Monday, October 13, 2014

Candida albicans and its effect on hormonal balance

In my previous blog, found here, I went over some of the research on Candida albicans.  This opportunistic fungus is the leading cause of fungal infection in humans and can cause issues ranging from mild skin and connective tissue irritation to vaginal yeast infections and hormonal disturbances in those with a candida overgrowth.  In this blog I will show the connection behind all 3 of these issues.

To better understand how Candida albicans can cause a hormonal imbalance, it's important to understand the basic physiology of the stress response.  The stress response is carried out by the HPA axis.  HPA is an acronym for Hypothalamus-Pituitary-Adrenal.

Stress 101

The stress response begins when stress is perceived, which causes the hypothalamus, a part of your brain that is essentially the master control center, to release something called corticotropin releasing hormone(CRH).  CRH, in turn, triggers a projection off of your hypothalamus called the the pituitary gland to release adrenocorticotropic hormone (ACTH).  ACTH travels in the bloodstream until it reaches an area on top of the kidneys called the adrenal glands and signals them to produce corticosteroids such as cortisol and aldosterone.  In turn, as cortisol is pumped out by the adrenals, it eventually makes its way back to the hypothalamus via the bloodstream and shuts off CRH production, which causes the pituitary to reduce production of ACTH which reduces cortisol production by the adrenal glands.  This is called a negative feedback loop as higher levels of cortisol help tell the hypothalamus to chill out with requesting more cortisol.  While the stress response is far more complicated than this, this is all you need to know to understand Candida albicans' role in causing hormonal disturbances.

Recall from my last blog that Candida albicans possesses a corticosteroid receptor capable of binding corticosterone and cortisol.  When Candida albicans binds cortisol, it prevents cortisol from binding to cells that need it, while at the same time blocking the negative feedback loop cortisol has on CRH production by the hypothalamus.  This can cause the hypothalamus to pump out more and more CRH as it never receives the "Cool it" signal which, in hormonal terms, means the perception of chronic stress.  It doesn't end here for the impact on hormonal balance, however.  By causing something called pregnenonlone steal, HPA axis mis-signaling due to Candida albicans can cause problems with sex hormones and, therefore, reproductive success.

Pregnenolone-hormonal stem cell

As far as hormones go, pregnenolone is the last common ancestor of all hormones.  All steroids begin as pregnenolone and are created based on the body's needs.

Pregnenolone is synthesized from cholesterol and becomes whichever steroid the body needs based on hormonal signaling. When cortisol is bound by Candida albicans and the negative feedback loop it has on the HPA axis is broken, CRH sends the signal to the adrenal glands via ACTH that pregnenolone should be converted in to the corticosteroids, particularly cortisol.  As pregnenolone is directed towards the corticosteroids, less can be used for formation of sex/reproductive hormones causing a hormonal imbalance.  In men, this can cause low testosterone and in women it can cause low testosterone and low levels of estrogens.  Estrone, estriol, and estrogen are estrogens and Candida albicans can directly bind estrogen.  Ironically, you really don't have to learn anything else to understand how Candida albicans can affect the skin and GI tract because it is by the same mechanism.

The HPA axis in the skin

In addition to the central HPA axis that regulates the stress response, humans have a peripheral HPA axis within the skin and hair follicles that actively produce the same hormones and contains the same negative feedback system of the central HPA axis(1, 2, 3, 4) with the only difference being that the end product of the skin HPA axis is corticosterone instead of cortisol.  The skin and hair follicles are also rich sources of collagen which is high in the amino acid L-Proline, the amino acid of choice for the conversion of yeast to hypha in Candida albicans.  When you look at the effect of unmitigated CRH secretion in the skin and GI tract, you can see how Candida albicans can wreak havoc in these tissues.

By binding corticosterone in the skin, Candida albicans can break the negative feedback loop in the skin's HPA axis which may cause CRH levels in the skin to increase.  CRH causes mast cells in the skin to release histamine, an immune compound that increases inflammation and the primary target of antihistamines, pharmaceuticals used to decrease allergic responses(3, 5).  Unfettered stimulation of mast cells by CRH could cause skin inflammation to grow out of control and cause major skin hypersensitivity reactions.  Increased levels of CRH in the skin are thought to play a role in skin conditions such as eczema, psoriasis, hypersensitivity to chemicals, poison ivy reactions, urticaria, acne, and certain types of hair loss.

Effects of CRH outside of the skin

High levels of CRH activate mast cells and cause them to release histamine in the intestinal tract, increasing intestinal(6, 7) permeability.  CRH is thought to have a major role in IBS(8, 9) which would jibe with the relationship between a exaggerated stress response and IBS.  Finally,  CRH activates mast cells in the brain and increase permeability of the blood brain barrier(10).  An additional effect of chronically high CRH levels in the brain is impaired function of the hippocampus(11), an area of the brain crucial for consolidating information from short-term to long-term memory as well as spatial memory. It is interesting that brain fog is often listed as a potential symptom of candida overgrowth as impaired hippocampal function would certainly be a mechanism for brain fog.


Above I have laid out possible mechanisms for the symptoms associated with overgrowth of Candida albicans.  It is important to point out that this doesn't mean that if you have one of these symptoms that you have an overgrowth of Candida albicans.  If Candida were disrupting signaling within the HPA axis, you wouldn't have a single symptom, you would have a suite of them.

It is interesting to note that many of the symptoms of a Candida overgrowth overlap with symptoms of what was once referred to as adrenal fatigue and is now more appropriately labeled HPA axis dysregulation.  Another interesting thing that pops up is that many of the symptoms of HPA dsyregulation are caused by an electrolyte imbalance.  It is important to note that the adrenal hormone aldosterone is one of the chief regulators of electrolyte balance, and corticosterone is the precursor to aldosterone.  Candida could only play a role here if it invaded the adrenal gland directly.

If these mechanisms turn out to be correct, overgrowth of Candida albicans causes HPA axis dysregulation.  That is not to say it is the only cause or even the most common cause, other commensal organisms could potentially bind hormones that are part of the HPA axis and could, therefore, cause it to function improperly if they grow out of whack.  The important thing to realize if this is the case is that nutrient deficiencies aren't causing the problem, blocking steps in a tightly regulated system is.  Therefore, taking high doses of nutrients that are used to manufacture cortisol won't fix the problem until you fix the signaling issue.

***I will likely follow this up with a blog on therapeutic approaches to fixing the problem.  However, I need a break from writing these super long, heavily referenced blogs as they take a ton of time and I am currently working on something work related.  Please stay patient and hopefully I will get to it soon if that was what you were waiting for.  I know, it sucks, but there are only so many hours in the day.