Vasoactive Intestinal Peptide (VIP)

Updated on August 2, 2016

The FDA may ban VIP. For those of us that have the financial means, tax deductible donations in support of FDA approval can be sent to this address. All monies go toward the IND approval process with no “administrative fees”.

Step 11: VIP Article Outline


April has been super hectic. I’d wanted to write an article on windows and doors in relation to mold but it didn’t happen. Given that I’m trying to publish an article once a month, I’ve decided to consolidate my notes on Vasoactive Intestinal Peptide (VIP) nasal spray. These are just notes I’ve collected over the years watching Dr. Shoemakers DVDs and reading various materials.

The eleventh and final step in Dr. Shoemaker’s protocol for treating Chronic Inflammatory Response Syndrome (CIRS) is using Vasoactive Intestinal Peptide (VIP) nasal spray. For many, VIP can be profoundly helpful. For starters, VIP raises endorphins that are so important for reducing pain and bringing back that love for Life. VIP also corrects a whole host of other biomarkers that for some can not be fixed using Shoemaker’s protocol. VIP is the “icing on the cake”. Getting to the point where patients can take VIP is the goal of physicians following Dr. Shoemaker’s protocol. In this VIP trial, VIP improved the quality of life in 100% of people.

What is VIP?

Vasoactive Intestinal Peptide (VIP) is a master hormone (neuro-polypeptide) that is made in the gut, lungs, respiratory tract, pancreas, and a special part of the hypothalamus in your brain called the suprachiasmatic nuclei (SCN). When it comes to CIRS, VIP supports healthy hormone levels, works to limit inflammation, regulates the immune system, and helps the brain heal. Given the systemic impact of VIP, it’s not surprising that when VIP goes low (<25 pg/mL)., as it does in about 91% of folks with CIRS, people feel bad on many levels. As Dr. Shoemaker often says, CIRS is a multi-system and multi-symptom illness. Note: Interestingly, if you read Nasal Antifungals – Why Using Nasal Antifungals May Help, you learned that biotoxins can travel along the olfactory (smell) system and enter directly into the hypothalamus. Could this be a contributing factor in low VIP levels?

What Does VIP Help?

The question should be what VIP doesn’t help. Here’s a CIRS related list.

