observed,namely the correlation between stress and a leaky gut. Testudy showed that when young rats were separated romtheir mothers, the layer o cells lining their gut weakened andbecame more permeable, allowing bacteria rom the intestineto pass through the bowel walls and stimulate immune cells.

On the ip side, several actors lend credence to physiologyas the source o intestinal dys unctions. For example, whenthe mast cells activate an immune response resultingin mucosal inammation, the release o inammatorycytokines - tumour necrosis actor ( NF-), interleukin

(IL)-1, and IL-6 - generates an acute stimulation o thehypothalamic-pituitary-adrenal (HPA) axis. In otherwords, GI inammation triggers an increased ring o theguts sensory neurons, culminating in a kind o sensoryhyperactivity. Serotonin provides another interestingargument supporting the gut-over-brain theory. Tis keyneurotransmitter essential to our well-being is stored at 95percent in the ENS where it is synthesized. Among otherthings, serotonin acts as a go-between, keeping the brain upto date with what is happening in the gut. Contrary to earlierassumptions, it has been ound that 90 percent o the bers inthe vagus nerve carry in ormation rom the gut to the brain,and not the other way around. Finally, the emerging conceptthat bacteria teeming in the gut - collectively known as themicrobiome - can affect not only the gut but also the mind,may shed additional light on our understanding o the gut-brain axis.

Commensal Gut MicrobiotaWe are all born with a sterile gut, but over time it getscolonized by a diverse and distinct brew o bacterial speciesdetermined by genetics and by bacteria surrounding us. Teincredible 100 trillion microbes - more than ten times theamount o cells in our entire body! - that make the GI tracttheir playground, are absolutely critical to our health. Overthe last ew years, increasing evidence rom studies in rodentsare pointing to an effect o commensal gut microbiota onthe CNS. Researchers have ound that the gut microbiomecan inuence neural development, brain chemistry, and a

Lifeevents

StressExteroceptive

Autonomicresponse

Sensorymodulation

Neuroendocrineresponse

GI pathopsychologysymptoms

StressInteroceptiveEMS

Vigilancearousal

Emotionalfeelings

Figure 1. Emotional Motor System (EMS) Pathways (Adapted From: Mayer, EA. 2000.)


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wide range o behavioral phenomenaincluding emotional behavior, painperception and the stress response.

In a 2011 study, Bienenstock andcolleagues ed a broth enhanced withthe probiotic Lactobacillus rhamnosus to a group o mice, and plain broth tothe control group. Afer 28 days, theresearchers subjected the mice to abattery o tests to detect signs o anxietyand depression. What they discoveredis that mice who had been ed theprobiotic solution demonstrated less

ear-response behaviors and anxietycompared to the control group. In themice that were ed L. rhamnosus, somebrain regions showed an increase in

the number o receptors or gamma-aminobutyric acid (GABA), the mainCNS inhibitory neurotransmitter.Alterations in central GABA receptorexpression are implicated in thepathogenesis o anxiety and depression,which are highly comorbid with

unctional bowel disorders. Probiotic-ed mice also produced lower levels o

the stress hormone corticosterone thancontrol mice. Interestingly, when the

vagus nerve was severed, the effectso gut bacteria on brain biochemistry,stress response and behavior evaporated.Te researchers concluded that thesendings highlight the importantrole o bacteria in the bidirectionalcommunication o the gut-brain axisand suggest that certain organisms mayprove to be use ul therapeutic adjunctsin stress-related disorders such asanxiety and depression.

In another study, Bercik andcolleagues investigated the role oBidobacterium longum in temperinganxiety and depression related to GIdisorders. 16 Tey rst in ected micewith the parasite richuris muris , which

caused moderate gut inammationand anxiety-like behavior linkedto decreased hippocampal brain-derived neurotrophic actor (BDNF).Lower hippocampal BDNF has beenassociated with anxiety and depressivebehavior. Te administration o theprobiotic ( B. longum) normalized bothbehavior and BDNF level. Tis resultdemonstrates that a member o theintestinal microbiota may affect the

brain biochemistry and behavior inadult mice.

Some studies also suggest thatgut bacteria are closely tied to earlybrain development and subsequentbehavior. According to Dr. RochellysDiaz Heijtz, a researcher specializedin the neurobiology o commonneurodevelopmental psychiatricdisorders such as Attention-Decit/Hyperactivity Disorder (ADHD) andautism: Te data suggests that there isa critical period early in li e when gutmicroorganisms affect the brain andchange the behavior in later li e.Could Autism Begin in the Gut?Many researchers around the world

have accumulated compelling evidenceo a link between brain disorders such asAutism Spectrum Disorders (ASDs) andGI dys unctions. Valicenti-McDermottand his colleagues demonstrated that70% o the children with ASDs haveGI issues. Adams and his team noticedthat gastrointestinal symptoms arestrongly correlated with the severityo autism. Certain people with ASDsalso have abnormal levels o exorphins,

Healthy Status

Healthy CNSfunction

Alterations inbehaviour, cognition,emotion, nociception

Abnormal gutfunction

Increased levels of inammatory cells/mediators

Intestinal dysbiosis

Normal gutphysiology

Physiological levels of inammatory cells/mediators

Normal gut microbiota

Stress/Disease

Gut and Brain Function in States of Health and Disease


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dietary peptides derived rom certaingrains (gluteomorphin) and dairyproducts (caseomorphins). Exorphinshave morphine-like opioid activityand can act like narcotics in the body.In a study published last year, Reicheltand his colleagues suggest that autismis based in a genetic polymorphismerror o peptide digestion - perhapso the enzyme diaminopeptidase IV(DPP-IV) - and that the brain stimulantactivity o the resulting exorphins canexplain most autism symptomatology.A recent meta-analysis conrms thata gluten and casein ree (GFCF) diet

can ameliorate core and peripheralsymptoms and improve developmentaloutcome in some cases o autismspectrum conditions. Tis conclusionis corroborated by many parentsreporting signicant improvementsin their childrens health and behaviorwhen they removed these substances

rom their diets.Happy Gut, Happy MindGiven the intimate eedback loopbetween the gut and the brain, we mustconsider addressing GI dys unctionswhen treating mood imbalances andbehavioral or developmental issues.

Te use o high quality probioticsincluding Lactobacillus rhamnosusand Bidobacterium longum alongwith digestive support such as DPP-IVenzyme and L-glutamine are provenstrategies. Restoring mood balanceis also crucial in achieving GI health.Adaptogenic herbs including as Siberianginseng, ashwagandha, Rhodiola orholy basil combined with adrenal tissueextracts can support a healthy stressresponse, while substances such asGABA, L-theanine, inositol, SAMe andB complex vitamins can help achieve abalanced mood.

References1. Gershon MD. Te Second Brain: Te Scientic Basis o Gut Instinct and a Groundbreaking New Understanding o Nervous Disorders o the

Stomach and Intestines. HarperCollins Publishers, Inc., New York, NY; 1998.

2. Rubin RP. A Brie History o Great Discoveries in Pharmacology: In Celebration o the Centennial Anniversary o the Founding o the AmericanSociety o Pharmacology and Experimental Terapeutics. Pharmacological Reviews. 2007; 59: 289-359.

3. American Association o Anatomists. Available at: http://www.anatomy.org/content/michael-gershon Accessibility veried February 20th,2012.

4. Mayer EA, Naliboff BD, Santo V, et al. Stress and the Gastrointestinal ract. V. Stress and irritable bowel syndrome. AJP GI. 2000; 280:G519-G524.

5. Brad ord K, Elizabeth J, Presson AP, et al. Association between early adverse li e events and irritable bowel syndrome. Clinical gastroenterologyand hepatology: the official clinical practice journal o the American Gastroenterological Association. 2012; 10(4): 385-390.

6. Mayer EA. Te neurobiology o stress and gastrointestinal disease. Gut. 2000;47:861-8697. Martinez V, ach Y. Corticotropin-releasing actor and the brain-gut motor response to stress. Can J Gastroenterol. 1999;13 Suppl A:18A-25A.8. Mayer EA., Saper CB, Ladd CO, et al. Long-term behavioral and neuroendocrine adaptations to adverse early experience. in Te biological

basis or mind body interactions. 2000; 122: 79101.9. Malaviya R, Abraham SN. Mast cell modulation o immune responses to bacteria. Immunol. Rev. 2001; 179: 16 24.

10. Teoharis C, Teoharidesa BC, David E. Critical role o mast cells in inammatory diseases and the effect o acute stress. Journal oNeuroimmunology. 2004; 146:1 1211. Perlstein RS, Whitnall MH, Abrams JS, et al. Synergistic roles o interleukin-6, interleukin-1, and tumor necrosis actor in adrenocorticotropin

response to bacterial lipopolysaccharide in vivo. Endocrinology. 1993; 132:946952.12. Drey us CF, Bornstein M B, Gershon MD. Synthesis o serotonin by neurons o the myenteric plexus in situ and in organotypic tissue culture.

Brain Research. 1977;128:12513913. Gershon MD. Te Second Brain: Te Scientic Basis o Gut Instinct and a Groundbreaking New Understanding o Nervous Disorders o the

Stomach and Intestines. 199814. Bravo JA, Forsythe P, Chew MV, et al. Ingestion o Lactobacillus strain regulates emotional behavior and central GABA receptor expression in

a mouse via the vagus nerve. Proc Natl Acad Sci U S A. 2011; 108:16050-160505.15. Harter MC, Conway KP, Merikangas KR. Associations between anxiety disorders and physical illness. Eur Arch Psychiatry Clin Neurosci.

