This post summarizes just one of many biohacks I have discovered that have changed my life.
“And those who were seen dancing were thought to be insane by those who could not hear the music.”
Executive Summary: Top Picks To Become Tolerant and Fix Autoimmune and Inflammatory Disease
I realize most people won’t make their way towards the bottom of the post, but this is really where this part belongs. Anyway, to understand why this works and for references, read on.
Note that there are many different types of intolerances resulting from different immune imbalances. I tried my best to give a general approach.
Step 1: Create dietary and lifestyle conditions for oral tolerance
You’re going to want to avoid lectins with diet, or even better go on an elemental diet if you can.
You’re also going to want Sun and if not use a UVB light. Some exercise is great, too.
Intermittently having a low protein diet is also a good idea.
Eat animals – all parts of the animal. Means don’t only eat the breast. Eat the whole chicken, including the marrow in the bones, the cartilage, etc… If you’re a vegan/vegetarian then I wish you luck trying to heal your autoimmune/inflammatory issues. I have nothing against these diets if you supplement right and don’t have inflammatory conditions.
As far as foods DHA is an absolute must. Black Cumin Seed Oil and Extra Virgin Olive Oil can help, too.
Jo’s resistant starch is also a must.
I’m not saying Resistant Starch will work for everyone because it does have some immune stimulating components – and it’s not even perfect for me, but it’s still good. Scroll to the bottom to see how it affects the immune system.
Step 2: Take These Important Supplements
Yes, take all of them, especially when you’re ingesting the protein you want to become tolerant to. Experiment with one at a time before you stack these.
- Slippery elm
Step 3 For Autoimmune Conditions: Use Glandulars and LLLT
For autoimmune conditions, put LLLT on your intestines.
Then ingest the following glandular, depending on your condition:
Hypothalamus, Adrenal, Thymus, Spleen, Thyroid, Liver, Pituitary, Pancreas, Brain, Stomach.
You want to take a high dosage of these. There’s no harm in taking all of them if you’ve got a system autoimmune condition.
Step 3 For Food Allergies
Ingest a very small dosage of the allergen and keep working up. If you have a reaction you’ve taken too much.
Alternatively, you can take a high dosage if you’re not in danger of anaphylactic shock. See the above picture regarding the effects of ingesting a low or high dose. The immune effects are different.
It’s Irrelevant Whether This Works By Oral Tolerance
This is a great regimen for autoimmune disease, even if it’s not actually helping you by creating ‘oral’ tolerance.
Oral tolerance is meant to nudge your disease so that you heal quicker.
The recommendations here generally are great for autoimmune conditions, regardless.
For example, even without anything else, lectin avoidance can cure autoimmune disease and inflammation .
Why Isn’t This Stuff More Well-Known?
There’re a few reasons why you don’t see this information anywhere else:
- The information is relatively new.
- Much of the information is buried in the scientific literature and sometimes read by a total of 100 people (one interesting study I found had about 100 views. Seriously.)
- The people who do read it don’t have the same self-hacking approach that I have. They have more of a stodgy, narrow, old-school mindset.
- People don’t understand the gamut of supplements and devices available to manipulate our biology. In this age of specialization people only see through a tiny lens.
- People haven’t experimented with the supplements on themselves. I can tell you it’s a world of a difference; reading a scientific paper about some substance and taking it. My experiments are invaluable in helping me understand how things work and meshing it with the science. Without these, my understanding would be much more limited.
Keep in mind, though, that it’s unknown how well my theoretical framework will work in practice. You need to experiment for yourself. All I’m presenting is a theoretical framework and some direction.
Use the comments section to let others know about your experience. And please give a detailed account of what you did and your immune system background.
I think it will be quite effective, but the degree will depend on your condition, how smartly you create a regimen, how diligent you are with keeping it, etc…
The biggest problem I see in people that don’t get better is being timid. People are scared to take big moves and get out of their comfort zones. We are an afraid species. We’re afraid what may happen, what people will think, etc…
I’ve tried out everything mentioned here with no side effects, so it’s all relatively safe if used right.
What Does it Mean To Be ‘Tolerant’?
Tolerance simply means that your immune system tolerates a protein and doesn’t attack it with inflammation.
This protein could be one that is a part of your body, such as thyroid peroxidase or myelin basic protein. Your body attacks these proteins in thyroiditis or multiple sclerosis, respectively.