  • ADH/MSH/VIP – these three hormones move together. When one falls the other two follow and visa versa. MSH is another master controlling hormone that among other functions is critical to having healthy gut and healthy endorphin levels. Low endorphin levels means everything just hurts more along with a lack in the pleasurable feeling of being in love – with someone or some activity. Unfortunately, MSH is not available as the FDA banned MSH replacement drugs – for no good reason as they had been used in the past with no ill effect. On the other hand, ADH is linked to feeling thirsty all the time along with all the unhealthy impacts of being dehydrated. ADH can be difficult to correct in people with CIRS and is often skipped especially when patients don’t’ complain about thirst or frequent urination. Without VIP, MSH and ADH/Osmolality would be difficult to correct in many with CIRS.
  • Androgens – step 5 in Dr. Shoemaker’s protocol works to try to correct the male hormones androgen and testosterone. CIRS folks will have lower levels. Unfortunately, the standard protocol of supplementing with DHEA at 25 mg taken three times a day and HCG (human chorionic gonadotropin) injections of 125 mg per week (or sublingually) doesn’t always work. Although tempting, going to your doctor for testosterone supplementation is not recommended for CIRS patients as the supplemental testosterone is often just converted to the female hormones estrone and estradiol. This is because low VIP causes the enzyme that converts male hormones to female hormones (aromatase) to become overactive. In addition, the body may have a difficult time later on when testosterone therapy is stopped. When testosterone levels don’t correct with DHEA and HCG, VIP can be tried at 4 sprays per day for 30 days.
  • TGF beta1 – if you read TGF beta 1 – Mold – Turmeric, you know that people with CIRS have high levels of inflammation that is indicated by high levels of the blood marker TGF beta1. As discussed in that article, Dr. Shoemaker, uses Losartan (Cozaar – blood pressure pill) when TGF beta 1 is high especially if CD4+CD25 combo cell levels are less than 17. However, the blood pressure on some folks with CIRS can drop too low. I mentioned trying curcumin to help bring down inflammation associated with high TGF beta 1. Happily, for those that are struggling to bring down TGF beta1, VIP comes to the rescue.
  • C4a/MMP9/MASP2 – similar to TGF beta1, C4a and MMP9 are two additional CIRS inflammatory markers that are down-regulated with the use of VIP. Furthermore, given that C4a is driven up by MASP2, it should be no surprise that this enzyme is also lowered.
  • Vitamin D – in Alternative Mold Therapies – Vitamin D, I discuss the fact that vitamin D is frequently low in folks suffering from CIRS. Typically, the 25-hydroxy vitamin D level is very high and the 125-hydroxy level is very low. VIP fixes this.
  • VEGF – inflammatory cytokines choke off blood vessels. Unfortunately, Vascular Endothelial Growth Factor (VEGF) responsible for stimulating new blood vessels is often low in CIRS. When VEGF is low, the body struggles to make new blood vessels to offset the restricted blood flow. When VEGF is low or TGF-beta 1 is high, people will not be getting enough oxygen into their bodies to support the complete conversion of glycogen (sugar) into ATP energy molecules. Instead of getting 38 ATP energy units for every unit of glycogen, people suffering from capillary hypoperfusion only make 2 ATP units of energy. In other words, 95% of the energy that was stored in the form of glycogen is wasted. If you don’t have oxygen, you can’t make energy. VIP raises VEGF levels. In addition, constricted blood vessels can cause Pulmonary Artery Hypertension (PAH). PAH reduces blood flow due to high blood pressure in the lungs that makes the right side of the heart work harder. VIP reduces pulmonary artery pressure resulting in improved blood flow during exercise.
  • PASP – VIP brings PASP (pulmonary artery systolic pressure) during exercise back to normal. In CIRS, PASP is measured by looking for tricuspid regurgitation in the heart – reverse blood flow in the heart. When VIP is low, heart arterial pressure will be too low; the body will compensate by increasing heart rate – tachycardia. VIP therapy will raise pulmonary artery systolic pressure during exercise within days. Tachycardia, palpitations, and shortness of breath may be due to low VIP. According to Dr. Nathan, mold can cause Postural Orthostatic Tachycardia Syndrome (POTS) and certainly lower systolic pressure due to low VIP could be a cause. Interestingly, Dr. Shoemaker has not found high blood pressure as measured with a cuff in those with CIRS.
  • Brain – eventually I want to write an article on how CIRS causes many parts of the brain to swell. One of the consequences of this is that other areas shrink (atrophy). The caudate nucleus near the center of the brain that is responsible for voluntary movement, learning, memory, sleep and social behavior is one of those areas in the brain that gets smaller. It takes at least 4 months (6 months is typical), but VIP can fix the caudate. According to Dr. Ackerley, VIP has a lot of anti-inflammatory effects on the brain.
  • VIP improves brain function, blood pressure, enhances innate and adaptive immune function, and changes the inflammatory expression of genes.
  • Multiple Chemical Sensitivity (MCS) correlates to low VIP so when VIP is used, chemical sensitivity markedly decreases.
  • VIP fixes gingival disease and receding gums common in CIRS.
  • VIP has the potential to dramatically help some of the worst CIRS patients. In addition, VIP can lengthen the time a susceptible person can be in a water-damaged building and reduce the symptoms they experience after re-exposure.

When to Take VIP?

For most, Vasoactive Intestinal Peptide (VIP) should not be taken until the following conditions are met.

  • Passing Visual Contrast Sensitivity (VCS) test score. A passing VCS score and a clean home are clear indicators that the person is not being substantially re-exposed to biotoxins.
  • ERMI mold testing is less than 2 or HERTSMI-2 less than or equal to 10. If a person is being continually re-exposed, they can forget about seeing any benefit from VIP.
  • MARCoNS must be eradicated for VIP to work. Don’t waste your money until you’re in a clean place and have cleared up this nasty nasal staph infection.
  • Fasting Lipase levels are normal.
  • The other 10 steps in Dr. Shoemaker’s protocol have been followed. Dr. Shoemaker likens using VIP before addressing the other 10 steps of his protocol to putting a coat of paint on a burning house. VIP can do wonders but don’t expect much if you haven’t addressed the other ten steps. For many, some steps can be skipped, and for others it may be difficult to resolve some of the biomarkers. Nonetheless, it’s important to really try to repair your body as much as possible so VIP has the best chance possible. Additionally, Dr. Shoemaker is very concerned over misuse of VIP ending up with the FDA pulling the product off the market – not to mention using VIP out of step with his treatment protocol may leave Physicians open to lawsuits.
  • Note: If there is a hidden tumor, the enzymes it releases can hydrolyze VIP so any active tumors must be addressed.

