The Risks and Nuances of Starting VIP Too Early

For individuals navigating the complex terrain of Chronic Inflammatory Response Syndrome (CIRS), reaching the final phases of healing can feel like a light at the end of a long tunnel. 

 

One of the most anticipated therapies in the Shoemaker Protocol is Vasoactive Intestinal Peptide (VIP)—a nasal spray that, when used appropriately, can help repair the hypothalamic-pituitary axis, enhance immune regulation, and restore quality of life. But despite its powerful benefits, initiating VIP therapy too early can lead to significant setbacks.

 

CIRS recovery is a delicate, nuanced process that must follow a precise order. Skipping ahead, especially to VIP, can worsen symptoms, reactivate inflammatory pathways, and undo progress made in earlier phases of treatment. 

 

We’ll explore the risks and nuances of starting VIP too soon, why timing matters at every stage of CIRS recovery, and how to approach this final step wisely with the guidance of your trusted practitioner.

 

What Is CIRS?

 

 

Chronic Inflammatory Response Syndrome, or CIRS, is a multifaceted condition that affects numerous systems throughout the body and can manifest in a wide range of symptoms. At its core, CIRS stems from a dysregulated immune response that leads to persistent, often overwhelming inflammation.

 

Diagnosing CIRS isn’t straightforward. It demands a holistic and investigative approach, including in-depth lab testing and a careful review of a patient’s health history to uncover patterns, symptoms, and environmental or infectious triggers.

 

Because of its broad and often confusing symptom picture, CIRS is frequently overlooked or misdiagnosed. It doesn’t typically show up on standard autoimmune panels, which makes it easy to miss in conventional medical settings. Identifying CIRS accurately requires specialized tools and clinical insight to pinpoint the root contributors. This targeted evaluation is essential for developing a treatment strategy that goes beyond symptom management and focuses on true, long-term recovery.

 

 

In CIRS, the immune system becomes highly reactive, often due to exposure to biotoxins—harmful substances that can provoke or intensify symptoms in genetically susceptible individuals. These toxins can come from various environmental and biological sources, including:

 

• Mold and Microbes in Water-Damaged Buildings: A significant portion of CIRS cases, estimated at around 80%, can be traced back to environments affected by water damage. These buildings often harbor mold spores, bacteria, and microbial fragments that linger in the air. Alarmingly, even dead mold particles can trigger severe immune responses and inflammation in sensitive individuals, impacting both cognitive and physical well-being.
• Insect Bites and Vector-Borne Illnesses: Certain bug bites, especially from ticks and spiders, can introduce pathogens like Borrelia burgdorferi (Lyme disease) and Babesia microti. Additionally, bites from recluse spiders have been associated with chronic symptoms in predisposed individuals, sometimes acting as a catalyst for CIRS.
• Toxin-Laden Seafood: Eating certain reef fish contaminated with ciguatoxins, a result of algal blooms, can expose individuals to dangerous biotoxins. These toxins accumulate as smaller fish are eaten by larger ones, making consumption of top predators particularly risky.
• Exposure to Contaminated Water: Lakes and rivers affected by harmful algal blooms, such as cyanobacteria or Pfiesteria, can release toxins that trigger immune activation. Inhalation or skin contact with contaminated water may be enough to contribute to CIRS onset or progression.
• Additional Biotoxin Sources: Other contributors include viral infections, some vaccines, volatile organic compounds (VOCs), endotoxins, and actinomycetes—all of which can challenge the immune system and worsen symptoms in those with CIRS.

 

 

 

Biotoxins are tiny, stealth-like molecules capable of slipping through cell membranes, which makes them incredibly difficult to detect using standard blood work. These toxic compounds often enter the body through breathing in contaminated air, but they can also be absorbed by eating tainted food, experiencing insect bites, or coming into contact with polluted water sources.

 

Interestingly, not everyone exposed to mold or other biotoxins will go on to develop CIRS. A person’s genetic makeup and life history play a crucial role in whether CIRS takes root. Certain life events—such as major illness, surgery, high fevers, pregnancy, chemical exposure, or emotional trauma—can overwhelm the immune system and spark what’s known as a cytokine storm. For individuals carrying specific HLA-DR genetic variants, this heightened immune reaction can activate CIRS, even if they’ve tolerated similar exposures in the past.

