Supplements for autoimmunity

Important Reminder: While supplements can be valuable in managing autoimmune conditions, they should be viewed as just one part of a comprehensive approach. It's essential to prioritize a balanced diet and address other lifestyle factors before considering supplements. Please note that the information provided in this guide is not intended as medical advice and should not be used for self-treatment.

Immunomodulation vs immunosupression — a new approach for managing autoimmunity

Immunomodulation and immunosuppression represent two distinct approaches in the management of autoimmune diseases, Immunosuppression involves the broad inhibition of the immune system to reduce inflammation and prevent tissue damage caused by autoimmune responses. While effective in controlling symptoms, this approach leaves patients vulnerable to infections and other complications due to the generalized dampening of immune activity. Traditional immunosuppressive therapies, such as corticosteroids and cytotoxic agents have been widely used but lead to significant side effects and long term health risks

In contrast, immunomodulatory compounds (the discussion of todays article) aim to restore balance or homeostasis within the immune system without completely suppressing its function. This approach focuses on selectively enhancing or inhibiting specific immune pathways (while possibly upregulating or sharpening others) to promote tolerance and reduce autoimmunity. Many nutraceutical therapies we will discuss exemplify this strategy. They’re also readily available in commercial form and do not require prescriptions — although you should always consult with a nutritionally informed physian first.

The recent widespread integration of immunomodulatory strategies (through supplements, nutrition and lifestyle) is slowly beginning to redefine the standard of care for individuals with autoimmune diseases. Lets get into some of those

modified citrus pectin

One of the notable mechanisms by which MCP exerts its effects is through the inhibition of galectin-3, a protein associated with inflammation and fibrosis. Elevated levels of galectin-3 are directly linked to various autoimmune conditions. By blocking G3, MCP helps to reduce inflammation and tissue damage associated with autoimmune reactions (an overly aggressive immune system)

In a previous instagram Q/A, I wrote the following — The innate immune response is the body's main line of defense so it responds quickly and aggressively. But Its also non-specific. This cytokine storm is essentially what killed people during Covid - body releases proteins like interferons and interleukins which recruit other immune cells and induce inflammation. You're essentially blow torching the house to kill a fly. The quicker your body can shift from M1 polarization of macrophages ( inflammatory phenotypes aka blow torch response) to M2, protective or ‘anti-inflammatory’ (fly swatter) phenotype, the better you’ll feel. Galectin-3 is a key inflammatory mediator in this innate, inflammatory immune response. Inhibiting galectin-3 (with compounds like MCP) quells inflammation and induces a repolarization of macrophages back towards the M2 (anti-inflammatory and repair) phenotype. This is important, especially in autoimmune conditions like arthritis where we also have to deal with residual tissue damage.

MCP also acts as a natural chelator, binding to heavy metals and even mycotoxins and facilitating their excretion from the body. Heavy metal toxicity and mold exposure has been implicated in exacerbating autoimmune conditions. By reducing the burden of these toxins, MCP alleviates some of the inflammatory burden that contributes to autoimmune diseases. Studies have shown that MCP can effectively lower levels of toxic metals like lead and cadmium without significantly affecting essential minerals. MCP is a multi-functional chelator AND immune system regulator — a rare find.

How is it used?

low dosing (at 1 tsp daily) can be effective, while higher doses (2-3 tsp daily) may be more desirable for autoimmune flair ups and or in the initial phases of aiming to modify disease trajectory. I always recommend that physians have their patient start extremely low (1/4 a tsp, so 1/4 of the lowest effective dose) since MCP can often cause diarrhea. Start with 1/4 tsp for a few days, then gradually increase to 1 tsp and then up. Take always on an empty stomach 30min before or 3 hours after food. Can be taken with probiotics but avoid taking with other supplements like enzymes.

