Integrative Medicine

Functional Ulcerative Colitis and Crohn’s Disease Treatment

By Kim Crawford, M.D. Last updated: March 18, 2021
Functional Ulcerative Colitis and Crohn’s Disease Treatment

Introduction to Inflammatory Bowel Disease

The etiology of Inflammatory bowel disease (ulcerative colitis and Crohn’s disease) is complex, with genetic predisposition, an altered microbiome, environmental factors and a weakened epithelial (“gut”) barrier function triggering a chronic immune response in the mucosal layer. These two disorders of chronic intestinal inflammation affect approximately three million people worldwide. U.C. therapy and Crohn’s disease treatment starts with a good understanding of the disease process itself.

Currently, allopathic (versus functional medicine) Crohn’s disease treatment, for example- starts off with with brain and gut damaging corticosteroids and 5-aminosalicylic acid products, adds “immunomodulators” (Azathioprine, 6-mercaptopurine, methotrexate), and eventually, “biological agents” which are “TNF-alpha inhibitors” (infliximab, adalimumab, certolizumab, and golimumab). The story is just about the same for Ulcerative colitis. Just. too. toxic. for. words.

Not one of these drugs are curative, and their long-term use often causes severe side effects including cancer. Around 30% of patients with inflammatory bowel disease (IBD) are refractory to current IBD drugs or relapse over time. As a result, patient surveys show that almost 40% of Crohn’s and U.C. patients use alternative therapies to complement their conventional medical care.

Furthermore, because we Functional docs (in conjunction with happy, cooperative patients) obtain such stellar symptomatic control with our IBD patients, many of them will switch entirely to Functional care, stay symptom free, and experience far less invasive colonoscopies, since a fecal calprotectin level is a great way to monitor all disease activity. U.C. and Crohn’s disease treatment is fairly easy in the “functional world”, and it is helpful to know what it is that you can do to prevent disease occurrence or at least, lessen your symptoms.

First, I’ll explain the five major factors that you can control regarding what causes inflammatory bowel disease to occur and to flare: the “root cause.”. Then, I’ll review the following list of items that will help you get into and more importantly-remain in remission:

  1. Change your diet to an autoimmune eating plan
  2. Be careful when it comes to consuming pharmaceuticals.
  3. Heal your gut lining
  4. Manage your stress (cortisol).
  5. Clear up toxins (if needed).
  6. Take herbals to clear up toxic bacteria and/or yeast.
  7. Get your hormones balanced.
  8. Re-balance gut motility (often needed).
  9. Eat prebiotic probiotics foods and choose probiotic supplements.
  10. Use peptides
  11. Use low-dose naltrexone
  12. Consider lowering TNF-alpha with supplements-it can’t hurt!

 

The Root Cause of Crohn’s Disease and Ulcerative Colitis

Traditional medicine teaches us that risk factors officially implicated with ulcerative colitis and Crohn’s disease include low fiber-high carbohydrate diets, smoking, altered microbiomes and gut permeability as well as medications such as non-steroidal anti-inflammatory drugs. Each of these things will cause leaky gut, so what you’ll read next will not contradict these conventions. Leaky gut is the root cause of all autoimmune disease, including ulcerative colitis and Crohn’s disease. Here are the reasons you are more likely than not to have some degree of gut hyper-permeability syndrome AKA “leaky gut.”

Environmental contaminants and toxins

Direct gastrointestinal toxins we consume or absorb such as the methylmercury in canned tuna fish, the excessive use of plastics for food storage and even the fluoride in unfiltered water- can all damage our gut lining and disturb our microbiome. We even accumulate toxins via skincare products, and from non-filtered showerhead water. We breathe polluted air if we are in or near a city or a factory. We don’t think of “bad air” as a gut issue, but it is. If we’re in a dusty house, even if we don’t have dust mite allergies, dust mites have been demonstrated to cause leaky gut.