 

In many people, the body naturally identifies and removes biotoxins. But those with CIRS-prone genetics often lack the immune capacity to recognize and eliminate these invaders, leading to toxin buildup, chronic inflammation, and lingering symptoms. This makes biotoxin illness especially insidious: it can begin suddenly, progress silently, and persist for years without a clear cause.

 

Even if you’re not currently experiencing symptoms, genetic testing can provide valuable insight into your risk for CIRS and help guide preventative or therapeutic strategies.

 

For a more detailed understanding of CIRS, click here.

 

Pro-Tip: If you think you’re suffering from CIRS, you can learn more about CIRS diagnostic testing here.

 

What Is the Shoemaker Protocol?

 

 

The Shoemaker Protocol, created by Dr. Ritchie Shoemaker, offers a systematic and clinically validated approach to treating CIRS and other biotoxin-related illnesses. It is currently the only peer-reviewed protocol specifically designed to address the complex, multi-system inflammation seen in these conditions. Rather than focusing solely on symptom management, the protocol provides a step-by-step roadmap that targets the immune dysregulation and biochemical imbalances at the root of CIRS.

 

The process begins with identifying and removing the sources that may be perpetuating the inflammatory response. While this often includes reducing biotoxin exposure, the broader goal is to lower the total body burden that overwhelms immune function.

 

Once that burden is reduced, the next phase involves the use of binding agents such as Cholestyramine (CSM) or Welchol to help the body clear out lingering biotoxins. These binders assist in interrupting the cycle of immune activation by physically removing toxins that continue to recirculate and trigger inflammation.

 

Subsequent steps focus on rebalancing the immune system, stabilizing inflammatory markers, correcting hormone dysregulation, and improving communication between various systems of the body. The goal is to restore resilience and function through carefully sequenced interventions.

 

The final step of the Shoemaker Protocol is the introduction of VIP (Vasoactive Intestinal Peptide)—a therapeutic tool reserved for when the body is ready. This step is only implemented after key markers have normalized, signaling that the immune system is stable enough to receive deeper regulatory support.

 

Each stage of the protocol builds upon the last, making timing and precision critical to long-term healing and remission.

 

What Is VIP?

 

 

VIP is a signaling molecule made by nerve cells, immune cells, and the gut. Think of it as a multitasking messenger that helps regulate the immune system. Some of its key roles include:

 

• Reduces inflammation by calming overactive immune signals. VIP helps quiet inflammatory messengers in the body, like TNF-alpha (Tumor Necrosis Factor-alpha) and IFN-gamma (Interferon-gamma), which are often elevated in people with chronic inflammation or immune dysfunction. By turning these signals down, VIP helps the body feel safer and less inflamed.

 

• Supports anti-inflammatory responses. VIP encourages the release of IL-10 (Interleukin-10), a calming chemical that helps the immune system stop attacking the body and focus on healing. This helps reduce chronic inflammation and autoimmunity.

 

• Guides how the immune system responds. VIP plays a key role in how T cells, the immune system’s coordinators, function. It helps balance different types of T cells, which can either promote inflammation or regulate it. This balance is critical in conditions like CIRS, autoimmunity, and chronic infections.

 

• Improves blood vessel health and circulation. VIP affects vascular function, helping blood vessels relax and improving oxygen and nutrient delivery throughout the body, which is especially important for healing tissues and the brain.

 

• Supports digestion and gut function. VIP helps regulate how much digestive fluid is produced, how quickly food moves through the gut (motility), and keeps the gut lining healthy. This is crucial for nutrient absorption and preventing leaky gut.

 

• Regulates sleep, memory, and mood. VIP is involved in setting your circadian rhythm—your body’s internal clock that controls sleep-wake cycles. It also plays a role in memory and emotional regulation, helping you feel more mentally clear and emotionally balanced.

