Supplements for Gut Issues, IBD, and IBS — How and Why They Work
Update: I’ve gotten a bunch of requests for what specific supplements I used, so I made this Amazon list with everything that I’ve taken. There are some additional supplements on the list that I haven’t written about yet. I’ll be updating this post in the near future with the science behind those too. I researched each supplement and tried to choose ones that were well regarded or rated well on www.labdoor.com (when available).
I have Ulcerative Colitis, an autoimmune disease that causes severe inflammation in the colon, ulcers, and potential long term damage. If you ask a doctor, they’ll tell you the only cure for Ulcerative Colitis is to remove the colon completely. This happens to about 25–30% of UC patients, and this was the path that I was on.
In November 2016, my colon was so severely inflamed that a test for inflammatory markers (Fecal Calprotectin) showed levels higher than what could be measured by the test. I consulted several doctors who all agreed that my last chance was a new drug (that had less than a 40% success rate), otherwise I’d have to have my colon removed. I didn’t like the sound of those odds, so I kindly thanked them and declined their suggestions. I spent the next several weeks 100% focused on researching gut inflammation, how to combat it, and how to repair the damage already done. I designed a supplement regime based on my research (and others’ research before me). After two months of a being on that regime, I repeated that same Fecal Calprotectin test and my inflammation markers were completely gone — zero signs of inflammation. My doctors were in shock.
Before I get into what specific supplements I took and why, it’s important to understand the science behind what’s happening in the gut and what chemical and biological pathways we can target to reduce inflammation and stimulate repair. So first, I want to explain the science behind:
- Antioxidants, free radicals, and Reactive Oxygen Species (ROS)
- TNF-alpha and the NF-kappaB inflammatory pathway
- The colonic mucosal membrane
A note on IBS (Irritable Bowel Syndrome) as well: IBS is a blanket term that doctors use to classify a huge range of gut issues. Essentially, it’s a term/diagnosis that doctors can use that lets them avoid saying, “I have no idea what’s wrong with you and unfortunately don’t know how to help you.” While my research has mostly focused on IBD (Inflammatory Bowel Disease) and the colon (large intestine), the more I learn, the more confident I’m getting that IBS is an early form/warning sign of the development of some larger type of gut disease like Crohn’s or Ulcerative Colitis. I still need to do more research to validate that theory, but if it’s correct, the information below should be helpful for people with IBS too (at least if it’s colon related).
Antioxidants, Free Radicals, and Reactive Oxygen Species (ROS)
Most of us have probably heard about antioxidants but are pretty unclear on what they actually do and how they do it. To understand antioxidants, we first have to understand free radicals and reactive oxygen species (ROS).
A free radical is simply an atom or group of atoms with an unpaired electron. They are a natural part of human chemistry/biology and are formed when oxygen interacts with certain molecules. Since free radicals contain an unpaired electron, they are highly unstable and try to capture electrons from other atoms or substances in order to neutralize themselves. While capturing an electron neutralizes that specific free radical, it can then cause a chain reaction which triggers thousands of other free radical reactions in a matter of seconds. This can destabilize other atoms, DNA, and cause cell damage. This is bad.
Reactive oxygen species (ROS) is a broad term which covers all chemically reactive species containing oxygen (this includes free radicals). When ROS levels are increased over an extended period of time, significant cell damage can result, which is known as oxidative stress. This is also bad — oxidative stress has been linked as a significant contributor to a huge number of diseases, including many autoimmune and all inflammatory diseases. In IBD (Crohn’s and Colitis), it is well documented that oxidative stress is a major contributing factor to the development and recurrence of the disease.
This is where antioxidants come in. Instead of free radicals stealing an electron from some other molecule (oxidizing it), the free radical steals an electron from an antioxidant in a way that stops the free radical chain reaction. Explained a simpler way, antioxidants neutralize free radicals. In healthy human biology, we should have the correct balance of free radicals and antioxidants, but with the Standard American Diet and the largely nutrient depleted food that we eat, this is often not the case. Some great data has come out in recent years on the positive impact of antioxidants on various inflammatory diseases, especially Ulcerative Colitis and Crohn’s. (This is one of the best reviews that I’ve found on ROS and antioxidant impact on IBD.)
TNF-alpha and the NF-kappaB Inflammatory Pathway
TNF-alpha is a cytokine. Cytokines are a broad term for small proteins that are important in cell signaling. Think of them like messengers. There are both pro-inflammatory and anti-inflammatory cytokines, and they are very important in the modulation of the immune system.