Lastly, another problem we don’t generally associate with gut health is mold. The reason I mention this outright is because 25% of us cannot (genetically) clear mold toxins so they not only damage our gut, they are responsible for a host of symptoms and long-term medical problems. If you have or had mold in your home (50% of structures in the U.S. fall into this category), you likely have mycotoxins in your HVAC that you’re breathing in and out of your lungs which may or may not ultimately damage your gut and may or may not cause ulcerative colitis or Crohn’s disease.

Depending on how well your detoxification systems both recognize and clear certain toxins, your toxin loads can build up to damaging levels. Something to keep in mind is the gut-brain barrier. Once the gut barrier is breached, so is the gut-brain barrier which then typically adds brain fog and things like concentration and mood issues to your “gut issue.” Now, let cover the most common way for Americans to wreak havoc on their guts: food.

Food

The food you eat can absolutely cause leaky gut. People who consume the “standard American diet” (SAD) with it’s high-processed and fast foods as well as it’s high-sugar content are putting their guts (and therefore their total health) at risk. As you are likely aware, gut-damaging GMO foods are now dominating the soy, wheat, and corn markets.  GMO-gluten used all too ubiquitously in our food supply is increasingly being blamed for non-celiac gluten sensitivity and leaky gut. It’s estimated that 25-75% of Americans have some type of food sensitivity. The most frequent offenders are (in this order) wheat, dairy, eggs, and corn.

Consuming gluten, artificial sweeteners, GMO foods, dyes and additives so non-food-like that they are now dubbed appropriately “franken-foods” as well as the massive amount of sugar (including HFCS and other hidden sugars) in our typical diet results in leaky gut. Add in non-sprouted grains and lectins (found-for example-in beans and nightshade vegetables), fruit juice and excessive caffeine and alcohol, and it’s a wonder we all don’t have leaky guts.

Actually those of you eating a standard inflammatory American diet likely do have a degree of leaky gut. Enough to trigger you to the other side of U.C. or Crohn’s disease? Do you really want to find out the hard way? And if you are someone who has I.B.D. and just “eat what you want” while taking a potentially harmful biologic drug-would you be willing to alter your eating style for improved health and a promise for a better chance for remission? What about your over-the-counter drugs habits? You can certainly alter those, can’t you? Sure you can! You, first, however need to know what is potentially problematic.

Pharmaceuticals

Americans pop OTC painkillers as if they’re candy. T.V. commercials feature actors who are pleased with themselves that they take just one non-steroidal anti-inflammatory gut irritant in the morning; and not again, until the end of the day!  Your gut lining can be interrupted by everything from Aleve and Ibuprofen to Vioxx or even Tylenol. The majority of people who take OTC pain relievers daily have some degree of leaky gut.

Another category of awful-for-the gut drugs is antibiotics. I hate to bash my own profession, but am always amazed at the amount of antibiotics my new patients tell me they were given for dubious bacterial infections. Antibiotics not only cause leaky gut, they also upset the good to bad ratio of bacteria in the GI microbiome. We now also have proton pump inhibitors sold over the counter; thus sky-rocketing their use. These drugs were never designed for more than short-term use. Many people use these PPI’s (Nexium, Prevacid or Protonix, ) for chronic heartburn and slowly etch away the lining of their GI tract.

Synthetic hormone medications such as birth control pills or cortisone-containing steroids (e.g.: prednisone or a Medrol dose-pack) can propagate the growth of excess candida (yeast), which also often damages the gut lining.

Hormonal imbalances can also cause chronic constipation such as low progesterone levels and low thyroid hormone levels. Indeed, this can readily lead to small intestinal bowel overgrowth (SIBO) as can many types of cancer chemotherapy agents. SIBO disrupts the gastrointestinal balance dysbiosis), often causing gas, bloating and eventually, leaky gut.

