Is Intestinal Alkaline Phosphatase a Link between Rosacea and Gastrointestinal Disease?

As I have written previously in a post about rosacea and digestive problems, many people believe that rosacea co-exists with gastrointestinal disorders. A recent paper by J. Whitehead (2009) discusses the hypothesis that rosacea and gastrointestinal symptoms can be linked through an enzyme found in the intestines, called intestinal alkaline phosphatase.

Intestinal alkaline phosphatase (IAP) is a membrane-bound enzyme found in the intestines, which function is to take away phosphate groups from a large number of molecules. For example, the absorption of the B6 vitamins pyridoxal phosphate and pyridoxamine phosphate is dependent on their dephosphorylation by intestinal alkaline phosphatase. IAP is also responsible for removing the phosphate from lipopolysaccharide (LPS), an endotoxin found on gram-negative bacteria that normally induces the fever response. A properly functioning intestinal alkaline phosphatase is important to prevent an immune response against the (good) gram-negative bacteria living in our gut.

Crohn’s disease and colitis are believed to be caused by an abnormal immune response to gram-negative bacteria in the intestine, a feature which may be shared with rosacea. Both Crohn’s disease and colitis are associated with reduced levels of intestinal alkaline phosphatase and the pathology of these diseases have been suggested to be triggered by LPS. Taking oral antibiotics for rosacea is believed to help eradicate these bacteria, resulting in a decreased immune response and subsequent improvement in rosacea symptoms.

Many people with rosacea are advised to modify their diet as many dietary triggers exist for rosacea. However, these dietary trigger factors vary from individual to individual and thus far no clinical evidence for a so-called anti-rosacea diet exists. The author of the paper further suggests that the typical Western diet (which is high in processed foods and low in fresh fruits and vegetables) results in a more acidic environment in the intestines. As its name implies, intestinal alkaline phosphatase works best in a more alkaline (or basic) environment with a pH in the range of 9-10.

Foods that lower IAP activity
IAP enzyme is inhibited by phytates, a substance found in grains and legumes. The only way to properly get rid of phytates is to cook grains and legumes well. In addition, the amino acid phenylalanine (found in some artificial sweeteners) also inhibits intestinal alkaline phosphatase.

Foods that stimulate IAP activity
Here are a number of foods that increase intestinal alkaline phosphatase activity:

  • Short chain fatty acids such as butyrate, derived from butter or from fermentation of dietary fiber in the gut
  • Fish oils (Omega 3, 6 and 9, either as a supplement or from fresh sea food)
  • Dietary Zinc (found in oysters or as a supplement)
  • Vitamin A (as found in carrots, sweet potatoes, pumpkins)

It is further suggested to increase the gut’s alkalinity by eating a variety of fresh fruits and vegetables and stay away from hard and processed cheeses and processed meat. Finally, adding probiotics to your diet may further decrease rosacea symptoms by the colonization of the g.i. tract with beneficial gram-positive bacteria while reducing the growth of LPS containing gram-negative bacteria.

Intestinal alkaline phosphatase is also stimulated by estrogen and inhibited by progesterone. For this reason, rosacea symptoms could appear during pregnancy and in women who use birth control pills.

Whitehead J. (2009) Intestinal alkaline phosphatase: The molecular link between rosacea and gastrointestinal disease? Med Hypotheses [Epub ahead of print Jun 30] doi:10.1016/j.mehy.2009.02.049

11 thoughts on “Is Intestinal Alkaline Phosphatase a Link between Rosacea and Gastrointestinal Disease?

  1. I have always had a healthy diet. I don’t have any G.I. problems, either. I do notice some symptoms & triggers from certain foods/drinks, though. I was shocked about cheese, & marinated meats! This is good to know, & always good to hear latest research. This disorder has, basically, ruined my life. Anything that may help future generations is great news! I hope the future will find some answers, & treatments so people won’t have to live with this horrible problem.

  2. i am already on a fairly restrictive diet due to IBS…I cannot eat any grains, rice, or beans. What are some key SAFE foods that will not trigger histamine or histamine production for my rosacea?