TNFα is a pro-inflammatory cytokine (messenger) that is necessary and highly important in the regulation of our immune function. But if too much TNFα is released; as in people with autoimmune diseases like IBD, Celiac Disease, Arthritis, and Psoriasis; it can lead to systemic inflammation through the over-activation of an inflammatory immune pathway called NF-kappaB. There are powerful pharmaceutical drugs on the market that target TNFα (Remicade, Humira), or NF-κB (Entyvio), but they carry some very severe potential side effects (like lymphoma) and have been shown to work 50% or less of the time (wtf, right?). I used to be on Remicade. And it didn’t work.
TNFα also has a negative effect on the tight junctions in the intestinal cell wall. Tight junctions are the connections between two cells that keep their cell membranes pressed tightly against each other (and don’t let other things pass between them). TNFα causes those tight junctions to loosen, which can lead to what’s known as leaky gut (where bacteria, food proteins, and toxins literally leak through cracks in the intestinal cell wall and into the bloodstream).
I still need to do some more reading to understand exactly why TNFα is so elevated in people with autoimmune diseases, but my preliminary research points to a combination of improper diet, microbiome imbalance, high levels of ROS, and some level of genetic predisposition.
Colonic Mucosal Membrane
Everyone’s large intestine has a mucosal membrane that separates the food/waste contents of the gut from the actual intestinal cell wall (called the epithelium). The mucosal membrane has two layers — an outer loose layer, and an inner “impenetrable” layer that protects the intestinal cell wall from bacteria, ROS, free radicals, food proteins, etc. Gut bacteria adhere to and live on the outer layer, which is very important for our intestinal function. But if that outer layer is broken down, then bacteria start penetrating the inner mucosal layer, make it to the intestinal cell wall, and start creating inflammation and leaky gut.
The mucosal membrane and TNFα are very interrelated. An increase in TNFα causes an increase in the expression of genes that lead to a breakdown of the mucosal membrane in the gut. And since TNFα is increased in people with IBD (Crohn’s and Colitis), IBS (and leaky gut), and Celiac Disease, anyone with those diseases are at risk for a damaged mucosal membrane.
First, I focused on adding antioxidants, which also serve as TNFα and NF-κB inhibitors. I also increased my intake of anti-inflammatory Omega 3s. After I started noticing a positive benefit, the next phase was adding supplements to support the mucosal membrane repair. My last step is microbiome rebalance, which is currently ongoing (I started daily fecal transplants on Monday!)
Several of the supplements below are either broken down in the stomach or absorbed too quickly in the small intestine to make it to the colon — so for the first couple weeks, I mixed a combo of multiple of these supplements with distilled water (NOT chlorinated tap water) into enemas. Yes, up the bum. Yes, it was a bit uncomfortable. Yes, it worked very well. And yes, I’m very glad I did it.
It was very important to me to come at this from a scientific perspective, not just based on people’s accounts of, “I think this worked.” So every supplement I took, I based on research about how it works on a chemical/biological level in the body, and ideally found clinical trials or other research trials on actual IBD or IBS patients. Sources are listed at the bottom.
Antioxidants (which also serve as TNFα inhibitors, and down-regulate NF-κB pathway):
Turmeric (Curcumin) — 750–1500 mg/day orally, 500 mg for enema
- Curcumin has been shown in many studies to be a powerful antioxidant and anti-inflammatory, and has been used to treat inflammation in Ayurvedic medicine for thousands of years.
Glutathione — 500 mg/day orally (liposomal glutathione), 300 mg for enema
- Glutathione is the body’s primary intracellular antioxidant. Patients with IBD have decreased glutathione synthesis and mucosal glutathione levels. Glutathione is absorbed very quickly in the stomach, so either liposomal glutathione needs to be taken orally to get it to the gut (still will be mostly absorbed in the small intestine), or taken via enema.
N acetyl cysteine (NAC) — 600 mg/day orally, 500 mg for enema
- NAC is a precursor to glutathione. It serves as an antioxidant and anti-inflammatory, inhibiting the NF-κB pathway.
Melatonin — 10 mg/day before bed
- Melatonin reduces inflammation and oxidative stress. One clinical trial showed that including melatonin in addition to standard UC treatments induced remission earlier and with greater amounts of mucosal healing compared to standard treatment alone.
Resveratrol — 500 mg/day orally, 300 mg for enema
- Resveratrol is an antioxidant that downregulates the NF-κB and MAPK inflammatory pathways. A trial with 500 mg daily supplementation of Resveratrol for IBD patients showed a decrease in TNFα levels and NF-κB activity.
