Zinc Undecylenate

By Kenneth Proefrock, NMD

Zinc undecylenate, C22H38O4Zn, is the zinc salt of undecylenic acid (10-undecenoic acid), an eleven-carbon monounsaturated fatty acid, C11H20O2. Undecylenic acid is a naturally occurring fatty acid found in the castor bean and as a product of human sweat glands. It is produced commercially through the vacuum distillation of castor bean oil and the pyrolysis of ricinoleic acid.¹ Since 1949, the undecylenate salts have been used as yeast and mold inhibitors in the food industry, and in medicine as topical and systemic antifungals. Zinc undecylenate has been shown to be an effective antifungal agent and is the active ingredient in many topical over-the-counter antifungal preparations.^2,3 Undecylenic acid has been shown to be approximately six times more effective in its antifungal action than caprylic acid. 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 These agents have also been shown to be effective in helping to maintain a healthy balance of intestinal and vaginal flora.⁵

In 1945, Wyss published the first scientific paper describing the fungicidal effects of medium chain fatty acids. He showed a directly proportional relationship between the fungicidal effect of a fatty acid and the number of carbon atoms in the compound, up to the point where the chain exceeded eleven carbon atoms, and solubility becomes the limiting factor.⁶

The clinical utility of these medium chain fatty acids has been limited in the past due to their irritating effect on mucus membranes, in addition, the more commonly used fungicidal fatty acids such as caprylic and undecylenic acids have an objectionable taste and odor (much like that of armpit perspiration). The calcium, magnesium, zinc and sodium salts of these fatty acids are more tolerable and considered more reasonable and effective 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 The antifungal effects of the 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 minimal inhibitory concentration of zinc undecylenate against Candida albicans is 200 ppm. In environments where the pH is above 6.0, the zinc salt is less effective than the free acid, due to an inability of the salt to ionize in a more alkaline environment.⁷

There are two proposed mechanisms by which undecylenic acid and its salts exert their fungicidal effects. The first effect is by inhibiting endogenous fungal fatty acid biosynthesis, which, in turn, inhibits germ tube (hyphae) formation.⁸ The second mechanism is through disruption of cell cytoplasm pH by acting as proton carriers.⁹

Some accepted therapeutic roles for zinc undecylenate

Vaginal/Gastrointestinal Candidiasis
In 1977, 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 As early as 1954, undecylenic acid was shown to be fungicidal against Candida albicans, thus helping achieve a healthy balance of normal vaginal and intestinal flora.⁵

Thrush
Since undecylenate salts have a systemic effect, oral administration can inhibit or even prevent oral candidiasis, also known as thrush. Milk ducts are modified sweat glands in most mammals so that during lactation, oral administration of undecylenic acid or its salts to nursing mothers can prevent thrush in babies.

Dermatomycoses
Zinc undecylenate is the active ingredient in Desenex^® 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.^2,3 A 1980 study of 151 patients with Tinea pedis demonstrated that a powder containing 2-percent undecylenic acid and 20-percent zinc undecylenate resulted in a statistically significant decrease in infection rate and symptomatology, 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 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 zinc undecylenate powder.⁷

Herpes Simplex Infection
Zinc undecylenate has been shown to have antibacterial and antiviral properties; it is specifically effective 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 subjects inoculated with herpes simplex virus. Patients also experienced a significant decrease in pain and tenderness at the lesion site. The antiviral activity was most pronounced when the fatty acid or its salts were applied during the prodromal stage of outbreak. Slight side effects consisting of local skin irritation and altered sense of taste were experience by some subjects.^11,12

Denture Stomatitis
Candida albicans is considered to be a major cause of denture stomatitis, inflammation of the tissues underlying dentures. This 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 in 2000, McLain et al demonstrated that liners containing undecylenic acid completely inhibited the conversion of the yeast form of Candidaalbicans to the hyphal form, thereby inhibiting proliferation of the yeast and halting the clinical presentation of stomatitis.⁸

Undecylenic acid and its salts have been shown to have powerful fungicidal effects at fairly small dosages.  The dosages necessary to achieve therapeutic benefit are very safe. The accepted oral LD50 for these compounds is 8.15 gm/kg,³ The typical therapeutic dosage range is 4.5-7.5 mg/kg or 450-750 mg undecylenic acid daily in three divided doses.¹³

References
1. Perkins, Cruz, Preparation of Undecylenic Acid from Castor Oil. J Am. Chem. Soc. 1927; 49:1073.
2. Shapiro AL, Rothman S. Undecylenic acid in the treatment of Dermatomycoses. ArchDermatol Syphilol 1945; 52:166-171.
3. O’Neil M, Sr. Ed. The Merck Index13th Ed. 2001:9916.
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. Neuhauser I. Successful treatment of intestinal moniliasis with fatty acid-resin complex. ArchIntern Med 1954; 93:53-60.
6. Wyss BJ, et al. The fungistatic and fungicidal action of fatty acids and related compounds. Arch Biochem 1945; 7:415.
7. Chretien JH, Esswein JG, Sharpe LM, et al. Efficacy of undecylenic acid-zinc undecylenate powder in culture positive tinea pedis. Int JDermatol 1980; 19:51-54.
8. McLain N, Ascanio R, Baker C, et al. Undecylenic acid inhibits morphogenesis ofCandida 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 through 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 Res1999; 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 InfectDis 1997; 176:78-83.13. Anonymous. Undecylenic Acid Monograph Alt Med Rev 2002; 7:68-70.