Undecylenic Acid Monograph
`
`Undecylenic Acid
`
`Introduction
`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
`monounsaturated fatty acid, C11H20O2. 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 antifungal prepara-
`tions.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
`
`CH2 = CH(CH2)8 CO2 H
`
`Biochemistry and Pharmacokinetics
`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, magne-
`sium, 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 intestinal flora imbalance,
`especially by C. 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 mu-
`cosa.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.
`
`Page 68 Alternative Medicine Review ◆ Volume 7, Number 1 ◆ 2002
`Copyright©2002 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission
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`Review Undecylenic Acid
`
`Mechanism of Action
`Undecylenic acid has long been known to
`have anti-fungal properties. At least one of the
`mechanisms underlying its anti-fungal 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 pos-
`sible 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 associ-
`ated 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 Can-
`dida in the digestive tract.10 Undecylenic acid has
`long been known to be fungicidal against Can-
`dida albicans, thus helping achieve a healthy bal-
`ance of normal vaginal and intestinal flora.2
`
`Thrush
`Since 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 re-
`ports confirm undecylenic acid’s efficacy in thrush.
`During lactation, oral administration of unde-
`cylenic 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 over-
`the-counter 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 contain-
`ing 2-percent undecylenic acid and 20-percent 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 ac-
`tive powder, and of these, 88 percent had negative
`cultures after four weeks, compared to 17 percent
`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-percent solution11 and the other a
`15-percent cream,12 demonstrated a decrease in the
`incidence and duration of viral shedding in sub-
`jects 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 irriation and dysgeusia (altered sense
`of taste) were experience by some subjects.9,10
`
`Denture Stomatitis
`Candida albicans is a major cause of den-
`ture stomatitis, an inflammation of the tissues un-
`derlying dentures. The organism exists in two cel-
`lular 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 stoma-
`titis, and 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
`
`Alternative Medicine Review ◆ Volume 7, Number 1 ◆ 2002 Page 69
`Copyright©2002 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission
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`Undecylenic Acid Monograph
`
`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.
`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.
`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.
`
`11.
`
`12.
`
`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 ap-
`plied directly to the skin, unless diluted in olive
`oil, as it may otherwise 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.
`
`2.
`
`3.
`
`4.
`
`5.
`
`References
`1.
`Shapiro AL, Rothman S. Undecylenic acid in
`the treatment of dermatomycoses. Arch
`Dermatol Syphilol 1945;52:166-171.
`Neuhauser I. Successful treatment of intestinal
`moniliasis with fatty acid-resin complex. Arch
`Intern Med 1954;93:53-60.
`Wyss BJ, et al. The fungistatic and fungicidal
`action of fatty acids and related compounds.
`Arch Biochem 1945;7:415.
`Peck SM, Rosenfeld H. The effects of hydro-
`gen ion concentration, fatty acids and vitamin
`C on the growth of fungi. J Invest Dermatol
`1938;1:237-265.
`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.
`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.
`Prince HN. Effect of pH on the antifungal
`activity of undecylenic acid and its calcium
`salt. J Bacteriol 1959;78:788-791.
`McLain N, Ascanio R, Baker C, et al. Unde-
`cylenic acid inhibits morphogenesis of
`Candida albicans. Antimicrob Agents
`Chemother 2000;44:2873-2875.
`
`6.
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`7.
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`8.
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`Page 70 Alternative Medicine Review ◆ Volume 7, Number 1 ◆ 2002
`Copyright©2002 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission
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