Quercetin — 300 mg for enema
- Quercetin is a powerful antioxidant and anti-inflammatory, and inhibits TNFα in epithelial cells. Quercetin is very quickly broken down in the stomach or absorbed in the small intestine, so if you want it to help your colon it needs to be administered rectally, or Rutin can be taken instead (see below).
Rutin (3‐O‐rhamnosyl‐glucosyl‐quercetin) — 900 mg/day orally
- Rutin is metabolised by colonic bacteria into quercetin. This stuff is great.
EGCG (green tea extract) — 400 mg/day orally
- EGCG improves the function of tight junctions in the gut, reducing symptoms of leaky gut.
Cannabidol (CBD) — 10 mg CBD orally before bed, 10 mg for enema (didn’t use this every day)
- Cannabidol is the non-psychoactive component of cannabis. Several studies have shown that it downregulates TNFalpha expression and regulates the colonic tissue response to excessive inflammation. In California, CBD pills can be purchased with a medical prescription.
Vitamin E — 2000–3000 IUs for enemas
- Vitamin E has some mixed results as an antioxidant (potentially because it is metabolized too quickly when taken orally), but one clinical study showed that 64% of UC patients achieved remission after 12 weeks of rectal Vitamin E supplementation. The study used 8000 IU/day, but I didn’t use quite that much.
Omega 3 DHA and EPA — 600–1200 mg/day DHA orally
- I’ve read a lot of inconclusive studies about supplementation with Omega 3s for IBD and UC, often due to poor experiment design. However, there is a lot of clear literature on the benefit of Omega 3s for reducing inflammation, and most of us get too few Omega 3s in our diet.
Colonic Mucosal Membrane Support
N acetyl glucosamine (NAG) — 700–1400 mg/day orally, 700mg for enema
- NAG is a precursor to a critical component of the colonic mucus layer called glycosaminoglycan. In one study, supplementation with NAG showed symptom improvement in 88% of IBD patients.
Mucin — 200 mg/day orally
- Mucin is one of the core components of the mucous membrane. Mucin is produced by goblet cells in the intestines, but UC has been associated with a decreased number of goblet cells, and therefore a decreased amount of mucin.
Phosphatidylcholine (PC) — 1000 mg/day orally, 1500 mg for enema
- PC is another essential component of intestinal mucous. Mucus PC content is reduced by 70% in UC patients, regardless of if they have active inflammation or not. Multiple clinical trials have shown that a delayed release form of PC can induce remission of UC. There isn’t a good source for delayed release PC in the US, but standard PC can be purchased easily and administered rectally for the same effect.
Zinc Picolinate — 22 mg/day orally, 22 mg for enema
- Diarrhea can lead to mineral deficiency in general. Zinc deficiency is commonly seen in UC patients and can lead to more severe IBD symptoms.
Magnesium — 500 mg/day orally before bed
- Similar to zinc, diarrhea can lead to magnesium deficiency. Be careful though, because too much magnesium can actually cause diarrhea.
A final disclaimer. I’m not a doctor, but I’m very personally invested in this and applied the scientific rigor to this research that I was taught as an engineer at MIT. The above supplement plan had a dramatic positive effect on me, far better than any of the plethora of pharmaceuticals that doctors have tried on me. What worked for me may not work for everyone as our bodies are incredibly complex systems. But I hope that by providing this information it might help steer some others in the right direction in their own research or self-healing plan.
As always, please comment, ask questions, send me an email with feedback (email@example.com), etc. And if think any of the above is innacurate, have different viewpoints, or contrary research/data, please please share! I’m a sponge for data right now and love reading any new information I can.
A note of thanks: I want to thank everyone who helped me along the way with my research, most of whom were complete strangers. I also want to thank all the researchers and scientists who have published studies on the above topics, and made this information available for people like me. Without those studies, I would have had no information to enable me to take this alternative approach to getting healthy. And finally, I want to thank Michael Briggs. Michael is someone who, like me, has UC and decided to take his health into his own hands. Michael wrote an excellent paper detailing his research on the gut, supplements, and how he healed his Colitis. His paper gave me the confidence that this type of approach could work and was one of the first resources that got me started down this path.
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Antioxidants, Free Radicals, ROS, TNFα, and NF-κB:
Omega 3 Supplements:
Colonic Mucous Membrane Supplements:
Michael Briggs’ Paper: