Autoimmunity

"All (autoimmune) disease begins in the gut"

There are many different diseases out there that are considered autoimmune, and in laymen's terms, autoimmune diseases are considered diseases where the body attacks itself (from the Greek αὐτός meaning self). However, many instead consider autoimmune diseases to be a situation where there is a lot of damage being done in the body and as a result, there is a lot of “debris” that the body is attempting to clean up, this leads to the overactive immune response, as opposed to the body just simply “attacking itself”.

There are a few things that people can do to improve their autoimmune disease symptoms. There are also many things people can do to protect themselves from being susceptible to developing an autoimmune disease.

First, it seems clear that estrogen plays a pathological role in autoimmune diseases. Keep in mind, almost all autoimmune diseases are heavily skewed towards women. This is a simplistic way of looking at things, but in women progesterone is the main “protector” against excess estrogen. When women are not producing enough progesterone in relation to estrogen, or simply when the ratio of estrogen to progesterone is off, then many issues can surface, including autoimmune diseases. Increasing progesterone production should be a top priority for women who either want to protect themselves from autoimmune diseases or attempt to reverse an existing condition. But, lowering excess estrogen should be a top priority for both men and women with autoimmune diseases.

“Estrogen shrinks the thymus, and contributes to many auto-immune conditions and tissue alterations including osteoarthritis” -Ray Peat Ph.D

Progesterone is a steroid hormone, thus it’s a hormone that comes from cholesterol. Vitamin A, cholesterol and active thyroid hormone (T3) are three important factors in the production of all the steroid hormones, but other nutrients such as vitamin B5 are also important, as is adequate light exposure. The body first makes pregnenolone out of cholesterol and then later on pregnenolone is converted to progesterone. Consuming enough vitamin A is one basic thing anyone can do to increase their natural production of steroid hormones. Increasing and optimizing thyroid function is also essential since active thyroid hormone is necessary for cholesterol conversion into steroids.

It is also very important to consume enough selenium which is a nutrient that plays a very important role in a well-functioning immune system and is also very important for thyroid function. Selenium specifically seems like it can help with certain autoimmune conditions such as arthritis and different autoimmune conditions of the thyroid. There is also some evidence that vitamin E can help with rheumatoid arthritis.

Progesterone is a very potent anti-inflammatory in the body and that fact alone is part of the reason why more progesterone is beneficial for many health conditions, especially ones where there is excessive inflammation and tissue destruction. Many women choose to supplement with progesterone directly, and this can be a very good idea especially because supplement progesterone does not inhibit a woman's endogenous production, but seems to actually increase her own production. It is very important for supplemental progesterone to be dissolved in vitamin E, regardless of if you are applying it topically or taking it orally. Topical creams exist as do oils, and the progesterone dissolved in vitamin E oils can be taken orally or used topically.

It is typically recommended to take progesterone 2 weeks out of the month per month, and if you are cycling then the recommendation is to only take it in the luteal phase. This does seem to be somewhat of a debated topic, but my stance is that it is better to try and take 1-2 weeks off of progesterone every month unless you have a very good reason for staying on it every day. This seems to have also been the view of Ray Peat. There are no catastrophic side effects if you stay on progesterone supplementation daily, but it seems to be much better if you take 1-2 weeks off every month nevertheless.

Another option for autoimmune diseases is to supplement the progesterone precursor, pregnenolone. This is the first steroid hormone, often referred to as the mother of all steroid hormones. Pregnenolone is a potent anti-inflammatory and is very useful for all sorts of issues including arthritis and neurodegenerative diseases. Taking pregnenolone increases pregnenolone levels, which in and of itself is very beneficial, but it will also lead to an increase in other beneficial steroids such as progesterone, DHEA, and allopregnanolone. While pregnenolone supplementation can increase DHEA, some may want to supplement DHEA as well. Taking DHEA with pregnenolone is a good idea, 5mg of DHEA is a good dose, I wouldn’t go higher than 15mg in a day. Pregnenolone dosage varies widely, most people can do well on 50-100mg 1-3x a week, but some may prefer to take a far higher dose, such as 1.5g (1500mg) daily for a period of time.

“Estrogen is known to produce a great variety of immunological defects, and DHEA, apparently by its balancing and restorative actions, is able to correct some of those immunological defects, including some "autoimmune" diseases.”

Hormones that are more downstream like estrogen and cortisol are very tightly regulated, so taking a hormone that is very high up in the chain (like pregnenolone) will not create an excess of a specialized hormone (like estrogen or testosterone) but will instead correct a potential deficiency of the downstream hormones. I don’t think there's a need to cycle on and off pregnenolone, and men and women can safely take it in a variety of doses. Many women prefer to do half the month with progesterone, the other half with pregnenolone. Pregnenolone can also be used topically, but taking it orally (as a powder or capsule) is a good idea as well. If you take it orally, as with progesterone, you should take it with a meal, and ideally one that contains fat such as butter or olive oil. Having the steroids with a meal that contains eggs seems like a great idea to me, it should help with the absorption.