 

 

VIP therapy is the final step in CIRS treatment as it helps repair lingering damage to the immune system, brain, and cellular function that can persist even after biotoxins have been removed and inflammation reduced. When properly timed, VIP therapy helps to:

 

• Restore brain function and oxygen delivery
• Correct immune system imbalances
• Raise low melanocyte-stimulating hormone (MSH) levels
• Support long-term resilience and stability in remission
• Improve sensitivities and intolerances to environmental and food exposures

 

The Risks of Starting VIP Too Early

 

 

The requirements for starting VIP therapy as the final step are passing the VCS test, having certain normalized inflammatory markers, being in a safe environment, and clearing MARCoNS.

 

Starting VIP therapy requires normalized inflammatory markers due to the following:

 

Potential Immune System Overload

If VIP is introduced while the body is still in a highly inflamed state, it can further dysregulate the immune system. 

 

• One of Dr. Shoemaker’s gene studies found that VIP helped lower inflammation-related genes, but only in patients whose bodies were already stable.
  In other words, VIP reduced certain immune and inflammation markers only when the person’s metabolism and immune system were already calm. If the body was still inflamed, VIP didn’t work the same way and could actually make things worse.

 

• Another long-term study by Dr. Shoemaker found that patients who started VIP too early, before meeting key requirements, often got worse instead of better.
  These patients had not yet normalized important inflammatory markers like TGF-β1 (which regulates immune suppression and tissue repair), MMP-9 (an enzyme linked to tissue inflammation), and C4a (a marker of immune system overactivation). When these markers are still elevated, the body is in a reactive, inflamed state and not ready for VIP. Waiting until these markers are in range helps ensure the body can respond to VIP as a true healing step, rather than triggering setbacks.

 

Avoiding Worsening of Symptoms

VIP influences T cell function and cytokine responses. If used too soon, it can drive the immune system into exhaustion, worsening chronic inflammation and autoimmunity.

 

 

 

T cells are a type of white blood cell that play a central role in how your immune system responds to threats. There are different kinds of T cells, and each has a specific job. Here’s what they do:

 

• Helper T cells (Th cells): These are like the “managers” of the immune system. They don’t fight directly, but they give instructions to other immune cells using signaling chemicals called cytokines. Their job is to coordinate a proper immune response when your body senses infection or danger.

 

• Regulatory T cells (Tregs): These are the peacekeepers of your immune system. They make sure your immune system doesn’t go overboard and start attacking your own healthy tissues—something that happens in autoimmune diseases.

 

• Cytotoxic T cells (also called CD8+ T cells): These are the soldiers of your immune system. They find and destroy cells that are infected with viruses or have turned cancerous.

 

• Th1 cells (a subset of helper T cells): Th1 cells are inflammation-promoting cells that help fight viruses and certain bacteria. They activate parts of the immune system that use inflammation as a weapon, which is useful short term, but can become a problem if stuck in overdrive.

 

• Th2 cells (another subset of helper T cells): These are more active during responses to parasites and allergens. They help your body produce antibodies and can also contribute to allergies and histamine problems if they become too dominant.

 

• Th17 cells (yet another subset of helper T cells): Th17 cells help fight fungi and bacteria that live outside cells (like on your skin or in the gut). However, they’re also heavily involved in autoimmune conditions and chronic inflammation when overactive.

 

Chronic inflammation overworks and exhausts T cells. If VIP is added during this highly inflammatory state, it might over-suppress the immune system. This can cause T cells to burn out, making them less effective at clearing infections and toxins. When T cells become overworked or “burn out,” the immune system can weaken, making the body more vulnerable to chronic infections like Epstein-Barr virus (EBV) and slowing down the overall healing process. 

 

Epstein-Barr virus (EBV) is a common virus that most people carry without issue, but in individuals with weakened or compromised immune systems, the body may struggle to keep it in check, leading to chronic symptoms or reactivation. T cell burnout happens when the immune cells are too exhausted to respond properly, leaving you more susceptible to lingering infections and inflammation that the body would normally be able to control.

