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Role that diet may play in the etiology of rosacea

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Dr. Cordain asked me to post this for him:

From: Dr. Loren Cordain

Subject: RE: RRDi Forum Help Page

Date: February 1, 2007 10:47:20 AM HST

To: director@irosacea.org

Hi Brady,

The clue to the role that diet may play in the etiology of rosacea comes from the observation that pharmaceutical eradication of the bacteria, Helicobacter pylori, improves or ameliorates symptoms in rosacea patients (1-3). H. pylori is the bacteria that causes gastric and duodenal ulcers. Although the physiological basis for the curative effect of H. pylori eradication is unknown, we believe that a mechanism in the human gut, the epidermal growth factor receptor (EGF-R) likely plays a crucial role in the etiology of rosacea. The EGF-R is unusual in that it is expressed luminally in the gut (4,5). The primary role of the luminally expressed gut EGF-R is to provide a healing mechanism for damaged epithelial cells in the gut. One of the endogenous ligands for the EGF-R is EGF which is found in saliva and when swallowed promotes healing in damaged epithelial cells lining the gut (5). Additionally, salivary EGF may also finds its way into circulation through this pathway based upon the observation that surgical removal of the salivary and parotid glands in experimental animals reduces blood concentrations of EGF.

Infection of the GI tract with H. pylori leading to ulcers causes an upregulation (increase in density) of the EGF-R (6). Hence any substance in the gut capable of binding the EGF-R will have increased access to the peripheral circulation. We believe the reason why eradication of H. pylori reduces rosacea symptoms is because it downregulates (or reduces the numbers of) the EGF-R. Hence gut borne substances which would have gained entry to the circulation through the EGF-R and which may cause rosacea are partially denied access into the circulation.

In support of the notion that the EGF-R is central to the development of rosacea is the observation that EGF-R blocking pharmaceuticals elicit erythematous papules and follicular pustules (7-9) that likely occur because of an overexpression of the EGF-R in keratinocytes (8).

In regard to diet, the following substances also bind the gut EGF-R and gain access to circulation:

1. Wheat germ agglutinin (WGA) a dietary lectin which is found in both whole and refined wheat products (10).

2. Peanut agglutinin (PNA) a dietary lectin which is found in peanuts (11).

3. Tomato lectin (TL), a dietary lectin which is found in tomatoes (12)

4. Phytohemmagglutinin (PHA) a dietary lectin which is found in kidney beans and all other Phaseolus vugaris bean varieties (13, 14)

5. Soybean agglutinin (SBA) a dietary lectin which is found in all soybeans and soy products, whose specifity is to one of the sugars in the EGF-R (15)

6. Betacellulin (BTC) a hormone found in milk and cheese which is a natural ligand for the EGF (16, 17).

7. Egg white lysozyme, a lectin found in the whites of eggs (18)

Hence, once these dietary ligands for the EGF-R bind the gut EGF-R, some eventually escape destruction in gut epithelial cell lysozomes and reach circulation intact where they can bind the keratinocyte EGF-R and cause increased proliferation and inflammation (19). Dietary factors which can bind the EGF-R should be strongly implicated in the etiology of rosacea. Randomized controlled clinical trials will be needed needed to test the efficacy of elimination diets using known dietary ligands for the EGF-R.

REFERENCES:

1. Boixeda de Miquel D, Vazquez Romero M, et al. Effect of Helicobacter pylori eradication therapy in rosacea patients. Rev Esp Enferm Dig. 2006 Jul;98(7):501- 509.

2. Utas S, Ozbakir O, Turasan A, Utas C. Helicobacter pylori eradication treatment reduces the severity of rosacea.J Am Acad Dermatol. 1999 Mar;40(3):433-5.

3. Diaz C, O'Callaghan CJ, Khan A, Ilchyshyn A. Rosacea: a cutaneous marker of Helicobacter pylori infection? Results of a pilot study. Acta Derm Venereol. 2003;83(4):282-6.

4. Hormi K, Lehy T. Developmental expression of transforming growth factor-alpha and epidermal growth factor receptor proteins in the human pancreas and digestive tract. Cell Tissue Res. 1994 Dec;278(3):439-50.

5. Montaner B, Perez-Tomas R. Epidermal growth factor receptor (EGF-R) localization in the apical membrane of the enterocytes of rat duodenum. Cell Biol Int. 1999;23(7):475-9.