2003;253:313320.16. Bercik, P., Verdu, E.F., Foster J.A., Macri, J., Potter M., Huang, X., Malinowski, P., Jackson, W., et al. Chronic Gastrointestinal Inammation

Induces Anxiety-Like Behavior and Alters Central Nervous System Biochemistry in Mice. Gastroenterology. 2010 Dec;139(6):2102-211217. Martinowich K, Manji H, Lu B. New insights into BDNF unction in depression and anxiety. Nat Neurosci 2007;10:10891093.18. Hejtz R.D, Wang S, Anuar F, et al. Te normal gut microbiota modulates brain development and behavior. Proceedings o the National

Academy o Sciences o the USA. 2011; 108: 3047-3052.19. Valicenti-McDermott M., McVicar K, Rapin I, et al. Frequency o gastrointestinal symptoms in children with autistic spectrum disorders and

association with amily history o autoimmune disease. J Dev Behav Pediatr. 2006; 27:S128-36.20. Adams JB, Johansen LJ, Powell LD, et al. Gastrointestinal ora and gastrointestinal status in children with autism -- comparisons to typical

children and correlation with autism severity. BMC Gastroenterol. 2011; 11: 22.21.Reichelt, KL, veiten D, Knivsberg A. et al. Peptides role in autism with emphasis on exorphins. Microbial Ecology in Health & Disease. 2012:2322. Whiteley P, Shattock P, Knivsberg AM, et al. Gluten and casein- ree dietary intervention or autism spectrum conditions. Front Hum Neurosci.

2012; 6:344.


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Integrity of the GutTe intestines are the largest mucosalinter ace between the environmentand us. A single layer o epithelial cellsis all that separates the bloodstreamand the contents o the intestines.Te small intestine has the complexand crucial role o allowing nutrientsinside the body while keeping bacteria,toxins, and wastes outside. Te tight

junctions separating the intestinalcells assume some o these unctions.Te tight junctions arent cementedas previously thought but are ratherdynamic structures.

Research has revealed that tight junctions are made up o a complexmeshwork o proteins, the interactiono which dictates their competency. odate, multiple proteins that make up

the tight junction strands have beenidentied: occludin, 1 members o theclaudin amily,2 and the junctionaladhesion molecule (JAM), a proteinbelonging to the immunoglobulinsuper amily which has been describedas an additional component o tight junction brils. 3 o meet the manydiverse physiological challenges towhich the intestinal epithelial barrieris subjected, tight junctions mustbe capable o rapid and coordinatedresponses that are involved indevelopmental, physiological, andpathological processes. o achievesuch responses, a complex regulatorysystem orchestrates the assembly anddisassembly o the multiprotein tight junction network.

Compromised tight junctions causeincreased intestinal permeability,commonly re erred to as leaky gut,and can result in the absorptiono incompletely digested proteinsand antigens that overstimulatethe immune system through thebloodstream. Emerging research showsthat most autoimmune conditionsmay share a common root hiding inthe intestinal linings o individualswith autoimmune diseases, even yearsbe ore the symptoms mani est.Te Development of Celiac DiseaseCeliac is an autoimmune disordero the small intestine that occurs ingenetically predisposed people o allages rom middle in ancy onward.Symptoms can include chronicdiarrhea, ailure to thrive (in children),and atigue but even these may beabsent, and symptoms in other organsystems could occur.

Increasingly, diagnoses are beingmade in asymptomatic persons as

a result o increased screening;4

the condition is thought to affectsomewhere between 1 in 1,750 and1 in 105 people in the United States. 5

An immune reaction to a main proteincomponent o gluten, gliadin, ound inwheat, and similar proteins ound in

riticeae crops (which includes othercommon grains such as barley andrye) can trigger the development oCeliac disease.6

Autoimmunity and the Gut:Taking a Closer Look at Immune SystemFunction and Celiac & IBD


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Upon exposure to gliadin, andspecically to three peptides oundin gluten proteins (also known asprolamins), the enzyme known as tissuetransglutaminase modies the protein,and the immune system cross-reactswith the small bowel tissue, causingan inammatory reaction. Tat leadsto destruction o the villi lining thesmall intestine (called villous atrophy).Tis inter eres with the absorption onutrients, because the intestinal villiare responsible or absorption. Tesimple effective treatment is a li elonggluten- ree diet.6 While the disease iscaused by a reaction to wheat proteins,it is not the same as wheat allergy.

Early in the development o celiacdisease, tight junctions are opened, 7,8

most likely secondary to zonulinupregulation, 9 and severe intestinaldamage ensues. 8 Zonulin is normallypresent in the intestines to control thepassage o uids, macromolecules, andleukocytes, but this protein appearsto be overexpressed in patients withautoimmune conditions, resulting inincreased intestinal permeability. Teupregulation o the zonulin innateimmunity pathway is directly inducedby exposure to the diseases antigenictrigger, gliadin. 10 Gliadin has also beenshown to be a potent stimulus ormacrophage proinammatory geneexpression and or cytokine release.11

Once gluten is removed rom thediet, serum zonulin levels decrease, theintestine resumes its baseline barrier

unction, auto antibody responses arenormalized, the autoimmune processshuts off and, consequently, theintestinal damage (which representsthe biological outcome o theautoimmune process) heals.

Te Autoimmune riadAlessio Fasano, MD, a pediatricgastroenterologist, research scientist,and ounder o the University oMaryland Center or Celiac Research,believes all autoimmune conditionshave three actors in common: a geneticsusceptibility, antigen exposure, andincreased intestinal permeability. 12 Besides celiac disease, several otherautoimmune diseases, including type

1 diabetes, multiple sclerosis, andrheumatoid arthritis, are characterizedby increased intestinal permeabilitysecondary to non-competent tight junctions that allow the passage oantigens rom the intestinal ora,challenging the immune system toproduce an immune response thatcan target any organ or tissue ingenetically predisposed individuals,Fasano wrote in the February 2012issue o Clinical Reviews in Allergyand Immunology. 12

While it was previously believed thatthe autoimmune process remainedongoing once activated, this recentevidence indicates that the processcould be modulated and possibly

reversed by interrupting one o themodiable actors involved in theautoimmune triad.SIBO as a Contributor toInammation

Small intestinal bacterialovergrowth (SIBO) has recently beenrecognized as an underlying cause omany cases o inammatory boweldisease (IBD), clinical relapses oCrohns disease, and celiac patients

unresponsive to a gluten- ree diet. 13-15 SIBO is a chronic in ection o the smallintestine, resulting in the excessive

ermentation o dietary carbohydratesand the accompanying atulence,bloating, abdominal pain, diarrhea,and constipation.

SIBO and autoimmunity are relatedin several ways. SIBO is commonin many autoimmune diseases suchas: IBD, scleroderma, celiac disease,and Hashimotos hypothyroidism,although the exact nature o theseassociations isnt ully known.

Increased intestinal permeability,which has been demonstrated in SIBO,is one o the three underlying causeso autoimmunity, as demonstrated

by Fasano and his team, alongwith an environmental trigger andgenetic predisposition. SIBO, withits high likelihood o generatingleaky gut, needs to be corrected

or both prevention and treatmento autoimmunity. SIBO can besuccess ully treated with antibioticsand possibly by natural means andspecic dietary protocols. Ri aximinand neomycin usually are pre erred

Dysfunctional Tight Junctions in Celiac Disease

Leaky Gut/Permeable IntestineIn a healthy intestine, links known

as tight junctions hold the intestinalcells together to prevent unusualpermeability. In persons with celiacdisease, these junctions are nottight and come apart; this allowsindigestible gluten particles to moveinto the underlying tissues andcause an inammatory response.Reducing the leakiness between thesetight junctions will potentially easeautoimmune conditions includingceliac disease.

Indigestibleglutenfragment

Enterocyte

Tight junction


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because their poor absorbabilityinto the bloodstream maximizestheir efficacy within the digestivetract while minimizing systemic sideeffects. Elemental diet ormulas which

are special nutrient drinks that donot contain whole oods, can provideall energy requirements or a periodo two to three weeks and is also analternative treatment option.

In summary, the classical paradigmo autoimmune pathogenesisinvolving a speci ic genetic makeupand exposure to environmentaltriggers has been challenged by theaddition o a third element: the losso intestinal barrier unction. Geneticpredisposition, miscommunicationbetween innate and adaptive immunity,exposure to environmental triggers,and loss o the intestinal barrier

unction secondary to dys unction ointercellular tight junctions, seem toall be key ingredients involved in thepathogenesis o autoimmune diseases.

his new theory implies that, oncethe autoimmune process is activated,it is not sel -perpetuating; rather, itcan be modulated or even reversed by

preventing the continuous interplaybetween genes and environment. Astight junction dys unction allowsthis interaction, new therapeuticstrategies including the use o dietarysupplements aimed at re-establishingthe intestinal barrier unctiono er innovative approaches orthe treatment o these devastatingdiseases.