Chronic Stress

If you constantly “feel stressed”, chances are very good that you have a high cortisol level. High cortisol-apart from everything else we’re discussing-can cause the breakdown of your GI lining. It does this by slowing down both GI motility (peristalsis) and the process of digestion. When this happens, some people experience reflux, or “heartburn” while others have absolutely no symptoms. Blood flow then decreases to all of the digestive organs. This results in a higher concentration of toxic metabolites which then whittle away at your gut lining.

Gut Dysbiosis

Dysbiosis of the gut means that your GI microbiome (gut-bacterial-environment) is out of balance. A properly balanced GI microbiome is absolutely crucial for optimal GI function, immune function, and  brain function. Yeast (candida) can invade the lining of the intestinal wall to cause SIFO; small intestinal fungal overgrowth. Toxic E. Coli species are common culprits in SIBO (small intestinal bacterial overgrowth) issues. Other organisms such as giardia (a parasite) and Helicobacter pylori (responsible for ulcers and cases of severe heartburn) can also chip away at the intestinal lining. Deserving of a mention in this section are three things that can lead to lower gut motility and therefore SIBO and SIFO: hypothyroidism, low progesterone levels and low serotonin levels. Lastly, toxins are increasingly found as a cause of leaky gut.

Toxins

This topic is worth re-visiting. Although the amount of plastics (as an example) we consume is escalating, what is getting a lot of attention as definite gut-busters are mold toxins called mycotoxins.  Since 50% of the buildings in the U.S. are estimated to have water damage-a set up to mold growth; with the increasing climate events, we are seeing more and more water damaged buildings and more mold (especially toxic mold) growth.

We know that approximately 25% of the population is genetically unable to recognize and clear mold toxins, leaving them vulnerable to all sorts of medical problems including fatigue, brain fog and leaky gut. Now that we’ve discussed what causes leaky gut which can then lead to ulcerative colitis or Crohn’s disease, let’s talk about how we treat these two conditions with the best Functional Medicine has to offer.

Treat Underlying Gut Issues as an Integral Part of your Ulcerative Colitis and Crohn’s Disease Treatment

Change your Diet

It’s necessary to eliminate foods from your diet that can directly cause leaky gut. Initially, this is typically a huge lifestyle modification that is structured as such so that treatment doesn’t miss any offending foods. Over time leaky gut can precipitate as host of  IGG-mediated food sensitivities which can cause a plethora of symptoms. It is much simpler to  start with a basic diet and then reintroduce certain foods (e.g.: eggs) when you have your symptoms under control.

If you are eating a standard American diet, you’ll notice that the modifications you need to make will cause you to shed some pounds, have more energy, and in general, you’ll feel better. The first thing to do is to clean out your pantry and make yourself a list of “allowed foods.”

The best diet to follow is an AIP (auto-immune protocol) diet which restricts the “usual gut offenders” such as gluten, dairy, eggs, corn, sugar, processed foods, fast foods, citrus, nightshade vegetables, legumes, grains, as well as alcohol and caffeine. Yes, just like the Paleo diet!  It also restricts high FODMAP foods if they cause GI distress, which for most patients, is necessary. You cannot blame your gastrointestinal symptoms on specific foods if you eat this way for the two months it takes to heal a leaky gut. Yes-this diet is restrictive, but it will help to get you well and in two months, you can reintroduce some food items.

The Crohn’s and U.C. Diet Plan

What Do You Eliminate?

