The range of candida treatments ranges from time-proven and safe fatty acids, to dangerous drugs that create resistant strains, to obscure treatments like turpentine. With candida being an orphaned condition by the medical profession, many people take advantage of this by selling anything and everything. While promising a quick cure, they put down everyone else and load their marketing materials with fear and emotional messages in an attempt to steer people away from following sound advise. Chitin Synthesis Inhibitors, also known as Lufenuron, are a good example of this trend. Designed and marketed as a flea medication for pets, at least two sites are trying to market it as a treatment for candida, in spite of the science that shows it doesn’t work against fungus.
Lufenuron is being pitched to candida sufferers as an effective anti-fungal due to its ability to act as a chitin synthesis inhibitor. Chitin makes up a good portion of the exoskeletons of insects and chitin inhibitors can prevent this exoskeleton from forming. Chitin is also found in the cell wall of candida to varying degrees, depending on the environmental stresses that candida encounters, but under normal conditions, it makes up 0-25% of candida’s cell wall. Unlike the exoskeleton of insects, candida has an ability to manipulate the chitin content in its cell wall membranes. If the environment that it finds itself in has chitin inhibitors, it will alter its chitin content to preserve the integrity of its cell wall membrane. Sites that sell lufenuron would like you to think that candida doesn’t have this ability, which reveals a deep misunderstanding of how candida functions.
Researchers from the University of California, San Francisco, decided to look at whether or not lufenuron had any anti-fungal effects. They found, “No evidence of inhibition, either by susceptibility testing or direct microscopic examination of treated cells, was obtained with lufenuron”. In contrast, they showed that a known chitin synthesis inhibitor, Nikkomycin Z, had a potent inhibitory effect against chitin in fungal cell wall membranes. Their conclusion – “lufenuron does not appear to possess anti-fungal properties”.
Examining the scientific literature on lufenuron reveals other information that these sites fail to mention:
Lufeneron showed initial promise as a treatment for fungal infections, but the early enthusiasm has dampened considerably as efficacy appears doubtful.
Adverse effects reported in dogs and cats after oral lufenuron include: vomiting, lethargy/depression, pruritus/urticaria, diarrhea, dyspnea, anorexia, and reddened skin. The manufacturer reports that the adverse reaction rate is less than 5 animals in one million doses.http://www.scribd.com/doc/72234998/76/LUFENURON
Of relevance to microbiology, chitin is present in fungal species such as mushrooms, where it can comprise from 5% to 20% of the weight of the organism. http://www.enotes.com/chitin-reference/chitin
Chitin synthesis inhibitors share a similar chemical structure as other benzoylphenyl ureas.Their mode of action is by interfering with the polymerization pathway of chitin, inducing accumulation of the monomer uridine diphospho-N-acetylglucosamine and blocking its synthesis (Beeman 1982). http://ddr.nal.usda.gov/bitstream/10113/8686/1/IND43666733.pdf
The final step of chitin biosynthesis is the polymerization of N-acetylglucosamine from the activated substrate UDP-N-acetylglucosamine, by the enzyme chitin synthase (EC 188.8.131.52). This enzyme has been well studied in fungi and yeasts (Gooday 1977)…Leighton e t al. (1981) have proposed that diflubenzuron acts indirectly on chitin synthase by inhibiting a proteolytic enzyme required for its activation from the zymogen form. http://www.publish.csiro.au/?act=view_file&file_id=BI9820491.pdf
Lufenuron is a benzoylphenylurea drug that interferes with chitin synthesis. It is used in veterinary medicine as a ﬂea prophylactic product, due to its non-speciﬁc inhibitory effect on chitin synthesis, probably related to serine protease inhibition.³ http://jfm.sagepub.com/content/11/2/91.full.pdf
OTHER REASONS NOT TO USE CHITIN SYNTHESIS INHIBITORS INCLUDE ITS ABILITY TO AFFECT INTESTINAL MEMBRANES AND FEMALE REPRODUCTION:
An unexpected result of lufenuron treatment was the inhibition of midgut epithelial cell differentiation. At concentrations of 0.5 and 1.0 ppm, partially differentiated epithelial cells were seen in the midgut of blood-fed fleas along with fully differentiated cells. http://www.ncbi.nlm.nih.gov/pubmed/10467778