References1. Furuse M, Hirase , Itoh M et al. Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol. 1993;123: 17771788.2. Furuse M, Fujita K, akashi H et al. Claudin-1 and -2: Novel integral membrane proteins localizing at tight junctions with no sequence

similarity to Occludin. J Cell Biol. 1998;141:15391550 .3. Martin-Padura I, Lostaglio S, Schneemann M et al. Junctional Adhesion Molecule, a novel member o the Immunoglobulin super amily that

distributes at intercellular junctions and modulates monocyte transmigration. J Cell Biol. 1998; 142: 117127.4. Van Heel D, West J. Recent advances in coeliac disease. Gut. 2006; 55 (7):103746.5. Rewers M. Epidemiology o celiac disease: what are the prevalence, incidence, and progression o celiac disease? NIH Consensus Development

Con erence on Celiac Disease. 2005; 128 (4 Suppl 1):S4751.6. Di Sabatino A, Corazza GR. Coeliac disease. Lancet. 2009; 373 (9673):148093.7. Madara JL, rier JS. Structural abnormalities o jejunal epithelial cell membranes in celiac sprue. Lab Invest. 1980;43: 254261.8. Schulzke JD, Bentzel CJ, Schulzke I et al. Epithelial tight junction structure in the jejunum o children with acute and treated celiac sprue.

Pediatric Research. 1998; 43:435441.9. Fasano A, Not , Wang W. et al. Zonulin, a newly discovered modulator o intestinal permeability, and its expression in coeliac disease. Lancet.

2000;355:15181519.10. Clemente MG, S De Virgiliis, J S Kang et al. Early effects o gliadin on enterocyte intracellular signalling involved in intestinal barrier unction.

Gut. 2003;52:218223.11. Nikulina M Habich C, Flohe SB et al. Wheat gluten causes dendritic cell maturation and chemokine secretion. J Immunol. 2004;173:19251933.12. Fasano A. Leaky gut and autoimmune diseases. Clinic Rev Allerg Immunol. 2012;42(1):71-78.13. Pimentel M, Chow EJ, Lin HC. Normalization o lactulose breath testing correlated with symptom improvement in irritable bowel syndrome: a

double-blind, randomized, placebo-controlled study. Am J Gastroenterol. 2003;98(2):412-419.14. Klaus J, Spaniol U, Adler G et al. Small intestinal bacterial overgrowth mimicking acute are as a pit all in patients with Crohns Disease. BMC

Gastroenterol. 2009;9:61.15. ursi A, Brandimarte G, Giorgetti G. High prevalence o small intestinal bacterial overgrowth in celiac patients with persistence o gastrointestinal

symptoms afer gluten withdrawal. Am J Gastroenterol. 2003;98(4):839-843.

1. Tight junctions are loosened when undigested gluten fragments induce the intestinal absorptive cells (enterocytes) torelease the protein zonulin. 2. Numerous gluten fragments accumulate beneath the intestinal absorptive cells after theycross the intestinal lining. 3. Immune cells called intraepithelial lymphocytes attack the intestinal absorptive cells as aresult of gluten causing them to secrete interleukin-15.

Indigestibleglutenfragments

Glutenfragments

Zonulin

Tight junction

Damaged area

Gluten inducesenterocytes

Disrupted junction

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bacteria (Helicobacter pylori) or drugs(non-steroidal anti-inammatorydrugs, NSAIDs). Tey are also used topromote healing in erosive esophagitis.

Common side effects rom thesemedications: Some o the common sideeffects o using these medications caninclude constipation, diarrhea, nausea,abdominal pain, dizziness, drowsiness,headache, runny nose, sore throat, rashand weakness.Heliobacter pylori (H. pylori) andGERD A Confusing IssueH. pylori (Camphylobacter) is a gram-negative bacterium ound in the

stomach. It is requently observed inpatients with chronic gastritis andgastric ulcers, conditions that werenot previously believed to have amicrobial cause. It is also linked tothe development o duodenal ulcersand stomach cancer. However, over 80percent o individuals in ected with thebacterium may be asymptomatic.

Te relation between H. pylori in ection and gastro-oesophageal reux

disease is controversial. Studies onthe prevalence o H. pylori in patientswith gastro-oesophageal reux diseasehave given conicting results. Recentguidelines recommend eradication oH. pylori in patients requiring long termproton pump inhibitors, essentially orreux disease.

In a systematic review o 20 GERDstudies, the prevalence o H. pyloriin ection was signicantly lower inpatients with GERD, than without.However, geographical location was astrong contributor to the differencesbetween studies. Patients rom the

Far East with reux disease had alower prevalence o H. pylori in ectionthan patients rom Western Europeand North America, despite a higherprevalence in the general population.What About Other Natural GERD

reatment Options?De-Glycyrrhized Licorice (DGL): Mostpeople dont get ulcers because o oversecretion o acid. Te cause in manycases is a breakdown in the integrity

o the intestinal lining. While commondrugs including antacid medicationscan block symptoms and promotetemporary healing, they dont addressthe underlying cause. DGL addressesthe underlying actors to help promotetrue healing. Rather than inhibit therelease o acid, licorice stimulatesthe normal de ense mechanisms thatprevent ulcer ormation. Specically,avonoids present in DGL inhibit thegrowth o H. pylori (in vitro), whilethe whole extract improves boththe quantity and the quality o theprotective substances which line the

intestinal tract, increases the li e spano intestinal cells, and improves bloodsupply to the intestinal lining.

Mastic Gum: has been shown to wipeout H. pylori bacteria, the cause behindthe majority o gastric and duodenalulcers. Clinical studies have clearlyshown the effectiveness o this resinwith 80% o patients receiving masticgum or two weeks reporting signicantimprovements in their symptoms.

12 Advances

Stomach

Relaxed loweresophageal

sphincter

Inamedesophagus

Acidreux

Esophagus

Figure 1. Acid Reux (Retrieved From: www.mayoclinic.com)


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Zinc-Carnosine: has received muchattention lately thanks to its ability toup-regulate key antioxidant enzymesthereby preventing ree radicals romdamaging cells. Studies have conrmedthat Zinc-Carnosine has antiulcerproperties and prevents gastric mucosalinjury. Animal studies also show thatZinc-Carnosine is indicated in H. pylori in ections as the molecule preventsthe development o H. pylori relatedgastritis.

Potassium Nitrate: is a precursor toNitric oxide. Nitric oxide is a potent vasodilator and increases blood owto the gastric mucosa, enhancingrepair and the inow o nutrients andoxygen. Higher nitric oxide levels in thestomach were also shown to increase

effective peristalsis movements. Studiesalso clearly demonstrate that Nitricoxide precursors are effective anti-inammatory agents with protectiveeffects against gastritis.

Alginic acid: a viscous substanceound in algae which absorbs water

extremely quickly to orm a raf ontop o the gastric contents. Tis rafhas two effects: it prevents the gastriccontents rom being pushed back up theesophagus and also coats the esophagusi the gastric contents were to reach

the esophagus. An added bonus is thatalginic acid works extremely quicklyproviding relie within a ew minutes.

Many o the previously mentionedingredients are ound in Gastro Relie(an AOR ormula). Te premise behindGastro Relie is to provide quick andeffective relie rom the symptomso heartburn while addressing any

undamental pathology which wouldcause the problem.

Heartburn is a very commoncondition that needs quick attention.Ignoring symptoms can lead to long termcomplications. Standard medicationsmay be help ul but may not address theunderlying causes, and long term usemay result in undesirable side effects.Natural treatments as outlined above canbe very effective or many individualsand should be seriously considered as anoption or rst line treatment.

References1. Brogden RN, Speight M, Avery GS. Deglycyrrhizinised liquorice: a report o its pharmacological properties and therapeutic efficacy in peptic ulcer.

Drugs. 1974; 8(5): 330-9.2. Al-Habbal MJ, Al-Habbal Z, Huwez FU. A double-blind controlled clinical trial o mastic and placebo in the treatment o duodenal ulcer. Clin Exp

Pharmacol Physiol. 1984; 11(5): 541-4.3. Huwez FU, Tirlwell D, Cockayne A, et al. Mastic gum kills Helicobacter pylori. N Engl J Med. 1998; 339(26): 1946.4. Larauche M, Anton PM, Garcia-Villar R, et al. Protective effect o dietary nitrate on experimental gastritis in rats. Br J Nutr. 2003; 89(6):777-86 5. Mandel KG, Daggy BP, Brodie DA, et al. Review article: alginate-raf ormulations in the treatment o heartburn and acid reux. Aliment Pharmacol

Ter. 2000;14(6):669-90.6. Marone P, Bono L, Leone E,et al. Bactericidal activity o Pistacia lentiscus mastic gum against Helicobacter pylori. J Chemother. 2001; 13(6): 611-4.7. Matsuu-Matsuyama M, Shichijo K, et al. Protection by polaprezinc against radiation-induced apoptosis in rat jejunal crypt cells. J Radiat Res ( okyo).

2008; 49(4):341-7.8. Strugala V, Avis J, Jolliffe IG, et al. Te role o an alginate suspension on pepsin and bile acids key aggressors in the gastric reuxate. Does this have

implications or the treatment o gastro-oesophageal reux disease? J Pharm Pharmacol. 2009; 61(8):1021-8.9. Ueda K, Ueyama , Oka M, et al. (Zinc L-carnosine) is a potent inducer o anti-oxidative stress enzyme, heme oxygenase (HO)-1 a new mechanism

o gastric mucosal protection. J Pharmacol Sci. 2009; (3):285-9410. Blaser MJ. Who are we? Indigenous microbes and the ecology o human diseases. EMBO Reports. 2006; 7 (10): 95660.11. Kahrilas PJ. Gastroesophageal reux disease. New England Journal o Medicine. 2008; 359(16): 1700-1707.12. Canadian Digestive Health Foundation. Statistics. Available at: http://www.cdh .ca/digestive-disorders/statistics.shtml#gerd. Accessiblity veried

February 27, 2013.13. Mayo Clinic. GERD. Available at: http://www.mayoclinic.com/health/gerd/DS00967. Accessiblity veried February 27, 2013.