Specialized pro resolving mediators

Specialized pro-resolving mediators (commonly referred to as SPMs) are a class of bioactive lipid mediators derived from PUFAs like omega-3. They play a massive role in the resolution of inflammation, which is particularly relevant in the context of autoimmune reactions with associated tissue damage. think common AI conditions like arthritis, where the immune system attacks the joints.

SPMs, (this includes resolvins, protectins, and maresins) are produced during the resolution phase of inflammation (clean up process). They actively promote the cessation of inflammatory responses by inhibiting neutrophil infiltration and enhancing the clearance of apoptotic cells through a process known as efferocytosis. This mechanism is important for restoring tissue homeostasis and preventing the chronic inflammation that is a characteristic feature of most autoimmune conditions

SPMs also modulate immune cell activity by acting on specific receptors. For instance, resolvins can activate macrophages to adopt an anti-inflammatory phenotype (like we mentioned above in the MCP example), reducing the production of pro-inflammatory cytokines. This shift in macrophage function is needed for controlling excessive immune responses.

Beyond their anti-inflammatory properties, SPMs also facilitate tissue repair and remodeling as mentioned — they’re a two in one solution, as they stimulate the production of growth factors and extracellular matrix components, which are key constituents involved in healing damaged tissues. SPM’s also upregulate specific immune responses that can help manage chronic infections. Another underlying driver of autoimmunity.

How are they used?

Physian guided Dosing: chronic, low dosing (at 1g or 2 capsules) can be effective, while higher doses (6-8 capsules daily) may be more desirable for autoimmune flair ups and or in the initial phases of aiming to modify disease trajectory.

Proline rich polypeptides

PRPs are bioactive immunomodulatory peptide compounds primarily derived from bovine colostrum, the first milk produced by cows after giving birth. These peptides have significant immunomodulatory properties. PRPs play a very important role in modulating the immune system, particularly by influencing the balance between T helper 1 and T helper 2 cells. Th1 cells are associated with cellular immunity, while Th2 cells are linked to humoral immunity. PRPs induce a shift from a Th2-dominated immune response, which is usually associated with allergic and autoimmune conditions, to a more balanced Th1 response. This shift help reduce inappropriate inflammatory cascades that characterize most autoimmune reactions

Interestly, PRP’s also enhance the activity of T-lymphocytes and promote the differentiation of these cells into either helper T-cells or suppressor T-cells.

Think about it like this —Helper T-cells activate B-lymphocytes, which produce antibodies, while suppressor T-cells help deactivate other lymphocytes to prevent excessive immune responses. This dual action helps maintain immune homeostasis — the ability to respond to infections and inflammation without going into overdrive

PRPs stimulate the production of cytokines, including both pro-inflammatory and anti-inflammatory cytokines. cytokine modulation is critical for regulating immune responses because it help mitigate the chronic inflammation associated with the more aggressive (but necessary) ‘arms’ of the immune system. When we promote the production of anti-inflammatory cytokines, PRPs can help counteract the inflammatory processes that contribute to autoimmune diseases without suppressing the innate immune system like immunosuppressant medications

PRPs enhance also enhance the activity of natural killer cells, which, as mentioned, are the body's main defense against infected or cancerous cells. By boosting NK cell function (key word) , PRPs help the immune system more effectively target and eliminate aberrant cells, reducing the risk of ‘off target’ autoimmune reactions triggered by cellular dysregulation. When we improve immune tolerance, as well as the ability of these cells to find their targets more effectively, there’s less of a chance they will attack benign antigens (think allergies) or self-antigens (your organs and tissues). You’ve essentially turned your immune system into a sniper rifle vs a shotgun — just as powerful, but with less collateral damage

How is it used?

PRP’s are soured from bovine colostrum. For PRP’s to be effective, you need a specific kind of bovine colostrum that’s extracted (or portified) specifically to maximize the PRP yield. I like one scoop of NuMedica’s TheraPRP colostrum. They make multiple colostrum’s, but this one in particular has the most PRP’s.