  3. I’ve had digestive issues for around 6+ years now. A lot of the signs have been pointing towards gluten intolerance but and I’ve gone off and on forms of exclusion diets over the years but never truly stuck to it. About 4 months ago I started having constant stomach distention with a variety of other digestion related issues. On top of that, my cheeks started to flush every day. For months, every day it starts around 11 a.m and will end around 3p.m. It’s pretty consistent and it accompanied by a lot of heat – it also comes on with emotional stress. So, I have to get serious about getting to the bottom of it because it’s really affecting my life. I’m on a variety of supplements and just changed brands of krill oil and coincidentally, I seem to be flushing less on a daily basis (but still really bad with emotional stress). So, I’m going to cut out the krill oil and go back to fish oil (never had issues while on that) and start a gluten intolerance diet to see if I can get some relief from the bloating, distention, flushing, etc. I may be having malabsorption issues too – vit D specifically. I’m getting retested in another month. If you have any clinical article/tests I can pass onto my dr. that would be great! Thanks!!

  4. This is in line with my experience: my rosacea was awful for about two months (my main symptom is “pimples” on my cheeks and clogged pores, relatively little redness/flushing) and I couldn’t figure out why. I couldn’t think of anything I was doing different….

    ….except I had stopped taking acidophilus capsules regularly. I started again and my skin improved within TWO DAYS.

    Right now I take the expensive enteric-coated ones, but I’ve gotten results from less expensive brands as well.

  5. Mammalian intestinal alkaline phosphatase (IAP) has many protective roles like gut differentiation, gut homeostasis, colon cancer prevention, etc. Homeostasis is achieved, whereby the so called good microflora are sustained in the alkaline intestinal environment. Other signal molecules like lipophilic vitamin, cholecaliferol, and the thyroid hormone too can modulte the overall expression of IAP in the gut.

  6. Anybody suffering from acne should investigate gluten intolerance as the link between the 2 is wellknown.

  7. To Tina ,

    It sounds to me that you may have a form of SIBO. I would ask your doctor for a breath hydrogen test.

  8. Thanks so much for posting this information. I was just diagnosed with rosacea yesterday and have been doing research and getting scared since. When I saw this post -alkaline phosphatase- stood out to me and I went back to look at the results of my last blood tests (in May)which showed that my level of alkaline phosphatase was below normal range. I’ve been being treated for hypothyroidism, but the tests in May showed that I was taking too much thyroid medication – so Dr. Pushpakaran’s comment is also helpful to me.

    Thank you again for the information you provide.

  9. At 43 I have suffered (miserably in autumn/winter) with Rosacea which affects my eyes also – at this time of year going from the cold into the stuffiness of a poor ill-ventilated hot office is a killer for my skin and people dont understand what they cant see under make-up. I refer to it as being washed vigorously with a brillo pad!! After many expensive lotions, serums – etc etc I finally plucked up the courage to go make up free to my Dr last month and she said “Its Rosacea” (yeah? well ive known that for years) and immediately prescribed me Doxycycline (I wanted to avoid antibiotics but thought heck,if they get me thru the winter). After 1 week, my skin HAS improved, the awful reaction to heat, the burning and stinging has reduced by 50% at least!! I can tolerate a cup of tea without having to leave the office for fresh air. I can continue these pills, at 50mg Im tolerating them well except for constipation which is the only side effect. (Was never much of a goer anyway lol – so maybe this IS intestinal related – I also have Gilberts and had eradication therapy for Helicobacter way back). Also had gall bladder removal at only 28 (I have always been fit,non-drinker, smoker so whats with all this>>). Anyway folks, if you are dreading the winter, try Doxycycline for your Rosacea – it should certainly make things a good bit easier and get us through the most horrible time of the year for Rosacea sufferers!)

  10. Excellent article. I, too, believe the link between the intestine and rosacea may be a very huge piece of the puzzle, While triggers may include diet, emotional stress, strenuous exercise, as well as other factors, research points strongly to proliferation of intestinal bacteria.

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