Alternatively, your body can attack a food protein, such as gluten, casein or any other protein found in foods.
Can We Become Tolerant of Lectins?
My current thinking is as follows:
Studies use the lectins PHA and ConA to see what our immune response is like. This is standard immunology practice. So lectins are inherently immune stimulants, just as LPS is (a bacterial substance). This is not a matter of simply being intolerant of a protein.
Why it affects people differently is because of the genetic make of our immune system (and environmental influence).
Most people don’t experience significant effects from dietary lectins, but lectins are to be taken seriously if you have inflammation for no reason and your diet and lifestyle is healthy.
If lectins are not balancing your immune system, then that will cause you to become intolerant to various proteins.
With greater understanding, I’ve been able to combat lectins in various ways and disable the immune response, but so far none of the solutions are cures or free of side effects.
A combination of all of the tools can surely make a massive difference, but again, no silver bullet yet.
The best subjective anti-lectin agents I’ve found so far are:
- Sialic Acid
- HCL with pepsin
And then there’re hundreds of ways to dampen the immune response. See how to fix Th1 dominance and Th2 dominance.
What is ‘Oral Tolerance’?
Oral tolerance is when you ingest a given protein and you become tolerant to that protein.
Think about this in terms of evolution. If you chronically ingest a given protein or ingest a very large dosage of said protein, it would be advantageous for you to develop a tolerance and not attack it.
This is because, in both situations, the likely scenario is that we wouldn’t be eating a huge amount of a pathogen or chronically ingesting it.
If we’re only exposed to certain kinds of foods, we ‘d be more likely to survive if we could build a tolerance to it.
Tolerance to ingested proteins is essential for the barrier function of the intestinal tract i.e. to prevent leaky gut .
Breakdown of tolerance is associated with the development of chronic inflammatory diseases, such as Crohn’s disease and ulcerative colitis, as well as food allergies and celiac disease .
Though the mechanisms aren’t completely understood, oral tolerance works by deactivating T and B cells that target our tissues – either by getting rid of them or by making them not respond to proteins anymore (clonal deletion and energy). The other mechanism is by Tregs directly suppressing these cells .
In autoimmune disease research, the goal of oral tolerance is to suppress the Th1/Th17 response (for most autoimmune diseases).
There are two ways that researchers try to create oral tolerance. The first is by giving a high dose of a protein once. The second is by ingesting the protein at a lower dosage multiple times, which is supposed to increase Tregs. The multiple-dose approach is more suited for autoimmune diseases .
What is Required For Oral Tolerance?
Creating tolerance for one kind of condition can be very different for creating tolerance in another.
For example, creating a tolerance to peanuts in IgE-related allergies (Th2 dominant) is very different than creating tolerance in a condition that is Th1 dominant. In fact, the treatments could oppose each other.
Creating tolerance is difficult, but there is some data that it can be effective for some people. Indeed, sometimes people spontaneously develop tolerance to foods over time .
Intestinal tolerance requires Tregs and T cells in the intestines (lamina propria) . Specifically, the Tregs that are created (iTreg) are required for tolerance (as opposed to thymic Tregs) .
Vitamin A plays a fundamental role here. Vitamin A is converted to retinoic acid (in Peyer’s patches), which encourages T Cells to travel to the gut  (by displaying proteins on the cells α4β7 and CCR9, which allows it to roll there).
Some types of immune cells found in the gut (CD103+ DCs) were recently found to take in proteins through intestinal cells.
These immune cells then migrate to lymph nodes in the gut and communicate with T Cells.
With the help of some other molecules (TGF-β, retinoic acid, IDO), these cells then program the T Cells to become Tregs .
These Tregs then proliferate in the gut and suppress the local immune response, which means we won’t respond to food proteins .
In particular, TGFb and IL-10 seem to be crucial for creating tolerance by Tregs .
Lymph nodes are all over the body and are connected to each other. They are simply a place where immune cells congregate.
Eventually, it’s thought the immune cells travel through the lymphatic network and communicate with other immune cells and tell them that a given protein is cool.
The enzyme that converts Tryptophan to 5-HTP (Tph-1) is also needed to create tolerance, but the tolerance effects are not because of serotonin .
The Dark Side of Tolerance
Realize that it’s mostly the case that the more our system is geared towards tolerance of various proteins, we are also more likely to become tolerant to cancer cells.