  • Processed foods
  • Legumes, such as beans, lentils, and peanuts.
  • Grains.
  • Dairy products.
  • Seed oils, such as vegetable and canola oil.
  • Nightshade vegetables, such as eggplant, potatoes, tomatoes, peppers, and okra.
  • Fast foods.
  • Refined sugars.
  • Eggs.
  • Soy.
  • Nuts and seeds.
  • Herbs from seeds, like coriander, cumin, and nutmeg.
  • Coffee.
  • Chocolate.
  • Dried fruits.
  • Food additives, like gums and emulsifiers.
  • Caffeinated teas: herbals are fine.
  • Spices made from nightshades, like chili powder, paprika, cayenne, chipotle, red pepper.
  • Alternative sweeteners such as xylitol and mannitol with stevia being OK in small amounts.
  • Alcohol.
After eliminating all potentially allergenic foods, the remaining basics are:
  • Meat, fish, shellfish, mollusks and poultry.
  • Low-sugar; small quantity fruits (berries only at first) and all vegetables, except for the nightshades.
  • Fruit oils (avocado, coconut, olive, MCT, palm) and animal fats such as ghee.
  • Bone broth (or gelatin/collagen).
  • Tea-Herbal is best, but some mildly caffeinated brands (loose, organic; not teabag) might be fine.
  • Vinegar: Restrict to apple cider initially.

Follow this eating plan (along with whatever else your Functional M.D. prescribes) until the “explosive diarrhea” wanes. For most people, this occurs within 3-4 weeks. At that time, you can add in a small cup of brewed coffee with a splash of additive free coconut or almond milk. Coconut milk is not included at first because it is a high FODMAP food  in more than tiny amounts. Reintroducing food is quite personalized, so I can’t advise you what to add back from this list-if ever-or when.

Pharmaceuticals

We’ve reviewed what not to take- so what do you use instead? Instead of NSAIDS for pain, use tylenol. Better still, if your GI tract is healed, use fish oil and curcumin- proven in clinical studies to out-perform even the priciest NSAIDS. For heartburn, try one white Rolaid or TUMS. Better yet: find good digestive enzymes. Herbals can often be substituted for antibiotics and anti-fungals, but you will need guidance for those. Hopefully, this article will make you aware of what you’re taking, and the effect it has on your gut.

Heal your Gut 

Getting you to remission and being asymptomatic from U.C. or Crohn’s disease starts with fixing your leaky gut. Changing your diet is the first step in healing your gut. Use (under medical care) proper gut-healing peptides ( discussed below) and (if needed), supplements for leaky gut such as l-glutamine and collagen powder. Vitamin D levels need to be normalized, and sporulating probiotics should be added when the symptoms start to subside so that they don’t “leak back” into the bloodstream. At this time, you’ll also add prebiotic fibrous carbohydrates (such as a half of an unripe banana) to your diet. More about re-balancing your microbiome (the prebiotics and probiotics)  coming up soon. But first, let’s talk about what’s plaguing most of us: stress.

Control Stress to Lower Cortisol

Stress is honestly just terrible for your health. We innately know this- but do you know the physiology of why this is? We know cortisol is a direct neurotoxin; likely being a risk factor for Alzheimer’s disease. We know it adds fat to the belly. When we’re talking about U.C., Crohn’s disease or any autoimmune disease for that matter, we’re looking at the direct effect high cortisol has on the gut. As previously mentioned, sustained high cortisol can be the sole reason for having a leaky gut. As a “not-so-fun-fact”-this is the probable reason so many “hardcore” bodybuilders (who all have high cortisol levels) have leaky gut.

Adrenal (herbal) adaptogens, glandulars, liposomal GABA and certain types of aromatherapy are proven to lower cortisol levels. Stress-busting techniques such as “vagal breathing,” meditation, and yoga are great relaxation practices. Finally, just activating your hypoglossal and therefore your vagal nerve to tone down your sympathetic nervous system will help. Simply sing, or even gargle!

Clear out Toxins

Common toxins that routinely cause leaky gut are the mycotoxins, the dust mites that usually are not numerous enough to be an issue unless there is actively growing mold, (AKA dust mite food) and lastly-heavy metals such as mercury. How do you know if mold is making you sick? If you have gut issues, fatigue and a foggy brain, with a history of mold exposure, there’s your answer. Dust mites? Not nearly as guilty– but in the line-up. Heavy metals? This depends on your environmental history and more. As does “toxicity” in general. Let me explain.

Toxins play more of a critical role if you have “faulty genetics” including glitches in your detoxification pathways. Having a few mercury amalgam fillings isn’t usually “enough” to cause leaky gut. We generally say “having eight or more fillings” is a problem that needs to be addressed after we get the general health of the patient under better control. However, be careful with your diet as a steady diet of canned tuna-fish or tuna sushi is actually enough to cause methylmercury build-up with effects on the gut and other organs.

Clear up Infections

If you have a history of vaginal yeast infections, you can cross-over infect your gut, especially if you have some sort of gut motility issue as mentioned earlier-things such as thyroid issues, low progesterone or low serotonin. Many cases of small-intestinal-bacterial-overgrowth (SIBO) occurs when colonic bacteria “backwash” into the usually sterile jejunum. The most common yeast (SIFO) and SIBO symptoms are gas, bloating and constipation. Also, be aware of Helicobacter infections, and parasites. When in doubt, breath test, and treat. Sometimes symptoms are just so obvious that we simply treat- especially since Functional doctors tend not to treat SIBO with antibiotics, nor do we treat SIFO with anti-fungals.

Balance your Hormones

Both female hormones and male hormones need to be balanced for optimal gut motility, necessary to prevent “backwash” and infections. The gut “works better,” and the microbiome stays more in balance when your hormones are in balance. A full discussion of this is beyond the scope of this article. Be aware, however that during menopause, the decrease in estrogen causes a rise in cortisol, something we just discussed. Also be aware that adequate progesterone is necessary, as is adequate thyroid hormone for optimal gut motility. Gut motility depends on a healed gut which includes a healed smooth muscle propulsive layer.

Re-balance Gut Motility  

As the gut lining becomes destroyed, some segments of the small and large intestine (depending on where the involvement of the disease is) get destroyed and therefore “out of sync.” As the gut heals, we sometimes need to use products to bulk up the stool and therefore improve the transport of “contents” such as modified citrus pectin or a multi-fiber blend. Sometimes we need to also improve GI transit at the smooth muscle level (by utilizing the serotonin precursor 5-HTP for example.) As mentioned, hormones need to be normalized as well. It’s strange to realize that diseases which produce “explosive” diarrhea can actually cause bloating and constipation while healing occurs, but indeed, this can happen. Now, let’s discuss what needs to happen to your microbiome.

Re-Balance your Microbiome

By definition, when you have leaky gut, you have more “bad bacteria” than “good bacteria” populating your GI tract.  Use prebiotic fiber to feed the good bacteria and (if you are not in a “mold situation”) a little bit of “good yeast” to re-create a healthy gut microbiome. State of the art care is to add a friendly yeast called Saccharomyces boulardii (by prescription: Florastor). Regarding prebiotic fiber, start with asparagus, Jerusalem artichokes, red onions and naturally fermented (not pickled) foods such as sauerkraut. If you like un-ripe bananas, they make great prebiotic fiber.

When your gut lining is coming together-usually the 2 to 3 week mark, add probiotics. Do not purchase or even make your own yogurt; you can’t have dairy yet, remember? Historically, we have recommended 50 to 100 billion probiotic CFU’s per day. A mixture (in your main probiotic) of Lactobacillus species and Bifidobacterium species is probably fine, but there is increasingly more evidence supporting the use of sporulating probiotics for an even better microbiome.  A generic product, VSL3, has yielded some positive remission studies, as have the probiotic strains Lactobacillus casei and Lactobacillus rhamnosus.

The most current research supports the use of sporulating (soil-based) probiotics to create a more diverse and therefore more healthy microbiome. These sporulating probiotics are so potent, you need to be careful not to “overdose”, or you can experience cramping and diarrhea. Start as low as 5 billion and increasing to as many as 25 billion CFU’s daily (best done under a doctor’s supervision). These probiotics are species of Bacillus with b. subtilis and b. coagulans being the most studied. Finally, if you see your diarrhea disappear but still have gas and bloating studies are promising for using 10 billion CFU’s of Lactobacillus plantarum. If that doesn’t work, consider the SIBO/SIFO angle if you haven’t done so already. Next, let’s discuss what has revolutionized the treatment of Crohn’s disease and ulcerative colitis: peptides and LDN. First, let’s discuss peptides.