VIP Biomarkers

According to Dr. Shoemaker, the first dose of VIP should be inhaled in the doctor’s office. For some, there will be in immediate improvement in joint pain, breathing, and cognition. For many others, no immediate improvement will be realized. Before the first nasal spray of VIP, tests should be performed to establish levels for MSH, VIP, ACTH, ADH/Osmolality, C4a, MMP-9, TGF beta-1, VEGF, testosterone, estradiol, vitamin D3 and lipase. After the first dose in the office, labs for TGF beta-1, C4a, MMP-9 and lipase should be redrawn.

By following many of these labs, improvement can be monitored. Especially important are TGF beta 1 and lipase. Any rise of TGF beta-1 greater or equal to 5,000 after administering VIP usually means that there is ongoing exposure to mold. When TGF beta-1 rises using VIP and ERMI/HERTSMI testing shows no mold exposure, then Lyme or a TH-17/T-reg cell imbalance may be the issue. A rise in lipase may indicate serious pancreatic damage is occurring.

Although rare (4 out of 600), lipases can rise due to VIP indicating increased pancreatic secretions and possible injury to the pancreas. This is serious, so make sure to also measure lipase before the first dose of VIP to establish a baseline. Subsequently, check lipase each month for the first three months and then every three months afterward to ensure levels are stable during VIP therapy.

Stop use of VIP at the first sign of a rising lipase in combination with stomach pain. Per Google, a normal lipase level is 0-160 U/L. Symptoms of pancreatitis may include abdominal pain and swelling, diarrhea, fever, muscle aches, and lower blood pressure.

VIP Dosage & Side Effects

The general guidelines for taking VIP (assuming the first dose is well tolerated) is to spray 50mcg in alternating nostrils 4 times daily for 30 days and then recheck blood pressure, VCS, C4a, TGF beta 1, and fasting lipase. If the labs like C4a and TGF beta 1 are improving, then start tapering down VIP over the next month to 2 doses daily. Continue taking Vasoactive Intestinal Peptide (VIP) at 2 doses daily for 1 more month and then stop. Six months after stopping VIP, recheck labs to make sure levels are stable and within range. Note: Some spray bottles deliver 50mcg in a single spray and some require two sprays.

A second alternative protocol is to take VIP for 2-3 months and then reduce the number of doses by one dose every month until symptoms worsen. A third protocol is to slowly increase the daily dosage until no further benefit is realized and then begin gradually reducing the dosage. Overtime, the goal is to reduce the dosage to zero in 3-12 months. With experience, patients will learn what dosage is right for them.

A person does not develop a tolerance for VIP necessitating higher doses over time. Some patients dose up to 36 times a day and some have used it more than 4 years with no ill affect. Except for the concern over lipase, there are very few side effects – low blood pressure, stomach ache, and rash. VIP may also cause dysphoria (depression). Dr. Ackerly believes this may be due to NMDA receptor activation. In these cases, dilute VIP to 1:10 or 1:100 and slowly titrate up to standard doses.

As an aside, some chemically sensitive people take 4 doses in the morning and 8 more doses before bed. In the September 2015 presentation When Inflammation Becomes Chronic given by Dr. Shoemaker and sponsored by Hopkinton Drug, Dr. Shoemaker remarked in the Question/Answer session that VIP should be slowly titrated up to maximize benefit. Dr. Shoemaker took as many as 28 doses daily at one point in time but now is down to nearly zero. Once the maximum dosage is reached, you can begin titrating down overtime to see what the minimum dose is that still provides maximum benefit. It’s impossible to overdose on VIP.

VIP – Exceptions to the Rules

  • Those that are particularly sensitive may need to start with diluted doses of VIP.
  • If you’ve read some about Dr. Shoemaker’s protocol, you know that fish oil is a mainstay. Fish oil used in step 4 helps lower antigliadin antibodies. Fish oil is also important to those post-Lyme folks that are having difficulty tolerating cholestyramine (CSM). Unfortunately, some people can not tolerate fish oil. In these cases, VIP must be relied upon.
  • VIP can be used to prop up patients that couldn’t tolerate binders, treating MARCoNS, and are just really stuck. In the Saturday 2015 Mold Conference, Mrs. Velletri described how her extremely weak daughter, Mia, was given VIP. Initially, Mia could only take slivers of Welchol and was extremely tired. She was started on VIP diluted to 1:10 that was later increased to 1:4. As a result, Mia felt better, went back to school, and starting taking full doses of Welchol.
  • At 1:49:00 in the September 2015 presentation entitled ” When Inflammation Becomes Chronic“, Dr. Shoemaker said VIP diluted at 1/10 to 1/100 can help deal with food intolerances. For some, the list of foods that don’t cause reactions is very limited. VIP can be helpful in these cases.
  • Dr. Ackerley commonly sees people that feel good the first few days and then begin feeling toxic. She believes this is because the body is letting go and down-regulating. If this happens, cut the dosage in half, or to a quarter, for a few days until you feel better and then gradually increase the dosage.

