It's been a few years since I posted the earlier comment in November 2007. After reading my strongly-worded and shrill earlier comment, I felt embarrassed and asked PLoS to take it down. They refused. I suppose I should take that as a compliment, since I feel that my comment borders on violating 8. Good Practices of the Comment Guidelines (http://www.plosbiology.or...).

The conclusion of Monroe's article says that Wolcott is worried about being branded as an alternative-medicine type. Like Wolcott, I'm not interested in selling diluted potions of arsenic (arsenicum is a popular homeopathic remedy). I'd like to try to justify my my comment on "conventional medicine ignoring a natural, effective treatment", a comment which implied that "alternative" naturopaths were more likely to adopt it. Naturopaths may be more likely to adopt it, but unfortunately they appear to be more likely to adopt ineffective medicines as well, such as homeopathy. For example, a survey of Canadian naturopaths found that 98.3% (n = 298) use homeopathy (doi:10.1016/j.socscimed.2006.01.008). Naturopathy was extensively critiqued by Atwood (http://www.ncbi.nlm.nih.g...), and these critiques have not been adequately rebutted.

Nevertheless, as my original comment implied, I tend to agree with Wolcott that there are very promising natural agents which need to be investigated and brought into medicine. Unfortunately, these agents are obscured by the high-profile discussions and investigations into medical dead-ends such as chelation therapy, thimerosal and autism, homeopathy, chiropractic, and acupuncture. Briefly, the medical field appears to be as polarized as it has ever been. It appears that forces and circumstances are working to legitimize alternative medicine, including the ineffective dead-ends mentioned above, as complementary and alternative medicine (CAM). This reaction seems to stem partly from a reaction to evidence which suggests that mainstream medicine is corrupted by pharmaceutical money, mismanaged, and not evidence-based. I think it is related to increased environmentalism and toxin concerns (even though Bisphenol A headlines peaked after the initial rise of CAM).

The rise of alternative medicine is evident in the increased funding for alt-med at the NIH (with largely negative results) due to the creation of the NCCAM, and in the 2005 National Academies book on the subject which documents the explosion in research and ultimately takes a largely favorable view of alternative medicine (http://www.nap.edu/catalo...). The FDA recently approved its first "botanical" prescription pharmaceuticals, an epigallocatechin (EGCG, from green tea) ointment for genital warts, and an omega-three fatty acid pharmaceutical for triglycerides (http://www.naturopathydig...). Evidence of issues in mainstream medicine exist in the Vioxx scandal, publication bias with antidepressants (trials with negative or questionable findings not published, http://content.nejm.org/c...), long-term studies on ADHD stimulants lacking (http://www.ncbi.nlm.nih.g...), the comprehensive review of Cochrane systematic reviews which found over 49% of medical interventions were unsupported by evidence, and 7% harmful (http//:dx.doi.org/10.1111/j.1365-2753.2007.00886.x/). Doctors' are viewed as close-minded, arrogant, and even incompetent in today's world of do-it-yourself medicine, and perhaps the view is not entirely unwarranted. In 2007, a survey of statin patients found that about half reported that their doctor dismissed complaints about muscle adverse effects, which every medical doctor should know about (see http://www.ncbi.nlm.nih.g...).

Despite the general lack of rigor in alternative medicine naturopathy, there are promising natural products and a few rigorous researchers. At the risk of offending PLoS with too much information for a comment, I'll summarize a bit of what I mean. For example, randomized-controlled trials provide evidence that SAM-e could fight depression, osteoarthritis pain, and liver disease with fewer side-effects than conventional agents [9]. 5-HTP, the precursor to serotonin, could fight depression. Silymarin could protect the liver. Probiotics and soluble fiber could alleviate or eliminate irritable bowel syndrome. Green tea extract, while perhaps not completely safe, helps the body clear HPV (as in the EGCG above). Numerous promising cognitive agents exist which have been little-studied. As for good researchers, most in the area have heard of Edzard Ernst, or Barrie Cassileth and Andrew Vickers at the Memorial Sloan-Kettering Center. Additionally, there's an Indian dietary supplement manufacturer, Himalaya Herbals, which has been conducting promising clinical trials since the 1970s - but rarely has anyone else bothered to try replicating them. The Alternative Medicine Review often publishes well-supported papers, which is probably why it is listed on PubMed. Inside the field of naturopathy, Dugald Seely at the Canadian College of Naturopathic Medicine published a critique of chelation therapy (http://www.biomedcentral....); this is noteworthy since critiques from within alternative medicine of its practices are relatively rare.