6. Coyle WJ, Sedlack RE, Nemec R, Peterson R, Duntemann T, Murphy M, Lawson JM Eradication of Helicobacter pylori normalizes elevated mucosal levels of epidermal growth factor and its receptor. Am J Gastroenterol. 1999 Oct;94(10):2885-9

7. Dewitt CA, Siroy AE, Stone SP. Acneiform eruptions associated with epidermal growth factor receptor-targeted chemotherapy. J Am Acad Dermatol. 2006 Dec 11; [Epub ahead of print]

8. Hannoud S, Rixe O, Bloch J, Le Pelletier F, Lebrun-Vignes B, Doarika A, Khayat D, Chosidow O. [skin signs associated with epidermal growth factor inhibitors] Ann Dermatol Venereol. 2006 Mar;133(3):239-42.

9. Molinari E, De Quatrebarbes J, Andre T, Aractingi S. Cetuximab-induced acne.Dermatology. 2005;211(4):330-3.

10. Gabor F, Bogner E, Weissenboeck A, Wirth M. The lectin-cell interaction and its implications to intestinal lectin-mediated drug delivery. Adv Drug Deliv Rev. 2004 Mar 3;56(4):459-80.

11. Wang Q, Yu LG, Campbell BJ, Milton JD, Rhodes JM. Identification of intact peanut lectin in peripheral venous blood. Lancet. 1998 Dec 5;352(9143):1831-2.

12. Kilpatrick DC, Pusztai A, Grant G, Graham C, Ewen SW. Tomato lectin resists digestion in the mammalian alimentary canal and binds to intestinal villi without deleterious effects. FEBS Lett. 1985 Jun 17;185(2):299-305.

13. Rebbaa A, Yamamoto H, Moskal JR, Bremer EG Binding of erythroagglutinating phytohemagglutinin lectin from Phaseolus vulgaris to the epidermal growth factor receptor inhibits receptor function in the human glioma cell line, U373 MG. J Neurochem. 1996 Dec;67(6):2265-72.

14. Pusztai A, Greer F, Grant G. Specific uptake of dietary lectins into the systemic circulation of rats. Biochem Soc Trans 1989;17:481-2.

15. Rao VS, Lam K, Qasba PK. Three dimensional structure of the soybean agglutinin Gal/GalNAc complexes by homology modeling. J Biomol Struct Dyn. 1998 Apr;15(5):853-60.

16. Bastian SE, Dunbar AJ, Priebe IK, Owens PC, Goddard C. Measurement of betacellulin levels in bovine serum, colostrum and milk. J Endocrinol. 2001 Jan;168(1):203-12

17. Dunbar AJ, Priebe IK, Belford DA, Goddard C. Identification of betacellulin as a major peptide growth factor in milk: purification, characterization and molecular cloning of bovine betacellulin. Biochem J. 1999 Dec 15;344 Pt 3:713-21.

18. Hashida S, Ishikawa E, Nakamichi N, Sekino H. Concentration of egg white lysozyme in the serum of healthy subjects after oral administration.Clin Exp Pharmacol Physiol. 2002 Jan-Feb;29(1-2):79-83

19. Cordain L, Toohey L, Smith MJ, Hickey MS. Modulation of immune function by dietary lectins in rheumatoid arthritis. Br J Nutr. 2000 Mar;83(3):207-17.

Loren Cordain, Ph.D., Professor

Department of Health and Exercise Science

Colorado State University

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Anti-inflammatory 'antibiotics' which improve rosacea are the same used as part of complex but short regimens (7-14 days) to cure H pylori form the GI tract. When you look at patients 3 months after the cure of H pylori, the Hp is no longer present yet the rosacea is unchanged. http://www.ncbi.nlm.nih.gov/entrez/query.f...t_uids=10376693

It is expected that while on those medications rosacea would improve rosacea while taken and for some time after completing them. If that improvement was due to their effect on Hp it should be a permanent benefit.

The low glycemic diet effect on acne and androgen levels are strong points to suggest the diet should be further tested with acne and rosacea. The main question of funding remains to do the work

I suggest my rosacea patients try the South Beach diet because it is well known. After I get a copy of the Paleo Diet, I imagine I'll suggest Dr. Cordain's specific program. Annecdotally patients tell me that following that SB diet can be a important help.

This ligand information is very interesting to consider. Thank you Dr. Cordain

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