Candidiasis Part 3: Treatment Options

In part one and two of Clinical Consequences and Considerations of Chronic Candidiasis, I discussed various pathogenicity mechanisms of invasive candida and testing methods, respectively. In this final article I will outline various agents useful for chronic candidiasis, including medications, as well as a focus on certain botanicals and some of their known or suspected modes of action. There is an abundance of herbal remedies that have a long tradition of use as antimicrobials and to cover all aspects of all herbs would require more depth than we need here. Therefore, I have focused on five botanicals that are often found in combination herbal supplements and have been used successfully over many years in combating chronic candidiasis: bilberry extract, echinacea (angustifolia and purpurea), goldenseal, oregano, and tea tree oil.

This article will profile three distinct categories of chronic candidiasis intervention, namely Nystatin (non-systemic), Fluconazole (systemic) and botanicals. We begin this discussion with Nystatin in the non-systemic category.

Nystatin

Nystatin, a.k.a. Mycostatin, is an antifungal medication used for fungal infections of the mouth, intestines, skin, and vagina (1). It is not appreciably absorbed from the skin or mucus membranes, including the digestive tract. Available in various forms such as capsules, oral suspension, powder, and tablets, it has been a long-time favorite of many conventional and integrative doctors for the effective treatment of gastrointestinal candidiasis and oral thrush. A good safety profile for long-term use offers flexibility in usage for different age groups and provides good tolerance. Certain side effects of Nystatin include diarrhea, hives, nausea, hypersensitivity reactions and stomach pains (2). These are rarely encountered based on the author’s experience.

Nystatin, and a similar medication called Amphotericin B, act as an ionophore. These substances affect the cell membrane by either binding to an ion (e.g. sodium, potassium) and/or aiding in the transport of ions across the membrane (3).

Nystatin binds to a fungal cell membrane chemical called ergosterol (i.e. a chemical sterol) which disrupts cell wall integrity by forming pores and allowing for leakage of intracellular potassium. This process also causes acidification within the yeast cell leading to its death (4). Ergosterol is unique to fungi (e.g. yeast, mold), but is similar to the mammalian sterol called cholesterol. The main systemic toxic effects of Nystatin (and Amphotericin B) are linked to kidney damage via cholesterol disruption. However, this effect is primarily an issue with intravenous forms of these medications, not oral forms.

Systemic Antifungals

There are many systemic antifungals, e.g. Fluconazole (Diflucan), Itraconazole (Sporanox), Terbinafine (Lamisil) useful in the treatment of various fungal infections. A medication becoming “systemic” refers to its ability to be absorbed in high amounts from the digestive system into the bloodstream with wide distribution throughout the body. These highly absorbable medications are quite different from oral Nystatin which is considered to be a non-absorbable antifungal and has its effect locally. For the sake of simplicity, our focus will be on the medication Fluconazole.

Fluconazole, as an antifungal medication, is useful for a wide range of fungal infections, including candidiasis, blastomycosis, coccidiomycosis, cryptococcosis and others (5). The side effect profile of Fluconazole (and other systemic antifungals) is more extensive than oral Nystatin due to high systemic absorption and blood and tissue distribution. This tissue distribution includes the liver so it requires monitoring liver enzymes. In addition, QT prolongation reflective of cardiac electrical activity, vomiting, diarrhea, and seizures are known side effects too.

Fluconazole works by inhibiting a fungal cell cytochrome P450 enzyme called 14α-demethylase . This enzyme is involved in the formation of ergosterol, an essential component of the fungal cell membrane. Adversely affecting

14α-demethylase has fungistatic effects against fungal behavior, but at higher dosages fungicidal properties exist (6).

Botanicals

Botanicals for the use of eradicating fungal infections have a long history of use in herbal medicine. Either the whole plant or components of a plant may contain various compounds, e.g. active substances, that provide antifungal properties, i.e. either inhibitory (fungistatic) or killing (fungicidal). As mentioned previously, we are going to focus on five common herbs known to be helpful in chronic candidiasis.

Bilberry Extract

Bilberry is an edible fruit from the plant species Vaccinium myrtillus. The berry has similarities to the American blueberry and goes by various names such as “wimberry”, “wortleberry”, and European blueberry (7). Much of the beneficial effects of bilberry extract focus on its antioxidant and circulatory properties for improved cardiovascular function. However, bilberry extract is known to contain cell-wall degrading enzymes that provide antimicrobial activity useful against opportunistic organisms (8).

Echinacea Angustifolia and Purpurea

Echinacea, as a group, are flowering plants found within the daisy family. There are ten known species referred to as coneflowers with some being used as herbal medicines, e.g. Echinacea purpurea (9). E. angustifolia has a long tradition as a folk remedy used by North American indigenous peoples as a remedy for cough, headache, pain, and sore throat (10).

Various studies have shown that polysaccharides from Echinacea provide protection against various bacteria, e.g. Listeria and Candida albicans. These polysaccharides likely stimulate immune cells such as macrophages (11). E. purpurea seems to specifically activate various leukocytes and natural killer cells too (12).

Goldenseal

Goldenseal, a.k.a. Hydratis canadensis, has extensive use amongst Native American tribes as both a medicine for digestive problems, but also an eyewash and diuretic. Various compounds within Goldenseal allow the herb to be used as a coloring agent too. Goldenseal is a perennial herb that flourishes in the eastern regions of the United States and Canada (southeastern).

Because of its various chemical properties as an astringent it can be helpful as an insect repellant (13). As an antimicrobial, an interesting characteristic is a proposed efflux pump inhibition effect (14). Efflux pumps are intracellular mechanisms of various organisms that allow it to excrete antimicrobial chemicals that are transported or diffuse into the cell.

Oregano

Oregano, a.k.a. Origanum vulgare, is in the mint family of plants. It too has been used in traditional folk medicine for centuries and as an oil extracted from the oregano plant it is used extensively in dietary herbal supplements with a good safety profile (16).

Its antimicrobial properties are diverse, but much of it comes down to two polyphenols called carvacrol and thymol (17). Other medicinal constituents of oregano oils are various terpenes which also contain antimicrobial properties.

Tea Tree Oil

The essential oil of tea tree, a.k.a. Melaleuca alternifolia, like oregano, contains various terpenes which appear to damage the cell membrane of various microorganisms, including Candida albicans, Staph aureus and Escherichia coli. Research has shown that the greatest mode of action of tea tree oil against candida is through cell membrane viability and cellular respiration disruption (18).

There are many other botanical remedies such as black walnut, garlic, gentian, grapeseed extract, lavender, raspberry and more that have their own unique antimicrobial properties and complementary affects when used along with other herbs. One of the greatest advantages of botanical remedies is their multi-use potential and cross-reactivity against various pathogens, e.g. bacterial, fungal, parasitic. In addition, botanical remedies often do not have the same side effect profiles seen with common prescription medications and are typically well tolerated by most children and adults alike.

BioBotanical Research (BBR)

BBR has a variety of botanical formulations that support digestive health and aide in the reduction and/or elimination of opportunistic pathogens, including candida.

Biocidin in its various forms (capsule, liquid, liposomal), combines bilberry extract, echinacea (both angustifolia and purpurea), goldenseal, oregano, tee tree oil and other complementary ingredients into a pleasant-tasting, well-tolerated, highly effective combination botanical supplement. Biocidin is often combined with additional BBR products such as Olivirex (combination of olive leaf extract, garlic, goldenseal and more) and Proflora 4R (soil-based organisms of Bacillus coagulans, Bacillus subtilis and Bacillus clausii) comprising a complementary trio offering excellent support for digestive health and maintenance.

For more information about Bio-Botanical Research and the clinical application of their products, contact a BBR representative at Bio-Botanical Research, Biocidin.com.

Conclusion

Chronic candidiasis can be a challenging condition for many individuals. Effective intervention requires reliable diagnostic testing, as well as understanding the various pathogenic mechanisms inherent to these sophisticated organisms.

The use of medications such as Nystatin at varying dosages, i.e. 250,000 units to 750,000 units three times daily for 30 to 90 days may be required for control of chronic candidiasis. Fluconazole is always and option too, but typically is used in shorter durations, e.g. 2 to 4 weeks, unless consistent blood liver enzyme levels can be monitored. Resistant candidiasis may require Fluconazole at 100mg to 200mg daily other interventions have failed.

Finally, Biocidin in varying dosages, i.e. 1 to 2 capsules two to three times daily can have positive outcomes for chronic candidiasis. The length of intervention is variable, but for most individuals dealing with long-standing problems, use of Biocidin for 60 to 90 is typical.

It is critical to understand that every individual dealing with a chronic candidiasis condition may require individualized dosing based on their unique health circumstances and tolerance. Therefore, tailoring a supplement program to each person is often helpful and BioBotanical Research, with its various botanical supplements, provides great flexibility in product usage.

References:

  1. 1. Nystatin" . American Society of Health-System Pharmacists . Archived from the original on 2016-02-03. Retrieved 2016-01-27.
  2. Hilal-Dandan, Randa; Knollmann, Bjorn; Brunton, Laurence (2017-12-05). Goodman & Gilman's the pharmacological basis of therapeutics. Brunton, Laurence L., Knollmann, Björn C., Hilal-Dandan, Randa (Thirteenth ed.).
  3. P., Rang, H. (2015-01-21). Rang and Dale's pharmacology. Dale, M. Maureen, Flower, R. J. (Rod J.), 1945–, Henderson, G. (Graeme) (Eighth ed.). [United Kingdom].
  4. Hammond, S.M. (1977). Biological activity of polyene antibiotics. Progress in Medicinal Chemistry. 14. pp. 105–79.
  5. The American Society of Health-System Pharmacists. Archived from the original on 20 December 2016. Retrieved 8 December 2016.
  6. Longley, Nicky; Muzoora, Conrad; Taseera, Kabanda; Mwesigye, James; Rwebembera, Joselyne; Chakera, Ali; Wall, Emma; Andia, Irene; Jaffar, Shabbar; Harrison, Thomas S. (2008). "Dose Response Effect of High-Dose Fluconazole for HIV-Associated Cryptococcal Meningitis in Southwestern Uganda" Clinical Infectious Diseases. 47 (12): 1556–1561.
  7. Bilberry: Science and Safety | NCCIH" . Nccih.nih.gov. Retrieved 2018-03-19.
  8. J. Agric. Food Chem. 2008, 56, 3, 681–688. Publication Date: January 23, 2008
  9. Kelly K. "The Conservation Status of Echinacea Species" (PDF). USDA. Retrieved 29 October 2014.
  10. Moerman DE (1998). Native American Ethnobotany . Timber Press. p. 205. ISBN 978-0-88192-453-4 .
  11. Roesler J, Steinmüller C, Kiderlen A, Emmendörffer A, Wagner H, Lohmann-Matthes ML. Application of purified polysaccharides from cell cultures of the plant Echinacea purpurea to mice mediates protection against systemic infections with Listeria monocytogenes and Candida albicans. Int J Immunopharmacol. 1991;13:27–37.
  12. Barnes J, Anderson LA, Gibbons S, Phillipson JD. Echinacea species (Echinacea angustifolia (DC.). Hell, Echinacea pallida (Nutt.) Nutt Echinacea purpurea (L.) Moench): A review of their chemistry, pharmacology, and clinical properties. J Pharm Pharmacol. 2005;57:929–54.
  13. Niering, William A. ; Olmstead, Nancy C. (1985) [1979]. The Audubon Society Field Guide to North American Wildflowers, Eastern Region. Knopf. p. 737. ISBN 0-394-50432-1 .
  14. Ettefagh K.A., Burns J.T., Junio H.A., Kaatz G.W., Cech N.B., "Goldenseal (Hydrastis canadensis L.) Extracts Synergistically Enhance the Antibacterial Activity of Berberine via Efflux Pump Inhibition", Planta Medica 2010.
  15. Garlic" . National Center for Complementary and Integrative Health, US National Institutes ofHealth. April 2012. Retrieved May 4, 2016.
  16. Oregano" . MedlinePlus, US National Library of Medicine. 2016. Retrieved 7 October 2016.
  17. V Manohar 1 , C Ingram , J Gray , N A Talpur , B W Echard , D Bagchi , H G Preuss Mol Cell Biochem. 2001 Dec;228(1-2):111-7. Antifungal activities of origanum oil against Candida albicans.
  18. Sean D. Cox , 1,* Cindy M. Mann , 1 Julie L. Markham , 1 John E. Gustafson , 2 John R. Warmington, and S. Grant Wyllie 1 Molecules . 2001 Feb; 6(2): 87–91. Published online 2001 Jan 16. Determining the Antimicrobial Actions of Tea Tree Oil.