Chapter One
Intestinal Health
Terri was a sixty-year-old executive who had enjoyed a very active lifestyle and ran a very successful business. She cares for her elderly mother, whom she moved into her home a few years prior, and loves caring for her four young granddaughters a few days each week.
Even though she was happily remarried following a traumatic divorce several years prior,Terry retained the trauma of her previous marriage that left her with some fairly significant PTSD, which manifested as intestinal symptoms: debilitating diarrhea, significant weight loss, and so on. Though she has a family history of Crohn’s disease and many of her symptoms were similar, thus far it had not been found in her.
The diarrhea and weight loss begin to affect her ability to function in the boardroom, in the weight room, at her home, and in the bedroom. “I can’t go on like this,” she told me tearfully. “What is happening to me?”
The Source of All Illness?
For many years, allopaths and even functional medicine doctors did not hear our naturopathic colleagues telling us that the large and small intestines are the source of all illness.The immune system lives right around the intestinal wall, just one cell layer between the outside world and the inside; it’s parked there, like a centurion, just waiting for the entry of an invader.
What sort of invaders are we talking about? It varies from person to person, but certain gluten, stress, or infections, like bacteria or viruses, can cause the breakdown of that one cell layer and allow entry of food particles and infections into the body, which triggers the immune response.An activated immune system will wreak havoc all over the body, causing things like skin rashes, brain fog, heart problems, and liver malfunction, just to name a few.
As you navigate through your health journey, keep this in mind: If your intestines are working the way they are supposed to, everything else falls into place.
Therefore, a raised awareness of symptoms that indicate something is out of whack is required. For instance, you should be moving your bowels at least once a day, and it should be easy to pass. In children, their bowels move after just about every meal, and it’s fantastic if you can move them as often as an adult. Regardless, you shouldn’t have to stress or strain to move them.
If you're doing anything less than one easy pass per day, then it's probably a little bit of constipation. If you’re passing very loose, more liquid than solid stools, it’s diarrhea. If those bowels are watery, not only does this suggest infection, but you can also easily become dehydrated.
Another ailment directly linked to intestinal health is increased intestinal permeability, commonly known as “leaky gut syndrome.” Remember, only one cell layer stands between the world and your body—the intestinal epithelial cells.That cell layer is the gatekeeper, and it can be breached by things like gluten, stress, viruses, and bacteria. Now things can get into the body that aren't supposed to get into the body, and we can develop allergies and food sensitivities. The immune system then attacks what should just be amino acids and vitamins that have already been
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digested, but because of the breakdown of the intestinal epithelial layer,now these things can “leak”in and gain access to our immune system,which immediately creates an antibody to what it perceives as an invader.
This is more than just diarrhea,constipation,and leaky gut, however; smaller things,like bloating after eating a particular food, or experiencing heartburn or reflux need more than a cursory acknowledgement; this indicates that you may not digest certain foods well, but this also dials directly into your immune system before more severe complications occur. Those random moments, too, where you just feel kind of “off,” should not be dismissed, either—that could be an early indicator that is linked to your intestinal health, too.
What’s Happening at the Cellular Level?
One of the coolest concepts to grasp here is the way that intestinal cells work.There is this beautiful, symbiotic relationship between the healthy bugs that live in your gut and the intestinal epithelial cells—that one-cell layer thick between the world and your body that I mentioned earlier. This beautiful relationship is recognized when you eat fiber; it goes into your intestines. Your happy,healthy intestinal bugs will eat that fiber and convert it into your intestinal epithelial cells’preferred fuel source called butyrate. This is a fat that gives those cells all the energy they need.
Just like the other cells in your body, those cells have the option to choose which foods they prefer; kind of like when we’re trying to decide what to eat, we have the choice of eating Twizzlers, a chicken breast, a baked potato, and so on. The cells have the choice of sugar without oxygen,sugar with oxygen,or fat.
��Sugar without oxygen produces about two packets of energy (called ATP).
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��Sugar with oxygen produces about thirty packets of energy.
��Fat, used as a substitute for sugar, produces about a hundred packages of energy.
It’s clear that fat is way more efficient, and the cell functions optimally when it has plenty of energy.
Bottom line: a happy, intestinal epithelial cell, a happy brain cell, a happy heart muscle cell, or a happy liver cell all function optimally when they have as much energy as they can possibly have in order to accomplish their job for the day. By the same token, bugs in the intestine eat fiber that you consume and create delicious butyrate for your intestinal epithelial cells. They take that fat and make a hundred packets of energy.They suck up all the oxygen from the bloodstream, leaving the lumen an oxygenless space perfect for the “good bugs” that function well without oxygen. If you have a colonoscopy prep, three days of antibiotics, or a stomach flu, this erases those ‘good bugs’from the lumen and now the ‘bad bugs’take over and steal all the oxygen so your intestinal epithelial cells (IECs) aren’t able to make the energy they need. Stressed cells may ultimately result in diseases like ulcerative colitis or colon cancer; they love to be in a nooxygen environment that gives all the energy-making resources to your intestinal epithelial cells.In turn,the intestinal epithelial cells aren’t panicking,because they have all the nutrients,all the oxygen, everything they need.This is a beautiful, symbiotic relationship.
