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

Vitamin B6 plays a major role in hundreds of enzymatic reactions in the body, including the synthesis of amino acids, nucleic acids (DNA/RNA), phospholipids (which are part of cell membranes), histamine, certain neurotransmitters (such as serotonin, norepinephrin, GABA), heme (the center part of hemoglobin) and the processing of carbohydrates.

Vitamin B6 is believed to have a major impact on the skin as when vitamin B6 levels are insufficient, inflammation of the skin can develop, in particular seborrheic dermatitis. Vitamin B6 used to be called anti-dermatitis factor and is also one of the main ingredients in topical treatments for seborrheic dermatitis.

Vitamin B6 deficiency
Since vitamin B6 is involved in the production of the “building blocks” for every tissue in the body, tissues that regenerate frequently such as blood and skin, are affected most when vitamin B6 is deficient. Symptoms of a vitamin B6 deficiency include anemia, fatigue and skin conditions such as eczema and (seborrheic) dermatitis.

Vitamin B6 is absorbed from our food in the intestines via passive diffusion. The absorption of B6 vitamins pyridoxal phosphate and pyridoxamine phosphate involves the dephosphorylation catalyzed by intestinal alkaline phosphatase, which is a a membrane-bound enzyme. Vitamin B6 deficiencies are relatively rare, but people with inflammatory bowel conditions (such as Crohn’s disease and celiac disease), people who drink large quantities of alcohol and people taking certain drugs (corticosteroids, anticonvulsants) are at risk for developing a vitamin B6 deficiency.

Because vitamin B6 plays a major role in the healthy functioning of our nervous system and skin, a severe deficiency of B6 can result in seizures, convulsions and inflammatory skin conditions.

Vitamin B6 is also important for the synthesis of vitamin B3 and for the absorption of vitamin B12. Foods that contain high amounts of vitamin B6 are meats, fish (tuna) and vegetables such as spinach, broccolli, Brussels sprouts, cauliflower and more. Cooked and processed food however, have lost most of the active vitamin B6 and for that reason, supplementation with vitamin B6 may be beneficial to your health if you suspect a B6 deficiency. In addition, several studies have reported that vitamin B6 supplementation can be helpful for managing symptoms of autism.

In addition to the chemically synthesized antihistamines, there exists a fair number of plants and herbs that contain natural antihistamine compounds. Most of these can either be taken as an herbal tea or as an herbal extract. Some are popular culinary herbs.

• Basil (Ocimum basilicum) is an herb most often used in Italian and South-East Asian cuisine. It has a sweet, anise and mint-like flavor and is considered one of the most popular herbs. Basil contains the compound (E)-beta-caryophyllene (BCP), which selectively activates the cannabinoid CB2 receptor, thereby blocking inflammation. Basil may be useful in treating arthritis and inflammatory bowel diseases.

• Chamomile (Matricaria recutita, or German Chamomile) is a popular herb taken for a variety of health issues. Chamomille’s anti-histamine property comes from the compound quercetin. Chamomile can be taken as an herbal tea and has been reported to have antimicrobial and antioxidant properties as well. In addition, it also has anti-platelet activity, so care must be taken when someone is taking blood thinners.

• Echinacea (Echinacea purpurea), also known as the purple coneflower, belongs to the same family as chamomile and has been shown to have antihistamine properties. Echinacea is a widely used herbal remedy for treatment of upper respiratory tract infections and has been suggested to reduce the duration of the common cold. While Echinacea is believed to stimulate the immune system, no definite scientific proof exists whether or not Echinacea is able to speed up the recovery from a cold. This is mostly due to the fact that herbal extracts are hard to standardize (different parts of the plant, different sources).

• Fennel (Foeniculum vulgare), used classically for indigestion, spasm of the G.I. tract as well as expelling mucus from the lungs. In addition to phyto-estrogens, fennel also contains the antioxidant flavonoid quercetin. Quercetin is a strong natural antihistamine shown to be very useful for allergies and histamine-related inflammation.

• Thyme (Thymus vulgaris) is a popular culinary herb that also has anti-histamine properties. Its main component, thymol, is an antiseptic that is being used in Listerine mouthwash. Thymol also has anti-fungal activities and is useful for treating nail fungus. A tea made with thyme herb is useful for treating cough and bronchitis. Thyme is also thought to have oxytocin-like properties.

• Reishi (Ganoderma lucidum) has anti-microbial, anti-viral and anti-cancer properties. Reishi has also been reported to act as an antihistamine, making it useful for treating allergies. Lanostane, a compound found in reishi, is a powerful antimicrobial compound.

