A few years ago I wrote a blog post on the 4-R protocol. Since then it’s been updated to the “5-R Protocol by the Institute for Functional Medicine”, and I figured it would be a good idea to update and expand on the original post I wrote on this topic. If you’re not familiar with this protocol then you’ll quickly realize that it relates to the healing of the gut, and a leaky gut is a factor with most, if not all autoimmune conditions, including Graves’ Disease and Hashimoto’s Thyroiditis. And while the information in this post will focus greatly on thyroid autoimmunity, even if you don’t have an autoimmune thyroid condition, I feel that a lot of people can benefit from this information.
So let’s dive right into the protocol and discuss each of the five components
1. Remove. Although genetics is a factor with most, if not all autoimmune conditions, in order for someone to develop autoimmunity they must be exposed to an environmental trigger. And in order to reverse the autoimmune component and restore the person’s health it is necessary to find and remove the trigger. The same is true with regards to healing a leaky gut. While many people with a leaky gut will take supplements such as L-glutamine, and eat gut-healing foods such as bone broth, you won’t be able to heal your gut if you don’t detect and remove the leaky gut trigger.
This of course is easier said than done at times, as it’s not always easy to find out what the trigger is. However, these are some of the common factors which can cause a leaky gut:
Food allergens. Although many food allergens can potentially cause an increase in intestinal permeability, in the research I was able to find evidence for gluten (1) , corn oil (2) , and red wine (3)  being factors which can cause a leaky gut.
Gut infections. In the literature there are numerous infections which can cause an increase in intestinal permeability. This includes candida (4)  (5) , H. Pylori (6) , Blastocystis hominis (7)  (8) , and giardia (9) . There is also evidence that small intestinal bacterial overgrowth can cause an increase in intestinal permeability (10)  (11) .
Systemic Inflammation. I also came across a study which showed that systemic inflammation can cause an increase in intestinal permeability (16) .
Finding the trigger is arguably the most difficult component of the 5-R protocol. But once this has been accomplished you can move onto the next four components, which I’m about to discuss.
2. Replace. The next component is to replace certain factors which play a role in digestion. Many people reading this have taken digestive enzymes. These include enzymes to break down protein (proteases), carbohydrates (amylase), and fat (lipase). Many people with low gastric acid (stomach acid) can benefit from taking betaine HCL with meals. Gastric acid consists mostly of hydrochloric acid, which is released from the parietal cells of the stomach. It plays a role in activating pepsinogen into the active enzyme pepsin, which in turn breaks down proteins.
Some people can also benefit from supplementing with bile salts. This is especially true for those people who have had their gallbladder removed, as getting gallbladder surgery doesn’t address the bile metabolism issues commonly associated with these conditions. But some other people can also benefit from taking bile salts, such as those who have problems emulsifying fats.
Although dietary fiber doesn’t fall under the same category as digestive enzymes, betaine HCL, and bile salts, many people don’t consume enough dietary fiber, which is important for numerous reasons. First of all, fiber helps to feed the good bacteria of the microbiota. In addition, having sufficient dietary fiber is important for having regular bowel movements.
3. Reinoculate. Many people take probiotic supplements, which is one method of reinoculating, or repopulating the gut flora. And of course there are ways to accomplish this through diet as well. But why do people have to reinoculate in the first place? Well, there are many different factors which have a negative effect on the microbiota, including the foods we eat, taking antibiotics, being exposed to other environmental toxins, and even chronic stress can have a negative impact on our gut flora.
So what is the best way to reinoculate? To be honest, we’re still in the beginning stages of dealing with probiotics, and so the approach we take now very likely won’t be the approach we take five to ten years from now. I commonly recommend a probiotic supplement to my patients, but even this comes with some controversy, as not all probiotic supplements are created equally. And some healthcare professionals like myself will recommend formulations with specific, well-researched probiotic strains, while other doctors won’t pay as much attention to the strains included, but instead will focus more on the diversity. In other words, some will recommend a probiotic which has many different species, without worrying about the specific strains.
While it can be beneficial to take a probiotic supplement, it also is a good idea to take some prebiotics, and eat food sources of probiotics. With regards to prebiotics, one can take a prebiotic supplement such as inulin or larch arabinogalactan, or you can eat prebiotic foods such as Jerusalam artichokes, asparagus, onions, chicory, bananas and other fruit, and even green tea is considered to be a source of prebiotics (17)  (18) . The reason why prebiotic foods are important is because they feed the good bacteria such as bifidobacteria and lactobacilli, and these foods also are good sources of short chain fatty acids.