Peptides assist in making your cells happy!
Individual Peptides
Peptides are strings of fewer than fifty amino acids with a signaling function within or between cells. As I mentioned in the Introduction, most peptides are known by numerical and alphabet
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letter names because they are not owned by a pharmaceutical company yet (familiar exceptions to this are the peptides Bacitracin, a topical antibiotic and losartan, an oral blood pressure medicine). Peptides work synergistically with your intestinal epithelial cells.
If you take an antibiotic, prepare for colonoscopy, or have an intestinal bug like a viral gastroenteritis or stomach flu, all of a sudden you have completely changed your microbiome and allowed for the overgrowth of bugs that like to be in an oxygenated environment. Now your intestinal epithelial cells are competing with the microbes in your intestines for oxygen; if they don’t have enough oxygen to make the energy they need, your intestinal epithelial cells begin to participate in the inflammatory response. Working in tandem with lifestyle changes, dietary changes, and supplements, peptides can be the final push that rights the ship.
When it comes to intestinal health, I commonly prescribe any of the following peptides:
BPC-157
This is a fifteen-amino acid fragment of the naturally occurring body-protection compound that comes from your stomach. It was first discovered in 1990, as a crucial mediator of stomach stress-coping response.
While most peptides are available by injection, BPC157 is available orally because the original peptide from which it was taken is an intestinal peptide from the stomach. It can actually tolerate the very, very low acidic pH of the stomach.
BPC-157 is a membrane stabilizer, and treats leaky gut by improving capillary permeability (i.e., the blood flow to the area). It also protects organs outside the intestinal tract, like the endothelium, which is the lining of the blood
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vessels. Because of its effect on many receptors in the body on different cells, it has tremendous anti-inflammatory effects; BPC-157 even has effects on the dopamine and serotonin systems in the brain, which influence mood and energy.
It decreases ulcers of the stomach and duodenal, which is the first part of the small intestine, after stress exposure. They exposed rats, mice, and chickens to heat-cold restraint alcohol acid; the animals developed ulcers in their stomach as a result. When they were given BPC-157,and it resolved their ulcerations.
One of the problems with reflux or heartburn is that the tight band at the bottom of the esophagus—located between the esophagus and the stomach—relaxes, allowing acid to reflux back up into the esophagus, which isn't supposed to see any acid.That’s actually the cause of reflux. Anti-inflammatories like Motrin, Advil, and others will cause relaxation of that lower esophageal sphincter. In a separate trial, rats were given an anti-inflammatory drug, which caused relaxation of the lower esophageal sphincter. When given BPC-157, each one’s lower esophageal sphincter function was restored.
While the focus of this chapter is intestinal health, BPC157 has also benefited patients with osteoarthritis, Parkinson's Disease, and spinal cord injury.This peptide is amazing!
Vasoactive Intestinal Peptide (VIP)
VIP is a twenty-eight amino acid neuropeptide that was isolated from the small intestine of pigs in 1970. It’s produced by neurons in the brain,nerve cells,and immune cells,but it’s present in most of the organs of the body.It regulates the secretion process and motility of the intestinal tract; that’s how it functions in the intestine, regulating insulin and other hormone releases for metabolic function. In one study,VIP reduced the clinical severity
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of Crohn's disease, including weight loss, diarrhea, and macroscopic inflammation.Examining intestinal specimens under the microscope, researchers saw that they had a significant decrease in their inflammation. They also looked at the chemical messengers of inflammation, like tumor necrosis factor alpha (TNF-alpha) and IL-6, and discovered they had decreased, resulting in a reduced food allergy response.
Ipamorelin
Ipamorelin is a growth-hormone secretagogue, which means it increases secretion of growth hormone. Using Ipamorelin, patients won’t overdose on growth hormone because they’re not receiving actual growth hormone; instead, they receive something that's going to encourage the secretion of their own growth hormone.
The best thing about Ipamorelin as opposed to growth hormone itself is that it will release growth hormone within a respectable high potency and effectiveness, but it doesn't increase stress hormone levels, which growth hormone itself would increase.
Ipamorelin has benefited postoperative cases where the intestines are very slow to respond; it increases stool frequency, food intake, and restores body weight after surgery. There are several studies showing that—for patients who struggle with constipation—ipamorelin is a great way to improve the way the intestinal epithelial cells choose to use energy.
AT-1001
AT-1001 is an oral peptide that is locally active in the intestines. It is a tight junction regulator. Remember those intestinal epithelial cells, the gatekeepers? Remember that behind
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the gate sits the immune system.And if that tight junction or that gate is broken down, then things can get into the body that aren't supposed to,like bacteria,viruses,and broccoli.AT-1001 regulates that barrier, and prevents it from opening, which prevents things from reaching your intestinal immunity and triggering this inflammatory response. It improves leaky gut or intestinal permeability, and is specifically being studied in patients with celiac disease.
In fact,patients who actually took this and then consumed gluten, AT-1001 prevented their gluten-induced symptoms. It decreased their antibody production, it improved their leaky gut, and the production of all the inflammatory chemicals with a safety profile that was comparable to placebo.
There is also evidence that indicates AT-1001 works against Covid,which is awesome.The interesting thing about AT1001 is that you will know within two weeks if your body will respond well to it; patients should expect to see significant improvement in their skin and intestinal symptoms.
LL37
LL37 is a thirty-seven amino acid, positively charged antimicrobial peptide that is produced by the colon cells. And I have to admit, I think it’s so cool that our own colon cells make their own antimicrobials!
Then, someone who was really smart found it and said, “Oh, we can make this in a lab. So if someone’s intestines aren't working properly, we can actually give them this so that they can have an antibacterial or antimicrobial effect!”LL37 penetrates the bacterial membrane and forms pores in the cell wall so that the bacteria cannot survive.
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When these bacteria invade your body, they produce this film that lays over them that is created by other bacteria,yeast,and other things to hide from your immune system. We call that a biofilm.That biofilm is protective of the dominant bacteria or dominant virus, hiding it from your immune system by covering itself in this blanket of schmutz—mucus, other bugs, and immune cells that tried to help and got killed in the process.
LL37 reduces the biofilm so that now you can actually see the bugs that are there, including the dominant bug; you can actually recruit your immune system to kill it rather than be distracted by all the schmutz. It is effective against all kinds of pathogens!
This little peptide can be effective against bacteria; viruses like herpes and rhinovirus (common cold); Borrelia, which causes Lyme disease; lots of intestinal bugs, like Klebsiella and E.coli. That said,proceed with caution: when used in excess,LL37 can act as an antigen and can ultimately assist a flare-up of psoriasis,when psoriasis is already present in the body. So if you already have psoriasis, I would not recommend using LL37.
Peptide Stacks
There are thousands of peptides working every day in your body, doing their jobs all together at the same time. When we prescribe peptides, we often will provide them in “stacks,” or combinations of multiple peptides—usually,anywhere from two to five,depending on what the circumstances are.An anti-aging stack would look different than an intestinal health stack; an intestinal health stack would look different in someone with Crohn’s disease than in someone with stomach ulcerations versus someone who was trying to recover from workouts. Peptide stacks are based on
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your baseline health, how they work in your body, and what we know about the disease state, if there is one present.
For example, if someone suffers from intestinal ailments, like acid reflux disease, we would of course begin by thoroughly reviewing and implementing any lifestyle changes—are they drinking too much coffee, too much alcohol, are they “eating” ibuprofen,and so on.We would also coordinate with their primary care provider to ensure our course of treatment complements any other strategies that are in place for the patient. I would probably start them with two double doses of BPC-157 per day; they would open one capsule and pour the contents in water, and take with another capsule that is still intact.
In many cases, these patients take proton pump inhibitors (PPIs), like Nexium, and this regimen can help them to gradually wean off of them, as chronic PPI use has been associated with development of osteoporosis and recurrent infections. If their symptoms are stress-induced, I would add the AT-1001, have them taking it at least once a day before their heaviest meal,or the meal that might include wheat (even though my preference would be that they give up wheat altogether). So if they typically don’t have pasta for dinner, but always have a croissant for breakfast, then they would want to take it before the croissant. But if they always have pasta for dinner, then they would want to take it before the pasta.
If a patient came in with Crohn's disease,I would probably add VIP to that regimen,as long as they weren’t having diarrhea— VIP moves the bowels along pretty quickly—and Thymus Alpha 1,which is a peptide we’ll dig into in the next chapter.A standard, leaky gut protocol would probably include VIP, AT-1001, and a third peptide called KPV, which is anti-inflammatory, and we’ll also discuss more in-depth in the next chapter.
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These peptides work in slightly different ways, but they all work at the cellular level. We use them together to optimize and synergize the effects.Stacking them in this way gives you far more benefits than taking a single one by itself.Think about it like this: You could eat a chicken breast for dinner and get some nutrients that way; but if you had one that’s Parmesan-encrusted, and came with roasted asparagus and mushrooms with créme fraîche, that meal would give you all the nutrients that you might need (not to mention a delicious taste!).