 

VIP reduces Th1 and increases Th2/Th17 (often overactive in autoimmunity). If these pathways are still imbalanced, VIP can trigger T cell exhaustion while suppressing natural killer (NK) activity, leaving infections unaddressed. NK cell activity refers to the ability of NK cells to recognize and eliminate infected or abnormal cells.

 

VIP can also drive Th2 and Th17 dominance, worsening autoimmunity, triggering histamine flares/MCAS symptoms, and/or exacerbating allergies and sensitivities. 

 

While many peptides gently nudge the body toward healing, VIP is a cytokine-like peptide that directly influences the Th1/Th2/Th17 balance, Treg function, and inflammatory cytokine signaling. If inflammation is still too high, introducing VIP too soon can amplify the wrong pathways, leading to immune dysfunction and worsening of symptoms.    

 

Suppressing Key Immune Functions

One study reported that VIP antagonists enhance antiviral immunity by boosting NK and CD8+ T cell function, showing that endogenous VIP can inhibit immunity under certain conditions (e.g., when the body is still inflamed). 

 

TGF-beta 1 is a key inflammatory marker in CIRS. VIP supports TGF-beta 1 production in immune-suppressive contexts, but this could suppress immunity if inflammation remains unresolved. In other words, while VIP does help regulate it and VIP therapy can lower stubborn TGF-beta 1 in certain cases, if the inflammation is still uncontrolled, VIP can push TGF-beta 1 too low.

 

Low TGF-beta 1 has been linked to:

• Fibrosis (scarring) of organs
• Immunospression 
• Loss of proper gut barrier integrity (leaky gut) 

 

What About Low-Dose VIP At the Beginning or Middle of the Protocol?

Low-dose VIP is used in certain cases at the beginning and/or middle of CIRS treatment. Low-dose VIP can help some individuals tolerate treatment better, making it a beneficial option when used correctly. The key here is microdosing—dilutions as low as 1:100, 1:1,000, or even 1:10,000 can offer a safer approach for individuals who still have systemic inflammation. 

 

This is often used as a temporary measure, but it is different from case to case. 

 

Why Am I Not Tolerating VIP Therapy?

 

 

 

There are various factors to troubleshoot if you’re unable to tolerate VIP therapy at this time:

 

• Ongoing Inflammation: If you have vector-borne illnesses like Lyme, chronic infections, or other root causes causing too much systemic inflammation, the reasons above could be a factor as to why you’re not tolerating VIP therapy. (Note: Some individuals start Lyme treatment after the Shoemaker Protocol and can tolerate VIP, so this doesn’t apply to everyone.)

 

• MCAS/Histamine Intolerance: VIP can flare histamines, making it important to start titrating at a lower dilution for onboarding. If your histamine issues are still severe after normalizing CIRS markers and being in a safe environment, it may be time to look into other root cause issues.  

 

• Too High of a Dose: It’s ideal to start onboarding VIP generally at 1:1,000 dilution. Some ultra-sensitive individuals may need to start as low as 1:10,000, and others may be able to tolerate a bit higher at 1:100. The dosing schedule should increase every other day—this is a low and slow process, if you’re starting at one spray of the 1:1,000 dilution, it should take you more than six months to reach the full strength dose at four sprays a day. 

 

• Being in Exposure: Some people experience symptoms while on VIP if they’re in ongoing exposure and taking too high of dose.      

 

There is a small population that doesn’t tolerate VIP therapy but has been able to successfully complete the Shoemaker Protocol with other therapeutic options such as LDN and Synapsin Spray. 

 

Why VIP Timing Matters

To summarize, VIP therapy is best started after systemic inflammation has calmed down, so it won’t be hijacked by an overactive immune system and can properly regulate cytokines without unexpected side effects. The body will be in a state where it can accept the repair process rather than push deeper into dysfunction.  

 

TLDR: Summary On the Importance of VIP Timing

Here’s a quick overview of everything we’ve discussed:

 

What Is VIP?

VIP (vasoactive intestinal peptide) is a natural chemical made by your nerves, gut, and immune cells. It acts like a messenger that helps calm inflammation, support gut health, improve brain function, and regulate the immune system. In the CIRS protocol, it’s the final step, meant to repair lingering damage after the body has already been stabilized.