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Te original denition o probiotics was established in 1953 butwas somewhat con using. oday, probiotics simply mean livemicroorganisms which when reaching the intestines in largenumbers will exert positive health effects. Probiotic literallymeans pro-li e or health promoting organisms. Tere aretrillions o bacteria that have set up shop in our intestines (bothsmall and large) and represent a very large and diverse group.Not all o these are riendly; there are a signicant number thatare hostile such as E. coli or Salmonella or Cryptosporidiumthat causes ood and water poisoning, but overwhelminglymost are riendly.Te Vast Microbiota

Most o us know some o the more popular ones like theacidophilus or Bidobacterium species that we read on the oodlabels in the supermarkets. Tere is however, no such speciesas Lactobacillus acidophilus regularis that the Danish ood giantDanone claims is present in their Activia yougurt. Still, out othe hundreds o kingdoms o strains, there are only our majorgroups which predominate. Tis reects the difficult natureo the conditions in which they must be able to survive, andequally important, the adaptive mechanisms developed by thebugs to survive. Tis is signicant as not every bacteria cansurvive or colonize. Tese bugs are collectively re erred to as

the microbiota, and represent a reserve pool o several milliongenes, in contrast to the twenty three thousand that human cellscollectively provide. Biologists are ond o viewing organisms aspart o an ecosystem which includes ALL other organisms, theirhabitats, ood sources, competitors and so on. Likewise, the bestway to view these organisms (largely bacteria) is as colonists oour gastrointestinal tract (GI ) orming a complete ecosystem.

Each o the bacteria is an individual in its own right; itcompetes or ood and seeks shelter and space with everyother organism whether it is a riend or oe. Te GI is a battlezone, and its a bug-eat-bug world in there. Furthermore, theorganisms communicate with each other as well as the host

cells (which they easily outnumber by a actor o ten or more)by means o various cellular signaling systems. Tis cellularchatter or cross-talk occurs day and night, and is responsible

or sensing any changes and danger, so as to allow the bugs torespond appropriately.

Our evolutionary system unctions in a manner whichtakes into account the interests o both the host (us) and thebugs, with neither wishing the other any harm. In bad timeshowever, or example, during periods o stress, poor diet,inappropriate li estyle, indiscriminate use o antibiotics andother pharmaceuticals, exposure to environmental toxins etc.,

The World of ProbioticsUnderstanding Different Strains of Bacteria, Symbiosis,Many Probiotics Dont Work

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the alignment o interest breaks downand our allies begin to misbehave so as tocause disease. Te nature and the rangeo diseases affected by our gut ora isdiverse, rom obesity, cancer, allergies,diabetes, and a host o inammatoryconditions such as rheumatoid arthritisand other autoimmune conditions, todisorders like autism.

What we tend to orget is that themicrobial ecosystem is quite uniqueand different among people. No twodigestive systems are the same. Not onlyare the inhabitants somewhat different,so are the unctions these bugs per orm.Because the microbes carry such a largearray o genes with them, they are able tocarry out many more biological unctionsthan what the human genome allows.

For example, many nutrients like milk orthe plant based bers that we consume may not be effectivelybroken down by our enzymes present in our digestive juices.However, the microbes have no such issues as they have sucha large repertoire o genes that can per orm ar more tasks.Likewise, in certain populations, or example in Venezuelans,the microbes allow synthesis o certain vitamins like vitamin B2to a much greater extent than in a Canadian.Microbes in Health and DiseaseClearly, the microbes play an important part in disease interms o both prevention and as a causative actor. Microbesproduce chemicals called bacteriocins that can inhibit othernasty bacteria (pathogens). But equally likely, bacteria can anddo cause ood poisoning, diarrhea, bloating and many otherproblematic conditions including peptic ulcers, inammationo the gut, and even cancer.

Te benets o probiotics have long been recognized; theEgyptians, Greeks, Romans and subsequent cultures (punintended) consumed oods treated with bacteria. Tis is thebasis o ermentation techniques, which means letting thebacteria mellow the ood e.g. cabbage, meats, milk, soy, vinegar, etc. Tese early ood scientists realized that the bacteriawas digesting the ood and allowing or better availability onutrients or our bodies. O course one o the best examples isthe yogurt made amous by the residents o the Caucuses and

Bulgaria.Te role that the bacteria in our gut play in health anddisease is becoming more and more recognized and acceptedby researchers worldwide. For example, some elaborateexperiments by Pro essor Jeffery Gordon rom WashingtonUniversity in St. Louis have shown that thin individuals havedifferent bacterial mixes than obese populations. 1 Interestingly,when individuals changed their diets and lost weight, their gutbacterial ecosystem changed accordingly and was similar tothin individuals. 2 Tis is a signicant nding that suggests ithe bacterial mix present in thin individuals is given to obese

individuals, then obese people may lose weight! In act Gordonhas demonstrated this very point in animals. 3

Te Japanese are world leaders in probiotic and ermentationresearch. Tey were the rst to study the health benets o various probiotics or ood supplementation back in the 1930s.Unlike the North American consumer mindset which has beenlargely brainwashed by industry to ocus on the number and thedifferent strains o bacteria present in the probiotic supplement,Japanese companies place greater emphasis on the specics othe strains and how well researched these strains are in humanclinical studies; this is a very important point discussed later.Not many strains have relevant human data; in act, over95% o the products on the North American market have noclinical data and only promote test tube data. est tube data issomewhat unreliable in regards to extrapolating how these bugsbehave in our complex gastrointestinal ecosystem. Nonetheless,most companies keep stressing the numbers game instead othe actual species and the strains present.

What should the consumer look or in terms o selecting theright probiotic supplement?

Te answer in rst, second and third place is, Show me theclinical research; Im not interested in test tube data or animalstudies. Rather, I want to see human data. One will nd thatthere is a sparse amount o human data. Te most likely answer

seems to be, Every other company is offering these strains, andthese strains have been used or so long in oods so they must beeffective, or, We have a study that ten individuals used it andtheir diarrhea improved or their immune system was boosted.Un ortunately, these arent very convincing answers, and onesmall human study does not make or a convincing statement.In act, one needs a number o studies to be conducted to provethe point that the probiotic is indeed benecial. Moreover, oneneeds studies with much greater numbers o participants. Mostbiostaticians (people that determine whether a study has anystatistical power and thus i it is o any signicance) will tell you

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that most o these studies prove nothing.No wonder these studies are dismissedby serious researchers. However, thereare companies that have researched theright mix o bacteria, using much largernumbers o study participants, and theyhave done so or thirty, orty or even fyyears! Go with one o these products.

Characteristics o a benecial orapopulation in the human GI include:1) their tolerance to acid, bile andpancreatic enzymes 2) their ability toadhere to the intestinal wall and competesuccess ully or the Hollywood-like realestate that is our gut 3) their ability toovercome the resistance offered by theexisting bacteria present. Te normalbacterial residents offer considerableresistance to newcomers via a variety omeans including ormation o biolms,crowding out the recent immigrants,altering the pH or by other means 4) their

lack o toxicity (the bacteria do not passon their genes to human cells or developresistance to antibiotics). Pre erably theprobiotics ought to be sourced romhumans, compatible with other strainspresent in the supplement. In otherwords, the bugs dont eat each other 5)their ability to modulate the immunesystem rather than cause continual over-stimulation 6) are shel stable or do notrequire re rigeration.

It is not easy or manu acturers toensure that their strains meet the abovecriteria. O course that doesnt preventthem rom making exaggerated claims,but the truth is out there and someevidence-based products do indeedmeet the above criteria. ake the caseo OA, a Japanese company that hasmarketed a probiotic blend calledBio-Tree or over fy years, andequally important has kept publishing

human clinical studies regarding sa etyand efficacy during that course. Teprobiotic consists o three lesser knownbut well researched and documentedstrains. wo o the strains provideprotection against antibiotic-associatedor travelers diarrhea and Clostridiumdifficile, anti-inammatory effects,improvement o the gut barrier, allergyprotection and more. Te third strain isa ood source or the other two, so asto provide nutrients and keep the two

unctioning optimally.Tis strategy is unique and provides

or a stable, effective and well researchedprobiotic which has its own ood source,alleviating the need to add additionalprebiotics like ructo-oligosaccharidesthat are all too common in many o the

probiotics. Furthermore, the numberor guessing game isnt played with sucha probiotic; afer all, it isnt the numbero CFUs (colony orming units) presentthat is important, it is evidence baseddocumentation and compatibility thatis critical. One can have twelve billionCFUs or more, and over a dozendifferent strains all thrown together butits insignicant i there is no research!

Probiotics have been success ullyused throughout history. In recenttimes there have been urther advancesin the isolation, identication andclassication o them. By studying theirclinical efficacy, probiotics can provideus with additional weapons to keep ourgut healthy and protected. However, thiscannot happen by chance or by wishingthat a bunch o bacteria thrown into acapsule or tablet will work - research isrequired.

References1. Jumpertz, R et-al.Energy-balance studies reveal association between gut microbes, caloric load, and nutrient absorption in human. Am J Clin Nutr.

2011; 94: 58-652. Ley R E et al. Microbial Ecology: human gut microbes associated with obesity. Nature. 2006: 444: 1022-10233. urnbaugh PJ et al. Diet-induced obesity is linked to marked but reversible alteration in the mouse distal gut microbiome. Cell Host. Microbe 2008; 17:

213-223 Additional Re erences:Shanahan F. Probiotics and inammatory disease: rom ads and antasy to acts and uture. Br J Nutr. 2002; 88: s5-s9Hart A L and Stagg M A. Use o probiotics in the treatment o inammatory bowel disease. J Clin Gastroenterol. 2003; 36: 111-119Gill HS, Ruther urd KJ, Prasad J, et al. Enhancement o immunity in the elderly by dietary supplementation with probiotics Bidobacterium lactis. Am J

o Clin Nutr. 2001; 20: 149-156 Goektepe I, Juneja VK, Mohamed Ahmedna M, et al. Probiotics in Food Sa ety and Human Health. CRC Press. 2006


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Nature offers many compoundsthat may be benecial or alleviatingdigestive disorders such as IBS, IBD,cancer, ulcers, acid reux and others.A ew o the more widely studied andsuccess ully used natural supplementsinclude: DGL, boswellia, mastica,curcumin, and ber.DGL (De-glycyrrhizinated licorice)

raditionally, licorice has been usedthroughout history by many cultures or various diseases. It is a key componentin syrups and herbal teas and is use ul

or treating cough and cold symptoms,as well as or a host o gastric issues,the latter due mainly or its demulcentor soothing properties. Un ortunately,while being highly effective as ananti-viral, anti-inammatory andimmune modulator, licorice does have

a shortcoming. One o its components,glycyrrhizin, causes sodium retentionand thus raises blood pressure.Glycyrrhizin limits the use o licorice asa natural treatment or gastrointestinalsymptoms such as heartburn, healingulcers and pain relie .

Over fy years ago a new orm olicorice lacking glycyrrhizin calleddeglycyrrhized licorice (DGL) wasintroduced; it showed that the healing

powers o licorice were still retainedwithout the side effects o high bloodpressure. DGL is thought to work byseveral mechanisms, rstly by directlyinhibiting the bacteria Helicobacter pylori (H. pylori) , the bacteria nowstrongly linked to causing peptic ulcersand stomach cancer. It is thought thatDGL directly kills the H pylori .1 Second,DGL assists the healing o the liningo the stomach wall. It does this byincreasing the mucus secretion whichprotects the stomach cells rom attack bythe acid present in the stomach, as wellas by improving blood ow and quickerdelivery o nutrients to the cells so as tospeed up the healing process. Studieshave shown that when DGL is takenalong with aspirin there is a signicantreduction in stomach bleeding. 2

Un ortunately, there have been nostudies in the last three decades; one othe last studies did show that when DGLwas taken together with ranitidine, astandard prescription at the time ortreatment o ulcers, the rate o remissionwas increased. 3 Interestingly, DGL waseffective in both stomach and duodenalulcers. 2BoswelliaBoswellia is a herb that has a long and

established use in various traditionalmedicines. Te Boswellia plant exudesa gummy like resin that is collectedand used in various ormulations. Itis use ul or the treatment o nervousdisorders including depression andanxiety, or boosting the immunesystem, or topical use o wound healingand as an anti-bacterial and anti- ungal.Boswellia is probably best known orits anti-inammatory activity and itsuse in a variety o conditions includingosteoarthritis, rheumatoid arthritisand other autoimmune disorders. Notsurprisingly, Boswellias use in digestivehealth has been a ocal point o research

or many years.Inammatory conditions including

IBS and IBD (Crohns and ulcerative

colitis) have shown signicantimprovements ollowing Boswelliaconsumption. 4 Animal studies haveshown that Boswellia reduces thegastric irritation and the subsequenterosion o the gastric lining causedby non-steroidal anti-inammatorydrugs (NSAIDs) like indomethacinand phenylbutazone. 5 Te result is thatthere is signicantly less bloodloss asdetected in the eces, all the more reasonto take Boswellia along with any NSAIDtherapy. Researchers have shown thatBoswellia has a protective effect in micewhen they are treated with a chemicalcalled dextran sodium sul ate (DSS) thatis used or an animal model or IBD thatinduces damage to the mucosal lining othe gut. 6 Boswellia prevents much o thedamage as shown in the histology o themice gut.

Te active constituent(s) in Boswelliaremain the subject o heated debate.Initially, some researchers viewedboswellic acids (a mixture o eight or so

different compounds) to be the activecomponent. However, others thoughtthat specic boswellic acid ractions likeacetyl-beta-boswellic acid (AKBA) werethe most power ul raction. Still, othersregard an entirely different componentcalled incensole acetate to be the keymolecule. Whichever molecule turnsout to be active, it is likely the synergybetween all these components that is themost important actor.

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Te mechanism o action oBoswellias biological effects is viamultiple pathways typical o theaction o many natural ingredientsand includes the ollowing: rst, theinhibition o NF- B, a key actorinvolved in copying the portion oDNA involved in inammation. 7 I thecopying o the DNA portion involvedwith inammation is inhibited, theninammation will also be slowedor stopped. Second, Boswellia has apower ul immune stimulating effectlocally in the gut. Since the gut is therecipient o all sorts o orally consumed

oods, pharmaceutical drugs, toxinslike alcohol, carcinogens etc., the bodyis designed to be able to deal with theseunwanted and dangerous intrudersimmediately, by positioning a portiono the immune system right within thegut. Tird, Boswellia has antimicrobialactivity against bacteria likeStaphylococcus which is responsible or

ood poisoning, and Candida albicans

which causes yeast in ections.8

Mastica (Mastic Gum)Mastic gum is extracted rom the resino a plant that grows almost exclusivelyon the Greek island o Chios. It has beentraditionally used as a ood additive, asan antioxidant to keep oods resh, andas a gum in combatting various diseasesincluding high cholesterol, weight loss,tooth and gum decay, halitosis and orheartburn and stomach ulcers.

Tere are currently over seventyknown components in mastic gumand no one molecule is consideredactive on its own, hence there is nostandardization or the raw material.

A 2010 study rom Greece looked at52 patients divided into our groups. 9

wo groups were given a 350mg doseo mastica three times a day, and onewas untreated; a ourth group was givenconventional antibiotic and prescriptiontherapy or H. pylori . H. pylori is aninvasive bacterium that burrows into thestomach lining and is a common causeo stomach ulcers. Five out o the 13people in the mastica group recoveredcompletely, compared with zero inthe untreated group. However, theantibiotic/prescription therapy resultedin complete improvement in 10 out o13 patients.

A 2009 study utilizing the standardanimal model o IBD using the DSS inmice, once again conrmed the activityo mastica in relieving the symptoms o

IBD.10

CurcuminCurcumin is by ar the most dominant othe three biologically active componentspresent in the spice turmeric collectivelycalled curcuminoids, the other twobeing demethoxy and bisdemethoxycurcumin.

Curcumin has traditionally been usedin the Indian subcontinent or gastrichealth, treating periodontal disease,

ulcers o the mouth, duodenal andpeptic ulcers, various protozoal diseases

rom amebiasis to dysentery, variousinammatory conditions and muchmore.

Curcumin is probably the mostwell researched natural product onthe market, and its biological effectson the gut are well documented.

ypically, turmeric spice has beenadded to hot milk and taken orally incopious amounts. Tere is a reasonwhy curcumin is given in this manner:this is due to the poor bioavailabilityo the curcumin or the amount thatreaches the active site, in this case thegastrointestinal tract. Hot milk improvesthe delivery o the curcumin molecule,and researchers attribute this increased

activity to the various milk proteinsand peptides that orm a coating ormiscelle-like structures that are quicklytaken up into the blood.

est tube studies, animal studies,and human clinical studies have shownthe ollowing: rst, curcumin is poorlyabsorbed due to its rapid elimination

rom the body, and hence the need ormore bioavailable orms. Second, doseso up to 8000 mg o curucmin per dayare sa e.11 Tird, curcumin has beenused in conjunction with other therapiesespecially in the treatment o various

orms o cancer such as pancreatic,stomach, colon and oral cancers inconjunction with chemotherapy andradiation. 12 Fourth, curcumin worksthrough multiple pathways rather thanexhibiting one specic mechanism whichis typical o many pharmaceuticals.

Colon cancer is the third leadingcause o death in North America. Teincidence varies over 20 old, rom thehighest in North America to the lowest

in India. Population studies suggestthat the regular intake o oods suchas turmeric may partly be responsible

or the lower rates. 13 Since curcuminworks through more than one pathway,it offers an alternative and an attractiveapproach to combatting colon cancer.

Numerous human studies haveshown that curcumin is a goodcandidate or various orms o canceras well as inammatory conditions like

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IBD, but studies require larger numberso subjects to be able to draw anymeaning ul signicance. An excitingarea o research is the development omore bioavailable curcumin products.One approach has been to use piperine( rom black pepper) as an adjunct, sinceit prevents curcumin elimination byknocking out the phase II enzymesthat the body uses as a detoxicationsystem to protect itsel . However, thismay not be sa e in that i the phase IIenzymes are inactivated, this may allowentry o other toxins and carcinogensalong with the curcumin.

Alternative and better deliverysystems have been developed;one such system is the solid lipidnanoparticle (SLP) developed using

natural technology and patented by theresearchers at University o Cali orniaat Los Angeles (UCLA) under the tradename Longvida. Longvida is the mostbioavailable curcumin ingredient onthe market, and has been shown inclinical study to be over 100 times morebioavailable than regular curcumin.In addition, unlike many o the otherproducts on the market claiming higherbioavailabilities, Longvida comparesthe blood levels o ree curcumin ratherthan some other detoxied compoundthat other companies measure.Longvida curcumin products provide atruly enhanced delivery system.FiberWe all know that ber is good or us, yetthe subject is never a part o any politeconversation. All too ofen ber is stillbeing thought o as a laxative, yet beroffers so much more than just being anexcellent laxative. Its health benets goway beyond digestive health.

Fiber is a remarkable nutrient that

has wide ranging physiological andhealth benets including heart health,cholesterol control, glycemic control,insulin response and sensitivity, guthealth, satiety, immune enhancement,and as a particularly strong preventativeo colon cancer. Indeed, ber couldpossibly be one o the most importantarsenals in every household to ward offa host o diseases. In act, the clinicalevidence on ber is more robust than

many other nutritional interventionmolecules such as vitamins, mineralsand many herbs.

Te Institute o Medicine (IOM)recommends that a daily intake ober should be 38g or males, and25g or emales, women requiringmore during pregnancy and nursing.However, the average North Americanadult consumes around hal that gure,despite the heavy promotion o thehealth benets by the government.Over 90% o North American adults view digestive health as a top priority,yet less than hal think that they needmore ber in their diets. Clearly greatereducation on the role o ber is required

or consumer awareness.What is Fiber?Dietary ber is the indigestible portiono the plant which usually requires muchmore chewing, hence the synonymousword roughage. Fiber is abundantin various ruits and vegetables and iscommonly ound in roots, stems and

nuts.Fiber types range rom cellulose,the main component o the vegetablekingdom to pectin ound in apples andgrape ruit, to beta-glucan derived romoats and yeast.

Fiber is a collective term used todescribe a large and diverse variety oplant constituents that are resistant tobreakdown by gastrointestinal enzymesin the small intestines, but which

undergo ermentation in the largeintestines. Dietary ber is classiedas water soluble or water insoluble,though plants usually contain somecombination o the two.

Water insoluble bers are chieyderived rom cellulose and are abundantin vegetables and cereal grains like wheatand corn. Water insoluble bers easilyabsorb water and help to regulate bowelmovement by increasing bulk, sofeningstools, and quickening the time o passagethrough the intestinal tract.

Soluble bers are generally gelorming, highly viscous, and include

pectins, mucilage and various gumslike guar and xanthan. Dried beans,oats, and barley are major sources othis type o ber. Te soluble bers arecarried to the large intestines where theyare broken down by the gut bacteria torelease various benecial components.SoluFibre - A Clear Solution to YourDaily Fiber Needs.Recently, the Japanese company aiyo

has taken the large molecules o guargum and broken them down to muchsmaller units that become completelysoluble in water and other beverageswithin two to three minutes. Tisprocess leaves an odourless, taste-

ree and clear solution. Te productis called SoluFibre; it has distinctadvantages over other bers that dontdissolve and ofen have a distinctivetaste. Te complete solubility o

Figure 1.H. pylori Burrowing Into Stomach Lining


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SoluFibre makes the product very userriendly.

What Are the Benets of SoluFibre?1. Production o short chain atty acids(SCFA) - Fiber is not digested in thesmall intestines, but once in the colon itis broken down by the specic bacteriaresiding there. Various by-productsare produced, such as SCFAs includingbutyrate, as well as other compounds.Butyrate is an energy source or thecolon cells. In addition, SCFAs regulatethe pH thus making the environmentinhospitable to various pathogens.2. Promoting weight loss - Fiber provides

ew calories, but it does give one theeeling o ullness or satiety unlike many

processed oods which are energy dense(lots o calories) yet provide little or no

eeling o satiety. Some studies showthat ber signicantly reduces body atin animals and humans, while others

report no weight loss effect. Womenconsuming at least one serving o wholegrain had a signicantly lower meanbody mass index (BMI) and waistcircum erence than women not takingthe whole grain.3. Nutrient absorption - Fiber alsoenhances mineral absorption o calcium,magnesium, zinc and so on. Tis effectis particularly use ul or pre-teens aswell as postmenopausal women.4. Prebiotic effect - Te breakdownproduct o ber which occurs via

ermentation in the large intestinesgenerates many by-products. Temetabolites provide ood andnourishment or the riendly bacteriawhich colonize there. Tis is calledthe prebiotic effect. Support and well-

being or these bacteria is critical, asthese bacteria have an important roleto play in various biological pathways

such as immune stimulation, nutrientbreakdown, synthesizing vitamins,and in preventing the colonizing oun riendly bacteria.5. Improves digestive health - Besidesalleviating constipation, a high ber dietmay prevent stress induced diarrheaby preventing the release o varioushormones produced by the body whichnormally quicken the passage o oodthrough the small intestines whichresults in diarrhea.6. Fiber and Inammation - Recentstudies show signicant reductions ininammation in subjects consuminghigh ber diets. Reduction oinammatory markers, especiallyC-Reactive Protein (CRP), has been

requently reported. One o these

mechanisms might be the generationo butyrate which is particularly anti-inammatory.

References1. Larkworthy W, Holgate PF, McIllmurray MB, et al. Deglycyrrhizinated liqourice duodenal ulcer. Br Med J 1977; 6095: 1123-1126 2. van Marle J, Aarsen PN, Lind A et al. Deglycyrrhizinated liquorice (DGL) and the renewal o stomach epithelium. Eur J Pharmacol 1981; 72: 219-2253. Morgan AG, Pacsoo C, aylor P, et al. Does Caved S decrease the gastric ulcer relapse rate during maintenance treatment with ranitidine? Aliment

Pharmacol Ter. 1897; 1: 633-6384. Anthoni C, Laukoetter MG, Rijcken E et al. Mechanisms underlying the anti-inammatory effects o boswellic acids in experimental colitis. Am J

Physiol Gastrointest Liver Physiol. 2006; 290: G1131-G1137 5. Gupta I, Parihar A, Malhotra P, et al. Effects o gum resin o boswellia serrate in patients with choronic colitis. Planta Med. 2001; 67: 391-3956. Moussaie A and Mechoulam R. Boswellia resin: rom religious ceremonies to medical uses; a review o in-vitro, in-vivo and clinical trials. J o Pharmacy

and Pharmacology 2009; 61: 1281-12937. Poeckel D, Werz O. Boswellic acids: biological actions and molecular targets. Curr Med Chem. 2006; 13: 3359-33698. Moussaieff A, Shohami E, Kashman Y et al. Incensole acetate; a novel anti-inammatory compound isolated rom Boswellia resin, inhibits nuclear

actor kappa B activation. Mol Pharmacol. 2007; 72: 267-2739. Dabos KJ, Ska E, Vlatta LJ et al. Te effect o mastic gum on Helicobacter pylori: a randomized pilot study. Phytomedicine. 2010; 17: 296-29910. Paraschos S, Mitakou S, Skaltsounis AL et al. Chios gum mastic: A review o its biological activities. Curr Med Chem. 2010: 19: 2292-230211. Cheng AL, Hsu CH, Lin JK. Phase I clinical trial o curcumin, a chemopreventive agent, in patients with high risk or pre-malignant lesions. Anticancer

Res 2001; 21: 2895-290012. Rao CV, Rivenson A, Simi B et al. Chemoprevention o colon carcinogenesis by dietary curcumin, a naturally occurring plant phenolic compound.

Cancer Res 1995; 55: 259-266 13. Sharma RA, McLelland HR, Hill KA et al. Pharmacodynamic and pharmacokinetic study o oral curcumin in patients with colorectal cancer. Clin

Cancer Res 2001; 7: 1894-1900 Additional Re erences:Pylkas AM, Juneja LR, Slavin JL et al Comparison o different bers or in-vitro production o short chain atty acids by intestinal microora J o Med F2005; 8: 113-116

opping D L and Clifon P M Short chian atty acids and human colonic unction: Roles o resistant starch and non starch polysaccharides Physiol Rev 2001: 81031-1064King DE, Egan BM, Woolson RF, et al. Effecto a high ber diet vs. a ber supplemented diet on C-reactive protein level. Arch Intern Med. 2007; 167: 502-506 Huang M , Lou YR, Ma W, et-al. Inhibitory effects o dietary curcumin on orestomach, duodenal, and colon cancer in mice. Cancer Res 1994; 54: 5841-5847 Ammon HP. Boswellic acids in chronic inammation. Planta Med. 2006; 12: 1100-1116 Asl MN and Hosseinzadeh H. Review o pharmacological effects o Glycyrrhizia sp. And its bioactive components. Phytother Res. 2008; 6: 709-724Huwez FU, Tirlwell D, Cockayne A, et al. Mastic gum kills Helicobacter pylori. N Engl J Med. 1998; 339: 1946-1948Hyun-Jo Kim and Neophytou C. Natural anti-inammatory compounds or the management and adjuvant therapy o Inammatory Bowel Disease and its drugdelivery system. Arch Pharm Res. 2009, 22: 997-1004

rianta yllou A, Chaviaras N, Sergentanis N et al. Chios mastic gum modulates serum biochemical parameters in a human population. J Ethanopharmacol.2007: 111: 43-49


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As research continues to grow, itbecomes more evident just howcrucial the integrity o the digestivesystem is to overall health. It is themain barrier and rst de ense betweenthe outer world and inner body. Fromthis basic standpoint, the importanceo maintaining a healthy gut lining ismonumental. Here is a closer look at

some key nutritional therapeutics orthe purpose o enhancing gut health:L-Glutamine: Maintaining GutIntegrity L-Glutamine is well known as amajor uel and nitrogen source orcolonocytes, as well as a componento glutathione.1 Tese actors alonemake it clear that the amino acid is akey nutrient in the intestinal mucosaand or combatting oxidative stress.

