Candida Facts Paper
This Candida Facts Paper contains 75+ candida research studies, taken from the over 62,000 studies available. Many of the doctors who have consulted with me over the past 34 years have asked for more information and references to better educate themselves, their patients and fellow doctors. To assist them, I gathered together a few of the references that we are including in our online Candida Library. In this article, you’ll find over 75 research references that provide information on how Candida goes from a harmless normal constituent of the gastrointestinal tract to a pathogenic systemic problem that can affect anyone and everyone. I’m providing this information here for you to become better educated about Candida, like the many doctors with whom I’ve consulted. Pass it along to your family, friends, and doctors, if you feel that it can also assist them in learning and understanding more about a problem that affects virtually everyone.
The human digestive tract is said to contain some 100 trillion cells compared to about only 10 trillion human cells in the body. This particular arrangement has led to man being classified as a “super-organism,” whose health is directly related to the function of the thousands of species of micro-organisms that make up the 100 trillion cells in the intestinal tract. For years, research suggested that there were 400-500 species that made up this microbial population. Recent advances in research have now put that number at anywhere from 3,300 to 5,700 or more, (9) to upwards of 30,000 species. The Human Microbiome Project now lists at least 10,000 species. The intestinal tract houses what has been called “the densest ecosystem on the planet,” and is approximately 25-28 ft long. The surface area of the intestinal tract measures approximately 200 square meters, roughly the size of a tennis court.
Modern medicine states that systemic Candida exists only in immunocompromised individuals, as a result of AIDS, immunosuppressive therapy, such as in organ transplants, or chemotherapy. Science states otherwise, and extends that list to include: diabetes, premature infants, surgical patients; (7)(10)(66) hematological malignancies; (8) hospitalized patients, especially in Intensive Care Units, or having major injuries;(10) burn victims; (54) nutritional deficiencies; (22) as well as aging. (22)(35)(36)(37) alcoholism, cirrhosis, tuberculosis, cancer, corticosteroids, marrow hyperplasia;
Researchers continuously broaden the scope of those being affected. Valdimarsson et al. state that there are no common immunological denominators. (1) Senet states that the pathogenic behavior of Candida may appear following even a slight modification of the host. (55) Berg et al. on behalf of Biocodex Pharmaceuticals states that Candida spreads in immunocompetent individuals. (68)
The widespread use of antibiotics, which induce neutropenia, an abnormally low number of neutrophils (white blood cells), and immune system suppression is commonly attributed by science to be the most consistent cause of systemic Candida.(3)(9)(12)(13)(14)(16)(17)(18)(19)(20)(21)(22)(55)(56)(57)(64)(67)(68)(69)(76)(77) Corticosteroids suppress immune system function. (11)(17)(68) Intestinal homeostasis is critical for human health. (6)(7)(55)(57)(68)(71)
Candida has been shown to be capable of causing systemic immuno-suppression via its cell wall proteins, (2) TLR2-mediated IL-10 release, (30) protease cleaving of leukocyte integrin CD11/CD18, (25)(31)(34)(62)(63) and intracellular components. (72)
Candida can manipulate inflammatory responses as needed (31)(32) and inflammatory responses can have systemic effects. (44)(45)(46)(47)
Candida has the ability to destroy immune cells, (3)(23)(24)(26)(49) hide from the immune system, (4)(19) adapt to the inner environment of immune cells, (5)(38)(39) resist and suppress ROI and NO production of immune cells, (15)(16)(27)(43) destroy binding sites and receptors of immune cells, (25)(31)(33)(34) manipulate immune responses, (28)(53)(70)(74) and affect immune cell structure. (42)(73)
Stress can cause accumulation of iron at the luminal surface of intestinal cells (75) and iron overload leads to impaired neutrophil function. (14) Stress can lead to immunosuppression facilitating the spread of Candida. (55) Sanchez et al. discuss the affect of starches vs. sugars on the immune system response to Candida. (29)
Macrophages, which are widely distributed immune system cells that play an indispensable role in homeostasis and defense, and are cells that function as a first line of defense against invading microorganisms, are historically ineffective against Candida albicans. (40)(41)
While evidence suggests that intestinal Dendritic Cells are critical for regulation of immunity in the gut, (50) Dendritic Cells are poor in both intracellular killing and damaging of C. albicans hyphae, (48) and only kill as effectively as macrophages. (51) Ingestion of hyphae by Dendritic Cells inhibits Th1 immune responses. (52)
Candida Albicans’ Secreted Aspartyl Proteases (SAPs) are a highly specific family of enzymes that assists in its ability to cause disease in the body. SAPs are believed to play a role in Candida’s ability to induce inflammation, invade and breakdown tissue barriers, digest proteins for nutrients, destroy and evade immune defenses, and spread throughout the body. (25)(33)(34)(58)(59)(60)(61)(62)(63)(65) Research has shown that the destructive effects of protease enzymes are associated with diabetes, hypertension, and immune system suppression. (25)(31)(34)(62)
Additional enzymes secreted by Candida albicans include phospholipases, lipases, glucoamylases, phosphatases, and β-N-acetylglucosaminidase.