 

Why You Shouldn’t Start VIP Too Early

Even though VIP sounds amazing, it’s not safe to jump in too soon. Here’s why timing matters:  

 

• Your body has to be ready. If your body is still inflamed or your immune system is dysregulated, VIP can backfire. Instead of calming things down, it may throw your immune system further off balance. Think of it like planting seeds during a storm—it just won’t work.

 

• It can exhaust your immune system. VIP changes how your immune cells behave. If you’re still inflamed, VIP can overstimulate tired immune cells (especially T cells), making it harder to fight infections like Epstein-Barr virus (EBV). This can lead to more fatigue, autoimmune flares, or worse.

 

• It can worsen autoimmunity and histamine issues. VIP can increase parts of the immune system (like Th2 and Th17) that are often already too active in people with autoimmune conditions or histamine sensitivity. This can make symptoms like allergies, rashes, and sensitivities worse.

 

• It can suppress key defenses. VIP lowers certain immune functions (like natural killer cell activity) that help fight viruses and keep your gut strong. If your body isn’t ready, VIP can weaken your defenses instead of helping.

 

When to Start VIP

 

 

VIP is most effective after: 

 

• Inflammation is under control
• MARCoNS is cleared
• The VCS test is passed
• Key labs are in normal range
• You’re in a safe (low mold) environment

 

Only then can VIP help repair and regulate, rather than cause setbacks.

 

Timing Is Everything

VIP is powerful, but it needs to be used at the right time. If you start too early, it may disrupt your immune system even more. While we all want to rush to VIP (after all, who doesn’t want to heal), starting too soon can actually set you back. 

 

For some people, the effects can be detrimental. There’s a saying: slow and steady wins the race, and when it comes to root-cause healing, that couldn’t be more true. Waiting to start VIP when your body is ready is far better than risking the chance of never being able to use it at all. We’ve seen this clinically hold true, and that’s not even factoring in the high monthly cost if VIP ends up not working because it was introduced too early.

 

Frequently Asked Questions About VIP

1) If VIP can normalize TGF-β1, why can’t we use it earlier to fix high TGF-β1 levels?

Because context matters more than the number.

 

VIP can lower TGF-β1, but only when the immune system is already stable. If you use VIP while TGF-β1 is high and the body is still inflamed or in a toxic environment (like ongoing mold exposure or untreated MARCoNS), VIP may actually suppress the immune system too soon, making things worse.

 

In some cases, VIP could even drive TGF-β1 too low, which brings its own risks, like poor gut barrier repair, reduced immune surveillance, and increased fibrosis (organ scarring).

 

The same goes for C4a and MMP-9. While VIP can lower these elevated inflammatory markers as well, it may lead to short-term suppression without true resolution, resulting in relapse or poor long-term outcomes.

 

Bottom line: VIP isn’t a band-aid for one marker. It’s meant to balance the system once the foundation (detox, inflammation control, infection clearance) has already been laid.

 

2) If VIP helps raise androgens (like testosterone), why not use it to fix hormone imbalances sooner?

Since hormone imbalances in CIRS are usually secondary and not the root cause.

 

Androgens like testosterone or DHEA often fall in CIRS because of:

• Chronic inflammation
• Low MSH (melanocyte-stimulating hormone)
• HPA axis suppression
• Toxic or mold exposure

 

VIP helps bring hormones back into balance once the upstream causes have been addressed. Using it too early might raise androgens temporarily, but without solving the deeper issues, the benefits won’t last and can actually stress the system.

 

Plus, if inflammation is still high, VIP may worsen immune imbalance (like pushing Th2/Th17 dominance), which can lead to more hormone disruption down the line.

 

Pro-Tip: Are you looking for more in-depth practitioner resources and a like-minded community to support you through your CIRS journey? Join our exclusive CIRS Support Group for the latest research, step-by-step protocol tools, and support to successfully achieve root-cause healing.

 

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DISCLAIMER: This content is for educational purposes only. While we are board-certified in holistic nutrition and are functional practitioners, we are not providing medical advice. Whenever you start a new diet or protocol, always consult with your trusted practitioner first.