Monroe mentions that Wolcott thinks there are six or seven natural agents, in addition to phages, which can help manage biofilms, but Monroe stops short of stating them explicitly. Wolcott states these explicitly elsewhere, but apparently only in journals which are not easily accessible (for example, Wolcott & Rhoads 2008 in the relatively obscure Journal of Wound Care, which I have no access to). Citing Wolcott, Widgerow [2] summarizes agents which "interfere with the formation of biofilm (xylitol, dispersin B, gallium), the attachment to the matrix (iron scavengers, deferoxamine, lactoferrin, ethylene diamine tetraacetic acid [EDTA]) degrade EPS (dispersin B, alginase, phage depolymerases) or inhibit the QS virulence producing mechanism described above (RIP – RNA III inhibiting peptide; furanone C30)". Widgerow notes that a study by Wolcott and Rhoads reported a 77% rate of healing after patients with critical limb ischemia were treated with xylitol and lactoferrin.

Although xylitol's effect on dental biofilms has been studied with promising results since the Turku sugar studies beginning in 1972 [3], it is still regarded as controversial by some dentists [4]. As a natural product, it has been by default "unproven" and neglected in the profit-driven North American market; one 2002 review on biofilms never mentions xylitol [5]. Xylitol administered 5 times/day has been shown in an double-blind randomized controlled trial to prevent acute otitis media (which biofilms are implicated in) [6] and xylitol may strengthen bones [7]. In perhaps the first official North American recommendation of xylitol, In 2006 the American Academy of Pediatrics noted that children who breastfed from mothers' using xylitol had "70% reduction in caries" at the age of 5 compared to varnish and chlorhexidine controls [8]. Given zero toxicity and several possible benefits, why has it taken so long for this to be recommended, and why does it remain unrecommended by major dental groups in the United States?

1. Wolcott RD, Rhoads DD. (April 2008). A study of biofilm-based wound management in subjects with critical limb
ischaemia. J Wound Care; April2008; 17, 145–155. Neither of my to undergraduate libraries subscribe to this journal.

2. Widgerow AD. (2008). Persistence of the chronic wound – implicating biofilm. Wound Healing Southern Africa 1(2):05-07. http://www.awcs.co.za/doc...

3. Maguire A, Rugg-Gunn AJ. (2003). Xylitol and caries prevention—is it a magic bullet? British Dental Journal 194(8):429-436.

4. See, for example, Giertsen and Guggenheim (http://iadr.confex.com/ia...), who compare xylitol to sorbitol and find an equivalent effect on biofilms. Badet et al. 2008 (http://www.ncbi.nlm.nih.g...) find that xylitol has an effect on biofilms, but have no comparison to sorbitol. Badet et al.'s finding is more common in the literature.

5. Donlan RM, Costerton JW. (2002). Biofilms: Survival Mechanisms of Clinically Relevant Microorganisms. Clinical Microbiology Reviews 15(2):167-193. doi:10.1128/CMR.15.2.167-193.2002.

6. Hautalahti O et al. (2007). Failure of Xylitol Given Three Times a Day for Preventing Acute Otitis Media. The Pediatric Infectious Disease Journal 26(5):423-427. doi: 10.1097/01.inf.0000259956.21859.dd

7. Mattila PT, Svanberg MJ, Jämsä T, Knuuttila ML (2002). Improved bone biomechanical properties in xylitol-fed aged rats.Metabolism 51(1):92-6.

8. American Academy on Pediatric Dentistry Council on Clinical Affairs. Policy on the use of xylitol in caries prevention. Pediatr Dent. 30(7 Suppl):36-7. http://www.ncbi.nlm.nih.g.... http://www.aapd.org/media....