Probiotic Supplements vs. Food Sources
But why take a probiotic supplement when there are some excellent food sources of probiotics? After all, foods such as sauerkraut, kimchi, kombucha, kefir, and a good quality source of yogurt can all be good sources of probiotics. Well, I recommend getting probiotics from both supplements and food sources, and the reason for this is because the supplements you take will have different strains than the food sources. Plus, many people simply don’t eat enough food sources of probiotics.
What About Soil-Based Probiotics and Fecal Transplants?
Over the past year I’ve had a lot of people ask me about soil-based probiotics, and I only recently started using these in my practice, and so I can’t say I have much experience with these. Some examples of soil-based probiotics include bacillus subtilis and bacillus coagulans. These are also known as spore-based probiotics. These not only are more resistant to the gastric acid of the stomach than some other probiotic strains, but some sources claim that they colonize the gut more effectively. If anyone reading this has had a positive experience while taking spore-based probiotics please feel free to share your experience in the comments section below.
I don’t get asked as much about fecal microbiota transplants, but I figured it was worth mentioning this here because this can potentially help with many different conditions. This essentially involves transplanting healthy bacteria from one individual to another individual. It seems to be very effective in helping people with Clostridium difficile, and while it hasn’t been approved for other conditions in the United States, this probably will change in the future.
4. Repair. Many people reading this are familiar with a “leaky gut”, which I briefly spoke about earlier. This is when the intestinal barrier is compromised, which allows larger proteins to pass into the bloodstream, where they normally shouldn’t be. As a result, the immune system sees them as being foreign and mounts an immune system response. Some claim that in order for autoimmunity to develop you need 1) a genetic predisposition, 2) an environmental trigger, and 3) a leaky gut. I briefly spoke about this earlier when I discussed the “remove” component of the 5R protocol. And of course this component is focusing on repairing the gut.
But before talking about how to repair the gut, it probably is a good idea to explain how one can determine if they have a leaky gut in the first place. There is testing available, as there is a test called the Lactulose/Mannitol test that can determine if someone has an increase in intestinal permeability (a leaky gut), and there is also a test from the company Cyrex Labs called the Intestinal Antigenic Permeability Screen. I have used both of these tests in the past, but these days I usually just assume that my patients have a leaky gut, especially those with Graves’ Disease and Hashimoto’s Thyroiditis.
As for how to repair the gut, this can be accomplished through a combination of supplementation and diet. One of the most common nutrients recommended by healthcare professionals is L-glutamine, which is an amino acid that serves as fuel for the cells of the small intestine. Vitamin A and zinc can also play important roles in gut healing, and herbs such as slippery elm, licorice, and marshmallow root can also help to support the gut. Foods which can help heal the gut include bone broth, cabbage juice, and fermented foods such as sauerkraut.
5. Rebalance. This used to be called the “4R protocol”, but not too long ago the Institute for Functional Medicine added a fifth component, which is to rebalance your body through sleep, stress management, etc. I’m not going to discuss this in detail here, but this of course doesn’t mean that this component isn’t important. I’m always talking about the importance of stress handling, as doing a poor job of managing your stress can have a profound effect on your health. And most people are aware of the importance of getting sufficient sleep, although in some cases it is necessary to improve other aspects of one’s health in order to help them sleep better.
Can You Address More Than One Of These Components Simultaneously?
Some people might wonder if they can address more than one component at the same time. In other words, if someone has a gut infection, can someone take digestive enzymes and probiotics at the same time that the infection is being eradicated? Without question the answer to this is “yes”, as most healthcare professionals address different components simultaneously, including myself. And so it isn’t necessary to focus on one of these components at a time.
In summary, the 5-R protocol relates to the healing of the gut, and a leaky gut is a factor with most, and possibly all autoimmune conditions such as Graves’ Disease and Hashimoto’s Thyroiditis. The first, and perhaps most important component is removal of the trigger, which can include a food allergen, an infection, environmental toxin, and even stress. The remaining four components of the 5-R protocol are replace, reinoculate, repair, and rebalance.