The peptides are a contributor to the solution, however. Treating the intestines includes a lot of dietary changes and natural supplement treatment, like collagen, glutamine, marshmallow, slippery elm…peptides are part of the solution, not the solution itself. The impact gut health has on other body systems cannot be ignored, either. Anytime we see someone who has depression, dementia, skin rashes, heart issues, among others, we are always going to look at what is happening with their intestines first. Nothing is going to get better if we’re not starting there.
FinalThoughts
Peptide therapy is not a magic cure-all, and patients must remain active participants in their health journey. There may be dietary and lifestyle changes,or supplements that need to be taken. If I’m treating someone with peptides, the strategy is not turnkey; many who are used to allopathic practitioners may think you visit a functional medicine doctor, they write you a prescription for the peptide, and you move on with your life. In fact, there are several steps we take to ensure optimal results, including any lifestyle changes that may need to be employed, coordinating with their primary care provider, and so on.
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In Terri’s case, we discovered she had a food allergy. She was treated with an elimination diet and repair supplements, plus BPC-157 (one open 500 mg capsule in water, taken with one 500 mg capsule intact).We resolved her diarrhea, and was able to gain back to her baseline weight and build muscle mass again. Today, she has a beautifully sculpted body, the energy to launch and sustain a new company . . . and still has energy left to keep going!
If you and your provider don’t pay attention to your intestinal health, you will increase your chances of developing an autoimmune disease. Increased intestinal permeability exposes us to things not usually seen by the immune system. Because the immune system should only see the outside of that cell or the breakdown products of broccoli, the permeability of the intestines gives it access, and therefore, now sees that cell or food fragment as a foreign entity. Exposure to the outside environment is due to increased intestinal permeability with stress or infections,exposing us to things we aren’t always aware of. If your intestinal health is problematic, your immune system may create an antibody to what it considers an invader.
A Closer Look at Leaky Gut
There is pathophysiology of antibiotics and other things that create leaky gut. Your intestinal epithelial cells recruit the immune system to help them fight off this threat; they’re telling your immune system, Hey I’m stressed out. I need some help.
The stress doesn’t always come from antibiotics; it can be a change in your diet, like keto, which has very low carbohydrates and fiber. Your cells can even get stressed just prepping for a colonoscopy. These destroy your microbiome and your intestines.
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The immune system also requires energy and oxygen, and now they begin to compete with the intestinal epithelial cells, resulting in the breakdown of the intestinal wall. If you have the wrong kind of bacteria inside the intestine; then you have a breakdown of the intestinal wall…and now those wrong kinds of bacteria begin to invade the body or the intestines. An inflammatory response has been set up, and one way to fix this is by increasing the amount of fiber in your diet so that you’re feeding your good bugs, and they’re making your intestines their favorite food.Taking a quality probiotic is another treatment strategy.
There are many books and even more opinions about this; simply put, knowing specific amounts of what your epithelial intestinal cells need is highly individualized, which makes it more difficult. Sometimes, you have to take the preferred fuel source directly; since fat is the preferred source for colon cells, administering butyrate rectally can be highly effective, as it helps your body and good bacteria with energy production. The exact dose would likely need to be sent to a compounding pharmacy.
A liquid form of ketones, another energy source, is available through a company called KetoneAid, sold as Ke4. A capsule called Tributyrin is also available, and finally, butyrate can be administered intravenously as sodium butyrate.
Fermented foods contain a lot of good bacteria. Foods like kimchi, yogurt, and sauerkraut are all good sources. Sauerkraut, in particular, actually contains glutamine, which also can help restore the mucosal layer on the inside of your intestinal epithelial cells— just one more barrier to protect you.
With leaky gut, the problem is not the overgrowth of bad bacteria; the problem is a stressed out intestinal epithelial cell that doesn't have the ability to make the energy it needs to perform its job. It’s competing with not only the bad bacteria in your gut, but
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also with the immune system for energy resources that are dwindling because of the presence of the bad bacteria.
If you elect to visit a functional medicine doctor, ask them, “What is your protocol for treating leaky gut?” That’s actually a great question, because if they don’t agree or believe that leaky gut actually exists, that’s a doctor you probably should stay away from.
Instead, if they mention things like slippery elm, marshmallow root, and glutamine, those are all supplements with evidence-based research backing their use in repairing the mucosal lining as well as the intestinal barrier, which maintains gut integrity.
Finally, if their answer is to take Pepcid or Nexium, then that’s a doctor you may want to avoid, and seek additional care from a functional medicine doctor.
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