So when there is a deficiency of the Tph-1 enzyme, it causes inflammation because we lose tolerance, but it also causes tumors to stop growing .
We want our body to become intolerant to cancer cells, but tolerant to our healthy cells. So there’s usually some kind of tradeoff involved.
Much research speaks about cancer/autoimmune tradeoff.
Some Supplements/Factors That Help Create Tolerance
- High doses of the allergic protein  – This is best to create immune unresponsiveness in Th1 dominance type allergy (causes IL-4 release) .
- Low doses of an allergic protein  – This leads to the release of TGF-beta.
- Jo’s resistant starch/Butyrate [10, 11] HDAC(-) . Initially, HDAC inhibitors were thought to be predominantly immunosuppressive, but more recent reports have challenged this view . See butyrate’s effects on the immune system.
- Thymus glandular  – The thymus is the origin of a population of ‘natural’ Tregs. I would try this out as people do find it helpful for autoimmune conditions and it’s got some animal study support  I found it to be quite an immune stimulant and care should be taken with Th1 dominant folks.
- Whey  – induces oral tolerance in Th1/delayed food sensitivities. I do better without whey, overall, but it helped when I was still eating lectins.
- Fish oil is rich in ingredients that help tolerance: DHA , Vitamin A , Zn , Vitamin D3 
- VIP  (found in Hypothalamus, Stomach, Pancreas)
- Breast milk 
- Low Protein diet  – for Th2 dominance/IgE and IgG allergies (decreases IL-4).
- Chitosan 
- Probiotics: L. casei , L. lactis , B. infantis 
- Curcumin 
- Ursolic acid  – this is interesting when it comes to tolerance because it doesn’t function via Tregs. Rather, it gets rid of the T cells which attack our body.
Others, unobtainable: Sublingual antigen attached to cholera toxin B , E. coli , D, L-PLG microspheres , IgA  – in early life? (stomach, lung), Salbutamol , Ephedrine (beta-2 adrenergic agonist), PLGA , E. coli .
Mechanisms That Influence Oral Tolerance
I’ve compiled a list of mechanisms that influence oral tolerance and some ways to influence these mechanisms.
Tregs and Tolerance
Tregs are critical for creating tolerance and are by far the most important aspect. See my post on how to increase Tregs.
IL-10 and Tolerance
IL-10 seems to be crucial for tolerance induction by Tregs .
I recommend reading my post on IL-10.
TGF Beta and Oral Tolerance
Studies have shown that TGFb in the gut area is necessary to create tolerance orally .
TGF-beta also leads to the death of T cells that attack our tissue (clonal deletion) .
See my post of TGF and how to increase it in the intestines.
Inflammation, Nf-kB, and Oral Tolerance
NF-κB activation prevents oral tolerance from occurring. This is because of the proinflammatory cytokines in the gut area .
Indeed, TNF, IL-1 and-6 block the ability of Tregs to induce tolerance  IL-17 also blocks the creation of tolerance, in part by increasing IL-6 .
I highly recommend reading through those posts to see why these cytokines might be out of whack for you.
Some supplements can increase Nf-kB in the gut such as Lithium  and Goji berries . You want to stay away from these.
As long as you are having a source of inflammation, it will be very difficult to build a tolerance.
If you have lectin sensitivity and you are consuming lots of lectins, it will be tough or impossible to create tolerance.
Read my posts to understand the factors that influence NF-kB, TNF, IL-1, IL-17, and IL-6.
Interferon Gamma and Oral Tolerance
Interferon-gamma is a Th1 cytokine.
In people with IgE-related allergies (peanuts, etc…), giving Interferon gamma with the allergic protein got rid of these allergies.
All 5 people given the interferon were cured of their IgE allergies, while none of the 5 people who weren’t given it were cured .
The way you would go about this without interferon itself is to rebalance your Th2 dominant immune system and then introduce tiny amounts of the antigen.
Germanium is pretty effective at increasing interferon-gamma . My bet is Thymus glandular works as well . If you have a serious and potentially fatal allergy, then you want to do this in a medical setting and try to get the interferon itself.
Interferon won’t create tolerance in non-IgE allergies and it could worsen your condition if you’re Th1 dominant.
IL-12 and Oral Tolerance
IL-12 is part of a Th1 response, so supplements that generally increase Th1 will elevate IL-12, but this isn’t always the case.