Anecdotally, many practitioners swearby L-glutamine in its ability to heal thedigestive tract under inammatorycircumstances and suboptimalgut integrity. However, researchsurrounding this topic is ar romconclusive.

Much research has shownL-glutamine to have positive

applications in regulating orimproving intestinal permeability.A double-blind trial o L-glutamineshowed improvement in AIDS-related diarrhea in individuals takingantiretroviral drugs. 2 Similarly,patients receiving chemotherapyhave been shown to benet romreduced requency o diarrhea versuscontrol groups without a decrease inthe efficacy o chemotherapeutics.3,4

esting using the lactulose-manitolratio test (the pre erred measurement

or determining the presence orabsence o Leaky Gut Syndrome)conrmed measureable improvementsin intestinal permeability withL-glutamine supplementation in theseindividuals. Again, in otherwise healthychildren suffering rom gastroenteritis,L-glutamine supplementation reducedthe duration o acute diarrhea by26% compared to placebo. 5 Animalstudies also show improved intestinalpermeability and preserved gutmucosal integrity using L-glutamine,although an extraordinarily high doseo 500 mg/kg/day was administeredin one particular study. 6 Clearly, thereis a role or L-glutamine in impaired

intestinal permeability and diarrheacases.Te application o L-glutamine

or Crohns Disease (CD) is lessapparent. Despite multiple studiesshowing impaired glutamine levels inCD patients, 7 oral supplementationwith L-glutamine has not necessarilyshown to be o benet. One study

ound that glutamine did not helpto improve intestinal permeabilityin individuals with CD, 8 yet in vitroresearch shows a signicant reductionin levels o inammatory molecules afersimultaneous exposure o glutamine andarginine to the colonocytes o CD.9

Various practitioners and researchershave postulated that clinical trials havenot shown a clear benet in glutaminesupplementation with Crohns patients

or a ew reasons: dosing is notadequate in various studies, glutaminemust be studied in combination withother nutritional actors, and depletedglutamine may merely be a secondary

marker or a separate causativeactor.1,10 It is evident that moreresearch is necessary to determine theexact role that L-glutamine plays insuch inammatory conditions o thedigestive tract.

Other applications or L-glutamineinclude decreasing the severity ochemotherapy-induced mucositisand gastrointestinal toxicity. 10 Also, parenteral administration o

Nutrient Supplements for theDigestive System


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22 Advances

L-glutamine has shown promisingapplication in those with acutepancreatitis (based on decreasedcomplication rates and mortalityrates). 11, 12

Essential Fatty Acids: ControversialBenetsTere are two types o essential attyacids (EFA) that the human bodycannot synthesize on its own: anomega-3 type, alpha-linolenic acid(ALA), and an omega-6 type, linoleicacid (LA). Both types serve a varietyo crucial unctions throughout thehuman physiology, most notably asprecursors to various prostaglandinsand leukotrienes (thereby regulating

inammatory pathways) and ascomponents o cell membranes. 13Although ALA is converted in

the body to the biologically activeeicosapentaenoic acid (EPA) anddocohexaenoic acid (DHA), itsconversion rate is quite limited. 13 Asa result, health practitioners ofenrecommend supplementation o EPAand DHA directly in the orm o shoil. From a digestive health ocus,

these crucial omega-3 atty acids haveshown possible benet in CrohnsDisease (CD), ulcerative colitis (UC),gastritis and proctitis, 14,15 although theresearch is conicting.

For example, certain studies haveshown supplementation with sh oilor EPA/DHA to prevent relapses inCD patients while in remission, 6,17 yet other studies have ailed to nd asignicant effect, i any effect at all.18,19 Nevertheless, some experts hypothesizethat the minimum dose needed or sucha condition appears to be quite high (9-12 grams per day), possibly explainingthe equivocal results as not all studiesreached this dosage. 1

Similarly, research evaluating theefficacy o sh oil in UC patients hasshown clinical improvement anddecreased medication need, 20 yet manystudies show disappointing results. 21 Prospective cohort studies support apossible protective eature o increasedomega-3 atty acid intake or UC.22

A systematic review was per ormedin 2012 to better evaluate whetheromega-3 atty acids are indeed use ul

in CD or UC patients. Researcherswere unable to come to a conclusionon the recommendations or clinicaluse based on poor study design

eatures (ie. inappropriate placebo,small number o participants, variabledesigns). Despite this, they did leantoward the idea that available datadoes not support the use o omega-3supplementation or the treatment oactive and inactive inammatory boweldisease.23 A previous meta-analysis in2011 came to similar conclusions. 24

For completions sake, it shouldbe noted that supplementation withomega-6 oils has been shown to beclinically relevant as well, particularlyin the orm o gamma-linolenic acid(GLA, converted rom LA within the

body). Animal research has shown GLAto protect against induced ulcers 25 andGLA does have antineoplastic activityagainst hepatocellular carcinoma in vitro.26 However, very little researchhas ocused on digestive applicationso GLA as opposed to other conditionssuch as arthritis and eczema.

Finally, while the trend in modernmedicine has been toward highdose omega-3 supplementation tocounterbalance the low ratio o omega-3s to omega-6s ound in todays diet,some have posed the question owhether we are actually overdosingon omega-3 atty acids.27 Tis theoryis supported by the act that EPA andDHA are only converted in smallamounts within the body becausethat is all that we physiologicallyneed. More clinical research must beper ormed to determine the optimalratio o EFAs or supplementation anddietary purposes, as well as the exactrole in treating clinical conditions.

Zinc Carnosine: An Anti-ulcer AgentIt has long been known that zincis essential or the human bodyin physiological processes such aswound healing, immune unction andhormonal regulation. 28 However, novelresearch has examined the role o zinccarnosine ([ZnC], zinc combinedwith the amino acids beta-alanineand histidine) or its gastroprotectivecapabilities and potential as a gastric

22 Advances

Inammation

Healthy intestinal lining

Undigestedfood particles

Toxins

Parasites andharmful bacteria

Intestinal liningGap junction

Blood stream

Yeast/Fungi

Leaky gut

Damaged intestinal lining

Intestinal Permeability


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ulcer treatment therapy. In act, itsapplication as an anti-ulcer drug hasbeen in clinical use or quite some timenow in Japan. 29

Numerous clinical studies o ZnCexamining its anti-ulcer effects haveshown great sa ety and efficacythrough endoscopic measures.Optimum healing appears to beachieved afer 8 weeks o treatment(as high as 72% achieving remarkableimprovement in one study),although 4 weeks demonstrates greatimprovements as well. 29 Anotherstudy showed that co-administrationo ZnC with indomethacin (a Non-Steroidal Anti-Inammatory Drug[NSAID]) eliminated the increase ingut permeability in humans when the

NSAID was given alone. In addition,this coadministration also negatedthe ormation o gastric ulcers inrats versus the damage seen whenindomethacin was the sole therapy. 30

ZnC also shows strong potentialas an anti- Helicobacter pylori agent(thereby adding to its role as an anti-ulcer supplement). In a clinical trialexamining the efficacy o H. pylorieradication using ZnC in combinationwith triple therapy (lansoprazole,amoxicillin and clarithromycin),signicant improvements were seenwhen compared to triple therapyalone. 31 Tese results have beenattributed to its bactericidal, anti-urease and anti-adhesive propertiestoward H. pylori specically.32

Aside rom anti-bacterial action, themechanism o action or ZnC appearsquite complex and multi-targeted.L-carnosine specically preventsgastric epithelial injury by inhibitingDNA ragmentation,33 whereas ZnC

together acts as an antioxidant, inducesthe expression o Heat Shock Protein72 (HSP72) and inhibits Nuclear FactorkB (NF-kB) in the colonic mucosa. 34 Tis increase in HSP72 activity anddecreased NF-kB level has been shownto have cytoprotective effects ondigestive organs. Other actions includethe restoration o glutathione levels ininjured gastric mucosa, promotion ogrowth actor ormation, promotion o

polyamine synthesis and inhibition oproinammatory cytokine production(such as umor Necrosis Factor-alpha[ NF-]) all o which are essentialprocesses in mucosal protection andulcer healing in the gut. 35

Overall, the actions o ZnC make it asuitable pairing or optimal gut healthand protection. As an added benet,ZnC has also shown application inimproving taste sensitivity in cases oidiopathic taste disorders. 36

Nitric Oxide: Not Just a VasodilatorClassically, nitric oxide (NO) hasbeen considered or its cardiovascularrole as a potent vasodilator. However,many are unaware that the effectso NO are much more ar reaching;it is also a proven anti-microbial, anecessary agent or tissue protectionunder ischemic circumstances and agastroprotective agent. 37 With this inmind, NO and its precursors (nitrates

and nitrites) have tremendoustherapeutic potential that is still yet tobe ully realized.

