What the Heck is Undecylenic Acid?

Most organic fatty acids are fungicidal and have been used for centuries as antimicrobial agents, originally in the manufacture of soaps. In the last 50 years, however, they have found use both in vitro as yeast and mold inhibitors in food stuffs, and as topical and systemic antifungals. Undecylenic acid (10-undecenoic acid) is an eleven-carbon mono-unsaturated fatty acid, [C.sub.11] [H.sub.20] [O.sub.2]. A substance found naturally in the body (occurring in sweat), undecylenic acid is produced commercially by the vacuum distillation of castor bean oil, via the pyrolysis of ricinoleic acid. It is an economical antifungal agent and is the active ingredient in many topical over-the-counter (OTC) antifungal preparations.(1) Undecylenic acid has been shown to be approximately six times more effective as an antifungal than caprylic acid, and is effective in maintaining a healthy balance of intestinal and vaginal flora.(2)

Biochemistry and Pharmacokinetics

B.J. Wyss, et al, demonstrated more than 50 years ago that the greater the number of carbon atoms in the fatty acid chain, the greater the fungicidal activity, up to the point exceeding eleven carbon atoms, where solubility becomes the limiting factor.(3)

Although the fungistatic and fungicidal effects of fatty acids have been well documented, they can be somewhat irritating to mucous membranes in certain people, and commonly used fatty acids such as caprylic and undecylenic acids have an objectionable taste and odor. Consequently, the calcium, magnesium, and sodium salts of these fatty acids have been offered as reasonable alternatives. Undecylenate salts have been shown to possess as much as four times the fungicidal effect of undecylenic acid, and may be over 30 times more effective than caprylic acid.(4) Unfortunately, the antifungal effects of these fatty acid salts are more sensitive to pH than the free fatty acids. When tested over a pH range from 4.5 to 6.0, the antifungal activities of both undecylenic acid and calcium undecylenate are quite pronounced; the minimal inhibitory concentration of calcium undecylenate against Candida albicans is 200 ppm at pH 6.0. However, above pH 6.0, the calcium salt is less active than the free acid, perhaps due to the suppression of ionization of the salt at higher pH levels.(5)

Alkaline pH levels in the intestinal tract are known to be caused by an intestinal flora imbalance, especially by Candida albicans.(6) Therefore, for fatty acid salts to be effective in vivo, they must be delivered to the site of fungal overgrowth in the intestinal tract at an acid pH, thus avoiding both the release of excess bicarbonate from the pancreas (which would alkalinize the pH) and damage to the sensitive intestinal mucosa.(7) This can most efficiently be accomplished with a nominal amount of a substance in a time-release form, such as betaine HCl, that gradually liberates small quantities of the acid throughout the intestinal tract, simultaneously releasing the fatty acid salt.

Mechanism of Action

Undecylenic acid has long been known to have antifungal properties. At least one of the mechanisms underlying its antifungal effect is its inhibition of morphogenesis of Candida albicans. In a study on denture liners, undecylenic acid in the liners was found to inhibit conversion of yeast to the hyphal form.(8) Hyphae were associated with active infection. The authors speculated on possible mechanisms including interference with fatty acid biosynthesis, which can inhibit germ tube (hyphae) formation. Medium-chain fatty acids have also been shown to disrupt the pH of the cell cytoplasm by being proton carriers.(9)

Clinical Indications

Vaginal/Gastrointestinal Candidiasis: Undecylenic acid has been shown to be effective in preventing fungal overgrowth associated with vaginal and gastrointestinal candidiasis via its fungicidal activity. A study published in the Journal of the American Medical Association found a direct correlation between vaginal yeast infections and simultaneous overgrowth of Candida in the digestive tract.(10) Undecylenic acid has long been known to be fungicidal against Candida albicans, thus helping achieve a healthy balance of normal vaginal and intestinal flora.(2)

Thrush: Because undecylenic acid acts systemically, oral administration can inhibit or even prevent oral candidiasis, or thrush. While large-scale clinical studies have not been conducted, many case reports confirm undecylenic acid’s efficacy in thrush. During lactation, oral administration of undecylenic acid to nursing mothers can prevent thrush in babies. The milk, however, may taste slightly different to the infant.