As impressive as I find the above research to be, it is just a small representation of the research on Candida albicans and its effects in humans. With over 54,000 studies on Candida albicans since the introduction of antibiotics in the mid-1940s, there is much more to be analyzed and reported. What is readily apparent from this data is the fact that systemic fungal Candida infections are a common occurrence in most individuals as a result of antibiotic use and other contributing factors.
– Dr. Jeffrey McCombs, DC
1. Immunological phenomena associated with chronic mucocutaneous candidiasis have recently been intensively studied by many workers (reviewed by Kirkpatrick, Rich & Bennett, 1971). The results have shown that there is no common immunological denominator in this disease. The most common finding, however, is defective cellular immunity, which may or may not be accompanied by failure of in vitro lymphocyte transformation.
Immunological Feautures in a Case of Chronic Granulomatous Candidiasis and its Treatment with Transfer Factor
H. VALDIMARSSON, C. B. S. WOOD, J. R. HOBBS AND P. J. L. HOLT
2. The ability of Candida albicans to establish an infection involves multiple components of this fungal pathogen, but its ability to persist in host tissue may involve primarily the immunosuppressive property of a major cell wall glycoprotein, mannan. Mannan and oligosaccharide fragments of mannan are potent inhibitors of cell-mediated immunity and appear to reproduce the immune deficit of patients with the mucocutaneous form of candidiasis. However, neither the exact structures of these inhibitory species nor their mechanisms of action have yet been clearly defined. Different investigators have proposed that mannan or mannan catabolites act upon monocytes or suppressor T lymphocytes, but research from unrelated areas has provided still other possibilities for consideration. These include interference with cytokine activities, lymphocyte-monocyte interactions, and leukocyte homing. To stimulate further research of the immunosuppressive property of C. albicans mannan, we have reviewed (i) the relationship of mannan to other antigens and virulence factors of the fungus; (ii) the chemistry of mannan, together with methods for preparation of mannan and mannan fragments; and (iii) the historical evidence for immunosuppression by Candida mannan and the mechanisms currently proposed for this property; and (iv) we have speculated upon still other mechanisms by which mannan might influence host defense functions. It is possible that understanding the immunosuppressive effects of mannan will provide clues to novel therapies for candidiasis that will enhance the efficacy of both available and future anti-Candida agents. Immunosuppressive properties observed for isolated Candida mannan and its catabolites in vivo and in vitro provide additional evidence that fungal mannan is responsible for patient immune dysfunction.
Candida mannan: chemistry, suppression of cell-mediated immunity, and possible mechanisms of action.