Other than optimizing the beneficial antiinflammatory antistress hormones, there are other things someone can do to help with their autoimmune disease. Increasing vitamin D levels is thought to be very important for this group of diseases, as is increasing vitamin A levels. Getting your blood level of vitamin D to at least 50ng/ml or 125nmol/L is a very good idea, but some may benefit from getting it even higher. If you can do this with sun exposure alone, be my guest and good luck to you. But if you are struggling with an autoimmune disease and your vitamin D levels are low (like in the 30s) then you probably would benefit from supplementing vitamin D, potentially in doses from 5-10 thousand IUs a day. If you want to get vitamin D from the sun, then don’t sunbathe fasted. It helps to have eaten when getting sun exposure for vitamin D synthesis, one study found fasting “decimates” vitamin D levels. Supplementing vitamin K2, and consuming enough calcium and magnesium is important when increasing vitamin D, as these nutrients do not work alone. Furthermore, eating about a pound of liver a month is a good idea for increasing vitamin A levels, but supplementation may be warranted if you simply can’t stomach liver in any preparation.

What is very common with essentially all autoimmune diseases is that they appear to (at least partially) “begin in the gut”. As Hippocrates said, all diseases begin in the gut. A lot of the time, people that restrict certain foods will find that their autoimmune symptoms improve dramatically. A major reason for this is that anything that irritates the intestines can cause horrific systemic effects, even if you don’t “feel” the irritation in the intestines. Gut inflammation can lead to issues anywhere in the body, from the brain to the toes. This is especially true when someone has a “leaky gut” where particles such as bacteria or other things can get out of the intestines and into the body/bloodstream inappropriately. This always involves an immune response.

“There is good evidence that a variety of bowel bacteria are involved in arthritis and other autoimmune diseases.” - Ray Peat

One common cause of this intestinal inflammation is bacterial overgrowth. Stopping certain foods sometimes isn’t even about the food, it’s about stopping the food for the bacteria that are overgrown. This isn’t a long-term solution, because if you fast from all food and you find you’re feeling better, it could just be that you are avoiding irritating foods, or that you aren’t feeding a bacterial overgrowth that already exists. But once you eat again the bacterial overgrowth wakes up from its dormancy and starts wreaking havoc again. Endotoxin, also called LPS (lipopolysaccharide), is the outer shell of gram-negative bacteria and is highly inflammatory. The more bacteria, the more endotoxin.

Endotoxin or other material absorbed from intestinal bacteria contributes to a variety of autoimmune problems, including thyroiditis (PenhaleandYoung,1988). Combining an indigestible fibre, such as raw carrot, with mild germicides, such as vinegar and coconut oil, can improve the hormonal environment while reducing the immunological burden.

-Ray Peat

This is why Ray Peat consistently suggested different methods to “clean the intestines”, especially the small intestine, of bacterial overgrowth. His most typical recommendation was the “daily raw carrot salad” which is grated raw carrots, vinegar, olive/coconut oil and salt. The idea is that all of the ingredients have synergy together, leading to an overall effect of lessening the bacterial count in the intestines and relieving the symptoms associated with bacterial overgrowth. If done consistently it is thought that the situation can be rectified. He also suggested boiled white button mushrooms, it being very important for them to be boiled as raw white button mushrooms have certain toxins that you do not want to consume. Another idea from him was activated charcoal, but if the charcoal was too fine, ie. if the particles were too small, it could cause issues.

Bile production and flow are very relevant here. First, bile is needed to break down and utilize fat-soluble vitamins, and we have already seen how important fat-soluble vitamins, like vitamin A, are for protection against autoimmunity. Second, bile is needed to keep the small intestine clean and free of SIBO. Good thyroid function is essential for optimal bile production and flow, but that is a long-term strategy. Estrogen also interferes with bile flow and is a common cause of gallbladder issues. Increasing consumption (or supplementation) of taurine, choline and glycine can be very useful for bile production and flow. You can also supplement TUDCA (a bile acid) or ox bile extract directly if you think you are having issues producing your own bile in sufficient amounts. Bitters (like orange peel) and coffee help improve bile flow.

I think it is also important to try and rectify a “leaky gut”. Some things that seem to be able to help here are glycine, which is an amino acid that is very high in collagen, bone broth and certain cuts of meat like ox tail. Zinc carnosine is shown to be very helpful for leaky gut, as are a few choice supplements like aloe vera gel/juice. Creatine monohydrate seems to also be able to help, 5g a day is a good dose.