Micrographs of ovaries, from animals treated with lufenuron, showed some space between the follicular epithelium and the oocyte membrane. The in vivo incorporation of radioactive N-acetylglucosamine into chitin was inhibited by the presence of lufenuron. http://journals2.scholarsportal.info/details.xqy?uri=/00483575/v98i0001/59_te…
LUFENURON BUILDS UP IN THE TISSUES:
Lufenuron bioaccumulates. http://www.syngenta.co.nz/msds/syngentanz/MATCH_24106015.pdf
Disturbance of the epithelial barrier and epithelial transport processes is often discussed to be a major factor in the pathogenesis of intestinal inflammation and inflammatory bowel disease. http://www.hindawi.com/journals/iji/2010/574568/
The intestinal epithelium provides a critical protective barrier against enteric pathogens, food antigens, and physiochemical stresses caused by digestive and microbial products, and yet must be selectively permeable to beneficial nutrients and fluids. Tightly regulated control of barrier function and integrity is critical, as the pathogenesis of intestinal diseases such as Crohn’s disease, ulcerative colitis, inflammatory bowel diseases (IBD), and autoimmune diseases are linked to intestinal barrier dysfunction and increased intestinal permeability (1). The intestinal epithelium is a single layer of linked columnar epithelial cells that regulates, through the paracellular pathway, the selective passage of ions, fluid, and macromolecules from the intestinal lumen into the underlying tissues.
The intestinal epithelium serves as a major protective barrier between the mammalian host and the external environment. Here we show that the transmembrane serine protease matriptase plays a pivotol role in the formation and integrity of the intestinal epithelial barrier. St14 hypomorphic mice, which have a 100-fold reduction in intestinal matriptase mRNA levels, display a 35% reduction in intestinal transepithelial electrical resistance (TEER). Matriptase is expressed during intestinal epithelial differentiation and colocalizes with E-cadherin to apical junctionalcomplexes (AJC) in differentiated polarized Caco-2 monolayers. Inhibition of matriptase activity using a specific peptide inhibitor or by knockdown of matriptase by siRNA disrupts the development of TEER in barrier-forming Caco-2 monolayers and increases paracellular permeability to macromolecular FITC-dextran. Loss of matriptase was associated with enhanced expression and incorporation of the permeability-associated, “leaky” tight junction protein claudin-2 at intercellular junctions. These results support a key role for matriptase in regulating intestinal epithelial barrier competence, and suggest an intriguing link between pericellular serine protease activity and tight junction assembly in polarized epithelia. http://www.pnas.org/content/107/9/4200.full
“Mechanisms terminating the short physiological life cycle of epithelial cells are supposed to have an impact on these essential functions and have influence on inflammatory reactions in the intestinal mucosa. A disturbance of the epithelial barrier is thought to be a major factor in the pathogenesis of inflammatory bowel disease.
Disturbance of the epithelial barrier and epithelial transport processes is often discussed to be a major factor in the pathogenesis of intestinal inflammation and inflammatory bowel disease.”
One website that sells lufenuron has pictures of inflammatory skin conditions that responded to lufenuron treatment. A deficiency of serine protease inhibitors can play a role in creating inflammatory skin conditions. The website implies that the healing seen in the pictures was created by lufenuron’s anti-fungal affect against candida. It is much more likely that this was due to its serine protease inhibition effect. I’ve talked frequently about how people misinterpret what they see and notice. This would be a classic example.
Lufenuron has demonstrated the ability to damage intestinal cells and intestinal cell junctions. As noted above, intestinal cells play a critical role in the maintenance of the homeostasis of the intestinal tract. Lufenuron can also interfere with the structure of healthy intestinal bacteria. It had initially demonstrated a possible role in affecting candida fungal growth that subsequent studies dismissed. The goal of any approach in restoring balance to the intestinal flora, immune responses, and candida overgrowth, should not also present known risks to the body. Based on this, I would never recommend lufenuron.