Peptides

Peptides are short strings of amino acids, typically composed of 2–50 amino acids. The peptides used in functional medicine are derived from human secretions and therefore bioidentical; meaning no side effects such as what we see with pharmaceuticals. There are many peptides being used for many functions in functional and integrative medicine, but three in particular which are used in various forms, combinations and doses for ulcerative colitis and Crohn’s disease treatment.

BPC-157

The pentadecapeptide Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val, M.W. 1419, named BPC 157 has been demonstrated to counteract peritonitis and heal intestinal lesions-especially colitis lesions.

Gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419 as above) is stable in human gastric juice, now found to be effective both in the upper and lower GI tract, and remarkably free of side effects. BPC 157 has been demonstrated to be an efficient therapy of inflammatory bowel disease. It has been shown  to interact with the nitric oxide protective system, providing endothelium protection and counteracting severe complications of advanced and poorly controlled inflammatory bowel disease.

GHK-Cu

The human peptide GHK-Cu (glycyl-l-histidyl-l-lysine) has multiple biological actions, all of which appear to be positive. It stimulates blood vessel and nerve outgrowth, increases collagen, elastin, and glycosaminoglycan synthesis and supports the function of dermal fibroblasts. GHK’s ability to improve tissue repair has been demonstrated for skin, lung connective tissue, bone, liver, and stomach lining. It has been extrapolated to have reparative effects on the lining of the entire gut.

KPV

α-Melanocyte-stimulating hormone (α-MSH) is a cleavage product of a melanocortin that has protective and anti-inflammatory effects. Its anti-inflammatory activity has been shown to be mediated by three N-terminal amino acids: lysine-proline-valine (KPV). The KPV peptide alone has been found to exert an even stronger anti-inflammatory effect than the whole α-MSH peptide.

KPV has been demonstrated to attenuate the inflammatory responses of colonic epithelial and immune cells and reduce the incidence of colitis  upon oral administration. KPV exerts its anti-inflammatory function inside cells, where it inactivates inflammatory pathways by a decrease in pro-inflammatory cytokine expression. Very importantly, unlike the drugs currently used for U.C. therapy and Crohn’s disease treatment, KPV is a naturally derived tripeptide without any notable side effects. And now to what many of us consider the “game changer” for all autoimmune disorders: low dose naltrexone.

Low Dose Naltrexone 

Close to a third of patients with inflammatory bowel disease are resistant to all currently available pharmaceuticals, or they relapse over time. Investigators have turned their eyes to studying the effects of “LDN” on the gut epithelial barrier in treatment resistant patients with ulcerative colitis and Crohn’s disease.

One study utilized low dose naltrexone for 47 patients who were followed prospectively for 12 weeks. Where available, endoscopic data including tissue biopsies were collected. The effect of LDN on wound healing and tissue biopsies from endoscopic procedures were evaluated. The results? Spectacular in my book. Low dose naltrexone resulted in “significant clinical improvement” in 75%, and complete remission in 25% of patients.

Another clinical study involves close to 600 inflammatory bowel patients. Among the 250 or so patients who became persistent LDN takers, there were reductions in the number of users of all previously consumed drugs (down by 12%), intestinal anti-inflammatory agents (down by 17%), other immunosuppressants (down by a whopping 29%), intestinal corticosteroids (also markedly decreased by 32%), and aminosalicylates (decreased by 17%). Of importance: this study did not manipulate diet or use any other gut-healing agents. Not even any probiotics!

