Rosacea and Gastrointestinal Complaints – The role of intestinal alkaline phosphatase in rosacea

Since the 1940’s and early 1950’s when physicians started noting and publishing that rosacea sufferers often report gastrointestinal problems and that these usually correlated with rosacea flares and flushing, a great deal of research has been performed to determine if there was a true physiological disturbance at the gastrointestinal level.

Gastroenterologists, physicians who specialize in diagnosing and treating disorders of the stomach, small intestine and large intestine, have performed dozens of clinical studies on rosacea sufferers over the past few decades and have reported mixed results.  Utilizing gastrocameras that can view and analyze most of the gastrointestinal tract, punch biopsies of the intestine to evaluate inflammation, histological evaluation of the bowel for dilator hormone release, and multiple endoscopic minimally-invasive surgical procedures, some physicians have found clear evidence that a significant percentage of rosacea sufferers do suffer from chronic inflammation of the  intestine and high levels of dilator hormones, proteins and peptides in the intestine that can be released into the systemic blood circulation and cause facial inflammation. 

Recently a molecular link has been proposed between an intestinal enzyme’s dysfunction and rosacea symptoms — this particular enzyme disorder may be overlooked by many physicians because there are no real physical signs.  This is now a “hot” research topic in the rosacea community.

Intestinal Alkaline Phosphatase Enzyme Function and Importance to Rosacea Sufferers

The Intestinal Alkaline Phosphatase (IAP) enzyme that resides in the brush border of the intestine where primary defenses, detoxification and absorption occur are key protectors of the gastrointestinal tract and are the primary “gate keepers” to what gets into the systemic circulation.  This dense population of enzymes is responsible for protecting against pathogens, bacterial assaults, detoxification of heavy metals, and blockade of potent dilators and inflammatory hormones.  The IAP must be healthy, active and able to mitotically divide to replace dysfunctional, inactive or dead IAP enzymes as 60% of our immune system resides in the gastrointestinal tract.

The IAP enzyme also regulates the passage of strong dilator hormones such as gastrin, vasoactive intestinal peptide, secretins and a dozen other hormones that could cause rosacea flares if left to freely pass through the intestinal brush border.

IAP enzymes, the role a healthy brush boarder plays for your general health and your rosacea

They also aid in the detoxification of foods, medications and drinks that consist of strong dilators and pro-inflammatory peptide fragments that can contribute to rosacea inflammation. [ref. #1]  The focus of many rosacea sufferers and naturopathic doctors has been in keeping the “good” bacteria in your intestine at high levels with probiotics, but the real key now seems to reside in keeping the IAP enzymes, healthy, functional and densely populated…. which probiotics have no effect on.

Intestinal Alkaline Phosphatase Enzyme Disturbances, Dysfunction and Death and their Effect on Rosacea Symptoms

In a recent medical journal article, “Intestinal alkaline phosphatase: the molecular link between rosacea and gastrointestinal disease?”, Dr. Joanne Whitehead discusses the importance of IAP in relation to rosacea.  “Rosacea is a common inflammatory condition of the facial skin of unknown etiology, which frequently occurs in combination with gastrointestinal disorders. Many dietary and hormonal factors are known to affect the severity of rosacea symptoms, several of which also modulate the activity of the enzyme intestinal alkaline phosphatase (IAP). The role of IAP in inhibiting an inflammatory response to intestinal bacteria suggests a mechanism by which intestinal pathologies may be linked to the skin inflammation characteristic of rosacea. Analysis of alkaline phosphatase activity is routinely performed on blood samples, and methods to quantify enzyme activity of the intestinal isoform specifically have been described. Correlations between IAP activity and rosacea symptoms in patients and controls can thus be screened by noninvasive and inexpensive means. If IAP activity is found to be low in rosacea patients, acute symptoms could be treated with oral IAP supplementation, and trials of IAP-activating medications currently used in gastrointestinal disease could be initiated in rosacea patients. More importantly, the safe and long-term control of rosacea could be undertaken by patients themselves through dietary modification to naturally increase IAP activity.” [ref. #2]

IAP’s effect on rosacea has been discussed in-depth at the 2011 and 2012 American Academy of Dermatology meetings and  is a keen area of research and treatment interest.  Most physicians note that when the IAP enzymes are dysfunctional, dying or dead, that most times rosacea sufferers only report minor gastrointestinal tract problems that can be easily misdiagnosed.  These cells just stop functioning and after they die, holes are left that trigger inflammatory hormone release of gastrin, vasoactive intestinal peptide, secretins and allow inflammatory immune cells, and dilator food particles to enter the systemic blood stream and trigger facial redness, flushing and skin inflammation.

[message_box title=”A Simple Test Often Overlooked” color=”red”]If you are one of the many rosacea sufferers that experience any form of gastrointestinal distress you should discuss getting a simple blood test that screens for IAP activity to quantify the number of active, healthy cells.  This blood test is called the IAP Intestinal Isoform analysis and can be performed on an outpatient basis and should be covered by most insurance companies.[/message_box]

IAP Treatment Options: Sulforaphane to the Rescue To Help With Treatment For IAP Dysfunction That May Be Contributing To Your Rosacea Flare Ups And Gastrointestinal Stress.

