You probably don’t have enough VIP.  98% of people with CFS don’t.  The MCS crowd hasn’t yet been testing, but when you learn what this neuropeptide does, you’ll probably surmise that low levels play a big role in that syndrome as well.

In Ritchie Shoemaker’s 2011 IACFS paper, “Vasoactive intestinal polypeptide (VIP) lowers C4a and TGF beta-1, corrects refractory symptoms and normalizes abnormal biomarkers in patients with CFS”, the role of VIP is elaborated in detail.

He wrote:  “VIP raises cAMP; lowers pulmonary artery (PASP) responses to exercise, blocks peripheral innate immune activation; reduces apoptosis of glial cells undergoing oxidative stress; raises VEGF; restores circadian rhythm; regulates response to olfactory stimuli in the suprachiasmatic nucleus; regulates dendritic calls; regulates Th17 function in autoimmunity; enhances IL-10 production; and modulates innate immunity.”

Let’s put that into lay person’s terms.

  1. Raises cAMP, short for cyclic Adenosine Mono Phosphate.This molecule is one step away from ATP, the energy molecule, the one that mitochondria make in great abundance when they work properly.  All of us with fatiguing illnesses have low ATP, some from mitochondria damage, as Dr. Sarah Myhill has shown, some from interference in the citric acid cycle due to heavy metals (especially mercury and aluminum), some from poor metabolism of sugars that feed the citric acid cycle with pyruvate, some from a deficiency of oxygen transport into the mitochondria, etc.   From Wikipedia we read, “cAMP is… used for … transferring the effects of hormones like glucagon and adrenaline, which cannot pass through the cell membrane. It is involved in the activation of protein kinases and regulates the effects of adrenaline and glucagon. It also regulates the passage of calcium ions through ion channels.”   If you have issues with sugar metabolism (but not diabetes) and with adrenaline, you probably have low cAMP and would benefit from raising it.  In addition, cAMP affects cognitive function (not a big surprise since those brain cells of ours need to work properly.  By researchers have found a specific relationship between low cAMP and the cognitive deficits in age-related illnesses and ADHD.
  2. PASP (pulmonary artery response to exercise) may contribute to our exercise intolerance.Shoemaker found that patients on VIP could tolerate more exercise.  It still remains to be seen if raising VIP eliminates the phenomenon Drs Snell and VanNess documented at Pacific Fatigue Lab, results unique to CFS in which repeating a stress test within 24 hours showed markedly reduced capacity to produce energy and metabolize oxygen.  It would also be valuable to know if the changes in receptor activity in CFS patients during exercise, documented by Drs. Kathleen and Alan Light, ceases to operate after normalization of VIP levels.
  3. Peripheral innate immune activation makes us itch, swell from bugbites and scratches, get extreme reactions to poison ivy.
  1. Reduces apoptosis of glial cells undergoing oxidative stress. Apoptosis is another way of saying that brain cells which have been damaged by free radicals commit suicide (a normal process to make way for new, healthy cells).  Yet when there is more death than replacement, cognitive function deteriorates.  It’s been said that we don’t notice cognitive deficiencies until we’ve lost about 70% of our brain cells.  Good to reduce this depletion of our brains by restoring optimal levels of VIP.  If the cells don’t commit suicide, they can be repaired and restored to optimal health with reduction in toxins and inflammation and increase in nutrients.
  2. Raises VEGF, a molecule which helps us build new blood vessels.  When too high, VEGF can support the growth of cancer.  Too low means less repair of damaged vessels, especially those tiny capillaries which feed every cell in our body.  Hence degeneration as tissues which are deprived of the blood bath bringing oxygen and nutrients hold onto the toxins that reduce optimal function.
  3. Restores circadian rhythm, the daily rhythm of hormones like cortisol, an important adrenal hormone which serves as a buffer against stress and inflammation.  Cortisol is highest in the early morning, drops to about half by noon, and then slowly declines in the evening until we are desirous of sleep.   Good to reverse an inverted or flat rhythm; the former keeps us up late at night, the latter leaves us in perpetual lethargy.  Disturbed adrenal circadian rhythms have been found in CFS-ME, as documented by data at Sabre Sciences, Inc, a lab which offers salivary testing of the circadian rhythm.  The majority of indexed studies on adrenal issues in this illness looked a total serum cortisol, finding no pattern other than disturbed regulation of the hypothalamic-pituitary-adrenal axis, while salivary hormone testing measures free cortisol inside the cells.  If cAMP is low, cortisol transfer into the cells will suffer.  Consequently, when I tested an 8 am serum cortisol and did an 8 am saliva sample at the same time, we found a very high normal serum level and a below normal salivary level.  My adrenals were working fine, but my cortisol was all bound by globulins as it couldn’t be transported into the cells which needed it.  No wonder I couldn’t tolerate taking Cortef (a cortisol replacement).
  4. Regulates response to olfactory stimuli in the suprachiastic nucleus, e.g. to smells and chemicals that we breath.   Those with MCS are hyper-sensitive and get the kind of response to 1/10000th of a scent or odorless chemical that normals get to amounts 10,000 times greater than normal.  (From Martin Pall, whose theory of MCS involves upregulation of OH and ONOO with NMDA receptor hyper-response.)
  5. Regulates dendritic cells, immune cells which present antigens to other immune cells so that these antigens can be eliminated.  Dendritic cells are found everywhere the body is in contact with the external environment: on the skin and in the inner lining of the nose, lungs, stomach and intestines.
  6. Regulates Th17 function in autoimmunity, a type of T cell makes interleukin 17 which is found in excessive amounts in MS, psoriasis, rheumatoid arthritis, and other autoimmune disease.  They serve an important function at the mucosal barrier by producing cytokines which stimulate these cells to produce chemicals to fight candida, staph, and other microbes.  Without Th17 cells, there are more opportunistic infections.
  7. Enhances IL-10, an important anti-inflammatory cytokine which plays a role in the gut-based immune system.
  8. Modulates innate immunity.  This is the part of the immune system that we are born with, our first line of defense against invading pathogens.  It is the part that goes wacky in CIRS, and presumably also in CFS.

From a study of 1682 patients meeting the criteria for CFS, 98% had low VIP.  In comparison, fewer than 10% of controls have low VIP.  The range for VIP that Shoemaker uses is 23-63 pg/ml.  Shoemaker is working with VIP replacement, as a patented hormone replacement has been produced by Hopkinton Drug.  A talk he gave to other physicians used to be available at . It can still be accessed as streaming video on Shoemaker’s site at

But beware of the fact that taking VIP right away doesn’t do any good.  As Shoemaker states repeatedly in his book, Surviving Mold, it’s crucial to eliminate environmental mold toxins, detoxify the mycotoxins in the body, and lower inflammation before you take VIP.  It might also be helpful to first balance some of the upstream regulatory hormones, such as ADH and cortisol.

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