We treat a lot of biotoxin illness (mold and Lyme or other tick-borne illnesses) and CIRS (Chronic Inflammatory Response Syndrome) at Nature Cure Family Health, using many of the principles first put forth by Dr Ritchie Shoemaker.

There is a bit of a debate among doctors who treat biotoxin illness regarding whether or not the last recommended step in Dr Shoemaker’s protocol, Vasoactive Intestinal Peptide (VIP) nasal spray, is necessary or advisable. Here’s what the data says.

What VIP Does

Regulates Cortisol and Circadian Rhythms

VIP is a hormone produced in the hypothalamus of the brain, and it acts on the HPA Axis: the “stress” axis of the hypothalamus, pituitary, and adrenal glands to regulate adrenal hormone production and release. This means everything downstream from the adrenals improves, including cortisol, DHEA (the precursor to sex hormones) and aldosterone, which regulates fluid volume in conjunction with ADH.

Data suggests that VIP also directly stimulates production of the “core” stress hormone too: norepinephrine. For someone in constant fight-or-flight, you might not think this is a good thing—but these people are actually depleted in catecholamines like norepinephrine more often than not, and increasing overall stores of it can be very helpful.

The HPA axis has a strong effect on circadian rhythms, so it helps regulate sleep cycles and melatonin as well.

Improves Digestion

Since out-of-whack cortisol levels lead to a thinned gut lining and a predisposition to food sensitivities, VIP also helps to repair leaky gut. This is also in part because VIP directly increases blood flow to the gut, improves gut motility, and stimulates release of enzymes, stomach acid, and bile in the gut.

Improves Immune Tolerance

Hypersensitive individuals who seem to react poorly to everything know how important this one is. Specifically, this refers to VIP decreasing Th1 autoimmune responses and promoting Th2 (allergic) responses instead, since this is always a trade-off.

But ultimately, VIP lowers most inflammatory cytokines (those second messengers of the immune system that trigger it to jump into action) and encourage production of the T regulatory cells that help promote immune tolerance.

Why VIP for Biotoxin Illness?

It might be obvious that all of the above benefits apply to those with CIRS and biotoxin illness, but there are other reasons more specific to CIRS patients too. Most CIRS patients have low VIP, and the suspicion is that this is because the biotoxins can cross the blood brain barrier via the olfactory system in the nose and directly affect hormone production via the hypothalamus.

Two other hormones produced by the hypothalamus, MSH (Melanocyte Stimulating Hormone) and ADH (Antidiuretic Hormone, also known as vasopressin) are also often affected. Low MSH in biotoxin patients often goes along with a colony of MARCoNS (antibiotic-resistant bacteria) in the nose, and improves when the colony is treated. Low ADH (or Diabetes Insipidus if severe enough) manifests with constant thirst and feelings of dehydration. This study shows that VIP raises ADH levels (and also raises oxytocin, aka “the cuddle hormone”.)

Perhaps because of the DHEA effect (the adrenal hormone that acts as a precursor for estrogen and testosterone), VIP also raises sex hormone levels, including DHEA, testosterone, and estradiol, which tend to be chronically low in biotoxin patients.

Chronically elevated TGFb1 even after mold is treated and Lyme is either treated or ruled out also tends to come down with VIP (though there are other ways to do this too, involving a strategy similar to Low Dose Immunotherapy for toxic mold, if that is the issue.)

Those with low VIP often also have low VEGF (Vascular Endothelial Growth Factor), which is required for production of new blood vessels. This can manifest as fatigue, which is really oxygen depletion—since the process of turning sugar (glycogen) into energy without oxygen is dramatically less efficient than the process with oxygen (38 ATP molecules to 2, to be exact). Raising VIP has been shown to correct this.

Pulmonary artery systolic pressure (PASP) is often low in biotoxin illness. This means the blood ejection fraction from the heart is lower, which can lead to palpitations, shortness of breath, and even potentially POTS (Positional Orthostatic Tachycardia Syndrome), very often connected to biotoxin illness. VIP has been found to correct PASP.

VIP also directly decreases neuroinflammation and the excitotoxicity which is often secondary to toxic exposures. Because of its effects on decreasing neuroinflammation, it’s also being studied for Alzheimer’s, Parkinson’s, and Autism. It has specifically been shown to decrease neurodegeneration from amyloid beta and fibrillary tangles characteristic of Alzheimer’s.

This study shows that 100% of the 20 patients in the trial had increased quality of life and decreased symptoms from VIP nasal spray. And this paper shows that over 90% of patients given VIP have a positive response, including reduction of symptoms and biotoxin markers on labs, with no significant adverse effects reported.

Possible Concerns with VIP

While the studies listed did not show many side effects, there are still a few to watch for.

  • VIP suppresses appetite. If this is already a concern, it’s something to consider.
  • VIP decreases metabolism. If you’re concerned about a slow metabolism or weight gain already, this is also something to watch for.
  • VIP increases insulin secretion. Anyone with metabolic syndrome or insulin resistance in addition to biotoxin illness would want to keep an eye on this.
  • There are concerns that as a growth factor (like VEGF), VIP might encourage  growth of existing breast or prostate cancer. It can also activate certain oncogenes (cancer-causing genes). Those with a personal or strong family history of cancer might therefore want to avoid VIP. 
  • Because VIP increases digestive secretions, there’s a possibility (though a rare one) of damage to the pancreas if enzymes are overstimulated. This can be tracked by measuring lipase (an enzyme produced by the pancreas) before and during treatment.
  • VIP has been found to be higher in people who have eczema. This is probably because, as mentioned above, VIP shifts Th1 to Th2 (allergies), so anything allergy-related has the potential to worsen. By extension, anyone struggling with severe allergies might want to think twice.
  • VIP is also higher in those with chronic migraines, which again is likely because of the Th2 shift, since migraines often have an allergy or histamine related cause. Those with migraines might want to proceed with caution.
  • Initial treatment with VIP can trigger a “toxic” feeling or irritation at first. This should resolve with lower doses and slow titration. 

Conditions to Meet Prior to VIP

As mentioned before, Dr Shoemaker strongly recommends holding off on VIP until after you’re already in a clean, mold-free environment and MARCoNS (the bacterial nasal colony mentioned above) is gone. This is because it’s not likely to do any good prior to this—if biotoxins still have a clear route to the brain via the nose, then VIP levels are just likely to fall right back down again.

Natural Ways to Increase VIP

Aside from compounded intranasal VIP, there are a few natural ways to try to increase VIP.

Since VIP is so intricately linked to the HPA Axis, anything that dials down the sympathetic (fight or flight) nervous system and increases the parasympathetic (rest and digest) also helps to raise VIP. Here are a list of options that do this by stimulating the vagus nerve.

Fasting, in addition to all its other immune benefits, also helps to increase VIP substantially. Intermittent fasting is a popular way to get the benefits of fasting without interfering with your schedule too dramatically.

Two amino acids have been shown to increase production of VIP as well: L-arginine,

and glycine, given at 3 grams before bedtime. Incidentally, glycine at this dose is often also helpful at inducing deeper stages of sleep, which may be part of the reason why it increases VIP (since VIP levels rise with cortisol in the morning). 

The Upshot

Intranasal VIP can be a helpful addition at the end of biotoxin treatment, once the environment is clean—provided the possible side effects are taken into account. 

Alternatively, some of the natural strategies for raising VIP such as fasting and vagus nerve stimulation are healthy choices anyway, and glycine is a very non-invasive strategy to try first.