Dermatomycoses: Undecylenic acid is the active ingredient in Desinex® cream and a number of other OTC antifungals. It is responsible for the antifungal effect of these medications against such organisms as Candida albicans, Trichophyton species, Epidermophyton inguinale, and Microsporum audouini.(1)

A double-blind study of 151 patients with tinea pedis demonstrated that a powder containing 2% undecylenic acid and 20% zinc undecylenate resulted in a remarkable decrease in infection rate and symptomology, when compared to patients given a placebo powder. Eighty-five patients, who were culture positive for Trychophyton rubrum or Trychophyton mentagrophytes, were assigned to receive the active powder, and of these, 88% had negative cultures after four weeks, compared to only 17% of those treated with placebo powder. There were no side effects or adverse reactions to the powder containing undecylenic acid and its zinc salt.(5)

Herpes Simplex Infection: Undecylenic acid has been shown to have antibacterial and antiviral properties in vitro and is effective topically against the herpes simplex virus in both animals and humans. Two studies, one using a 20% solution(11) and the other a 15% cream,(12) demonstrated a decrease in the incidence and duration of viral shedding in subjects inoculated with herpes simplex virus. Patients also experienced a significant decrease in pain and tenderness at the lesion site. The antiviral activity was, however, of relatively short duration and most pronounced when undecylenic acid was applied during the prodromal stage of outbreak. Slight local skin irritation and dysgeusia (altered sense of taste) were experience by some subjects.(9,10)

Denture Stomatitis: Candida albicans is a major cause of denture stomatitis, an inflammation of the tissues underlying dentures. The organism exists in two cellular morphologies – the round yeast form found in asymptomatic carrier states and the branching hyphal form found in active infections. Resilient liners are frequently used to treat denture stomatitis, and N. McLain, et al, demonstrated that liners containing undecylenic acid completely inhibited the conversion of the yeast form of Candida albicans to the hyphal form, thereby inhibiting proliferation of the yeast.(8)

Safety/Toxicity

Relatively small doses of undecylenic acid and its salts have been shown to have powerful antifungal properties, and the dosages necessary to achieve therapeutic benefit appear to be safe. Capsules or gelcaps of undecylenic acid should not be opened and mixed with food or drink as the taste and odor is objectionable and it may also be irritating to mucous membranes. Additionally, undecylenic acid in an oil base should not be applied directly to the skin, unless diluted in olive oil, because it might result in skin irritation.

Dosage

Undecylenic acid, given orally, is typically in an oil-based gelcap or as powder (in the case of its salts) in a two-part capsule. Adult dosage is usually 450-750 mg undecylenic acid daily in three divided doses. Ask your doctor if undecylenic acid is right for you. J

References

(1) Shapiro AL, Rothman S. Undecylenic acid in the treatment of dermatomycoses. Arch Dermatol Syphilol 1945;52:166-171.

(2) Neuhauser I. Successful treatment of intestinal moniliasis with fatty acid-resin complex. Arch Intern Med 1954;93:53-60.

(3) Wyss BJ, et al. The fungistatic and fungicidal action of fatty acids and related compounds. Arch Biochem 1945;7:415.

(4.) Peck SM, Rosenfeld H. The effects of hydrogen ion concentration, fatty acids and vitamin C on the growth of fungi. J Invest Dermatol 1938;1:237-265.

(5.) Chretien JH, Esswein JG, Sharpe LM, et al. Efficacy of undecylenic acid-zinc undecylenate powder in culture positive tinea pedis. Int J Dermatol 1980;19:51-54.

(6.) Barrie SA. Comprehensive Digestive Stool Analysis; In: Pizzorno JE, Murray MT, eds. A Textbook of Natural Medicine. Seattle: JBC Press, 1986: II: CDSA-1-4.

(7.) Prince HN. Effect of pH on the antifungal activity of undecylenic acid and its calcium salt. J Bacteriol 1959;78:788-791.

(8) McLain N, Ascanio R, Baker C, et al. Undecylenic acid inhibits morphogenesis of Candida albicans. Antimicrob Agents Chemother 2000;44:2873-2875.

(9.) Steven S, Hofemyer JHS. Effects of ehtnaol, octanoic and decanoic acids on fermentation and the passive influx of protons throught the plasma membrane of Saccharomyces cerevisiae. Appl Microbiol Biotechnol 1993;38:356-363.

(10.) Miles MR, Olsen L, Rogers A. Recurrent vaginal candidiasis. JAMA 1977;238:1836-1837.

(11.) Bourne N, Ireland J, Stanberry LR, Bernstein DI. Effect of undecylenic acid as a topical microbicide against genital herpes infection in mice and guinea pigs. Antiviral Res 1999;40:139-144.

(12.) Shafran SD, Sacks SL, Aoki FY, et al. Topical undecylenic acid for herpes simplex labialis: a multicenter, placebo-controlled trial. J Infect Dis 1997;176:78-83.