Additional Reading

1. antihistamines natural healing herb – if you want to get rid of side effects, the best herb solution would be antihistamine herb. there are numerous unnoticed herbs that are a far better option for instance pau’d arco, catnip, chinese licorice root, cat’s claw extract, …
2. natural allergy relief with herbs and home remedies – the primary antihistamine herb is stinging nettle, which is one of the most popular herbs among those seeking natural allergy relief. one study found that it may offer relief to people with hayfever. sixty-nine patients completed the …

Histamine is also thought to make rosacea symptoms worse. Since we also ingest histamine through our diet, I thought it was helpful to look at what foods contain the highest amount of histamine. Aged and fermented foods are naturally high in histamine, so these kind of foods dominate the list. I have gathered the information below from various sources on the internet as well as from a number of scientific papers.

The amounts of histamine are given as mg per serving size (either 3.5 Oz., 4 Oz. or pint). Please note that the same food item from different sources vary tremendously in their histamine content: food items that are close to their expiration date have a higher histamine content. Therefore, the numbers given below are for illustrative purposes only.

Here are the top 10 foods high in histamine:

1. Champagne (76 mg/4 Oz.)
2. Sauerkraut (23 mg/3.5 Oz.)
3. Tofu (as high as 22 mg/3.5 Oz.)
4. Parmesan Cheese (15 mg/3.5 Oz.)
5. Beer (7 mg/pint) Beers vary in histamine content, with top fermented beers being higher in histamine.
6. Sausage (6 mg/3.5 Oz.) Fresh sausage is often lower in histamine than the cured/aged sausage.
7. Blue Cheese (5 mg/3.5 Oz.)
8. Red Wine (3.5 mg/4 Oz.)
9. Eggplant (3 mg/3.5 Oz.)
10. Tomato Ketchup (2 mg/3.5 Oz.)
11. Canned Fish (tuna, salmon, herring) (2 mg/3.5 Oz.)

“Numbers shown are approximate”

Foods that stimulate the release of histamine

Certain foods (even food that is low in histamine) can stimulate the release of histamine from mast cells (a type of immune cell). These foods include bananas, tomatoes, strawberries, pineapple, nuts, peanuts, shellfish, spinach, egg white and chocolate. Eating these foods can thus have an indirect effect on rosacea.

Some of the most tasteful food is high in histamine. High histamine levels however, can cause headaches, runny nose, sneezing, stomach aches/cramps and flushing skin.

Maintz, L. and Novak, N. (2007) Histamine and histamine intolerance. Am J Clin Nutr 85: 1185–96.

Chronic stress activates the so-called HPA axis, which is the connection between the hypothalamus and pituitary gland in the brain and the adrenal glands on the kidneys. Activation of the HPA axis by stress leads to higher levels of the stress hormones corticotropin-releasing hormone (CRH) and cortisol, which have a profound effect on our health, skin and brain. The HPA axis is kept balanced by neurotransmitters such as serotonin, adrenaline and dopamine. However, if the HPA axis gets chronically stimulated by stress, a major imbalance in neurotransmitters can result and may lead to the development of anxiety and depression.

Research suggests that the breakdown of the skin’s barrier function (or matrix degeneration) in combination with excessive exposure to the sun, forms a central part of rosacea development. A breakdown of the collagen fibers is thought to play a major part in the degeneration of the skin’s matrix. Poor connective tissue support for blood vessels just underneath the skin can therefore result in the pooling of serum, metabolic waste and immune mediators, which over time leads to more flushing, edema, chronic erythema and telangiestacias. The involvement of a matrix breakdown in rosacea is likely, because blood vessels in rosacea are still able to respond to vasoactive substances.

An out-of-balance HPA axis (particularly prominent in depression and anxiety), results in high levels of corticotropin-releasing hormone (CRH). CRH has been shown to increase the permeability of peripheral blood vessels through the stimulation of mast cells, which in turn release immune mediators such as histamine and nitric oxide. Anti-depressant drugs are thought to “calm” an over-active HPA axis by increasing the availability of neurotransmitters such as serotonin, dopamine and adrenaline. Therefore, the use of antidepressants for a prolonged period of time may reduce the severity of rosacea symptoms. Reducing stress levels in our lives could have a significant impact on the progression and stabilization of rosacea symptoms.

Fimmel S. et al. (2008) New aspects of the pathogenesis of rosacea. Drug Discovery Today: Disease Mechanisms 5: 103-111.

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• comment on mental health in the workplace: food for thought by … – a very well written article. unfortunately mental health isn’t openly discussed as much as it should be. maybe one day it will be.