At  this time there is no medical treatment for IAP dysfunction.  Scientists are able to feed mice with various forms of IAP enzymes and reverse the disorder, but this has not been tested on humans.  However, supplementation with pharmaceutical-grade sulforaphane has been shown to be very effective in reversing this important enzyme disorder in scientific and clinical studies  In several clinical studies published in Gastroenterology Therapeutics (2013) high oral doses of sulforaphane were able to reverse most of this disorder and also protect future damage [ref. 3] :

  • Sulforaphane increased the function, activity and effectiveness of IAP enzymes across the entire intestinal brush border
  • Sulforaphane was able to save many cells from cellular death and reincorporate them into the brush border membrane
  • Sulforaphane increased the growth and number of these cells by activating DNA and transcription factors – which initiated mitosis and new enzyme growth
  • Sulforaphane was able to synergistically aid in the detoxification and thus was able to protect IAP enzymes from damage and resultant drops in enzyme activity
  • Sulforaphane blocked many of the damaging free radicals that circulate around these enzymes resulting in excellent protection and even higher levels of IAP activity

[message_box title=”Rosadyn Inside” color=”red”]Sulforaphane is one of the best nutraceuticals for gastrointestinal health and this is one of the reasons why we incorporated pharmaceutical-grade, clinical-strength Sulforaphane into our Rosadyn formulation.[/message_box]

Other supplements have been shown to improve IAP activity and health:

  • Phosphorus
  • Zinc
  • Vitamin A
  • Vitamin B12

All Sulforaphane is not created equally

Many vitamins, minerals, supplements and nutraceuticals can be purchased generically at low prices and still have the same effectiveness as higher cost brand products.  This is definitely not the case with Sulforaphane as this nutraceutical is very hard and expensive to extract and develop the correct way — if you want a sulforaphane supplement to contain medicinal qualities to address IAP enzyme disorders you must purchase pharmaceutical-grade sulforaphane (there are only two products on the market right now and one is Rosadyn) and make sure they have been tested in clinical studies.  Because of Sulforaphane”s many beneficial actions on the human body the market has been flooded with these supplements and, sadly, most are completely ineffective.  These products have been imported from countries known for their poor quality supplements that use alcohol, solvents and heat to extract the product cheaply, do not harvest the product at the right growth dates and do not test to see if they are biologically active in the human body.  Many sulforaphane products don’t even convert into its active form and thus are completely ineffective.  To highlight this important point:

  • Sulforaphane must be harvested from young broccoli or brussel sprouts  when they are three to five days old because if they are younger or older they contain 75% less sulforaphane.  Very few companies do this because it is very expensive.
  • Sulforaphane should be extracted and isolated using the latest solvent- free super critical extraction with CO2  because alcohol, solvents, and heat inactivate this ingredient.

[message_box title=”The  Rosadyn Difference ” color=”red”]

  • The Sulforaphane in Rosadyn is derived from young natural sources during its peak to ensure optional nutraceutical value.
  • Rosadyn’s Sulforaphane uses this latest “Green” technology for extraction, isolation and nutraceutical incorporation.
  • Rosadyn’s Sulforaphane has incorporated phospholipids for greater absorption and penetration into the inflamed cells and enzymes of the intestine

[/message_box]rosadyn is a natural rosacea product that helps with rosacea flair ups, break outs and flushing from the inside out.

Could you have undiagnosed IAP Enzyme Dysfunction?  Please Add your Comments!

Do you flush or flare after eating, experience gastrointestinal distress or suffer from spontaneous rosacea flares ? If yes have you thought about getting a simple blood test to determine if IAP enzyme dysfunction plays a role in your rosacea?

If you have been treated for IAP Enzyme Dysfunction and it has helped you with your rosacea  please also feel free to  share what worked for you. Your experience just may help others who may be experiencing the same contributor to their flushing and flare ups.


1.  Bol-Schoenmakers M, Fiechter D, Raaben W, Hassing I, Bleumink R, Kruijswijk D, Maijoor K, Tersteeg-Zijderveld M, Brands R, Pieters R  Intestinal alkaline phosphatase contributes to the reduction of severe intestinal epithelial damage.  Eur J Pharmacol. 2010 May 10;633(1-3):71-7. doi: 10.1016/j.ejphar.2010.01.023. Epub  2010 Feb 2.

2.  Whitehead J.  Intestinal alkaline phosphatase: the molecular link between rosacea and gastrointestinal disease?  Med Hypotheses. 2009 Dec;73(6):1019-22. doi: 10.1016/j.mehy.2009.02.049. Epub  2009 Jul 1.

3.  Kutler D., Sandstrom P.  Sulforaphanes action on the intestinal brush border and intestinal alkaline phosphatase enzyme: in vitro and in vivo studies.  Journal of Gastroenterology Therapeutics 2013 Feb: 84 (7): 85-97