Effects of Toxic Exposure to Molds and Mycotoxins

in Building-Related Illnesses.
Rea WJ, Didriksen N, Simon TR, Pan Y, Fenyves EJ, Griffiths B
Environmental Health Center-Dallas, Dallas, Texas 75231-4262, USA. wjr@ehcd.com

The authors studied 100 patients who had been exposed to toxic molds in their homes. The predominant molds identified were Alternaria, Cladosporium, Aspergillus, Penicillium, Stachybotrys, Curvularia, Basidiomycetes, Myxomycetes, smuts, Epicoccus, Fusarium, Bipolaris, and Rhizopus.

A variety of tests were performed on all, or on subgroups of, these patients. Sensitivities and exposures were confirmed in all patients by intradermal skin testing for individual molds (44-98% positive), and by measurement of serum antibodies. Abnormalities in T and B cells, and subsets, were found in more than 80% of the patients.

The findings of trichothecene toxin and breakdown products in the urine, serum antibodies to molds, and positive intradermal skin tests confirmed mycotoxin exposure. Respiratory signs (e.g., rhinorrhea, sinus tenderness, wheezing) were found in 64% of all patients, and physical signs and symptoms of neurological dysfunction (e.g., inability to stand on the toes or to walk a straight line with eyes closed, as well as short-term memory loss) were identified in 70% of all patients. Objective abnormal autonomic nervous system tests were positive in all 100 patients tested. Brain scans, conducted using triple-head single photon emission computed tomography, were abnormal in 26 (86%) of 30 (subgroup of the 100) patients tested. Objective neuropsychological evaluations of 46 of the patients who exhibited symptoms of neurological impairment showed typical abnormalities in short-term memory, executive function/judgment, concentration, and hand/eye coordination.

This research was funded by the Danish Agricultural and Veterinary Research Council and participating institutions.

Scientists have given us another reason to eat carrots – a compound found in the popular root vegetable has been found to have an effect on the development of cancer.

A team of researchers, from the University of Newcastle upon Tyne in England and Denmark, found the natural pesticide, falcarinol, reduced the risk of cancer developing in rats by one third.

Although experts have recommended that people eat carrots for their anti-cancer properties, it has not been known exactly what component of the vegetable has this effect.

The study results, published today in the Journal of Agricultural and Food Chemistry, are significant because they could contribute to healthy eating advice for consumers and recommendations for growers and may eventually aid the development of anti-cancer drugs.

Falcarinol protects carrots from fungal diseases, such as licorice rot, that causes black spots on the roots during storage. The scientists investigated the compound after a previously published study suggested it could prevent the development of cancer.

The research team carried out tests on 24 rats with pre-cancerous tumors in laboratory conditions. They divided them into three groups and fed them different diets.

The team found that, after 18 weeks, rats who ate carrots (the popular orange variety) along with their ordinary feed and the group that consumed falcarinol with their feed - in a quantity equal to that contained in the carrots – were one third less likely to develop full-scale tumors than the rats in the control group.

Dr Kirsten Brandt, a senior lecturer with Newcastle University’s School of Agriculture, Food and Rural Development, carried out the research with the University of Southern Denmark and the Danish Institute of Agricultural Sciences. She said: “We already know that carrots are good for us and can reduce the risk of cancer, but until now we have not known which element of the vegetable has these special properties.

“Our research allows us to make a more qualitative assessment of the vegetables we are eating, rather than quantitative. We now need to take it a step further by finding out how much falcarinol is needed to prevent the development of cancer and if certain types of carrot are better than others, as there are many varieties in existence, of different shapes, colors and sizes.”

“We could also expand our research to include other vegetables. For consumers, it may soon no longer be a case of advising them to eat five portions of fruit and vegetables per day but to eat particular types of these in certain quantities. The research could also lead to more tailored advice for growers regarding the methods they should use when growing vegetables.”

The experiment was conducted using raw carrots so researchers do not yet know if eating boiled carrots or drinking carrot juice, for example, would have the same effect. (My claim is that eating boiled carrots cannot produce this effect because the goodness in the carrot gets thrown away with the water before you serve this dish.)

Dr Brandt, who says she eats “more carrots than most” and grows her own organic varieties, recommended that consumers should eat one small carrot every day, together with other vegetables and fruits, to benefit from their health-giving properties.

Falcarinol is toxic in large amounts, but to obtain a lethal dose you would have to eat 400 kilograms of carrots at once. Researchers suspect it is effective because it stimulates mechanisms in the body that fight cancer, although they have yet to carry out a detailed analysis in this respect. (I say it is effective because it is antifungal, and I’m pretty sure at this point that it is fungus that causes the DNA damage that starts cancer.)