R D Nelson, N Shibata, R P Podzorski, and M J Herron
Continue reading References below…
3. Phagocytic cells of the innate immune system, such as macrophagesand neutrophils, are a primary line of defense against microbialinfections. Patients with defects in innate immunity, such asthose with chronic granulomatous disease or neutropenia, areextremely sensitive to a variety of infections. When a phagocyterecognizes the presence of an invading cell, it engulfs themicrobe with its membrane to form the phagosome, an intracellularcompartment containing the microbe. This compartment maturesby fusion with lysosomes to create the phagolysosome, an organellereplete with antimicrobial compounds and an acidic pH. Internalizationcreates a hostile environment for the microorganism, which,of course, is the intent. The phagolysosome is a precarious neighborhood even before theonslaught of antimicrobial compounds. Engulfment by the macrophagethrusts the microorganism into an alien milieu, one devoid ofkey nutrients necessary for metabolism and division. Survivingthe antimicrobial assault in the phagolysosome depends on themicrobe’s ability to synthesize the proteins and other cellularcomponents necessary to counteract these stresses. Thus, a pathogenmust find the requisite nutrients to provide the building blocksfor these complex macromolecules and the energy with which tosynthesize them.
In this article we consider the initial responses of severalmicrobes to nutrient deprivation inside the macrophage. Thefirst of these, Mycobacterium tuberculosis, the bacterium thatcauses tuberculosis, resides for prolonged periods within themacrophage, in which it can proliferate and subsequently spreadthroughout the body. The second, the yeast Saccharomyces cerevisiae,is killed efficiently by the macrophage. The third, the opportunisticfungal pathogen Candida albicans, survives ingestion by changingrapidly from a yeast to a filamentous morphology, lysing themacrophage from the inside out. Once free, C. albicans cellsare able to disseminate through the body. The interaction ofC. albicans with the macrophage is transient, as opposed tothe long-term persistence of M. tuberculosis. Although the outcomesof this macrophage capture are quite different among the threemicrobes, the initial responses of all three to the internalenvironment are remarkably similar: induction of the glyoxylatecycle, a pathway that permits the utilization of compounds withtwo carbons (C2 compounds), such as acetate, to satisfy cellularcarbon requirements.
Systemic fungal infections have increased dramatically in prevalenceand severity over the last few decades, in concert with thenumber of patients living for extended periods with significantimmune dysfunction. AIDS, cancer chemotherapy, and organ transplantationhave all contributed to this rise, as has the widespread useof antibiotics. The most common systemic fungal infection iscandidiasis, which accounts for well over half of these invasivemycoses (3). A single species, C. albicans, causes the majorityof these infections. C. albicans, which also causes oropharyngealthrush and vaginitis, is normally a commensal of the mammaliangastrointestinal tract, in which it lives without adverse effectson the host. Both C. albicans and S. cerevisiae are readily phagocytosedby cultured macrophages in the presence of serum. While themacrophages efficiently kill S. cerevisiae, engulfment inducesC. albicans cells to grow in a filamentous morphology. Thesehyphal filaments can penetrate through the membrane of the phagocyticcell, releasing the fungal cell back into the extracellularmedium while killing the macrophage in the process. The differentoutcomes are not surprising; C. albicans is a common pathogenwhile S. cerevisiae is rarely found in human hosts.
The primary function of the glyoxylate cycle is to permit growthwhen C2 compounds, such as ethanol and acetate, are the onlysources of carbon. The glyoxylate pathway (also dubbed the glyoxylate shunt, forclear reasons) bypasses these decarboxylations, allowing C2compounds to serve as carbon sources in gluconeogenesis andto be incorporated into glucose and, from there, into aminoacids, DNA, and RNA. Glucose, as the preferred carbon sourcein most organisms, can be both converted into five-carbon sugars(such as ribose and deoxyribose) via the pentose phosphate pathwayand catabolized to acetyl-CoA via glycolysis. In microorganisms, however, glucose is frequently not available,and simple carbon compounds provide the only accessible carbon.
With the population of immunocompromisedpeople on the rise, the frequency of invasive fungal infectionscontinues to increase, making the need for effective treatmentsmore imperative.