From a gastroprotective standpoint,research has ocused on the ability oNO to prevent and treat gastric ulcers.More specically, nitrates, nitritesand NO have been shown to mitigategastric ulcerations commonly causedby non-steroidal anti-inammatorydrugs (NSAIDs), endotrachealintubation and Helicobacter pylori

through a variety o mechanisms.38,39,40

NO appears to mitigate epithelialpermeability, reduce tissueinammation, increase gastric mucosalblood ow and, subsequently, increasemucus generation. 38,39 Collectively,these actions provide supportiveprotection in bacterial overgrowthand they help to offset the depletiono gastric NO due to common medicalinterventions. 41

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Keeping in mind the crucial role thata well-balanced gut microora playsin our digestive health, NO helps toregulate this ecosystem through itsbroad-spectrum antibiotic effect. In vitro, NO and nitrites have proven tocombat Shigella, Yersinia and Salmonellaspecies, as well as Helicobacter pylori, Clostridium botulinum andPseudomonas aerguinosa .40, 42, 43 Tisinhibition o H. pylori by nitrites and

NO may be a separate and additiveprotective mechanism or gastric ulcerprevention, while simultaneouslypromoting healing o the mucosallining.43

Terapeutically, the most effectiveway to increase NO levels in thebody and provide gastrointestinalprotection is to deliver nitrates directlyand drive the nitratenitritenitricoxide pathway (also known as the

NOx3,2,1 pathway). Tis deliverymethod holds many advantages overthe classic L-arginine-Nitric oxidepathway including stimulation o theentero-salivary nitrate cycle. In themost basic sense, this cycle allowsnitrate conversion to nitrite in theoral cavity by commensal bacteria,

ollowed by reduction to NO in thestomach. 37 Te cycle continues asnitrates and remaining nitrites arerapidly absorbed into the bloodstream and recirculated to the salivaryglands, where urther reduction andactivation o NO can take place.37 Interestingly, animal research showsthat the gastroprotective effect onitrate supplementation is eliminatedi topical antibiotics are used in the oral

cavity to disrupt the oral microora.44

As a nal note, administering NOprecursors in a clinical setting may becontraindicated in patients suffering

rom reux esophagitis, as NO alsoappears to trigger relaxation o thelower esophageal sphincter. 45 However,given the gastroprotective effectsdiscussed above, clinical judgmentmust be exercised, as this aggravatingeffect is merely theoretical.

References1. Yarnell E. Natural approach to gastroenterology. WA, Healing Mountain Pub: 2011. pp 987-988.2. Bushen, OY, Davenport JA, Lima AB, et al. Diarrhea and reduced levels o anti-retroviral drugs: improvement with glutamine or alanyl-glutamine in

a randomized control trial in northeast Brazil. Clin In ect Dis. 2004; 38:1764-17703. Daniele B, Perrone F, Gallo C, et al. Oral glutamine in the prevention o uorouracil induced intestinal toxicity: A double blind, placebo controlled,

randomised trial. Gut. 2001; 48(1):28-334. Li Y, Yu Z, Liu F, et al. Oral glutamine ameliorates chemotherapy-induced changes o intestinal permeability and does not inter ere with the antitumor

effect o chemotherapy in patients with breast cancer: A prospective randomized trial. umori. 2006; 92(5):396-4015. Yalcin SS, Yurdakok K, ezcan I, et al. Effect o glutamine supplementation on diarrhea, interleukin-8 and secretory immunoglobulin A in children with

acute diarrhea. J Pediatr Gastroenterol Nutr. 2004; (38):494-5016. Dos Santos RG, Viana ML, Generoso SV, et al. Glutamine supplementation decreases intestinal permeability and preserves gut mucosa integrity in an

experimental mouse model. JPEN J Parenter Enteral Nutr. 2010; 34(4):408-4137. Balasubramanian K, Kumar S, Singh RR, et al. Metabolism o the colonic mucosa in patients with in ammatory bowel diseases: An in vitro proton

magnetic resonance spectroscopy study. Magn Reson Imaging. 2009; 27(1):79-86

8. Hond ED, Hiele M, Peeters M, et al. Effect o long-term oral glutamine supplements on small intestinal permeability in patients with crohns disease. JPEN J Parenter Enteral Nutr. 1999; 23:7-11

9. Lecleire S, Hassan A, Marion-Letellier R, et al. Combined glutamine and arginine decrease proin ammatory cytokine production by biopsies romcrohns patients in association with changes in nuclear actor-kappaB and p38 mitogen-activated protein kinase pathways. J Nutr. 2008; 38(12):2481-2486

10. Gaby, A. Nutritional medicine. Concord, N.H, Fritz Perlberg Publishing. 2011. Pp. 1221.11. Sahin H, Mercanligil SM, Inan N, et al. Effects o glutamine-enriched total parenteral nutrition on acute pancreatitis. Eur J Clin Nutr. 2007; 61:1429

143412. Fuentes-Orozco C, Cervantes-Guevara G, Mucino-Hernandez I, et al. L-alanyl-glutamine supplemented parental nutrition decreases in ectious

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13. Gaby, A. Nutritional medicine. Concord, N.H, Fritz Perlberg Publishing. 2011. Pp 227-23414. Almallah YZ, Richardson S, OHanrahan , et al. Distal procto-colitis, natural cytotoxicity and essential atty acids. Am J Gastroenterol. 1998; 93:804-

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in healthy volunteers. J Rheumatol. 1996; 23(10):1770-177316. Belluzzi A, Brignola C, Campierei M, et al. Effect o enteric-coated sh-oil preparation on relapses in crohns disease. N Engl J Med. 1996; 334(24):1557-

156017. Romano C, Cucchiara S, Barabino et al. Use ullness o omega-3 atty acid supplementation in addition to mesalazine in maintaining remission in

pediatric Crohns disease: a double-blind, randomized, placebo-controlled study. World J Gastroenterol. 2005; 11:7118-712118. Feagan BC, Sandborn WJ, Mittmann U, et al. Omega-3 ree atty acids or the maintenance o remission in crohns disease. Te epic randomized

controlled trials. JAMA. 2008; 299(14):1690-169719. Lorenz-Meyer H, Bauer P, Nicolay C, et al. Omega-3 atty acids and low carbohydrate diet or maintenance o remission in Crohns disease. N Engl J

Med 1996; 334:1557-156020. Salomon P, Kornbluth AA, Janowitz HD. reatment o ulcerative colitis with sh oil n-3-omega- atty acid: an open trial. J Clin Gastroenterol. 1990;

12:157-16121. Dichi I, Frenhane P, Dichi JB, et al. Comparison o omega-3 atty acids and sul asalazine in ulcerative colitis. Nutrition. 2000;16:87-9022. John S, Luben R, Srethsa SS et al. Dietary n-3 polyunsaturated atty acids and the aetiology o ulcerative colitis: a UK prospective cohort study. Eur J

Gastroenterol Hepatol. 2010 May; 22(5):602-6 23. Cabr E, Maosa M, Gassull MA. Omega-3 atty acids and inammatory bowel diseases - a systematic review. Br J Nutr. 2012; 107(2):240-5224. urner D, Shah PS, Steinhart AH, et al. Maintenance o remission in inammatory bowel disease using omega-3 atty acids (sh oil): a systematic

review and meta-analyses. Inamm Bowel Dis. 2011; 17(1):336-4525. Das UN, Reddy DN, Rao PN, et al. Essential atty acids and peptic ulcer disease. Gut. 1987; 28:914-91526. Itoh S, aketomi A, Harimoto N, et al. Antineoplastic effects o gamma linolenic acid on hepatocellular carcinoma cell lines. J Clin Biochem Nutr. 2010;

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Prevent It. Pinnacle Pr. 2012.28. Gaby A. Nutritional medicine. Concord, N.H, Fritz Perlberg Publishing. 2011. Pp 151.29. Matsukura , anaka H. Applicability o zinc complex o L-carnosine or medical use. Biochemistry. 2000; 65(7):817-82330. Mahmood A, FitzGerald AJ, Marchbank et al. Zinc carnosine, a health ood supplement that stabilises small bowel integrity and stimulates gut repair

processes. Gut. 2007 Feb; 56(2):168-17531. Kashimura H, Suzuki K, Hassan M et al. Polaprezinc, a mucosal protective agent, in combination with lansoprazole, amoxicillin and clarithromycin

increases the cure rate o Helicobacter pylori in ection. Aliment Pharmacol Ter. 1999; 13:483-487 32. Sunair M, anaka N, Kuwayama H, et al. Effect o Z-103, a new antiulcer agent, on Helicobacter pylori antimicrobial, antiurease, and antiadhesive

activities. Jpn Pharmacol Ter. 1994; 22(9):31-533. Suzuki H, Mori M, Seto K et al. Polaprezinc, a gastroprotective agent: attenuation o monochloramine-evoked gastric DNA ragmentation. J

Gastroenterol. 1999; 34(11):436 34. Odashima M, Otaka M, Jin M et al. Zinc L-carnosine protects colonic mucosal injury through induction o heat shock protein

aor digestive healthvol 4 issue 3

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