The most recent clinical study assessing LDN in IBD involved 28 patients affected by Crohn’s disease and 19 by ulcerative colitis. Patients with an intractable (meaning basically untreatable by conventional methods) active phase of IBD received a daily dose of LDN  in addition to standard treatment. Follow-up lasted for approximately 3 months and 35 patients (75%!) responded to therapy with  a decrease in disease activity which lasted for at least a month. Six patients achieved full clinical remission, including five of them having a complete endoscopic remission.

Just imagine if the above patients had been put on my autoimmune diet, given peptides, vitamin D, sporulating probiotics with good prebiotics- along with their LDN? And just imagine that we could add in some supplements? What, then would the response rate be? Let’s finish up with some possibly helpful supplements.

Supplements and more for TNF-alpha Reduction

“Conventional medicine” offers Crohn’s and U.C. patients “biologics,” which come with an array of potentially fatal side effects. I’m not saying they don’t work, and I also don’t suggest that you stop anything “cold-turkey.”  We know that these drugs all lower a laboratory biomarker called TNF-alpha. Disease activity appears to correlate with the level of this marker. We don’t yet know if reducing this marker will reduce disease activity in humans. However we know that TNF-alpha is likely a toxic lab value that we’d probably prefer to get as low as possible, no matter what. If that’s the case, then the following “in vitro” information is relevant.

We know that nutritional ketosis will inhibit TNF-alpha. Resveratrol, curcumin, melatonin, PQQ and vitamin D will also all inhibit TNF-alpha. We understand that some activities (ice baths, FIR saunas, and even cold showers, and baths) will suppress TNF-alpha, and have other beneficial physiologic effects. So, as a last thought on these things, why not?

Finally, this article contains a great deal of information that can inform you- the patient and can also inform your doctor. It is not information that is intended to diagnose or treat patients who have inflammatory bowel disease. As with all procedures and “meds” used in the practice of medicine, the dose, timing, mixture, and monitoring of symptoms and laboratory tests is crucial to obtain optimal results. Not to mention the cooperation between the patient and an experienced, board-certified Functional doctor.

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Antonija Duzel, Josipa Vlainic, Marko Antunovic, Dominik Malekinusic, Borna Vrdoljak, Mariam Samara, Slaven Gojkovic, Ivan Krezic, Tinka Vidovic, Zdenko Bilic, Mario Knezevic, Marko Sever, Nermin Lojo, Antonio Kokot, Marijan Kolovrat, Domagoj Drmic, Jaksa Vukojevic, Tamara Kralj, Katarina Kasnik, Marko Siroglavic, Sven Seiwerth, and Predrag Sikiric
Review:Curr Med Chem

doi: 10.2174/092986712803414015.

Focus on ulcerative colitis: stable gastric pentadecapeptide BPC 157

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Review:Inflammopharmacology

Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, PL 14736, Pliva, Croatia). Full and distended stomach, and vascular response

P Sikiric1S SeiwerthL BrcicA B BlagaicI ZoricicM SeverR KlicekB RadicN KellerK SiposA JakirM UdovicicA TonkicN KokicB TurkovicS MiseT Anic
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PMID: 29986520

Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data

Loren Pickart and Anna Margolina*
 2017 Jul 5; 25(7): 1628–1640.
PMID: 28143741

Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis

Bo Xiao, Zhigang Xu, Emilie Viennois, Yuchen Zhang, Zhan Zhang, Mingzhen Zhang, Moon Kwon Han, Yuejun Kang, and Didier Merlin

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Guillaume Dalmasso, Laetitia Charrier-Hisamuddin, Hang Thi Thu Nguyen, Yutao Yan, Shanthi Sitaraman, and Didier Merlin
Inflamm Bowel Dis
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doi: 10.1002/ibd.20334.

Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease

Klaus Kannengiesser1Christian MaaserJan HeidemannAndreas LuegeringMatthias RossThomas BrzoskaMarkus BohmThomas A LugerWolfram DomschkeTorsten Kucharzik