Spore based probiotics

The gut microbiome has a massive role to play in maintaining immune homeostasis and regulating immune responses. In fact, it’s probably the most important topic we’ll discuss in todays article.

One of the key components of this system is the gut associated lymphoid tissue (often referred to as the GALT), which houses a significant portion of the body's immune cells. Within GALT, regulatory T cells are key for maintaining immune tolerance and preventing autoimmune reactions, specifically to dietary antigens consumed in food.

The microbiome influences the differentiation and proliferation of Tregs through metabolites produced by gut bacteria, particularly a key ‘post biotic’ called butyrate. This short chain fatty acid is generated during the fermentation of dietary fibers by beneficial gut bacteria and enhance Treg populations by increasing the expression of the transcription factor like foxp3. In promoting Tregs, butyrate helps suppress excessive inflammatory responses and maintains that balanced immune response we want to see

butyrate also influences the activity of various immune cells, including dendritic cells and effector T cells. It helps to reduce the activation and function of pro-inflammatory T cell subsets, such as Th1 and Th17 cells, which are often implicated and or over active in autoimmune conditions. butyrate strengthens the gut barrier, preventing the translocation of harmful bacteria and toxins into the bloodstream (like endotoxin) which can trigger inflammatory responses and immune system over activation. Endotoxin can also get into the joints and other organs, where the immune system attacks it directly, contributing tosustained, chronic immune overaction and tissue damage

Spore forming bacteria, chiefly those from the genera bacillus, can improve key functions of the gut, including the production of butyrate and other beneficial metabolites. spore-forming bacteria are resilient and can survive harsh gastrointestinal conditions, and are able to effectively colonizing the gut and enhancing the overall microbial balance.

Spore forming bacteria also lower levels of key pathogenic bacteria and fungi in the gut, many of which configure to autoimmunity through the release of inflammatory mediators and endotoxin above. Spores also help to seal up the lining of the gut to prevent endotoxin and other stomach contents from spilling over into the bloodstream

How are they used?

1 serving of a spore based probiotic, preferably everyday, microbiome labs megaspore or just thrive are my favorite products

Paraprobiotics

Plasmacytoid dendritic cells (I’ll refer to them as pDCs from here on out) are a specialized subset of dendritic cells that play an important role in the immune system for those with autoimmunity. These cells are known for their ability to produce large amounts of type I interferons in response to viral infections and other stimuli. The immune system's interaction with pDCs is significant, since the activation of these cells has the potential to lead to both protective immunity (ideal) and the development of autoimmune pathology. In autoimmune conditions, pDCs become dysregulated, causing excessive IFN production, which contributes to the inflammatory processes characteristic of diseases such as systemic lupus erythematosus, arthritis and psoriasis in particular. The overproduction of IFN promotes the activation of self-reactive T cells and exacerbates that tissue damage we discussed above. pDCs appear to have a dual role to play in both immunity and autoimmunity.

The relationship between pDCs and autoimmunity is complex as mention , since these cells can also promote immune tolerance under certain conditions. For instance, pDCs induce regulatory T cells, which are needed (as mentioned above) for maintaining immune homeostasis and preventing autoimmunity. The balance between the pro-inflammatory and regulatory functions of pDCs is central here; when this balance is disrupted, it’s causes autoimmunity.

One of the key mechanisms by which paraprobiotics — which are basically dead probiotics that have beneficial effects on the immune system in this non-viable state — work is by influencing pDCs and the modulation of cytokine production. Paraprobiotics enhance treg populations, and suppress the inflammatory responses mediated by over active pDCs, restoring immune homeostasis. Paraprobiotics help to prevent the self-directed immune responses that characterize many autoimmune conditions, while 1. sharpening the immune systems ability to mount a proper response (say to an infection or foreign invader ) while creating tolerance to things like self and dietary antigens. Paraprobiotics make the immune system ‘smarter’

How are they used?

1 serving of a paraprobiotic like immuse (from nootropics depot). Can be in cycles (1-2 months off, then cycled off)