IL-12 blocks oral tolerance, at least in colitis and likely other Th1 dominant conditions .
By inhibiting IL-12, we can create conditions more suitable for oral tolerance.
Since I don’t have a dedicated post to it, here are some factors that decrease IL-12:
- Sun/UVB light 
- Calorie Restriction 
- Testosterone 
- Estradiol  (high)
- Serotonin 
- Jo’s resistant starch/Butyrate 
- Molecular hydrogen 
- Blueberry 
- Curcumin 
- Carob/D-pinitol 
- Cinnamon 
- EGCG 
- Theaflavins 
- Quercetin 
- Aspirin 
- Apigenin 
- Myricetin 
- Fisetin 
- Boswellia 
- Silymarin 
- Forskolin 
- Baicalin  (increased Treg numbers, TGFb, IL-10, and FOXP3) 
- Antler velvet 
- Hydroxytyrosol 
- Sialic Acid , maybe. The question is if ingesting it has an influence on it being found on cells.
- MDMA 
- Pathways: PPARδ(+) …
Factors that increase IL-12: Nucleotides , JAK-STAT .
Dendritic Cells and Oral Tolerance
Dendritic cells, in general, are critical for immune tolerance – to our own proteins as well. When we have a low level of stimulating molecules on these immune cells, it’s thought that the body learns to stop responding to the protein it was programmed to attack [71, 72]. These stimulating molecules on the surface of dendritic cells can also help this immune response, making them worse in two ways .
When the clearance mechanism of cells isn’t working well, the proteins in these cells build up. As a result of the abundance, the dendritic cells start to consume these proteins, which results in a programmed immune response against them and thus our own tissue .
Probiotics help create more of the variety of dendritic cells that can help us create tolerance.
The following are good for increasing these dendritic cells: L. Salivarius, L. Plantarum, L. Lactis .
Intestinal Mucus and Oral Tolerance
The mucus of our gut forms a barrier so that stuff doesn’t go through. Recently, it was found that this mucus barrier was also important for creating oral tolerance and suppressing the gut immune system .
Now, if your mucus barrier is fine then I don’t know if making it stronger will have any effect. But the point is to make sure that your mucus barrier is fine…
The following increase intestinal mucus:
- Gum – the process of chewing increases intestinal mucus.
- Colostrum (contains TGFb)
- Antler velvet (contains TGFb)
- Artichoke 
- Slippery elm
- DGL 
- Collagen 
- Sialic Acid and NAG perhaps – both are building blocks of the mucus.
- Bile … Bile Acid Conjugates/TUDCA, or Liver (These also increase bile: T3, Time Restricted eating, Melatonin, Curcumin, Ginger, Cumin, Curry, Garlic, Licorice, Silymarin, Nettle, Peppermint, Berberine, Artichoke, Celery, Caffeoylquinic acids, Andrographis)
- Quercetin glycoside 
Others, but not recommended for this purpose: Whey , Tulsi , Amla , Black Cumin Seed Oil – contradictory .
Oxidative Stress and Tolerance
Oxidative stress/ROS actually help Tregs suppress immune activation.
Particularly, NADPH oxidase is important (produces superoxide). In fact, Tregs are able to suppress the secretion of cysteine in order to suppress the immune response .
This puts a damper on NAC and Spirulina, both of which inhibit the oxidant in question.
So, do not take NAC and Spirulina while trying to create oral tolerance.
If you aren’t actively trying to do so, then you can take them without an issue.
NAC is quite useful for autoimmune diseases , so it’s good to take it.
Just don’t take it during an 8 hour period that you are trying to create tolerance.
Forskolin, cAMP, and Tolerance
cAMP is a very popular molecule that is used to communicate messages in the cell.
cAMP molecules in T Cells relay the message to not activate or proliferate in response to a protein 
It sends the message that all is cool with whatever protein is presented to T cells .
This results in a situation where the immune cells learn to become unresponsive to proteins .
Forskolin is a supplement used in research to increase cAMP .
It goes well with Luteolin because it inhibits an enzyme (PDE4) that breaks down cAMP. This results in more cAMP for longer periods.
Adrenal glandular and ephedrine also increases cAMP via Beta-2 adrenoreceptor agonism .
Surface Molecules and Oral Tolerance
‘CD’ and some number just refers to a protein that’s lodged on the surface of an immune cell. These proteins are an important aspect of immune system communication.