Testing and Ordering VIP

VIP Bottle

According to the Physician’s Order Sheet, the blood draw to measure Vasoactive Intestinal Peptide (VIP) is simply a matter of collecting a sample at room temperature into a lavender top (EDTA) vial. It doesn’t get any easier. Just make sure it’s goes through Quest labs. The normal range is 23-63 pg/mL.

VIP can be ordered from Hopkinton Drug. The cost as of January 2015 was $190 plus $40 shipping. Each spray contains 50 mcg (micrograms). Each dark brown, glass vial holds 120 doses and lasts 90 days when refrigerated in an upright position. It’s very important to keep VIP refrigerated. VIP arrives in the mail in a Styrofoam box containing ice packs. Patients should blow their nose to remove mucus, dust or debris prior to administration of VIP into the nostrils.

Update August 2, 2016
Caleb from Toxic Mould Support Australia wrote to me with some additional information about where to get VIP. He wrote, “VIP is available at two other pharmacies in the USA (Mixtures, Remedies) as freeze dried capsules that the patient mixes up at home, I’ve attached the info file that a member, Rebecca, uploaded. It’s not exactly the same formula as Hopkinton. There are two pharmacies in Australia that sell it too, one Your Solutions, consulted with Hopkinton over the formula. The other did not.” Thanks Rebecca and Caleb!
Update End

VIP Package Temps 2

In conversation with pharmacist, the following points were made.

  • VIP is a peptide and as such doesn’t tend to break down until 100°F is reached.
  • Upon arrival, the bottle should be cool to the touch (36-66°F).
  • Hopkinton has tested VIP by leaving it out for a week and it was OK.
  • Hopkinton has tested VIP by freezing it twice and it was OK.
  • VIP should not have any odor to it. Bad VIP smells “foul”.
  • VIP begins to lose its potency after the expiration date as VIP is a peptide that degrades with time.
  • Even though the pharmacist couldn’t say VIP was still safe past expiration for legal reasons, the suggestion made was that it most likely would be.
  • It’s OK to dilute VIP with over-the-counter sterile saline solution. For example, 1 part VIP to 9 parts saline yields a 1:10 ratio.

Hopkinton VIP Drug Directions – see image to the right.

Hopkinton VIP Directions

Note: I called and spoke with Dennis from Hopkinton Drug about a warm VIP shipment. I’d received a USPS Styrofoam package containing ice packs that were at 67°F and the VIP bottle was at 74°F. Apparently, the USPS flight had been delayed causing the delivery to be a day late. Dennis said the VIP was most likely OK, but they sent a new bottle just to be on the safe side. Dr. Shoemaker has commented in the past that VIP will become useless if left to sit out at room temperature for 8 hours. Dennis felt that Dr. Shoemaker may just have wanted to be extra careful in his recommendations.

Natural Ways to Raise VIP and Links

In VIP: A Potent Anti-Inflammatory and Natural Ways to Increase It, Joe Cohen mentions several ways to increase VIP levels naturally. Among them is taking 3 grams of the supplement Glycine before bed. According to The Effects of Glycine on Subjective Daytime Performance in Partially Sleep-Restricted Healthy Volunteers, Glycine can help with sleep by lowering body temperature. Glycine also raises daytime levels of VIP by about 3 times and Arginine Vasopressin (AVP) by about 4 times.

14 thoughts on “Vasoactive Intestinal Peptide (VIP)

  1. Any adverse reactions to VIP noted? I’m very stuck. I can’t even take the tiniest bit of CSM or another binder. I had a huge intensification after taking 1/8 the dose of CSM for 4 days and have been sicker ever since. It was very scary. Ackerley wants me to try VIP 1/100, but I’m really nervous of adverse side effects.

    • Debra,
      I totally get how scary it can be. I feel really lucky that I was able to tolerate CSM. I’m assuming you pre-treated with fish oil to help bring down inflammation along with supplements like turmeric. Personally, I did start feeling toxic after the first few days of VIP but my house wasn’t as clean as it should have been. Nevertheless, starting to feel toxic with VIP can happen.

      The main point is to go really slow. The girl, Mia, I mention in this article couldn’t tolerate anything. It was VIP at super dilute doses that brought her around. You may also want to take a look at Binders – Side Effects & Complications.