Certain safe laxatives can also have a very powerful effect. Ones that contain the quinone “emodin” seem to be the safest and most useful. Well-aged cascara sagrada bark was Ray’s favourite and contains emodin, aloe vera juice/gel contains aloe-emodin and is also very useful.

Certain antibiotics may be warranted and can be highly beneficial depending on the context of the situation. The antibiotic minocycline seems to be the most effective. Minocycline, at lower doses, is actually less of an antibiotic and more of a powerful anti-inflammatory agent. Taking minocycline in doses less than 50mg a day will cause a strong anti-inflammatory effect in the intestines, which should help with virtually any health condition, especially autoimmune diseases. It will also likely have the benefit of killing off some bacteria in someone with a potential bacterial overgrowth. But for those who worry about antibiotics killing all the “good bacteria”, then low-dose minocycline is the way to go, because to reiterate, the low doses are not really antibiotic doses.

Natural antibiotics are often preferred by people as they seem to be less of an issue and they typically have the benefit of being both antibacterial and antifungal, which pharmaceutical antibiotics are not. Oregano, thyme, cinnamon, sage, clove, monolaurin, garlic, raw honey, and caprylic acid are all potent anti-bacterial and antifungals that can be used in someone who suspects they have bacterial (or fungal) overgrowth. Many people also find benefits in using spore-based probiotics, such as CoreBiotic, which contain strains of bacteria that can act like an antibiotic. Spore-based probiotics should be taken for 1-3 months to see an effect.

Intestinal parasites seem to also be a major issue for those with autoimmune diseases. This is a tricky topic, as it is unclear how useful natural vermifuge can be. Having said that, things like wormwood, clove, black walnut hull, berberine and some other things seem to be useful antiparasitics/vermifuge/vermicide. My friend Andra Sitoianu ND knows far more about parasites than me, I believe she uses iron-reducing substances to deal with parasites as well. I think lactoferrin is a common supplement she uses with clients, I would check her out on Instagram or Twitter to find out more.

Furthermore, iron excess, or “iron overload”, also seems to play a role in exacerbating autoimmunity in general. If iron overload is contributing to someone’s autoimmune condition, they may benefit from iron-reducing practices such as therapeutic phlebotomy (blood donation), lactoferrin, turmeric, coffee and other iron-lowering approaches such as colostrum (which is a good source of substances that seem to be able to help with autoimmunity in general). If someone is anemic, they should look into the various other causes of anemia, other than just a simple iron deficiency. For example, vitamin B2, vitamin C, vitamin A, copper, folate and vitamin B12 are all very important for preventing anemia, as the condition is not just one of iron deficiency.

There are a few receptors in the intestines that when activated cause alarm and inflammation, these are the “toll-like receptors”. TLR4 is the main one discussed. Many things can activate TLR4, such as LPS “endotoxin” which, to reiterate, is the outer shell of gram-negative bacteria. Gluten from wheat and some other things can directly activate TLR4, so it’s probably best to avoid gluten. Many additives like talc, silica and titanium dioxide all can activate TLR4, so beware of what you eat, and what you take as a supplement or medication. Lots of packaged foods have these additives that can cause the activation of TLR4 and the subsequent inflammatory response. A big reason why candy can lead to ADHD symptoms seems to be more so the additives and food colourings, and less the “sucrose/sugar” contained in the candy.

A lot of autoimmune sufferers find it hugely beneficial to take substances that “block TLR4”. Vitamin D and B2 seem to be able to do this, phosphatidylcholine, pregnenolone and progesterone have some effects here as well. Drugs that block TLR4 are naloxone and naltrexone but also Benadryl seems to be able to block TLR4, as well as “tricyclic” structured medication, like loratadine (Claritin), which is a tricyclic antihistamine. Many people feel much between when they take low-dose naltrexone, this is likely at least partly due to its ability to block TLR4. This should be especially useful for Crohn’s disease.

High levels of eicosanoids (prostaglandins, leukotrienes and thromboxanes) are involved with autoimmune diseases. These eicosanoids can cause a lot of inflammation, and leukotrienes are thought to be involved in many diseases such as multiple sclerosis. Inhibiting the enzyme LOX prevents leukotriene production, and inhibiting COX prevents prostaglandin production. Natural COX and LOX inhibitors can therefore be very useful. Vitamin E, pycnogenol, Boswellia Serrata (boswellic acid), clove (eugenol) and ginger all have either LOX and/or COX-blocking activity. Some OTC pain relievers, like aspirin, are COX inhibitors. Estrogen can increase LOX and COX, progesterone can lower their activity. Things that inhibit phospholipase A2 (PLA2) can also help because PLA2 ends up increasing the activity of LOX and COX. So, lowering PLA2 is another way to keep the eicosanoids down. Gingko Biloba, Pycgnogenol, Vitamin E, Progesterone and Clove seem to be able to inbibit PLA2 to some degree. I talk about these enzymes at length in my article on asthma.