CD80 is a protein that immune cells need for communication. This protein is needed to create and sustain tolerance. When it’s blocked oral tolerance and tolerance of our own tissue is blocked as well. This protein is also important to make cells unresponsive when challenged with the allergic protein [87, 88].
In order of power: L. lactis  (powerful), L. plantarum , L. salivarius  (not powerful), – all in gut… L. plantarum , spleen.
CD103 is a protein found on immune cells (dendritic cells) that hang out by our intestinal surface. These cells can communicate with the proteins we ingest with a tentacle-like structure.
These cells, with the CD103 protein, are necessary for oral tolerance . It’s only cells with these proteins that create special types of Treg cells when TGF was present (Foxp3) .
Probiotics such L. Salivarius, L. Plantarum, L. Lactis can help in that order  The Probiotic B Breve helps the cells with CD103 create tolerance (by stimulating their production of IL-10 and IL-27) .
CD40 is a protein on immune cells and its purpose is to stimulate it i.e. cause inflammation. It blocks us, to a degree, from creating immune tolerance .
The following inhibit CD40 and it happens to be I’m a fan of all of these supplements:
- Red Wine Polyphenols 
- Curcumin 
- Fish oil 
- Jo’s resistant starch/Butyrate/HDAC- 
- Andrographis/andrographolide 
- Berberine 
- EGCG 
- Fisetin 
- Black Cumin Seed Oil 
- Bilberry 
- Quercetin 
- Extra Virgin Olive Oil 
- Luteolin [102, 103, 104, 105]
- Apigenin 
Things That Block Tolerance
Citrus pectin , Palmitate , Retinoic acid+IL-15 , Skin sensitization , Alginate , Appendectomy , Thymectomy , Alcohol-induced gastritis , H Pylori , MCT (for Th2 dominance) .
Diseases And Oral Tolerance
First, you want to set the stage for creating oral tolerance by implementing the above measures that I’ve described.
Once all systems are in place, you then ingest a protein that your body is attacking.
You can try to get any protein they use in the scientific literature. It’s just expensive and going to be hard to obtain.
I’ve tried all of the glandulars.
As we know, this is a disease that attacks our joints. Therefore, I recommend ingesting Collagen.
Life extension claims that commercial collagen is denatured and that only this Collagen type 2 can create oral tolerance. It also cites studies that show it survives the GI tract and creates oral tolerance in people .
In MS, myelin is attacked.
Chronically feeding mice low doses of the myelin basic protein stopped MS in its tracks through the production of Tregs (via TGFb) [2, 117].
I recommend Sphingolin or Brain glandular.
Hashimoto’s and Graves
Thyroid proteins are attacked in these conditions.
You want to ingest Thyroid glandular. Make sure to get one without thyroid hormones in there. It does have significant amounts of iodine, however, based on my experience…
Intestinal tissue is attacked in Colitis and Crohn’s.
Studies use ‘Haptenized Colonic Protein’ for Colitis .
But until this cool-sounding protein becomes mass marketed, you might want to try Stomach glandular.
Type 1 Diabetes
In Type 1 diabetes, pancreatic cells are attacked. You want to ingest Pancreas glandular.
Pancreas glandular contains insulin, but it gets digested and doesn’t function the same way as when you inject it.
Ingesting insulin itself has some interesting effects such as increasing TGF-beta . I wouldn’t expect this since much of it gets digested.
Addison’s disease is an autoimmune condition where your adrenals are attacked and destroyed, resulting in very little cortisol being produced.
I recommend taking Adrenal glandular.
Systemic Autoimmune Diseases
SLE/Lupus is an example of a systemic autoimmune disease that attacks a certain protein in the nucleus of our cells. For a disease such as these, I would recommend just ingesting animal-based foods and excluding plant-based foods, except leafy greens or Sauer kraut.
Animal foods have much of the proteins that we have. Don’t just stick to one part of the animal such as the muscle, but instead, eat as much of the animal as possible.
When I buy a chicken I eat the cartilage, the marrow in the bones, the bits of organs found inside, the skin, the ends of the bones, etc. Barely anything is left when I’m done with it.
When you buy a steak, you’re only eating the muscle. This is fine in moderation, but it’s better to diversify.
I’m not going to give the full gamut of autoimmune diseases here, but the point is you should research exactly what part of the body is being attacked and ingest those proteins from animals. The proteins are similar enough to ours to have an effect.