  2. I have recently experienced the same awful situation.
    I had been living in a 1990’s leaky condo in a wet climate ( Vancouver Canada )

    the siding was removed in some areas where the mdf board was rotten, putting out toxins making us sick.
    there was no visible mold in the house, but I’m positive it was in a couple of the rooms carpet.
    I now have MCS from it all

    We have moved, got rid of porous items, couches, beds. mdf furniture
    My question is what everything else?
    wood furniture

    any advice you can give would be great I could not find this on your site?
    we are going crazy with the whole thing

    • Jenean,

      It sounds like you’re moving in the right direction – getting away from the mold and discarding porous items.

      Wood furniture can be cleaned – unless it’s really rustic with a really rough surface. I like to use QUAT but Gregg Weatherman recommends diluting isopropyl alcohol. A typical bottle of isopropyl alcohol is 70%. If you mix this with 7 parts of water, you get roughly 10% alcohol. Using a bunch of clean microfiber cloths, dip one cloth in your clean 10% solution, wring it out well, and wipe the surfaces in many directions. Refold the cloth often using different sides. Discard cloths frequently. Never dip a used cloth in your clean alcohol solution. Follow up with a clean, dry cloth. Run used clothes through the washer and then re-use. Video Series
      Condensed Remediation Plan for Small Microbial

      Clothes can be washed in Borax. The worse the toxin and level of exposure, the more washing that may be required. Really toxic clothes may need to be washed three times. Of course, make sure the washer is not moldy – front loaders are the worst. Alternatively, clothes can be dry-cleaned but then there’s an issue with chemicals especially since you have some MCS.

      I’d also recommend you sign up at Lisa Petrison’s Mold Avoiders Forum for answers to these kinds of questions. I’ve heard there’s lots of information there.

      • thank you Greg your the best.
        we moved to a very newly built home, and I’m feeling like I’m back in the toxin condo.
        Do you feel this is due to the new building materials?

        • New places have a lot of off-gassing chemicals. For example, I always check to make sure the hotels I book are at least a few years old. I got totally fried recently from the chemicals on a new pull-out couch at a hotel. Also, new does not mean mold free. You really have to test.

          • I left the new home to get away from the chemicals, but am still having a bad time with MCS, any advice?

            • Hi Jenean,

              It’s great you moved away from mold but now it sounds like you’re having trouble with off-gassing from new building materials. Nevertheless, make sure to test for mold at your new place (if you haven’t already). For myself, I was surprised to discover that I had developed some chemical sensitivity after CIRS got bad for me. It’s not uncommon for folks with CIRS to have some chemical sensitivity.

              I hate to say it, but it can take years for building material chemicals to off-gas enough. You could look at getting an Austin or Foust air cleaner. Both have large carbon elements to trap the VOCs. I know for a fact that the Austin isn’t true HEPA, but in your case, it’s mostly about the VOCs. I’ve never tested a Foust. Personally, I’d get an Austin or an IQAir if you can afford it. Run the unit in your bedroom at night.

              If the MCS is bad enough, you could consider using VIP as is outlined in this article under VIP Dosage. If it were me, I’d keep looking for a mold and chemical free place, treat CIRS (assuming I’d been diagnosed), and add on whatever other therapies made my situation more workable.

  3. HI, excellent blog and info. I’m starting VIP today and just noticing the sprayer tube they sent me is too long so you can’t secure it to the stupid glass bottle. The instructions have in bold not to cut the TUBE! LOL- Is this for real??? Anyone else get the same set up from Hopkinton?

    • Hi Chris,

      The sprayer tubes are always longer than the bottle. Just gently press the nozzle onto the bottle and screw into place. The tube will bow inside the bottle ensuring the end is at the bottom of the bottle so you get every last drop.

  4. Greg,
    Thanks for all of your posts. They have been a godsend!
    I am wondering why VIP can cause a “detox” reaction? What is the mechanism? Is it just that the system is “down-regulating.” I just started VIP yesterday and I just doing 1 spray a day to start. I have been very nervous. Thanks for your insight.

    • Sarito,

      I haven’t read anything specific related to why some folks don’t feel well initially using VIP and need to go slow. We do know that Dr. Shoemaker found that haplotypes like 11-3-52b and 4-3-53 typically don’t get better without VIP. This is because their bodies don’t reset otherwise – markers like TGFB1 and the like remain out of balance without VIP. We also know that the body sequesters toxins in fat as a way of limiting the damage they can do.

      So if a person starts taking VIP, perhaps bound up toxins are being released. Also, what is the impact on the body of a person that’s been suffering from CIRS for decades when it begins to re-balance a whole host of hormones, neurotransmitters, and other regulatory peptides/proteins. That’s a lot of chemistry to re-align with substantially higher VIP levels. I like your idea of going slow initially.

      Woo-hoo, you made it to VIP!

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