Histamine seems to play a large role in autoimmune diseases, and sometimes certain antihistamine approaches are useful. Estrogen seems to have the effect of increasing histamine in the body. A lot of the foods autoimmune sufferers avoid can increase histamine in the body, such as tomatoes. But other antihistamine approaches would be a useful addition. Histamine is released from mast cells, and it seems that theanine, an amino acid, can stabilize mast cells. Quercetin is an antihistamine, but some people feel anxious when they take it. Stinging nettle-leaf tea, vitamin B6, vitamin C, copper, zinc, and vitamin A all help with histamine breakdown to some degree. Antihistamine drugs can be useful, such as Benadryl, cyproheptadine (those two are sedating) and Claritin (loratadine) which is not sedating.

So to recap, so far we have discussed:

1. lowering estrogen, and increasing progesterone.

   1. possibly supplementing with progesterone and pregnenolone

2. Increasing vitamin D and vitamin A levels

3. Clearing the gut, and lessening gut inflammation

   1. Fixing a leaky gut (zinc carnosine, glycine, creatine)

   2. Clearing out bacterial overgrowth (raw carrot salad, boiled white button mushrooms, natural laxatives like cascara or aloe)

   3. Low-dose Minocycline as an anti-inflammatory

   4. Natural antimicrobials like oregano oil, spore-based probiotics

4. Lowering the overproduction of leukotrienes and prostaglandins by lowering LOX and COX enzyme activity.

5. High histamine is involved in autoimmune disorders, antihistamine interventions can be useful.

6. Importance of selenium and vitamin E for autoimmune conditions

Some other things that can help with autoimmune diseases:

Niacinamide, a form of vitamin B3, seems to be useful in many autoimmune conditions. Part of the reason may be that increasing NAD levels seems to be able to calm down autoimmune conditions, and one way that someone can increase NAD levels is by supplementing vitamin B3. I talk more about NAD in this article. Vitamin B1 (Thiamine) also seems to be helpful for many autoimmune conditions.

“Niacinamide is a nutrient that inhibits the release of fatty acids, and it also activates phagocytic activity and lowers phosphate. It protects against the development of scars in spinal cord injuries, facilitates recovery from traumatic brain injury, and accelerates healing generally. While it generally supports immunity, it’s protective against autoimmunity. It can cause tumor cells to either mature or disintegrate, but it prolongs the replicative life of cultured cells, and protects against excitotoxicity.” -Ray Peat

I want to mention that it seems that light exposure is very important and beneficial for those with autoimmune diseases. Particularly red light. People can get morning and evening sun for the natural red light, but can also buy red lights themselves and use them all over. Red light is particularly useful for those who have lost hair (on the scalp, eyebrows etc). It helps increase hormone production, increases energy via the electron transport chain, and is overall anti-inflammatory and highly beneficial. Sunlight itself, is a gift.

“Adequate light is another important factor in maintaining a high-energy respiratory state and preventing the whole complex of inflammatory, autoimmune, and degenerative diseases.”

-Ray Peat

When it comes to drugs, out of the OTC pain relievers, aspirin is the safest and most useful. Tylenol is toxic and should be avoided at all costs. When taking high doses of aspirin consistently (like 1-4g a day) then vitamin K2 is a useful supplement to take to counteract potential excessive blood thinning.

There is a lot more to autoimmune diseases, but for the purposes of this article (which is meant to be a simple and quick article with practical advice for those with autoimmune diseases) ill wrap it up here. This information, albeit general, should be useful for any autoimmune disease whether someone has arthritis, lupus or MS, to varying degrees of course. I will go over MS (and other neurodegenerative diseases) in far more detail in my future article “Maintain Your Brain”, which should be released sometime in the fall of 2023.

If you enjoyed this article, please consider checking out the other articles I’ve written. Also, please feel free to subscribe (it is free to do so) and share the articles with others. Thank you!

*None of this is medical advice. I am not a medical professional, always talk to your doctor*

BTW: I am a frequent guest on the podcast “Stuff Your Doctor Should Know”.

Discount code DEAN works at:

1. Ona’s Naturals (progesterone oil, topical progesterone and pregnenolone creams)

2. LifeBlud (Magnesium products, Taurine, Theanine, B vitamins, Methylene Blue)

3. Health Natura (oral pregnenolone, Methylene Blue)

4. Saturee (skin care products, desiccated liver, aged Cascara Sagrada)